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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 -
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 -
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 -
Annals of the Rheumatic Diseases Jun 2020To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis.
OBJECTIVE
To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS
This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS
56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION
Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Interleukin-17; Interleukin-23 Subunit p19; Molecular Targeted Therapy; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32381564
DOI: 10.1136/annrheumdis-2020-217163 -
American Journal of Cancer Research 2020The initiation and progression of cancer is dependent on the acquisition of mutations in oncogenes or tumor suppressor genes that ultimately leads to the dysregulation... (Review)
Review
The initiation and progression of cancer is dependent on the acquisition of mutations in oncogenes or tumor suppressor genes that ultimately leads to the dysregulation of key regulatory pathways. Though these mutations often occur in direct regulators of such pathways, some may confer tumorigenic potential by indirectly targeting several pathways congruently thereby exerting pleiotropic effects. In recent years, the tumor suppressor gene Speckle Type POZ Protein (SPOP) has gained a lot of attention as it has been found to be altered in a variety of different cancers. SPOP appears to exert pleiotropic tumorigenic effects as multiple different regulatory pathways become dysregulated upon SPOP alterations. SPOP has been identified as an E3 ubiquitin ligase substrate binding subunit of the proteasome complex. Since protein degradation is critical in regulating proper cellular function it is not surprising that the proteasome pathway is often found to be disrupted in cancer. Many studies have now indicated that mutations or changes in the expression of SPOP are one of several underlying reasons of proteasome pathway disruption in different cancers. Ultimately, either SPOP downregulation or mutation promotes stabilization of direct SPOP targets which subsequently promotes cancer through the dysregulation of key regulatory pathways. In this review, we will discuss the current literature on cancer-specific SPOP alterations as well the SPOP targets that are stabilized, and the pathways that are dysregulated, as a result.
PubMed: 32266086
DOI: No ID Found -
BioMed Research International 2020Studies on the number and proportion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) patients have been controversial, which has led to a disagreement... (Meta-Analysis)
Meta-Analysis
Studies on the number and proportion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) patients have been controversial, which has led to a disagreement regarding the role of Tregs in the pathogenesis of AS. To clarify this debate, we conducted a meta-analysis to verify the reported changes in Tregs during AS. We systematically searched the PubMed, Foreign Medical Retrieval System (FMRS), and China National Knowledge Infrastructure (CNKI) web of knowledge databases for eligible articles. A meta-analysis of studies that examined the proportion and number of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4 T cells was performed using Stata software. Further, subgroup analysis was performed based on Treg definition markers and disease activity to identify potential sources of heterogeneity. Forty-seven studies involving a total of 4373 participants were included in the meta-analysis. The Treg/PBMC and Treg/CD4 T cell ratios were significantly lower in AS patients than those in healthy controls (HCs). A subgroup analysis indicated that patients defined by CD4CD25, CD4CD25CD127, and CD4CD25FOXP3 had much lower Treg/PBMC and Treg/CD4 T cell ratios than HCs. Active AS patients also had a substantially lower proportion of Tregs/PBMCs and Treg/CD4 T cells than HCs. The proportion of Tregs among both PBMCs and CD4 T cells was significantly decreased in AS patients. Treg definition markers and disease activity may influence the proportion of Tregs measured among the PBMC and CD4 T cell populations. Further study of the correlation between AS disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association. This study implies that loss of Tregs may play a role in the pathogenesis of AS and helps clarify the contradictory Treg results in AS patients. This trial is registered with PROSPERO (CRD42019147064).
Topics: Biomarkers; CD4-Positive T-Lymphocytes; Databases, Factual; Humans; Interleukin-2 Receptor alpha Subunit; Leukocytes, Mononuclear; Lymphocyte Count; Spondylitis, Ankylosing; T-Lymphocytes, Regulatory
PubMed: 32149142
DOI: 10.1155/2020/8709804 -
BioMed Research International 2019. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients.
METHODS
A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors.
RESULTS
Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; <0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07.
CONCLUSIONS
Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients.
Topics: Calpain; Cancer Survivors; Carcinogenesis; Databases, Factual; Disease-Free Survival; Female; Humans; Male; Odds Ratio; Prognosis
PubMed: 32083121
DOI: 10.1155/2019/8053706 -
BMC Pulmonary Medicine Feb 2020Obstructive sleep apnea syndrome (OSAS) is a common disorder that is accompanied by structural brain changes. This meta-analysis aimed to evaluate the effect of OSAS on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea syndrome (OSAS) is a common disorder that is accompanied by structural brain changes. This meta-analysis aimed to evaluate the effect of OSAS on the serum levels of astrocytic protein (S100B) and neuron-specific enolase (NSE) in observational studies.
METHODS
A comprehensive search was performed in the PubMed/Medline, Web of Science, Scopus, ScienceDirect, and Cochrane Library databases to assess the serum level of S100B and/or NSE in patients with OSAS and/or controls. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using RevMan 5.3 with the mean difference (MD) and 95% confidence intervals (CIs).
RESULTS
Out of 63 studies found in the mentioned databases and one identified by a manual search, nine studies were included and analyzed in this meta-analysis (three cross-sectional and six case-control studies). The analysis showed that the S100B [MD = 53.58 pg/ml, 95%CI: 1.81, 105.35; P = 0.04] and NSE levels [MD = 3.78 ng/ml, 95%CI: 2.07, 5.48; P < 0.0001] were significantly higher in patients than the controls. However, there were no significant differences between the S100B [MD = -28.00 pg/ml, 95%CI: - 79.48, 23.47; P = 0.29] and NSE levels [MD = 0.49 ng/ml, 95%CI: - 0.82, 1.80; P = 0.46].
CONCLUSIONS
This meta-analysis found elevated serum S100B and NSE levels in OSAS patients compared to the controls, which suggests that these markers may be used as peripheral indicators of brain damage in OSAS.
Topics: Biomarkers; Brain Damage, Chronic; Humans; Observational Studies as Topic; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Sleep Apnea, Obstructive
PubMed: 32024492
DOI: 10.1186/s12890-020-1063-8 -
International Journal of Environmental... Dec 2019Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor...
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.
Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like () , adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) , ADD1, , MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Topics: DNA Methylation; Essential Hypertension; Female; Genotype; Humans
PubMed: 31805646
DOI: 10.3390/ijerph16234829