[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Next Issue
Volume 13, November
Previous Issue
Volume 13, September
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Volume 13
Issue 10
ijms-logo

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

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

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
461 KiB  
Article
Transcriptome Analysis Reveals Putative Genes Involved in Iridoid Biosynthesis in Rehmannia glutinosa
by Peng Sun, Shuhui Song, Lili Zhou, Bing Zhang, Jianjun Qi and Xianen Li
Int. J. Mol. Sci. 2012, 13(10), 13748-13763; https://doi.org/10.3390/ijms131013748 - 23 Oct 2012
Cited by 44 | Viewed by 8675
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)
►▼ Show Figures


<p>Overview of iridoid biosynthesis in plants. CPR: cytochrome P450 reductase; <span class="html-small-caps">dmapp:</span> dimethylally diphosphate; DXP: 1-deoxy-<span class="html-small-caps">d</span>-xylulose 5-phosphate; DXS: 1-deoxy-<span class="html-small-caps">d</span>-xylulose-5-phosphate synthase; DXR: 1-deoxy-<span class="html-small-caps">d</span>-xylulose-5-phosphate reductoisomerase; FPP-farnesyl diphosphate; FPPS-farnesyl diphosphate synthase; GPP: geranyl diphosphate; GPPS: geranyl diphosphate synthase; GES: geraniol synthase; GGPP: geranylgeranyl diphosphate; GGPPS: geranylgeranyl diphosphate synthase; G10H: geraniol 10-hydroxylase; 10HGO: 10-hydroxygeraniol oxidoreductase; HMBPP: 1-Hydroxy-2-methyl-2-butenyl-4 diphosphate; HMGR: 3-hydroxy-3-methylglutaryl-CoA reductase; IPP: ispentenyl diphosphate; IDI: IPP isomerase; LAMT: sadenosyl-<span class="html-small-caps">l</span>-methionine: loganic acid methyl transferase; MEP: 2-<span class="html-italic">C</span>-methyl-<span class="html-small-caps">d</span>-erythritol 4-phosphate; MVA: mevalonic acid; SLS: secologanin synthase; STR: strictosidine synthase; Route I: the route leading to the biosynthesis of secologanin, Route II: the route leading to the biosynthesis of catalpol.</p> Full article ">
<p>Gene Ontology analysis of genes in the 454 sequence collection of <span class="html-italic">R. glutinosa</span>.</p> Full article ">
<p>Pathway assignment based on Kyoto Encyclopedia of Genes and Genomes (KEGG). (<b>A</b>) Classification based on metabolism categories; (<b>B</b>) Classification based on secondary metabolism categories.</p> Full article ">
<p>The expression pattern of four selected short-chain prenyltransferase genes in tissues of <span class="html-italic">R. glutinosa</span>. GPP: geranyl diphosphate synthase; FPPS: farnesyl diphosphate synthase; GGPPS: geranylgeranyl diphosphate synthase; Means ± SE; Three replicates of each qRT-PCR were performed.</p> Full article ">
165 KiB  
Review
The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation
by Ai-Di Gu, Mu-Sheng Zeng and Chao-Nan Qian
Int. J. Mol. Sci. 2012, 13(10), 13737-13747; https://doi.org/10.3390/ijms131013737 - 23 Oct 2012
Cited by 18 | Viewed by 6841
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))
412 KiB  
Article
Synthesis and Characterization of Mesoporous Silica Functionalized with Calix[4]arene Derivatives
by Sana M. Alahmadi, Sharifah Mohamad and Mohd Jamil Maah
Int. J. Mol. Sci. 2012, 13(10), 13726-13736; https://doi.org/10.3390/ijms131013726 - 23 Oct 2012
Cited by 26 | Viewed by 7846
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)
►▼ Show Figures


<p>Preparation of modified mesoporous silica with calix[<a href="#b4-ijms-13-13726" class="html-bibr">4</a>]arene derivatives.</p> Full article ">
<p>Fourier transform infrared spectroscopy (FTIR) spectra of MCM-41 (<b>A</b>) and MCM-toluene 2,4-di-iso-cyanate (TDI) (<b>B</b>).</p> Full article ">
<p>FTIR spectra of MC4 (<b>A</b>); MC4S (<b>B</b>) and MPC4 (<b>C</b>).</p> Full article ">
<p>TGA-DTA analysis of MC4; MC4S and MPC4.</p> Full article ">
<p>X-ray powder diffraction (XRD) analysis of MPC4 (<b>A</b>); MC4S (<b>B</b>) and MC4 (<b>C</b>).</p> Full article ">
<p>Nitrogen adsorption-desorption isotherms of (Δ) MC4; (<b>⋄</b>) MC4S; and (□) MPC4.</p> Full article ">
397 KiB  
Review
The Role of Neurotrophins in Multiple Sclerosis—Pathological and Clinical Implications
by Alicja Kalinowska-Lyszczarz and Jacek Losy
Int. J. Mol. Sci. 2012, 13(10), 13713-13725; https://doi.org/10.3390/ijms131013713 - 22 Oct 2012
Cited by 34 | Viewed by 7697
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)
►▼ Show Figures


<p>Neurotrophic factor family classification. NGF: nerve growth factor, BDNF: brain-derived neurotrophic factor, NT-3: neurotrophin 3, NT-4/5: neurotrophin 4/5, TGF beta: transforming growth factor beta, GDNF: glial derived neurotrophic factor, BMP: bone morphogenic proteins, NTN: neurturin, PSP: persephin, CNTF: ciliary neurotrophic factor, IL-6: interleukin 6, LIF: leukemia inhibitory factor, IL-11: interleukin 11, OSM: oncostatin M, CT-1: kardiotrophin-1, CLC: cardiothrophin<span class="html-italic">-</span>like cytokine.</p> Full article ">
<p>Interactions between neurotrophins and the immune cells. NGF: nerve growth factor, BDNF: brain-derived neurotrophic factor, NT-3: neurotrophin 3, NT-4/5: neurotrophin 4/5, trk: tropomyosin related kinase receptor, M: macrophage, T: T lymphocyte, B: B lymphocyte. Dotted lines indicate secretion. Straight lines indicate affinity towards receptors.</p> Full article ">
468 KiB  
Article
Detection of Ricin Intoxication in Mice Using Serum Peptide Profiling by MALDI-TOF/MS
by Siyan Zhao, Wen-Sen Liu, Meng Wang, Jiping Li, Yucheng Sun, Nan Li, Feng Hou, Jia-Yu Wan, Zhongyi Li, Jun Qian and Linna Liu
Int. J. Mol. Sci. 2012, 13(10), 13704-13712; https://doi.org/10.3390/ijms131013704 - 22 Oct 2012
Cited by 8 | Viewed by 6326
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)
►▼ Show Figures


<p>The distribution chart of ricin infection sample III and control samples (red: control; green: ricin infection). The coordinates represent the related protein intensities, and the large ellipses represent the standard deviations of the peak area class average. The small ellipses show that the protein peaks selected could distinguish ricin infection from controls. (<b>A</b>) Serum pretreated with MB-HIC-8 (34,3885 Da on the <span class="html-italic">x</span> axis, and 1,1017 Da on the <span class="html-italic">y</span> axis); (<b>B</b>), serum treated with MB-HIC-18; (<b>C</b>), serum treated with IMAC-Cu; (<b>D</b>), serum treated with MB-WCX. There was a minor overlapping area in serum samples treated with MB-WCX. Therefore, we used it to enrich serum peptides in this study.</p> Full article ">
<p>Serum peptide mass spectrum of subgroup C and III treated by MB-WCX. Every group has five replicates. Subgroup C, the ① to ⑤ samples, Subgroup III, the ⑧ to ⑩ samples.</p> Full article ">
234 KiB  
Article
Lack of Association of Estrogen Receptor Alpha Gene Polymorphisms with Cardiorespiratory and Metabolic Variables in Young Women
by Ana Cristina Rebelo, Rozangela Verlengia, Vandeni Kunz, Nayara Tamburus, Alvaro Cerda, Rosario Hirata, Mario Hirata and Ester Silva
Int. J. Mol. Sci. 2012, 13(10), 13691-13703; https://doi.org/10.3390/ijms131013691 - 22 Oct 2012
Cited by 5 | Viewed by 6457
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
216 KiB  
Review
Involvement of Oxidative Stress in Suppression of Insulin Biosynthesis under Diabetic Conditions
by Hideaki Kaneto and Taka-aki Matsuoka
Int. J. Mol. Sci. 2012, 13(10), 13680-13690; https://doi.org/10.3390/ijms131013680 - 22 Oct 2012
Cited by 31 | Viewed by 10291
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)
►▼ Show Figures


