Etiopathogenesis of Psoriasis from Genetic Perspective: An updated Review.

Psoriasis is an organ-specific autoimmune disease characterized by the aberrant proliferation and differentiation of keratinocytes, leading to skin lesions. Abnormal immune responses mediated by T cells and dendritic cells and increased production of inflammatory cytokines have been suggested as underlying mechanisms in the pathogenesis of psoriasis. Emerging evidence suggests that there is a heritable basis for psoriatic disorders. Moreover, numerous gene variations have been associated with the disease risk, particularly those in innate and adaptive immune responses and antigen presentation pathways. Herein, this article discusses the genetic implications of psoriatic diseases' etiopathogenesis to develop novel investigative and management options.

Plasminogen Activator Inhibitor-1 Polymorphisms and Risk of Coronary Artery Disease: Evidence From Meta-Analysis and Trial Sequential Analysis.

A systematic review and meta-analysis were conducted to find out if there was association between Plasminogen Activator Inhibitor-1 (PAI-1) gene polymorphisms (- 844 G > A and - 675 4G > 5G) and susceptibility to coronary artery disease (CAD). Search of electronic databases was performed and the pooled odds ratio (OR) and 95% confidence interval (CI) were exerted to evaluate the pooled association between the single-nucleotide polymorphisms (SNPs) and risk of CAD. For - 675 4G > 5G SNP, dominant (OR = 0.90), recessive (OR = 0.90), allelic (OR = 0.91), homozygous (OR = 0.84), and heterozygous (OR = 0.96) models were significantly associated with decreased risk of CAD. Moreover, all five genetic models were associated significantly with decreased CAD risk in the Causation and Arab populations. The results in Asians were marginally significant in recessive, allelic, and homozygote models. The male gender was found to be a risk factor in individuals with PAI-1 4G > 5G SNP in the dominant model (OR = 0.89), recessive model (OR = 0.91), allelic model (OR = 0.92), homozygous model (OR = 0.86), and heterozygous model (OR = 0.91). The results of pooled ORs for overall populations and subgroup analysis by ethnicity reject any association between PAI-1 gene - 844 G > A polymorphism and CAD risk under all genetic comparisons. The results of this meta-analysis indicated that PAI-1 4G > 5G SNP was associated with decreased risk of CAD in the overall population as well as in the Asians, Caucasians, and Arab populations. However, the PAI-1 gene - 844 G > A polymorphism had no significant association with susceptibility to CAD.

Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which has emerged as a global health crisis. Recently, more than 50 different types of potential COVID-19 vaccines have been developed to elicit a strong immune response against SARS-CoV-2. However, genetic mutations give rise to the new variants of SARS-CoV-2 which is highly associated with the reduced effectiveness of COVID-19 vaccines. There is still no efficient antiviral agent to specifically target the SARS-CoV-2 infection and treatment of COVID-19. Therefore, understanding the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 may contribute to discovering a novel potential therapeutic approach to the management of COVID-19. Recently, extracellular vesicle (EV)-based therapeutic strategies have received great attention on account of their potential benefits in the administration of viral diseases. EVs are extracellular vesicles containing specific biomolecules which play an important role in cell-to-cell communications. It has been revealed that EVs are involved in the pathogenesis of different inflammatory diseases such as cancer and viral infections. EVs are released from virus-infected cells which could mediate the interaction of infected and uninfected host cells. Hence, these extracellular nanoparticles have been considered a novel approach for drug delivery to mediate the treatment of a wide range of diseases including, COVID-19. EVs are considered a cell-free therapeutic strategy that could ameliorate the cytokine storm and its complications in COVID-19 patients. Furthermore, EV-based cargo delivery such as immunomodulatory agents in combination with antiviral drugs may have therapeutic benefits in patients with SARS-CoV-2 infection. In this review, we will highlight the potential of EVs as a therapeutic candidate in the diagnosis and treatment of COVID-19. Also, we will discuss the future perspectives regarding the beneficial effects of Evs in the development of COVID-19 vaccines.

