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Int. J. Mol. Sci., Volume 13, Issue 5 (May 2012), Pages 5290-6533

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Open AccessArticle Reduced Photoinhibition under Low Irradiance Enhanced Kacip Fatimah (Labisia pumila Benth) Secondary Metabolites, Phenyl Alanine Lyase and Antioxidant Activity
Int. J. Mol. Sci. 2012, 13(5), 5290-5306; doi:10.3390/ijms13055290
Received: 4 January 2012 / Revised: 22 March 2012 / Accepted: 5 April 2012 / Published: 25 April 2012
Cited by 10 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila [...] Read more.
A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila var. alata, under four levels of irradiance (225, 500, 625 and 900 µmol/m2/s) for 16 weeks. As irradiance levels increased from 225 to 900 µmol/m2/s, the production of plant secondary metabolites (total flavonoids, phenolics and antocyanin) was found to decrease steadily. Production of total flavonoids and phenolics reached their peaks under 225 followed by 500, 625 and 900 µmol/m2/s irradiances. Significant positive correlation of production of total phenolics, flavonoids and antocyanin content with Fv/Fm, Fm/Fo and photosynthesis indicated up-regulation of carbon-based secondary metabolites (CBSM) under reduced photoinhibition on the under low light levels condition. At the lowest irradiance levels, Labisia pumila extracts also exhibited a significantly higher antioxidant activity (DPPH) than under high irradiance. The improved antioxidative activity under low light levels might be due to high availability of total flavonoids, phenolics and anthocyanin content in the plant extract. It was also found that an increase in the production of CBSM was due to high PAL activity under low light, probably signifying more availability of phenylalanine (Phe) under this condition. Full article
Open AccessArticle Rational Mutagenesis of Cyclodextrin Glucanotransferase at the Calcium Binding Regions for Enhancement of Thermostability
Int. J. Mol. Sci. 2012, 13(5), 5307-5323; doi:10.3390/ijms13055307
Received: 9 January 2012 / Revised: 8 March 2012 / Accepted: 13 April 2012 / Published: 25 April 2012
Cited by 10 | PDF Full-text (1247 KB) | HTML Full-text | XML Full-text
Abstract
Studies related to the engineering of calcium binding sites of CGTase are limited. The calcium binding regions that are known for thermostability function were subjected to site-directed mutagenesis in this study. The starting gene-protein is a variant of CGTase Bacillus sp. G1, [...] Read more.
Studies related to the engineering of calcium binding sites of CGTase are limited. The calcium binding regions that are known for thermostability function were subjected to site-directed mutagenesis in this study. The starting gene-protein is a variant of CGTase Bacillus sp. G1, reported earlier and denoted as “parent CGTase” herein. Four CGTase variants (S182G, S182E, N132R and N28R) were constructed. The two variants with a mutation at residue 182, located adjacent to the Ca-I site and the active site cleft, possessed an enhanced thermostability characteristic. The activity half-life of variant S182G at 60 °C was increased to 94 min, while the parent CGTase was only 22 min. This improvement may be attributed to the formation of a shorter α-helix and the alleviation of unfavorable steric strains by glycine at the corresponding region. For the variant S182E, an extra ionic interaction at the A/B domain interface increased the half-life to 31 min, yet it reduced CGTase activity. The introduction of an ionic interaction at the Ca-I site via the mutation N132R disrupted CGTase catalytic activity. Conversely, the variant N28R, which has an additional ionic interaction at the Ca-II site, displayed increased cyclization activity. However, thermostability was not affected. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Aβ-40 Y10F Increases βfibrils Formation but Attenuates the Neurotoxicity of Amyloid-β Peptide
Int. J. Mol. Sci. 2012, 13(5), 5324-5337; doi:10.3390/ijms13055324
Received: 11 March 2012 / Revised: 11 April 2012 / Accepted: 23 April 2012 / Published: 25 April 2012
Cited by 6 | PDF Full-text (888 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aβ-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the [...] Read more.
Alzheimer’s disease (AD) is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aβ-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an Aβ-40 analogue (Aβ-40 Y10F) in which the tyrosine residue was substituted by a structurally similar residue, phenylalanine. The aggregation rate was determined by the Thioflavin T (ThT) assay, in which Aβ-40 Y10F populated an ensemble of folded conformations much quicker and stronger than the wild type Aβ. Biophysical tests subsequently confirmed the results of the ThT assay, suggesting the measured increase of β-aggregation may arise predominantly from enhancement of hydrophobicity upon substitution and thus the propensity of intrinsic β-sheet formation. Nevertheless, Aβ-40 Y10F exhibited remarkably decreased neurotoxicity compared to Aβ-40 which could be partly due to the reduced generation of hydrogen peroxide. These findings may lead to further understanding of the structural perturbation of Aβ to its fibrillation. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)
Open AccessArticle Neurotrophic Effect of Citrus Auraptene: Neuritogenic Activity in PC12 Cells
Int. J. Mol. Sci. 2012, 13(5), 5338-5347; doi:10.3390/ijms13055338
Received: 16 March 2012 / Revised: 9 April 2012 / Accepted: 23 April 2012 / Published: 27 April 2012
Cited by 10 | PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
The activation of extracellular signal-regulated kinases (ERK) leads to a number of cellular changes associated with the development of long-term memory. Using cultured cortical neurons, we previously showed that the n-hexane extract prepared from the peels of Citrus grandis (Kawachi bankan) [...] Read more.
The activation of extracellular signal-regulated kinases (ERK) leads to a number of cellular changes associated with the development of long-term memory. Using cultured cortical neurons, we previously showed that the n-hexane extract prepared from the peels of Citrus grandis (Kawachi bankan) induces the activation of ERK1/2 and that one of the compounds with this ability in the extract is 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), a Citrus polymethoxyflavone. In fact, we found that HMF has the ability to rescue mice from drug-induced learning impairment. This hexane extract contains auraptene (AUR), a coumarin derivative with a monoterpene unit, together with HMF. The present study was designed to investigate the effect of AUR in vitro. Our results show that 1) AUR had the ability to induce the activation of ERK1/2 in not only cortical neurons but also the rat pheochromocytoma cell line (PC12 cells), which is a model system for studies on neuronal proliferation and differentiation; and 2) AUR had the ability to promote neurite outgrowth from PC12 cells. Full article
Open AccessArticle Combined Structure-Based Pharmacophore and 3D-QSAR Studies on Phenylalanine Series Compounds as TPH1 Inhibitors
Int. J. Mol. Sci. 2012, 13(5), 5348-5363; doi:10.3390/ijms13055348
Received: 2 February 2012 / Revised: 13 April 2012 / Accepted: 25 April 2012 / Published: 2 May 2012
Cited by 12 | PDF Full-text (770 KB) | HTML Full-text | XML Full-text
Abstract
Tryptophan hydroxylase-1 (TPH1) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. In this study, a combination of ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity [...] Read more.
Tryptophan hydroxylase-1 (TPH1) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. In this study, a combination of ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity relationship (QSAR) of known TPH1 inhibitors. A multicomplex-based pharmacophore (MCBP) guided method has been suggested to generate a comprehensive pharmacophore of TPH1 kinase based on three crystal structures of TPH1-inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 32 structurally diverse substituted phenylalanine derivatives. The QSAR analyses have been performed on these TPH1 inhibitors based on the MCBP guided alignment. These results may provide important information for further design and virtual screening of novel TPH1 inhibitors. Full article
Open AccessArticle Role of 14-3-3ζ in Platelet Glycoprotein Ibα-von Willebrand Factor Interaction-Induced Signaling
Int. J. Mol. Sci. 2012, 13(5), 5364-5374; doi:10.3390/ijms13055364
Received: 21 March 2012 / Revised: 13 April 2012 / Accepted: 26 April 2012 / Published: 2 May 2012
PDF Full-text (392 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The interaction of platelet glycoprotein (GP) Ib-IX with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus [...] Read more.
The interaction of platelet glycoprotein (GP) Ib-IX with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus formation. 14-3-3ζ has been verified to regulate the VWF binding function of GPIb-IX by interacting with the cytoplasmic domains of GPIb-IX. However, the data regarding the role of 14-3-3ζ in GPIb-IX-VWF interaction-induced signaling still remain controversial. In the present study, the data indicate that the S609A mutation replacing Ser609 of GPIbα with alanine (S609A) significantly prevented the association of 14-3-3ζ with GPIbα before and after the VWF binding to GPIbα. GPIb-IX-VWF interaction-induced activations of Src family kinases and protein kinase C were clearly reduced in S609A mutation. Furthermore, S609A mutation significantly inhibited GPIb-IX-VWF interaction-induced elevation of cytoplasmic Ca2+ levels in flow cytometry analysis. Taken together, these data indicate that the association of 14-3-3ζ with the cytoplasmic domain of GPIbα plays an important role in GPIb-IX-VWF interaction-induced signaling. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids
Int. J. Mol. Sci. 2012, 13(5), 5406-5419; doi:10.3390/ijms13055406
Received: 19 March 2012 / Revised: 24 April 2012 / Accepted: 28 April 2012 / Published: 4 May 2012
Cited by 13 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects [...] Read more.
The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. Full article
Open AccessArticle Extraction Optimization of Water-Extracted Mycelial Polysaccharide from Endophytic Fungus Fusarium oxysporum Dzf17 by Response Surface Methodology
Int. J. Mol. Sci. 2012, 13(5), 5441-5453; doi:10.3390/ijms13055441
Received: 15 March 2012 / Revised: 13 April 2012 / Accepted: 25 April 2012 / Published: 4 May 2012
Cited by 11 | PDF Full-text (443 KB) | HTML Full-text | XML Full-text
Abstract
Water-extracted mycelial polysaccharide (WPS) from the endophytic fungus Fusarium oxysporum Dzf17 isolated from Dioscorea zingiberensis was found to be an efficient elicitor to enhance diosgenin accumulation in D. zingigerensis cultures, and also demonstrated antioxidant activity. In this study, response surface methodology (RSM) [...] Read more.
Water-extracted mycelial polysaccharide (WPS) from the endophytic fungus Fusarium oxysporum Dzf17 isolated from Dioscorea zingiberensis was found to be an efficient elicitor to enhance diosgenin accumulation in D. zingigerensis cultures, and also demonstrated antioxidant activity. In this study, response surface methodology (RSM) was employed to optimize the extraction process of WPS from F. oxysporum Dzf17 using Box-Behnken design (BBD). The ranges of the factors investigated were 1–3 h for extraction time (X1), 80–100 °C for extraction temperature (X2), and 20–40 (v/w) for ratio of water volume (mL) to raw material weight (g) (X3). The experimental data obtained were fitted to a second-order polynomial equation using multiple regression analysis. Statistical analysis showed that the polynomial regression model was in good agreement with the experimental results with the determination coefficient (R2) of 0.9978. By solving the regression equation and analyzing the response surface contour plots, the extraction parameters were optimized as 1.7 h for extraction time, 95 °C for extraction temperature, 39 (v/w) for ratio of water volume (mL) to raw material weight (g), and with 2 extractions. The maximum value (10.862%) of WPS yield was obtained when the WPS extraction process was conducted under the optimal conditions. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Lipid Oxidation Inhibitory Effects and Phenolic Composition of Aqueous Extracts from Medicinal Plants of Colombian Amazonia
Int. J. Mol. Sci. 2012, 13(5), 5454-5467; doi:10.3390/ijms13055454
Received: 1 April 2012 / Revised: 23 April 2012 / Accepted: 2 May 2012 / Published: 4 May 2012
Cited by 10 | PDF Full-text (347 KB) | HTML Full-text | XML Full-text
Abstract
Diverse plants of ethnobotanic interest in Amazonia are commonly used in traditional medicine. We determined the antioxidant potential against lipid peroxidation, the antimicrobial activity, and the polyphenol composition of several Amazonian plants (Brownea rosademonte, Piper glandulosissimum, Piper krukoffii, [...] Read more.
Diverse plants of ethnobotanic interest in Amazonia are commonly used in traditional medicine. We determined the antioxidant potential against lipid peroxidation, the antimicrobial activity, and the polyphenol composition of several Amazonian plants (Brownea rosademonte, Piper glandulosissimum, Piper krukoffii, Piper putumayoense, Solanum grandiflorum, and Vismia baccifera). Extracts from the plant leaf, bark, and stem were prepared as aqueous infusions, as used in folk medicine, and added to rat liver microsomes exposed to iron. The polyphenolic composition was detected by reverse-phase HPLC coupled to diode-array detector and MS/MS analysis. The antimicrobial activity was tested by the spot-on-a-lawn method against several indicator microorganisms. All the extracts inhibited lipid oxidation, except the P. glandulosissimum stem. The plant extracts exhibiting high antioxidant potential (V. baccifera and B. rosademonte) contained high levels of flavanols (particularly, catechin and epicatechin). By contrast, S. grandiflorum leaf, which exhibited very low antioxidant activity, was rich in hydroxycinnamic acids. None of the extracts showed antimicrobial activity. This study demonstrates for the first time the presence of bioactive polyphenolic compounds in several Amazonian plants, and highlights the importance of flavanols as major phenolic contributors to antioxidant activity. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
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Open AccessArticle A LEA Gene Regulates Cadmium Tolerance by Mediating Physiological Responses
Int. J. Mol. Sci. 2012, 13(5), 5468-5481; doi:10.3390/ijms13055468
Received: 29 February 2012 / Revised: 22 April 2012 / Accepted: 26 April 2012 / Published: 4 May 2012
Cited by 6 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the function of a LEA gene (TaLEA1) from Tamrix androssowii in response to heavy metal stress was characterized. Time-course expression analyses showed that NaCl, ZnCl2, CuSO4, and CdCl2 considerably increased the expression [...] Read more.
In this study, the function of a LEA gene (TaLEA1) from Tamrix androssowii in response to heavy metal stress was characterized. Time-course expression analyses showed that NaCl, ZnCl2, CuSO4, and CdCl2 considerably increased the expression levels of the TaLEA1 gene, thereby suggesting that this gene plays a role in the responses to these test stressors. To analyze the heavy metal stress-tolerance mechanism regulated by TaLEA1, TaLEA1-overexpressing transgenic poplar plants (Populus davidiana Dode × P. bollena Lauche) were generated. Significant differences were not observed between the proline content of the transgenic and wild-type (WT) plants before and after CdCl2 stress. However, in comparison with the WT plants, the TaLEA1-transformed poplar plants had significantly higher superoxide dismutase (SOD) and peroxidase (POD) activities, and lower malondialdehyde (MDA) levels under CdCl2 stress. Further, the transgenic plants showed better growth than the WT plants did, indicating that TaLEA1 provides tolerance to cadmium stress. These results suggest that TaLEA1 confers tolerance to cadmium stress by enhancing reactive oxygen species (ROS)-scavenging ability and decreasing lipid peroxidation. Subcellular-localization analysis showed that the TaLEA1 protein was distributed in the cytoplasm and nucleus. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods
Int. J. Mol. Sci. 2012, 13(5), 5482-5497; doi:10.3390/ijms13055482
Received: 24 February 2012 / Revised: 9 April 2012 / Accepted: 16 April 2012 / Published: 7 May 2012
Cited by 6 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
L-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were [...] Read more.
