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Int. J. Mol. Sci., Volume 14, Issue 9 (September 2013) – 111 articles , Pages 17238-19360

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Editorial

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156 KiB  
Editorial
Editorial of the Special Issue Antimicrobial Polymers
by Antonella Piozzi and Iolanda Francolini
Int. J. Mol. Sci. 2013, 14(9), 18002-18008; https://doi.org/10.3390/ijms140918002 - 03 Sep 2013
Cited by 5 | Viewed by 7463
Abstract
The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks [...] Read more.
The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)

Research

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247 KiB  
Article
Differential Proinflammatory and Oxidative Stress Response and Vulnerability to Metabolic Syndrome in Habitual High-Fat Young Male Consumers Putatively Predisposed by Their Genetic Background
by Pedro González-Muniesa, María Pilar Marrades, José Alfredo Martínez and María Jesús Moreno-Aliaga
Int. J. Mol. Sci. 2013, 14(9), 17238-17255; https://doi.org/10.3390/ijms140917238 - 22 Aug 2013
Cited by 27 | Viewed by 7312
Abstract
The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in [...] Read more.
The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21–35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Article
Assessing the Effect of Loop Mutations in the Folding Space of β2-Microglobulin with Molecular Dynamics Simulations
by Sílvia G. Estácio, Eugene I. Shakhnovich and Patrícia F. N. Faísca
Int. J. Mol. Sci. 2013, 14(9), 17256-17278; https://doi.org/10.3390/ijms140917256 - 22 Aug 2013
Cited by 14 | Viewed by 8324
Abstract
We use molecular dynamics simulations of a full atomistic Gō model to explore the impact of selected DE-loop mutations (D59P and W60C) on the folding space of protein human β2-microglobulin (Hβ2m), the causing agent of dialysis-related amyloidosis, a conformational [...] Read more.
We use molecular dynamics simulations of a full atomistic Gō model to explore the impact of selected DE-loop mutations (D59P and W60C) on the folding space of protein human β2-microglobulin (Hβ2m), the causing agent of dialysis-related amyloidosis, a conformational disorder characterized by the deposition of insoluble amyloid fibrils in the osteoarticular system. Our simulations replicate the effect of mutations on the thermal stability that is observed in experiments in vitro. Furthermore, they predict the population of a partially folded state, with 60% of native internal free energy, which is akin to a molten globule. In the intermediate state, the solvent accessible surface area increases up to 40 times relative to the native state in 38% of the hydrophobic core residues, indicating that the identified species has aggregation potential. The intermediate state preserves the disulfide bond established between residue Cys25 and residue Cys80, which helps maintain the integrity of the core region, and is characterized by having two unstructured termini. The movements of the termini dominate the essential modes of the intermediate state, and exhibit the largest displacements in the D59P mutant, which is the most aggregation prone variant. PROPKA predictions of pKa suggest that the population of the intermediate state may be enhanced at acidic pH explaining the larger amyloidogenic potential observed in vitro at low pH for the WT protein and mutant forms. Full article
(This article belongs to the Special Issue Protein Folding)
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Article
Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels
by Ju-Hwa Kim, Ae-Ran Choi, Yong Kee Kim, Hyung Sik Kim and Sungpil Yoon
Int. J. Mol. Sci. 2013, 14(9), 17304-17318; https://doi.org/10.3390/ijms140917304 - 22 Aug 2013
Cited by 17 | Viewed by 7078
Abstract
The present study identified a novel salinomycin (Sal)-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules [...] Read more.
The present study identified a novel salinomycin (Sal)-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules PI3K, PDK1, GSK3β, p70S6K, mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal sensitization positively correlates with large reductions in p70S6K activation. Interestingly, Akt was the only signal protein to be significantly activated by Sal treatment. The Akt activation appeared to require the PI3K pathway as its activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt activation by Sal was conserved in the other cell lines analyzed, which originated from other organs. Both Akt activation and C-PARP production were proportionally increased with increased doses of Sal. In addition, the increased levels of pAkt were not reduced over the time course of the experiment. Co-treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The results thereby suggest that Akt activation is increased in cells that survive Sal treatment and resist the cytotoxic effect of Sal. Taken together; these results indicate that Akt activation may promote the resistance of cancer cells to Sal. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Article
Materials Characterization of Feraheme/Ferumoxytol and Preliminary Evaluation of Its Potential for Magnetic Fluid Hyperthermia
by John P. Bullivant, Shan Zhao, Brad J. Willenberg, Bettina Kozissnik, Christopher D. Batich and Jon Dobson
Int. J. Mol. Sci. 2013, 14(9), 17501-17510; https://doi.org/10.3390/ijms140917501 - 26 Aug 2013
Cited by 100 | Viewed by 11088
Abstract
Feraheme, is a recently FDA-cleared superparamagnetic iron oxide nanoparticle (SPION)-based MRI contrast agent that is also employed in the treatment of iron deficiency anemia. Feraheme nanoparticles have a hydrodynamic diameter of 30 nm and consist of iron oxide crystallites complexed with a low [...] Read more.
Feraheme, is a recently FDA-cleared superparamagnetic iron oxide nanoparticle (SPION)-based MRI contrast agent that is also employed in the treatment of iron deficiency anemia. Feraheme nanoparticles have a hydrodynamic diameter of 30 nm and consist of iron oxide crystallites complexed with a low molecular weight, semi-synthetic carbohydrate. These features are attractive for other potential biomedical applications such as magnetic fluid hyperthermia (MFH), since the carboxylated polymer coating affords functionalization of the particle surface and the size allows for accumulation in highly vascularized tumors via the enhanced permeability and retention effect. This work presents morphological and magnetic characterization of Feraheme by transmission electron microscopy (TEM), Energy dispersive X-ray spectroscopy (EDX), and superconducting quantum interference device (SQUID) magnetometry. Additionally, the results of an initial evaluation of the suitability of Feraheme for MFH applications are described, and the data indicate the particles possess promising properties for this application. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Article
Functional and Molecular Changes of the Bladder in Rats with Crushing Injury of Nerve Bundles from Major Pelvic Ganglion to the Bladder: Role of RhoA/Rho Kinase Pathway
by Su Jin Kim, Dong Sup Lee, Woong Jin Bae, Seol Kim, Sung Hoo Hong, Ji Youl Lee, Tae-Kon Hwang and Sae Woong Kim
Int. J. Mol. Sci. 2013, 14(9), 17511-17524; https://doi.org/10.3390/ijms140917511 - 27 Aug 2013
Cited by 10 | Viewed by 7935
Abstract
Voiding dysfunction is a common complication after radical pelvic surgery. To reduce this complication, nerve-sparing radical pelvic surgery was introduced. However, several patients experienced voiding difficulty despite nerve-sparing radical pelvic surgery. Thus, we investigated the functional and molecular changes of the bladder in [...] Read more.
Voiding dysfunction is a common complication after radical pelvic surgery. To reduce this complication, nerve-sparing radical pelvic surgery was introduced. However, several patients experienced voiding difficulty despite nerve-sparing radical pelvic surgery. Thus, we investigated the functional and molecular changes of the bladder in rats, which demonstrated voiding dysfunction induced by nerve damage during nerve-sparing radical pelvic surgery. Male rats were used and assigned to normal, sham-operated, and bilateral crushing nerve bundles from major pelvic ganglion (MPG) to bladder group. After one, two, and four-week crushing injury, significantly decreased contractile response and increased connective tissue of the detrusor were observed and these results were reliable findings with voiding difficulty following nerve-sparing radical pelvic surgery. After crushing injury, significantly increased M2 muscarinic receptor expression was observed and this might be regarded as the compensatory response. However, M3 muscarinic receptor expression was not significantly changed. The expression of RhoA, ROCK-α, and ROCK-β was significantly increased after one, two, and four-week crushing injury. From these results, the down-regulation of RhoA/Rho kinase pathway might lead to the decreased bladder contractility after crushing injury of nerve bundles from MPG to the bladder despite of the compensated up-regulation of M2 muscarinic receptor. Full article
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Article
Cytogenetic Abnormalities in Lymphocytes from Victims Exposed to Cobalt-60 Radiation
by Jia Cao, Jing Zhang, Yan Wang, Li Qing Du, Chang Xu, Qin Wang, Jian Xiang Liu, Xu Su, Fei Yue Fan, Qiang Liu and Sai Jun Fan
Int. J. Mol. Sci. 2013, 14(9), 17525-17535; https://doi.org/10.3390/ijms140917525 - 27 Aug 2013
Cited by 9 | Viewed by 10732
Abstract
The present study investigates cytogenetic damage in lymphocytes, derived from three victims who were unfortunately exposed to cobalt-60 (60Co) radiation (the 1999 accident occurred in a village in China’s Henan province). Case A of the three victims was exposed to a [...] Read more.
The present study investigates cytogenetic damage in lymphocytes, derived from three victims who were unfortunately exposed to cobalt-60 (60Co) radiation (the 1999 accident occurred in a village in China’s Henan province). Case A of the three victims was exposed to a higher dose of 60Co radiation than Cases B and C. The chromosomal aberrations, cytokinesis-block micronucleus (CBMN, the CBMN assay), and DNA double-strand breaks (DSBs, the comet assay) examined in this study are biomarkers for cytogenetic abnormalities. After the lymphocytes collected from the victims were cultured, the frequencies of dicentric chromosomes and rings (dic + r) and CBMN in the first mitotic division detected in the lymphocytes of Case A were found to be substantially higher than in Cases B and C. Similarly, the DNA-DSB level found in the peripheral blood collected from Case A was much higher than those of Cases B and C. These results suggest that an acutely enhanced induction of the 60Co-induced cytogenetic abnormality frequency in humans depends on the dose of 60Co radiation. This finding is supported by the data obtained using practical techniques to evaluate early lymphoid-tissue abnormalities induced after exposure to acute radiation. Full article
(This article belongs to the Collection Radiation Toxicity in Cells)
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Article
Assessment of Blood Flow in Hepatocellular Carcinoma: Correlations of Computed Tomography Perfusion Imaging and Circulating Angiogenic Factors
by Ya-Wen Chen, Huay-Ben Pan, Hui-Hwa Tseng, Yu-Ting Hung, Jer-Shyung Huang and Chen-Pin Chou
Int. J. Mol. Sci. 2013, 14(9), 17536-17552; https://doi.org/10.3390/ijms140917536 - 27 Aug 2013
Cited by 17 | Viewed by 7084
Abstract
Hepatocellular carcinoma (HCC) is a highly vascular tumor through the process of angiogenesis. To evaluate more non-invasive techniques for assessment of blood flow (BF) in HCC, this study examined the relationships between BF of HCC measured by computer tomography (CT) perfusion imaging and [...] Read more.
Hepatocellular carcinoma (HCC) is a highly vascular tumor through the process of angiogenesis. To evaluate more non-invasive techniques for assessment of blood flow (BF) in HCC, this study examined the relationships between BF of HCC measured by computer tomography (CT) perfusion imaging and four circulating angiogenic factors in HCC patients. Interleukin 6 (IL-6), interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) in plasma were measured using Bio-Plex multiplex immunoassay in 21 HCC patients and eight healthy controls. Circulating IL-6, IL-8 and VEGF showed higher concentrations in HCC patients than in controls (p < 0.05), and predicted HCC occurrence better than chance (p < 0.01). Twenty-one patients with HCC received 21-phase liver imaging using a 64-slice CT. Total BF, arterial BF, portal BF, arterial fraction (arterial BF/total BF) of the HCC and surrounding liver parenchyma, and HCC-parenchyma ratio were measured using a dual-vessel model. After analyzing the correlations between BF in HCC and four circulating angiogenic factors, we found that the HCC-parenchyma ratio of arterial BF showed a significantly positive correlation with the level of circulating IL-8 (p < 0.05). This circulating biomarker, IL-8, provides a non-invasive tool for assessment of BF in HCC. Full article
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Article
Nanoconfinement-Induced Structures in Chiral Liquid Crystals
by Michael Melle, Madlona Theile, Carol K. Hall and Martin Schoen
Int. J. Mol. Sci. 2013, 14(9), 17584-17607; https://doi.org/10.3390/ijms140917584 - 28 Aug 2013
Cited by 14 | Viewed by 6280
Abstract
We employ Monte Carlo simulations in a specialized isothermal-isobaric and in the grand canonical ensemble to study structure formation in chiral liquid crystals as a function of molecular chirality. Our model potential consists of a simple Lennard-Jones potential, where the attractive contribution has [...] Read more.
We employ Monte Carlo simulations in a specialized isothermal-isobaric and in the grand canonical ensemble to study structure formation in chiral liquid crystals as a function of molecular chirality. Our model potential consists of a simple Lennard-Jones potential, where the attractive contribution has been modified to represent the orientation dependence of the interaction between a pair of chiral liquid-crystal molecules. The liquid crystal is confined between a pair of planar and atomically smooth substrates onto which molecules are anchored in a hybrid fashion. Hybrid anchoring allows for the formation of helical structures in the direction perpendicular to the substrate plane without exposing the helix to spurious strains. At low chirality, we observe a cholesteric phase, which is transformed into a blue phase at higher chirality. More specifically, by studying the unit cell and the spatial arrangement of disclination lines, this blue phase can be established as blue phase II. If the distance between the confining substrates and molecular chirality are chosen properly, we see a third structure, which may be thought of as a hybrid, exhibiting mixed features of a cholesteric and a blue phase. Full article
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Article
Spin Polarization and Quantum Spins in Au Nanoparticles
by Chi-Yen Li, Sunil K. Karna, Chin-Wei Wang and Wen-Hsien Li
Int. J. Mol. Sci. 2013, 14(9), 17618-17642; https://doi.org/10.3390/ijms140917618 - 28 Aug 2013
Cited by 9 | Viewed by 7647
Abstract
The present study focuses on investigating the magnetic properties and the critical particle size for developing sizable spontaneous magnetic moment of bare Au nanoparticles. Seven sets of bare Au nanoparticle assemblies, with diameters from 3.5 to 17.5 nm, were fabricated with the gas [...] Read more.
The present study focuses on investigating the magnetic properties and the critical particle size for developing sizable spontaneous magnetic moment of bare Au nanoparticles. Seven sets of bare Au nanoparticle assemblies, with diameters from 3.5 to 17.5 nm, were fabricated with the gas condensation method. Line profiles of the X-ray diffraction peaks were used to determine the mean particle diameters and size distributions of the nanoparticle assemblies. The magnetization curves M(Ha) reveal Langevin field profiles. Magnetic hysteresis was clearly revealed in the low field regime even at 300 K. Contributions to the magnetization from different size particles in the nanoparticle assemblies were considered when analyzing the M(Ha) curves. The results show that the maximum particle moment will appear in 2.4 nm Au particles. A similar result of the maximum saturation magnetization appearing in 2.3 nm Au particles is also concluded through analysis of the dependency of the saturation magnetization MP on particle size. The MP(d) curve departs significantly from the 1/d dependence, but can be described by a log-normal function. Magnetization can be barely detected for Au particles larger than 27 nm. Magnetic field induced Zeeman magnetization from the quantum confined Kubo gap opening appears in Au nanoparticles smaller than 9.5 nm in diameter. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Article
Apigenin Protects Endothelial Cells from Lipopolysaccharide (LPS)-Induced Inflammation by Decreasing Caspase-3 Activation and Modulating Mitochondrial Function
by Silvia Duarte, Daniel Arango, Arti Parihar, Patrice Hamel, Rumana Yasmeen and Andrea I. Doseff
Int. J. Mol. Sci. 2013, 14(9), 17664-17679; https://doi.org/10.3390/ijms140917664 - 28 Aug 2013
Cited by 65 | Viewed by 10907
Abstract
Acute and chronic inflammation is characterized by increased reactive oxygen species (ROS) production, dysregulation of mitochondrial metabolism and abnormal immune function contributing to cardiovascular diseases and sepsis. Clinical and epidemiological studies suggest potential beneficial effects of dietary interventions in inflammatory diseases but understanding [...] Read more.
Acute and chronic inflammation is characterized by increased reactive oxygen species (ROS) production, dysregulation of mitochondrial metabolism and abnormal immune function contributing to cardiovascular diseases and sepsis. Clinical and epidemiological studies suggest potential beneficial effects of dietary interventions in inflammatory diseases but understanding of how nutrients work remains insufficient. In the present study, we evaluated the effects of apigenin, an anti-inflammatory flavonoid abundantly found in our diet, in endothelial cells during inflammation. Here, we show that apigenin reduced lipopolysaccharide (LPS)-induced apoptosis by decreasing ROS production and the activity of caspase-3 in endothelial cells. Apigenin conferred protection against LPS-induced mitochondrial dysfunction and reestablished normal mitochondrial complex I activity, a major site of electron leakage and superoxide production, suggesting its ability to modulate endothelial cell metabolic function during inflammation. Collectively, these findings indicate that the dietary compound apigenin stabilizes mitochondrial function during inflammation preventing endothelial cell damage and thus provide new translational opportunities for the use of dietary components in the prevention and treatment of inflammatory diseases. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Article
Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice
by Shuna Yu, Jie Zheng, Zhengchen Jiang, Caixing Shi, Jin Li, Xiaodong Du, Hailiang Wang, Jiying Jiang and Xin Wang
Int. J. Mol. Sci. 2013, 14(9), 17680-17693; https://doi.org/10.3390/ijms140917680 - 29 Aug 2013
Cited by 22 | Viewed by 6009
Abstract
The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury [...] Read more.
The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury. Full article
(This article belongs to the Section Biochemistry)
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Article
Increased Chondrocyte Apoptosis Is Associated with Progression of Osteoarthritis in Spontaneous Guinea Pig Models of the Disease
by Zaitunnatakhin Zamli, Michael A. Adams, John F. Tarlton and Mohammed Sharif
Int. J. Mol. Sci. 2013, 14(9), 17729-17743; https://doi.org/10.3390/ijms140917729 - 29 Aug 2013
Cited by 41 | Viewed by 6932
Abstract
Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression [...] Read more.
