novel coronavirus disease, SARS-CoV-2, cytokine storm, MSC-therapy COVID-19 pandemic has accounted for ~ 4.3 million confirmed cases and ~ 292,000 deaths (till 12 th May, 2020) across the globe since its outbreak. Several anti-viral drugs such as RNA dependent RNA polymerase inhibitors (remdesivir, favipiravir, ribavirin), protease inhibitors (lopinavir, ritonavir) and drugs targeting endocytic pathway (hydroxychloroquine) are being evaluated for COVID-19 but standard therapeutics yet not available. Severe health deterioration in critically ill patients is characterized by pulmonary edema, severe respiratory distress, cytokine storm and septic shock. To combat cytokine storm, immune-therapy targeting IL-1, IL-2, IL-6 and TNFα are being evaluated and one of the promising immune-modulator is the mesenchymal stem cells (MSCs) that can surmount the severity of COVID-19 infections. Recent studies have shown that MSC-therapy significantly dampens the cytokine storm in critically ill COVID-19 patients. This communication endows with the insight of stem cell therapy and summarizes the recent studies on COVID-19 patients.
There are a plethora of publications on the role of miRNA gene polymorphism and its association with recurrent pregnancy loss (RPL), but a lack of uniformity in the studies available due to the variable subject population, heterogeneity and contrary results of significance. Rigorous data mining was done through PubMed, SCOPUS, Cochrane library, Elsevier and Google Scholar to extract the studies of interest published until June 2021. A total of eight SNPs of miRNAs have been included, where ≥2 studies per SNPs were available. Analysis was done on the basis of pooled odds ratios and 95% CI. This is the first meta-analysis on miRNA SNPs in RPL that suggests that rs11614913, rs3746444 and rs2292832 biomarkers may decrease the risk of RPL under different genetic models.
Kawasaki disease (KD) is a common childhood systemic vasculitis with a special predilection for coronary arteries. Even after more than five decades of the initial description of the disease, the etiology of KD remains an enigma. This transcriptome data re-analysis study aimed to elucidate the underlying pathogenesis of KD using a bioinformatic approach to identify differentially expressed genes (DEGs) to delineate common pathways involved in KD. Array datasets from the Gene Expression Omnibus database were extracted and subjected to comparative meta-analysis for the identification of prominent DEGs. Fifteen hub genes with high connectivity were selected from these DEGs (IL1B, ITGAM, TLR2, CXCL8, SPI1, S100A12, MMP9, PRF1, TLR8, TREM1, CD44, UBB, FCER1G, IL7R, and FCGR1A). Of these 15 genes, five genes (CXCL8, FCGR1A, IL1B, TLR2, and TLR8) were found to be involved in neutrophil degranulation. To gain further insight into the molecular mechanism, a protein–protein network was established. Significantly enriched pathways based on the above-mentioned genes were mainly centered on biological regulation and signaling events. In addition, the pathway analysis also indicated that the majority of the DEGs in KD were enriched in systemic lupus erythematosus, suggesting a strong interplay between immunological and genetic factors in the pathogenesis of KD. These findings could significantly aid in identifying therapeutic targets and understanding KD biosignatures to design a biomarker panel for early diagnosis and severity of the disease.
Background Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). The worldwide prevalence of SHOX variations in ISS varies from 2.5–15%. This study aims to assess the implication of SHOX variation in ISS in North India and its overall prevalence in Asian population. Methods SHOX gene analysis carried out by Multiplex ligation dependent probe amplification (MLPA) followed by Sanger sequencing in 54 patients with variable phenotypes. Meta-analysis was done to evaluate its prevalence which comprises 11 previous studies including present, carried out on a total of 979 participants. Results SHOX gene analysis resulted in 12.9% of positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in female sex (P-value: 0.047). Short arms and forearms were the only significantly associated trait seen in 51.85% of children. We have found a rare association of multiple exostosis with LWD in a child with deletion. The prevalence of SHOX variation came as 15.2% in Asians. No significant difference was found in geographical region-specific analysis. Conclusion This meta-analysis compiles findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients.
Treg cells play an important role in development of tolerance in maternal immune system against the semi-allogenic embryo. Human forkhead box protein 3 (FOXP3) gene, is the major transcription factor responsible for the regulation of Treg function during pregnancy. Single nucleotide polymorphisms (SNPs) of FOXP3 gene have been reported as a risk factor for Recurrent Pregnancy Loss (RPL), however, results from previous studies are inconsistent. In this meta-analysis, we collected data from different studies to investigate the overall association of FOXP3 SNPs with risk of RPL. PubMed, Google Scholar, Elsevier, and Cochrane databases were searched to identify eligible studies. Odds Ratio (OR) and 95% Confidence Interval (CI), calculated via fixed effect or random effect models, were used to evaluate strength of association. This meta-analysis included 11 studies (1383 RPL cases and 1413 controls) of 6 SNPs: rs3761548 A/C, rs2232365 A/G, rs2294021 T/C, 2280883 T/C, rs5902434del/ATT and rs141704699 C/T, with ≥ 2 studies per SNPs and at least 1 significant result. We observed that FOXP3 polymorphism was predominantly present in Asian women with history of RPL. rs2232365 A/G, rs3761548 A/C, rs2294021 T/C, rs2280883 T/C and rs5902434del/ATT polymorphisms were significantly associated with risk of RPL in Indian population. Further, among the most commonly seen polymorphism, rs3761548 A/C was significantly associated with risk of RPL in women from Kazakhstan, China and Gaza, Palestine; rs2232365 A/G in populations of Kazakhstan, Egypt, Iran and Gaza, Palestine. Results of this study indicates that FOXP3 polymorphism is significantly associated with risk of RPL, especially in Asians.
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