L-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Metabolic Difference of CZ48 in Human and Mouse Liver Microsomes
Int. J. Mol. Sci. 2012, 13(5), 5498-5505; doi:10.3390/ijms13055498
Received: 27 March 2012 / Revised: 27 April 2012 / Accepted: 28 April 2012 / Published: 8 May 2012
Cited by 3 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
CZ48, chemically camptothecin-20-O-propionate hydrate, is currently under clinical investigation. The kinetics of the metabolite camptothecin (CPT) formation and of CZ48 depletion in mouse and human liver microsomes in the presence or absence of NADPH was examined. The formation rate of [...] Read more.
CZ48, chemically camptothecin-20-O-propionate hydrate, is currently under clinical investigation. The kinetics of the metabolite camptothecin (CPT) formation and of CZ48 depletion in mouse and human liver microsomes in the presence or absence of NADPH was examined. The formation rate of camptothecin in human liver microsomes was significantly higher than that in mouse with mean Kms of 1.9 and 0.5 nM and Vmaxs of 9.3 and 2.2 pmol/min/mg, respectively. However, the apparent intrinsic clearance (Vmax/Km) ratios for camptothecin in human and mouse liver microsomes were not significantly different from each other (4.9 versus 4.4) in the presence of NADPH. The depletion of CZ48 in human microsomes was four times faster with 4.55% of CZ48 remaining intact while in mouse 19.11% of the drug remained unchanged after 60 min. These results suggest that there is a remarkable species difference of CZ48 biotransformation between human and mouse. The depletion rate of CZ48 in human liver microsomes is considerably higher than that in the mouse. Full article
Open AccessArticle Evaluation of Antioxidant and Antiproliferative Properties of Three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) Extracts in Vitro
Int. J. Mol. Sci. 2012, 13(5), 5506-5518; doi:10.3390/ijms13055506
Received: 9 April 2012 / Revised: 27 April 2012 / Accepted: 3 May 2012 / Published: 8 May 2012
Cited by 15 | PDF Full-text (449 KB) | HTML Full-text | XML Full-text
Abstract
The total phenolic content, total flavonoid content, vitamin C content, and antioxidant activities of ethanol extracts from different kiwifruit varieties (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) were determined in this study. Multiple scavenging activity assays including the hydroxyl radical, O2·radical, DPPH, and the ABTS+ radical scavenging activity assays were used to identify the antioxidant activities of Actinidia extracts. The cell viability of HepG2 and HT-29 cells was also examined in this study. The results demonstrated that the Actinidia kolomikta extract had a higher antioxidant activity than the other two Actinidia extracts. There is a positive correlation between antioxidant activity and the polyphenols and vitamin C content in all three extracts (R2 ≥ 0.712, p < 0.05). The Actinidia arguta extract had the highest inhibitory effect on HepG2 and HT-29 cell growth. These results provide new insight into the health functions of fruit and demonstrate that Actinidia extracts can potentially have health benefits. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Evaluation of HER2 Gene Amplification in Breast Cancer Using Nuclei Microarray in Situ Hybridization
Int. J. Mol. Sci. 2012, 13(5), 5519-5527; doi:10.3390/ijms13055519
Received: 10 April 2012 / Revised: 26 April 2012 / Accepted: 27 April 2012 / Published: 8 May 2012
Cited by 1 | PDF Full-text (195 KB) | HTML Full-text | XML Full-text
Abstract
Fluorescence in situ hybridization (FISH) assay is considered the “gold standard” in evaluating HER2/neu (HER2) gene status. However, FISH detection is costly and time consuming. Thus, we established nuclei microarray with extracted intact nuclei from paraffin embedded breast cancer tissues for FISH [...] Read more.
Fluorescence in situ hybridization (FISH) assay is considered the “gold standard” in evaluating HER2/neu (HER2) gene status. However, FISH detection is costly and time consuming. Thus, we established nuclei microarray with extracted intact nuclei from paraffin embedded breast cancer tissues for FISH detection. The nuclei microarray FISH (NMFISH) technology serves as a useful platform for analyzing HER2 gene/chromosome 17 centromere ratio. We examined HER2 gene status in 152 cases of invasive ductal carcinomas of the breast that were resected surgically with FISH and NMFISH. HER2 gene amplification status was classified according to the guidelines of the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP). Comparison of the cut-off values for HER2/chromosome 17 centromere copy number ratio obtained by NMFISH and FISH showed that there was almost perfect agreement between the two methods (κ coefficient 0.920). The results of the two methods were almost consistent for the evaluation of HER2 gene counts. The present study proved that NMFISH is comparable with FISH for evaluating HER2 gene status. The use of nuclei microarray technology is highly efficient, time and reagent conserving and inexpensive. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessArticle Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach
Int. J. Mol. Sci. 2012, 13(5), 5528-5541; doi:10.3390/ijms13055528
Received: 24 March 2012 / Revised: 25 April 2012 / Accepted: 3 May 2012 / Published: 9 May 2012
Cited by 5 | PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further [...] Read more.
To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. Full article
(This article belongs to the Special Issue Composite Materials in Skeletal Engineering)
Open AccessArticle A Practical Chemo-enzymatic Approach to Highly Enantio-Enriched 10-Ethyl-7,8-dihydro-γ-ionone Isomers: A Method for the Synthesis of 4,5-Didehydro-α-Ionone
Int. J. Mol. Sci. 2012, 13(5), 5542-5553; doi:10.3390/ijms13055542
Received: 15 March 2012 / Revised: 23 April 2012 / Accepted: 2 May 2012 / Published: 9 May 2012
PDF Full-text (460 KB) | HTML Full-text | XML Full-text
Abstract
An efficient and convenient strategy for the enantioselective synthesis of enantiomerically enriched 10-ethyl-7,8-dihydro-γ-ionone isomers (R)-(+)-7, and (S)-(−)-7 are described utilizing a lipase mediated resolution protocol, and reductive elimination of the secondary allylic alcohol [...] Read more.
An efficient and convenient strategy for the enantioselective synthesis of enantiomerically enriched 10-ethyl-7,8-dihydro-γ-ionone isomers (R)-(+)-7, and (S)-(−)-7 are described utilizing a lipase mediated resolution protocol, and reductive elimination of the secondary allylic alcohol as the key step. The enantioselective and diastereoselective lipase kinetic acetylation of 4-hydroxy-γ-ionone derivatives 6a afforded the 4-acetyl-γ-ionone derivatives (−)-8, and the 4-hydrox-γ-ionone derivatives (+)-6a, which are suitable precursors of the desired products. Stereospecific palladium-mediated elimination of allylic acetate provides the target compounds with an excellent enantiomeric excess and yield. Additionally, the novel 4,5-didehydro-α-ionone 13 is obtained from readily prepared (2,6,6-trimethylcyclohexa-2,4-dien-1-yl) methanol 9. The structures of all newly synthesized compounds have been elucidated by 1H, 13C NMR, GC-MS, and IR spectrometry. These compounds represent a new class of odorants that may be of pivotal relevance in industrial perfumery. Full article
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Open AccessArticle Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture
Int. J. Mol. Sci. 2012, 13(5), 5554-5570; doi:10.3390/ijms13055554
Received: 15 February 2012 / Revised: 15 April 2012 / Accepted: 30 April 2012 / Published: 9 May 2012
Cited by 63 | PDF Full-text (1064 KB) | HTML Full-text | XML Full-text
Abstract
Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles [...] Read more.
Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles. Full article
(This article belongs to the Special Issue Nanotoxicology)
Open AccessArticle Effect of Tea Polyphenol on Oxidative Injury in S180 Cells Induced Hepatocarcinoma Mice
Int. J. Mol. Sci. 2012, 13(5), 5571-5583; doi:10.3390/ijms13055571
Received: 15 March 2012 / Revised: 27 April 2012 / Accepted: 28 April 2012 / Published: 9 May 2012
Cited by 2 | PDF Full-text (230 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of [...] Read more.
The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels. Full article
Open AccessArticle Loss of Genetic Diversity in the Cultured Stocks of the Large Yellow Croaker, Larimichthys crocea, Revealed by Microsatellites
Int. J. Mol. Sci. 2012, 13(5), 5584-5597; doi:10.3390/ijms13055584
Received: 14 March 2012 / Revised: 23 April 2012 / Accepted: 2 May 2012 / Published: 9 May 2012
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Abstract
The large yellow croaker (Larimichthys crocea) is the most important mariculture fish species in China and the wild stocks of this croaker have collapsed in the past decades due to high fishing pressure and habitat degradation. Due to a lack [...] Read more.
The large yellow croaker (Larimichthys crocea) is the most important mariculture fish species in China and the wild stocks of this croaker have collapsed in the past decades due to high fishing pressure and habitat degradation. Due to a lack of wild croaker samples, however, studies concerning the genetic changes of the cultured croaker stocks compared to their wild counterparts were never conducted. Here, we collected three wild populations in the northern and central East China Sea during fisheries survey and investigated the differences in terms of genetic diversity and differentiation between and within cultured stocks and wild populations. Our results demonstrated that the cultured croaker had significantly reduced genetic diversity in contrast to the wild populations, and also presented statistically significant differentiation from the wild, indicating that enhancement of the current wild stock should be conducted with caution. These changes may be caused by founder effects, artificial selection and random genetic drift. With a relatively high level of genetic diversity, the wild populations showed important value for improving the ongoing breeding program of this croaker. Further, we detected no differentiation among the wild populations, suggesting that the wild croaker in the northern and central East China Sea should be considered as one unit for management and conservation. Full article
Open AccessArticle Screening of New Microsatellite DNA Markers from the Genome of Platyeriocheir formosa
Int. J. Mol. Sci. 2012, 13(5), 5598-5606; doi:10.3390/ijms13055598
Received: 20 February 2012 / Revised: 22 April 2012 / Accepted: 24 April 2012 / Published: 9 May 2012
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Abstract
The catadromous Platyeriocheir formosa is a crab endemic in Taiwan. To conserve P. formosa population diversity and ensure the sustainable use of this natural resource, we have developed new genetic markers, 17 polymorphic microsatellite loci, to promote the study of its population [...] Read more.
The catadromous Platyeriocheir formosa is a crab endemic in Taiwan. To conserve P. formosa population diversity and ensure the sustainable use of this natural resource, we have developed new genetic markers, 17 polymorphic microsatellite loci, to promote the study of its population genetics in the future. In this study, more than 70 microsatellite sequences were found. Among these, 18 loci were selected to analyze the genetic diversity of P. formosa. With the exception of the Pfo15 locus, all of the remaining loci were polymorphic with allelic numbers ranging from 3–14. Heterozygosity within all 17 polymorphic loci ranged from 0.2–0.95 with an average of 0.55, which suggested that these loci are proper markers for studying population genetics. After we tested cross-specific amplification, eight and six primer sets could be successfully used for the amplification of microsatellite loci in morphologically similar Eriocheir sinensis and E. japonica, respectively; this suggests that they are useful markers for closely related species. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Modification of MCF-10A Cells with Pioglitazone and Serum-Rich Growth Medium Increases Soluble Factors in the Conditioned Medium, Likely Reducing BT-474 Cell Growth
Int. J. Mol. Sci. 2012, 13(5), 5607-5627; doi:10.3390/ijms13055607
Received: 13 February 2012 / Revised: 25 April 2012 / Accepted: 28 April 2012 / Published: 10 May 2012
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Abstract
In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or [...] Read more.
In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy. Full article
(This article belongs to the Special Issue Advances in Molecular Immunology)
Open AccessArticle Anti-TNF-α Activity of Portulaca oleracea in Vascular Endothelial Cells
Int. J. Mol. Sci. 2012, 13(5), 5628-5644; doi:10.3390/ijms13055628
Received: 20 February 2012 / Revised: 20 April 2012 / Accepted: 2 May 2012 / Published: 10 May 2012
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Abstract
Vascular inflammation plays a key role in the pathogenesis and progression of atherosclerosis, a main complication of diabetes. The present study investigated whether an aqueous extract of Portulaca oleracea (AP) prevents the TNF-α-induced vascular inflammatory process in the human umbilical vein endothelial [...] Read more.
Vascular inflammation plays a key role in the pathogenesis and progression of atherosclerosis, a main complication of diabetes. The present study investigated whether an aqueous extract of Portulaca oleracea (AP) prevents the TNF-α-induced vascular inflammatory process in the human umbilical vein endothelial cell (HUVEC). The stimulation of TNF-α induced overexpression of adhesion molecules affects vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1 and E-selectin for example. However, AP significantly suppressed TNF-α-induced over-expression of these adhesion molecules in a dose-dependent manner. In addition, pretreatment with AP dose-dependently reduced an increase of the adhesion of HL-60 cells to TNF-α-induced HUVEC. Furthermore, we observed that stimulation of TNF-α significantly increased intracellular reactive oxygen species (ROS) production. However, pretreatment with AP markedly blocked TNF-α-induced ROS production in a dose-dependent manner. The western blot and immunofluorescence analysis showed that AP inhibited the translocation of p65 NF-κB to the nucleus. In addition, AP suppressed the TNF-α-induced degradation of IκB-α and attenuated the TNF-α-induced NF-κB binding. AP also effectively reduced TNF-α-induced mRNA expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 in a dose-dependent manner. Taken together, AP prevents the vascular inflammatory process through the inhibition of intracellular ROS production and NF-κB activation as well as the reduction of adhesion molecule expression in TNF-α-induced HUVEC. These results suggested that AP might have a potential therapeutic effect by inhibiting the vascular inflammation process in vascular diseases such as atherosclerosis. Full article
Open AccessArticle Genetic Diversity of Pinus nigra Arn. Populations in Southern Spain and Northern Morocco Revealed By Inter-Simple Sequence Repeat Profiles
Int. J. Mol. Sci. 2012, 13(5), 5645-5658; doi:10.3390/ijms13055645
Received: 13 April 2012 / Revised: 3 May 2012 / Accepted: 7 May 2012 / Published: 10 May 2012
Cited by 13 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
Eight Pinus nigra Arn. populations from Southern Spain and Northern Morocco were examined using inter-simple sequence repeat markers to characterize the genetic variability amongst populations. Pair-wise population genetic distance ranged from 0.031 to 0.283, with a mean of 0.150 between populations. The highest [...] Read more.