Osteoarthritis (OA) is the most common joint disease characterised by degradation of articular cartilage and bone remodelling. For almost a decade chondrocyte apoptosis has been investigated as a possible mechanism of cartilage damage in OA, but its precise role in initiation and/or progression of OA remains to the determined. The aim of this study is to determine the role of chondrocyte apoptosis in spontaneous animal models of OA. Right tibias from six male Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs were collected at 10, 16, 24 and 30 weeks of age. Fresh-frozen sections of tibial epiphysis were microscopically scored for OA, and immunostained with caspase-3 and TUNEL for apoptotic chondrocytes. The DH strain had more pronounced cartilage damage than BS2, especially at 30 weeks. At this time point, the apoptotic chondrocytes were largely confined to the deep zone of articular cartilage (AC) with a greater percentage in the medial side of DH than BS2 (DH: 5.7%, 95% CI: 4.2–7.2), BS2: 4.8%, 95% CI: 3.8–5.8), p > 0.05). DH had a significant progression of chondrocyte death between 24 to 30 weeks during which time significant changes were observed in AC fibrillation, proteoglycan depletion and overall microscopic OA score. A strong correlation (p ≤ 0.01) was found between chondrocyte apoptosis and AC fibrillation (r = 0.3), cellularity (r = 0.4) and overall microscopic OA scores (r = 0.4). Overall, the rate of progression in OA and apoptosis over the study period was greater in the DH (versus BS2) and the medial AC (versus lateral). Chondrocyte apoptosis was higher at the later stage of OA development when the cartilage matrix was hypocellular and highly fibrillated, suggesting that chondrocyte apoptosis is a late event in OA. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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Article
Citrus Leaf Volatiles as Affected by Developmental Stage and Genetic Type
by Muhammad Azam, Qian Jiang, Bo Zhang, Changjie Xu and Kunsong Chen
Int. J. Mol. Sci. 2013, 14(9), 17744-17766; https://doi.org/10.3390/ijms140917744 - 29 Aug 2013
Cited by 49 | Viewed by 7237
Abstract
Major volatiles from young and mature leaves of different citrus types were analyzed by headspace-solid phase microextraction (HS-SPME)-GC-MS. A total of 123 components were identified form nine citrus cultivars, including nine aldehydes, 19 monoterpene hydrocarbons, 27 oxygenated monoterpenes, 43 sesquiterpene hydrocarbons, eight oxygenated [...] Read more.
Major volatiles from young and mature leaves of different citrus types were analyzed by headspace-solid phase microextraction (HS-SPME)-GC-MS. A total of 123 components were identified form nine citrus cultivars, including nine aldehydes, 19 monoterpene hydrocarbons, 27 oxygenated monoterpenes, 43 sesquiterpene hydrocarbons, eight oxygenated sesquiterpenes, two ketones, six esters and nine miscellaneous. Young leaves produced higher amounts of volatiles than mature leaves in most cultivars. The percentage of aldehyde and monoterpene hydrocarbons increased, whilst oxygenated monoterpenes and sesquiterpenes compounds decreased during leaf development. Linalool was the most abundant compound in young leaves, whereas limonene was the chief component in mature ones. Notably, linalool content decreased, while limonene increased, during leaf development in most cultivars. Leaf volatiles were also affected by genetic types. A most abundant volatile in one or several genotypes can be absent in another one(s), such as limonene in young leaves of lemon vs. Satsuma mandarin and β-terpinene in mature leaves of three genotypes vs. the other four. Compositional data was subjected to multivariate statistical analysis, and variations in leaf volatiles were identified and clustered into six groups. This research determining the relationship between production of major volatiles from different citrus varieties and leaf stages could be of use for industrial and culinary purposes. Full article
(This article belongs to the Section Biochemistry)
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Article
PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy
by Alain Ruffion, Marian Devonec, Denis Champetier, Myriam Decaussin-Petrucci, Claire Rodriguez-Lafrasse, Philippe Paparel, Paul Perrin and Virginie Vlaeminck-Guillem
Int. J. Mol. Sci. 2013, 14(9), 17767-17780; https://doi.org/10.3390/ijms140917767 - 29 Aug 2013
Cited by 32 | Viewed by 6989
Abstract
While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting [...] Read more.
While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
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Article
Biomolecular Characterization of Diazotrophs Isolated from the Tropical Soil in Malaysia
by Umme Aminun Naher, Radziah Othman, Mohammad Abdul Latif, Qurban Ali Panhwar, Puteri Aminatulhawa Megat Amaddin and Zulkifli H Shamsuddin
Int. J. Mol. Sci. 2013, 14(9), 17812-17829; https://doi.org/10.3390/ijms140917812 - 30 Aug 2013
Cited by 6 | Viewed by 7360
Abstract
This study was conducted to evaluate selected biomolecular characteristics of rice root-associated diazotrophs isolated from the Tanjong Karang rice irrigation project area of Malaysia. Soil and rice plant samples were collected from seven soil series belonging to order Inceptisol (USDA soil taxonomy). A [...] Read more.
This study was conducted to evaluate selected biomolecular characteristics of rice root-associated diazotrophs isolated from the Tanjong Karang rice irrigation project area of Malaysia. Soil and rice plant samples were collected from seven soil series belonging to order Inceptisol (USDA soil taxonomy). A total of 38 diazotrophs were isolated using a nitrogen-free medium. The biochemical properties of the isolated bacteria, such as nitrogenase activity, indoleacetic acid (IAA) production and sugar utilization, were measured. According to a cluster analysis of Jaccard’s similarity coefficients, the genetic similarities among the isolated diazotrophs ranged from 10% to 100%. A dendogram constructed using the unweighted pair-group method with arithmetic mean (UPGMA) showed that the isolated diazotrophs clustered into 12 groups. The genomic DNA rep-PCR data were subjected to a principal component analysis, and the first four principal components (PC) accounted for 52.46% of the total variation among the 38 diazotrophs. The 10 diazotrophs that tested highly positive in the acetylene reduction assay (ARA) were identified as Bacillus spp. (9 diazotrophs) and Burkholderia sp. (Sb16) using the partial 16S rRNA gene sequence analysis. In the analysis of the biochemical characteristics, three principal components were accounted for approximately 85% of the total variation among the identified diazotrophs. The examination of root colonization using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) proved that two of the isolated diazotrophs (Sb16 and Sb26) were able to colonize the surface and interior of rice roots and fixed 22%–24% of the total tissue nitrogen from the atmosphere. In general, the tropical soils (Inceptisols) of the Tanjong Karang rice irrigation project area in Malaysia harbor a diverse group of diazotrophs that exhibit a large variation of biomolecular characteristics. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
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Article
Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
by Patrizia Marinelli, Virginia Castillo and Salvador Ventura
Int. J. Mol. Sci. 2013, 14(9), 17830-17844; https://doi.org/10.3390/ijms140917830 - 30 Aug 2013
Cited by 10 | Viewed by 6736
Abstract
Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small [...] Read more.
Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small all-α protein that populates a molten globule (MG) at low pH. Despite the fact that this conformation maintains most of the domain native secondary structure, it progressively converts into β-sheet enriched and highly ordered amyloid fibrils. In this study, we investigated if 2,2,2-trifluoroethanol (TFE) induced conformational changes that affect URN1-FF amyloid formation. Despite TFE having been shown to induce or increase the aggregation of both globular and disordered proteins at moderate concentrations, we demonstrate here that in the case of URN1-FF it reinforces its intrinsic α-helical structure, which competes the formation of aggregated assemblies. In addition, we show that TFE induces conformational diversity in URN1-FF fibrils, in such a way that the fibrils formed in the presence and absence of the cosolvent represent different polymorphs. It is suggested that the effect of TFE on both the soluble and aggregated states of URN1-FF depends on its ability to facilitate hydrogen bonding. Full article
(This article belongs to the Special Issue Protein Folding)
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Icariin Protects Rat Cardiac H9c2 Cells from Apoptosis by Inhibiting Endoplasmic Reticulum Stress
by Qiufang Zhang, Hongliang Li, Shanshan Wang, Ming Liu, Yibin Feng and Xuanbin Wang
Int. J. Mol. Sci. 2013, 14(9), 17845-17860; https://doi.org/10.3390/ijms140917845 - 30 Aug 2013
Cited by 50 | Viewed by 7962
Abstract
Endoplasmic reticulum stress (ERS) is one of the mechanisms of apoptotic cell death. Inhibiting the apoptosis induced by ERS may be a novel therapeutic target in cardiovascular diseases. Icariin, a flavonoid isolated from Epimedium brevicornum Maxim, has been demonstrated to have cardiovascular protective [...] Read more.
Endoplasmic reticulum stress (ERS) is one of the mechanisms of apoptotic cell death. Inhibiting the apoptosis induced by ERS may be a novel therapeutic target in cardiovascular diseases. Icariin, a flavonoid isolated from Epimedium brevicornum Maxim, has been demonstrated to have cardiovascular protective effects, but its effects on ERS are unknown. In the present study, we focused on icariin and investigated whether it might protect the cardiac cell from apoptosis via inhibition of ERS. In H9c2 rat cardiomyoblast cells, pretreatment of icariin significantly inhibited cell apoptosis by tunicamycin, an ERS inducer. Icariin also decreased generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential and activation of caspase-3. Moreover, icariin inhibited upregulation of endoplasmic reticulum markers, GRP78, GRP94 and CHOP, elicited by tunicamycin. These results indicated that icariin could protect H9c2 cardiomyoblast cells from ERS-mitochondrial apoptosis in vitro, the mechanisms may be associated with its inhibiting of GRP78, GRP94 and CHOP and decreasing ROS generation directly. It may be a potential agent for treating cardiovascular disease. Full article
(This article belongs to the Section Biochemistry)
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Article
The DNA-Damage Response to γ-Radiation Is Affected by miR-27a in A549 Cells
by Andrea Di Francesco, Cristiano De Pittà, Francesca Moret, Vito Barbieri, Lucia Celotti and Maddalena Mognato
Int. J. Mol. Sci. 2013, 14(9), 17881-17896; https://doi.org/10.3390/ijms140917881 - 02 Sep 2013
Cited by 33 | Viewed by 7886
Abstract
Perturbations during the cell DNA-Damage Response (DDR) can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs), small non-coding RNAs that act as post-transcriptional regulators of gene expression. The oncogenic miR-27a is over-expressed in several tumors and, in [...] Read more.
Perturbations during the cell DNA-Damage Response (DDR) can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs), small non-coding RNAs that act as post-transcriptional regulators of gene expression. The oncogenic miR-27a is over-expressed in several tumors and, in the present study, we investigated its interaction with ATM, the gene coding for the main kinase of DDR pathway. Experimental validation to confirm miR-27a as a direct regulator of ATM was performed by site-direct mutagenesis of the luciferase reporter vector containing the 3'UTR of ATM gene, and by miRNA oligonucleotide mimics. We then explored the functional miR-27a/ATM interaction under biological conditions, i.e., during the response of A549 cells to ionizing radiation (IR) exposure. To evaluate if miR-27a over-expression affects IR-induced DDR activation in A549 cells we determined cell survival, cell cycle progression and DNA double-strand break (DSB) repair. Our results show that up-regulation of miR-27a promotes cell proliferation of non-irradiated and irradiated cells. Moreover, increased expression of endogenous mature miR-27a in A549 cells affects DBS rejoining kinetics early after irradiation. Full article
(This article belongs to the Collection Radiation Toxicity in Cells)
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Article
Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion
by Shen-Jie Lin, Kun-Hua Yu, Jhih-Ru Wu, Chin-Fa Lee, Cheng-Ping Jheng, Hau-Ren Chen and Cheng-I Lee
Int. J. Mol. Sci. 2013, 14(9), 17943-17957; https://doi.org/10.3390/ijms140917943 - 03 Sep 2013
Cited by 5 | Viewed by 6436
Abstract
Prion diseases or transmissible spongiform encephalopathies are a rare group of fatal neurodegenerative illnesses in humans and animals caused by misfolding of prion protein (PrP). Prion protein is a cell-surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed mostly in the central and peripheral nervous system, and [...] Read more.
Prion diseases or transmissible spongiform encephalopathies are a rare group of fatal neurodegenerative illnesses in humans and animals caused by misfolding of prion protein (PrP). Prion protein is a cell-surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed mostly in the central and peripheral nervous system, and this membrane-bound protein can be cleaved from the cell membranes by phosphoinositide phospholipase C. Numerous studies have investigated GPI-free recombinant PrP, but the role of GPI on misfolding of PrP is not well known. In this study, we synthesized a GPI analog that was covalently linking to a PrP S230C mutant, resulting in S230C-GPI. The structural changes in S230C-GPI upon binding to lipid vesicles composed of mixtures of the zwitterionic lipid (POPC) and the anionic lipid (POPG) were analyzed by circular dichroism spectroscopy, and the amyloid aggregation of S230C-GPI in the liberation from phospholipid vesicles was monitored by proteinase K-digestion assay. Our results indicate that S230C-GPI in the liberation of lipid vesicles has high tendency to misfold into amyloid fibrils, while the membrane-bound S230C-GPI proteins are highly stable and rarely convert into amyloid forms. In addition, the role of cholesterol in S230C-GPI was studied. The effect of GPI, cholesterol and phospholipid vesicles on misfolding of PrP is further discussed. Full article
(This article belongs to the Special Issue Protein Folding)
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Article
Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts
by Karin Zins, Anita Thomas, Trevor Lucas, Mouldy Sioud, Seyedhossein Aharinejad and Dietmar Abraham
Int. J. Mol. Sci. 2013, 14(9), 17958-17971; https://doi.org/10.3390/ijms140917958 - 03 Sep 2013
Cited by 12 | Viewed by 6698
Abstract
The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the [...] Read more.
The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Article
Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy
by Hye Jin Jin, Yun Kyung Bae, Miyeon Kim, Soon-Jae Kwon, Hong Bae Jeon, Soo Jin Choi, Seong Who Kim, Yoon Sun Yang, Wonil Oh and Jong Wook Chang
Int. J. Mol. Sci. 2013, 14(9), 17986-18001; https://doi.org/10.3390/ijms140917986 - 03 Sep 2013
Cited by 474 | Viewed by 25808
Abstract
Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation [...] Read more.
Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS)-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1α (IL-1α), IL-6, and IL-8 via angiopoietin-1 (Ang-1). Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA), we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy. Full article
(This article belongs to the Section Biochemistry)
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Celf1 Is Required for Formation of Endoderm-Derived Organs in Zebrafish
by Naoyuki Tahara, Yasumasa Bessho and Takaaki Matsui
Int. J. Mol. Sci. 2013, 14(9), 18009-18023; https://doi.org/10.3390/ijms140918009 - 03 Sep 2013
Cited by 5 | Viewed by 8041
Abstract
We recently reported that an RNA binding protein called Cugbp Elav-like family member 1 (Celf1) regulates somite symmetry and left-right patterning in zebrafish. In this report, we show additional roles of Celf1 in zebrafish organogenesis. When celf1 is knocked down by using an [...] Read more.
We recently reported that an RNA binding protein called Cugbp Elav-like family member 1 (Celf1) regulates somite symmetry and left-right patterning in zebrafish. In this report, we show additional roles of Celf1 in zebrafish organogenesis. When celf1 is knocked down by using an antisense morpholino oligonucleotides (MO), liver buds fail to form, and pancreas buds do not form a cluster, suggesting earlier defects in endoderm organogenesis. As expected, we found failures in endoderm cell growth and migration during gastrulation in embryos injected with celf1-MOs. RNA immunoprecipitation revealed that Celf1 binds to gata5 and cdc42 mRNAs which are known to be involved in cell growth and migration, respectively. Our results therefore suggest that Celf1 regulates proper organogenesis of endoderm-derived tissues by regulating the expression of such targets. Full article
(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)
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Article
Progressive Changes in Inflammatory and Matrix Adherence of Bronchial Epithelial Cells with Persistent Respiratory Syncytial Virus (RSV) Infection (Progressive Changes in RSV Infection)
by Xiaoai Liu, Xiaoqun Qin, Yang Xiang, Huijun Liu, Ge Gao, Ling Qin, Chi Liu and Xiangping Qu
Int. J. Mol. Sci. 2013, 14(9), 18024-18040; https://doi.org/10.3390/ijms140918024 - 03 Sep 2013
Cited by 8 | Viewed by 6725
Abstract
In addition to the acute manifestations of respiratory syncytial virus (RSV), persistent infection may be associated with long-term complications in the development of chronic respiratory diseases. To understand the mechanisms underlying RSV-induced long-term consequences, we established an in vitro RSV (strain A2) infection [...] Read more.
In addition to the acute manifestations of respiratory syncytial virus (RSV), persistent infection may be associated with long-term complications in the development of chronic respiratory diseases. To understand the mechanisms underlying RSV-induced long-term consequences, we established an in vitro RSV (strain A2) infection model using human bronchial epithelial (16HBE) cells that persists over four generations and analyzed cell inflammation and matrix adherence. Cells infected with RSV at multiplicity of infection (MOI) 0.0067 experienced cytolytic or abortive infections in the second generation (G2) or G3 but mostly survived up to G4. Cell morphology, leukocyte and matrix adherence of the cells did not change in G1 or G2, but subsequently, leukocyte adherence and cytokine/chemokine secretion, partially mediated by intercellular adhesion molecule-1 (ICAM-1), increased drastically, and matrix adherence, partially mediated by E-cadherin, decreased until the cells died. Tumor necrosis factor-α (TNF-α) secretion was inhibited by ICAM-1 antibody in infected-16HBE cells, suggesting that positive feedback between TNF-α secretion and ICAM-1 expression may be significant in exacerbated inflammation. These data demonstrate the susceptibility of 16HBE cells to RSV and their capacity to produce long-term progressive RSV infection, which may contribute to inflammation mobilization and epithelial shedding. Full article
(This article belongs to the Section Biochemistry)
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Article
Ziyuglycoside II Inhibits the Growth of Human Breast Carcinoma MDA-MB-435 Cells via Cell Cycle Arrest and Induction of Apoptosis through the Mitochondria Dependent Pathway
by Xue Zhu, Ke Wang, Kai Zhang, Biao Huang, Jue Zhang, Yi Zhang, Lan Zhu, Bin Zhou and Fanfan Zhou
Int. J. Mol. Sci. 2013, 14(9), 18041-18055; https://doi.org/10.3390/ijms140918041 - 03 Sep 2013
Cited by 41 | Viewed by 10024
Abstract
Ziyuglycoside II is one of the major active compounds of Sanguisorba officinalis L., which has a wide range of clinical applications including hemostasis, antibiosis, anti-inflammation and anti-oxidation. This study investigated the effect of ziyuglycoside II on the growth of human breast carcinoma MDA-MB-435 [...] Read more.
Ziyuglycoside II is one of the major active compounds of Sanguisorba officinalis L., which has a wide range of clinical applications including hemostasis, antibiosis, anti-inflammation and anti-oxidation. This study investigated the effect of ziyuglycoside II on the growth of human breast carcinoma MDA-MB-435 cells for the first time. The results showed that ziyuglycoside II could significantly inhibit the growth of MDA-MB-435 cells through blocking cell cycle progression at G0/G1 and S phase as well as via inducing cell apoptosis. Accumulation of reactive oxygen species (ROS) was observed in the progression of cell cycle arrest, which was associated with the increased expression of cell cycle regulating factors, p53 and p21. Subsequent apoptosis induced by ziyuglycoside II was accompanied with the activation of mitochondrial pathway, in particular a decreased mitochondrial membrane potential (MMP) as well as increased Bax/Bcl-2 ratio, cytochrome c release and the activity of caspase-3 and caspase-9. In conclusion, our study was the first to report that ziyuglycoside II has inhibitory effect on the growth of MDA-MB-435 cells, which might become a potential therapeutic approach of breast cancer in the future. Full article
(This article belongs to the Section Biochemistry)
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Article
X-Ray Induced DNA Damage and Repair in Germ Cells of PARP1−/− Male Mice
by Paola Villani, Anna Maria Fresegna, Roberto Ranaldi, Patrizia Eleuteri, Lorena Paris, Francesca Pacchierotti and Eugenia Cordelli
Int. J. Mol. Sci. 2013, 14(9), 18078-18092; https://doi.org/10.3390/ijms140918078 - 04 Sep 2013
Cited by 13 | Viewed by 7256
Abstract
Poly(ADP-ribose)polymerase-1 (PARP1) is a nuclear protein implicated in DNA repair, recombination, replication, and chromatin remodeling. The aim of this study was to evaluate possible differences between PARP1/ and wild-type mice regarding induction and repair of DNA lesions in irradiated male [...] Read more.
