International Journal of Molecular Sciences

16 pages, 461 KiB

Open AccessArticle

Transcriptome Analysis Reveals Putative Genes Involved in Iridoid Biosynthesis in Rehmannia glutinosa

by Peng Sun¹, Shuhui Song², Lili Zhou¹, Bing Zhang², Jianjun Qi¹ and Xianen Li^1,*

¹ Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China

² CAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China

Int. J. Mol. Sci. 2012, 13(10), 13748-13763; https://doi.org/10.3390/ijms131013748 - 23 Oct 2012

Cited by 44 | Viewed by 8804

Abstract

Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R [...] Read more.

Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R. glutinosa and investigate genes involved in iridoid biosynthesis, we used massively parallel pyrosequencing on the 454 GS FLX Titanium platform to generate a substantial EST dataset. Based on sequence similarity searches against the public sequence databases, the sequences were first annotated and then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) based analysis. Bioinformatic analysis indicated that the 454 assembly contained a set of genes putatively involved in iridoid biosynthesis. Significantly, homologues of the secoiridoid pathway genes that were only identified in terpenoid indole alkaloid producing plants were also identified, whose presence implied that route II iridoids and route I iridoids share common enzyme steps in the early stage of biosynthesis. The gene expression patterns of four prenyltransferase transcripts were analyzed using qRT-PCR, which shed light on their putative functions in tissues of R. glutinosa. The data explored in this study will provide valuable information for further studies concerning iridoid biosynthesis. Full article

(This article belongs to the Section Biochemistry)

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11 pages, 165 KiB

Open AccessReview

The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation

by Ai-Di Gu^1,2, Mu-Sheng Zeng¹ and Chao-Nan Qian^1,3,*

¹ State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, China

² Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA

³ Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, 333 Bostwick Ave. NE, Grand Rapids, MI 49503, USA

Int. J. Mol. Sci. 2012, 13(10), 13737-13747; https://doi.org/10.3390/ijms131013737 - 23 Oct 2012

Cited by 18 | Viewed by 7006

Abstract

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from [...] Read more.

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1) epidemiological studies should reveal EBV infection as a risk factor; (2) the introduction of EBV into an animal model should produce NPC; (3) in the animal model NPC, the main molecular event(s) or the involved signaling pathway(s) should be identical to that in human NPC; and (4) finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))

11 pages, 412 KiB

Open AccessArticle

Synthesis and Characterization of Mesoporous Silica Functionalized with Calix[4]arene Derivatives

by Sana M. Alahmadi^1,2,*, Sharifah Mohamad¹ and Mohd Jamil Maah¹

¹ Department of Chemistry, Faculty of Science, University Malaya, Kuala Lumpur 50603, Malaysia

² Department of Chemistry, Faculty of Science, Taibah University, Almadina Almonwara 30001, Saudi Arabia

Int. J. Mol. Sci. 2012, 13(10), 13726-13736; https://doi.org/10.3390/ijms131013726 - 23 Oct 2012

Cited by 28 | Viewed by 8007

Abstract

This work reports a new method to covalently attach calix[4]arene derivatives onto MCM-41, using a diisocyanate as a linker. The modified mesoporous silicates were characterized by fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and elemental analysis. The FTIR spectra and TGA analysis [...] Read more.

This work reports a new method to covalently attach calix[4]arene derivatives onto MCM-41, using a diisocyanate as a linker. The modified mesoporous silicates were characterized by fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and elemental analysis. The FTIR spectra and TGA analysis verified that the calix[4]arene derivates are covalently attached to the mesoporous silica. The preservation of the MCM-41 channel system was checked by X-ray diffraction and nitrogen adsorption analysis. Full article

(This article belongs to the Section Materials Science)

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13 pages, 397 KiB

Open AccessReview

The Role of Neurotrophins in Multiple Sclerosis—Pathological and Clinical Implications

by Alicja Kalinowska-Lyszczarz^1,2,* and Jacek Losy^3,4

¹ Department of Neurochemistry and Neuropathology, Chair of Neurology, Poznan University of Medical Sciences, 49, Przybyszewskiego st., 60-355 Poznan, Poland

² Heliodor Swiecicki University Hospital, 60-355 Poznan, Poland

³ Department of Clinical Neuroimmunology, Chair of Neurology, Poznan University of Medical Sciences, Poland

⁴ Neuroimmunological Unit, Institute of Experimental and Clinical Medicine, Polish Academy of Sciences, 60-355 Poznan, Poland

Int. J. Mol. Sci. 2012, 13(10), 13713-13725; https://doi.org/10.3390/ijms131013713 - 22 Oct 2012

Cited by 34 | Viewed by 7841

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in [...] Read more.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in the CNS of MS patients. Neurotrophins are polypeptides belonging to the neurotrophic factor family. While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells fraction (PBMCs) of immunological system. In MS additional neurotrophic support from PBMCs might compensate relative neurotrophins deficiency in the damaged CNS tissue that needs to be repaired. Failure to produce the adequate neurotrophins concentrations might result in decreased protection of the CNS, consequently leading to increased atrophy, which is the main determinant of MS patients’ end-point disability. There are several lines of evidence, both from clinical research and animal models, suggesting that neurotrophins play a pivotal role in neuroprotective and neuroregenerative processes that are often defective in the course of MS. It seems that neuroprotective strategies might be used as potentially valuable add-on therapies, alongside traditional immunomodulatory treatment in multiple sclerosis. Full article

(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)

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9 pages, 468 KiB

Open AccessArticle

Detection of Ricin Intoxication in Mice Using Serum Peptide Profiling by MALDI-TOF/MS

by Siyan Zhao^1,2,†, Wen-Sen Liu^1,2,†, Meng Wang^1,2, Jiping Li^1,2, Yucheng Sun^1,2, Nan Li^1,2, Feng Hou^1,2, Jia-Yu Wan^1,2, Zhongyi Li^1,2, Jun Qian^1,2,* and Linna Liu^1,2,*

¹ Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, Jilin 130122, China

² Zoonosis Prevention and Control Key Laboratory, 666 West Liuying Road, Changchun, Jilin 130122, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2012, 13(10), 13704-13712; https://doi.org/10.3390/ijms131013704 - 22 Oct 2012

Cited by 8 | Viewed by 6432

Abstract

Ricin toxin has been regarded as one of the most potent poisons in the plant kingdom, and there is no effective therapeutic countermeasure or licensed vaccine against it. Consequently, early detection of ricin intoxication is necessary. In this study, we took mice as [...] Read more.