Eight Pinus nigra Arn. populations from Southern Spain and Northern Morocco were examined using inter-simple sequence repeat markers to characterize the genetic variability amongst populations. Pair-wise population genetic distance ranged from 0.031 to 0.283, with a mean of 0.150 between populations. The highest inter-population average distance was between PaCU from Cuenca and YeCA from Cazorla, while the lowest distance was between TaMO from Morocco and MA Sierra Mágina populations. Analysis of molecular variance (AMOVA) and Nei’s genetic diversity analyses revealed higher genetic variation within the same population than among different populations. Genetic differentiation (Gst) was 0.233. Cuenca showed the highest Nei’s genetic diversity followed by the Moroccan region, Sierra Mágina, and Cazorla region. However, clustering of populations was not in accordance with their geographical locations. Principal component analysis showed the presence of two major groups—Group 1 contained all populations from Cuenca while Group 2 contained populations from Cazorla, Sierra Mágina and Morocco—while Bayesian analysis revealed the presence of three clusters. The low genetic diversity observed in PaCU and YeCA is probably a consequence of inappropriate management since no estimation of genetic variability was performed before the silvicultural treatments. Data indicates that the inter-simple sequence repeat (ISSR) method is sufficiently informative and powerful to assess genetic variability among populations of P. nigra. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Comparison of Standard 1.5 T vs. 3 T Optimized Protocols in Patients Treated with Glatiramer Acetate. A Serial MRI Pilot Study
Int. J. Mol. Sci. 2012, 13(5), 5659-5673; doi:10.3390/ijms13055659
Received: 22 March 2012 / Revised: 23 April 2012 / Accepted: 3 May 2012 / Published: 10 May 2012
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Abstract
This study explored the effect of glatiramer acetate (GA, 20 mg) on lesion activity using the 1.5 T standard MRI protocol (single dose gadolinium [Gd] and 5-min delay) or optimized 3 T protocol (triple dose of Gd, 20-min delay and application of an off-resonance saturated magnetization transfer pulse). A 15-month, phase IV, open-label, single-blinded, prospective, observational study included 12 patients with relapsing-remitting multiple sclerosis who underwent serial MRI scans (Days −45, −20, 0; the minus ign indicates the number of days before GA treatment; and on Days 30, 60, 90, 120, 150, 180, 270 and 360 during GA treatment) on 1.5 T and 3 T protocols. Cumulative number and volume of Gd enhancing (Gd-E) and T2 lesions were calculated. At Days −45 and 0, there were higher number (p < 0.01) and volume (p < 0.05) of Gd-E lesions on 3 T optimized compared to 1.5 T standard protocol. However, at 180 and 360 days of the study, no significant differences in total and cumulative number of new Gd-E and T 2 lesions were found between the two protocols. Compared to pre-treatment period, at Days 180 and 360 a significantly greater decrease in the cumulative number of Gd-E lesions (p = 0.03 and 0.021, respectively) was found using the 3 T vs. the 1.5 T protocol (p = NS for both time points). This MRI mechanistic study suggests that GA may exert a greater effect on decreasing lesion activity as measured on 3 T optimized compared to 1.5 T standard protocol. Full article
(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)
Open AccessArticle Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet
Int. J. Mol. Sci. 2012, 13(5), 5674-5699; doi:10.3390/ijms13055674
Received: 19 April 2012 / Revised: 26 April 2012 / Accepted: 2 May 2012 / Published: 10 May 2012
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Abstract
The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four [...] Read more.
The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four linear peptide epitopes that mimic the three-dimensional structure of bridging sheet by using molecular modeling. Chemically synthesized peptides BS3 and BS4 showed a fair degree of antigenicity when tested in ELISA with IgG purified from HIV+ broadly neutralizing sera while the production of synthetic peptides BS1 and BS2 failed due to their high degree of hydrophobicity. To overcome this limitation, we linked all four BS peptides to the COOH-terminus of GST protein to test both their antigenicity and immunogenicity. Only the BS1 peptide showed good antigenicity; however, no envelope specific antibodies were elicited upon mice immunization. Therefore we performed further analyses by linking BS1 peptide to the NH2-terminus of the E2 scaffold from the Geobacillus Stearothermophylus PDH complex. The E2-BS1 fusion peptide showed good antigenic results, however only one immunized rabbit elicited good antibody titers towards both the monomeric and oligomeric viral envelope glycoprotein (Env). In addition, moderate neutralizing antibodies response was elicited against two HIV-1 clade B and one clade C primary isolates. These preliminary data validate the peptide mimotope approach as a promising tool to obtain an effective HIV-1 vaccine. Full article
(This article belongs to the Special Issue Advances in Molecular Immunology)
Open AccessArticle Characterization of CdTe Films Deposited at Various Bath Temperatures and Concentrations Using Electrophoretic Deposition
Int. J. Mol. Sci. 2012, 13(5), 5706-5714; doi:10.3390/ijms13055706
Received: 31 December 2011 / Revised: 13 April 2012 / Accepted: 24 April 2012 / Published: 11 May 2012
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Abstract
CdTe film was deposited using the electrophoretic deposition technique onto an ITO glass at various bath temperatures. Four batch film compositions were used by mixing 1 to 4 wt% concentration of CdTe powder with 10 mL of a solution of methanol and [...] Read more.
CdTe film was deposited using the electrophoretic deposition technique onto an ITO glass at various bath temperatures. Four batch film compositions were used by mixing 1 to 4 wt% concentration of CdTe powder with 10 mL of a solution of methanol and toluene. X-ray Diffraction analysis showed that the films exhibited polycrystalline nature of zinc-blende structure with the (111) orientation as the most prominent peak. From the Atomic Force Microscopy, the thickness and surface roughness of the CdTe film increased with the increase of CdTe concentration. The optical energy band gap of film decreased with the increase of CdTe concentration, and with the increase of isothermal bath temperature. The film thickness increased with respect to the increase of CdTe concentration and bath temperature, and following, the numerical expression for the film thickness with respect to these two variables has been established. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Immune Responses in Pigs Induced by Recombinant DNA Vaccine Co-Expressing Swine IL-18 and Membrane Protein of Porcine Reproductive and Respiratory Syndrome Virus
Int. J. Mol. Sci. 2012, 13(5), 5715-5728; doi:10.3390/ijms13055715
Received: 21 February 2012 / Revised: 15 April 2012 / Accepted: 3 May 2012 / Published: 11 May 2012
Cited by 6 | PDF Full-text (518 KB) | HTML Full-text | XML Full-text
Abstract
In this study, two DNA vaccines, which express the membrane (M) protein of porcine respiratory and reproductive syndrome virus (PRRSV) (pEGFP-M) and co-express both M and swine IL-18 (pEGFP-IL18-M), were constructed and their abilities to induce humoral and cellular responses in piglets were comparatively evaluated. Experimental results showed that both recombinant DNA vaccines could not elicit neutralizing antibodies in the immunized piglets. However, both DNA vaccines elicited Th1-biased cellular immune responses. Notably, pigs immunized with the plasmid pEGFP-IL18-M developed significantly higher levels of IFN-γ and IL-2 production response and stronger specific T-lymphocyte proliferation response than the pigs inoculated with the plasmids pEGFP-M and pEGFP-IL18 (P < 0.05). These results illustrated that co-expression of M and IL-18 proteins could significantly improve the potency of DNA vaccination on the activation of vaccine-induced virus-specific cell-mediated immune responses in pigs, which may be used as a strategy to develop a new generation of vaccines against highly pathogenic PRRSV. Full article
Open AccessArticle Ginsenoside Rg3 Reduces Lipid Accumulation with AMP-Activated Protein Kinase (AMPK) Activation in HepG2 Cells
Int. J. Mol. Sci. 2012, 13(5), 5729-5739; doi:10.3390/ijms13055729
Received: 28 February 2012 / Revised: 10 April 2012 / Accepted: 7 May 2012 / Published: 11 May 2012
Cited by 24 | PDF Full-text (152 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD) is one of the main causes of mortality worldwide, and dyslipidemia is a major risk factor for CVD. Ginseng has been widely used in the clinic to treat CVD. Ginsenoside Rg3, one of the major active components of ginseng, [...] Read more.
Cardiovascular disease (CVD) is one of the main causes of mortality worldwide, and dyslipidemia is a major risk factor for CVD. Ginseng has been widely used in the clinic to treat CVD. Ginsenoside Rg3, one of the major active components of ginseng, has been reported to exhibit antiobesity, antidiabetic, and cardioprotective effects. However, the effect of ginsenoside Rg3 on hepatic lipid metabolism remains unclear. Therefore, we investigated whether ginsenoside Rg3 would regulate hepatic lipid metabolism with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Ginsenoside Rg3 significantly reduced hepatic cholesterol and triglyceride levels. Furthermore, ginsenoside Rg3 inhibited expression of sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR). Ginsenoside Rg3 increased activity of AMPK, a major regulator of energy metabolism. These results suggest that ginsenoside Rg3 reduces hepatic lipid accumulation with inhibition of SREBP-2 and HMGCR expression and stimulation of AMPK activity in HepG2 cells. Therefore, ginsenoside Rg3 may be beneficial as a food ingredient to lower the risk of CVD by regulating dyslipidemia. Full article
Open AccessArticle Gastroprotective Effect of Selenium on Ethanol-Induced Gastric Damage in Rats
Int. J. Mol. Sci. 2012, 13(5), 5740-5750; doi:10.3390/ijms13055740
Received: 11 April 2012 / Revised: 1 May 2012 / Accepted: 7 May 2012 / Published: 11 May 2012
Cited by 4 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to [...] Read more.
In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 μg/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 μg/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Streptozotocin-Induced Cytotoxicity, Oxidative Stress and Mitochondrial Dysfunction in Human Hepatoma HepG2 Cells
Int. J. Mol. Sci. 2012, 13(5), 5751-5767; doi:10.3390/ijms13055751
Received: 7 March 2012 / Revised: 12 April 2012 / Accepted: 26 April 2012 / Published: 11 May 2012
Cited by 19 | PDF Full-text (680 KB) | HTML Full-text | XML Full-text
Abstract
Streptozotocin (STZ) is an antibiotic often used in the treatment of different types of cancers. It is also highly cytotoxic to the pancreatic beta-cells and therefore is commonly used to induce experimental type 1 diabetes in rodents. Resistance towards STZ-induced cytotoxicity in [...] Read more.
Streptozotocin (STZ) is an antibiotic often used in the treatment of different types of cancers. It is also highly cytotoxic to the pancreatic beta-cells and therefore is commonly used to induce experimental type 1 diabetes in rodents. Resistance towards STZ-induced cytotoxicity in cancer cells has also been reported. Our previous studies have reported organ-specific toxicity and metabolic alterations in STZ-induced diabetic rats. STZ induces oxidative stress and metabolic complications. The precise molecular mechanism of STZ-induced toxicity in different tissues and carcinomas is, however, unclear. We have, therefore, investigated the mechanism of cytotoxicity of STZ in HepG2 hepatoma cells in culture. Cells were treated with different doses of STZ for various time intervals and the cytotoxicity was studied by observing the alterations in oxidative stress, mitochondrial redox and metabolic functions. STZ induced ROS and RNS formation and oxidative stress as measured by an increase in the lipid peroxidation as well as alterations in the GSH-dependent antioxidant metabolism. The mitochondria appear to be a highly sensitive target for STZ toxicity. The mitochondrial membrane potential and enzyme activities were altered in STZ treated cells resulting in the inhibition of ATP synthesis. ROS-sensitive mitochondrial aconitase activity was markedly inhibited suggesting increased oxidative stress in STZ-induced mitochondrial toxicity. These results suggest that STZ-induced cytotoxicity in HepG2 cells is mediated, at least in part, by the increase in ROS/RNS production, oxidative stress and mitochondrial dysfunction. Our study may be significant for better understanding the mechanisms of STZ action in chemotherapy and drug induced toxicity. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)
Open AccessArticle Expression of Selected Ginkgo biloba Heat Shock Protein Genes After Cold Treatment Could Be Induced by Other Abiotic Stress
Int. J. Mol. Sci. 2012, 13(5), 5768-5788; doi:10.3390/ijms13055768
Received: 21 March 2012 / Revised: 26 April 2012 / Accepted: 2 May 2012 / Published: 15 May 2012
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Abstract
Heat shock proteins (HSPs) play various stress-protective roles in plants. In this study, three HSP genes were isolated from a suppression subtractive hybridization (SSH) cDNA library of Ginkgo biloba leaves treated with cold stress. Based on the molecular weight, the three genes [...] Read more.
Heat shock proteins (HSPs) play various stress-protective roles in plants. In this study, three HSP genes were isolated from a suppression subtractive hybridization (SSH) cDNA library of Ginkgo biloba leaves treated with cold stress. Based on the molecular weight, the three genes were designated GbHSP16.8, GbHSP17 and GbHSP70. The full length of the three genes were predicted to encode three polypeptide chains containing 149 amino acids (Aa), 152 Aa, and 657 Aa, and their corresponding molecular weights were predicted as follows: 16.67 kDa, 17.39 kDa, and 71.81 kDa respectively. The three genes exhibited distinctive expression patterns in different organs or development stages. GbHSP16.8 and GbHSP70 showed high expression levels in leaves and a low level in gynoecia, GbHSP17 showed a higher transcription in stamens and lower level in fruit. This result indicates that GbHSP16.8 and GbHSP70 may play important roles in Ginkgo leaf development and photosynthesis, and GbHSP17 may play a positive role in pollen maturation. All three GbHSPs were up-regulated under cold stress, whereas extreme heat stress only caused up-regulation of GbHSP70, UV-B treatment resulted in up-regulation of GbHSP16.8 and GbHSP17, wounding treatment resulted in up-regulation of GbHSP16.8 and GbHSP70, and abscisic acid (ABA) treatment caused up-regulation of GbHSP70 primarily. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
Open AccessArticle Relationships Between Base-Catalyzed Hydrolysis Rates or Glutathione Reactivity for Acrylates and Methacrylates and Their NMR Spectra or Heat of Formation
Int. J. Mol. Sci. 2012, 13(5), 5789-5800; doi:10.3390/ijms13055789
Received: 13 March 2012 / Revised: 26 April 2012 / Accepted: 8 May 2012 / Published: 15 May 2012
Cited by 3 | PDF Full-text (254 KB) | HTML Full-text | XML Full-text
Abstract
The NMR chemical shift, i.e., the π-electron density of the double bond, of acrylates and methacrylates is related to the reactivity of their monomers. We investigated quantitative structure-property relationships (QSPRs) between the base-catalyzed hydrolysis rate constants (k1) or the [...] Read more.
The NMR chemical shift, i.e., the π-electron density of the double bond, of acrylates and methacrylates is related to the reactivity of their monomers. We investigated quantitative structure-property relationships (QSPRs) between the base-catalyzed hydrolysis rate constants (k1) or the rate constant with glutathione (GSH) (log kGSH) for acrylates and methacrylates and the 13C NMR chemical shifts of their α,β-unsaturated carbonyl groups (δCα and δCβ) or heat of formation (Hf) calculated by the semi-empirical MO method. Reported data for the independent variables were employed. A significant linear relationship between k1 and δCβ, but not δCα, was obtained for methacrylates (r2 = 0.93), but not for acrylates. Also, a significant relationship between k1 and Hf was obtained for both acrylates and methacrylates (r2 = 0.89). By contrast, log kGSH for acrylates and methacrylates was linearly related to their δCβ (r2 = 0.99), but not to Hf. These findings indicate that the 13C NMR chemical shifts and calculated Hf values for acrylates and methacrylates could be valuable for estimating the hydrolysis rate constants and GSH reactivity of these compounds. Also, these data for monomers may be an important tool for examining mechanisms of reactivity. Full article
Open AccessArticle In Vitro Antioxidant and Anti-Proliferation Activities of Polysaccharides from Various Extracts of Different Mushrooms
Int. J. Mol. Sci. 2012, 13(5), 5801-5817; doi:10.3390/ijms13055801
Received: 14 March 2012 / Revised: 28 April 2012 / Accepted: 7 May 2012 / Published: 15 May 2012
Cited by 16 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
Polysaccharides were extracted from eight kinds of Chinese mushrooms using three solvents and were evaluated for their total carbohydrate, polyphenolic and protein contents, and antioxidant and anti-proliferation activities. The results suggested that all the polysaccharides had significant antioxidant capacities (EC50 ranged [...] Read more.