Poly(ADP-ribose)polymerase-1 (PARP1) is a nuclear protein implicated in DNA repair, recombination, replication, and chromatin remodeling. The aim of this study was to evaluate possible differences between PARP1/ and wild-type mice regarding induction and repair of DNA lesions in irradiated male germ cells. Comet assay was applied to detect DNA damage in testicular cells immediately, and two hours after 4 Gy X-ray irradiation. A similar level of spontaneous and radiation-induced DNA damage was observed in PARP1/ and wild-type mice. Conversely, two hours after irradiation, a significant level of residual damage was observed in PARP1/ cells only. This finding was particularly evident in round spermatids. To evaluate if PARP1 had also a role in the dynamics of H2AX phosphorylation in round spermatids, in which γ-H2AX foci had been shown to persist after completion of DNA repair, we carried out a parallel analysis of γ-H2AX foci at 0.5, 2, and 48 h after irradiation in wild-type and PARP1/ mice. No evidence was obtained of an effect of PARP1 depletion on H2AX phosphorylation induction and removal. Our results suggest that, in round spermatids, under the tested experimental conditions, PARP1 has a role in radiation-induced DNA damage repair rather than in long-term chromatin modifications signaled by phosphorylated H2AX. Full article
(This article belongs to the Collection Radiation Toxicity in Cells)
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Article
Demagnetization Treatment of Remanent Composite Microspheres Studied by Alternating Current Susceptibility Measurements
by Susanne Van Berkum and Ben H. Erné
Int. J. Mol. Sci. 2013, 14(9), 18093-18109; https://doi.org/10.3390/ijms140918093 - 04 Sep 2013
Cited by 2 | Viewed by 6599
Abstract
The magnetic remanence of silica microspheres with a low concentration of embedded cobalt ferrite nanoparticles is studied after demagnetization and remagnetization treatments. When the microspheres are dispersed in a liquid, alternating current (AC) magnetic susceptibility spectra reveal a constant characteristic frequency, corresponding to [...] Read more.
The magnetic remanence of silica microspheres with a low concentration of embedded cobalt ferrite nanoparticles is studied after demagnetization and remagnetization treatments. When the microspheres are dispersed in a liquid, alternating current (AC) magnetic susceptibility spectra reveal a constant characteristic frequency, corresponding to the rotational diffusion of the microparticles; this depends only on particle size and liquid viscosity, making the particles suitable as a rheological probe and indicating that interactions between the microspheres are weak. On the macroscopic scale, a sample with the dry microparticles is magnetically remanent after treatment in a saturating field, and after a demagnetization treatment, the remanence goes down to zero. The AC susceptibility of a liquid dispersion, however, characterizes the remanence on the scale of the individual microparticles, which does not become zero after demagnetization. The reason is that an individual microparticle contains only a relatively small number of magnetic units, so that even if they can be reoriented magnetically at random, the average vector sum of the nanoparticle dipoles is not negligible on the scale of the microparticle. In contrast, on the macroscopic scale, the demagnetization procedure randomizes the orientations of a macroscopic number of magnetic units, resulting in a remanent magnetization that is negligible compared to the saturation magnetization of the entire sample. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Article
Biohybrid Nanostructured Iron Oxide Nanoparticles and Satureja hortensis to Prevent Fungal Biofilm Development
by Ion Anghel, Alexandru Mihai Grumezescu, Alina Maria Holban, Anton Ficai, Alina Georgiana Anghel and Mariana Carmen Chifiriuc
Int. J. Mol. Sci. 2013, 14(9), 18110-18123; https://doi.org/10.3390/ijms140918110 - 04 Sep 2013
Cited by 83 | Viewed by 7702
Abstract
Cutaneous wounds are often superinfected during the healing process and this leads to prolonged convalescence and discomfort. Usage of suitable wound dressings is very important for an appropriate wound care leading to a correct healing. The aim of this study was to demonstrate [...] Read more.
Cutaneous wounds are often superinfected during the healing process and this leads to prolonged convalescence and discomfort. Usage of suitable wound dressings is very important for an appropriate wound care leading to a correct healing. The aim of this study was to demonstrate the influence of a nano-coated wound dressing (WD) on Candida albicans colonization rate and biofilm formation. The modified WD was achieved by submerging the dressing pieces into a nanofluid composed of functionalized magnetite nanoparticles and Satureja hortensis (SO) essential oil (EO). Chemical composition of the EO was established by GC-MS. The fabricated nanostructure was characterized by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Differential Thermal Analysis (DTA) and Fourier Transform-Infrared Spectroscopy (FT-IR). The analysis of the colonized surfaces using (Scanning Electron Microscopy) SEM revealed that C. albicans adherence and subsequent biofilm development are strongly inhibited on the surface of wound dressing fibers coated with the obtained nanofluid, comparing with regular uncoated materials. The results were also confirmed by the assay of the viable fungal cells embedded in the biofilm. Our data demonstrate that the obtained phytonanocoating improve the resistance of wound dressing surface to C. albicans colonization, which is often an etiological cause of local infections, impairing the appropriate wound healing. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Article
Pattern-Recognition Receptor Signaling Regulator mRNA Expression in Humans and Mice, and in Transient Inflammation or Progressive Fibrosis
by Roman Günthner, Vankayala Ramaiah Santhosh Kumar, Georg Lorenz, Hans-Joachim Anders and Maciej Lech
Int. J. Mol. Sci. 2013, 14(9), 18124-18147; https://doi.org/10.3390/ijms140918124 - 04 Sep 2013
Cited by 26 | Viewed by 6981
Abstract
The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs) are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2 [...] Read more.
The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs) are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2, CD180, SIGIRR, TANK, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, SHP1, SHP2, TOLLIP, IRF4, SIKE, NLRX1, ERBIN, CENTB1, and Clec4a2 in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. Additionally, we characterized their expression profiles in mononuclear blood cells upon bacterial endotoxin, which showed a consistent induction of A20, SOCS3, IRAK-M, and Clec4a2 in human and murine cells. Furthermore, we studied the expression pattern in transient kidney ischemia-reperfusion injury versus post-ischemic atrophy and fibrosis in mice. A20, CD180, ST2, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, IRF4, CENTB1, and Clec4a2 were all induced, albeit at different times of injury and repair. Progressive fibrosis was associated with a persistent induction of these factors. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to PRR-mediated innate immunity, which seems to be involved in tissue injury, tissue regeneration and in progressive tissue scarring. Full article
(This article belongs to the Section Biochemistry)
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Article
Synthesis and Characterizations of Melamine-Based Epoxy Resins
by Laura Ricciotti, Giuseppina Roviello, Oreste Tarallo, Fabio Borbone, Claudio Ferone, Francesco Colangelo, Michelina Catauro and Raffaele Cioffi
Int. J. Mol. Sci. 2013, 14(9), 18200-18214; https://doi.org/10.3390/ijms140918200 - 05 Sep 2013
Cited by 50 | Viewed by 12420
Abstract
A new, easy and cost-effective synthetic procedure for the preparation of thermosetting melamine-based epoxy resins is reported. By this innovative synthetic method, different kinds of resins can be obtained just by mixing the reagents in the presence of a catalyst without solvent and [...] Read more.
A new, easy and cost-effective synthetic procedure for the preparation of thermosetting melamine-based epoxy resins is reported. By this innovative synthetic method, different kinds of resins can be obtained just by mixing the reagents in the presence of a catalyst without solvent and with mild curing conditions. Two types of resins were synthesized using melamine and a glycidyl derivative (resins I) or by adding a silane derivative (resin II). The resins were characterized by means of chemical-physical and thermal techniques. Experimental results show that all the prepared resins have a good thermal stability, but differ for their mechanical properties: resin I exhibits remarkable stiffness with a storage modulus value up to 830 MPa at room temperature, while lower storage moduli were found for resin II, indicating that the presence of silane groups could enhance the flexibility of these materials. The resins show a pot life higher than 30 min, which makes these resins good candidates for practical applications. The functionalization with silane terminations can be exploited in the formulation of hybrid organic-inorganic composite materials. Full article
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Article
Bicistronic Gene Transfer Tools for Delivery of miRNAs and Protein Coding Sequences
by Michelle L. Stoller, Henry C. Chang and Donna M. Fekete
Int. J. Mol. Sci. 2013, 14(9), 18239-18255; https://doi.org/10.3390/ijms140918239 - 05 Sep 2013
Cited by 6 | Viewed by 8582
Abstract
MicroRNAs (miRNAs) are a category of small RNAs that modulate levels of proteins via post-transcriptional inhibition. Currently, a standard strategy to overexpress miRNAs is as mature miRNA duplexes, although this method is cumbersome if multiple miRNAs need to be delivered. Many of these [...] Read more.
MicroRNAs (miRNAs) are a category of small RNAs that modulate levels of proteins via post-transcriptional inhibition. Currently, a standard strategy to overexpress miRNAs is as mature miRNA duplexes, although this method is cumbersome if multiple miRNAs need to be delivered. Many of these miRNAs are found within introns and processed through the RNA polymerase II pathway. We have designed a vector to exploit this naturally-occurring intronic pathway to deliver the three members of the sensory-specific miR-183 family from an artificial intron. In one version of the vector, the downstream exon encodes the reporter (GFP) while another version encodes a fusion protein created between the transcription factor Atoh1 and the hemaglutinin epitope, to distinguish it from endogenous Atoh1. In vitro analysis shows that the miRNAs contained within the artificial intron are processed and bind to their targets with specificity. The genes downstream are successfully translated into protein and identifiable through immunofluorescence. More importantly, Atoh1 is proven functional through in vitro assays. These results suggest that this cassette allows expression of miRNAs and proteins simultaneously, which provides the opportunity for joint delivery of specific translational repressors (miRNA) and possibly transcriptional activators (transcription factors). This ability is attractive for future gene therapy use. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Article
Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures
by Na Young Jung, Kyung Hee Lee, Ran Won and Bae Hwan Lee
Int. J. Mol. Sci. 2013, 14(9), 18256-18268; https://doi.org/10.3390/ijms140918256 - 05 Sep 2013
Cited by 10 | Viewed by 6748
Abstract
Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC) and [...] Read more.
Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC) and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 µM) treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS) formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 µM) or ATTN (100 µM) significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF) fluorescence and levels of thiobarbiturate reactive substances (TBARS) were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Article
Magnetic Nanosystem for Cancer Therapy Using Oncocalyxone A, an Antitomour Secondary Metabolite Isolated from a Brazilian Plant
by Antônio C. H. Barreto, Vivian R. Santiago, Rafael M. Freire, Selma E. Mazzetto, Juliano C. Denardin, Giuseppe Mele, Igor M. Cavalcante, Maria E. N. P. Ribeiro, Nágila M. P. S. Ricardo, Tamara Gonçalves, Luigi Carbone, Telma L. G. Lemos, Otília D. L. Pessoa and Pierre B. A. Fechine
Int. J. Mol. Sci. 2013, 14(9), 18269-18283; https://doi.org/10.3390/ijms140918269 - 05 Sep 2013
Cited by 26 | Viewed by 7665
Abstract
This paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series [...] Read more.
This paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series of pharmacological properties: antioxidant, cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was associated with magnetite nanoparticles in order to obtain magnetic properties. The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and Magnetization curves. The MO-20 presented a size of about 30 nm and globular morphology. In addition, drug releasing experiments were performed, where it was observed the presence of the anomalous transport. The results found in this work showed the potential of onco A for future applications of the MO-20 as a new magnetic drug release nanosystem for cancer treatment. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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1066 KiB  
Article
Design of Phosphonium-Type Zwitterion as an Additive to Improve Saturated Water Content of Phase-Separated Ionic Liquid from Aqueous Phase toward Reversible Extraction of Proteins
by Yoritsugu Ito, Yuki Kohno, Nobuhumi Nakamura and Hiroyuki Ohno
Int. J. Mol. Sci. 2013, 14(9), 18350-18361; https://doi.org/10.3390/ijms140918350 - 05 Sep 2013
Cited by 27 | Viewed by 6663
Abstract
We designed phosphonium-type zwitterion (ZI) to control the saturated water content of separated ionic liquid (IL) phase in the hydrophobic IL/water biphasic systems. The saturated water content of separated IL phase, 1-butyl-3-methyimidazolium bis(trifluoromethanesulfonyl)imide, was considerably improved from 0.4 wt% to 62.8 wt% by [...] Read more.
We designed phosphonium-type zwitterion (ZI) to control the saturated water content of separated ionic liquid (IL) phase in the hydrophobic IL/water biphasic systems. The saturated water content of separated IL phase, 1-butyl-3-methyimidazolium bis(trifluoromethanesulfonyl)imide, was considerably improved from 0.4 wt% to 62.8 wt% by adding N,N,N-tripentyl-4-sulfonyl-1-butanephosphonium-type ZI (P555C4S). In addition, the maximum water content decreased from 62.8 wt% to 34.1 wt% by increasing KH2PO4/K2HPO4 salt content in upper aqueous phosphate buffer phase. Horse heart cytochrome c (cyt.c) was dissolved selectively in IL phase by improving the water content of IL phase, and spectroscopic analysis revealed that the dissolved cyt.c retained its higher ordered structure. Furthermore, cyt. c dissolved in IL phase was re-extracted again from IL phase to aqueous phase by increasing the concentration of inorganic salts of the buffer solution. Full article
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1436 KiB  
Article
The Role of Initial Oligomers in Amyloid Fibril Formation by Human Stefin B
by Ajda Taler-Verčič, Tiina Kirsipuu, Merlin Friedemann, Andra Noormägi, Mira Polajnar, Julia Smirnova, Magda Tušek Žnidarič, Matjaž Žganec, Miha Škarabot, Andrej Vilfan, Rosemary A. Staniforth, Peep Palumaa and Eva Žerovnik
Int. J. Mol. Sci. 2013, 14(9), 18362-18384; https://doi.org/10.3390/ijms140918362 - 05 Sep 2013
Cited by 12 | Viewed by 9918
Abstract
Oligomers are commonly observed intermediates at the initial stages of amyloid fibril formation. They are toxic to neurons and cause decrease in neural transmission and long-term potentiation. We describe an in vitro study of the initial steps in amyloid fibril formation by human [...] Read more.
Oligomers are commonly observed intermediates at the initial stages of amyloid fibril formation. They are toxic to neurons and cause decrease in neural transmission and long-term potentiation. We describe an in vitro study of the initial steps in amyloid fibril formation by human stefin B, which proved to be a good model system. Due to relative stability of the initial oligomers of stefin B, electrospray ionization mass spectrometry (ESI MS) could be applied in addition to size exclusion chromatography (SEC). These two techniques enabled us to separate and detect distinguished oligomers from the monomers: dimers, trimers, tetramers, up to decamers. The amyloid fibril formation process was followed at different pH and temperatures, including such conditions where the process was slow enough to detect the initial oligomeric species at the very beginning of the lag phase and those at the end of the lag phase. Taking into account the results of the lower-order oligomers transformations early in the process, we were able to propose an improved model for the stefin B fibril formation. Full article
(This article belongs to the Special Issue Protein Folding)
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1129 KiB  
Article
Flavonoids from Orostachys japonicus A. Berger Inhibit the Invasion of LnCaP Prostate Carcinoma Cells by Inactivating Akt and Modulating Tight Junctions
by Dong Yeok Shin, Won Sup Lee, Ji Hyun Jung, Su Hyun Hong, Cheol Park, Hye Jung Kim, Gi-Young Kim, Hye Jin Hwang, Gon Sup Kim, Jin-Myung Jung, Chung Ho Ryu, Sung Chul Shin, Soon Chan Hong and Yung Hyun Choi
Int. J. Mol. Sci. 2013, 14(9), 18407-18420; https://doi.org/10.3390/ijms140918407 - 06 Sep 2013
Cited by 20 | Viewed by 7564
Abstract
Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins [...] Read more.
Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway. Full article
(This article belongs to the Section Molecular Toxicology)
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Article
CREG Promotes the Proliferation of Human Umbilical Vein Endothelial Cells through the ERK/Cyclin E Signaling Pathway
by Jie Tao, Chenghui Yan, Xiaoxiang Tian, Shaowei Liu, Yang Li, Jian Zhang, Mingyu Sun, Xinliang Ma and Yaling Han
Int. J. Mol. Sci. 2013, 14(9), 18437-18456; https://doi.org/10.3390/ijms140918437 - 06 Sep 2013
Cited by 13 | Viewed by 7771
Abstract
Cellular repressor of E1A-stimulated genes (CREG) is a recently discovered secreted glycoprotein involved in homeostatic modulation. We previously reported that CREG is abundantly expressed in the adult vascular endothelium and dramatically downregulated in atherosclerotic lesions. In addition, CREG participates in the regulation of [...] Read more.
Cellular repressor of E1A-stimulated genes (CREG) is a recently discovered secreted glycoprotein involved in homeostatic modulation. We previously reported that CREG is abundantly expressed in the adult vascular endothelium and dramatically downregulated in atherosclerotic lesions. In addition, CREG participates in the regulation of apoptosis, inflammation and wound healing of vascular endothelial cells. In the present study, we attempted to investigate the effect of CREG on the proliferation of vascular endothelial cells and to decipher the underlying molecular mechanisms. Overexpression of CREG in human umbilical vein endothelial cells (HUVEC) was obtained by infection with adenovirus carrying CREG. HUVEC proliferation was investigated by flow cytometry and 5-bromo-2'-deoxy-uridine (BrdU) incorporation assays. The expressions of cyclins, cyclin-dependent kinases and signaling molecules were also examined. In CREG-overexpressing cells, we observed a marked increase in the proportion of the S and G2 population and a decrease in the G0/G1 phase population. The number of BrdU positively-stained cells also increased, obviously. Furthermore, silencing of CREG expression by specific short hairpin RNA effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVEC). CREG overexpression induced the expression of cyclin E in both protein and mRNA levels to regulate cell cycle progression. Further investigation using inhibitor blocking analysis identified that ERK activation mediated the CREG modulation of the proliferation and cyclin E expression in HUVEC. In addition, blocking vascular endothelial growth factor (VEGF) in CREG-overexpressed HUVEC and supplementation of VEGF in CREG knocked-down HUVEC identified that the pro-proliferative effect of CREG was partially mediated by VEGF-induced ERK/cyclin E activation. These results suggest a novel role of CREG to promote HUVEC proliferation through the ERK/cyclin E signaling pathway. Full article
(This article belongs to the Section Biochemistry)
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Article
Ibuprofen Rescues Abnormalities in Periodontal Tissues in Conditional Presenilin 1 and Presenilin 2 Double Knockout Mice
by Jiansheng Su, Jiamei Gu, Zhuo Dong and Bing Mei
Int. J. Mol. Sci. 2013, 14(9), 18457-18469; https://doi.org/10.3390/ijms140918457 - 06 Sep 2013
Cited by 9 | Viewed by 6242
Abstract
We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice) that exhibit symptoms of neurodegenerative diseases, especially Alzheimer’s disease, to investigate whether ibuprofen can rescue brain and periodontal tissue abnormalities by attenuating the [...] Read more.