Ricin toxin has been regarded as one of the most potent poisons in the plant kingdom, and there is no effective therapeutic countermeasure or licensed vaccine against it. Consequently, early detection of ricin intoxication is necessary. In this study, we took mice as test subjects, and used the technique of Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) and ClinProt™ microparticle beads to set up an effective detection model with an accuracy of almost 100%. Eighty-two peaks in the mass range 1000–10,000 m/z were detected by ClinProTools software, and five different peaks with m/z of 4982.49, 1333.25, 1537.86, 4285.05 and 2738.88 had the greatest contribution to the accuracy and sensitivity of this model. They may therefore provide biomarkers for ricin intoxication. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)

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13 pages, 234 KiB

Open AccessArticle

Lack of Association of Estrogen Receptor Alpha Gene Polymorphisms with Cardiorespiratory and Metabolic Variables in Young Women

by Ana Cristina Rebelo^1,*, Rozangela Verlengia², Vandeni Kunz³, Nayara Tamburus⁴, Alvaro Cerda⁵, Rosario Hirata⁵, Mario Hirata⁵ and Ester Silva⁴

¹ Department of Morphology, (Campus II), Federal University of Goiás, 74001-970, Goiânia, GO, Brazil

² College of Health Sciences, Methodist University of Piracicaba, Rodovia Açucar, Km 151, 13400-911, Piracicaba, SP, Brazil

³ Adventist University Center São Paulo, 13165-970, Engenheiro Coellho, SP, Brazil

⁴ Federal University of São Carlos, Rodovia Washington Luís, km 235-SP-310, 13565-905, Sao Carlos, SP, Brazil

⁵ University of São Paulo, Lab Applied Molecular Biology and Pharmacogenomics, Federal University of São Paulo, Av. Prof. Lineu Prestes, 58005508-900, Sao Paulo, SP, Brazil

Int. J. Mol. Sci. 2012, 13(10), 13691-13703; https://doi.org/10.3390/ijms131013691 - 22 Oct 2012

Cited by 5 | Viewed by 6564

Abstract

This study examined the association of estrogen receptor alpha gene (ESR1) polymorphisms with cardiorespiratory and metabolic parameters in young women. In total, 354 healthy women were selected for cardiopulmonary exercise testing and short-term heart rate (HR) variability (HRV) evaluation. The HRV [...] Read more.

This study examined the association of estrogen receptor alpha gene (ESR1) polymorphisms with cardiorespiratory and metabolic parameters in young women. In total, 354 healthy women were selected for cardiopulmonary exercise testing and short-term heart rate (HR) variability (HRV) evaluation. The HRV analysis was determined by the temporal indices rMSSD (square root of the mean squared differences of successive R–R intervals (RRi) divided by the number of RRi minus one), SDNN (root mean square of differences from mean RRi, divided by the number of RRi) and power spectrum components by low frequency (LF), high frequency (HF) and LF/HF ratio. Blood samples were obtained for serum lipids, estradiol and DNA extraction. ESR1 rs2234693 and rs9340799 polymorphisms were analyzed by PCR and fragment restriction analysis. HR and oxygen uptake (VO₂) values did not differ between the ESR1 polymorphisms with respect to autonomic modulation. We not find a relationship between ESR1 T–A, T–G, C–A and C–G haplotypes and cardiorespiratory and metabolic variables. Multiple linear regression analysis demonstrated that VO₂, total cholesterol and triglycerides influence HRV (p < 0.05). The results suggest that ESR1 variants have no effect on cardiorespiratory and metabolic variables, while HRV indices are influenced by aerobic capacity and lipids in healthy women. Full article

11 pages, 216 KiB

Open AccessReview

Involvement of Oxidative Stress in Suppression of Insulin Biosynthesis under Diabetic Conditions

by Hideaki Kaneto^* and Taka-aki Matsuoka

Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Int. J. Mol. Sci. 2012, 13(10), 13680-13690; https://doi.org/10.3390/ijms131013680 - 22 Oct 2012

Cited by 31 | Viewed by 10557

Abstract

Type 2 diabetes is characterized by pancreatic β-cell dysfunction and insulin resistance, and the number of patients has markedly increased worldwide. In the diabetic state, hyperglycemia per se and subsequent induction of oxidative stress decrease insulin biosynthesis and secretion, leading to the aggravation [...] Read more.

Type 2 diabetes is characterized by pancreatic β-cell dysfunction and insulin resistance, and the number of patients has markedly increased worldwide. In the diabetic state, hyperglycemia per se and subsequent induction of oxidative stress decrease insulin biosynthesis and secretion, leading to the aggravation of Type 2 diabetes. In addition, there is substantial reduction in expression and/or activities of several insulin gene transcription factors. This process is known as β-cell glucose toxicity, which is often observed under diabetic conditions. Taken together, it is likely that oxidative stress explains, at least in part, the molecular mechanism for β-cell glucose toxicity, which is often observed in Type 2 diabetes. Full article

(This article belongs to the Section Molecular Toxicology)

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13 pages, 676 KiB

Open AccessArticle

Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

by Jun Yan^1,*, Jia Liu¹, Clement Yihao Lin¹, ANZGene^†, Peter A. Csurhes^1,2, Michael P. Pender², Pamela A. McCombe¹ and Judith M. Greer^1,*

¹ The University of Queensland, Centre for Clinical Research, Royal Brisbane & Women’s Hospital, 4029 Brisbane, Australia

² School of Medicine, The University of Queensland, and Department of Neurology, Royal Brisbane & Women’s Hospital, 4029 Brisbane, Australia

^† Members of the ANZGene Consortium are listed in the Acknowledgements section.

Int. J. Mol. Sci. 2012, 13(10), 13667-13679; https://doi.org/10.3390/ijms131013667 - 22 Oct 2012

Cited by 16 | Viewed by 7916

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important [...] Read more.

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6). Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression. Full article

(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)

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46 pages, 1085 KiB

Open AccessReview

Tanshinones: Sources, Pharmacokinetics and Anti-Cancer Activities

by Yong Zhang¹, Peixin Jiang¹, Min Ye², Sung-Hoon Kim³

, Cheng Jiang^1,* and Junxuan Lü^1,*

¹ Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center School of Pharmacy, 1300 S. Coulter, Amarillo, TX 79106, USA

² State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

³ Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee University, Seoul 130-701, Korea

Int. J. Mol. Sci. 2012, 13(10), 13621-13666; https://doi.org/10.3390/ijms131013621 - 22 Oct 2012

Cited by 215 | Viewed by 15437

Abstract

Tanshinones are a class of abietane diterpene compound isolated from Salvia miltiorrhiza (Danshen or Tanshen in Chinese), a well-known herb in Traditional Chinese Medicine (TCM). Since they were first identified in the 1930s, more than 40 lipophilic tanshinones and structurally related compounds have [...] Read more.