<p>Production of reactive oxygen species (ROS) under diabetic conditions. ROS are produced by various pathways under diabetic conditions and are involved in the deterioration of pancreatic β-cell function. Hyperglycemia induces ROS through activation of the glycation reaction and electron transport chain in mitochondria.</p> Full article ">
<p>Involvement of oxidative stress in pancreatic β-cell glucose toxicity in Type 2 diabetes. Hyperglycemia and subsequent induction of oxidative stress suppress nuclear expression of pancreatic transcription factors PDX-1 and MafA, which leads to suppression of insulin biosynthesis and secretion. Therefore, it is likely that induction of oxidative stress and suppression of PDX-1 and MafA are involved in β-cell glucose toxicity found in Type 2 diabetes.</p> Full article ">
<p>Possible molecular mechanism for suppression of insulin biosynthesis in Type 2 diabetes. Oxidative stress and subsequent activation of the JNK pathway translocate Foxo1 from cytoplasm to nuclei, leading to translocation of PDX-1 from nuclei to cytoplasm in pancreatic β-cells. In addition, oxidative stress and subsequent induction of c-Jun expression suppress nuclear expression of MafA in β-cells. Therefore, it is likely that activation of the JNK pathway and induction of c-Jun expression are involved in suppression of insulin biosynthesis found in Type 2 diabetes.</p> Full article ">
676 KiB  
Article
Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis
by Jun Yan, Jia Liu, Clement Yihao Lin, ANZGene, Peter A. Csurhes, Michael P. Pender, Pamela A. McCombe and Judith M. Greer
Int. J. Mol. Sci. 2012, 13(10), 13667-13679; https://doi.org/10.3390/ijms131013667 - 22 Oct 2012
Cited by 16 | Viewed by 7797
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)
►▼ Show Figures


<p>Meta analysis of the odds ratios in the five studies that have investigated −174 <span class="html-italic">IL6</span> promoter region polymorphisms in MS. <b>*</b> This study inferred the −174 genotypes from the −597 genotype.</p> Full article ">
<p>(<b>A</b>) Distribution of MS Severity Scores (MSSS) according to patient −572 genotype. Each bar on the graphs represents the median and interquartile range. The whiskers represent the 5th and 95th percentiles, and outliers are shown as black circles above and below the plots; (<b>B</b>) Distribution of MSSS in patients subdivided on basis of −174 genotype.</p> Full article ">
<p>MS Severity Scores in females and males, by −572 <span class="html-italic">IL6</span> genotype.</p> Full article ">
<p>Cumulative fraction of patients carrying different <span class="html-italic">IL6</span> promoter genotypes <span class="html-italic">vs.</span> age of onset of MS. (<b>A</b>) Patients grouped according to −572 <span class="html-italic">IL6</span> genotype; (<b>B</b>) Patients grouped according to −174 <span class="html-italic">IL6</span> genotype.</p> Full article ">
<p>MS Severity Scores in patients who initially have a RR-MS course, compared to a PP-MS course, by −572 <span class="html-italic">IL6</span> genotype.</p> Full article ">
<p>MSSS of patients with different <span class="html-italic">IL6</span> promoter region haplotypes. There were no significant differences between patients with different haplotypes.</p> Full article ">
Full article ">
1085 KiB  
Review
Tanshinones: Sources, Pharmacokinetics and Anti-Cancer Activities
by Yong Zhang, Peixin Jiang, Min Ye, Sung-Hoon Kim, Cheng Jiang and Junxuan Lü
Int. J. Mol. Sci. 2012, 13(10), 13621-13666; https://doi.org/10.3390/ijms131013621 - 22 Oct 2012
Cited by 210 | Viewed by 14952
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))
►▼ Show Figures


<p>Chemical structures of major tanshinones and tanshinlactones.</p> Full article ">
<p>Proposed biosynthetic pathways of tanshinones in <span class="html-italic">Salvia miltiorrhiza</span> [<a href="#b48-ijms-13-13621" class="html-bibr">48</a>]. Modified based on Wang &amp; Wu 2010. By permission of Springer.</p> Full article ">
<p>Structures of tanshinone derivatives with increased water solubility. ATA and its likely metabolism [<a href="#b116-ijms-13-13621" class="html-bibr">116</a>]. By permission of Elsevier Limited.</p> Full article ">
<p>Schematic representations of reported cellular and molecular effects of tanshinones in cell culture models related to cancer. Arrows indicate induction effects. Block T indicates suppression effects. TI: tanshinone I; TIIA: tanshinone IIA; CT: cryptotanshinone; DH-TI: dihydrotanshinone I. ↑: up-regulation or activation; ↓: down-regulation or inactivation.</p> Full article ">
1120 KiB  
Article
Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL) Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2
by Yu Dong, Qingguo Zhang, Yunxia Li, Jia Jiang and Shiyi Chen
Int. J. Mol. Sci. 2012, 13(10), 13605-13620; https://doi.org/10.3390/ijms131013605 - 22 Oct 2012
Cited by 58 | Viewed by 7810
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)
►▼ Show Figures


<p>Efficiency of infection of bMSCs with lentivirus. During the exponential growth phase, bMSCs were infected with Lv-BMP2 at an MOI = 20. After 72 h, GFP expression was examined by fluorescence microscopy at the indicated magnifications.</p> Full article ">
<p>Determination of cell viability. During the exponential growth phase, bMSCs were infected with either the Lv-Control or Lv-BMP-2 at an MOI = 20 and seeded into 96-well plates at 1 × 10<sup>5</sup>/well 72 h later, followed by incubation under normal culture conditions. The MTT assay was performed as described in the Materials and Methods. The absorbance (A) at 490 nm was determined to estimate changes in cell viability. * <span class="html-italic">p</span> &lt; 0.05 <span class="html-italic">vs.</span> bMSCs and ** <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs</span>. bMSCs.</p> Full article ">
<p>Determination of mRNA content. During the exponential growth phase, bMSCs were infected with either the Lv-Control or Lv-BMP-2 at an MOI = 20 and subjected to RNA extraction 72 h later. The RNA was transcribed into cDNA using reverse transcriptase and analyzed by real-time PCR. The results of relative quantification were analyzed by the ΔCt method. B-Actin served as the internal control. ** <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs</span>. bMSCs.</p> Full article ">
<p>Protein contents determined by Western blotting. During the exponential growth phase, bMSCs were infected with either the Lv-Control or Lv-BMP-2 at an MOI = 20 and subjected to Western blotting 72 h later. Cell lysates were prepared, electrophoresed and immunoblotted for BMP-2 and β-actin (<b>a</b>) The optical densities of bands were analyzed by TotalLab and the relative quantification of BMP-2 was performed (<b>b</b>). ** <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs</span>. bMSCs.</p> Full article ">
<p>Mechanical examination of graft-bone healing in a rabbit model at various time points after surgery. (<b>a</b>) Maximal load; (<b>b</b>) Displacement at maximum load; (<b>c</b>) Stiffness. * LSD <span class="html-italic">t</span>-test, <span class="html-italic">p</span> &lt; 0.01; ** LSD <span class="html-italic">t</span>-test, <span class="html-italic">p</span> &lt; 0.05.</p> Full article ">
<p>Haematoxylin and eosin (H &amp; E) staining of tendon–bone at four and eight weeks after surgery. This figure shows the histology of the tendon (<b>T</b>)-bone (<b>B</b>) interface among the control group, bMSCs and bMSCs infected with BMP-2 either four (<b>a</b>, <b>c</b> and <b>e</b>) or eight (<b>b</b>, <b>d</b> and <b>f</b>) weeks after surgery. Fibrous tissue was observed eight weeks after surgery in the control group (<b>b</b>). However, chondrocytes and a greater number of perpendicular fibers were observed at the interface between tendon and bone (magnification 100×) in the bMSCs (<b>c</b> and <b>d</b>) and BMP-2-transfected bMSCs (<b>e</b> and <b>f</b>) groups.</p> Full article ">
476 KiB  
Article
A Bead-Based Multiplexed Immunoassay to Evaluate Breast Cancer Biomarkers for Early Detection in Pre-Diagnostic Serum
by Annemieke W. J. Opstal-van Winden, Wendy Rodenburg, Jeroen L. A. Pennings, Conny T. M. Van Oostrom, Jos H. Beijnen, Petra H.M. Peeters, Carla H. Van Gils and Annemieke De Vries
Int. J. Mol. Sci. 2012, 13(10), 13587-13604; https://doi.org/10.3390/ijms131013587 - 22 Oct 2012
Cited by 45 | Viewed by 8584
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)
►▼ Show Figures