Polysaccharides were extracted from eight kinds of Chinese mushrooms using three solvents and were evaluated for their total carbohydrate, polyphenolic and protein contents, and antioxidant and anti-proliferation activities. The results suggested that all the polysaccharides had significant antioxidant capacities (EC50 ranged from 1.70 ± 0.42 to 65.98 ± 1.74 μM TE/g crude polysaccharide inhibition of ABTS+, EC50 ranged from 5.06 ± 0.12 to 127.38 ± 1.58 mg VCE/g CP scavenging of OH· and EC50 ranged from 0.70 ± 0.04 to 33.54 ± 0.49 mg VCE/g CP inhibition of lipid peroxidation) (TE: trolox equivalent; VCE: VC equivalent; CP: crude polysaccharide). The acid extracts of Russula vinosa Lindblad had the highest ABTS+ scavenging activity. Aqueous extracts of Dictyophora indusiata and Hohenbuehelia serotina possessed, respectively, the highest OH· scavenging capacity and ability to inhibit lipid peroxidation. Mushroom extracts also inhibited proliferation of HeLa and HepG2 cells in a dose-dependent manner. These results indicate that the mushroom polysaccharides might be potential antioxidant resources. Full article
Open AccessArticle Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703
Int. J. Mol. Sci. 2012, 13(5), 5818-5831; doi:10.3390/ijms13055818
Received: 6 April 2012 / Revised: 23 April 2012 / Accepted: 7 May 2012 / Published: 15 May 2012
Cited by 11 | PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results [...] Read more.
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Isolation and Expression of Glucosinolate Synthesis Genes CYP83A1 and CYP83B1 in Pak Choi (Brassica rapa L. ssp. chinensis var. communis (N. Tsen & S.H. Lee) Hanelt)
Int. J. Mol. Sci. 2012, 13(5), 5832-5843; doi:10.3390/ijms13055832
Received: 6 February 2012 / Revised: 22 April 2012 / Accepted: 27 April 2012 / Published: 15 May 2012
Cited by 2 | PDF Full-text (230 KB) | HTML Full-text | XML Full-text
Abstract
CYP83A1 and CYP83B1 are two key synthesis genes in the glucosinolate biosynthesis pathway. CYP83A1 mainly metabolizes the aliphatic oximes to form aliphatic glucosinolate and CYP83B1 mostly catalyzes aromatic oximes to synthesis corresponding substrates for aromatic and indolic glucosinolates. In this study, two CYP83A1 genes named BcCYP83A1-1 (JQ289997), BcCYP83A1-2 (JQ289996) respectively and one CYP83B1 (BcCYP83B1, HM347235) gene were cloned from the leaves of pak choi (Brassica rapa L. ssp. chinensis var. communis (N. Tsen & S.H. Lee) Hanelt) “Hangzhou You Dong Er” cultivar. Their ORFs were 1506, 1509 and 1500 bp in length, encoding 501, 502 and 499 amino acids, respectively. The predicted amino acid sequences of CYP83A1-1, CYP83A1-2 and CYP83B1 shared high sequence identity of 87.65, 86.48 and 95.59% to the corresponding ones in Arabidopsis, and 98.80, 98.61 and 98.80% to the corresponding ones in Brassica pekinensis (Chinese cabbage), respectively. Quantitative real-time PCR analysis indicated that both CYP83A1 and CYP83B1 expressed in roots, leaves and petioles of pak choi, while the transcript abundances of CYP83A1 were higher in leaves than in petioles and roots, whereas CYP83B1 showed higher abundances in roots. The expression levels of glucosinolate biosynthetic genes were consistent with the glucosinolate profile accumulation in shoots of seven cultivars and three organs. The isolation and characterization of the glucosinolate synthesis genes in pak choi would promote the way for further development of agronomic traits via genetic engineering. Full article
Open AccessArticle Isolation and Characterization of 15 New Microsatellite Markers in Oncomelania hupensis, the Snail Intermediate Host of Schistosoma japonicum in Mainland China
Int. J. Mol. Sci. 2012, 13(5), 5844-5850; doi:10.3390/ijms13055844
Received: 27 March 2012 / Revised: 19 April 2012 / Accepted: 10 May 2012 / Published: 15 May 2012
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Abstract
Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, which plays a key role during the transmission of schistosomiasis. It is mainly found in the Yangtze River valley and mountains or hills in southwest China. In this paper, we described [...] Read more.
Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, which plays a key role during the transmission of schistosomiasis. It is mainly found in the Yangtze River valley and mountains or hills in southwest China. In this paper, we described 15 new microsatellite makers in O. hupensis. Polymorphism of each locus was assessed in 80 individuals from four wild populations (n = 20 per population). The number of alleles per locus ranged from 6 to 29, with an average of 15.8. The observed (HO) and expected (HE) heterozygosities varied from 0.397 to 0.851 and from 0.696 to 0.948, respectively. These microsatellite markers will be useful for population genetic studies and genome mapping in O. hupensis. Full article
Open AccessArticle Room-Temperature Fluorescence Lifetime of Pseudoisocyanine (PIC) J Excitons with Various Aggregate Morphologies in Relation to Microcavity Polariton Formation
Int. J. Mol. Sci. 2012, 13(5), 5851-5865; doi:10.3390/ijms13055851
Received: 7 March 2012 / Revised: 12 April 2012 / Accepted: 3 May 2012 / Published: 15 May 2012
Cited by 5 | PDF Full-text (635 KB) | HTML Full-text | XML Full-text
Abstract
The results of room-temperature fluorescence lifetime measurements are reported for the excitation of J aggregates (Js) of pseudoisocyanine chloride (PIC-Cl) prepared in potassium polyvinyl sulfate (PVS) polymer thin films, their aqueous solutions, and NaCl aqueous solutions. Variations of the microscopic morphologies of [...] Read more.
The results of room-temperature fluorescence lifetime measurements are reported for the excitation of J aggregates (Js) of pseudoisocyanine chloride (PIC-Cl) prepared in potassium polyvinyl sulfate (PVS) polymer thin films, their aqueous solutions, and NaCl aqueous solutions. Variations of the microscopic morphologies of the aggregates were investigated. The results show that fluorescence decay features correlated to the morphology change. The observed fluorescence lifetime and quantum efficiency of PIC J aggregates (PIC-Js) in a NaCl aqueous solution were 310 ps and 28%, respectively. The lifetime of the fibril-shaped macroaggregates prepared in PVS thin films was below the instrumental time resolution of 5 ps, and the efficiency decreased to below 3%. The results indicate that PIC-Js prepared with PVS polymers have an increased nonradiative contribution to the excitation deactivation process. In particular, macro-Js with isolated fibril-shaped structures revealed nonradiative pathway(s) that are closely associated to the specific packaging morphology of the constituent meso-Js. The possibility of a destructive effect on the formation of cavity-polaritons is also discussed. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Loss of p16Ink4a Function Rescues Cellular Senescence Induced by Telomere Dysfunction
Int. J. Mol. Sci. 2012, 13(5), 5866-5877; doi:10.3390/ijms13055866
Received: 11 February 2012 / Revised: 3 May 2012 / Accepted: 10 May 2012 / Published: 16 May 2012
Cited by 5 | PDF Full-text (465 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
p16Ink4a is a tumor suppressor and a marker for cellular senescence. Previous studies have shown that p16Ink4a plays an important role in the response to DNA damage signals caused by telomere dysfunction. In this study, we crossed Wrn [...] Read more.
p16Ink4a is a tumor suppressor and a marker for cellular senescence. Previous studies have shown that p16Ink4a plays an important role in the response to DNA damage signals caused by telomere dysfunction. In this study, we crossed Wrn−/− and p16Ink4a−/− mice to knock out the p16Ink4a function in a Wrn null background. Growth curves showed that loss of p16Ink4a could rescue the growth barriers that are observed in Wrn−/− mouse embryonic fibroblasts (MEFs). By challenging the MEFs with the global genotoxin doxorubicin, we showed that loss of p16Ink4a did not dramatically affect the global DNA damage response of Wrn−/− MEFs induced by doxorubicin. However, in response to telomere dysfunction initiated by the telomere damaging protein TRF2∆B∆M, loss of p16Ink4a could partially overcome the DNA damage response by disabling p16Ink4a up-regulation and reducing the accumulation of γ-H2AX that is observed in Wrn−/− MEFs. Furthermore, in response to TRF2∆B∆M overexpression, Wrn−/− MEFs senesced within several passages. In contrast, p16Ink4a−/− and p16Ink4a−/−Wrn−/− MEFs could continuously grow and lose expression of the exogenous TRF2∆B∆M in their late passages. In summary, our data suggest that in the context of telomere dysfunction, loss of p16Ink4a function could prevent cells from senescence. These results shed light on the anti-aging strategy through regulation of p16Ink4a expression. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle A Comparative Study on the Mechanical, Thermal and Morphological Characterization of Poly(lactic acid)/Epoxidized Palm Oil Blend
Int. J. Mol. Sci. 2012, 13(5), 5878-5898; doi:10.3390/ijms13055878
Received: 29 March 2012 / Revised: 24 April 2012 / Accepted: 8 May 2012 / Published: 16 May 2012
Cited by 20 | PDF Full-text (1296 KB) | HTML Full-text | XML Full-text
Abstract
In this work, poly(lactic acid) (PLA) a fully biodegradable thermoplastic polymer matrix was melt blended with three different epoxidized palm oil (EPO). The aim of this research was to enhance the flexibility, mechanical and thermal properties of PLA. The blends were prepared [...] Read more.
In this work, poly(lactic acid) (PLA) a fully biodegradable thermoplastic polymer matrix was melt blended with three different epoxidized palm oil (EPO). The aim of this research was to enhance the flexibility, mechanical and thermal properties of PLA. The blends were prepared at various EPO contents of 1, 2, 3, 4 and 5 wt% and characterized. The SEM analysis evidenced successful modification on the neat PLA brittle morphology. Tensile tests indicate that the addition of 1 wt% EPO is sufficient to improve the strength and flexibility compared to neat PLA. Additionally, the flexural and impact properties were also enhanced. Further, DSC analysis showed that the addition of EPO results in a decrease in Tg, which implies an increase in the PLA chain mobility. In the presence of 1 wt% EPO, TGA results revealed significant increase in the thermal stability by 27%. Among the three EPOs used, EPO(3) showed the best mechanical and thermal properties compared to the other EPO’s, with an optimum loading of 1 wt%. Conclusively, EPO showed a promising outcome to overcome the brittleness and improve the overall properties of neat PLA, thus can be considered as a potential plasticizer. Full article
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Open AccessArticle In Vitro Inhibition of Histamine Release Behavior of Cetirizine Intercalated into Zn/Al- and Mg/Al-Layered Double Hydroxides
Int. J. Mol. Sci. 2012, 13(5), 5899-5916; doi:10.3390/ijms13055899
Received: 31 March 2012 / Revised: 3 May 2012 / Accepted: 7 May 2012 / Published: 16 May 2012
Cited by 22 | PDF Full-text (641 KB) | HTML Full-text | XML Full-text
Abstract
The intercalation of cetirizine into two types of layered double hydroxides, Zn/Al and Mg/Al, has been investigated by the ion exchange method to form CTZAN and CTMAN nanocomposites, respectively. The basal spacing of the nanocomposites were expanded to 31.9 Å for CTZAN [...] Read more.
The intercalation of cetirizine into two types of layered double hydroxides, Zn/Al and Mg/Al, has been investigated by the ion exchange method to form CTZAN and CTMAN nanocomposites, respectively. The basal spacing of the nanocomposites were expanded to 31.9 Å for CTZAN and 31.2 Å for CTMAN, suggesting that cetirizine anion was intercalated into Layered double hydroxides (LDHs) and arranged in a tilted bilayer fashion. A Fourier transform infrared spectroscopy (FTIR) study supported the formation of both the nanocomposites, and the intercalated cetirizine is thermally more stable than its counterpart in free state. The loading of cetirizine in the nanocomposite was estimated to be about 57.2% for CTZAN and 60.7% CTMAN. The cetirizine release from the nanocomposites show sustained release manner and the release rate of cetirizine from CTZAN and CTMAN nanocomposites at pH 7.4 is remarkably lower than that at pH 4.8, presumably due to the different release mechanism. The inhibition of histamine release from RBL2H3 cells by the free cetirizine is higher than the intercalated cetirizine both in CTZAN and CTMAN nanocomposites. The viability in human Chang liver cells at 1000 μg/mL for CTZAN and CTMAN nanocomposites are 74.5 and 91.9%, respectively. Full article
Open AccessArticle Diversity and Biosynthetic Potential of Culturable Actinomycetes Associated with Marine Sponges in the China Seas
Int. J. Mol. Sci. 2012, 13(5), 5917-5932; doi:10.3390/ijms13055917
Received: 2 March 2012 / Revised: 27 April 2012 / Accepted: 7 May 2012 / Published: 16 May 2012
Cited by 16 | PDF Full-text (441 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The diversity and secondary metabolite potential of culturable actinomycetes associated with eight different marine sponges collected from the South China Sea and the Yellow sea were investigated. A total of 327 strains were isolated and 108 representative isolates were selected for phylogenetic [...] Read more.
The diversity and secondary metabolite potential of culturable actinomycetes associated with eight different marine sponges collected from the South China Sea and the Yellow sea were investigated. A total of 327 strains were isolated and 108 representative isolates were selected for phylogenetic analysis. Ten families and 13 genera of Actinomycetales were detected, among which five genera represent first records isolated from marine sponges. Oligotrophic medium M5 (water agar) proved to be efficient for selective isolation, and “MicromonosporaStreptomyces” was proposed as the major distribution group of sponge-associated actinomycetes from the China Seas. Ten isolates are likely to represent novel species. Sponge Hymeniacidon perleve was found to contain the highest genus diversity (seven genera) of actinomycetes. Housekeeping gene phylogenetic analyses of the isolates indicated one ubiquitous Micromonospora species, one unique Streptomyces species and one unique Verrucosispora phylogroup. Of the isolates, 27.5% displayed antimicrobial activity, and 91% contained polyketide synthase and/or nonribosomal peptide synthetase genes, indicating that these isolates had a high potential to produce secondary metabolites. The isolates from sponge Axinella sp. contained the highest presence of both antimicrobial activity and NRPS genes, while those from isolation medium DNBA showed the highest presence of antimicrobial activity and PKS I genes. Full article
Open AccessArticle Combinatorial Signal Integration by APETALA2/Ethylene Response Factor (ERF)-Transcription Factors and the Involvement of AP2-2 in Starvation Response
Int. J. Mol. Sci. 2012, 13(5), 5933-5951; doi:10.3390/ijms13055933
Received: 15 March 2012 / Revised: 21 April 2012 / Accepted: 8 May 2012 / Published: 16 May 2012
Cited by 7 | PDF Full-text (1243 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Transcription factors of the APETALA 2/Ethylene Response Factor (AP2/ERF)-family have been implicated in diverse processes during development, stress acclimation and retrograde signaling. Fifty-three leaf-expressed AP2/ERFs were screened for their transcriptional response to abscisic acid (ABA), 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), methylviologen (MV), sucrose and high [...] Read more.
Transcription factors of the APETALA 2/Ethylene Response Factor (AP2/ERF)-family have been implicated in diverse processes during development, stress acclimation and retrograde signaling. Fifty-three leaf-expressed AP2/ERFs were screened for their transcriptional response to abscisic acid (ABA), 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), methylviologen (MV), sucrose and high or low light, respectively, and revealed high reactivity to these effectors. Six of them (AP2-2, ARF14, CEJ1, ERF8, ERF11, RAP2.5) were selected for combinatorial response analysis to ABA, DCMU and high light. Additive, synergistic and antagonistic effects demonstrated that these transcription factors are components of multiple signaling pathways. AP2-2 (At1g79700) was subjected to an in depth study. AP2-2 transcripts were high under conditions linked to limited carbohydrate availability and stress and down-regulated in extended light phase, high light or in the presence of sugar. ap2-2 knock out plants had unchanged metabolite profiles and transcript levels of co-expressed genes in extended darkness. However, ap2-2 revealed more efficient germination and faster early growth under high sugar, osmotic or salinity stress, but the difference was abolished in the absence of sugar or during subsequent growth. It is suggested that AP2-2 is involved in mediating starvation-related and hormonal signals. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
Open AccessArticle Biological Properties of Acidic Cosmetic Water from Seawater
Int. J. Mol. Sci. 2012, 13(5), 5952-5971; doi:10.3390/ijms13055952
Received: 16 March 2012 / Revised: 26 April 2012 / Accepted: 2 May 2012 / Published: 16 May 2012
Cited by 11 | PDF Full-text (518 KB) | HTML Full-text | XML Full-text
Abstract
This current work was to investigate the biological effects of acidic cosmetic water (ACW) on various biological assays. ACW was isolated from seawater and demonstrated several bio-functions at various concentration ranges. ACW showed a satisfactory effect against Staphylococcus aureus, which reduced [...] Read more.