Association between IL7 Receptor Alpha (Il7ra) gene rs6897932 polymorphism and the risk of Multiple Sclerosis: A meta-regression and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to find a consistent conclusion for the association between the interleukin 7 receptor alpha (IL7RA) gene rs6897932 single nucleotide polymorphism (SNP) and multiple sclerosis (MS) risk. METHODS: Here, we performed a comprehensive systematic search in PubMed, Scopus, and Web of Science to find relevant studies published before November 2020 investigating the association between rs6897932 SNP and MS risk. In the pooled analysis, we determined the odds ratio (OR) and the corresponding 95% confidence interval (CI) for the association level between rs6897932 SNP and the risk of MS. RESULTS: In the current meta-analysis 33 case-control studies (30 articles) containing 19351 patients and 21005 healthy controls certify the inclusion criteria. According to the pooled analysis, a statistically significant association of IL7RA gene rs6897932 SNP with MS risk was found across recessive model (OR= 0.84, 95% CI= 0.77-0.92, P< 0.001, FEM), allelic model (OR= 0.91, 95% CI= 0.85-0.99, P= 0. 02, REM), TT vs. CC model (OR= 0.79, 95% CI= 0.67-0.93, P= 0.005, REM). Moreover, the subgroup analysis based on the ethnicity indicated a negative significant association in Europeans; dominant model (OR= 0.88, 95% CI= 0.78-1.01, P= 0.06, REM), recessive model (OR= 0.79, 95% CI= 0.71-0.88, P< 0.001, REM), allelic model (OR= 0.88, 95% CI= 0.81-0.96, P= 0.003, REM), TT vs. CC model (OR= 0.74, 95% CI= 0.61-0.88, P<0.001, REM) models. Nonetheless, no significant association was detected in Asians and Americans. CONCLUSIONS: IL7RA gene rs6897932 SNP decreases MS susceptibility in overall population and Europeans.

Effect of resveratrol on inflammatory cytokines: A meta-analysis of randomized controlled trials.

The aim of the current study was to perform a meta-analysis of randomized clinical trials regarding the effect of resveratrol in decreasing the levels of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in a combination of inflammatory diseases. Literature search was carried out in Scopus, ISI web of science, Medline, and Cochrane Library databases by up to September 2020. The pooled effect size was determined through measuring the weighted mean differences (WMD) and their corresponding 95% confidence intervals (CI) for the difference between the resveratrol-receiving and control groups. Finally, 33 publications, including 3 studies on IL-1, 26 studies on IL-6, 4 studies on IL-8, and 21 studies on TNF-α met our final inclusion criteria and included in the quantitative analysis. Analysis in the overall population showed a significant effect of resveratrol consumption in reducing serum TNF-α levels (WMD = -0.66 pg/ml, 95% CI = -1.05 to -0.27, P = 0.001). A significant reduction of IL-6 concentration was observed only in the patients receiving ≥500 mg/day dose of resveratrol (WMD = -1.89 pg/ml, 95% CI = -3.73 to -0.05, P = 0.04) with inter-study heterogeneity (I2 = 94.4%, P < 0.001). Nonetheless, no significant alteration was observed in IL-1 (WMD = -0.14 pg/ml, 95% CI = -0.31 to 0.03, P = 0.10) and IL-8 (WMD = 0.18 pg/ml, 95% CI = -1.04 to 1.40, P = 0.73) levels following resveratrol consumption. Based on the present findings, resveratrol is able to decrease TNF-α and IL-6 (in ≥500 mg/day dose) levels but not IL-1 and IL-8 levels.

Systematic review and meta-analytic findings on the association between killer-cell immunoglobulin-like receptor genes and susceptibility to pulmonary tuberculosis.

Several studies have evaluated the association between killer-cell immunoglobulin-like receptors (KIR) genes and susceptibility risk to tuberculosis (TB) infection. Nonetheless, their outcomes have not been conclusive and consistent. Here we implemented a systematic review and meta-analysis of KIR genes association to susceptibility risk of pulmonary TB (PTB) infection to attain a clear understanding of the involvement of these genes in susceptibility to PTB infection. A systematic search was conducted in the MEDLINE/PubMed and Scopus databases to find case-control studies published before November 2020. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated to determine the association between KIR genes and risk of PTB infection. After comprehensive searching and implementing the inclusion and exclusion criteria, 10 case-control studies were included in the meta-analysis. Four KIR genes were found to have significant positive association with PTB susceptibility risk of infection, including 2DL3 (OR = 1.454, 95% CI = 1.157-1.827; P = 0.001), 2DS1 (OR = 1.481, 95% CI = 1.334-1.837; P < 0.001), 2DS4 (OR = 1.782, 95% CI = 1.273-2.495; P = 0.001) and 3DL1 (OR = 1.726, 95% CI = 1.277-2.333; P < 0.001). However, the results showed that the remaining KIR genes (2DS2-4, 2DL1, 2, 4, 3DL1-2) and two pseudogenes (2DP1 and 3DP1) did not have significant associations with risk of PTB infection. This meta-analysis provides reliable evidence that the KIR genes 2DL3, 2DS1, 2DS4, and 3DL1 may be associated with an increased risk of PTB infection.