<p>Principal component analysis (PCA) 3D view for protein profiles. Legend: (<b>A</b>) for 68 cases (black dots) and 68 controls (gray dots) and (<b>B</b>) for the subset consisting of 24 cases and 24 controls. The PCA in both <b>A</b> and <b>B</b> is based on all ten proteins. The first three components are shown.</p> Full article ">
696 KiB  
Article
The Properties of Sintered Calcium Phosphate with [Ca]/[P] = 1.50
by I-Ming Hung, Wei-Jen Shih, Min-Hsiung Hon and Moo-Chin Wang
Int. J. Mol. Sci. 2012, 13(10), 13569-13586; https://doi.org/10.3390/ijms131013569 - 22 Oct 2012
Cited by 64 | Viewed by 8786
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)
►▼ Show Figures


<p>The size distribution of the as-dried calcium phosphate powders with [Ca]/[P] = 1.50.</p> Full article ">
<p>The X-ray diffraction (XRD) pattern of pellet sample of calcium phosphate powders with [Ca]/[P] = 1.50. (<b>a</b>) As-dried state and (<b>b</b>) Sintered at 600 °C for 4 h (○: HA, ■: NaCaPO<sub>4</sub>, ⋆: β-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub>).</p> Full article ">
<p>XRD pattern of the pellet sample of as-dried calcium phosphate powders with [Ca]/[P] = 1.50 sintered at 700 °C for 4 h (○: HA, ■: NaCaPO<sub>4</sub>, ⋆: β-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub>).</p> Full article ">
<p>(<b>a</b>) XRD patterns of pellet samples of as-dried calcium phosphate powders with [Ca]/[P] = 1.50 sintered between 800 °C and 1200 °C for 4 h and (<b>b</b>) zoom on the 30–35° (2<span class="html-italic">θ</span>) area (○: HA, ■: NaCaPO<sub>4</sub>, ⋆: β-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub>).</p> Full article ">
<p>XRD patterns of pellet samples of as-dried calcium phosphate powders with [Ca]/[P] = 1.50 sintered at (<b>a</b>) 1300 °C and (<b>b</b>) 1400 °C for 4 h (α: α-TCP, ■: NaCaPO<sub>4</sub>, ⋆: β-Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub>, ○: HA, ×: Ca<sub>2</sub>P<sub>2</sub>O<sub>7</sub>).</p> Full article ">
<p>Fourier-transform infrared (FT-IR) spectra of pellet samples of as-dried calcium phosphate powders sintered at various temperatures for 4 h.</p> Full article ">
<p>The density of pellet samples of as-dried HA powders with [Ca]/[P] = 1.50 sintered at 800 °C for various durations.</p> Full article ">
<p>The density of pellet samples with [Ca]/[P] = 1.50 sintered at various temperatures for 4 h.</p> Full article ">
<p>The surface Vickers Hardness (HV) of pellet samples with [Ca]/[P] = 1.50 sintered at various temperatures for 4 h.</p> Full article ">
551 KiB  
Review
E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair
by Renier Vélez-Cruz and David G. Johnson
Int. J. Mol. Sci. 2012, 13(10), 13554-13568; https://doi.org/10.3390/ijms131013554 - 19 Oct 2012
Cited by 14 | Viewed by 8000
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)
►▼ Show Figures


<p>E2F1 accumulates at sites of UV-induced DNA damage. Normal human fibroblasts were untreated (−UV) or locally irradiated with 100 J/m<sup>2</sup> of UV-C (+UV) through polycarbonate filters with pores of 3 μm as indicated. Cells were fixed 30 min post-irradiation, and stained for CPD photoproducts (red) and E2F1 (green) by indirect immunofluorescence.</p> Full article ">
<p>Histone acetylation and chromatin accessibility are important for both global genome NER (GG-NER) and transcription-coupled NER (TC-NER). (<b>A</b>) Regions of the genome that are not transcribed are generally in a hypoacetylated state; (<b>B</b>) During GG-NER transcription factors p53 and E2F1 are recruited to the damaged sites and facilitate the recruitment of HATs p300 and GCN5, which in turn increase histone H3 and H4 acetylation; (<b>C</b>) Hyperacetylation of chromatin at these sites increases access to NER factors (XPC, TFIIH, and XPA) to initiate repair; (<b>D</b>) During TC-NER an RNA polymerase II stalled in front of a transcription-blocking lesions recruits CSB, which in turn recruits p300 to the site of a DNA lesion; (<b>E</b>) p300 maintains a hyperacetylated chromatin state, thus providing accessibility to the other NER factors (TFIIH, and XPA).</p> Full article ">
320 KiB  
Article
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
Int. J. Mol. Sci. 2012, 13(10), 13542-13553; https://doi.org/10.3390/ijms131013542 - 19 Oct 2012
Cited by 20 | Viewed by 8098
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)
►▼ Show Figures


<p>(<span class="html-italic">R</span>)-(−)-3-Quinuclidinol production system with 3-quinuclidinone reductase (QNR) and <span class="html-italic">Leifsonia</span> alcohol dehydrogenase (LSADH).</p> Full article ">
<p>pET28-bacC-LSADH plasmid.</p> Full article ">
<p>Effect of organic solvents on enzyme stability. Residual activity is shown after incubation of designated concentration of 2-propanol or acetone and time for the purified enzymes. (<b>a</b>) 2-propanol on QNR; (<b>b</b>) acetone on QNR; (<b>c</b>) 2-propanol on bacC; (<b>d</b>) acetone on bacC. Data are the mean value of three independent measurements with standard deviation as shown.</p> Full article ">
<p>Effect of organic solvents on enzyme activity. Activity of QNR and bacC was measured in the presence of 0, 3, 5, 10 and 15% (<span class="html-italic">v</span>/<span class="html-italic">v</span>) 2-propanol/acetone in the assay mixture. Enzyme activity in the presence of 2-propanol is shown as open squares for QNR and open triangles for bacC. Activity in the presence of acetone is shown as closed squares for QNR and closed triangles for bacC. Data are the mean value of three independent measurements with standard deviation as shown.</p> Full article ">
<p>Time course of the production of (<span class="html-italic">R</span>)-(−)-3-quinuclidinol by immobilized <span class="html-italic">E. coli</span> biocatalysts. The concentration of (<span class="html-italic">R</span>)-(−)-3-quinuclidinol is represented by a solid line and that of 3-quinuclidinone by a dashed line. Data are the mean value of three independent measurements with standard deviation as shown.</p> Full article ">
4127 KiB  
Article
A Simple Bioconjugate Attachment Protocol for Use in Single Molecule Force Spectroscopy Experiments Based on Mixed Self-Assembled Monolayers
by Simon J. Attwood, Anna M. C. Simpson, Rachael Stone, Samir W. Hamaia, Debdulal Roy, Richard W. Farndale, Myriam Ouberai and Mark E.Welland
Int. J. Mol. Sci. 2012, 13(10), 13521-13541; https://doi.org/10.3390/ijms131013521 - 19 Oct 2012
Cited by 8 | Viewed by 7649
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)
►▼ Show Figures