This current work was to investigate the biological effects of acidic cosmetic water (ACW) on various biological assays. ACW was isolated from seawater and demonstrated several bio-functions at various concentration ranges. ACW showed a satisfactory effect against Staphylococcus aureus, which reduced 90% of bacterial growth after a 5-second exposure. We used cultured human peripheral blood mononuclear cells (PBMCs) to test the properties of ACW in inflammatory cytokine release, and it did not induce inflammatory cytokine release from un-stimulated, normal PBMCs. However, ACW was able to inhibit bacterial lipopolysaccharide (LPS)-induced inflammatory cytokine TNF-α released from PBMCs, showing an anti-inflammation potential. Furthermore, ACW did not stimulate the rat basophilic leukemia cell (RBL-2H3) related allergy response on de-granulation. Our data presented ACW with a strong anti-oxidative ability in a superoxide anion radical scavenging assay. In mass spectrometry information, magnesium and zinc ions demonstrated bio-functional detections for anti-inflammation as well as other metal ions such as potassium and calcium were observed. ACW also had minor tyrosinase and melanin decreasing activities in human epidermal melanocytes (HEMn-MP) without apparent cytotoxicity. In addition, the cell proliferation assay illustrated anti-growth and anti-migration effects of ACW on human skin melanoma cells (A375.S2) indicating that it exerted the anti-cancer potential against skin cancer. The results obtained from biological assays showed that ACW possessed multiple bioactivities, including anti-microorganism, anti-inflammation, allergy-free, antioxidant, anti-melanin and anticancer properties. To our knowledge, this was the first report presenting these bioactivities on ACW. Full article
Open AccessArticle Multiplex PCR for 17 Y-Chromosome Specific Short Tandem Repeats (STR) to Enhance the Reliability of Fetal Sex Determination in Maternal Plasma
Int. J. Mol. Sci. 2012, 13(5), 5972-5981; doi:10.3390/ijms13055972
Received: 27 March 2012 / Revised: 2 May 2012 / Accepted: 9 May 2012 / Published: 16 May 2012
Cited by 8 | PDF Full-text (307 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to demonstrate the influence of target gene and amplification product length on the performance of fetal gender determination systems using maternal plasma. A total of 40 pairs of plasma DNA samples from pregnant women and genomic [...] Read more.
The aim of the study was to demonstrate the influence of target gene and amplification product length on the performance of fetal gender determination systems using maternal plasma. A total of 40 pairs of plasma DNA samples from pregnant women and genomic DNA samples from maternal blood, amniotic fluid and paternal blood were isolated for gender determination by amplification of the amelogenin gene and 17 Y-chromosome STR loci, using three different commercial kits. The gender of the fetuses was confirmed by cytogenetic analysis or phenotype at birth. Both the AmpFℓSTR-Identifiler amplification kit and the Mini-STR Amplification kit for amelogenin gene detection were reliable in determining fetal gender (92.0% and 96.0%, respectively), but false negatives were present in both systems. AmpFℓSTR-Yfiler was found to be fully reliable as it amplified Y-STR in all cases of pregnancies with male fetuses and thus was 100% correct in determining fetal gender. The results demonstrated that multiple fluorescent PCR for 17 Y-STR loci was more reliable than AMELY gene testing in fetal sex determination with maternal plasma. We also found that the shorter amplification products could improve the performance of fetal gender determination systems. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma
Int. J. Mol. Sci. 2012, 13(5), 5982-5997; doi:10.3390/ijms13055982
Received: 22 March 2012 / Revised: 9 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012
Cited by 15 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text
Abstract
The receptor for advanced glycation end products (RAGE) is oncogenic and overexpressed in human cancers, but its role in hepatocellular carcinoma remains unclear. Here we demonstrated that RAGE is overexpressed in primary hepatocellular carcinoma (PHC) compared to adjacent para-neoplastic liver samples. Serum endogenous secretory RAGE levels were also increased in PHC patients (p < 0.01). Moreover, we demonstrated that RAGE regulates cellular proliferation in Hepatocellular carcinoma (HCC). Knockdown of RAGE by specific siRNA inhibited cellular growth in the hepatocellular carcinoma cell line, Huh7, whereas the RAGE ligand, high mobility group box 1 protein (HMGB1) increased cellular proliferation. In addition, knockdown of RAGE by siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.01), while HMGB1 protein decreased the number of cells in the G1 phase and increased the number in the S phase (p < 0.05). Furthermore, quantitative real time RT-PCR (qRT-PCR) and Western Blot results demonstrated that RAGE and HMGB1 positively regulate NF-κB p65 expression in Huh7 cells. These studies suggest that RAGE and RAGE ligands are important targets for therapeutic intervention in hepatocellular carcinoma. Full article
Open AccessArticle Immobilization of Laccase for Oxidative Coupling of Trans-Resveratrol and Its Derivatives
Int. J. Mol. Sci. 2012, 13(5), 5998-6008; doi:10.3390/ijms13055998
Received: 5 April 2012 / Revised: 4 May 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 11 | PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
Trametes villosa Laccase (TVL) was immobilized through physical adsorption on SBA-15 mesoporous silica and the immobilized TVL was used in the oxidative coupling of trans-resveratrol. Higher loading and activity of the immobilized enzyme on SBA-15 were obtained when compared with the free [...] Read more.
Trametes villosa Laccase (TVL) was immobilized through physical adsorption on SBA-15 mesoporous silica and the immobilized TVL was used in the oxidative coupling of trans-resveratrol. Higher loading and activity of the immobilized enzyme on SBA-15 were obtained when compared with the free enzyme. The effects of reaction conditions, such as buffer type, pH, temperature and substrate concentration were investigated, and the optimum conditions were screened and resulted in enzyme activity of up to 10.3 μmol/g·h. Furthermore, the oxidative couplings of the derivatives of trans-resveratrol were also catalyzed by immobilized TVL. The immobilized TVL was recyclable and could maintain 78% of its initial activity after reusing it four times. Full article
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
Open AccessArticle Quantitative Structure-Activity Relationship Studies on Indenoisoquinoline Topoisomerase I Inhibitors as Anticancer Agents in Human Renal Cell Carcinoma Cell Line SN12C
Int. J. Mol. Sci. 2012, 13(5), 6009-6025; doi:10.3390/ijms13056009
Received: 9 March 2012 / Revised: 4 May 2012 / Accepted: 11 May 2012 / Published: 18 May 2012
Cited by 5 | PDF Full-text (648 KB) | HTML Full-text | XML Full-text
Abstract
Topoisomerase I is important for DNA replication and cell division, making it an attractive drug target for anticancer therapy. A series of indenoisoquinolines displaying potent Top1 inhibitory activity in human renal cell carcinoma cell line SN12C were selected to establish 3D-QSAR models [...] Read more.
Topoisomerase I is important for DNA replication and cell division, making it an attractive drug target for anticancer therapy. A series of indenoisoquinolines displaying potent Top1 inhibitory activity in human renal cell carcinoma cell line SN12C were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated, as well as some measures taken, including region focusing, bootstrapping and the “leave-group-out” cross-validation method. The satisfactory CoMFA model predicted a q2 value of 0.659 and an r2 value of 0.949, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic and H-bond acceptor descriptors, predicted a q2 value of 0.523 and an r2 value of 0.902. The models were graphically interpreted by contour plots which provided insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active anticancer agents. Full article
Open AccessArticle Beta-Glucans Improve Growth, Viability and Colonization of Probiotic Microorganisms
Int. J. Mol. Sci. 2012, 13(5), 6026-6039; doi:10.3390/ijms13056026
Received: 16 April 2012 / Revised: 10 May 2012 / Accepted: 11 May 2012 / Published: 18 May 2012
Cited by 23 | PDF Full-text (283 KB) | HTML Full-text | XML Full-text
Abstract
Probiotics, prebiotics and synbiotics are frequently-used components for the elaboration of functional food. Currently, most of the commercialized probiotics are limited to a few strains of the genera Bifidobacteria, Lactobacillus and Streptococcus, most of which produce exopolysaccharides (EPS). This suggests [...] Read more.
Probiotics, prebiotics and synbiotics are frequently-used components for the elaboration of functional food. Currently, most of the commercialized probiotics are limited to a few strains of the genera Bifidobacteria, Lactobacillus and Streptococcus, most of which produce exopolysaccharides (EPS). This suggests that the beneficial properties of these microorganisms may be related to the biological activities of these biopolymers. In this work we report that a 2-substituted-(1,3)-β-D-glucan of non-dairy bacterial origin has a prebiotic effect on three probiotic strains. Moreover, the presence of this β-D-glucan potentiates in vitro adhesion of the probiotic Lactobacillus plantarum WCFS1 to human intestinal epithelial cells. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Molecular Characterization of Cultivated Bromeliad Accessions with Inter-Simple Sequence Repeat (ISSR) Markers
Int. J. Mol. Sci. 2012, 13(5), 6040-6052; doi:10.3390/ijms13056040
Received: 14 March 2012 / Revised: 4 May 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 6 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bromeliads are of great economic importance in flower production; however little information is available with respect to genetic characterization of cultivated bromeliads thus far. In the present study, a selection of cultivated bromeliads was characterized via inter-simple sequence repeat (ISSR) markers with [...] Read more.
Bromeliads are of great economic importance in flower production; however little information is available with respect to genetic characterization of cultivated bromeliads thus far. In the present study, a selection of cultivated bromeliads was characterized via inter-simple sequence repeat (ISSR) markers with an emphasis on genetic diversity and population structure. Twelve ISSR primers produced 342 bands, of which 287 (~84%) were polymorphic, with polymorphic bands per primer ranging from 17 to 34. The Jaccard’s similarity ranged from 0.08 to 0.89 and averaged ~0.30 for the investigated bromeliads. The Bayesian-based approach, together with the un-weighted paired group method with arithmetic average (UPGMA)-based clustering and the principal coordinate analysis (PCoA), distinctly grouped the bromeliads from Neoregelia, Guzmania, and Vriesea into three separately clusters, well corresponding with their botanical classifications; whereas the bromeliads of Aechmea other than the recently selected hybrids were not well assigned to a cluster. Additionally, ISSR marker was proven efficient for the identification of hybrids and bud sports of cultivated bromeliads. The findings achieved herein will further our knowledge about the genetic variability within cultivated bromeliads and therefore facilitate breeding for new varieties of cultivated bromeliads in future as well. Full article
Open AccessArticle Evaluation of Antioxidant and Free Radical Scavenging Capacities of Polyphenolics from Pods of Caesalpinia pulcherrima
Int. J. Mol. Sci. 2012, 13(5), 6073-6088; doi:10.3390/ijms13056073
Received: 27 February 2012 / Revised: 9 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
Cited by 6 | PDF Full-text (763 KB) | HTML Full-text | XML Full-text
Abstract
Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-D-glucoside (3), methyl 6- [...] Read more.
Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-D-glucoside (3), methyl 6-O-galloyl-β-D-glucoside (4), methyl 3,6-di-O-galloyl-α-D-glucopyranoside (5), gentisic acid 5-O-α-D-(6'-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-β-D-(6'-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-β-D-(6'-O-galloyl)glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Neuroprotective Effects of Ischemic Preconditioning and Postconditioning on Global Brain Ischemia in Rats through the Same Effect on Inhibition of Apoptosis
Int. J. Mol. Sci. 2012, 13(5), 6089-6101; doi:10.3390/ijms13056089
Received: 27 March 2012 / Revised: 3 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012
Cited by 23 | PDF Full-text (399 KB) | HTML Full-text | XML Full-text
Abstract
Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic [...] Read more.
Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic challenge. Therefore, we investigated the effect of ischemic preconditioning and postconditioning on neural cell apoptosis in rats. The result showed that both ischemic preconditioning and postconditioning may attenuate the neural cell death and DNA fragment in the hippocampal CA1 region. Further western blot study suggested that ischemic preconditioning and postconditioning down-regulates the protein of cleaved caspase-3, caspase-6, caspase-9 and Bax, but up-regulates the protein Bcl-2. These findings suggest that ischemic preconditioning and postconditioning have a neuroprotective role on global brain ischemia in rats through the same effect on inhibition of apoptosis. Full article
Open AccessArticle Physiochemical, Optical and Biological Activity of Chitosan-Chromone Derivative for Biomedical Applications
Int. J. Mol. Sci. 2012, 13(5), 6102-6116; doi:10.3390/ijms13056102
Received: 10 April 2012 / Revised: 12 May 2012 / Accepted: 15 May 2012 / Published: 18 May 2012
Cited by 26 | PDF Full-text (831 KB) | HTML Full-text | XML Full-text
Abstract
This paper describes the physiochemical, optical and biological activity of chitosan-chromone derivative. The chitosan-chromone derivative gels were prepared by reacting chitosan with chromone-3-carbaldehyde, followed by solvent exchange, filtration and drying by evaporation. The identity of Schiff base was confirmed by UV-Vis absorption [...] Read more.
This paper describes the physiochemical, optical and biological activity of chitosan-chromone derivative. The chitosan-chromone derivative gels were prepared by reacting chitosan with chromone-3-carbaldehyde, followed by solvent exchange, filtration and drying by evaporation. The identity of Schiff base was confirmed by UV-Vis absorption spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. The chitosan-chromone derivative was evaluated by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photoluminescence (PL) and circular dichroism (CD). The CD spectrum showed the chitosan-chromone derivative had a secondary helical structure. Microbiological screening results demonstrated the chitosan-chromone derivative had antimicrobial activity against Escherichia coli bacteria. The chitosan-chromone derivative did not have any adverse effect on the cellular proliferation of mouse embryonic fibroblasts (MEF) and did not lead to cellular toxicity in MEFs. These results suggest that the chitosan-chromone derivative gels may open a new perspective in biomedical applications. Full article
Open AccessArticle Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway
Int. J. Mol. Sci. 2012, 13(5), 6117-6128; doi:10.3390/ijms13056117
Received: 28 March 2012 / Revised: 3 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
Cited by 24 | PDF Full-text (398 KB) | HTML Full-text | XML Full-text
Abstract
Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a [...] Read more.
Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer (CRC). However, the precise mechanism of its anti-tumor activity remains largely unclear. Using a CRC mouse xenograft model, in the present study we evaluated the effect of the ethanol extract of Hedyotis diffusa Willd (EEHDW) on tumor growth in vivo and investigated the underlying molecular mechanisms. We found that EEHDW reduced tumor volume and tumor weight, but had no effect on body weight gain in CRC mice, demonstrating that EEHDW can inhibit CRC growth in vivo without apparent adverse effect. In addition, EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. Moreover, EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, i.e., decreased expression of Cyclin D1, CDK4 and Bcl-2 as well as up-regulated p21 and Bax. These results suggest that suppression of the STAT3 pathway might be one of the mechanisms by which EEHDW treats colorectal cancer. Full article
Open AccessArticle Effect of FTY720 on Some Physiological Indexes of Non-Obese Diabetic (NOD) Mice
Int. J. Mol. Sci. 2012, 13(5), 6129-6137; doi:10.3390/ijms13056129
Received: 27 February 2012 / Revised: 2 May 2012 / Accepted: 7 May 2012 / Published: 18 May 2012
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Abstract
The studies were performed to investigate the physiological characteristics of non-obese diabetic (NOD) mice treated with FTY720. At the age of 12 weeks, each mouse was fed with FTY720 or physiological saline once a day for 10 weeks running, and their blood glucose, weight, anti-GAD antibody and organ indexes were determined. No mouse in group FTY720 (NOD mice treated with FTY720) showed diabetic symptoms. The average content of serum anti-GAD antibody in group FTY720 decreased 48.75% (P < 0.01). It was concluded that the spleen, kidney and liver of NOD mice treated with FTY720 shriveled significantly in the progression of diabetes (P < 0.01 or P < 0.05). The body weight of group FTY720 mice was slightly lower than that of the model control (MC) group and these two groups both had less body weight than the normal control (NC) group (P Full article
Open AccessArticle The Three Dimensional Quantitative Structure Activity Relationships (3D-QSAR) and Docking Studies of Curcumin Derivatives as Androgen Receptor Antagonists
Int. J. Mol. Sci. 2012, 13(5), 6138-6155; doi:10.3390/ijms13056138
Received: 17 April 2012 / Revised: 8 May 2012 / Accepted: 13 May 2012 / Published: 18 May 2012
Cited by 7 | PDF Full-text (854 KB) | HTML Full-text | XML Full-text
Abstract
Androgen receptor antagonists have been proved to be effective anti-prostate cancer agents. 3D-QSAR and Molecular docking methods were performed on curcumin derivatives as androgen receptor antagonists. The bioactive conformation was explored by docking the potent compound 29 into the binding site of [...] Read more.
Androgen receptor antagonists have been proved to be effective anti-prostate cancer agents. 3D-QSAR and Molecular docking methods were performed on curcumin derivatives as androgen receptor antagonists. The bioactive conformation was explored by docking the potent compound 29 into the binding site of AR. The constructed Comparative Molecular Field Analysis (CoMFA) and Comparative Similarity Indices Analysis (CoMSIA) models produced statistically significant results with the cross-validated correlation coefficients q2 of 0.658 and 0.567, non-cross-validated correlation coefficients r2 of 0.988 and 0.978, and predicted correction coefficients r2pred of 0.715 and 0.793, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of novel potent AR antagonists. A set of 30 new analogs were proposed by utilizing the results revealed in the present study, and were predicted with potential activities in the developed models. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Simple and Rapid Molecular Techniques for Identification of Amylose Levels in Rice Varieties
Int. J. Mol. Sci. 2012, 13(5), 6156-6166; doi:10.3390/ijms13056156
Received: 17 February 2012 / Revised: 3 May 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 2 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text
Abstract
The polymorphisms of Waxy (Wx) microsatellite and G-T single-nucleotide polymorphism (SNP) in the Wx gene region were analyzed using simplified techniques in fifteen rice varieties. A rapid and reliable electrophoresis method, MetaPhor agarose gel electrophoresis (MAGE), was effectively employed as [...] Read more.
The polymorphisms of Waxy (Wx) microsatellite and G-T single-nucleotide polymorphism (SNP) in the Wx gene region were analyzed using simplified techniques in fifteen rice varieties. A rapid and reliable electrophoresis method, MetaPhor agarose gel electrophoresis (MAGE), was effectively employed as an alternative to polyacrylamide gel electrophoresis (PAGE) for separating Wx microsatellite alleles. The amplified products containing the Wx microsatellite ranged from 100 to 130 bp in length. Five Wx microsatellite alleles, namely (CT)10, (CT)11, (CT)16, (CT)17, and (CT)18 were identified. Of these, (CT)11 and (CT)17 were the predominant classes among the tested varieties. All varieties with an apparent amylose content higher than 24% were associated with the shorter repeat alleles; (CT)10 and (CT)11, while varieties with 24% or less amylose were associated with the longer repeat alleles. All varieties with intermediate and high amylose content had the sequence AGGTATA at the 5'-leader intron splice site, while varieties with low amylose content had the sequence AGTTATA. The G-T polymorphism was further verified by the PCR-AccI cleaved amplified polymorphic sequence (CAPS) method, in which only genotypes containing the AGGTATA sequence were cleaved by AccI. Hence, varieties with desirable amylose levels can be developed rapidly using the Wx microsatellite and G-T SNP, along with MAGE. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
Open AccessArticle Genetic and Association Mapping Study of Wheat Agronomic Traits Under Contrasting Water Regimes
Int. J. Mol. Sci. 2012, 13(5), 6167-6188; doi:10.3390/ijms13056167
Received: 14 March 2012 / Revised: 2 May 2012 / Accepted: 15 May 2012 / Published: 18 May 2012
Cited by 10 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Genetic analyses and association mapping were performed on a winter wheat core collection of 96 accessions sampled from a variety of geographic origins. Twenty-four agronomic traits were evaluated over 3 years under fully irrigated, rainfed and drought treatments. Grain yield was the most sensitive trait to water deficit and was highly correlated with above-ground biomass per plant and number of kernels per m2. The germplasm was structured into four subpopulations. The association of 46 SSR loci distributed throughout the wheat genome with yield and agronomic traits was analyzed using a general linear model, where subpopulation information was used to control false-positive or spurious marker-trait associations (MTAs). A total of 26, 21 and 29 significant (P < 0.001) MTAs were identified in irrigated, rainfed and drought treatments, respectively. The marker effects ranged from 14.0 to 50.8%. Combined across all treatments, 34 significant (P < 0.001) MTAs were identified with nine markers, and R2 ranged from 14.5 to 50.2%. Marker psp3200 (6DS) and particularly gwm484 (2DS) were associated with many significant MTAs in each treatment and explained the greatest proportion of phenotypic variation. Although we were not able to recognize any marker related to grain yield under drought stress, a number of MTAs associated with developmental and agronomic traits highly correlated with grain yield under drought were identified. Full article
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Open AccessArticle Phytochemicals Analysis and Medicinal Potentials of Hydroalcoholic Extract from Curtisia dentata (Burm.f) C.A. Sm Stem Bark
Int. J. Mol. Sci. 2012, 13(5), 6189-6203; doi:10.3390/ijms13056189
Received: 20 January 2012 / Revised: 29 March 2012 / Accepted: 3 May 2012 / Published: 21 May 2012
Cited by 7 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
Curtisia dentata (CD) is a vulnerable medicinal plant used for the treatment of stomach ailments in South Africa. However, there is a lack of sufficient data on its phytochemical components and medicinal properties. The phytochemical analysis of the extract was estimated [...] Read more.
Curtisia dentata (CD) is a vulnerable medicinal plant used for the treatment of stomach ailments in South Africa. However, there is a lack of sufficient data on its phytochemical components and medicinal properties. The phytochemical analysis of the extract was estimated using standard assay methods while its antibacterial activity was determined by the agar dilution method against selected bacteria. The antioxidant activity of the extract was done using ferric reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic-acid (ABTS), nitric oxide (NO), hydrogen peroxide (H2O2) and lipid peroxidation (LPO). The cytotoxicity assay of the extract was assessed using the brine shrimp lethality test with LC50 value of 0.302 mg/mL. The antibacterial activity of the extract demonstrated an appreciable broad spectrum activity against the tested bacteria with minimum inhibitory concentration (MIC) ranges between 5000 and 0.5 mg/L. Both phenol and flavonoid concentrations were 14.86 mg tannic acid equivalent/g and 13.64 mg quercetin equivalent/g, respectively. The percentage composition of saponins (13.26) was highest, followed by steroids (1.42), while alkaloids and tannins had the same value of 0.51. Similarly, IC50 values of the extract against DPPH, ABTS, H2O2, LPO and NO were 0.017, 0.018, 0.159, 0.06 and 0.052 mg/mL, respectively. The reducing power of the extract was found to be concentration dependent. Our data suggest that the 70% ethanol extract from the CD extract has antibacterial and antioxidant properties due to the presence of bio-active compounds and thus support its folkloric use in the treatment of diseases. Full article
Open AccessArticle Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms
Int. J. Mol. Sci. 2012, 13(5), 6204-6219; doi:10.3390/ijms13056204
Received: 22 March 2012 / Revised: 24 April 2012 / Accepted: 9 May 2012 / Published: 21 May 2012
Cited by 7 | PDF Full-text (394 KB) | HTML Full-text | XML Full-text
Abstract
Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of [...] Read more.
Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC-driven B cell lymphomas. ARF-BP1 was expressed at high levels in cell lines from lymphomas with either wild type or mutated p53 but not in ARF-deficient cells. Downregulation of ARF-BP1 resulted in elevated steady state levels of p53, growth arrest and apoptosis. Co-immunoprecipitation studies identified a multiprotein complex comprised of ARF-BP1, ARF, p53, MYC and the multifunctional DNA-binding factor, CTCF, which is involved in the transcriptional regulation of MYC, p53 and ARF. ARF-BP1 bound and ubiquitylated CTCF leading to its proteasomal degradation. ARF-BP1 and CTCF thus appear to be key cofactors linking the MYC proliferative and p53-ARF apoptotic pathways. In addition, ARF-BP1 could be a therapeutic target for MYC-driven B lineage neoplasms, even if p53 is inactive, with inhibition reducing the transcriptional activity of MYC for its target genes and stabilizing the apoptosis-promoting activities of p53. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessArticle Antioxidative Characteristics of Anisomeles indica Extract and Inhibitory Effect of Ovatodiolide on Melanogenesis
Int. J. Mol. Sci. 2012, 13(5), 6220-6235; doi:10.3390/ijms13056220
Received: 9 April 2012 / Revised: 10 May 2012 / Accepted: 14 May 2012 / Published: 21 May 2012
Cited by 9 | PDF Full-text (622 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging [...] Read more.
The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and metal ion chelating capacity as well as total phenolic content of the extract were investigated. In addition, the inhibitory effects of ovatodiolide on mushroom tyrosinase, B16F10 intracellular tyrosinase and melanin content were determined spectrophotometrically. Our results revealed that the antioxidant capacities of A. indica methanol extract increased in a dose-dependent pattern. The purified ovatodiolide inhibited mushroom tyrosinase activity (IC50 = 0.253 mM), the compound also effectively suppressed intracellular tyrosinase activity (IC50 = 0.469 mM) and decreased the amount of melanin (IC50 = 0.435 mM) in a dose-dependent manner in B16F10 cells. Our results concluded that A. indica methanol extract displays antioxidant capacities and ovatodiolide purified from the extract inhibited melanogenesis in B16F10 cells. Hence, A. indica methanol extract and ovatodiolide could be applied as a type of dermatological whitening agent in skin care products. Full article
Open AccessArticle Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway
Int. J. Mol. Sci. 2012, 13(5), 6236-6245; doi:10.3390/ijms13056236
Received: 4 April 2012 / Revised: 7 May 2012 / Accepted: 14 May 2012 / Published: 21 May 2012
Cited by 15 | PDF Full-text (653 KB) | HTML Full-text | XML Full-text
Abstract
Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two [...] Read more.
Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC50 dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle A Novel Apoptosis Correlated Molecule: Expression and Characterization of Protein Latcripin-1 from Lentinula edodes C91–3
Int. J. Mol. Sci. 2012, 13(5), 6246-6265; doi:10.3390/ijms13056246
Received: 13 March 2012 / Revised: 9 May 2012 / Accepted: 11 May 2012 / Published: 21 May 2012
Cited by 5 | PDF Full-text (1091 KB) | HTML Full-text | XML Full-text
Abstract
An apoptosis correlated molecule—protein Latcripin-1 of Lentinula edodes C91-3—was expressed and characterized in Pichia pastoris GS115. The total RNA was obtained from Lentinula edodes C91–3. According to the transcriptome, the full-length gene of Latcripin-1 was isolated with 3'-Full Rapid Amplification of cDNA Ends (RACE) and 5'-Full RACE methods. The full-length gene was inserted into the secretory expression vector pPIC9K. The protein Latcripin-1 was expressed in Pichia pastoris GS115 and analyzed by Sodium Dodecylsulfonate Polyacrylate Gel Electrophoresis (SDS-PAGE) and Western blot. The Western blot showed that the protein was expressed successfully. The biological function of protein Latcripin-1 on A549 cells was studied with flow cytometry and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl-tetrazolium Bromide (MTT) method. The toxic effect of protein Latcripin-1 was detected with the MTT method by co-culturing the characterized protein with chick embryo fibroblasts. The MTT assay results showed that there was a great difference between protein Latcripin-1 groups and the control group (p < 0.05). There was no toxic effect of the characterized protein on chick embryo fibroblasts. The flow cytometry showed that there was a significant difference between the protein groups of interest and the control group according to apoptosis function (p < 0.05). At the same time, cell ultrastructure observed by transmission electron microscopy supported the results of flow cytometry. The work demonstrates that protein Latcripin-1 can induce apoptosis of human lung cancer cells A549 and brings new insights into and advantages to finding anti-tumor proteins. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessArticle Low Diversity Bacterial Community and the Trapping Activity of Metabolites from Cultivable Bacteria Species in the Female Reproductive System of the Oriental Fruit Fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae)
Int. J. Mol. Sci. 2012, 13(5), 6266-6278; doi:10.3390/ijms13056266
Received: 28 March 2012 / Revised: 4 May 2012 / Accepted: 4 May 2012 / Published: 21 May 2012
Cited by 8 | PDF Full-text (276 KB) | HTML Full-text | XML Full-text
Abstract
Our goal was to identify the bacteria inhabiting the reproductive system of the female oriental fruit fly, Bactrocera dorsalis (Hendel), and evaluate the chemotaxis of B. dorsalis to the metabolites produced by the bacteria. Based on 16S rRNA-based polymerase chain reaction-denaturing [...] Read more.
Our goal was to identify the bacteria inhabiting the reproductive system of the female oriental fruit fly, Bactrocera dorsalis (Hendel), and evaluate the chemotaxis of B. dorsalis to the metabolites produced by the bacteria. Based on 16S rRNA-based polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), 18 operational taxonomic units (OTUs) were assigned to the five bacterial classes Betaproteobacteria, Alphaproteobacteria, Gammaproteobacteria, Bacilli and Actinobacteria. Nine OTUs were assigned to Gammaproteobacteria, which was the most highly represented class. Enterobacteriaceae constituted the dominant family, and within this family, three genera and five species were identified, including Enterobacter sakazakii, Klebsiella oxytoca, Klebsiella pneumoniae, Raoultella terrigena and Enterobacter amnigenus. In this set, the first two species were the dominant components, and the latter three species were the minor ones. Finally, we found that the metabolites produced by R. terrigena, K. oxytoca and K. pneumoniae were attractive to the B. dorsalis adults, and in field studies, B. dorsalis adults were most attracted to K. oxytoca. Collectively, our results suggest that the female reproductive system plays an important role in the transfer of enterobacteria from the gut to fruit. Our data may prompt the development of a female-targeted population control strategy for this fly. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Synthesis and Characterization of Hybrid Materials Consisting of n-octadecyltriethoxysilane by Using n-Hexadecylamine as Surfactant and Q0 and T0 Cross-Linkers
Int. J. Mol. Sci. 2012, 13(5), 6279-6291; doi:10.3390/ijms13056279
Received: 12 April 2012 / Revised: 3 May 2012 / Accepted: 10 May 2012 / Published: 21 May 2012
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Abstract
Novel hybrid xerogel materials were synthesized by a sol-gel procedure. n-octadecyltriethoxysilane was co-condensed with and without different cross-linkers using Q0 and T0 mono-functionalized organosilanes in the presence of n-hexadecylamine with different hydroxyl silica functional groups at the [...] Read more.