We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice) that exhibit symptoms of neurodegenerative diseases, especially Alzheimer’s disease, to investigate whether ibuprofen can rescue brain and periodontal tissue abnormalities by attenuating the inflammatory response. Mandibles were dissected for alveolar bone-height analysis. Maxillae were fixed and decalcified for histological observation and osteoclast detection. ELISA measurements from the hippocampus, cortex, and gingiva of the mandibular incisor teeth were used to assay inflammatory mediators. We confirmed periodontal tissue abnormalities and inflammatory responses in brain and periodontal tissues in naive nine- and 12-month-old dKO mice. The other two groups of age-matched dKO mice that received 375-ppm ibuprofen treatment for six consecutive months exhibited significantly attenuated damage in periodontal tissues and reduction in several inflammation-related factors in brain and periodontal tissues. Our findings showed that the anti-inflammatory drug ibuprofen significantly decreased inflammation through the cyclooxygenase (COX) pathway in brain and periodontal tissues in dKO mice, and then attenuated abnormalities in periodontal tissues. This suggests that ibuprofen could be an ideal drug for preventing both nervous system and periodontal tissue damage caused by inflammatory responses. Full article
(This article belongs to the Section Biochemistry)
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Article
Green Fluorescent Protein (GFP)-Based Overexpression Screening and Characterization of AgrC, a Receptor Protein of Quorum Sensing in Staphylococcus aureus
by Lina Wang, Chunshan Quan, Baoquan Liu, Yongbin Xu, Pengchao Zhao, Wen Xiong and Shengdi Fan
Int. J. Mol. Sci. 2013, 14(9), 18470-18487; https://doi.org/10.3390/ijms140918470 - 06 Sep 2013
Cited by 16 | Viewed by 9590
Abstract
Staphylococcus aureus AgrC is an important component of the agr quorum-sensing system. AgrC is a membrane-embedded histidine kinase that is thought to act as a sensor for the recognition of environmental signals and the transduction of signals into the cytoplasm. However, the difficulty [...] Read more.
Staphylococcus aureus AgrC is an important component of the agr quorum-sensing system. AgrC is a membrane-embedded histidine kinase that is thought to act as a sensor for the recognition of environmental signals and the transduction of signals into the cytoplasm. However, the difficulty of expressing and purifying functional membrane proteins has drastically hindered in-depth understanding of the molecular structures and physiological functions of these proteins. Here, we describe the high-yield expression and purification of AgrC, and analyze its kinase activity. A C-terminal green fluorescent protein (GFP) fusion to AgrC served as a reporter for monitoring protein expression levels in real time. Protein expression levels were analyzed by the microscopic assessment of the whole-cell fluorescence. The expressed AgrC-GFP protein with a C-terminal His-tagged was purified using immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC) at yields of ≥10 mg/L, following optimization. We also assessed the effects of different detergents on membrane solubilization and AgrC kinase activity, and polyoxyethylene-(23)-lauryl-ether (Brij-35) was identified as the most suitable detergent. Furthermore, the secondary structural stability of purified AgrC was analyzed using circular dichroism (CD) spectroscopy. This study may serve as a general guide for improving the yields of other membrane protein preparations and selecting the appropriate detergent to stabilize membrane proteins for biophysical and biochemical analyses. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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496 KiB  
Article
Functional Diversity of Genes for the Biosynthesis of Paeoniflorin and Its Derivatives in Paeonia
by Yuan Yuan, Jun Yu, Chao Jiang, Minhui Li, Shufang Lin, Xumin Wang and Luqi Huang
Int. J. Mol. Sci. 2013, 14(9), 18502-18519; https://doi.org/10.3390/ijms140918502 - 09 Sep 2013
Cited by 23 | Viewed by 7888
Abstract
The Paeonia root, with or without bark, are considered vital traditional Chinese medicine materials; the examples are those of Bai Shao, Chi Shao, and Dan Pi. In this study, we examine 24 genes and their expressions involved in the biosynthesis of paeoniflorin and [...] Read more.
The Paeonia root, with or without bark, are considered vital traditional Chinese medicine materials; the examples are those of Bai Shao, Chi Shao, and Dan Pi. In this study, we examine 24 genes and their expressions involved in the biosynthesis of paeoniflorin and its derivatives, which are active compounds of the Paeonia root, in Paeonia lactiflora and P. suffruticosa, as well as other related plants, Punica granatum, Rhus radicans, and Coriaria nepalensis. Our phylogenetic analyses suggest that these genes have functional diversity, and analysis of the transcriptional level shows paeoniflorin and gallic acid biosynthesis-related genes exhibit different transcription profiles in flowers, carpels, bark-free roots, and bark of P. lactiflora. The correlation analysis of gene expression and active compound contents support the idea that hydroxymethylglutaryl-CoA synthase and phosphomevalonate kinase in the mevalonate pathway and 3-dehydroquinate dehydratase/shikimate dehydrogenase in shikimate biosynthesis are potentially closely related to the accumulation of paeoniflorin and benzoylpaeoniflorin. Coupling gene diversity with chemical analysis, we show that paeoniflorin and its derived aromatic amino acids are predominant in bark. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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754 KiB  
Article
Differential Polarization Nonlinear Optical Microscopy with Adaptive Optics Controlled Multiplexed Beams
by Masood Samim, Daaf Sandkuijl, Ian Tretyakov, Richard Cisek and Virginijus Barzda
Int. J. Mol. Sci. 2013, 14(9), 18520-18534; https://doi.org/10.3390/ijms140918520 - 09 Sep 2013
Cited by 14 | Viewed by 8120
Abstract
Differential polarization nonlinear optical microscopy has the potential to become an indispensable tool for structural investigations of ordered biological assemblies and microcrystalline aggregates. Their microscopic organization can be probed through fast and sensitive measurements of nonlinear optical signal anisotropy, which can be achieved [...] Read more.
Differential polarization nonlinear optical microscopy has the potential to become an indispensable tool for structural investigations of ordered biological assemblies and microcrystalline aggregates. Their microscopic organization can be probed through fast and sensitive measurements of nonlinear optical signal anisotropy, which can be achieved with microscopic spatial resolution by using time-multiplexed pulsed laser beams with perpendicular polarization orientations and photon-counting detection electronics for signal demultiplexing. In addition, deformable membrane mirrors can be used to correct for optical aberrations in the microscope and simultaneously optimize beam overlap using a genetic algorithm. The beam overlap can be achieved with better accuracy than diffraction limited point-spread function, which allows to perform polarization-resolved measurements on the pixel-by-pixel basis. We describe a newly developed differential polarization microscope and present applications of the differential microscopy technique for structural studies of collagen and cellulose. Both, second harmonic generation, and fluorescence-detected nonlinear absorption anisotropy are used in these investigations. It is shown that the orientation and structural properties of the fibers in biological tissue can be deduced and that the orientation of fluorescent molecules (Congo Red), which label the fibers, can be determined. Differential polarization microscopy sidesteps common issues such as photobleaching and sample movement. Due to tens of megahertz alternating polarization of excitation pulses fast data acquisition can be conveniently applied to measure changes in the nonlinear signal anisotropy in dynamically changing in vivo structures. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
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777 KiB  
Article
Photochemistry and Cytotoxicity Evaluation of Heptamethinecyanine Near Infrared (NIR) Dyes
by David S. Conceição, Diana P. Ferreira and Luís F. Vieira Ferreira
Int. J. Mol. Sci. 2013, 14(9), 18557-18571; https://doi.org/10.3390/ijms140918557 - 09 Sep 2013
Cited by 46 | Viewed by 9864
Abstract
The present study investigates the photochemical properties of potential photosensitizers for photodynamic therapy, namely four commercial heptamethinecyanine dyes (IR125, IR780, IR813, IR820). Spectroscopic studies were made by means of laser induced fluorescence and laser flash photolysis in order to obtain fluorescence quantum yields [...] Read more.
The present study investigates the photochemical properties of potential photosensitizers for photodynamic therapy, namely four commercial heptamethinecyanine dyes (IR125, IR780, IR813, IR820). Spectroscopic studies were made by means of laser induced fluorescence and laser flash photolysis in order to obtain fluorescence quantum yields and transient absorption spectra. Fluorescence lifetimes were also determined. The differences encountered were essentially related with the interaction of the sulfonate groups with the solvent, and also regarding the rigidification of the central bridge connecting the two nitrogen-containing heterocyclic groups. Transient absorption studies were performed both in aerated and oxygen free samples, to conclude about the formation of photoisomers and triplet state. For the four dyes under study, a cytotoxic evaluation in the dark and after irradiation was performed using HeLa cells as the model cell line, which revealed significant changes after irradiation mainly in IR125 and IR813 dyes. Confocal microscopy analysis showed that these dyes tend to enter to the intracellular space. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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244 KiB  
Article
Distribution of Alpha Thalassaemia Gene Variants in Diverse Ethnic Populations in Malaysia: Data from the Institute for Medical Research
by Rahimah Ahmad, Mohamed Saleem, Nisha Sabrina Aloysious, Punithawathy Yelumalai, Nurul Mohamed and Syahzuwan Hassan
Int. J. Mol. Sci. 2013, 14(9), 18599-18614; https://doi.org/10.3390/ijms140918599 - 10 Sep 2013
Cited by 41 | Viewed by 7341
Abstract
Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 [...] Read more.
Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, ––SEA, ––THAI, ––FIL; two single-gene deletions, α3.7 and –α4.2; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α3.7 deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the ––SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α3.7 deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α+ thalassaemia traits, 973 heterozygous α0 thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
879 KiB  
Article
Molecular Cloning and Functional Analysis of the Duck TLR4 Gene
by Wenming Zhao, Zhengyang Huang, Yang Chen, Yang Zhang, Guanghui Rong, Chunyu Mu, Qi Xu and Guohong Chen
Int. J. Mol. Sci. 2013, 14(9), 18615-18628; https://doi.org/10.3390/ijms140918615 - 10 Sep 2013
Cited by 16 | Viewed by 7079
Abstract
Toll-like receptor 4 (TLR4) recognizes pathogen-associated molecular patterns in some animals and has been shown to be closely associated with several diseases such as tumors, atherosclerosis, and asthma. However, its function in ducks is not clear. Alternative splicing of the TLR4 gene has [...] Read more.
Toll-like receptor 4 (TLR4) recognizes pathogen-associated molecular patterns in some animals and has been shown to be closely associated with several diseases such as tumors, atherosclerosis, and asthma. However, its function in ducks is not clear. Alternative splicing of the TLR4 gene has been identified in pigs, sheep, mice, and other species, but has not yet been reported in the duck. In this study, alternative splicing of the duck TLR4 gene was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Duck TLR4 gene (duTLR4, accession number: KF278109) was found to consist of 3367 nucleotides of coding sequence. An alternative splice form, TLR4-b, was identified and shown by alignment to retain the intron between exons 1 and 2. Real-time quantitative polymerase chain reaction (qPCR) analyses suggested that duTLR4-a (wild-type) mRNA is widely expressed in various healthy tissues, whereas TLR4-b is expressed at only low levels. Following stimulation of normal duck embryo fibroblasts with lipopolysaccharide, the expression of both isoforms initially increased and then decreased. Expression of the wild-type isoform subsequently increased again, while that of the variant remained low. The expression levels of wild-type TLR4 were further analyzed by transient transfection of a pcDNA3.1(+)-TLR4-a overexpression vector into duck embryo fibroblasts. qRT-PCR analyses showed that after stimulation with LPS and poly(I:C) the expression levels of IL-1β, IL6, and MHC II increased with a response-efficacy relationship. Our experimental results indicate that TLR4 plays an important role in resistance to both bacterial and viral infections in the duck. Full article
(This article belongs to the Section Biochemistry)
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529 KiB  
Article
High-Level Overproduction of Thermobifida Enzyme in Streptomyces lividans Using a Novel Expression Vector
by Jun-Xia Li, Long-Mei Zhao, Ru-Juan Wu, Zhao-Jun Zheng and Ri-Jun Zhang
Int. J. Mol. Sci. 2013, 14(9), 18629-18639; https://doi.org/10.3390/ijms140918629 - 10 Sep 2013
Cited by 13 | Viewed by 6424
Abstract
In this study, we constructed a novel Streptomyces-E.coli shuttle vector pZRJ362 combining the xylose isomerase promoter and amylase terminator. A gene encoding the endoglucanase Cel6A in Thermobifida fusca was amplified by PCR, cloned into Streptomyces lividans host strain using the novel [...] Read more.
In this study, we constructed a novel Streptomyces-E.coli shuttle vector pZRJ362 combining the xylose isomerase promoter and amylase terminator. A gene encoding the endoglucanase Cel6A in Thermobifida fusca was amplified by PCR, cloned into Streptomyces lividans host strain using the novel expression vector and Pichia pastoris GS115 host strain using the vector pPICZα-C, respectively. Afterwards, the expression pattern and the maximum expression level were comparatively studied in both expression systems. The maximum enzyme activity of Cel6A-(His)6 secreted in S. lividans supernatant after 84-h of cultivation amounted to 5.56 U/mL, which was dramatically higher than that secreted in P. pastoris about 1.4 U/mL after 96-h of cultivation. The maximum expression level of Cel6A-(His)6 in S. lividans supernatant reached up to 173 mg/L after 84-h of cultivation. The endoglucanase activity staining SDS-PAGE showed that there were some minor proteins in S. lividans supernatant which may be the Cel6A derivant by proteolytic degradation, while there was no proteolytic product detected in supernatant of P. pastoris. Full article
(This article belongs to the Section Biochemistry)
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2207 KiB  
Article
Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension
by Stella P. Hartono, Bruce E. Knudsen, Adeel S. Zubair, Karl A. Nath, Stephen J. Textor, Lilach O. Lerman and Joseph P. Grande
Int. J. Mol. Sci. 2013, 14(9), 18640-18656; https://doi.org/10.3390/ijms140918640 - 10 Sep 2013
Cited by 17 | Viewed by 7200
Abstract
Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic [...] Read more.
Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Article
Neuroprotective Effect of Arctigenin via Upregulation of P-CREB in Mouse Primary Neurons and Human SH-SY5Y Neuroblastoma Cells
by Nan Zhang, Qingping Wen, Lu Ren, Wenbo Liang, Yang Xia, Xiaodan Zhang, Dan Zhao, Dong Sun, Yv Hu, Haiguang Hao, Yaping Yan, Guangxian Zhang, Jingxian Yang and Tingguo Kang
Int. J. Mol. Sci. 2013, 14(9), 18657-18669; https://doi.org/10.3390/ijms140918657 - 10 Sep 2013
Cited by 32 | Viewed by 8994
Abstract
Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and [...] Read more.
Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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2017 KiB  
Article
The MAPKKK Gene Family in Gossypium raimondii: Genome-Wide Identification, Classification and Expression Analysis
by Zujun Yin, Junjuan Wang, Delong Wang, Weili Fan, Shuai Wang and Wuwei Ye
Int. J. Mol. Sci. 2013, 14(9), 18740-18757; https://doi.org/10.3390/ijms140918740 - 11 Sep 2013
Cited by 36 | Viewed by 7871
Abstract
Mitogen-activated protein kinase (MAPK) cascades are conserved signal transduction pathways in all eukaryotic organisms. MAPKKKs (MAPK kinase kinases) operate at the top levels of these cascades. Recently, this family of genes has been systematically investigated in Arabidopsis, rice and maize, but has not [...] Read more.
Mitogen-activated protein kinase (MAPK) cascades are conserved signal transduction pathways in all eukaryotic organisms. MAPKKKs (MAPK kinase kinases) operate at the top levels of these cascades. Recently, this family of genes has been systematically investigated in Arabidopsis, rice and maize, but has not yet been characterized in cotton. In this study, we identified 78 putative MAPKKK genes in the genome of the diploid cotton, Gossypium raimondii. They were classified into three subfamilies, of which 12 were ZIK, 22 were MEKK and 44 were Raf. The ZIK and MEKK genes displayed a scattered genomic distribution across 11 of the 13 chromosomes, whereas Raf genes were distributed across the entire genome. Their conserved patterns observed for introns and additional domains were consistent with the evolutionary relationships inferred from the phylogenetic analysis within subfamily. Transcriptome sequencing data were used to investigate their transcript profiles in mature leaves, 0 day and 3 days post-anthesis (DPA) ovules. Sixty MAPKKK genes were expressed, of which 41 were strongly expressed in mature leaves. Twelve MAPKKK genes were more highly expressed in 3-DPA ovules than in 0-DPA ovules. Our results provide a foundation for future evolutionary and functional characterizations of MAPKKK genes in cotton and probably other Gossypium plants. Full article
(This article belongs to the Section Biochemistry)
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585 KiB  
Article
Synthesis and Thermotropic Studies of a New Series of Teraryl Liquid Crystals 2-(4'-Alkoxybiphen-4-yl)-5-Cyanopyridines
by Win-Long Chia and Xue-Ming Lin
Int. J. Mol. Sci. 2013, 14(9), 18809-18823; https://doi.org/10.3390/ijms140918809 - 12 Sep 2013
Cited by 8 | Viewed by 5948
Abstract
A new series of teraryl 2-(4'-alkoxybiphen-4-yl)-5-cyanopyridines (nO-PPPyCN, n = 2–8) compounds, bearing a cyanopyridine terminus, were synthesized using a short 2-step reaction with overall yields between 33% and 69%. Spectral analyses were in accord with the expected structures. Thermotropic behavior of [...] Read more.
A new series of teraryl 2-(4'-alkoxybiphen-4-yl)-5-cyanopyridines (nO-PPPyCN, n = 2–8) compounds, bearing a cyanopyridine terminus, were synthesized using a short 2-step reaction with overall yields between 33% and 69%. Spectral analyses were in accord with the expected structures. Thermotropic behavior of the teraryl compounds was investigated using polarised optical microscopy and differential scanning calorimetry. All compounds exhibited both enantiotropic nematic and smectic A phases, with an additional enantiotropic smectic C phase when n = 7 and 8. Polymesomorphism appears to be a common behavior in this series of linear liquid crystal compounds. Full article
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698 KiB  
Article
A Facile and Efficient Synthesis of Diaryl Amines or Ethers under Microwave Irradiation at Presence of KF/Al2O3 without Solvent and Their Anti-Fungal Biological Activities against Six Phytopathogens
by Liang-Zhu Huang, Pan Han, You-Qiang Li, Ying-Meng Xu, Tao Zhang and Zhen-Ting Du
Int. J. Mol. Sci. 2013, 14(9), 18850-18860; https://doi.org/10.3390/ijms140918850 - 12 Sep 2013
Cited by 14 | Viewed by 7138
Abstract
A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to [...] Read more.
