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Cytokine Dec 2020Published studies on association between IL12B (G/A) rs10045431, (T/C)rs6887695 polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian population have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Published studies on association between IL12B (G/A) rs10045431, (T/C)rs6887695 polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian population have yielded conflicting results. The aim of this study was to potentially provide more reliable conclusions by conducting a meta-analysis.
METHODS
Published studies concerned association between IL12B rs10045431, rs6887695 polymorphisms and IBD were searched from the Wiley Online Library, PubMed, Web of Science and the CNKI database. The odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of the relationship. The false positive report probabilities (FPRPs) test and trial sequential analysis (TSA) was performed to investigated the reliability of results.
RESULTS
A total of 20 studies comprising 10761 Crohn's disease (CD), 10921 ulcerative colitis (UC) and 18381 controls were included in this meta-analysis. Overall, the pooled results showed that IL12B rs6887695 polymorphism significantly increased both CD and UC risk under all model, while IL12B rs10045431 polymorphism dramatically decreased both CD and UC risk under all model. FPRP and TSA demonstrated that above associations was confirmed in the present study.
CONCLUSION
The results of meta-analysis indicate IL12B rs10045431 and rs6887695 polymorphisms significantly associate with IBD in Caucasian population.
Topics: Humans; Inflammatory Bowel Diseases; Interleukin-12 Subunit p40; Polymorphism, Genetic; White People
PubMed: 32947150
DOI: 10.1016/j.cyto.2020.155296 -
Journal of Cellular Physiology Apr 2021Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments....
Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments. Pathways of the viral entry into cells are interesting subjects for targeted therapy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aims to provide a systematic evaluation of the most recent in vitro and in vivo investigations targeting SARS-CoV-2 cell entry. A systematic search was carried out in major medical sources, including MEDLINE (through PubMed), Web of Science, Scopus, and EMBASE. Combinations of the following search terms were used: SARS-CoV-2, in vitro, in vivo, preclinical, targeted therapy, and cell entry. A modified version of the Consolidated Standards of Reporting Trials and Systematic Review Centre for Laboratory Animal Experimentation assessment tools were applied for evaluating the risk of bias of in vitro and in vivo studies, respectively. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. A total of 2,649 articles were identified through searching PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and Biorxiv. Finally, 22 studies (one in vivo study and 21 in vitro studies) were included. The spike (S) glycoprotein of the SARS-CoV-2 was the main target of investigation in 19 studies. SARS-CoV-2 can enter into the host cells through endocytosis or independently. SARS-CoV-2 S protein utilizes angiotensin-converting enzyme 2 or CD147 as its cell-surface receptor to attach host cells. It consists of S1 and S2 subunits. The S1 subunit mediates viral attachment to the host cells, while the S2 subunit facilitates virus-host membrane fusion. The cleavage of the S1-S2 protein, which is required for the conformational changes of the S2 subunit and processing of viral fusion, is regulated by the host proteases, including cathepsin L (during endocytosis) and type II membrane serine protease (independently). Targeted therapy strategies against SARS-CoV-2 cell entry mechanisms fall into four main categories: strategies targeting virus receptors on the host, strategies neutralizing SARS-CoV-2 spike protein, strategies targeting virus fusion to host cells, and strategies targeting endosomal and non-endosomal dependent pathways of virus entry. Inhibition of the viral entry by targeting host or virus-related components remains the most potent strategy to prevent and treat COVID-19. Further high-quality investigations are needed to assess the efficacy of the proposed targets and develop specific antivirals against SARS-CoV-2.
Topics: Animals; Antiviral Agents; COVID-19; Humans; SARS-CoV-2; Virus Internalization; COVID-19 Drug Treatment
PubMed: 32901936
DOI: 10.1002/jcp.30032 -
The Journal of International Medical... Aug 2020Interleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the impacts of the IL-12 rs3212227 and rs568408 gene polymorphisms on HCC.
METHODS
We searched PubMed, Embase, Web of Science, and Chinese Knowledge Infrastructure databases for studies on the associations between HCC and IL-12 rs568408 and rs3212227 polymorphisms published prior to 1 May 2020. The effects of the polymorphisms on HCC susceptibility were presented as odds ratios (ORs) and associated 95% confidence intervals.