<p>Protocol for protein attachment onto gold surfaces. <b>(A)</b> A mixed monolayer is formed from a solution containing different proportions of amine- (APA) and hydroxyl- (APH) terminating thiols; <b>(B)</b> A heterobifunctional crosslinker is then bound to the mixed SAM at available amine groups via its NHS terminus; <b>(C)</b> and <b>(D)</b> biotin and avidin respectively bound to the monolayer via sulfhydryl groups.</p> Full article ">
<p>Detection of coupling steps via QCM. <b>(A)</b> Formation of APA alkanethiol monolayer on gold coated QCM chip; <b>(B)</b> Bonding of crosslinker to monolayer followed by coupling of avidin via Traut’s reagent.</p> Full article ">
<p>Topography (<b>A,C,E</b>) and phase (<b>B,D,F</b>) images recorded in air using AC mode. (<b>A,B</b>) Full protocol except avidin at 3 <span class="html-italic">μ</span>M; (<b>C,D</b>) Full protocol (avidin at 1 <span class="html-italic">μ</span>M); (<b>E,F</b>) Full protocol except APA replaced with APH; (<b>G</b>) Enlarged view of red box in <b>C</b>; (<b>H</b>) Height profile through red line in <b>G</b>.</p> Full article ">
<p>Detection via ELISA assay of the presence of either avidin or biotin bound to TSG via the monolayer (solid), avidin physisorbed to glass slides (stripes) and avidin bound to the wells of a 96-well plate (open). Avidin bound to all surfaces was readily detectable, as indicated by the significant increase in signal compared to the controls. Biotin coupled TSG was also detected. Errors are standard deviations based on 2 (TSG), 5 (glass slides) and 6 (96-well plate) replicates. Additional positive results were recorded for TSG on different days (data not shown).</p> Full article ">
<p><b>(A)</b> Example biotin-avidin data set. Cantilever deflection (left vertical axis) and tip-surface separation (right vertical axis) are plotted versus the piezo displacement. Approach and retract for the deflection data are represented by the blue and red data points respectively. Approach and retract for the tip-surface separation data are represented by the black and green data points respectively. The areas enclosed by boxes I and II are enlarged in the respective sub-plots. The unbinding piezo length (<span class="html-italic">L</span><span class="html-italic"><sub>up</sub></span> = 36.5 ± 0.4 nm) and deflection unbinding length (<span class="html-italic">L</span><span class="html-italic"><sub>ud</sub></span> = 2.6 ± 0.2 nm) are also indicated. Box enclosed numbers are references for the diagrams in <b>(B)</b>. Blue and red boxed numbers again refer to approach and retract respectively. <b>(B)</b> Time series pictorial illustration of the evolution of the dynamic interactions between the tip, substrate and bound molecules.</p> Full article ">
<p>Measurement of interaction force between single biotin-avidin pairs with tips and substrates modified using the new protocol. <b>(A)</b> Example force-displacement curve showing specific biotin-avidin unbinding. The calculated most probable rupture force was 89±13 pN and the loading rate was 4091 ± 69 pN s<sup>−1</sup>. <b>(B)</b> Example force-displacement curve after blocking with free avidin. <b>(C)</b> Empirical probability density functions representing force distributions acquired without inhibition (solid line) and in the presence of free avidin (dotted line). Unbinding probabilities were 27% and 4% for uninhibited and blocked experiments respectively.</p> Full article ">
<p>Peak analysis of probability density function corresponding to biotin-avidin data. <b>(A)</b> Raw data represented by solid line, model based on sum of four Gaussian distributions shown with a dotted line. The calculated peak values of 89 pN, 142 pN, 181 pN and 266 pN are indicated by arrows. <b>(B)</b> The four individual Gaussian components are shown (dashed lines) for clarity.</p> Full article ">
3576 KiB  
Article
A Systems Biology Approach to Understanding the Mechanisms of Action of Chinese Herbs for Treatment of Cardiovascular Disease
by Bohui Li, Xue Xu, Xia Wang, Hua Yu, Xiuxiu Li, Weiyang Tao, Yonghua Wang and Ling Yang
Int. J. Mol. Sci. 2012, 13(10), 13501-13520; https://doi.org/10.3390/ijms131013501 - 19 Oct 2012
Cited by 85 | Viewed by 12526
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
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">
<p>Network of 64 ligands (M) predicted to have 261 protein targets (P). The red nodes represent the ligands, while the black ones represent the proteins.</p> Full article ">
<p>Network of 64 ligands (M, triangle, Layer I) predicted to have 54 protein targets (P, circle) after molecular docking validation. The black circles (Layer II) are the common targets of the three Chinese herbs <span class="html-italic">Ligusticum chuanxiong, Dalbergia odorifera</span> and <span class="html-italic">Corydalis yanhusuo</span>; the purple circles (Layer III) are the common targets of <span class="html-italic">Ligusticum chuanxiong</span> and <span class="html-italic">Dalbergia odorifera</span>; the red circles (Layer III) are the common targets of <span class="html-italic">Ligusticum chuanxiong</span> and <span class="html-italic">Corydalis yanhusuo</span>; and the blue circles (Layer III) are the common targets of <span class="html-italic">Dalbergia odorifera</span> and <span class="html-italic">Corydalis yanhusuo</span>. P9 (Layer IV) represent the protein target that is only identified for <span class="html-italic">Corydalis yanhusuo</span> (brown triangle); P34, P134, P184 and P186 (Layer IV) are only recognized by <span class="html-italic">Ligusticum chuanxiong</span> (pink triangle); and P75, P216, P252, P260, P261 (Layer IV) are only involved in <span class="html-italic">Dalbergia odorifera</span> (green triangle).</p> Full article ">
<p>Network of 54 targets (P, black) connected to cardiovascular disease (red) and 12 other diseases (blank).</p> Full article ">
<p>Network of nine signal pathways (green, layer 3) connected to 23 targets (P, black, layer 2). The ligands (M, red, layer 1) are linked to the targets.</p> Full article ">
747 KiB  
Article
Injury-Induced Accumulation of Glial Cell Line-Derived Neurotrophic Factor in the Rostral Part of the Injured Rat Spinal Cord
by Takuya Hara, Hidefumi Fukumitsu, Hitomi Soumiya, Yoshiko Furukawa and Shoei Furukawa
Int. J. Mol. Sci. 2012, 13(10), 13484-13500; https://doi.org/10.3390/ijms131013484 - 19 Oct 2012
Cited by 7 | Viewed by 6496
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)
►▼ Show Figures