Tanshinones are a class of abietane diterpene compound isolated from Salvia miltiorrhiza (Danshen or Tanshen in Chinese), a well-known herb in Traditional Chinese Medicine (TCM). Since they were first identified in the 1930s, more than 40 lipophilic tanshinones and structurally related compounds have been isolated from Danshen. In recent decades, numerous studies have been conducted to investigate the isolation, identification, synthesis and pharmacology of tanshinones. In addition to the well-studied cardiovascular activities, tanshinones have been investigated more recently for their anti-cancer activities in vitro and in vivo. In this review, we update the herbal and alternative sources of tanshinones, and the pharmacokinetics of selected tanshinones. We discuss anti-cancer properties and identify critical issues for future research. Whereas previous studies have suggested anti-cancer potential of tanshinones affecting multiple cellular processes and molecular targets in cell culture models, data from in vivo potency assessment experiments in preclinical models vary greatly due to lack of uniformity of solvent vehicles and routes of administration. Chemical modifications and novel formulations had been made to address the poor oral bioavailability of tanshinones. So far, human clinical trials have been far from ideal in their design and execution for the purpose of supporting an anti-cancer indication of tanshinones. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))

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16 pages, 1120 KiB

Open AccessArticle

Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL) Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

by Yu Dong¹, Qingguo Zhang², Yunxia Li¹, Jia Jiang¹ and Shiyi Chen^1,*

¹ Department of Sports Medicine, Huashan Hospital, No. 12, Wulumuqi Zhong Road, Shanghai 200040, China

² Department of Orthopedics, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, China

Int. J. Mol. Sci. 2012, 13(10), 13605-13620; https://doi.org/10.3390/ijms131013605 - 22 Oct 2012

Cited by 58 | Viewed by 7981

Abstract

At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal [...] Read more.

At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2) on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs) were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control), and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2) were used to reconstruct the anterior cruciate ligament (ACL) in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N) (P = 0.041 and P = 0.001, respectively). In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3) was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4) or control groups (12.4 ± 6.0) (p = 0.036 and 0.001, respectively). Based on the histological findings, there was an increased amount of perpendicular collagen fibers formed between the tendon and bone in the bMSCs+Lv-Control and bMSCs+Lv-BMP-2 group, compared with the gastrocnemius tendons. The proliferation of cartilage-like cells and the formation of fibrocartilage-like tissue were highest within the bone tunnels in the bMSCs+Lv-BMP-2 group. These results suggest that this lentivirus can be used to efficiently infect bMSCs with BMP-2. Furthermore, tendons wrapped by bMSCs+Lv-BMP-2 improved tendon–bone healing. Full article

(This article belongs to the Section Biochemistry)

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18 pages, 476 KiB

Open AccessArticle

A Bead-Based Multiplexed Immunoassay to Evaluate Breast Cancer Biomarkers for Early Detection in Pre-Diagnostic Serum

by Annemieke W. J. Opstal-van Winden^1,2, Wendy Rodenburg³, Jeroen L. A. Pennings³, Conny T. M. Van Oostrom³, Jos H. Beijnen^2,4, Petra H.M. Peeters^1,5, Carla H. Van Gils^1,* and Annemieke De Vries³

¹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands

² Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute and Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands

³ Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), A. van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands

⁴ Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Section of Drug Toxicology, Faculty of Science, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands

⁵ Department of Epidemiology, Public Health and Primary Care, Faculty of Medicine, Imperial College, Norfolk Place, London W2 1PG, UK

Int. J. Mol. Sci. 2012, 13(10), 13587-13604; https://doi.org/10.3390/ijms131013587 - 22 Oct 2012

Cited by 46 | Viewed by 8738

Abstract

This study investigates whether a set of ten potential breast cancer serum biomarkers and cancer antigens (osteopontin (OPN), haptoglobin, cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prolactin, cancer antigen 19-9 (CA19-9), α-fetoprotein (AFP), leptin and migration inhibitory factor (MIF)) [...] Read more.

This study investigates whether a set of ten potential breast cancer serum biomarkers and cancer antigens (osteopontin (OPN), haptoglobin, cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prolactin, cancer antigen 19-9 (CA19-9), α-fetoprotein (AFP), leptin and migration inhibitory factor (MIF)) can predict early stage breast cancer in samples collected before clinical diagnosis (phase III samples). We performed a nested case-control study within the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. We examined to what extent the biomarker panel could discriminate between 68 women diagnosed with breast cancer up to three years after enrollment and 68 matched healthy controls (all 56-64 years at baseline). Using a quantitative bead-based multiplexed assay, we determined protein concentrations in serum samples collected at enrollment. Principal Component Analysis (PCA) and Random Forest (RF) analysis revealed that on the basis of all ten proteins, early cases could not be separated from controls. When we combined serum protein concentrations and subject characteristics related to breast cancer risk in the RF analysis, this did not result in classification accuracy scores that could correctly classify the samples (sensitivity: 50%, specificity: 50%). Our findings indicate that this panel of selected tumor markers cannot be used for diagnosis of early breast cancer. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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18 pages, 696 KiB

Open AccessArticle

The Properties of Sintered Calcium Phosphate with [Ca]/[P] = 1.50

by I-Ming Hung¹, Wei-Jen Shih², Min-Hsiung Hon³ and Moo-Chin Wang^4,*

¹ Yuan Ze Fuel Cell Center, Department of Chemical Engineering and Materials Science, Yuan Ze University, No. 135, Yuan-Tung Road, Chungli, Taoyuan 320, Taiwan

² Metal Industries Research and Development Centre, 1001 Kaonan Highway, Kaohsiung 81160, Taiwan

³ Department of Materials Science and Engineering, National Cheng Kung University, 1 Ta–Hsueh Road, Tainan 70101, Taiwan

⁴ Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80782, Taiwan

Int. J. Mol. Sci. 2012, 13(10), 13569-13586; https://doi.org/10.3390/ijms131013569 - 22 Oct 2012

Cited by 66 | Viewed by 8966

Abstract

In order to obtain the properties of the sintered as-dried calcium phosphate with [Ca]/[P] = 1.50, the characteristics of sintered pellets have been investigated using X-ray diffraction (XRD), inductively coupled plasma-mass spectrometry (ICP-MS), Fourier-transform infrared (FT-IR) spectra, Vickers hardness indentation and scanning electron [...] Read more.

In order to obtain the properties of the sintered as-dried calcium phosphate with [Ca]/[P] = 1.50, the characteristics of sintered pellets have been investigated using X-ray diffraction (XRD), inductively coupled plasma-mass spectrometry (ICP-MS), Fourier-transform infrared (FT-IR) spectra, Vickers hardness indentation and scanning electron microscopy (SEM). When the pellet samples were sintered between 700 °C and 1200 °C for 4 h, the hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, HA) still maintained the major phase, accompanied with the rhenanite (NaCaPO₄) as the secondary phase and β-tricalcium phosphate (β-Ca₃(PO₄)₂, β-TCP) as the minor phases. In addition, the HA partially transformed to α-tricalcium phosphate (α-Ca₃(PO₄)₂, α-TCP) and tetracalcium phosphate (Ca₄(PO4)₂O, TTCP), when the pellet samples were sintered at 1300 °C and 1400 °C, respectively, for 4 h. The maximum density and Vickers Hardness (HV) of sintered pellet samples were 2.85 g/cm³ (90.18% theoretical density (T.D.)) and 407, which appeared at 1200 °C and 900 °C, respectively. Full article

(This article belongs to the Section Materials Science)

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15 pages, 551 KiB

Open AccessReview

E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

by Renier Vélez-Cruz and David G. Johnson^*

Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, 1801 Park Road 1C, Smithville, TX 78957, USA

Int. J. Mol. Sci. 2012, 13(10), 13554-13568; https://doi.org/10.3390/ijms131013554 - 19 Oct 2012

Cited by 14 | Viewed by 8151

Abstract

Many of the biochemical details of nucleotide excision repair (NER) have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms [...] Read more.