RESULTS
Seven studies were ultimately included, including 2375 cases and 3445 controls. The rs3212227 polymorphism was significantly associated with the risk of HCC in both the dominant model (CC+AC vs. AA, OR=1.22) and the allele model (C vs. A, OR=1.12). Combined analysis of rs568408 yielded a significant relative risk for HCC in the dominant (AA+AG vs. GG, OR=1.13), recessive (AA vs. AG+GG, OR=1.72), allele (A vs. G, OR=1.29), heterozygote (AG vs. GG, OR=1.27), and homozygote models (AA vs. GG, OR 1.17).
CONCLUSION
The IL-12 rs3212227 and rs568408 gene polymorphisms are associated with an increased risk of HCC.
Topics: Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Interleukin-12; Interleukin-12 Subunit p35; Liver Neoplasms; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 32809897
DOI: 10.1177/0300060520943420 -
BioMed Research International 2020Arsenic is a toxic metalloid widely present in nature, and arsenic poisoning in drinking water is a serious global public problem. Glutathione is an important reducing...
BACKGROUND
Arsenic is a toxic metalloid widely present in nature, and arsenic poisoning in drinking water is a serious global public problem. Glutathione is an important reducing agent that inhibits arsenic-induced oxidative stress and participates in arsenic methylation metabolism. Therefore, glutathione plays an important role in regulating arsenic toxicity. In recent years, a large number of studies have shown that arsenic can regulate glutathione synthesis in many ways, but there are many contradictions in the research results. At present, the mechanism of the effect of arsenic on glutathione synthesis has not been elucidated.
OBJECTIVE
We will conduct a meta-analysis to illustrate the effects of arsenic on GSH synthesis precursors Glu, Cys, Gly, and rate-limiting enzyme -GCS in mammalian models, as well as the regulation of p38/Nrf2 of -GCS subunit GCLC, and further explore the molecular mechanism of arsenic affecting glutathione synthesis.
RESULTS
This meta-analysis included 30 studies in vivo and 58 studies in vitro, among which in vivo studies showed that arsenic exposure could reduce the contents of GSH (SMD = -2.86, 95% CI (-4.45, -1.27)), Glu (SMD = -1.11, 95% CI (-2.20,-0.02)), and Cys (SMD = -1.48, 95% CI (-2.63, -0.33)), with no statistically significant difference in p38/Nrf2, GCLC, and GCLM. In vitro studies showed that arsenic exposure increased intracellular GSH content (SMD = 1.87, 95% CI (0.18, 3.56)) and promoted the expression of p-p38 (SMD = 4.19, 95% CI (2.34, 6.05)), Nrf2 (SMD = 4.60, 95% CI (2.34, 6.86)), and GCLC (SMD = 1.32, 95% CI (0.23, 2.41)); the p38 inhibitor inhibited the expression of Nrf2 (SMD = -1.27, 95% CI (-2.46, -0.09)) and GCLC (SMD = -5.37, 95% CI (-5.37, -2.20)); siNrf2 inhibited the expression of GCLC, and BSO inhibited the synthesis of GSH. There is a dose-dependent relationship between the effects of exposure on GSH in vitro. These indicate the difference between in vivo and in vitro studies of the effect of arsenic on glutathione synthesis. In vivo studies have shown that arsenic exposure can reduce glutamate and cysteine levels and inhibit glutathione synthesis, while in vitro studies have shown that chronic low-dose arsenic exposure can activate the p38/Nrf2 pathway, upregulate GCLC expression, and promote glutathione synthesis.
Topics: Animals; Arsenic; Arsenic Poisoning; Glutamate-Cysteine Ligase; Glutathione; Humans; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 32802886
DOI: 10.1155/2020/9414196 -
International Immunopharmacology Sep 2020The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)....
The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no vaccine or approved treatment for this infectious virus so the invention of an efficient vaccine is certainly a high priority. Some studies have employed several techniques to facilitate the combination of the immunoinformatics approach and comparative genomic approach in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the 2019-nCoV envelope protein as a target. Via screening the bioimmunoinformatic SARS-CoV2 derived B-cell and T-cell epitopes within the basic immunogenic of SARS-CoV2 proteins, we presented a set of inferred B-cell and T-cell epitopes from the spike (S) and nucleocapsid (N) proteins with high antigenicity and without allergenic property or toxic effects. Our findings provide a screened set of epitopes that can be introduced as potential targets for developing peptide vaccines against the SARS-CoV-2 virus.