<p>Glial cell line-derived neurotrophic factor (GDNF) protein distributes differentially in concentration by position in the spinal cord of adult rats. (<b>A</b>) The spinal cords were dissected from normal adult rats and cut into nine segments of 5 mm length. Arrows indicate the rostral and caudal sides. (<b>B</b>) Each segment was pulse-sonicated, centrifuged, and the supernatant fluids were subjected to enzyme immunoassay (EIA). The values are represented as mean ± SE of five animals.</p> Full article ">
<p>Spinal cord injury (SCI) increases GDNF protein in the rostral part of the spinal cord. (<b>A</b>) The wavy line indicates the hemi-transection site at T10. Arrows indicate the rostral or caudal side. The spinal cords were dissected at the indicated time and divided in the middle into the injured (<b>left</b>) or non-injured (<b>right</b>) side. Both were cut into nine segments of 5 mm length. (<b>B</b>) Each segment was pulse-sonicated, centrifuged, and the supernatant fluids were subjected to EIA. Values are represented as mean ± SE of 3–8 animals. Closed arrows on the left side indicate the transected position, and open arrows on the right side indicate the position corresponding to the contralateral transection site. Significance: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 <span class="html-italic">vs</span>. the value of corresponding segment of normal animals (Student’s <span class="html-italic">t</span>-test).</p> Full article ">
<p>Two-point-transection model confirms a lack of GDNF transport from the caudal to rostral side. (<b>A</b>) Wavy lines indicate a complete transection site at T9 and a hemi-transection site at T10. Arrows indicate the rostral or caudal side. The spinal cords were similarly processed as described in the legend of <a href="#f2-ijms-13-13484" class="html-fig">Figure 2A</a>. (<b>B</b>) Each segment was treated similarly as described in the legend of <a href="#f2-ijms-13-13484" class="html-fig">Figure 2B</a>. Values are represented as mean ± SE of five animals. Arrows indicate the position of transection. Significance: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 <span class="html-italic">vs</span>. the value of corresponding segment of normal animals (Student’s <span class="html-italic">t</span>-test).</p> Full article ">
<p>SCI induces GDNF mRNA expression in the rostral and caudal stumps adjacent to the injury sites. (<b>A</b>) Same as described in the legend of <a href="#f2-ijms-13-13484" class="html-fig">Figure 2A</a>. (<b>B</b> and <b>C</b>) Total RNA was isolated from each segment using TRIZOL Reagent (Invitrogen) according to the manufacturer’s instructions. All RNA samples were treated with DNase I to remove contaminating genomic DNA. RT-PCR was performed to assess the GDNF mRNA level using G3PDH mRNA as the internal control. A closed arrow in (<b>B</b>) indicates transection site of the spinal cord, and an open arrow in (<b>C</b>) demonstrates the corresponding position to the contralateral transection site.</p> Full article ">
<p>SCI-induced GFRα1 mRNA expression in the rostral and caudal stumps. (<b>A</b>) As described in the legend of <a href="#f2-ijms-13-13484" class="html-fig">Figure 2A</a>. (<b>B</b> and <b>C</b>) RT-PCR was performed to assess the GFRα1 mRNA level as described in the <a href="#f4-ijms-13-13484" class="html-fig">Figure 4</a> legend using G3PDH as the internal control.</p> Full article ">
<p>GDNF-ir in intact and injured spinal cord. GDNF-ir in coronal sections of the intact (<b>A</b>, <b>B</b>, <b>C</b>, site around T9-10) or injured (<b>D</b>, rostral part to the injury site at T9-10, 12 h post injury (POI)) spinal cord was shown in low- (<b>A</b>, <b>D</b>) and high-power photographs (<b>B</b>, <b>C</b>). (<b>B</b>) and (<b>C</b>) are enlargements of boxes “b” and “c” in (<b>A</b>), respectively. Scale bars: single line, 500 μm; double line, 100 μm.</p> Full article ">
<p>GDNF-ir-positive cells near the injury site are bearing ED-1 antigen. GDNF-ir (red color) (<b>A</b>, <b>B</b>, <b>D</b>) and ED-1 antigen (green color) (<b>C</b>, <b>E</b>) in sagittal sections of the injured spinal cord were shown in low- (<b>A</b>), middle- (<b>B</b>, <b>C</b>) and high-power photographs (<b>D</b>, <b>E</b>). It was shown that GDNF-ir-positive cells present in the rim of the injury site expressing ED-1 antigen, a specific marker for microglia/macrophages. The box in (<b>A</b>) was enlarged into (<b>B</b>) and (<b>C</b>). The box “d” in (<b>B</b>) and the box “e” in (<b>C</b>) were enlarged into (<b>D</b>) and (<b>E</b>), respectively. Scale bars: single line, 500 μm; double line, 100 μm; line with arrowheads, 20 μm.</p> Full article ">
1041 KiB  
Article
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 and François Feron
Int. J. Mol. Sci. 2012, 13(10), 13461-13483; https://doi.org/10.3390/ijms131013461 - 19 Oct 2012
Cited by 6 | Viewed by 9014
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)
►▼ Show Figures


<p>Dose escalation of vitamin D3 (mcg/day) and calcium (cg/day) supplementation, serum levels of 25(OH)D in nmol/L (endpoint 25(OH)D level &gt; 85 nmol/L), PTH in % upper reference limit (URL) (endpoint PTH level &lt; 30 %URL) and 1,25(OH)2D in pmol/L (NR 1,25(OH)2D 50–180 pmol/L). (<b>a</b>) Vitamin D3 supplementation (mcg/day), serum levels of 25(OH)D in nmol/L, serum levels of PTH in %URL and serum levels of 1,25(OH)2D in pmol/L; (<b>b</b>) Calcium supplementation (cg/day), serum levels of 25(OH)D in nmol/L, serum levels of PTH in %URL and serum levels of 1,25(OH)2D in pmol/L.</p> Full article ">
<p>Dose escalation of vitamin D3 (mcg/day) and calcium (cg/day) supplementation, serum levels of 25(OH)D in nmol/L (endpoint 25(OH)D level &gt; 85 nmol/L), PTH in % upper reference limit (URL) (endpoint PTH level &lt; 30 %URL) and 1,25(OH)2D in pmol/L (NR 1,25(OH)2D 50–180 pmol/L). (<b>a</b>) Vitamin D3 supplementation (mcg/day), serum levels of 25(OH)D in nmol/L, serum levels of PTH in %URL and serum levels of 1,25(OH)2D in pmol/L; (<b>b</b>) Calcium supplementation (cg/day), serum levels of 25(OH)D in nmol/L, serum levels of PTH in %URL and serum levels of 1,25(OH)2D in pmol/L.</p> Full article ">
<p>Ambulation, walking distance expressed in km/day and vitamin D3 supplementation (mcg/day).</p> Full article ">
0 pages, 542 KiB  
Review
RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies
by Amedeo Amedei, Domenico Prisco and Mario Milco D’Elios
Int. J. Mol. Sci. 2012, 13(10), 13438-13460; https://doi.org/10.3390/ijms131013438 - 19 Oct 2012
Cited by 69 | Viewed by 11549 | 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)
►▼ Show Figures