Many of the biochemical details of nucleotide excision repair (NER) have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER. Full article

(This article belongs to the Special Issue Excising DNA Damage from Chromosomes: Entry Visas and Exit Strategies)

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12 pages, 320 KiB

Open AccessArticle

Production of (R)-3-Quinuclidinol by E. coli Biocatalysts Possessing NADH-Dependent 3-Quinuclidinone Reductase (QNR or bacC) from Microbacterium luteolum and Leifsonia Alcohol Dehydrogenase (LSADH)

by Kentaro Isotani, Junji Kurokawa and Nobuya Itoh^*

Department of Biotechnology, Faculty of Engineering, Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan

Int. J. Mol. Sci. 2012, 13(10), 13542-13553; https://doi.org/10.3390/ijms131013542 - 19 Oct 2012

Cited by 20 | Viewed by 8251

Abstract

We found two NADH-dependent reductases (QNR and bacC) in Microbacterium luteolum JCM 9174 (M. luteolum JCM 9174) that can reduce 3-quinuclidinone to optically pure (R)-(−)-3-quinuclidinol. Alcohol dehydrogenase from Leifsonia sp. (LSADH) was combined with these reductases to regenerate NAD⁺ [...] Read more.

We found two NADH-dependent reductases (QNR and bacC) in Microbacterium luteolum JCM 9174 (M. luteolum JCM 9174) that can reduce 3-quinuclidinone to optically pure (R)-(−)-3-quinuclidinol. Alcohol dehydrogenase from Leifsonia sp. (LSADH) was combined with these reductases to regenerate NAD⁺ to NADH in situ in the presence of 2-propanol as a hydrogen donor. The reductase and LSADH genes were efficiently expressed in E. coli cells. A number of constructed E. coli biocatalysts (intact or immobilized) were applied to the resting cell reaction and optimized. Under the optimized conditions, (R)-(−)-3-quinuclidinol was synthesized from 3-quinuclidinone (15% w/v, 939 mM) giving a conversion yield of 100% for immobilized QNR. The optical purity of the (R)-(−)-3-quinuclidinol produced by the enzymatic reactions was >99.9%. Thus, E. coli biocatalysis should be useful for the practical production of the pharmaceutically important intermediate, (R)-(−)-3-quinuclidinol. Full article

(This article belongs to the Special Issue Organic Synthesis Using Biocatalyst)

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21 pages, 4127 KiB

Open AccessArticle

A Simple Bioconjugate Attachment Protocol for Use in Single Molecule Force Spectroscopy Experiments Based on Mixed Self-Assembled Monolayers

by Simon J. Attwood¹, Anna M. C. Simpson², Rachael Stone², Samir W. Hamaia², Debdulal Roy³, Richard W. Farndale², Myriam Ouberai¹ and Mark E.Welland^1,*

¹ Nanoscience Centre, Department of Engineering, Cambridge University, Cambridge, CB3 0FF, UK

² Department of Biochemistry, Cambridge University, Cambridge, CB2 1QW, UK

³ National Physical Laboratory, Teddington, TW11 0LW, UK

Int. J. Mol. Sci. 2012, 13(10), 13521-13541; https://doi.org/10.3390/ijms131013521 - 19 Oct 2012

Cited by 8 | Viewed by 7746

Abstract

Single molecule force spectroscopy is a technique that can be used to probe the interaction force between individual biomolecular species. We focus our attention on the tip and sample coupling chemistry, which is crucial to these experiments. We utilised a novel approach of [...] Read more.

Single molecule force spectroscopy is a technique that can be used to probe the interaction force between individual biomolecular species. We focus our attention on the tip and sample coupling chemistry, which is crucial to these experiments. We utilised a novel approach of mixed self-assembled monolayers of alkanethiols in conjunction with a heterobifunctional crosslinker. The effectiveness of the protocol is demonstrated by probing the biotin-avidin interaction. We measured unbinding forces comparable to previously reported values measured at similar loading rates. Specificity tests also demonstrated a significant decrease in recognition after blocking with free avidin. Full article

(This article belongs to the Special Issue Advances in Single Molecule Spectroscopy)

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20 pages, 3576 KiB

Open AccessArticle

A Systems Biology Approach to Understanding the Mechanisms of Action of Chinese Herbs for Treatment of Cardiovascular Disease

by Bohui Li^1,2,†, Xue Xu^1,2,†, Xia Wang^1,2, Hua Yu^1,2, Xiuxiu Li^1,2, Weiyang Tao^1,2, Yonghua Wang^1,2,* and Ling Yang³

¹ Center of Bioinformatics, Northwest A & F University, Yangling 712100, Shaanxi, China

² College of Life Sciences, Northwest A & F University, Yangling 712100, Shaanxi, China

³ Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy Sciences, Dalian, Liaoning 116023, China

Int. J. Mol. Sci. 2012, 13(10), 13501-13520; https://doi.org/10.3390/ijms131013501 - 19 Oct 2012

Cited by 86 | Viewed by 12739

Abstract

Traditional Chinese Medicine (TCM) involves a broad range of empirical testing and refinement and plays an important role in the health maintenance for people all over the world. However, due to the complexity of Chinese herbs, a full understanding of TCM’s action mechanisms [...] Read more.