Topics: Betacoronavirus; COVID-19; Computational Biology; Coronavirus Infections; Drug Development; Epitopes, B-Lymphocyte; Epitopes, T-Lymphocyte; Humans; Nucleocapsid Proteins; Pandemics; Pneumonia, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccines, Subunit; Viral Vaccines
PubMed: 32683296
DOI: 10.1016/j.intimp.2020.106738 -
Sexual Medicine Reviews Oct 2020Several treatment strategies are nowadays available for erectile dysfunction (ED) patients. Currently, oral phosphodiesterase type 5 inhibitors (PDE5Is) are the...
INTRODUCTION
Several treatment strategies are nowadays available for erectile dysfunction (ED) patients. Currently, oral phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line therapy for ED. However, they are effective in all treated cases with variable non-responsiveness. Many factors have been listed for this behavior, but the possibility of gene polymorphisms as an underlying cause has not been systematically investigated.
OBJECTIVES
This review aimed to assess the possible involvement of gene polymorphisms affecting the response to PDE5Is in men with ED.
METHODS
A systematic review was conducted based on a search of all relevant articles in various electronic sites such as PubMed, Medline Medical Subject Headings, Cochrane Library, Science Direct, Scopus, Embase, CINAHL, and Egyptian Knowledge Bank databases. Keywords used for relevant associations were sexual health, genes, variants, erectile dysfunction, polymorphisms, PDE5Is, and cavernous tissues.
RESULTS
Several studies have been carried out to determine the contribution of different encoded genes to ascertain the association between different genotypes and ED men who were non-responders for PDE5Is. 11 studies were selected for this review. In these studies, 6 investigated eNOS genetic polymorphism with variable outcomes. Only 1 study was carried out for each of the following genetic polymorphisms: phosphodiestrase 5A, G-protein β3 subunit, angiotensin converting enzyme, dimethylarginine dimethylaminohydrolase, arginase, and vascular endothelial growth factor with variable results.
CONCLUSION
Despite the relative shortage of available studies and the varied methodologies used, most of the research articles demonstrated a significant association between genetic polymorphism and the response to PDE5Is, especially for endothelial nitric oxide synthase polymorphism. The limited number of studies that investigated the possible effect of genetic polymorphism and the response to PDE5Is are challenged by many factors, particularly for the definition of responders and non-responders. This should be a motivating factor for researchers to perform further studies with a standardized methodology to address the influence of genetic variations on the response to PDE5Is. Mostafa T, Hassan A, Alghobary MF, et al. Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal. J Sex Med 2020;8:573-585.
Topics: Erectile Dysfunction; Genotype; Humans; Male; Phosphodiesterase 5 Inhibitors; Polymorphism, Genetic; Treatment Outcome
PubMed: 32636154
DOI: 10.1016/j.sxmr.2020.05.005 -
Journal of Dermatological Science Jul 2020Complete lesion clearance is important to patients with psoriasis.
BACKGROUND
Complete lesion clearance is important to patients with psoriasis.
OBJECTIVE
To conduct a network meta-analysis of randomized controlled trials of biologic agents available for psoriasis in Japan, using mixed-treatment comparisons.
METHODS
MEDLINE and EMBASE were searched to identify randomized clinical trials (placebo-controlled or head-to-head) of infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, risankizumab or guselkumab in adult patients with moderate-to-severe plaque psoriasis published in English between 01 January 2000 and 31 August 2019. We assessed the proportion of patients who achieved a 100 %, 90 % and 75 % reduction in their Psoriasis Area and Severity Index (PASI) score (PASI100, PASI90 and PASI75) at 10, 12 or 16 weeks after starting biologic treatment, using contrast-based network meta-analysis methods and risk difference (RD). Probabilities of rank and surface under the cumulative ranking (SUCRA) were also estimated.
RESULTS
Data were pooled from 41 trials in 19,248 patients. All biologics were significantly more effective than placebo for PASI100, PASI90 and PASI75. The RD for PASI100 for brodalumab vs ixekizumab was 0.05 (95 % Confidence intervals [CI] -0.02, 0.11), brodalumab vs risankizumab was 0.04 (95 %CI -0.03, 0.11), and risankizumab vs ixekizumab was -0.01 (95 %CI -0.08, 0.06). The SUCRA for PASI100 and PASI90 achievement was 96.8 % and 86.8 %, respectively, for brodalumab, 82.6 % and 90.3 %, respectively for risankizumab, and 78.3 %, 80.9 %, respectively, for ixekizumab.