<p>The Remnant Epitopes Generate Autoimmunity (REGA) model. Multiple sclerosis is a multifactorial autoimmune disease of unknown etiology. Different factors (host genetics, environmental determinants, and especially the immune system) can influence the disease progression.</p> Full article ">
<p>T helper cell differentiation. When naïve CD4+ T cells, classified by absence of CD25 and high levels of CD62L, encounter specific antigens, they can differentiate into different effector subsets. It is likely that several “master” transcription factors, individually required for T-cell differentiation towards one of the end effector stages, are initially expressed upon engagement of the TCR with costimulatory receptors. Each transcription factor drives a specific set of genes required for lineage commitment and the expression of signature cytokines and negatively affects alternative pathways. However, the microenvironment is the driving force that determines the outcome of the differentiation course. Th1 cells are established in the presence of IFN-γ and IL-12 and signaling via STAT1 and STAT4, resulting in the expression of the master transcription factor T bet. Th2 cells depend on IL-4 and STAT6 for the increased expression of GATA3, whereas the simultaneous presence of TGF-β results in the development of Th9 cells, utilizing an undefined master transcription factor. The presence of TGF-β, with IL-2 signaling via STAT5, is known to generate, at least <span class="html-italic">in vitro</span>, inducible Treg, which utilize Foxp3. Also, it is TGF-β in combination with IL-6 signaling via STAT3 that drives the expression of RORγt, resulting in the differentiation of Th17 cells.</p> Full article ">
340 KiB  
Review
The Role of MicroRNAs in Breast Cancer Migration, Invasion and Metastasis
by Joy Tang, Aamir Ahmad and Fazlul H. Sarkar
Int. J. Mol. Sci. 2012, 13(10), 13414-13437; https://doi.org/10.3390/ijms131013414 - 18 Oct 2012
Cited by 167 | Viewed by 13237
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))
►▼ Show Figures


<p>Venn diagram showing an overlapping role of several miRNAs in breast cancer migration, invasion and metastasis.</p> Full article ">
2252 KiB  
Article
Proteomic Analysis of Albumins and Globulins from Wheat Variety Chinese Spring and Its Fine Deletion Line 3BS-8
by Chao-Ying Ma, Li-Yan Gao, Ning Li, Xiao-Hui Li, Wu-Jun Ma, Rudi Appels and Yue-Ming Yan
Int. J. Mol. Sci. 2012, 13(10), 13398-13413; https://doi.org/10.3390/ijms131013398 - 18 Oct 2012
Cited by 6 | Viewed by 7492
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)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">
<p>Diagrams of 3B chromosome of Chinese Spring (CS) and its fine deletion lines. The dashed boxes indicated the deleted chromosome segments gwm493 and gwm566. S–short arm; L–long arm; C–centromere.</p> Full article ">
<p>Amplifications of Chinese Spring and fine deletion lines. A and B showed the amplification products of gwm493 and gwm566, respectively. (1: DNA size marker; 2 &amp; 3: Chinese Spring; 4 &amp; 5: 3BS-8; 6 &amp; 7: 3BS-9).</p> Full article ">
<p>Spikes of euploid Chinese Spring and deletion line 3BS-8 (awns by arrow).</p> Full article ">
<p>2-DE patterns of leaf albumins and globulins from Chinese Spring (<b>A</b>) and 3BS-8 (<b>B</b>).</p> Full article ">
<p>2-DE patterns of albumins and globins from mature seeds of CS (<b>A</b>) and 3BS-8 (<b>B</b>).</p> Full article ">
<p>Functional distribution of 21 differentially expressed seed proteins between CS and 3BS-8.</p> Full article ">
205 KiB  
Review
Genetic Variability in DNA Repair Proteins in Age-Related Macular Degeneration
by Janusz Blasiak, Ewelina Synowiec, Antero Salminen and Kai Kaarniranta
Int. J. Mol. Sci. 2012, 13(10), 13378-13397; https://doi.org/10.3390/ijms131013378 - 18 Oct 2012
Cited by 26 | Viewed by 6664
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)
938 KiB  
Article
NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer
by Vladimir Kashuba, Alexey A. Dmitriev, George S. Krasnov, Tatiana Pavlova, Ilya Ignatjev, Vasily V. Gordiyuk, Anna V. Gerashchenko, Eleonora A. Braga, Surya P. Yenamandra, Michael Lerman, Vera N. Senchenko and Eugene Zabarovsky
Int. J. Mol. Sci. 2012, 13(10), 13352-13377; https://doi.org/10.3390/ijms131013352 - 18 Oct 2012
Cited by 26 | Viewed by 8477
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)
►▼ Show Figures


<p>Principal scheme of <span class="html-italic">Not</span>I microarray analysis protocol. (<b>A</b>) Isolation of genomic DNA; (<b>B</b>) digestion with methyl-specific rare-cutter enzyme <span class="html-italic">Not</span>I; (<b>C</b>) ligation of fragments with <span class="html-italic">Not</span>I-linker containing biotin; (<b>D</b>) digestion with 4-base pair recognizing restriction enzyme Sau3AI; (<b>E</b>) conjugation to microbeads containing streptavidin; washing; (<b>F</b>) amplification of DNA sequences that has been attached to microbeads. The standard procedures are performed: microarray hybridization, cloning, and sequencing analysis.</p> Full article ">
<p>Hybridization pattern of DNA from Epithelial ovarian cancer (EOC) and benign ovarian adenomas (BOA) samples on <span class="html-italic">Not</span>I-microarrays. (<b>A</b>) Vertically, 180 <span class="html-italic">Not</span>I sites arranged according to their localization on chromosome 3 (from 3p26.2 to 3p11.1 and from 3q11.2 to 3q29). Horizontally, 25 ovarian samples (18 EOC and 7 BOA); (<b>B</b>) Vertically, 35 <span class="html-italic">Not</span>I sites arranged by methylation/deletion frequency (from 33% to 17%).</p> Full article ">
<p>Bisulfite sequencing of <span class="html-italic">ITGA9</span> in EOC samples. CG-pairs containing methylated cytosine are shown in bold and yellow (<b>A</b>). Primers for bisulfite sequencing (A) are shown in italics below example of sequencing diagrams (<b>B</b>) demonstrating methylated sequence of <span class="html-italic">ITGA9</span> is shown. In the two tables (<b>C</b>) methylated (+) and unmethylated (−) CG pairs are shown in eight sequenced clones for T1 and T3 samples.</p> Full article ">
1932 KiB  
Article
Ischemic Postconditioning Alleviates Neuronal Injury Caused by Relief of Carotid Stenosis in a Rat Model of Cerebral Hypoperfusion
by Chunsheng Feng, Tianfei Luo, Li Qi, Boyu Wang, Yinan Luo and Pengfei Ge
Int. J. Mol. Sci. 2012, 13(10), 13338-13351; https://doi.org/10.3390/ijms131013338 - 18 Oct 2012
Cited by 8 | Viewed by 5658
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)
►▼ Show Figures