A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to substrates and simple workup procedure. At the same time, their antifungal biological activities against six phytopathogen were evaluated. Most of the compounds (3b, 3c, 3go) are more potent than thiophannate-methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether moiety may be helpful in finding a fungicide against Magnaporthe oryzae. Full article
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Article
Oleic Acid Increases Synthesis and Secretion of VEGF in Rat Vascular Smooth Muscle Cells: Role of Oxidative Stress and Impairment in Obesity
by Gabriella Doronzo, Michela Viretto, Cristina Barale, Isabella Russo, Luigi Mattiello, Giovanni Anfossi and Mariella Trovati
Int. J. Mol. Sci. 2013, 14(9), 18861-18880; https://doi.org/10.3390/ijms140918861 - 13 Sep 2013
Cited by 11 | Viewed by 7833
Abstract
Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF) action on vascular smooth muscle cells (VSMC). Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic [...] Read more.
Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF) action on vascular smooth muscle cells (VSMC). Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic acid (OA) enhances VEGF synthesis/secretion in VSMC, and whether this effect is impaired in obesity. In cultured aortic VSMC from lean and obese Zucker rats (LZR and OZR, respectively) we measured the influence of OA on VEGF-A synthesis/secretion, signaling molecules and reactive oxygen species (ROS). In VSMC from LZR we found the following: (a) OA increases VEGF-A synthesis/secretion by a mechanism blunted by inhibitors of Akt, mTOR, ERK-1/2, PKC-beta, NADPH-oxidase and mitochondrial electron transport chain complex; (b) OA activates the above mentioned signaling pathways and increases ROS; (c) OA-induced activation of PKC-beta enhances oxidative stress, which activates signaling pathways responsible for the increased VEGF synthesis/secretion. In VSMC from OZR, which present enhanced baseline oxidative stress, the above mentioned actions of OA on VEGF-A, signaling pathways and ROS are impaired: this impairment is reproduced in VSMC from LZR by incubation with hydrogen peroxide. Thus, in OZR chronically elevated oxidative stress causes a resistance to the action on VEGF that OA exerts in LZR by increasing ROS. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Article
Spectroscopic Studies of Model Photo-Receptors: Validation of a Nanosecond Time-Resolved Micro-Spectrophotometer Design Using Photoactive Yellow Protein and α-Phycoerythrocyanin
by Namrta Purwar, Jason Tenboer, Shailesh Tripathi and Marius Schmidt
Int. J. Mol. Sci. 2013, 14(9), 18881-18898; https://doi.org/10.3390/ijms140918881 - 13 Sep 2013
Cited by 8 | Viewed by 6936
Abstract
Time-resolved spectroscopic experiments have been performed with protein in solution and in crystalline form using a newly designed microspectrophotometer. The time-resolution of these experiments can be as good as two nanoseconds (ns), which is the minimal response time of the image intensifier used. [...] Read more.
Time-resolved spectroscopic experiments have been performed with protein in solution and in crystalline form using a newly designed microspectrophotometer. The time-resolution of these experiments can be as good as two nanoseconds (ns), which is the minimal response time of the image intensifier used. With the current setup, the effective time-resolution is about seven ns, determined mainly by the pulse duration of the nanosecond laser. The amount of protein required is small, on the order of 100 nanograms. Bleaching, which is an undesirable effect common to photoreceptor proteins, is minimized by using a millisecond shutter to avoid extensive exposure to the probing light. We investigate two model photoreceptors, photoactive yellow protein (PYP), and α-phycoerythrocyanin (α-PEC), on different time scales and at different temperatures. Relaxation times obtained from kinetic time-series of difference absorption spectra collected from PYP are consistent with previous results. The comparison with these results validates the capability of this spectrophotometer to deliver high quality time-resolved absorption spectra. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
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Article
Emulsifying Activity and Stability of a Non-Toxic Bioemulsifier Synthesized by Microbacterium sp. MC3B-10
by Juan Carlos Camacho-Chab, Jean Guézennec, Manuel Jesús Chan-Bacab, Elvira Ríos-Leal, Corinne Sinquin, Raquel Muñiz-Salazar, Susana Del C. De la Rosa-García, Manuela Reyes-Estebanez and Benjamín Otto Ortega-Morales
Int. J. Mol. Sci. 2013, 14(9), 18959-18972; https://doi.org/10.3390/ijms140918959 - 13 Sep 2013
Cited by 52 | Viewed by 9140
Abstract
A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan [...] Read more.
A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 °C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)
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Article
A Polymorphism at the 3'-UTR Region of the Aromatase Gene Is Associated with the Efficacy of the Aromatase Inhibitor, Anastrozole, in Metastatic Breast Carcinoma
by Lei Liu, Yu-Xian Bai, Jian-Hua Zhou, Xiu-Wei Sun, Hong Sui, Wen-Jie Zhang, Heng-Heng Yuan, Rui Xie, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Yan-Jing Li, Jing-Xuan Wang, Shu Zhao and Qing-Yuan Zhang
Int. J. Mol. Sci. 2013, 14(9), 18973-18988; https://doi.org/10.3390/ijms140918973 - 13 Sep 2013
Cited by 30 | Viewed by 6815
Abstract
Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the [...] Read more.
Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-β-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole. Full article
(This article belongs to the Section Biochemistry)
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Short Note
Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion
by Nadja Schulz, Oliver Kluth, Martin Jastroch and Annette Schürmann
Int. J. Mol. Sci. 2013, 14(9), 18989-18998; https://doi.org/10.3390/ijms140918989 - 16 Sep 2013
Cited by 13 | Viewed by 7382
Abstract
An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. A rise in plasma glucose leads to increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway, one or more [...] Read more.
An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. A rise in plasma glucose leads to increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway, one or more amplifying pathways—activated by amino acids or fatty acid—enhance secretion by promoting insulin granule recruitment to, and priming at, the plasma membrane. The aim of this study was to clarify the impact of the mitochondrial respiratory activity on fatty acid-induced insulin secretion that was assessed by an extracellular flux analyzer. Treatment of isolated mouse islets with glucose (20 mM) increased insulin secretion 18-fold and correlated with ATP-synthesizing respiration. Furthermore, oxygen consumption rate (OCR) significantly increased by 62% in response to glucose, whereas the addition of palmitate resulted only in a minor increase of OCR at both 2.8 mM (11%) and 20 mM glucose (21%). The addition of palmitate showed a pronounced increase of coupling efficiency (CE) at 2.8 mM glucose but no further insulin secretion. However, treatment with palmitate at 20 mM glucose increased insulin secretion about 32-fold accompanied by a small increase in CE. Thus, fatty acid induced respiration has a minor impact on insulin secretion. Our data clearly demonstrate that fatty acids in contrast to glucose play a minor role for respiration-mediated insulin secretion. In the presence of high glucose, fatty acids contribute partially to amplifying pathways of insulin secretion by further increasing mitochondrial activity in the islets of Langerhans. Full article
(This article belongs to the Section Molecular Recognition)
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Article
Exposure to Enriched Environment Decreases Neurobehavioral Deficits Induced by Neonatal Glutamate Toxicity
by Gabor Horvath, Dora Reglodi, Gyongyver Vadasz, Jozsef Farkas and Peter Kiss
Int. J. Mol. Sci. 2013, 14(9), 19054-19066; https://doi.org/10.3390/ijms140919054 - 16 Sep 2013
Cited by 24 | Viewed by 7525
Abstract
Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG) is a [...] Read more.
Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG) is a commonly used taste enhancer causing excitotoxic effects when given in newborn animals. We have previously demonstrated that MSG leads to a delay in neurobehavioral development, as shown by the delayed appearance of neurological reflexes and maturation of motor coordination. In the present study we aimed at investigating whether environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal MSG treatment. Newborn pups were treated with MSG subcutaneously on postnatal days 1, 5 and 9. For environmental enrichment, we placed rats in larger cages, supplemented with different toys that were altered daily. Normal control and enriched control rats received saline treatment only. Physical parameters such as weight, day of eye opening, incisor eruption and ear unfolding were recorded. Animals were observed for appearance of reflexes such as negative geotaxis, righting reflexes, fore- and hindlimb grasp, fore- and hindlimb placing, sensory reflexes and gait. In cases of negative geotaxis, surface righting and gait, the time to perform the reflex was also recorded daily. For examining motor coordination, we performed grid walking, footfault, rope suspension, rota-rod, inclined board and walk initiation tests. We found that enriched environment alone did not lead to marked alterations in the course of development. On the other hand, MSG treatment caused a slight delay in reflex development and a pronounced delay in weight gain and motor coordination maturation. This delay in most signs and tests could be reversed by enriched environment: MSG-treated pups kept under enriched conditions showed no weight retardation, no reflex delay in some signs and performed better in most coordination tests. These results show that environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal excitotoxicity. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology)
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Article
Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding
by Ta-Jen Hung, Wei-Tang Chang, Noboru Tomiya, Yuan-Chuan Lee, Hao-Teng Chang, Chien-Jung Chen, Ping-Hsueh Kuo, Tan-chi Fan and Margaret Dah-Tsyr Chang
Int. J. Mol. Sci. 2013, 14(9), 19067-19085; https://doi.org/10.3390/ijms140919067 - 16 Sep 2013
Cited by 2 | Viewed by 6644
Abstract
Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on [...] Read more.
Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on bronchial epithelial Beas-2B cells. In this study, we demonstrate that the binding of EDN to cells requires cell surface glycosaminoglycans (GAGs), and the binding strength between EDN and GAGs depends on the sulfation levels of GAGs. Furthermore, in silico computer modeling and in vitro binding assays suggest critical roles for the following basic amino acids located within heparin binding regions (HBRs) of EDN 34QRRCKN39 (HBR1), 65NKTRKN70 (HBR2), and 113NRDQRRD119 (HBR3) and in particular Arg35, Arg36, and Arg38 within HBR1, and Arg114 and Arg117 within HBR3. Our data suggest that sulfated GAGs play a major role in EDN binding, which in turn may be related to the cellular effects of EDN. Full article
(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)
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Article
Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters
by Attila Kertész, Mariann Bombicz, Daniel Priksz, Jozsef Balla, Gyorgy Balla, Rudolf Gesztelyi, Balazs Varga, David D. Haines, Arpad Tosaki and Bela Juhasz
Int. J. Mol. Sci. 2013, 14(9), 19086-19108; https://doi.org/10.3390/ijms140919086 - 17 Sep 2013
Cited by 13 | Viewed by 8516
Abstract
The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as [...] Read more.
The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Article
Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation
by Joana S. Cristóvão, Sónia S. Leal, Isabel Cardoso and Cláudio M. Gomes
Int. J. Mol. Sci. 2013, 14(9), 19128-19145; https://doi.org/10.3390/ijms140919128 - 17 Sep 2013
Cited by 5 | Viewed by 7290
Abstract
Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein [...] Read more.
Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation. Full article
(This article belongs to the Special Issue Protein Folding)
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369 KiB  
Article
Probing Antigen-Antibody Interaction Using Fluorescence Coupled Capillary Electrophoresis
by Jianhao Wang, Lin Qiu, Cheli Wang, Yue Zhang, Jingyan Li, Jiang Xia and Pengju Jiang
Int. J. Mol. Sci. 2013, 14(9), 19146-19154; https://doi.org/10.3390/ijms140919146 - 17 Sep 2013
Cited by 11 | Viewed by 7004
Abstract
In this report, the use of fluorescence detection coupled capillary electrophoresis (CE-FL) allowed us to fully characterize the antigen-antibody interaction. CE-FL allowed separation of unbound quantum dots (QDs) and ligand bound QDs and also revealed an ordered assembly of biomolecules on QDs. Further, [...] Read more.
In this report, the use of fluorescence detection coupled capillary electrophoresis (CE-FL) allowed us to fully characterize the antigen-antibody interaction. CE-FL allowed separation of unbound quantum dots (QDs) and ligand bound QDs and also revealed an ordered assembly of biomolecules on QDs. Further, we observed FRET from QDs donor to DyLight acceptor, which were covalently conjugated with human IgG and goat anti-human IgG, respectively. The immunocomplex was formed and the mutual affinity of the antigen and antibody brought QDs and DyLight close enough to allow FRET to occur. This novel CE-based technique can be easily extended to other FRET systems based on QDs and may have potential application in the detection of antibodies. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Article
Formation of Apatite Coatings on an Artificial Ligament Using a Plasma- and Precursor-Assisted Biomimetic Process
by Hirotaka Mutsuzaki, Yoshiro Yokoyama, Atsuo Ito and Ayako Oyane
Int. J. Mol. Sci. 2013, 14(9), 19155-19168; https://doi.org/10.3390/ijms140919155 - 17 Sep 2013
Cited by 21 | Viewed by 6310
Abstract
A plasma- and precursor-assisted biomimetic process utilizing plasma and alternate dipping treatments was applied to a Leed-Keio artificial ligament to produce a thin coating of apatite in a supersaturated calcium phosphate solution. Following plasma surface modification, the specimen was alternately dipped in calcium [...] Read more.
A plasma- and precursor-assisted biomimetic process utilizing plasma and alternate dipping treatments was applied to a Leed-Keio artificial ligament to produce a thin coating of apatite in a supersaturated calcium phosphate solution. Following plasma surface modification, the specimen was alternately dipped in calcium and phosphate ion solutions three times (alternate dipping treatment) to create a precoating containing amorphous calcium phosphate (ACP) which is an apatite precursor. To grow an apatite layer on the ACP precoating, the ACP-precoated specimen was immersed for 24 h in a simulated body fluid with ion concentrations approximately equal to those in human blood plasma. The plasma surface modification was necessary to create an adequate apatite coating and to improve the coating adhesion depending on the plasma power density. The apatite coating prepared using the optimized conditions formed a thin-film that covered the entire surface of the artificial ligament. The resulting apatite-coated artificial ligament should exhibit improved osseointegration within the bone tunnel and possesses great potential for use in ligament reconstructions. Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
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Article
Involvement of Calcium-Mediated Reactive Oxygen Species in Inductive GRP78 Expression by Geldanamycin in 9L Rat Brain Tumor Cells
by Fang-Chun Sun, Hsin-Yi Shyu, Meng-Shiou Lee, Meng-Shiunn Lee and Yiu-Kay Lai
Int. J. Mol. Sci. 2013, 14(9), 19169-19185; https://doi.org/10.3390/ijms140919169 - 18 Sep 2013
Cited by 6 | Viewed by 8075
Abstract
Treatment with geldanamycin (GA) leads to an increase in [Ca2+]c and the production of reactive oxygen species (ROS) in rat brain tumor 9L RBT cells. GA-exerted calcium signaling was blocked by BAPTA/AM and EGTA. The effect of GA on [Ca [...] Read more.
Treatment with geldanamycin (GA) leads to an increase in [Ca2+]c and the production of reactive oxygen species (ROS) in rat brain tumor 9L RBT cells. GA-exerted calcium signaling was blocked by BAPTA/AM and EGTA. The effect of GA on [Ca2+]c was significantly reduced in the presence of thapsigargin (TG) and ruthenium red (RR). GA-induced GRP78 expression is significantly decreased in the presence of BAPTA/AM, EGTA and RR, suggesting that the calcium influx from the extracellular space and intracellular calcium store oscillations are contributed to by the calcium mobilization and GRP78 expression induced by GA. The induced GRP78 expression is sensitive to added U73122 and Ro-31-8425, pinpointing the involvement of phospholipase C (PLC) and protein kinase C (PKC) in GA-induced endoplasmic reticulum (ER) stress. The antioxidants N-acetylcysteine (NAC), BAPTA/AM, EGTA and H7 also have significant inhibitory effects on ROS generation. Finally, neither H7 nor NAC was able to affect the calcium response elicited by GA. Our results suggest that the causal signaling cascade during GA-inducted GRP78 expression occurs via a pathway that connects PLC to cytoplasmic calcium increase, PKC activation and, then, finally, ROS generation. Our data provides new insights into the influence of GA on ER stress response in 9L RBT cells. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Article
Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells
by Su-Tze Chou, Wen-Lun Chang, Chen-Tien Chang, Shih-Lan Hsu, Yu-Che Lin and Ying Shih
Int. J. Mol. Sci. 2013, 14(9), 19186-19201; https://doi.org/10.3390/ijms140919186 - 18 Sep 2013
Cited by 98 | Viewed by 11974
Abstract
Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available [...] Read more.
Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%). CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities; however, cis-2-methoxycinnamic acid did not demonstrate tyrosinase inhibitory activity. In murine B16 melanoma cells stimulated with α-melanocyte-stimulating hormone (α-MSH), CC-EO and cinnamaldehyde not only reduced the melanin content and tyrosinase activity of the cells but also down-regulated tyrosinase expression without exhibiting cytotoxicity. Moreover, CC-EO and cinnamaldehyde decreased thiobarbituric acid-reactive substance (TBARS) levels and restored glutathione (GSH) and catalase activity in the α-MSH-stimulated B16 cells. These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities that are coupled with antioxidant properties. Therefore, CC-EO may be a good source of skin-whitening agents and may have potential as an antioxidant in the future development of complementary and alternative medicine-based aromatherapy. Full article
(This article belongs to the Section Biochemistry)
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Article
Analysis of Gln223Agr Polymorphism of Leptin Receptor Gene in Type II Diabetic Mellitus Subjects among Malaysians
by Ali Etemad, Vasudevan Ramachandran, Seyyed Reza Pishva, Farzad Heidari, Ahmad Fazli Abdul Aziz, Ahmad Khairuddin Mohamed Yusof, Chong Pei Pei and Patimah Ismail
Int. J. Mol. Sci. 2013, 14(9), 19230-19244; https://doi.org/10.3390/ijms140919230 - 18 Sep 2013
Cited by 29 | Viewed by 7420
Abstract
Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play [...] Read more.
Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05). Full article
(This article belongs to the Section Biochemistry)
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Article
Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells
by Bin Hu, Alicia J El Haj and Jon Dobson
Int. J. Mol. Sci. 2013, 14(9), 19276-19293; https://doi.org/10.3390/ijms140919276 - 23 Sep 2013
Cited by 65 | Viewed by 9055
Abstract
Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and [...] Read more.
Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors—platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Article
Transcriptome-Wide Single Nucleotide Polymorphisms (SNPs) for Abalone (Haliotis midae): Validation and Application Using GoldenGate Medium-Throughput Genotyping Assays
by Aletta Bester-Van Der Merwe, Sonja Blaauw, Jana Du Plessis and Rouvay Roodt-Wilding
Int. J. Mol. Sci. 2013, 14(9), 19341-19360; https://doi.org/10.3390/ijms140919341 - 23 Sep 2013
Cited by 17 | Viewed by 7252
Abstract
Haliotis midae is one of the most valuable commercial abalone species in the world, but is highly vulnerable, due to exploitation, habitat destruction and predation. In order to preserve wild and cultured stocks, genetic management and improvement of the species has become crucial. [...] Read more.