CONCLUSION
Of the biologics assessed, brodalumab, ixekizumab and risankizumab were the greatest rates of PASI90 and PASI100 achievement, and a higher probability of being most effective in the induction phase, compared with the other biologics.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Dermatologic Agents; Humans; Interleukin-17; Interleukin-23 Subunit p19; Japan; Network Meta-Analysis; Psoriasis; Randomized Controlled Trials as Topic; Receptors, Interleukin-17; Remission Induction; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 32600737
DOI: 10.1016/j.jdermsci.2020.06.003 -
Molecular Brain Jun 2020The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum...
OBJECTIVES
The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD).
METHODS
A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions.
RESULTS
From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD.
CONCLUSIONS
Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype.
Topics: Autism Spectrum Disorder; Calcium Channels; Calcium Signaling; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Protein Subunits
PubMed: 32571372
DOI: 10.1186/s13041-020-00634-0 -
Gene Aug 2020The goal of our study is to investigate the contribution of the 13 single-nucleotide polymorphisms to inflammatory bowel disease (IBD), including Crohn's disease (CD)... (Meta-Analysis)
Meta-Analysis
AIMS
The goal of our study is to investigate the contribution of the 13 single-nucleotide polymorphisms to inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative colitis (UC).
METHODS
A total of 44 articles were retrieved from bibliographic databases including PubMed, Embase, SpingerLink, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang. Through a comprehensive filtering procedure, 13 single-nucleotide polymorphisms were collected in the meta-analysis, which was done by Review Manager 5.0.
RESULTS
After a systematic filtration, there were 13 single-nucleotide polymorphisms (SNPs) from 44 articles involved in our meta-analysis. Our results demonstrated that 3 SNPs were found to be significantly associated with CD/UC/IBD: IRF5 rs4728142 (UC: OR = 1.21, 95% CI = 1.09-1.35, P = 0.0003; OR = 1.30, 95% CI = 1.08-1.57, P = 0.006 in Asian), PTGER4 rs4613763 (CD: the overall OR = 1.28, 95% CI = 1.01-1.64, P = 0.04; IBD: OR = 1.31, 95% CI = 1.04-1.65, P = 0.02), IL12B rs6887695 (CD: the overall OR = 1.17, 95% CI = 1.06-1.30, P = 0.002; UC: the overall OR = 1.13, 95% CI = 1.01-1.26, P = 0.03; IBD: the overall OR = 1.15, 95% CI = 1.06-1.24, P = 0.0009).
CONCLUSION
Our meta-analyses have indicated the significant associations between SNPs (IRF5 rs4728142, PTGER4 rs4613763, and IL12B rs6887695) and CD/UC/IBD.
Topics: Asian People; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Disease Susceptibility; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Inflammatory Bowel Diseases; Interferon Regulatory Factors; Interleukin-12 Subunit p40; Phenotype; Polymorphism, Single Nucleotide; Receptors, Prostaglandin E, EP4 Subtype; White People
PubMed: 32464244
DOI: 10.1016/j.gene.2020.144814 -
Asian Pacific Journal of Cancer... May 2020Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting results warrant a meta-analysis to obtain more precise estimates.
METHODS
A comprehensive literate search on PubMed, Web of Science, Scopus, CNKI, and SciELO was performed to collect all eligible studies up to November 10, 2019. The pooled odds ratios (OR) and 95% confidence intervals (CI) were used to calculate the risk. This meta-analysis was carried out by utilizing CMA software.
RESULTS
A total of eleven case-control studies including four studies on IL-12B rs3212227 and seven studies on IL-6 rs1800795 were selected. Pooled ORs revealed that the IL-6 rs1800795 polymorphism was significantly associated with an increased risk of cervical cancer (C vs. G: OR = 1.294, 95% CI 1.071-1.564, p= 0.007; CC vs. GG: OR = 1.633, 95% CI 1.059-2.520, p= 0.027; CC+CG vs. GG: OR = 1.312, 95% CI 1.048-1.643, p= 0.018; and CC vs. CG+GG: OR = 1.592, 95% CI 1.268-1.999, p≤0.001), but not IL-12B rs3212227 polymorphism. Stratified analysis by ethnicity revealed that both IL-12B rs3212227 and IL-6 rs1800795 polymorphisms were associated with risk of cervical cancer in Asian women.
CONCLUSIONS
Our pooled data revealed that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms may be used to identify individuals at high risk of cervical cancer in Asian women.
.Topics: Biomarkers, Tumor; Female; Genetic Predisposition to Disease; Humans; Interleukin-12 Subunit p40; Polymorphism, Single Nucleotide; Prognosis; Uterine Cervical Neoplasms
PubMed: 32458622
DOI: 10.31557/APJCP.2020.21.5.1197