<p>Measurement of cerebral blood flow. (<b>A</b>) stage of carotid stenosis; (<b>B</b>) stage of stenosis relief. At carotid stenosis stage, cerebral blood flow (CBF) reduced markedly in each group when compared with that in sham group. However, when carotid stenosis was relieved, the CBF increased significantly in comparison with that in the stenosis group at indicated time point. Moreover, ischemic postconditioning improved CBF further, but there is no significant difference between stenosis relief group and ischemic postconditioning group at each corresponding time point. (<b>A: *</b> <span class="html-italic">p</span> &lt; 0.01, <span class="html-italic">vs.</span> sham group; <b>B: *</b> <span class="html-italic">p</span> &lt; 0.01, <span class="html-italic">vs.</span> carotid group)</p> Full article ">
<p>Histological examination of neuron death via hematoxylin-eosin (HE) staining and quantitative analysis of live neurons. When bilateral carotid stenosis was maintained, 55.5% ± 4.8% of the CA1 neurons was found to be alive at day 30. Despite the dead neurons appearing on day 3, the percentage of live neurons was 66.6% ± 6.2% on day 3 and 62.3% ± 9.8% on day 27 when carotid stenosis was relieved. By contrast, when ischemic postconditioning was administrated prior to carotid stenosis relief, the percentage of the live neurons was significantly improved to 92.5% ± 6.7% on day 3 and 88.6% ± 9.1% on day 27, respectively. <b>*</b> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> stenosis group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> stenosis relief group.</p> Full article ">
<p>Measurement of the level of oxidized products. At day 1, day 2 and day 3 following the relief of carotid stenosis, the levels of malondialdehyde (MDA) were 5.22 ± 1.31, 12.83 ± 2.11 and 9.62 ± 1.93 times, and 8-<span class="html-italic">iso</span>-PGF2α were 36.79 ± 6.18, 62.93 ± 9.42 and 46.58 ± 7.36 times higher than those in sham and carotid stenosis groups, respectively. By contrast, after being treated with ischemic postconditioning, the levels of MDA decreased to 4.12 ± 0.51, 5.49 ± 1.47 and 5.45 ± 1.26 times, and 8-<span class="html-italic">iso</span>-PGF2α decrease to 30.13 ± 4.32, 35.85 ± 6.72 and 33.87 ± 4.47 times, respectively. <b>*</b> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> sham group and stenosis group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> stenosis relief group.</p> Full article ">
<p>Measurement of the activities of anti-oxidative enzymes. In comparison with those in sham and carotid stenosis groups, the activities of superoxide dismutase (SOD) decreased to 120.98 ± 11.53, 68.26 ± 8.75 and 56.33 ± 6.72 U/mg·protein, and catalase (CAT) reduced to 11.96 ± 1.08, 7.64 ± 1.69 and 5.9 ± 1.45 U/mg·protein at day 1, day 2 and day 3, when carotid stenosis was relieved. However, ischemic postconditioning maintained the activities of SOD to 127.42 ± 12.18, 111 ± 10.76 and 103.66 ± 12.07 U/mg·protein, and CAT to 12.1 ± 1.17, 10.6 ± 1.03 and 9.95 ± 1.68 U/mg·protein. <b>*</b> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> sham group and stenosis group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> stenosis relief group.</p> Full article ">
<p>Measurement of the level of inflammatory factor. Compared with the values of sham operated group and carotid stenosis group, protein levels of IL-1β and TNF-α increased respectively to 2800 ± 310, 4000 ± 420 and 3400 ± 310 pg/mg·protein, and 52.66 ± 6.12, 90.18 ± 8.87 and 72.36 ± 6.79 pg/mg·protein at days 1, 2 and 3 after bilateral carotid artery stenosis was relieved. Nevertheless, treatment with ischemic postconditioning decreased the expression of IL-1β and TNF-α to 2100 ± 220, 2600 ± 290 and 2500 ± 270 pg/mg·protein, and 42.09 ± 3.87, 50.15 ± 4.77 and 46.65 ± 4.06 pg/mg·protein. <b>*</b> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> sham group and stenosis group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.01 <span class="html-italic">vs.</span> stenosis relief group.</p> Full article ">
<p>Schematic depicting the order of surgical procedures for Wistar rats undergoing sham operation, carotid stenosis, stenosis relief and ischemic postconditioning (ischemic postconditioning consisted of 3 cycles of 30-s/30-s reperfusion/clamping after 15 min ischemic episode).</p> Full article ">
267 KiB  
Review
Histone Displacement during Nucleotide Excision Repair
by Christoffel Dinant, Jiri Bartek and Simon Bekker-Jensen
Int. J. Mol. Sci. 2012, 13(10), 13322-13337; https://doi.org/10.3390/ijms131013322 - 17 Oct 2012
Cited by 9 | Viewed by 6205
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)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">
<p>Schematic representation of the “access, repair, restore” model for nucleotide excision repair (NER). For simplification purposes, DNA and chromatin (without DNA) are depicted separately. On the right, the remodeling proteins are listed at either the “access” or “restore” step. ATP-dependent chromatin remodelers are shown in blue and histone chaperones in red.</p> Full article ">
1687 KiB  
Article
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
Int. J. Mol. Sci. 2012, 13(10), 13308-13321; https://doi.org/10.3390/ijms131013308 - 17 Oct 2012
Cited by 96 | Viewed by 12246
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)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">
<p>The flow diagram of the selection of studies.</p> Full article ">
<p>The forest plot for the relation of non-A groups <span class="html-italic">vs</span>. blood group A based on meta-analysis.</p> Full article ">
<p>The forest plot for the relation of blood group B and non-B group based on meta-analysis.</p> Full article ">
<p>The forest plot for the relation of blood group O and non-O group based on meta-analysis.</p> Full article ">
<p>The forest plot for the relation of blood group AB and non-AB groups based on meta-analysis.</p> Full article ">
<p>The Begg’s funnel plot analysis for blood group A <span class="html-italic">vs</span>. non-A groups and gastric cancer risk (<b>upper left</b>), blood group B <span class="html-italic">vs</span>. non-B groups (<b>upper right</b>), blood group O <span class="html-italic">vs</span>. non-O groups (<b>lower left</b>) and blood group AB <span class="html-italic">vs</span>. non-AB groups (<b>lower right</b>). The vertical axis represents the log of OR. The horizontal axis represents the SE of log (OR). The funnel plots are drawn with 95% confidence limits. OR: odds ratio; SE: standard error.</p> Full article ">
305 KiB  
Article
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
Int. J. Mol. Sci. 2012, 13(10), 13294-13307; https://doi.org/10.3390/ijms131013294 - 17 Oct 2012
Cited by 7 | Viewed by 6243
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)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">
<p>β-cyclodextrin (β-CD) production by (<b>A</b>) <span class="html-italic">B. firmus</span> strain 7B cells and (<b>B</b>) <span class="html-italic">B. sphaericus</span> strain 41 cells, free and immobilized on different matrices. Different letters in different columns represent statistically significant differences (<span class="html-italic">p</span> &lt; 0.05). The same letters in different columns indicate no significant statistical difference.</p> Full article ">
<p>Storage stability in the β-CD production by (<b>A</b>) <span class="html-italic">B. firmus</span> strain 7B cells immobilized on a synthetic sponge matrix and (<b>B</b>) <span class="html-italic">B. sphaericus</span> strain 41 cells immobilized on a loofa sponge matrix.</p> Full article ">
<p>Single β-CD production batch over 12 consecutive days: (<b>A</b>) <span class="html-italic">B. firmus</span> strain 7B cells immobilized on a synthetic sponge matrix and (<b>B</b>) <span class="html-italic">B. sphaericus</span> strain 41 cells immobilized on a loofa sponge matrix; (■) immobilized cells and (▲) free cells.</p> Full article ">
<p>β-CD production in four consecutive cycles of 120 h each. (<b>A</b>) <span class="html-italic">B. firmus</span> strain 7B cells immobilized on a synthetic sponge matrix and (<b>B</b>) <span class="html-italic">B. sphaericus</span> strain 41 cells immobilized on a loofa sponge matrix; (□) free cells; (■) 4 days of immobilization; (■) 24 days of immobilization. * <span class="html-italic">P</span> &lt; 0.05 when the β-CD production by the immobilized cells was compared with production by free cells. <sup>•</sup> <span class="html-italic">P</span> &lt; 0.05 when β-CD production was compared between the immobilized cells for 4 and 24 days.</p> Full article ">
<p>Scanning electron microscopy of synthetic sponge (<b>A</b>); loofa sponge (<b>B</b>); <span class="html-italic">B. firmus</span> strain 7B cells immobilized on synthetic sponge (<b>C</b>) and <span class="html-italic">B. sphaericus</span> strain 41 cells immobilized on loofa sponge (<b>D</b>).</p> Full article ">
2055 KiB  
Article
The Effect of Sodium Dodecyl Sulfate (SDS) and Cetyltrimethylammonium Bromide (CTAB) on the Properties of ZnO Synthesized by Hydrothermal Method
by Donya Ramimoghadam, Mohd Zobir Bin Hussein and Yun Hin Taufiq-Yap
Int. J. Mol. Sci. 2012, 13(10), 13275-13293; https://doi.org/10.3390/ijms131013275 - 16 Oct 2012
Cited by 219 | Viewed by 18073
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)
►▼ Show Figures