Haliotis midae is one of the most valuable commercial abalone species in the world, but is highly vulnerable, due to exploitation, habitat destruction and predation. In order to preserve wild and cultured stocks, genetic management and improvement of the species has become crucial. Fundamental to this is the availability and employment of molecular markers, such as microsatellites and Single Nucleotide Polymorphisms (SNPs) . Transcriptome sequences generated through sequencing-by-synthesis technology were utilized for the in vitro and in silico identification of 505 putative SNPs from a total of 316 selected contigs. A subset of 234 SNPs were further validated and characterized in wild and cultured abalone using two Illumina GoldenGate genotyping assays. Combined with VeraCode technology, this genotyping platform yielded a 65%−69% conversion rate (percentage polymorphic markers) with a global genotyping success rate of 76%−85% and provided a viable means for validating SNP markers in a non-model species. The utility of 31 of the validated SNPs in population structure analysis was confirmed, while a large number of SNPs (174) were shown to be informative and are, thus, good candidates for linkage map construction. The non-synonymous SNPs (50) located in coding regions of genes that showed similarities with known proteins will also be useful for genetic applications, such as the marker-assisted selection of genes of relevance to abalone aquaculture. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Review

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524 KiB  
Review
Potential Targets for Colorectal Cancer Prevention
by Sally Temraz, Deborah Mukherji and Ali Shamseddine
Int. J. Mol. Sci. 2013, 14(9), 17279-17303; https://doi.org/10.3390/ijms140917279 - 22 Aug 2013
Cited by 61 | Viewed by 8565
Abstract
The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B [...] Read more.
The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research. Full article
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
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Review
Oxidative Stress and MicroRNAs in Vascular Diseases
by Alessandra Magenta, Simona Greco, Carlo Gaetano and Fabio Martelli
Int. J. Mol. Sci. 2013, 14(9), 17319-17346; https://doi.org/10.3390/ijms140917319 - 22 Aug 2013
Cited by 158 | Viewed by 14397
Abstract
Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the [...] Read more.
Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the development of cardiovascular diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of target messenger RNAs. They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance. In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity. In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity. In this review, we will discuss miRNAs modulated by ROS or involved in ROS production, and implicated in vascular diseases in which redox imbalance has a pathogenetic role. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Review
Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response
by Graziella Curtale and Franca Citarella
Int. J. Mol. Sci. 2013, 14(9), 17347-17377; https://doi.org/10.3390/ijms140917347 - 22 Aug 2013
Cited by 29 | Viewed by 9766
Abstract
Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, [...] Read more.
Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs) in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs) are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs) could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Review
Emerging Roles of Small Epstein-Barr Virus Derived Non-Coding RNAs in Epithelial Malignancy
by Raymond Wai-Ming Lung, Joanna Hung-Man Tong and Ka-Fai To
Int. J. Mol. Sci. 2013, 14(9), 17378-17409; https://doi.org/10.3390/ijms140917378 - 23 Aug 2013
Cited by 44 | Viewed by 9704
Abstract
Latent Epstein-Barr virus (EBV) infection is an etiological factor in the progression of several human epithelial malignancies such as nasopharyngeal carcinoma (NPC) and a subset of gastric carcinoma. Reports have shown that EBV produces several viral oncoproteins, yet their pathological roles in carcinogenesis [...] Read more.
Latent Epstein-Barr virus (EBV) infection is an etiological factor in the progression of several human epithelial malignancies such as nasopharyngeal carcinoma (NPC) and a subset of gastric carcinoma. Reports have shown that EBV produces several viral oncoproteins, yet their pathological roles in carcinogenesis are not fully elucidated. Studies on the recently discovered of EBV-encoded microRNAs (ebv-miRNAs) showed that these small molecules function as post-transcriptional gene regulators and may play a role in the carcinogenesis process. In NPC and EBV positive gastric carcinoma (EBVaGC), 22 viral miRNAs which are located in the long alternative splicing EBV transcripts, named BamH1 A rightward transcripts (BARTs), are abundantly expressed. The importance of several miR-BARTs in carcinogenesis has recently been demonstrated. These novel findings enhance our understanding of the oncogenic properties of EBV and may lead to a more effective design of therapeutic regimens to combat EBV-associated malignancies. This article will review the pathological roles of miR-BARTs in modulating the expression of cancer-related genes in both host and viral genomes. The expression of other small non-coding RNAs in NPC and the expression pattern of miR-BARTs in rare EBV-associated epithelial cancers will also be discussed. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Review
Delta Opioid Receptor and Its Peptide: A Receptor-Ligand Neuroprotection
by Meaghan Staples, Sandra Acosta, Naoki Tajiri, Mibel Pabon, Yuji Kaneko and Cesar V. Borlongan
Int. J. Mol. Sci. 2013, 14(9), 17410-17419; https://doi.org/10.3390/ijms140917410 - 23 Aug 2013
Cited by 20 | Viewed by 6888
Abstract
In pursuit of neurological therapies, the opioid system, specifically delta opioid receptors and delta opioid peptides, demonstrates promising therapeutic potential for stroke, Parkinson’s disease, and other degenerative neurological conditions. Recent studies offer strong evidence in support of the therapeutic use of delta opioid [...] Read more.
In pursuit of neurological therapies, the opioid system, specifically delta opioid receptors and delta opioid peptides, demonstrates promising therapeutic potential for stroke, Parkinson’s disease, and other degenerative neurological conditions. Recent studies offer strong evidence in support of the therapeutic use of delta opioid receptors, and provide insights into the underlying mechanisms of action. Delta opioid receptors have been shown to confer protective effects by mediating ionic homeostasis and activating endogenous neuroprotective pathways. Additionally, delta opioid agonists such as (D-Ala 2, D-Leu 5) enkephalin (DADLE) have been shown to decrease apoptosis and promote neuronal survival. In its entirety, the delta opioid system represents a promising target for neural therapies. Full article
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
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Review
Statistical Mechanical Treatments of Protein Amyloid Formation
by John S. Schreck and Jian-Min Yuan
Int. J. Mol. Sci. 2013, 14(9), 17420-17452; https://doi.org/10.3390/ijms140917420 - 23 Aug 2013
Cited by 2 | Viewed by 6462
Abstract
Protein aggregation is an important field of investigation because it is closely related to the problem of neurodegenerative diseases, to the development of biomaterials, and to the growth of cellular structures such as cyto-skeleton. Self-aggregation of protein amyloids, for example, is a complicated [...] Read more.
Protein aggregation is an important field of investigation because it is closely related to the problem of neurodegenerative diseases, to the development of biomaterials, and to the growth of cellular structures such as cyto-skeleton. Self-aggregation of protein amyloids, for example, is a complicated process involving many species and levels of structures. This complexity, however, can be dealt with using statistical mechanical tools, such as free energies, partition functions, and transfer matrices. In this article, we review general strategies for studying protein aggregation using statistical mechanical approaches and show that canonical and grand canonical ensembles can be used in such approaches. The grand canonical approach is particularly convenient since competing pathways of assembly and dis-assembly can be considered simultaneously. Another advantage of using statistical mechanics is that numerically exact solutions can be obtained for all of the thermodynamic properties of fibrils, such as the amount of fibrils formed, as a function of initial protein concentration. Furthermore, statistical mechanics models can be used to fit experimental data when they are available for comparison. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Review
The Characterisation of Pluripotent and Multipotent Stem Cells Using Fourier Transform Infrared Microspectroscopy
by Julie Cao, Elizabeth S. Ng, Donald McNaughton, Edouard G. Stanley, Andrew G. Elefanty, Mark J. Tobin and Philip Heraud
Int. J. Mol. Sci. 2013, 14(9), 17453-17476; https://doi.org/10.3390/ijms140917453 - 26 Aug 2013
Cited by 24 | Viewed by 7049
Abstract
Fourier transform infrared (FTIR) microspectroscopy shows potential as a benign, objective and rapid tool to screen pluripotent and multipotent stem cells for clinical use. It offers a new experimental approach that provides a holistic measurement of macromolecular composition such that a signature representing [...] Read more.
Fourier transform infrared (FTIR) microspectroscopy shows potential as a benign, objective and rapid tool to screen pluripotent and multipotent stem cells for clinical use. It offers a new experimental approach that provides a holistic measurement of macromolecular composition such that a signature representing the internal cellular phenotype is obtained. The use of this technique therefore contributes information that is complementary to that acquired by conventional genetic and immunohistochemical methods. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
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Review
Quorum Quenching Enzymes and Their Application in Degrading Signal Molecules to Block Quorum Sensing-Dependent Infection
by Fang Chen, Yuxin Gao, Xiaoyi Chen, Zhimin Yu and Xianzhen Li
Int. J. Mol. Sci. 2013, 14(9), 17477-17500; https://doi.org/10.3390/ijms140917477 - 26 Aug 2013
Cited by 218 | Viewed by 16577
Abstract
With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a [...] Read more.
With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics because the quorum quenching strategy does not aim to kill the pathogen or limit cell growth but to shut down the expression of the pathogenic gene. Quorum quenching enzymes have been identified in quorum sensing and non-quorum sensing microbes, including lactonase, acylase, oxidoreductase and paraoxonase. Lactonase is widely conserved in a range of bacterial species and has variable substrate spectra. The existence of quorum quenching enzymes in the quorum sensing microbes can attenuate their quorum sensing, leading to blocking unnecessary gene expression and pathogenic phenotypes. In this review, we discuss the physiological function of quorum quenching enzymes in bacterial infection and elucidate the enzymatic protection in quorum sensing systems for host diseases and their application in resistance against microbial diseases. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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Review
Renal Dopamine Receptors, Oxidative Stress, and Hypertension
by Santiago Cuevas, Van Anthony Villar, Pedro A. Jose and Ines Armando
Int. J. Mol. Sci. 2013, 14(9), 17553-17572; https://doi.org/10.3390/ijms140917553 - 27 Aug 2013
Cited by 63 | Viewed by 15275
Abstract
Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results [...] Read more.
Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1), paraoxonase 2 (PON2), and heme oxygenase 2 (HO-2), all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Review
Prevention of Carcinogenesis and Development of Gastric and Colon Cancers by 2-Aminophenoxazine-3-one (Phx-3): Direct and Indirect Anti-Cancer Activity of Phx-3
by Akio Tomoda, Keisuke Miyazawa and Takafumi Tabuchi
Int. J. Mol. Sci. 2013, 14(9), 17573-17583; https://doi.org/10.3390/ijms140917573 - 28 Aug 2013
Cited by 7 | Viewed by 5396
Abstract
2-Aminophenoxazine-3-one (Phx-3), an oxidative phenoxazine, exerts strong anticancer effects on various cancer cell lines originating from different organs, in vitro. This article reviews new aspects for the prevention of carcinogenesis and development of gastric and colon cancers by Phx-3, based on the [...] Read more.
2-Aminophenoxazine-3-one (Phx-3), an oxidative phenoxazine, exerts strong anticancer effects on various cancer cell lines originating from different organs, in vitro. This article reviews new aspects for the prevention of carcinogenesis and development of gastric and colon cancers by Phx-3, based on the strong anticancer effects of Phx-3 on gastric and colon cancer cell lines (direct anticancer effects of Phx-3 for preventing development of cancer), the bacteriocidal effects of Phx-3 against Helicobacter pylori associated with carcinogenesis of gastric cancer (indirect anticancer effects for preventing carcinogenesis of gastric cancer), and the proapoptotic activity of Phx-3 against human neutrophils involved in the incidence of ulcerative colitis associated with a high colon cancer risk (indirect anticancer effects for preventing carcinogenesis of colon cancer). Full article
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
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Review
Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases
by Chiara Cencioni, Francesco Spallotta, Fabio Martelli, Sergio Valente, Antonello Mai, Andreas M. Zeiher and Carlo Gaetano
Int. J. Mol. Sci. 2013, 14(9), 17643-17663; https://doi.org/10.3390/ijms140917643 - 28 Aug 2013
Cited by 169 | Viewed by 23240
Abstract
Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations [...] Read more.
Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Review
Small Molecule Inhibitors of AI-2 Signaling in Bacteria: State-of-the-Art and Future Perspectives for Anti-Quorum Sensing Agents
by Min Guo, Sonja Gamby, Yue Zheng and Herman O. Sintim
Int. J. Mol. Sci. 2013, 14(9), 17694-17728; https://doi.org/10.3390/ijms140917694 - 29 Aug 2013
Cited by 57 | Viewed by 16972
Abstract
Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different [...] Read more.
Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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Review
Green Leaf Volatiles: A Plant’s Multifunctional Weapon against Herbivores and Pathogens
by Alessandra Scala, Silke Allmann, Rossana Mirabella, Michel A. Haring and Robert C. Schuurink
Int. J. Mol. Sci. 2013, 14(9), 17781-17811; https://doi.org/10.3390/ijms140917781 - 30 Aug 2013
Cited by 328 | Viewed by 26226
Abstract
Plants cannot avoid being attacked by an almost infinite number of microorganisms and insects. Consequently, they arm themselves with molecular weapons against their attackers. Plant defense responses are the result of a complex signaling network, in which the hormones jasmonic acid (JA), salicylic [...] Read more.
Plants cannot avoid being attacked by an almost infinite number of microorganisms and insects. Consequently, they arm themselves with molecular weapons against their attackers. Plant defense responses are the result of a complex signaling network, in which the hormones jasmonic acid (JA), salicylic acid (SA) and ethylene (ET) are the usual suspects under the magnifying glass when researchers investigate host-pest interactions. However, Green Leaf Volatiles (GLVs), C6 molecules, which are very quickly produced and/or emitted upon herbivory or pathogen infection by almost every green plant, also play an important role in plant defenses. GLVs are semiochemicals used by insects to find their food or their conspecifics. They have also been reported to be fundamental in indirect defenses and to have a direct effect on pests, but these are not the only roles of GLVs. These volatiles, being probably one of the fastest weapons exploited, are also able to directly elicit or prime plant defense responses. Moreover, GLVs, via crosstalk with phytohormones, mostly JA, can influence the outcome of the plant’s defense response against pathogens. For all these reasons GLVs should be considered as co-protagonists in the play between plants and their attackers. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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Review
Epidermal Stem Cells and Their Epigenetic Regulation
by Qi Shen, Hongchuan Jin and Xian Wang
Int. J. Mol. Sci. 2013, 14(9), 17861-17880; https://doi.org/10.3390/ijms140917861 - 30 Aug 2013
Cited by 14 | Viewed by 7441
Abstract
Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the [...] Read more.
Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the potential to generate diversified types of progeny cells in the skin. Although its biology is still largely unclarified, epidermal stem cells are widely used in stem cell research and regenerative medicine given its easy accessibility and pluripotency. Despite the same genome, cells within an organism have different fates due to the epigenetic regulation of gene expression. In this review, we will briefly discuss the current understanding of epigenetic modulation in epidermal stem cells. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
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Review
Oxidative Stress in Aging-Matters of the Heart and Mind
by Krishnan Venkataraman, Sandhya Khurana and T. C. Tai
Int. J. Mol. Sci. 2013, 14(9), 17897-17925; https://doi.org/10.3390/ijms140917897 - 02 Sep 2013
Cited by 96 | Viewed by 9877
Abstract
Oxidative damage is considered to be the primary cause of several aging associated disease pathologies. Cumulative oxidative damage tends to be pervasive among cellular macromolecules, impacting proteins, lipids, RNA and DNA of cells. At a systemic level, events subsequent to oxidative damage induce [...] Read more.
Oxidative damage is considered to be the primary cause of several aging associated disease pathologies. Cumulative oxidative damage tends to be pervasive among cellular macromolecules, impacting proteins, lipids, RNA and DNA of cells. At a systemic level, events subsequent to oxidative damage induce an inflammatory response to sites of oxidative damage, often contributing to additional oxidative stress. At a cellular level, oxidative damage to mitochondria results in acidification of the cytoplasm and release of cytochrome c, causing apoptosis. This review summarizes findings in the literature on oxidative stress and consequent damage on cells and tissues of the cardiovascular system and the central nervous system, with a focus on aging-related diseases that have well-documented evidence of oxidative damage in initiation and/or progression of the disease. The current understanding of the cellular mechanisms with a focus on macromolecular damage, impacted cellular pathways and gross morphological changes associated with oxidative damage is also reviewed. Additionally, the impact of calorific restriction with its profound impact on cardiovascular and neuronal aging is addressed. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Review
Regulation of 3β-Hydroxysteroid Dehydrogenase/Δ54 Isomerase: A Review
by Martin Krøyer Rasmussen, Bo Ekstrand and Galia Zamaratskaia
Int. J. Mol. Sci. 2013, 14(9), 17926-17942; https://doi.org/10.3390/ijms140917926 - 02 Sep 2013
Cited by 63 | Viewed by 7576
Abstract
This review focuses on the expression and regulation of 3β-hydroxysteroid dehydrogenase/Δ54 isomerase (3β-HSD), with emphasis on the porcine version. 3β-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based [...] Read more.
This review focuses on the expression and regulation of 3β-hydroxysteroid dehydrogenase/Δ54 isomerase (3β-HSD), with emphasis on the porcine version. 3β-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based on currently available literature covering humans, rodents and pigs, this review provides an overview of the present knowledge concerning the regulatory mechanisms for 3β-HSD at all omic levels. The HSD isoenzymes are essential in steroid hormone metabolism, both in the synthesis and degradation of steroids. They display tissue-specific expression and factors influencing their activity, which therefore indicates their tissue-specific responses. 3β-HSD is involved in the synthesis of a number of natural steroid hormones, including progesterone and testosterone, and the hepatic degradation of the pheromone androstenone. In general, a number of signaling and regulatory pathways have been demonstrated to influence 3β-HSD transcription and activity, e.g., JAK-STAT, LH/hCG, ERα, AR, SF-1 and PPARα. The expression and enzymic activity of 3β-HSD are also influenced by external factors, such as dietary composition. Much of the research conducted on porcine 3β-HSD is motivated by its importance for the occurrence of the boar taint phenomenon that results from high concentrations of steroids such as androstenone. This topic is also examined in this review. Full article
(This article belongs to the Special Issue Xenobiotic Metabolism)
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Review
Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Mesalazine in the Chemoprevention of Colorectal Cancer
by Carmine Stolfi, Veronica De Simone, Francesco Pallone and Giovanni Monteleone
Int. J. Mol. Sci. 2013, 14(9), 17972-17985; https://doi.org/10.3390/ijms140917972 - 03 Sep 2013
Cited by 74 | Viewed by 11040
Abstract
Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. Although conclusive evidence is still lacking, epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has chemopreventive properties against CRC. Similarly, regular consumption of mesalazine, a drug structurally related to [...] Read more.
Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. Although conclusive evidence is still lacking, epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has chemopreventive properties against CRC. Similarly, regular consumption of mesalazine, a drug structurally related to NSAIDs, seems to reduce the risk of CRC in patients with ulcerative colitis. These observations are supported by a large body of experimental data showing the ability of such drugs to inhibit multiple pathways that sustain colon carcinogenesis. This review summarizes the current information on the molecular mechanisms by which NSAIDs and mesalazine could interfere with CRC cell growth and survival. Full article
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Review
Role of cMET in the Development and Progression of Colorectal Cancer
by Juan Carlos Samamé Pérez-Vargas, Pamela Biondani, Claudia Maggi, Manuela Gariboldi, Annunziata Gloghini, Alessandro Inno, Chiara Costanza Volpi, Ambra Vittoria Gualeni, Maria Di Bartolomeo, Filippo De Braud, Alessandra Castano, Ilaria Bossi and Filippo Pietrantonio
Int. J. Mol. Sci. 2013, 14(9), 18056-18077; https://doi.org/10.3390/ijms140918056 - 03 Sep 2013
Cited by 42 | Viewed by 9918
Abstract
Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET [...] Read more.
Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC), by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies. Full article
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
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Review
Emerging Roles of Claudins in Human Cancer
by Mi Jeong Kwon
Int. J. Mol. Sci. 2013, 14(9), 18148-18180; https://doi.org/10.3390/ijms140918148 - 04 Sep 2013
Cited by 151 | Viewed by 9552
Abstract
Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in [...] Read more.
Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Review
ARF1 and SAR1 GTPases in Endomembrane Trafficking in Plants
by Birsen Cevher-Keskin
Int. J. Mol. Sci. 2013, 14(9), 18181-18199; https://doi.org/10.3390/ijms140918181 - 05 Sep 2013
Cited by 18 | Viewed by 9097
Abstract
Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are commonly conserved among all eukaryotes with respect to both their functional [...] Read more.
Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are commonly conserved among all eukaryotes with respect to both their functional and sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved in the formation and budding of vesicles throughout plant endomembrane systems. ARF1 has been shown to play a critical role in COPI (Coat Protein Complex I)-mediated retrograde trafficking in eukaryotic systems, whereas SAR1 GTPases are involved in intracellular COPII-mediated protein trafficking from the ER to the Golgi apparatus. This review offers a summary of vesicular trafficking with an emphasis on the ARF1 and SAR1 expression patterns at early growth stages and in the de-etiolation process. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
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Review
Self-Organizing Cyclolinear Organosilicon Polymers in Bulk and on the Surface of Water
by Nataliya N. Makarova, Tat'yana V. Astapova, Alexander I. Buzin, Arkady P. Polishchuk, Nataliya V. Chizhova and Irina M. Petrova
Int. J. Mol. Sci. 2013, 14(9), 18215-18238; https://doi.org/10.3390/ijms140918215 - 05 Sep 2013
Cited by 5 | Viewed by 5597
Abstract
yclolinear organocarbosiloxane polymers with varying content and location of (CH2)n groups in the monomer unit were synthesized by reactions of heterofunctional polycondensation and polyaddition of difunctional organocyclosiloxanes and organocyclocarbosiloxanes. Their bulk properties were studied by differential scanning calorimetry and X-ray [...] Read more.
yclolinear organocarbosiloxane polymers with varying content and location of (CH2)n groups in the monomer unit were synthesized by reactions of heterofunctional polycondensation and polyaddition of difunctional organocyclosiloxanes and organocyclocarbosiloxanes. Their bulk properties were studied by differential scanning calorimetry and X-ray structural analysis. It was shown that on introduction of CH2 groups into the methylcyclohexasiloxane unit, the polymer retains the ability to self-organize with formation of a mesomorphic state in a wide temperature range, while on introduction of (CH2)2 fragments in a cyclotetrasiloxane unit or in a bridge connecting two methylcyclotetra(hexa)siloxane units it does not. Comparison of the X-ray data of dihydroxy derivatives of decamethylcyclohexasiloxane and decamethyl-5-carbocyclohexasiloxane with packing of cyclolinear organosilicon polymers in bulk shows that the polymer inherits the layered type of crystalline structure typical for monomers. Langmuir films of cyclolinear polymethylcarbosiloxanes with different design of monomer units were studied as well. It was revealed that all polymers form monomolecular films at the air/water interface, excluding those having longer hydrophobic fragment than hydrophilic ones. The ability to form multilayers depends on the surroundings of Si atom in the bridge between the cycles. Full article
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Review
Experimental Models of Status Epilepticus and Neuronal Injury for Evaluation of Therapeutic Interventions
by Doodipala Samba Reddy and Ramkumar Kuruba
Int. J. Mol. Sci. 2013, 14(9), 18284-18318; https://doi.org/10.3390/ijms140918284 - 05 Sep 2013
Cited by 181 | Viewed by 13717
Abstract
This article describes current experimental models of status epilepticus (SE) and neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. SE is an emergency condition associated with continuous seizures lasting [...] Read more.
This article describes current experimental models of status epilepticus (SE) and neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. SE is an emergency condition associated with continuous seizures lasting more than 30 min. It causes significant mortality and morbidity. SE can cause devastating damage to the brain leading to cognitive impairment and increased risk of epilepsy. Benzodiazepines are the first-line drugs for the treatment of SE, however, many people exhibit partial or complete resistance due to a breakdown of GABA inhibition. Therefore, new drugs with neuroprotective effects against the SE-induced neuronal injury and degeneration are desirable. Animal models are used to study the pathophysiology of SE and for the discovery of newer anticonvulsants. In SE paradigms, seizures are induced in rodents by chemical agents or by electrical stimulation of brain structures. Electrical stimulation includes perforant path and self-sustaining stimulation models. Pharmacological models include kainic acid, pilocarpine, flurothyl, organophosphates and other convulsants that induce SE in rodents. Neuronal injury occurs within the initial SE episode, and animals exhibit cognitive dysfunction and spontaneous seizures several weeks after this precipitating event. Current SE models have potential applications but have some limitations. In general, the experimental SE model should be analogous to the human seizure state and it should share very similar neuropathological mechanisms. The pilocarpine and diisopropylfluorophosphate models are associated with prolonged, diazepam-insensitive seizures and neurodegeneration and therefore represent paradigms of refractory SE. Novel mechanism-based or clinically relevant models are essential to identify new therapies for SE and neuroprotective interventions. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology)
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663 KiB  
Review
Noncoding RNA in Oncogenesis: A New Era of Identifying Key Players
by Guorui Deng and Guangchao Sui
Int. J. Mol. Sci. 2013, 14(9), 18319-18349; https://doi.org/10.3390/ijms140918319 - 05 Sep 2013
Cited by 95 | Viewed by 12189
Abstract
New discoveries and accelerating progresses in the field of noncoding RNAs (ncRNAs) continuously challenges our deep-rooted doctrines in biology and sometimes our imagination. A growing body of evidence indicates that ncRNAs are important players in oncogenesis. While a stunning list of ncRNAs has [...] Read more.
New discoveries and accelerating progresses in the field of noncoding RNAs (ncRNAs) continuously challenges our deep-rooted doctrines in biology and sometimes our imagination. A growing body of evidence indicates that ncRNAs are important players in oncogenesis. While a stunning list of ncRNAs has been discovered, only a small portion of them has been examined for their biological activities and very few have been characterized for the molecular mechanisms of their action. To date, ncRNAs have been shown to regulate a wide range of biological processes, including chromatin remodeling, gene transcription, mRNA translation and protein function. Dysregulation of ncRNAs contributes to the pathogenesis of a variety of cancers and aberrant ncRNA expression has a high potential to be prognostic in some cancers. Thus, a new cancer research era has begun to identify novel key players of ncRNAs in oncogenesis. In this review, we will first discuss the function and regulation of miRNAs, especially focusing on the interplay between miRNAs and several key cancer genes, including p53, PTEN and c-Myc. We will then summarize the research of long ncRNAs (lncRNAs) in cancers. In this part, we will discuss the lncRNAs in four categories based on their activities, including regulating gene expression, acting as miRNA decoys, mediating mRNA translation, and modulating protein activities. At the end, we will also discuss recently unraveled activities of circular RNAs (circRNAs). Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Review
A Molecular and Chemical Perspective in Defining Melatonin Receptor Subtype Selectivity
by King Hang Chan and Yung Hou Wong
Int. J. Mol. Sci. 2013, 14(9), 18385-18406; https://doi.org/10.3390/ijms140918385 - 06 Sep 2013
Cited by 28 | Viewed by 8001
Abstract
Melatonin is primarily synthesized and secreted by the pineal gland during darkness in a normal diurnal cycle. In addition to its intrinsic antioxidant property, the neurohormone has renowned regulatory roles in the control of circadian rhythm and exerts its physiological actions primarily by [...] Read more.
Melatonin is primarily synthesized and secreted by the pineal gland during darkness in a normal diurnal cycle. In addition to its intrinsic antioxidant property, the neurohormone has renowned regulatory roles in the control of circadian rhythm and exerts its physiological actions primarily by interacting with the G protein-coupled MT1 and MT2 transmembrane receptors. The two melatonin receptor subtypes display identical ligand binding characteristics and mediate a myriad of signaling pathways, including adenylyl cyclase inhibition, phospholipase C stimulation and the regulation of other effector molecules. Both MT1 and MT2 receptors are widely expressed in the central nervous system as well as many peripheral tissues, but each receptor subtype can be linked to specific functional responses at the target tissue. Given the broad therapeutic implications of melatonin receptors in chronobiology, immunomodulation, endocrine regulation, reproductive functions and cancer development, drug discovery and development programs have been directed at identifying chemical molecules that bind to the two melatonin receptor subtypes. However, all of the melatoninergics in the market act on both subtypes of melatonin receptors without significant selectivity. To facilitate the design and development of novel therapeutic agents, it is necessary to understand the intrinsic differences between MT1 and MT2 that determine ligand binding, functional efficacy, and signaling specificity. This review summarizes our current knowledge in differentiating MT1 and MT2 receptors and their signaling capacities. The use of homology modeling in the mapping of the ligand-binding pocket will be described. Identification of conserved and distinct residues will be tremendously useful in the design of highly selective ligands. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
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Review
Molecular Signatures in Urologic Tumors
by Spencer Larkin and Natasha Kyprianou
Int. J. Mol. Sci. 2013, 14(9), 18421-18436; https://doi.org/10.3390/ijms140918421 - 06 Sep 2013
Cited by 3 | Viewed by 6785
Abstract
Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing [...] Read more.
Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing great metastatic potential. The increasing need for more efficient and less invasive methods of cancer detection, as well as the ability to predict severity of the disease phenotype is readily evident—yet reliable methods remain elusive in a clinical setting today. Comprehensive panels of gene clusters are being developed toward the generation of molecular signatures in order to better diagnose urologic malignancies, and identify effective treatment strategies in the emerging era of personalized medicine. In this review, we discuss the current literature on the credibility and biomarker value of such molecular signatures in the context of clinical significance relating to the pathological aggressiveness of urologic tumors (prostate, bladder and renal cancer)—also exploiting their predictive potential in the response to treatment. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
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Review
Novel Strategies for the Prevention and Treatment of Biofilm Related Infections
by Meng Chen, Qingsong Yu and Hongmin Sun
Int. J. Mol. Sci. 2013, 14(9), 18488-18501; https://doi.org/10.3390/ijms140918488 - 06 Sep 2013
Cited by 329 | Viewed by 14252
Abstract
Biofilm formation by human bacterial pathogens on implanted medical devices causes major morbidity and mortality among patients, and leads to billions of dollars in healthcare cost. Biofilm is a complex bacterial community that is highly resistant to antibiotics and human immunity. As a [...] Read more.
Biofilm formation by human bacterial pathogens on implanted medical devices causes major morbidity and mortality among patients, and leads to billions of dollars in healthcare cost. Biofilm is a complex bacterial community that is highly resistant to antibiotics and human immunity. As a result, novel therapeutic solutions other than the conventional antibiotic therapies are in urgent need. In this review, we will discuss the recent research in discovery of alternative approaches to prevent or treat biofilms. Current anti-biofilm technologies could be divided into two groups. The first group focuses on targeting the biofilm forming process of bacteria based on our understanding of the molecular mechanism of biofilm formation. Small molecules and enzymes have been developed to inhibit or disrupt biofilm formation. Another group of anti-biofilm technologies focuses on modifying the biomaterials used in medical devices to make them resistant to biofilm formation. While these novel anti-biofilm approaches are still in nascent phases of development, efforts devoted to these technologies could eventually lead to anti-biofilm therapies that are superior to the current antibiotic treatment. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)
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Review
Microfluidic Biosensing Systems Using Magnetic Nanoparticles
by Ioanna Giouroudi and Franz Keplinger
Int. J. Mol. Sci. 2013, 14(9), 18535-18556; https://doi.org/10.3390/ijms140918535 - 09 Sep 2013
Cited by 49 | Viewed by 9593
Abstract
In recent years, there has been rapidly growing interest in developing hand held, sensitive and cost-effective on-chip biosensing systems that directly translate the presence of certain bioanalytes (e.g., biomolecules, cells and viruses) into an electronic signal. The impressive and rapid progress in micro- [...] Read more.
In recent years, there has been rapidly growing interest in developing hand held, sensitive and cost-effective on-chip biosensing systems that directly translate the presence of certain bioanalytes (e.g., biomolecules, cells and viruses) into an electronic signal. The impressive and rapid progress in micro- and nanotechnology as well as in biotechnology enables the integration of a variety of analytical functions in a single chip. All necessary sample handling and analysis steps are then performed within the chip. Microfluidic systems for biomedical analysis usually consist of a set of units, which guarantees the manipulation, detection and recognition of bioanalytes in a reliable and flexible manner. Additionally, the use of magnetic fields for performing the aforementioned tasks has been steadily gaining interest. This is because magnetic fields can be well tuned and applied either externally or from a directly integrated solution in the biosensing system. In combination with these applied magnetic fields, magnetic nanoparticles are utilized. Some of the merits of magnetic nanoparticles are the possibility of manipulating them inside microfluidic channels by utilizing high gradient magnetic fields, their detection by integrated magnetic microsensors, and their flexibility due to functionalization by means of surface modification and specific binding. Their multi-functionality is what makes them ideal candidates as the active component in miniaturized on-chip biosensing systems. In this review, focus will be given to the type of biosening systems that use microfluidics in combination with magnetoresistive sensors and detect the presence of bioanalyte tagged with magnetic nanoparticles. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Review
Archaeal Diversity in Biofilm Technologies Applied to Treat Urban and Industrial Wastewater: Recent Advances and Future Prospects
by Kadiya Calderón, Alejandro González-Martínez, Cinta Gómez-Silván, Francisco Osorio, Belén Rodelas and Jesús González-López
Int. J. Mol. Sci. 2013, 14(9), 18572-18598; https://doi.org/10.3390/ijms140918572 - 09 Sep 2013
Cited by 31 | Viewed by 10863
Abstract
Biological wastewater treatment (WWT) frequently relies on biofilms for the removal of anthropogenic contaminants. The use of inert carrier materials to support biofilm development is often required, although under certain operating conditions microorganisms yield structures called granules, dense aggregates of self-immobilized cells with [...] Read more.
Biological wastewater treatment (WWT) frequently relies on biofilms for the removal of anthropogenic contaminants. The use of inert carrier materials to support biofilm development is often required, although under certain operating conditions microorganisms yield structures called granules, dense aggregates of self-immobilized cells with the characteristics of biofilms maintained in suspension. Molecular techniques have been successfully applied in recent years to identify the prokaryotic communities inhabiting biofilms in WWT plants. Although methanogenic Archaea are widely acknowledged as key players for the degradation of organic matter in anaerobic bioreactors, other biotechnological functions fulfilled by Archaea are less explored, and research on their significance and potential for WWT is largely needed. In addition, the occurrence of biofilms in WWT plants can sometimes be a source of operational problems. This is the case for membrane bioreactors (MBR), an advanced technology that combines conventional biological treatment with membrane filtration, which is strongly limited by biofouling, defined as the undesirable accumulation of microbial biofilms and other materials on membrane surfaces. The prevalence and spatial distribution of archaeal communities in biofilm-based WWT as well as their role in biofouling are reviewed here, in order to illustrate the significance of this prokaryotic cellular lineage in engineered environments devoted to WWT. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)
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Review
Human Diseases Associated with Form and Function of the Golgi Complex
by Mariana G. Bexiga and Jeremy C. Simpson
Int. J. Mol. Sci. 2013, 14(9), 18670-18681; https://doi.org/10.3390/ijms140918670 - 10 Sep 2013
Cited by 65 | Viewed by 13034
Abstract
The Golgi complex lies at the heart of the secretory pathway and is responsible for modifying proteins and lipids, as well as sorting newly synthesized molecules to their correct destination. As a consequence of these important roles, any changes in its proteome can [...] Read more.
The Golgi complex lies at the heart of the secretory pathway and is responsible for modifying proteins and lipids, as well as sorting newly synthesized molecules to their correct destination. As a consequence of these important roles, any changes in its proteome can negatively affect its function and in turn lead to disease. Recently, a number of proteins have been identified, which when either depleted or mutated, result in diseases that affect various organ systems. Here we describe how these proteins have been linked to the Golgi complex, and specifically how they affect either the morphology, membrane traffic or glycosylation ability of this organelle. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
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Review
Design of Superparamagnetic Nanoparticles for Magnetic Particle Imaging (MPI)
by Yimeng Du, Pui To Lai, Cheung Hoi Leung and Philip W. T. Pong
Int. J. Mol. Sci. 2013, 14(9), 18682-18710; https://doi.org/10.3390/ijms140918682 - 11 Sep 2013
Cited by 56 | Viewed by 12384
Abstract
Magnetic particle imaging (MPI) is a promising medical imaging technique producing quantitative images of the distribution of tracer materials (superparamagnetic nanoparticles) without interference from the anatomical background of the imaging objects (either phantoms or lab animals). Theoretically, the MPI platform can image with [...] Read more.
Magnetic particle imaging (MPI) is a promising medical imaging technique producing quantitative images of the distribution of tracer materials (superparamagnetic nanoparticles) without interference from the anatomical background of the imaging objects (either phantoms or lab animals). Theoretically, the MPI platform can image with relatively high temporal and spatial resolution and sensitivity. In practice, the quality of the MPI images hinges on both the applied magnetic field and the properties of the tracer nanoparticles. Langevin theory can model the performance of superparamagnetic nanoparticles and predict the crucial influence of nanoparticle core size on the MPI signal. In addition, the core size distribution, anisotropy of the magnetic core and surface modification of the superparamagnetic nanoparticles also determine the spatial resolution and sensitivity of the MPI images. As a result, through rational design of superparamagnetic nanoparticles, the performance of MPI could be effectively optimized. In this review, the performance of superparamagnetic nanoparticles in MPI is investigated. Rational synthesis and modification of superparamagnetic nanoparticles are discussed and summarized. The potential medical application areas for MPI, including cardiovascular system, oncology, stem cell tracking and immune related imaging are also analyzed and forecasted. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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1191 KiB  
Review
Berry Phenolics of Grapevine under Challenging Environments
by António Teixeira, José Eiras-Dias, Simone D. Castellarin and Hernâni Gerós
Int. J. Mol. Sci. 2013, 14(9), 18711-18739; https://doi.org/10.3390/ijms140918711 - 11 Sep 2013
Cited by 336 | Viewed by 21463
Abstract
Plant phenolics have been for many years a theme of major scientific and applied interest. Grape berry phenolics contribute to organoleptic properties, color and protection against environmental challenges. Climate change has already caused significant warming in most grape-growing areas of the world, and [...] Read more.