Traditional Chinese Medicine (TCM) involves a broad range of empirical testing and refinement and plays an important role in the health maintenance for people all over the world. However, due to the complexity of Chinese herbs, a full understanding of TCM’s action mechanisms is still unavailable despite plenty of successful applications of TCM in the treatment of various diseases, including especially cardiovascular diseases (CVD), one of the leading causes of death. Thus in the present work, by incorporating the chemical predictors, target predictors and network construction approaches, an integrated system of TCM has been constructed to systematically uncover the underlying action mechanisms of TCM. From three representative Chinese herbs, i.e., Ligusticum chuanxiong Hort., Dalbergia odorifera T. Chen and Corydalis yanhusuo WT Wang which have been widely used in CVD treatment, by combinational use of drug absorption, distribution, metabolism and excretion (ADME) screening and network pharmacology techniques, we have generated 64 bioactive ingredients and identified 54 protein targets closely associated with CVD, of which 29 are common targets (52.7%) of the three herbs. The result provides new information on the efficiency of the Chinese herbs for the treatment of CVD and also explains one of the basic theories of TCM, i.e., “multiple herbal drugs can treat one disease”. The predicted potential targets were then mapped to target-disease and target-signal pathway connections, which revealed the relationships of the active ingredients with their potential targets, diseases and signal systems. This means that for the first time, the action mechanism of these three important Chinese herbs for the treatment of CVD is uncovered, by generating and identifying both their active ingredients and novel targets specifically related to CVD, which clarifies some of the common conceptions in TCM, and thus provides clues to modernize such specific herbal medicines. Full article

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17 pages, 747 KiB

Open AccessArticle

Injury-Induced Accumulation of Glial Cell Line-Derived Neurotrophic Factor in the Rostral Part of the Injured Rat Spinal Cord

by Takuya Hara^1,†, Hidefumi Fukumitsu¹, Hitomi Soumiya¹, Yoshiko Furukawa²

and Shoei Furukawa^1,*

¹ Laboratory of Molecular Biology, Gifu Pharmaceutical University, Daigaku-nishi 1-25-4, Gifu 501-1196, Japan

² Department of Pharmaceutical Pharmacology, Faculty of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

^† Present address: Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Higashimurayama, Tokyo 189-0022, Japan.

Int. J. Mol. Sci. 2012, 13(10), 13484-13500; https://doi.org/10.3390/ijms131013484 - 19 Oct 2012

Cited by 7 | Viewed by 6601

Abstract

The spinal cord of a 7-week-old female Wistar rat was hemi-transected at thoracic position 10 with a razor blade, and changes in glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expression levels in the spinal cord were examined. GDNF protein and mRNA [...] Read more.

The spinal cord of a 7-week-old female Wistar rat was hemi-transected at thoracic position 10 with a razor blade, and changes in glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expression levels in the spinal cord were examined. GDNF protein and mRNA expression levels were evaluated by enzyme immunoassay and reverse transcription polymerase chain reaction, respectively. Although GDNF is distributed in the healthy spinal cord from 150 to 400 pg/g tissue in a regionally dependent manner, hemi-transection (left side) of the spinal cord caused a rapid increase in GDNF content in the ipsilateral rostral but not in the caudal part of the spinal cord. On the other hand, injury-induced GDNF mRNA was distributed limitedly in both rostral and caudal stumps. These observations suggest the possibility that increased GDNF in the rostral part is responsible for the accumulation of GDNF that may be constitutively transported from the rostral to caudal side within the spinal cord. Although such local increase of endogenous GDNF protein may not be sufficient for nerve regeneration and locomotor improvement, it may play a physiological role in supporting spinal neurons including motoneurons. Full article

(This article belongs to the Section Biochemistry)

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23 pages, 1041 KiB

Open AccessArticle

Effect of High-Dose Vitamin D3 Intake on Ambulation, Muscular Pain and Bone Mineral Density in a Woman with Multiple Sclerosis: A 10-Year Longitudinal Case Report

by Barbara M. Van Amerongen^1,2,* and François Feron³

¹ Department of Molecular Cell Biology and Immunology, VU University Medical Center,1017 MB Amsterdam, The Netherlands

² Department of Cariology Endodontology Pedodontology, Academic Centre for Dentistry, 1081 LA Amsterdam, Amsterdam, The Netherlands

³ Aix Marseille Université, Centre National de la Recherche Scientifique (CNRS), NICN, UMR 7259, 13015, Marseille, France

Int. J. Mol. Sci. 2012, 13(10), 13461-13483; https://doi.org/10.3390/ijms131013461 - 19 Oct 2012

Cited by 6 | Viewed by 9237

Abstract

Mounting evidence correlate vitamin D3 (cholecalciferol) supplementation or higher serum levels of vitamin D (25(OH)D) with a lower risk of developing multiple sclerosis (MS), reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who [...] Read more.

Mounting evidence correlate vitamin D3 (cholecalciferol) supplementation or higher serum levels of vitamin D (25(OH)D) with a lower risk of developing multiple sclerosis (MS), reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed with MS in 1990. From 1980 to 2000, her ability to walk decreased from ~20 to 1 km per day. Since January 2001, a vitamin D3 supplement was ingested daily. The starting dose was 20 mcg (800 IU)/day and escalated to 100 mcg (4000 IU)/day in September 2004 and then to 150 mcg (6000 IU)/day in December 2005. Vitamin D3 intake reduced muscular pain and improved ambulation from 1 (February 2000) to 14 km/day (February 2008). Vitamin D intake over 10 years caused no adverse effects: no hypercalcaemia, nephrolithiasis or hypercalciuria were observed. Bowel problems in MS may need to be addressed as they can cause malabsorption including calcium, which may increase serum PTH and 1,25(OH)2D levels, as well as bone loss. We suggest that periodic assessment of vitamin D3, calcium and magnesium intake, bowel problems and the measurement of serum 25(OH)D, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS. Full article

(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)

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0 pages, 542 KiB

Open AccessReview

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

by Amedeo Amedei^1,2,3,*, Domenico Prisco^2,4 and Mario Milco D’Elios^1,2,3

¹ Department of Internal Medicine, University of Florence, Largo Brambilla 3, Florence 50134, Italy

² Department of Biomedicine, Patologia Medica Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, Firenze 20134, Italy

³ Center of Oncologic Minimally Invasive Surgery, University of Florence, Largo Brambilla 3, Florence 50134, Italy

⁴ Department of Medical and Surgical Critical Care, University of Florence, Largo Brambilla 3, Florence 50134, Italy

Int. J. Mol. Sci. 2012, 13(10), 13438-13460; https://doi.org/10.3390/ijms131013438 - 19 Oct 2012

Cited by 71 | Viewed by 11736 | Retraction

Abstract

Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration [...] Read more.

Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 340 KiB

Open AccessReview

The Role of MicroRNAs in Breast Cancer Migration, Invasion and Metastasis

by Joy Tang¹, Aamir Ahmad¹ and Fazlul H. Sarkar^1,2,*

¹ Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI 48201, USA

² Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI 48201, USA

Int. J. Mol. Sci. 2012, 13(10), 13414-13437; https://doi.org/10.3390/ijms131013414 - 18 Oct 2012

Cited by 167 | Viewed by 13628

Abstract

MicroRNAs (miRNAs) are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. [...] Read more.