<p>Powder X-ray diffraction (PXRD) patterns of as-prepared ZnO synthesized at different mole ratios of (<b>A</b>) cetyltrimethylammonium bromide (CTAB) (0, 0.5, 1, 1.5, 2) and (<b>B</b>) sodium dodecyl sulfate (SDS) (0, 0.2, 0.36, 0.5, 1, 1.5).</p> Full article ">
<p>Field emission scanning electron microscopy (FESEM) images of ZnO prepared using different mole ratios of CTAB to SDS, (<b>a</b>) SDS:CTAB = 1:0; (<b>b</b>) SDS:CTAB = 1:0.5; (<b>c</b>) SDS:CTAB = 1:1; (<b>d</b>) SDS:CTAB = 1:1.5; (<b>e</b>,<b>f</b>) SDS:CTAB = 1:2, 2d (inset) transmission electron microscopy (TEM) image of SDS:CTAB = 1:1.</p> Full article ">
<p>Field emission scanning electron microscopy (FESEM) images of ZnO prepared using different mole ratios of CTAB to SDS, (<b>a</b>) SDS:CTAB = 1:0; (<b>b</b>) SDS:CTAB = 1:0.5; (<b>c</b>) SDS:CTAB = 1:1; (<b>d</b>) SDS:CTAB = 1:1.5; (<b>e</b>,<b>f</b>) SDS:CTAB = 1:2, 2d (inset) transmission electron microscopy (TEM) image of SDS:CTAB = 1:1.</p> Full article ">
<p>SEM images of ZnO crystals prepared at (<b>a</b>) CTAB:SDS = 1:0; (<b>b</b>) CTAB:SDS = 1:0.2; (<b>c</b>) CTAB:SDS = 1:0.36; (<b>d</b>) CTAB:SDS=1:0.5; (<b>e</b>) CTAB:SDS = 1:1 and (<b>f</b>) CTAB:SDS = 1:1.5.</p> Full article ">
<p>SEM images of ZnO crystals prepared at (<b>a</b>) CTAB:SDS = 1:0; (<b>b</b>) CTAB:SDS = 1:0.2; (<b>c</b>) CTAB:SDS = 1:0.36; (<b>d</b>) CTAB:SDS=1:0.5; (<b>e</b>) CTAB:SDS = 1:1 and (<b>f</b>) CTAB:SDS = 1:1.5.</p> Full article ">
<p>TEM images of as-synthesized ZnO nanostructures with (<b>a</b>) CTAB:SDS = 1:0.5, (<b>b</b>) CTAB:SDS = 1:1 and (<b>c</b>) CTAB:SDS = 1:1.5.</p> Full article ">
<p>Thermogravimetric and differential thermogravimetric analysis (TGA-DTG) thermogravimetric analysis of as-synthesized ZnO samples prepared at different mole ratios of (<b>a</b>) SDS:CTAB = 1:0; (<b>i</b>) CTAB:SDS = 1:0.5; (<b>j</b>) CTAB:SDS = 1:1.</p> Full article ">
<p>Thermogravimetric and differential thermogravimetric analysis (TGA-DTG) thermogravimetric analysis of as-synthesized ZnO samples prepared at different mole ratios of (<b>a</b>) SDS:CTAB = 1:0; (<b>i</b>) CTAB:SDS = 1:0.5; (<b>j</b>) CTAB:SDS = 1:1.</p> Full article ">
<p>FTIR spectra of as-produced ZnO samples with constant amount of SDS and different mole ratios of (<b>A</b>) CTAB (SDS:CTAB); (<b>B</b>) SDS (CTAB:SDS).</p> Full article ">
<p>FTIR spectra of as-produced ZnO samples at different mole ratios of (<b>A</b>) SDS:CTAB = 1:0.5 and (<b>B</b>) CTAB:SDS = 1:1 before and after the calcinations at 500 °C for 5 h.</p> Full article ">
<p>Nitrogen adsorption-desorption isotherms and Barret-Joyner-Halenda (BJH) pore size distribution of as-obtained ZnO nanostructures with different mole ratio of (<b>A</b>) CTAB and (<b>B</b>) SDS.</p> Full article ">
2865 KiB  
Article
Over-Expression of Semaphorin4D, Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Is Related to Poor Prognosis in Ovarian Epithelial Cancer
by Ying Chen, Lei Zhang, Yi Pan, Xiubao Ren and Quan Hao
Int. J. Mol. Sci. 2012, 13(10), 13264-13274; https://doi.org/10.3390/ijms131013264 - 16 Oct 2012
Cited by 44 | Viewed by 6978
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)
►▼ Show Figures


<p>Representative images showing SEMA4D (<b>A</b>–<b>F</b>), VEGF (<b>G</b>–<b>I</b>) and HIF-1α (<b>J</b>–<b>L</b>) expressions. (<b>A</b>) SEMA4D negative expression in normal ovarian epithelia (400×); (<b>B</b>) mucinous ovarian adenocarcinoma (G2) with negative immunostaining of SEMA4D (200×); (<b>C</b>) serous ovarian adenocarcinoma (G2, FIGO Stage II) with immunostaining of SEMA4D in the membrane of tumor cells (400×; Evaluation: 5 points); (<b>D</b>) serous ovarian adenocarcinoma (G3, FIGO Stage I) with immunostaining of SEMA4D (400×; Evaluation: 3 points); (<b>E</b>) endometrioid ovarian adenocarcinoma (G2, FIGO Stage III) with immunostaining of SEMA4D (400×; Evaluation: 6 points); (<b>F</b>) ovarian adenocarcinoma (G3 to undifferentiated, FIGO Stage III) with immunostaining of SEMA4D (400×; Evaluation: 7 points); (<b>G</b>) serous ovarian adenocarcinoma (G2, FIGO Stage I) with immunostaining of VEGF in the cytoplasm of tumor cells (400×; Evaluation: 2 points); (<b>H</b>) endometrioid ovarian adenocarcinoma (G2, FIGO Stage II) with immunostaining of VEGF in the cytoplasm of tumor cells (400×; Evaluation: 4 points); (<b>I</b>) endometrioid ovarian adenocarcinoma (G3, FIGO Stage IV) with immunostaining of VEGF (400×; Evaluation: 7 points); (<b>J</b>) serous ovarian adenocarcinoma (G2, FIGO Stage II) with immunostaining of HIF-1α in the nuclei of tumor cells (400×; Evaluation: 1 point); (<b>K</b>) serous ovarian adenocarcinoma (G2, FIGO Stage III) with immunostaining of HIF-1α (400×; Evaluation: 5 points); (<b>L</b>) ovarian adenocarcinoma (G3 to undifferentiated, FIGO Stage III) with immunostaining of HIF-1α (400×; Evaluation: 7 points).</p> Full article ">
<p>Kaplan-Meier analysis for the disease-free survival and overall survival of epithelial ovarian cancer patients according to SEMA4D expression in cancer cells. The survival curves were analyzed by the log rank test. (<b>A</b>) Epithelial ovarian cancer patients with positive SEMA4D expression showed shorter progress-free survival than those with negative expression; (<b>B</b>) Epithelial ovarian cancer patients with positive SEMA4D expression showed shorter overall survival than those with negative expression.</p> Full article ">
233 KiB  
Review
The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer
by László Herszényi, István Hritz, Gábor Lakatos, Mária Zsófia Varga and Zsolt Tulassay
Int. J. Mol. Sci. 2012, 13(10), 13240-13263; https://doi.org/10.3390/ijms131013240 - 16 Oct 2012
Cited by 131 | Viewed by 9956
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))
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-91
Previous Issue
Next Issue
Back to TopTop