Plant phenolics have been for many years a theme of major scientific and applied interest. Grape berry phenolics contribute to organoleptic properties, color and protection against environmental challenges. Climate change has already caused significant warming in most grape-growing areas of the world, and the climatic conditions determine, to a large degree, the grape varieties that can be cultivated as well as wine quality. In particular, heat, drought and light/UV intensity severely affect phenolic metabolism and, thus, grape composition and development. In the variety Chardonnay, water stress increases the content of flavonols and decreases the expression of genes involved in biosynthesis of stilbene precursors. Also, polyphenolic profile is greatly dependent on genotype and environmental interactions. This review deals with the diversity and biosynthesis of phenolic compounds in the grape berry, from a general overview to a more detailed level, where the influence of environmental challenges on key phenolic metabolism pathways is approached. The full understanding of how and when specific phenolic compounds accumulate in the berry, and how the varietal grape berry metabolism responds to the environment is of utmost importance to adjust agricultural practices and thus, modify wine profile. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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Review
Peptide-Lipid Interactions: Experiments and Applications
by Stefania Galdiero, Annarita Falanga, Marco Cantisani, Mariateresa Vitiello, Giancarlo Morelli and Massimiliano Galdiero
Int. J. Mol. Sci. 2013, 14(9), 18758-18789; https://doi.org/10.3390/ijms140918758 - 12 Sep 2013
Cited by 91 | Viewed by 14911
Abstract
The interactions between peptides and lipids are of fundamental importance in the functioning of numerous membrane-mediated cellular processes including antimicrobial peptide action, hormone-receptor interactions, drug bioavailability across the blood-brain barrier and viral fusion processes. Moreover, a major goal of modern biotechnology is obtaining [...] Read more.
The interactions between peptides and lipids are of fundamental importance in the functioning of numerous membrane-mediated cellular processes including antimicrobial peptide action, hormone-receptor interactions, drug bioavailability across the blood-brain barrier and viral fusion processes. Moreover, a major goal of modern biotechnology is obtaining new potent pharmaceutical agents whose biological action is dependent on the binding of peptides to lipid-bilayers. Several issues need to be addressed such as secondary structure, orientation, oligomerization and localization inside the membrane. At the same time, the structural effects which the peptides cause on the lipid bilayer are important for the interactions and need to be elucidated. The structural characterization of membrane active peptides in membranes is a harsh experimental challenge. It is in fact accepted that no single experimental technique can give a complete structural picture of the interaction, but rather a combination of different techniques is necessary. Full article
(This article belongs to the Special Issue Computational Modelling of Biological Membranes)
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Review
Long Non-Coding RNAs and Complex Human Diseases
by Jing Li, Zhenyu Xuan and Changning Liu
Int. J. Mol. Sci. 2013, 14(9), 18790-18808; https://doi.org/10.3390/ijms140918790 - 12 Sep 2013
Cited by 165 | Viewed by 12055
Abstract
Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are generally defined as non-protein-coding transcripts longer than 200 nucleotides. Recently, an increasing number of studies have shown that lncRNAs can be involved in various critical biological processes, such as chromatin remodeling, [...] Read more.
Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are generally defined as non-protein-coding transcripts longer than 200 nucleotides. Recently, an increasing number of studies have shown that lncRNAs can be involved in various critical biological processes, such as chromatin remodeling, gene transcription, and protein transport and trafficking. Moreover, lncRNAs are dysregulated in a number of complex human diseases, including coronary artery diseases, autoimmune diseases, neurological disorders, and various cancers, which indicates their important roles in these diseases. Here, we reviewed the current understanding of lncRNAs, including their definition and subclassification, regulatory functions, and potential roles in different types of complex human diseases. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Review
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas
by Eleftherios P. Samartzis, Aurelia Noske, Konstantin J. Dedes, Daniel Fink and Patrick Imesch
Int. J. Mol. Sci. 2013, 14(9), 18824-18849; https://doi.org/10.3390/ijms140918824 - 12 Sep 2013
Cited by 124 | Viewed by 14470
Abstract
Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear [...] Read more.
Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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Review
Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke
by Kiyoshi Kikuchi, Salunya Tancharoen, Takashi Ito, Yoko Morimoto-Yamashita, Naoki Miura, Ko-ichi Kawahara, Ikuro Maruyama, Yoshinaka Murai and Eiichiro Tanaka
Int. J. Mol. Sci. 2013, 14(9), 18899-18924; https://doi.org/10.3390/ijms140918899 - 13 Sep 2013
Cited by 41 | Viewed by 10697 | Correction
Abstract
Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, [...] Read more.
Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. Full article
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
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Review
The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients
by Yahya I. Elshimali, Husseina Khaddour, Marianna Sarkissyan, Yanyuan Wu and Jaydutt V. Vadgama
Int. J. Mol. Sci. 2013, 14(9), 18925-18958; https://doi.org/10.3390/ijms140918925 - 13 Sep 2013
Cited by 197 | Viewed by 15736
Abstract
Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of [...] Read more.
Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of obtaining, using, and analyzing CCFDNA from blood will be discussed. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
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Review
hnRNP A1: The Swiss Army Knife of Gene Expression
by Jacques Jean-Philippe, Sean Paz and Massimo Caputi
Int. J. Mol. Sci. 2013, 14(9), 18999-19024; https://doi.org/10.3390/ijms140918999 - 16 Sep 2013
Cited by 205 | Viewed by 16615
Abstract
Eukaryotic cells express a large variety of RNA binding proteins (RBPs), with diverse affinities and specificities towards target RNAs. These proteins play a crucial role in almost every aspect of RNA biogenesis, expression and function. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a complex [...] Read more.
Eukaryotic cells express a large variety of RNA binding proteins (RBPs), with diverse affinities and specificities towards target RNAs. These proteins play a crucial role in almost every aspect of RNA biogenesis, expression and function. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a complex and diverse family of RNA binding proteins. hnRNPs display multiple functions in the processing of heterogeneous nuclear RNAs into mature messenger RNAs. hnRNP A1 is one of the most abundant and ubiquitously expressed members of this protein family. hnRNP A1 plays multiple roles in gene expression by regulating major steps in the processing of nascent RNA transcripts. The transcription, splicing, stability, export through nuclear pores and translation of cellular and viral transcripts are all mechanisms modulated by this protein. The diverse functions played by hnRNP A1 are not limited to mRNA biogenesis, but extend to the processing of microRNAs, telomere maintenance and the regulation of transcription factor activity. Genomic approaches have recently uncovered the extent of hnRNP A1 roles in the development and differentiation of living organisms. The aim of this review is to highlight recent developments in the study of this protein and to describe its functions in cellular and viral gene expression and its role in human pathologies. Full article
(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)
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602 KiB  
Review
Biochemistry and Molecular Biology of Carotenoid Biosynthesis in Chili Peppers (Capsicum spp.)
by María Del Rocío Gómez-García and Neftalí Ochoa-Alejo
Int. J. Mol. Sci. 2013, 14(9), 19025-19053; https://doi.org/10.3390/ijms140919025 - 16 Sep 2013
Cited by 147 | Viewed by 17909
Abstract
Capsicum species produce fruits that synthesize and accumulate carotenoid pigments, which are responsible for the fruits’ yellow, orange and red colors. Chili peppers have been used as an experimental model for studying the biochemical and molecular aspects of carotenoid biosynthesis. Most reports refer [...] Read more.
Capsicum species produce fruits that synthesize and accumulate carotenoid pigments, which are responsible for the fruits’ yellow, orange and red colors. Chili peppers have been used as an experimental model for studying the biochemical and molecular aspects of carotenoid biosynthesis. Most reports refer to the characterization of carotenoids and content determination in chili pepper fruits from different species, cultivars, varieties or genotypes. The types and levels of carotenoids differ between different chili pepper fruits, and they are also influenced by environmental conditions. Yellow-orange colors of chili pepper fruits are mainly due to the accumulation of α- and β-carotene, zeaxanthin, lutein and β-cryptoxanthin. Carotenoids such as capsanthin, capsorubin and capsanthin-5,6-epoxide confer the red colors. Chromoplasts are the sites of carotenoid pigment synthesis and storage. According to the most accepted theory, the synthesis of carotenoids in chili peppers is controlled by three loci: c1, c2 and y. Several enzymes participating in carotenoid biosynthesis in chili pepper fruits have been isolated and characterized, and the corresponding gene sequences have been reported. However, there is currently limited information on the molecular mechanisms that regulate this biosynthetic pathway. Approaches to gain more knowledge of the regulation of carotenoid biosynthesis are discussed. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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1061 KiB  
Review
Single-Chain Fragment Variable Passive Immunotherapies for Neurodegenerative Diseases
by Liang Huang, Xiaomin Su and Howard J. Federoff
Int. J. Mol. Sci. 2013, 14(9), 19109-19127; https://doi.org/10.3390/ijms140919109 - 17 Sep 2013
Cited by 35 | Viewed by 11031
Abstract
Accumulation of misfolded proteins has been implicated in a variety of neurodegenerative diseases including prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). In the past decade, single-chain fragment variable (scFv) -based immunotherapies have been developed to target abnormal proteins [...] Read more.
Accumulation of misfolded proteins has been implicated in a variety of neurodegenerative diseases including prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). In the past decade, single-chain fragment variable (scFv) -based immunotherapies have been developed to target abnormal proteins or various forms of protein aggregates including Aβ, SNCA, Htt, and PrP proteins. The scFvs are produced by fusing the variable regions of the antibody heavy and light chains, creating a much smaller protein with unaltered specificity. Because of its small size and relative ease of production, scFvs are promising diagnostic and therapeutic reagents for protein misfolded diseases. Studies have demonstrated the efficacy and safety of scFvs in preventing amyloid protein aggregation in preclinical models. Herein, we discuss recent developments of these immunotherapeutics. We review efforts of our group and others using scFv in neurodegenerative disease models. We illustrate the advantages of scFvs, including engineering to enhance misfolded conformer specificity and subcellular targeting to optimize therapeutic action. Full article
(This article belongs to the Special Issue Protein Folding)
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1262 KiB  
Review
Posttranscriptional Regulation of Insulin Family Ligands and Receptors
by Amaresh C. Panda, Ioannis Grammatikakis, Je-Hyun Yoon and Kotb Abdelmohsen
Int. J. Mol. Sci. 2013, 14(9), 19202-19229; https://doi.org/10.3390/ijms140919202 - 18 Sep 2013
Cited by 19 | Viewed by 9310
Abstract
Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis. Altered insulin system is associated with major pathological conditions like diabetes and cancer. The mRNAs encoding for these ligands and [...] Read more.
Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis. Altered insulin system is associated with major pathological conditions like diabetes and cancer. The mRNAs encoding for these ligands and their receptors are posttranscriptionally controlled by three major groups of regulators; (i) alternative splicing regulatory factors; (ii) turnover and translation regulator RNA-binding proteins (TTR-RBPs); and (iii) non-coding RNAs including miRNAs and long non-coding RNAs (lncRNAs). In this review, we discuss the influence of these regulators on alternative splicing, mRNA stability and translation. Due to the pathological impacts of insulin system, we also discussed the possibilities of discovering new potential regulators which will improve understanding of insulin system and associated diseases. Full article
(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)
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1499 KiB  
Review
Voltage-Gated Potassium Channel Kv1.3 Is Highly Expressed in Human Osteosarcoma and Promotes Osteosarcoma Growth
by Jin Wu, Daixing Zhong, Xinyu Wu, Mo Sha, Liangqi Kang and Zhenqi Ding
Int. J. Mol. Sci. 2013, 14(9), 19245-19256; https://doi.org/10.3390/ijms140919245 - 23 Sep 2013
Cited by 17 | Viewed by 5724
Abstract
Deregulation of voltage-gated potassium channel subunit Kv1.3 has been reported in many tumors. Kv1.3 promotes tumorigenesis by enhancing cell proliferation while suppressing apoptosis. However, the expression and function of Kv1.3 in osteosarcoma are unknown. In the present study, we detected the expression of [...] Read more.
Deregulation of voltage-gated potassium channel subunit Kv1.3 has been reported in many tumors. Kv1.3 promotes tumorigenesis by enhancing cell proliferation while suppressing apoptosis. However, the expression and function of Kv1.3 in osteosarcoma are unknown. In the present study, we detected the expression of Kv1.3 in human osteosarcoma cells and tissues by RT-PCR, Western blot and immunohistochemistry. We further examined cell proliferation and apoptosis in osteosarcoma MG-63 cells and xenografts following knockdown of Kv1.3 by short hairpin RNA (shRNA). We found that Kv1.3 was upregulated in human osteosarcoma. Knockdown of Kv1.3 significantly suppressed cell proliferation and increased apoptosis as demonstrated by enhanced cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of Caspase-3/7. Furthermore, adenovirus delivered shRNA targeting Kv1.3 significantly inhibited the growth of MG-63 xenografts. Taken together, our results suggest that Kv1.3 is a novel molecular target for osterosarcoma therapy. Full article
(This article belongs to the Section Biochemistry)
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1147 KiB  
Review
The Consequence of Oncomorphic TP53 Mutations in Ovarian Cancer
by Pavla Brachova, Kristina W. Thiel and Kimberly K. Leslie
Int. J. Mol. Sci. 2013, 14(9), 19257-19275; https://doi.org/10.3390/ijms140919257 - 23 Sep 2013
Cited by 75 | Viewed by 13019
Abstract
Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resistance. Currently, there are no biological markers that can [...] Read more.
Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resistance. Currently, there are no biological markers that can be used to predict patient response to chemotherapy. However, it is clear that mutations in the tumor suppressor gene TP53, which occur in 96% of serous ovarian tumors, alter the core molecular pathways involved in drug response. One subtype of TP53 mutations, widely termed gain-of-function (GOF) mutations, surprisingly converts this protein from a tumor suppressor to an oncogene. We term the resulting change an oncomorphism. In this review, we discuss particular TP53 mutations, including known oncomorphic properties of the resulting mutant p53 proteins. For example, several different oncomorphic mutations have been reported, but each mutation acts in a distinct manner and has a different effect on tumor progression and chemoresistance. An understanding of the pathological pathways altered by each mutation is necessary in order to design appropriate drug interventions for patients suffering from this deadly disease. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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1711 KiB  
Review
Oxidative Stress in the Pathogenesis of Keratoconus and Fuchs Endothelial Corneal Dystrophy
by Katarzyna A. Wojcik, Anna Kaminska, Janusz Blasiak, Jerzy Szaflik and Jacek P. Szaflik
Int. J. Mol. Sci. 2013, 14(9), 19294-19308; https://doi.org/10.3390/ijms140919294 - 23 Sep 2013
Cited by 115 | Viewed by 15480
Abstract
Due to its localization and function, the cornea is regularly exposed to sunlight and atmospheric oxygen, mainly dioxygen, which produce reactive oxygen species (ROS). Therefore, corneal cells are particularly susceptible to oxidative stress. The accumulation of ROS in the cornea may affect signal [...] Read more.
Due to its localization and function, the cornea is regularly exposed to sunlight and atmospheric oxygen, mainly dioxygen, which produce reactive oxygen species (ROS). Therefore, corneal cells are particularly susceptible to oxidative stress. The accumulation of ROS in the cornea may affect signal transduction, proliferation and may also promote cell death. The cornea has several enzymatic and non-enzymatic antioxidants involved in ROS scavenging, but in certain conditions they may not cope with oxidative stress, leading to diseases of the eye. Keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) are multifactorial diseases of the cornea, in which pathogenesis is not fully understood. However, increased levels of oxidative stress markers detected in these disorders indicate that oxidative stress may play an important role in their development and progression. These markers are: (i) decreased levels of non-enzymatic antioxidants, and (ii) decreased expression of genes encoding antioxidative enzymes, including thioredoxin reductase, peroxiredoxins, superoxide dismutase, glutathione S-transferase, and aldehyde dehydrogenase. Moreover, the FECD endothelium displays higher levels of oxidative DNA damage, especially in mitochondrial DNA (mtDNA), whereas KC cornea shows abnormal levels of some components of oxidative phosphorylation encoded by mtDNA. In this review we present some considerations and results of experiments supporting the thesis on the important role of oxidative stress in KC and FECD pathology. Full article
(This article belongs to the Section Biochemistry)
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374 KiB  
Review
Choosing an Appropriate Infection Model to Study Quorum Sensing Inhibition in Pseudomonas Infections
by Evelina Papaioannou, Putri Dwi Utari and Wim J. Quax
Int. J. Mol. Sci. 2013, 14(9), 19309-19340; https://doi.org/10.3390/ijms140919309 - 23 Sep 2013
Cited by 38 | Viewed by 9524
Abstract
Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene [...] Read more.
Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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Graphical abstract

Other

670 KiB  
Brief Report
Capillary-Seeding Crystallization and Preliminary Crystallographic Analysis of a Solvent-Tolerant Elastase from Pseudomonas aeruginosa Strain K
by Mohd Shukuri Mohamad Ali, Zatty Syamimi @ Adura Mat Said, Raja Noor Zaliha Raja Abd Rahman, Adam Leow Thean Chor, Mahiran Basri and Abu Bakar Salleh
Int. J. Mol. Sci. 2013, 14(9), 17608-17617; https://doi.org/10.3390/ijms140917608 - 28 Aug 2013
Cited by 2 | Viewed by 6383
Abstract
Seeding is a versatile method for optimizing crystal growth. Coupling this technique with capillary counter diffusion crystallization enhances the size and diffraction quality of the crystals. In this article, crystals for organic solvent-tolerant recombinant elastase strain K were successfully produced through microseeding with [...] Read more.
Seeding is a versatile method for optimizing crystal growth. Coupling this technique with capillary counter diffusion crystallization enhances the size and diffraction quality of the crystals. In this article, crystals for organic solvent-tolerant recombinant elastase strain K were successfully produced through microseeding with capillary counter-diffusion crystallization. This technique improved the nucleation success rate with a low protein concentration (3.00 mg/mL). The crystal was grown in 1 M ammonium phosphate monobasic and 0.1 M sodium citrate tribasic dihydrate pH 5.6. The optimized crystal size was 1 × 0.1 × 0.05 mm3. Elastase strain K successfully diffracted up to 1.39 Å at SPring-8, Japan, using synchrotron radiation for preliminary data diffraction analysis. The space group was determined to be monoclinic space group P1211 with unit cell parameters of a = 38.99 Ǻ, b = 90.173 Å and c = 40.60 Å. Full article
(This article belongs to the Section Materials Science)
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