Novel hybrid xerogel materials were synthesized by a sol-gel procedure. n-octadecyltriethoxysilane was co-condensed with and without different cross-linkers using Q0 and T0 mono-functionalized organosilanes in the presence of n-hexadecylamine with different hydroxyl silica functional groups at the surface. These polymer networks have shown new properties, for example, a high degree of cross-linking and hydrolysis. Two different synthesis steps were carried out: simple self-assembly followed by sol-gel transition and precipitation of homogenous sols. Due to the lack of solubility of these materials, the compositions of the new materials were determined by infrared spectroscopy, 13C and 29Si CP/MAS NMR spectroscopy and scanning electron microscopy. Full article
(This article belongs to the Special Issue Composite Materials in Skeletal Engineering)
Open AccessArticle Optimization of the Extraction of Anthocyanins from the Fruit Skin of Rhodomyrtus tomentosa (Ait.) Hassk and Identification of Anthocyanins in the Extract Using High-Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS)
Int. J. Mol. Sci. 2012, 13(5), 6292-6302; doi:10.3390/ijms13056292
Received: 13 March 2012 / Revised: 24 April 2012 / Accepted: 17 May 2012 / Published: 22 May 2012
Cited by 12 | PDF Full-text (314 KB) | HTML Full-text | XML Full-text
Abstract
Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants. In this study, the extraction of anthocyanins from freeze-dried fruit skin of downy rose-myrtle (Rhodomyrtus tomentosa (Ait.) Hassk var. Gangren) was optimized using response surface methodology (RSM). [...] Read more.
Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants. In this study, the extraction of anthocyanins from freeze-dried fruit skin of downy rose-myrtle (Rhodomyrtus tomentosa (Ait.) Hassk var. Gangren) was optimized using response surface methodology (RSM). Using 60% ethanol containing 0.1% (v/v) hydrochloric acid as extraction solvent, the optimal conditions for maximum yields of anthocyanin (4.358 ± 0.045 mg/g) were 15.7:1 (v/w) liquid to solid ratio, 64.38 °C with a 116.88 min extraction time. The results showed good fits with the proposed model for the anthocyanin extraction (R2 = 0.9944). Furthermore, the results of high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) analysis of the anthocyanins extracted from the fruit skin of downy rose-myrtle revealed the presence of five anthocyanin components, which were tentatively identified as delphinidin-3-glucoside, cyanidin-3-glucoside, peonidin-3-glucoside, petunidin-3-glucoside and malvidin-3-glucoside. Full article
Open AccessArticle Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep
Int. J. Mol. Sci. 2012, 13(5), 6303-6319; doi:10.3390/ijms13056303
Received: 9 April 2012 / Revised: 8 May 2012 / Accepted: 14 May 2012 / Published: 22 May 2012
Cited by 10 | PDF Full-text (763 KB) | HTML Full-text | XML Full-text
Abstract
Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state [...] Read more.
Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose) or 50 µmol/kg/h for 25 h (high dose) or vehicle only (control group), starting 90 min after the end of ischaemia), following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation). Both peptide infusion groups were associated with a transient significant increase in EEG power between 2–12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling), as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2012)
Open AccessArticle Anti-Hyperglycemic Effect of Chebulagic Acid from the Fruits of Terminalia chebula Retz
Int. J. Mol. Sci. 2012, 13(5), 6320-6333; doi:10.3390/ijms13056320
Received: 1 April 2012 / Revised: 14 May 2012 / Accepted: 16 May 2012 / Published: 22 May 2012
Cited by 17 | PDF Full-text (461 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% [...] Read more.
In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats. The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Investigation of Antigen-Antibody Interactions of Sulfonamides with a Monoclonal Antibody in a Fluorescence Polarization Immunoassay Using 3D-QSAR Models
Int. J. Mol. Sci. 2012, 13(5), 6334-6351; doi:10.3390/ijms13056334
Received: 5 March 2012 / Revised: 14 May 2012 / Accepted: 21 May 2012 / Published: 23 May 2012
Cited by 4 | PDF Full-text (564 KB) | HTML Full-text | XML Full-text
Abstract
A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The affinities of [...] Read more.
A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The affinities of the MAbSMR, expressed as Log10IC50, for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). The results demonstrated that the proposed pharmacophore model containing two hydrogen-bond acceptors, two hydrogen-bond donors and two hydrophobic centers characterized the structural features of the sulfonamides necessary for MAbSMR binding. Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR models of 15 sulfonamides based on CoMFA and CoMSIA resulted in q2cv values of 0.600 and 0.523, and r2 values of 0.995 and 0.994, respectively, which indicates that both methods have significant predictive capability. Connolly surface analysis, which mainly focused on steric force fields, was performed to complement the results from CoMFA and CoMSIA. This novel study combining FPIA with pharmacophore modeling demonstrates that multidisciplinary research is useful for investigating antigen-antibody interactions and also may provide information required for the design of new haptens. Full article
(This article belongs to the Section Molecular Recognition)
Open AccessArticle Revealing the Anti-Tumor Effect of Artificial miRNA p-27-5p on Human Breast Carcinoma Cell Line T-47D
Int. J. Mol. Sci. 2012, 13(5), 6352-6369; doi:10.3390/ijms13056352
Received: 9 April 2012 / Revised: 9 May 2012 / Accepted: 18 May 2012 / Published: 23 May 2012
Cited by 2 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for [...] Read more.
microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for cancer. This study investigates the anti-tumor effect of a novel artificial miRNA, miR P-27-5p, on breast cancer. In this study, we reveal that miR P-27-5p downregulates the differential gene expressions associated with the protein modification process and regulation of cell cycle in T-47D cells. Introduction of this novel artificial miRNA, miR P-27-5p, into breast cell lines inhibits cell proliferation and induces the first “gap” phase (G1) cell cycle arrest in cancer cell lines but does not affect normal breast cells. We further show that miR P-27-5p targets the 3′-untranslated mRNA region (3′-UTR) of cyclin-dependent kinase 4 (CDK4) and reduces both the mRNA and protein level of CDK4, which in turn, interferes with phosphorylation of the retinoblastoma protein (RB1). Overall, our data suggest that the effects of miR p-27-5p on cell proliferation and G1 cell cycle arrest are through the downregulation of CDK4 and the suppression of RB1 phosphorylation. This study opens avenues for future therapies targeting breast cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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Open AccessArticle Gelam Honey Has a Protective Effect against Lipopolysaccharide (LPS)-Induced Organ Failure
Int. J. Mol. Sci. 2012, 13(5), 6370-6381; doi:10.3390/ijms13056370
Received: 5 April 2012 / Revised: 4 May 2012 / Accepted: 7 May 2012 / Published: 23 May 2012
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Abstract
Gelam honey exerts anti-inflammatory and antioxidant activities and is thought to have potent effects in reducing infections and healing wounds. The aim of this study was to investigate the effects of intravenously-injected Gelam honey in protecting organs from lethal doses of lipopolysaccharide [...] Read more.
Gelam honey exerts anti-inflammatory and antioxidant activities and is thought to have potent effects in reducing infections and healing wounds. The aim of this study was to investigate the effects of intravenously-injected Gelam honey in protecting organs from lethal doses of lipopolysaccharide (LPS). Six groups of rabbits (N = 6) were used in this study. Two groups acted as controls and received only saline and no LPS injections. For the test groups, 1 mL honey (500 mg/kg in saline) was intravenously injected into two groups (treated), while saline (1 mL) was injected into the other two groups (untreated); after 1 h, all four test groups were intravenously-injected with LPS (0.5 mg/kg). Eight hours after the LPS injection, blood and organs were collected from three groups (one from each treatment stream) and blood parameters were measured and biochemical tests, histopathology, and myeloperoxidase assessment were performed. For survival rate tests, rabbits from the remaining three groups were monitored over a 2-week period. Treatment with honey showed protective effects on organs through the improvement of organ blood parameters, reduced infiltration of neutrophils, and decreased myeloperoxidase activity. Honey-treated rabbits also showed reduced mortality after LPS injection compared with untreated rabbits. Honey may have a therapeutic effect in protecting organs during inflammatory diseases. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Enrichment of Polychlorinated Biphenyls from Aqueous Solutions Using Fe3O4 Grafted Multiwalled Carbon Nanotubes with Poly Dimethyl Diallyl Ammonium Chloride
Int. J. Mol. Sci. 2012, 13(5), 6382-6398; doi:10.3390/ijms13056382
Received: 6 April 2012 / Revised: 16 May 2012 / Accepted: 17 May 2012 / Published: 23 May 2012
Cited by 8 | PDF Full-text (988 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, Fe3O4 nanoparticles (Fe3O4 NPs) grafted carboxyl groups of multiwalled carbon nanotubes with cationic polyelectrolyte poly (dimethyldiallylammonium chloride) (PDDA) (MWCNTs-COO/PDDA@Fe3O4), are successfully synthesized and used for the extraction [...] Read more.
In this paper, Fe3O4 nanoparticles (Fe3O4 NPs) grafted carboxyl groups of multiwalled carbon nanotubes with cationic polyelectrolyte poly (dimethyldiallylammonium chloride) (PDDA) (MWCNTs-COO/PDDA@Fe3O4), are successfully synthesized and used for the extraction of six kinds of major toxic polychorinated biphenyls (PCBs) from a large volume of water solution. The hydrophilicity of the PDDA cage can enhance the dispersibility of sorbents in water samples, and the superparamagnetism of the Fe3O4 NPs facilitate magnetic separation which directly led to the simplification of the extraction procedure. With the magnetic solid-phase extraction (MSPE) technique based on the MWCNTs-COO/PDDA@Fe3O4 sorbents, it requires only 30 min to extract trace levels of PCBs from 500 mL water samples. When the eluate condensed to 1.0 mL, concentration factors for PCBs became over 500. The spiked recoveries of several real water samples for PCBs were in the range of 73.3–98.9% with relative standard deviations varying from 3.8% to 9.4%, reflecting good accuracy of the method. Therefore, preconcentration of trace level of PCBs by using this MWCNTs-COO/PDDA@Fe3O4 sorbent, which are stable for multiple reuses, from water solution can be performed. Full article
Open AccessArticle CD146 Expression Correlates with Epithelial-Mesenchymal Transition Markers and a Poor Prognosis in Gastric Cancer
Int. J. Mol. Sci. 2012, 13(5), 6399-6406; doi:10.3390/ijms13056399
Received: 18 April 2012 / Revised: 15 May 2012 / Accepted: 15 May 2012 / Published: 23 May 2012
Cited by 26 | PDF Full-text (399 KB) | HTML Full-text | XML Full-text
Abstract
CD146 has been regarded as a novel potential therapeutic target for multiple cancers. The aim of the study was to investigate the expression of CD146 in gastric cancer and evaluate its clinical-pathological and prognostic significance. The expression of CD146 and three epithelial-mesenchymal [...] Read more.
CD146 has been regarded as a novel potential therapeutic target for multiple cancers. The aim of the study was to investigate the expression of CD146 in gastric cancer and evaluate its clinical-pathological and prognostic significance. The expression of CD146 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, β-catenin and vimentin) was examined in 144 gastric cancers by immunohistochemistry. Fifty-nine cases (41.0%) were defined as positive for CD146 expression. We found that CD146 expression correlated positively with lymph node involvement and a poor prognosis, and retained an independent prognostic factor for gastric cancer patients. Furthermore, positive expression of CD146 was strongly associated with loss of the epithelial marker E-cadherin and acquisition of the expression of the mesenchymal markers nuclear β-catenin and vimentin. These findings suggest that CD146 might promote EMT and progression in gastric cancer, and thus may be a potential therapeutic target for patients with gastric cancers. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessArticle Effect of Dieckol, a Component of Ecklonia cava, on the Promotion of Hair Growth
Int. J. Mol. Sci. 2012, 13(5), 6407-6423; doi:10.3390/ijms13056407
Received: 2 March 2012 / Revised: 13 April 2012 / Accepted: 14 May 2012 / Published: 23 May 2012
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Abstract
This study was conducted to evaluate the effect of Ecklonia cava, a marine alga native to Jeju Island in Korea, on the promotion of hair growth. When vibrissa follicles were cultured in the presence of E. cava enzymatic extract (which contains [...] Read more.
This study was conducted to evaluate the effect of Ecklonia cava, a marine alga native to Jeju Island in Korea, on the promotion of hair growth. When vibrissa follicles were cultured in the presence of E. cava enzymatic extract (which contains more than 35% of dieckol) for 21 days, E. cava enzymatic extract increased hair-fiber length. In addition, after topical application of the 0.5% E. cava enzymatic extract onto the back of C57BL/6 mice, anagen progression of the hair-shaft was induced. The treatment with E. cava enzymatic extract resulted in the proliferation of immortalized vibrissa dermal papilla cells (DPC). Especially, dieckol, among the isolated compounds from the E. cava enzymatic extract, showed activity that increased the proliferation of DPC. When NIH3T3 fibroblasts were treated with the E. cava enzymatic extract and the isolated compounds from the E. cava enzymatic extract, the E. cava enzymatic extract increased the proliferation of NIH3T3 fibroblasts, but the isolated compounds such as eckol, dieckol, phloroglucinol and triphlorethol-A did not affect the proliferation of NIH3T3 fibroblasts. On the other hand, the E. cava enzymatic extract and dieckol significantly inhibited 5α-reductase activity. These results suggest that dieckol from E. cava can stimulate hair growth by the proliferation of DPC and/or the inhibition of 5α-reductase activity. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle CD133-Positive Cells Might Be Responsible for Efficient Proliferation of Human Meningioma Cells
Int. J. Mol. Sci. 2012, 13(5), 6424-6439; doi:10.3390/ijms13056424
Received: 27 March 2012 / Revised: 20 April 2012 / Accepted: 14 May 2012 / Published: 23 May 2012
Cited by 3 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
Owing to lack of appropriate model systems, investigations of meningioma biology have come to a stop. In this study, we developed a comprehensive digestion method and defined a culture system. Using this method and system, primary meningioma cells in conditioned suspension medium [...] Read more.
Owing to lack of appropriate model systems, investigations of meningioma biology have come to a stop. In this study, we developed a comprehensive digestion method and defined a culture system. Using this method and system, primary meningioma cells in conditioned suspension medium and a hypoxic environment could be amplified in spheres and were passaged for more than ten generations. Meningioma sphere cells were positive for meningioma cell markers and negative for markers of neural cell types. Importantly, we found the cells expressed the stem cell marker, CD133, but not nestin. All of the tumor sphere cell populations showed a slower degree of cell proliferation than that of human glioma cells and fetal neural stem cells (NSCs). Further studies showed that the proliferative rate was positively correlated with CD133 expression. The higher the CD133 expression, the faster the cell proliferation. With the increase in cell generations, the cell proliferation rate gradually slowed down, and CD133 expression also decreased. Single CD133+ cells rather than CD133 cells could form spheres. Thus, the results above indicated that those cells expressing CD133 in spheres might be stem-like cells, which may be responsible for efficient amplification of human meningioma cells. Decreased expression of CD133 may lead to the failure of long-term passaging. Full article
Open AccessArticle Phytochemical and Biological Studies of Agave attenuata
Int. J. Mol. Sci. 2012, 13(5), 6440-6451; doi:10.3390/ijms13056440
Received: 27 March 2012 / Revised: 14 April 2012 / Accepted: 4 May 2012 / Published: 24 May 2012
Cited by 34 | PDF Full-text (173 KB) | HTML Full-text | XML Full-text
Abstract
The present study was conducted to examine various biological activities of a methanol extract of Agave attenuata leaves. GC-MS analysis of the n-hexane fraction from the extract revealed the presence of 31 compounds, with mono-2-ethylhexyl phthalate (11.37%), 1,2-benzenedicarboxylic acid (6.33%), n [...] Read more.