MicroRNAs (miRNAs) are a major class of small, noncoding RNA molecules that regulate gene expression by targeting mRNAs to trigger either translational repression or mRNA degradation. They have recently been more widely investigated due to their potential role as targets for cancer therapy. Many miRNAs have been implicated in several human cancers, including breast cancer. miRNAs are known to regulate cell cycle and development, and thus may serve as useful targets for exploration in anticancer therapeutics. The link between altered miRNA signatures and breast cancer development and metastasis can be observed either through the loss of tumor suppressor miRNAs, such as let-7s, miR-30a/31/34a/125s/200s/203/205/206/342 or the overexpression of oncogenic miRNAs, such as miR-10b/21/135a/155/221/222/224/373/520c in breast cancer cells. Some of these miRNAs have also been validated in tumor specimens of breast cancer patients, underscoring their potential roles in diagnostics, as well as targets for novel therapeutics for breast cancer. In this review article, we will provide an overview and update of our current understanding of the mode of action of several of these well characterized miRNAs in breast cancer models. Therefore, better understanding of the gene networks orchestrated by these miRNAs may help exploit the full potential of miRNAs in regards to cancer diagnosis, treatment, and therapeutics. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))

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16 pages, 2252 KiB

Open AccessArticle

Proteomic Analysis of Albumins and Globulins from Wheat Variety Chinese Spring and Its Fine Deletion Line 3BS-8

by Chao-Ying Ma^1,†, Li-Yan Gao^1,†, Ning Li^1,†, Xiao-Hui Li^1,†, Wu-Jun Ma², Rudi Appels² and Yue-Ming Yan^1,*

¹ College of Life Science, Capital Normal University, Beijing 100048, China

² State Agriculture Biotechnology Centre, Murdoch University, Western Australian Department of Agriculture and Food, Perth, WA 6150, Australia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2012, 13(10), 13398-13413; https://doi.org/10.3390/ijms131013398 - 18 Oct 2012

Cited by 6 | Viewed by 7591

Abstract

The relationship between chromosome deletion in wheat and protein expression were investigated using Chinese Spring and fine deletion line 3BS-8. Through 2-DE (2-D electrophoresis) analysis, no differentially expressed proteins (DEPs) were found in leaf samples; however, 47 DEPs showed at least two-fold abundance [...] Read more.

The relationship between chromosome deletion in wheat and protein expression were investigated using Chinese Spring and fine deletion line 3BS-8. Through 2-DE (2-D electrophoresis) analysis, no differentially expressed proteins (DEPs) were found in leaf samples; however, 47 DEPs showed at least two-fold abundance variation (p < 0.05) in matured wheat grains and 21 spots were identified by tandem MALDI-TOF/TOF-MS. Among the identified spots, four were cultivar-specific, including three (spots B15, B16, and B21) in Chinese Spring and one in 3BS-8 (spot B10). Among variety-different DEPs between Chinese Spring and 3BS-8, most spots showed a higher express profile in CS; only four spots showed up-regulated expression tendency in 3BS-8. An interesting observation was that more than half of the identified protein spots were involved in storage proteins, of which 11 spots were identified as globulins. According to these results, we can presume that the encoded genes of protein spots B15, B16, and B21 were located on the chromosome segment deleted in 3BS-8. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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20 pages, 205 KiB

Open AccessReview

Genetic Variability in DNA Repair Proteins in Age-Related Macular Degeneration

by Janusz Blasiak^1,*, Ewelina Synowiec¹, Antero Salminen^2,3 and Kai Kaarniranta^4,5

¹ University of Lodz, Faculty of Biology and Environmental Protection, Department of Molecular Genetics, Pomorska 141/143, Lodz 90-236, Poland

² Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio FI-70211, Finland

³ Department of Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland

⁴ Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio FI-70211, Finland

⁵ Department of Ophthalmology, Kuopio University Hospital, Kuopio FI-70211, Finland

Int. J. Mol. Sci. 2012, 13(10), 13378-13397; https://doi.org/10.3390/ijms131013378 - 18 Oct 2012

Cited by 26 | Viewed by 6789

Abstract

The pathogenesis of age-related macular degeneration (AMD) is complex and involves interactions between environmental and genetic factors, with oxidative stress playing an important role inducing damage in biomolecules, including DNA. Therefore, genetic variability in the components of DNA repair systems may influence the [...] Read more.

The pathogenesis of age-related macular degeneration (AMD) is complex and involves interactions between environmental and genetic factors, with oxidative stress playing an important role inducing damage in biomolecules, including DNA. Therefore, genetic variability in the components of DNA repair systems may influence the ability of the cell to cope with oxidative stress and in this way contribute to the pathogenesis of AMD. However, few reports have been published on this subject so far. We demonstrated that the c.977C>G polymorphism (rs1052133) in the hOGG1 gene and the c.972G>C polymorphism (rs3219489) in the MUTYH gene, the products of which play important roles in the repair of oxidatively damaged DNA, might be associated with the risk of AMD. Oxidative stress may promote misincorporation of uracil into DNA, where it is targeted by several DNA glycosylases. We observed that the g.4235T>C (rs2337395) and c.−32A>G (rs3087404) polymorphisms in two genes encoding such glycosylases, UNG and SMUG1, respectively, could be associated with the occurrence of AMD. Polymorphisms in some other DNA repair genes, including XPD (ERCC2), XRCC1 and ERCC6 (CSB) have also been reported to be associated with AMD. These data confirm the importance of the cellular reaction to DNA damage, and this may be influenced by variability in DNA repair genes, in AMD pathogenesis. Full article

(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)

26 pages, 938 KiB

Open AccessArticle

NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer

by Vladimir Kashuba^1,2,†, Alexey A. Dmitriev^3,†

, George S. Krasnov³, Tatiana Pavlova¹, Ilya Ignatjev¹, Vasily V. Gordiyuk², Anna V. Gerashchenko², Eleonora A. Braga⁴, Surya P. Yenamandra¹, Michael Lerman⁵, Vera N. Senchenko³ and Eugene Zabarovsky^1,3,6,*

¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm SE-171 77, Sweden

² Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics, NASU, Kiev 01000, Ukraine

³ Laboratory of Structural and Functional Genomics, Engelhard Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia

⁴ Russian State Genetics Center GosNIIgenetika, Moscow 117545, Russia

⁵ Affina Biotechnologies, Stamford, CT 06902, USA

⁶ Linköping University, Department of Clinical and Experimental Medicine, Linköping SE-581 85, Sweden

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2012, 13(10), 13352-13377; https://doi.org/10.3390/ijms131013352 - 18 Oct 2012

Cited by 26 | Viewed by 8644

Abstract

Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and [...] Read more.

Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and prognosis of HGSOC. Thirty five NotI markers showed frequency of methylation/deletion more or equal to 17%. To check the results of NMA hybridizations several samples for four genes (LRRC3B, THRB, ITGA9 and RBSP3 (CTDSPL)) were bisulfite sequenced and confirmed the results of NMA hybridization. A set of eight biomarkers: NKIRAS1/RPL15, THRB, RBPS3 (CTDSPL), IQSEC1, NBEAL2, ZIC4, LOC285205 and FOXP1, was identified as the most prominent set capable to detect both early and late stages of ovarian cancer. Sensitivity of this set is equal to (72 ± 11)% and specificity (94 ± 5)%. Early stages represented the most complicated cases for detection. To distinguish between Stages I + II and Stages III + IV of ovarian cancer the most perspective set of biomarkers would include LOC285205, CGGBP1, EPHB1 and NKIRAS1/RPL15. The sensitivity of the set is equal to (80 ± 13)% and the specificity is (88 ± 12)%. Using this technique we plan to validate this panel with new epithelial ovarian cancer samples and add markers from other chromosomes. Full article

(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer 2012)

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14 pages, 1932 KiB

Open AccessArticle

Ischemic Postconditioning Alleviates Neuronal Injury Caused by Relief of Carotid Stenosis in a Rat Model of Cerebral Hypoperfusion

by Chunsheng Feng¹, Tianfei Luo², Li Qi³, Boyu Wang⁴, Yinan Luo⁴ and Pengfei Ge^4,*

¹ Department of Anesthesiology, First Bethune Hospital of Jilin University, Changchun 130021, China

² Department of Neurology, First Bethune Hospital of Jilin University, Changchun 130021, China

³ Department of Neurology, Affiliated Hospital of Guilin Medical College, Guilin 541001, China

⁴ Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun 130021, China

Int. J. Mol. Sci. 2012, 13(10), 13338-13351; https://doi.org/10.3390/ijms131013338 - 18 Oct 2012

Cited by 9 | Viewed by 5770

Abstract

The effects of early relief of heavy bilateral carotid stenosis and ischemic postconditioning on hippocampus CA1 neurons are still unclear. In this study, we used a rat model to imitate severe bilateral carotid stenosis in humans. The rats were divided into sham group, [...] Read more.

The effects of early relief of heavy bilateral carotid stenosis and ischemic postconditioning on hippocampus CA1 neurons are still unclear. In this study, we used a rat model to imitate severe bilateral carotid stenosis in humans. The rats were divided into sham group, carotid stenosis group, stenosis relief group and ischemic postconditioning group. Ischemic postconditioning consisted of three cycles of 30 s ischemia and 30 s reperfusion. The cerebral blood flow was measured with a laser Doppler flowmeter. Neuronal death in the CA1 region was observed by hematoxylin-eosin staining, and the number of live neurons was assessed by cell counting under a light microscope. The levels of oxidative products MDA and 8-iso-PGF2α, inflammatory factors IL-1β and TNF-α, and the activities of anti-oxidative enzymes SOD and CAT were assayed by specific enzyme-linked immunosorbent assay (ELISA) kits, respectively. We found that relief of carotid stenosis and ischemic postconditioning could increase cerebral blood flow. When stenosis was relieved, the percentage of live neurons was 66.6% ± 6.2% on day 3 and 62.3% ± 9.8% on day 27, which was significantly higher than 55.5% ± 4.8% in stenosis group. Ischemic postconditioning markedly improved the live neurons to 92.5% ± 6.7% on day 3 and 88.6% ± 9.1% on day 27. Further study showed that, neuronal death caused by relief of stenosis is associated with increased oxidative stress and enhanced inflammatory response, and the protection of ischemic postconditioning is related to inhibition of oxidative stress and suppression of inflammatory response. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 267 KiB

Open AccessReview

Histone Displacement during Nucleotide Excision Repair

by Christoffel Dinant^1,*, Jiri Bartek^1,2 and Simon Bekker-Jensen^3,*

¹ Genome Integrity Unit, Danish Cancer Society Research Centre, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

² Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, CZ-775 15 Olomouc, Czech Republic

³ Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark

Int. J. Mol. Sci. 2012, 13(10), 13322-13337; https://doi.org/10.3390/ijms131013322 - 17 Oct 2012

Cited by 9 | Viewed by 6334

Abstract

Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex [...] Read more.

Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex called chromatin. The condensed nature of chromatin inhibits many DNA metabolizing activities, including NER. In order to promote efficient repair, detection of a lesion not only has to activate the NER pathway but also chromatin remodeling. In general, such remodeling is thought on the one hand to precede NER, thus allowing repair proteins to efficiently access DNA. On the other hand, after completion of the repair, the chromatin must be returned to its previous undamaged state. Chromatin remodeling can refer to three separate but interconnected processes, histone post-translational modifications, insertion of histone variants and histone displacement (including nucleosome sliding). Here we review current knowledge, and speculate about current unknowns, regarding those chromatin remodeling activities that physically displace histones before, during and after NER. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 1687 KiB

Open AccessArticle

ABO Blood Group System and Gastric Cancer: A Case-Control Study and Meta-Analysis

by Zhiwei Wang^†, Lei Liu^†, Jun Ji, Jianian Zhang, Min Yan, Jun Zhang, Bingya Liu, Zhenggang Zhu and Yingyan Yu^*

¹ Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2012, 13(10), 13308-13321; https://doi.org/10.3390/ijms131013308 - 17 Oct 2012

Cited by 98 | Viewed by 12618

Abstract

This study focuses on the association between the ABO blood group system and the risk of gastric cancer or Helicobacter pylori infection. The data for the ABO blood group was collected from 1045 cases of gastric cancer, whereby the patient underwent a gastrectomy [...] Read more.

This study focuses on the association between the ABO blood group system and the risk of gastric cancer or Helicobacter pylori infection. The data for the ABO blood group was collected from 1045 cases of gastric cancer, whereby the patient underwent a gastrectomy in Ruijin Hospital, Shanghai. The information on the ABO blood group from 53,026 healthy blood donors was enrolled as control. We searched the Pubmed database on the relationship between ABO blood groups and gastric cancer risk for meta-analysis. In our case-control study, the risk of gastric cancer in blood group A was significantly higher than that in non-A groups (O, B and AB) (odd ratio, OR1.34; 95% confidential interval, CI 1.25–1.44). Compared with non-O groups (A, B and AB), individuals with blood group O demonstrated a reduced risk of gastric cancer (OR = 0.80; 95% CI 0.72–0.88). The proportion of H. pylori infection in blood group A individuals was significantly higher than that in non-A blood groups (OR = 1.42; 95% CI 1.05–1.93). We further combined our data with the published data of others, and crossreferenced the risk of gastric cancer with the blood type, finding consistent evidence that gastric cancer risk in the blood A group was higher than that in the non-A groups (OR = 1.11; 95% CI 1.07–1.15), and that blood type O individuals were consistently shown gastric cancer risk reduction (OR = 0.91; 95% CI 0.89–0.94). Our study concluded that there was a slightly increased risk of gastric cancer in blood group A individuals, and people with blood type A are more prone to be infected by H. pylori than other ABO blood type individuals, whereas, a slightly decreased risk of gastric cancer was identified in blood type O individuals. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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14 pages, 305 KiB

Open AccessArticle

Improved Production of Cyclodextrins by Alkalophilic Bacilli Immobilized on Synthetic or Loofa Sponges

by Tieles Carina De Oliveira Delani, Rúbia Pazzetto, Camila Sampaio Mangolim, Vanderson Carvalho Fenelon, Cristiane Moriwaki and Graciette Matioli^*

Department of Pharmacy, State University of Maringá (UEM), Maringá-PR 87020-900, Brazil

Int. J. Mol. Sci. 2012, 13(10), 13294-13307; https://doi.org/10.3390/ijms131013294 - 17 Oct 2012

Cited by 7 | Viewed by 6335

Abstract

This study aimed to improve the production of β-cyclodextrin (β-CD) by microbial cells immobilized on synthetic or loofa sponges both with and without the use of alginate or chitosan. The most suitable matrix for the immobilization of Bacillus firmus strain 7B was synthetic [...] Read more.

