The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease may lead to finding potential drug targets and biomarkers. Here, we applied weighted gene co-expression network analysis and LIME as an explainable artificial intelligence algorithm to comprehensively characterize transcriptional changes in bronchial epithelium cells (primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study detected a network that significantly correlated to the pathogenicity of COVID-19 infection based on identified hub genes in each cell line separately. The novel hub gene signature that was detected in our study, including PGLYRP4 and HEPHL1, may shed light on the pathogenesis of COVID-19, holding promise for future prognostic and therapeutic approaches. The enrichment analysis of hub genes showed that the most relevant biological process and KEGG pathways were the type I interferon signaling pathway, IL-17 signaling pathway, cytokine-mediated signaling pathway, and defense response to virus categories, all of which play significant roles in restricting viral infection. Moreover, according to the drug–target network, we identified 17 novel FDA-approved candidate drugs, which could potentially be used to treat COVID-19 patients through the regulation of four hub genes of the co-expression network. In conclusion, the aforementioned hub genes might play potential roles in translational medicine and might become promising therapeutic targets. Further in vitro and in vivo experimental studies are needed to evaluate the role of these hub genes in COVID-19.
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients’ anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can’t excrete excess iron from the bloodstream. To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (βTM) patients. We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (βTM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses. Seventy–four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3–62.6) and in male was higher than female (61.9%, 95% CI 53.4–69.7 vs. 50.9%, CI 41.8–59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8–84 vs. 33.1%, CI 9.4–70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16–40.8). Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients’ complications.
14 September 2019 in Critical Reviews in Toxicology
Introduction: Tramadol is a synthetic opioid which is commonly used around the world to relieve moderate to severe pain. One of the serious possible complications of its use is seizures. The present study aims to investigate and summarize the studies related to tramadol and occurrences of seizures after tramadol use and factors influencing these seizures. Methodology: Our systematic review is compliant with PRISMA guidelines. Two researchers systematically searched PubMed/Medline, Web of Sciences, and Scopus. Cohort, case-control, cross-sectional studies, and clinical trials. The risk of bias was assessed using the Newcastle–Ottawa Scale After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed with using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn. Results: A total of 51 articles with total sample size of 101 770 patients were included. The results showed that seizure event rate in the subgroups of tramadol poisoning, therapeutic dosage of tramadol, and tramadol abusers was 38% (95% CI: 27–49%), 3% (95% CI: 2–3%), 37% (95% CI: 12–62%), respectively. Tramadol dose was significantly higher in the patients with seizures than those without (mean differences: 0.82, CI 95%: 0.17–1.46). The odds for occurrence of seizures were significantly associated with male gender (pooled OR: 2.24, CI 95%: 1.80–2.77). Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15–1.49). Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration. Given that, most of the evidence derives from studies utilizing a cross-sectional design, the association of tramadol with seizures should not be considered to be definitively established
28 August 2012 in DARU Journal of Pharmaceutical Sciences
Immune thrombocytopenia (ITP) is an immune disorder commonly presents as isolated thrombocytopenia. Generally corticosteroids are the main treatment of ITP. This study was designed to evaluate effectiveness of high dose dexamethasone comparing conventional corticosteroid therapy in the treatment of ITP.