The present study was conducted to examine various biological activities of a methanol extract of Agave attenuata leaves. GC-MS analysis of the n-hexane fraction from the extract revealed the presence of 31 compounds, with mono-2-ethylhexyl phthalate (11.37%), 1,2-benzenedicarboxylic acid (6.33%), n-docosane (6.30%) and eicosane (6.02%) as the major components. The leaves contained appreciable levels of total phenolic contents (10.541–39.35 GAE, mg/100 g) and total flavonoid contents (43.35–304.8 CE, mg/100 g). The extract and some of its fractions showed moderate antimicrobial effects. Leaves extract and fractions also exhibited a good antioxidant potential when measured by DPPH radical scavenging activity and inhibition of lipid peroxidation assays. The hemolytic effect of the plant was found to be in a range of 1.01%–2.64%. From the present study it is concluded that this plant could be used as a source of natural antioxidants and functional food nutraceutical applications. Full article
Open AccessArticle A Novel Preparation Method for 5-Aminosalicylic Acid Loaded Eudragit S100 Nanoparticles
Int. J. Mol. Sci. 2012, 13(5), 6454-6468; doi:10.3390/ijms13056454
Received: 13 February 2012 / Revised: 22 April 2012 / Accepted: 22 May 2012 / Published: 24 May 2012
Cited by 11 | PDF Full-text (633 KB) | HTML Full-text | XML Full-text
Abstract
In this study, solution enhanced dispersion by supercritical fluids (SEDS) technique was applied for the preparation of 5-aminosalicylic acid (5-ASA) loaded Eudragit S100 (EU S100) nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on [...] Read more.
In this study, solution enhanced dispersion by supercritical fluids (SEDS) technique was applied for the preparation of 5-aminosalicylic acid (5-ASA) loaded Eudragit S100 (EU S100) nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on morphology, particle size, 5-ASA loading and entrapment efficiency of nanoparticles were investigated. Under the appropriate conditions, drug-loaded nanoparticles exhibited a spherical shape and small particle size with narrow particle size distribution. In addition, the nanoparticles prepared were characterized by X-ray diffraction, Differential scanning calorimetry and Fourier transform infrared spectroscopy analyses. The results showed that 5-ASA was imbedded into EU S100 in an amorphous state after SEDS processing and the SEDS process did not induce degradation of 5-ASA. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Introgression Between Cultivars and Wild Populations of Momordica charantia L. (Cucurbitaceae) in Taiwan
Int. J. Mol. Sci. 2012, 13(5), 6469-6491; doi:10.3390/ijms13056469
Received: 20 March 2012 / Revised: 16 May 2012 / Accepted: 18 May 2012 / Published: 24 May 2012
Cited by 13 | PDF Full-text (557 KB) | HTML Full-text | XML Full-text
Abstract
The landrace strains of Momordica charantia are widely cultivated vegetables throughout the tropics and subtropics, but not in Taiwan, a continental island in Southeast Asia, until a few hundred years ago. In contrast, the related wild populations with smaller fruit sizes are [...] Read more.
The landrace strains of Momordica charantia are widely cultivated vegetables throughout the tropics and subtropics, but not in Taiwan, a continental island in Southeast Asia, until a few hundred years ago. In contrast, the related wild populations with smaller fruit sizes are native to Taiwan. Because of the introduction of cultivars for agricultural purposes, these two accessions currently exhibit a sympatric or parapatric distribution in Taiwan. In this study, the cultivars and wild samples from Taiwan, India, and Korea were collected for testing of their hybridization and evolutionary patterns. The cpDNA marker showed a clear distinction between accessions of cultivars and wild populations of Taiwan and a long divergence time. In contrast, an analysis of eight selectively neutral nuclear microsatellite loci did not reveal a difference between the genetic structures of these two accessions. A relatively short divergence time and frequent but asymmetric gene flows were estimated based on the isolation-with-migration model. Historical and current introgression from cultivars to wild populations of Taiwan was also inferred using MIGRATE-n and BayesAss analyses. Our results showed that these two accessions shared abundant common ancestral polymorphisms, and the timing of the divergence and colonization of the Taiwanese wild populations is consistent with the geohistory of the Taiwan Strait land bridge of the Last Glacial Maximum (LGM). Long-term and recurrent introgression between accessions indicated the asymmetric capacity to receive foreign genes from other accessions. The modern introduction of cultivars of M. charantia during the colonization of Taiwan by the Han Chinese ethnic group enhanced the rate of gene replacement in the native populations and resulted in the loss of native genes. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
Open AccessArticle Growth Promotion of Yunnan Pine Early Seedlings in Response to Foliar Application of IAA and IBA
Int. J. Mol. Sci. 2012, 13(5), 6507-6520; doi:10.3390/ijms13056507
Received: 21 February 2012 / Revised: 18 May 2012 / Accepted: 21 May 2012 / Published: 24 May 2012
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Abstract
A field experiment was conducted using a 3 × 3 orthogonal regression design to explore the growth promotion of one-year-old Yunnan pine seedlings (Pinus yunnanensis Franch.) in response to foliar application of IAA (indole-3-acetic acid) at rates of 0, 200 and [...] Read more.
A field experiment was conducted using a 3 × 3 orthogonal regression design to explore the growth promotion of one-year-old Yunnan pine seedlings (Pinus yunnanensis Franch.) in response to foliar application of IAA (indole-3-acetic acid) at rates of 0, 200 and 400 mg·L−1 and IBA (indole-3-butyric acid) at rates of 0, 200 and 400 mg·L−1 in order to promote the growth during the seedlings’ early stage. The experiment was conducted at the Lufeng Village Forest Farm of Yiliang County in Kunming, Yunnan, China. The results showed that IAA and IBA were effective in growth promotion of Yunnan pine seedlings. The response of both growth increment and biomass accumulation to the concentration of IAA and IBA can be modeled using a bivariate surface response, and each growth index had a peak value. Growth indexes increased with the increase of the dosage of photohormones before reaching a peak value, and then decreased. The different growth indexes had various responses to the concentrations and ratio of IAA and IBA. The foliar application of IAA in combination with IBA showed the largest improvement on the biomass of the needles, followed by stems and roots. The higher ratio of IAA promoted stem diameter growth, root system development and biomass accumulation in the needles, while a higher ratio of IBA contributed to height growth and biomass accumulation in the stem. Based on the auxin effect equations on the different growth indexes and surface response, the optimum concentrations and the (IAA:IBA) ratios can be obtained. The optimum concentrations of IAA and IBA were 167 and 186, 310 and 217, 193 and 159, 191 and 221, and 206 and 186 mg·L−1, with corresponding ratios of 1:1.11, 1:0.70, 1:0.82, 1:1.15 and 1:0.90, respectively, at the maximum seedling height and collar diameter growth as well as biomass accumulation at the root, stem and needle. The above growth indexes were 22.00%, 79.80%, 48.65%, 82.20% and 107.00% higher than the control treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Anti-Proliferation and Anti-Invasion Effects of Diosgenin on Gastric Cancer BGC-823 Cells with HIF-1α shRNAs
Int. J. Mol. Sci. 2012, 13(5), 6521-6533; doi:10.3390/ijms13056521
Received: 22 February 2012 / Revised: 2 April 2012 / Accepted: 9 May 2012 / Published: 24 May 2012
Cited by 9 | PDF Full-text (2441 KB) | HTML Full-text | XML Full-text
Abstract
Drug resistance is a major factor for the limited efficacy of chemotherapy in gastric cancer treatment. Hypoxia-inducible factor-1α (HIF-1α), a central transcriptional factor in hypoxia, is suggested to participate in the resistance. Here, we identified a hypoxia-mimic (cobalt chloride) sensitive gastric cell [...] Read more.
Drug resistance is a major factor for the limited efficacy of chemotherapy in gastric cancer treatment. Hypoxia-inducible factor-1α (HIF-1α), a central transcriptional factor in hypoxia, is suggested to participate in the resistance. Here, we identified a hypoxia-mimic (cobalt chloride) sensitive gastric cell line BGC-823 to explore whether diosgenin, an aglycone of steroidal saponins, can inhibit cancer cell invasion and survival of solid tumor in a hypoxic mimic microenvironment. We have shown that diosgenin is a potent candidate for decreasing the ability of invasion and survival in cobalt chloride treated BGC-823 cells. In addition, when combined with HIF-1α specific short hairpin RNA (shRNA), diosgenin can inhibit BGC-823 cells more effectively. The anti-invasion role of diosgenin may be related to E-cadherin, integrinα5 and integrinβ6. These results suggest that diosgenin may be a useful compound in controlling gastric cancer cells in hypoxia condition, especially when combined with down-regulated HIF-1α. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

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Open AccessReview The Role of Protein Crystallography in Defining the Mechanisms of Biogenesis and Catalysis in Copper Amine Oxidase
Int. J. Mol. Sci. 2012, 13(5), 5375-5405; doi:10.3390/ijms13055375
Received: 6 April 2012 / Revised: 22 April 2012 / Accepted: 26 April 2012 / Published: 3 May 2012
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Abstract
Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine [...] Read more.
Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer’s disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography. Full article
(This article belongs to the Special Issue Protein Crystallography in Molecular Biology)
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Open AccessReview Antibody Phage Display Libraries: Contributions to Oncology
Int. J. Mol. Sci. 2012, 13(5), 5420-5440; doi:10.3390/ijms13055420
Received: 1 March 2012 / Revised: 5 April 2012 / Accepted: 24 April 2012 / Published: 4 May 2012
Cited by 9 | PDF Full-text (340 KB) | HTML Full-text | XML Full-text
Abstract
Since the advent of phage display technology, dating back to 1985, antibody libraries displayed on filamentous phage surfaces have been used to identify specific binders for many different purposes, including the recognition of tumors. Phage display represents a high-throughput technique for screening [...] Read more.
Since the advent of phage display technology, dating back to 1985, antibody libraries displayed on filamentous phage surfaces have been used to identify specific binders for many different purposes, including the recognition of tumors. Phage display represents a high-throughput technique for screening billions of random fusion antibodies against virtually any target on the surface or inside cancer cells, or even soluble markers found in patient serum. Many phage display derived binders targeting important tumor markers have been identified. Selection directed to tumoral cells’ surfaces lead to the identification of unknown tumoral markers. Also the improvement of methods that require smaller amounts of cells has opened the possibility to use this approach on patient samples. Robust techniques combining an antibody library displayed on the phage surface and protein microarray allowed the identification of auto antibodies recognized by patient sera. Many Ab molecules directly or indirectly targeting angiogenesis have been identified, and one of them, ramucirumab, has been tested in 27 phase I–III clinical trials in a broad array of cancers. Examples of such antibodies will be discussed here with emphasis on those used as probes for molecular imaging and other clinical trials. Full article
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Open AccessReview Design and Synthesis of Binding Growth Factors
Int. J. Mol. Sci. 2012, 13(5), 6053-6072; doi:10.3390/ijms13056053
Received: 5 March 2012 / Revised: 10 April 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 15 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
Growth factors play important roles in tissue regeneration. However, because of their instability and diffusible nature, improvements in their performance would be desirable for therapeutic applications. Conferring binding affinities would be one way to improve their applicability. Here we review techniques for [...] Read more.
Growth factors play important roles in tissue regeneration. However, because of their instability and diffusible nature, improvements in their performance would be desirable for therapeutic applications. Conferring binding affinities would be one way to improve their applicability. Here we review techniques for conjugating growth factors to polypeptides with particular affinities. Conjugation has been designed at the level of gene fusion and of polypeptide ligation. We summarize and discuss the designs and applications of binding growth factors prepared by such conjugation approaches. Full article
(This article belongs to the Special Issue Protein Conjugates and Bioconjugate Chemistry)
Open AccessReview The Quiescent Cellular State is Arf/p53-Dependent and Associated with H2AX Downregulation and Genome Stability
Int. J. Mol. Sci. 2012, 13(5), 6492-6506; doi:10.3390/ijms13056492
Received: 11 April 2012 / Revised: 21 May 2012 / Accepted: 22 May 2012 / Published: 24 May 2012
Cited by 5 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is a disease associated with genomic instability and mutations. Excluding some tumors with specific chromosomal translocations, most cancers that develop at an advanced age are characterized by either chromosomal or microsatellite instability. However, it is still unclear how genomic instability and [...] Read more.
Cancer is a disease associated with genomic instability and mutations. Excluding some tumors with specific chromosomal translocations, most cancers that develop at an advanced age are characterized by either chromosomal or microsatellite instability. However, it is still unclear how genomic instability and mutations are generated during the process of cellular transformation and how the development of genomic instability contributes to cellular transformation. Recent studies of cellular regulation and tetraploidy development have provided insights into the factors triggering cellular transformation and the regulatory mechanisms that protect chromosomes from genomic instability. Full article
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Open AccessShort Note Development of Nine Markers and Characterization of the Microsatellite Loci in the Endangered Gymnogobius isaza (Gobiidae)
Int. J. Mol. Sci. 2012, 13(5), 5700-5705; doi:10.3390/ijms13055700
Received: 5 April 2012 / Revised: 28 April 2012 / Accepted: 7 May 2012 / Published: 11 May 2012
PDF Full-text (176 KB) | HTML Full-text | XML Full-text
Abstract
Gymnogobius isaza is a freshwater goby endemic to Lake Biwa, Japan. They experienced a drastic demographic bottleneck in the 1950s and 1980s and slightly recovered thereafter, but the population size is still very small. To reveal dynamics of genetic diversity of G. [...] Read more.
Gymnogobius isaza is a freshwater goby endemic to Lake Biwa, Japan. They experienced a drastic demographic bottleneck in the 1950s and 1980s and slightly recovered thereafter, but the population size is still very small. To reveal dynamics of genetic diversity of G. isaza, we developed nine microsatellite markers based on the sequence data of a related goby Chaenogobius annularis. Nine SSR (Simple Sequence Repeats) markers were successfully amplified for raw and formalin-fixed fish samples. The number of alleles and expected heterozygosities ranged from one to 10 and from 0.06 to 0.84, respectively, for the current samples, while one to 12 and 0.09 to 0.83 for historical samples. The markers described here will be useful for investigating the genetic diversity and gene flow and for conservation of G. isaza. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessCorrection Correction: Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction. Int. J. Mol. Sci. 2012, 13, 737-757
Int. J. Mol. Sci. 2012, 13(5), 6452-6453; doi:10.3390/ijms13056452
Received: 4 May 2012 / Revised: 7 May 2012 / Accepted: 8 May 2012 / Published: 24 May 2012
Cited by 7 | PDF Full-text (88 KB) | HTML Full-text | XML Full-text
Abstract We would like to change the authors’ names and E-Mail addresses on Page 737 of Article [1] from: [...] Full article

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