This study aimed to improve the production of β-cyclodextrin (β-CD) by microbial cells immobilized on synthetic or loofa sponges both with and without the use of alginate or chitosan. The most suitable matrix for the immobilization of Bacillus firmus strain 7B was synthetic sponge and for Bacillus sphaericus strain 41 was loofa sponge. After 330 days of storage, the β-CD production by Bacillus firmus and Bacillus sphaericus remained at around 41% and 49%, respectively, of initial levels. After 24 days of immobilization on loofa sponge, Bacillus sphaericus strain 41 achieved an improved operational stability, reaching 86.6 mM β-CD after 20 days of production, compared to only 32.8 mM of β-CD produced by free Bacillus sphaericus strain 41 cells. The expected increase in β-CD production by immobilized cells of Bacillus firmus strain 7B on synthetic sponge for 4 days was not statistically different to that for cells immobilized for 24 days. The application of this process on an industrial scale using loofa sponge, an inexpensive and renewable matrix, will allow the stable production of β-CD. Full article

(This article belongs to the Section Materials Science)

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19 pages, 2055 KiB

Open AccessArticle

The Effect of Sodium Dodecyl Sulfate (SDS) and Cetyltrimethylammonium Bromide (CTAB) on the Properties of ZnO Synthesized by Hydrothermal Method

by Donya Ramimoghadam¹, Mohd Zobir Bin Hussein^2,* and Yun Hin Taufiq-Yap²

¹ Advanced Material and Nanotechnology Laboratory (AMNL), Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

² Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

Int. J. Mol. Sci. 2012, 13(10), 13275-13293; https://doi.org/10.3390/ijms131013275 - 16 Oct 2012

Cited by 220 | Viewed by 18510

Abstract

ZnO nanostructures were synthesized by hydrothermal method using different molar ratios of cetyltrimethylammonium bromide (CTAB) and Sodium dodecyl sulfate (SDS) as structure directing agents. The effect of surfactants on the morphology of the ZnO crystals was investigated by field emission scanning electron microscopy [...] Read more.

ZnO nanostructures were synthesized by hydrothermal method using different molar ratios of cetyltrimethylammonium bromide (CTAB) and Sodium dodecyl sulfate (SDS) as structure directing agents. The effect of surfactants on the morphology of the ZnO crystals was investigated by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) techniques. The results indicate that the mixture of cationic-anionic surfactants can significantly modify the shape and size of ZnO particles. Various structures such as flakes, sheets, rods, spheres, flowers and triangular-like particles sized from micro to nano were obtained. In order to examine the possible changes in other properties of ZnO, characterizations like powder X-ray diffraction (PXRD), thermogravimetric and differential thermogravimetric analysis (TGA-DTG), FTIR, surface area and porosity and UV-visible spectroscopy analysis were also studied and discussed. Full article

(This article belongs to the Section Materials Science)

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11 pages, 2865 KiB

Open AccessArticle

Over-Expression of Semaphorin4D, Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Is Related to Poor Prognosis in Ovarian Epithelial Cancer

by Ying Chen¹, Lei Zhang¹, Yi Pan², Xiubao Ren^3,* and Quan Hao^1,*

¹ Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

² Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

³ Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

Int. J. Mol. Sci. 2012, 13(10), 13264-13274; https://doi.org/10.3390/ijms131013264 - 16 Oct 2012

Cited by 45 | Viewed by 7118

Abstract

Semaphorin4D (SEMA4D) has been regarded as an important protein in tumor angiogenesis, though originally identified in neurodevelopment. SEMA4D is extensively expressed in several malignant solid tumors. Nevertheless, the function and expression of SEMA4D in epithelial ovarian cancer (EOC) is as yet not well [...] Read more.

Semaphorin4D (SEMA4D) has been regarded as an important protein in tumor angiogenesis, though originally identified in neurodevelopment. SEMA4D is extensively expressed in several malignant solid tumors. Nevertheless, the function and expression of SEMA4D in epithelial ovarian cancer (EOC) is as yet not well understood. The aim of this study was to investigate SEMA4D expression in EOC and evaluate its clinical–pathological and prognostic significance. Immunohistochemistry was used to analyze SEMA4D expression and tumor angiogenesis-related proteins (HIF-1α and VEGF) in tissues from 40 patients with normal ovarian epithelia and 124 EOC patients. SEMA4D was found to be expressed in 61.3% of the 124 EOC tissues, which was significantly higher than in the normal ovarian epithelia (p < 0.001). SEMA4D expression correlated with HIF-1α and VEGF closely (ρ = 0.349 and 0.263, p < 0.001). Positive SEMA4D staining was significantly higher in tissues from patients with low histological grade, FIGO stage III-IV, lymph node metastasis and residual disease ≥1 cm (p < 0.05). In the Cox proportional hazard mode, SEMA4D expression and histologic grade were independent indicators of overall survival (OS) and progress-free survival (PFS) for EOC patients. These findings suggest that the cooperation of SEMA4D, HIF-1α, and VEGF may indicate poor prognosis for patients with EOC, thereby demonstrating that SEMA4D and its role in angiogenesis in EOC warrants further study. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 233 KiB

Open AccessReview

The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer

by László Herszényi^1,*, István Hritz^1,2, Gábor Lakatos^1,3, Mária Zsófia Varga¹ and Zsolt Tulassay¹

¹ Second Department of Medicine, Semmelweis University, H-1088 Budapest, Szentkirályi str. 46, H-1088, Hungary

² First Department of Medicine, Fejér County Szent György Hospital, Székesfehérvár, H-8000, Hungary

³ Department of Oncology, Szent László Hospital, Budapest, H-1097, Hungary

Int. J. Mol. Sci. 2012, 13(10), 13240-13263; https://doi.org/10.3390/ijms131013240 - 16 Oct 2012

Cited by 133 | Viewed by 10222

Abstract

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are [...] Read more.

Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))

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Int. J. Mol. Sci., Volume 13, Issue 10 (October 2012) – 91 articles , Pages 12153-13763

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