Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has killed over 2.5 million people worldwide, but effective care and therapy have yet to be discovered. We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients. MAIN TEXT: We searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients. A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis. Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group [odds ratio (OR) = 0.70, 95% confidential interval (C): 0.54-0.90, P = 0.007]. Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation (OR = 0.59, 95% CI, 0.37-0.93, P = 0.02). Among stratified analyses, reduction of overall mortality correlates with tocilizumab treatment in patients less than 65 years old (OR = 0.68, 95% CI: 0.60-0.77, P < 0.00001), and with intensive care unit patients (OR = 0.62, 95% CI: 0.55-0.70, P < 0.00001). Pooled estimates of hazard ratio showed that tocilizumab treatment predicts better overall survival in COVID-19 patients (HR = 0.45, 95% CI: 0.24-0.84, P = 0.01), especially in severe cases (HR = 0.58, 95% CI 0.49-0.68, P < 0.00001). CONCLUSIONS: Our study shows that tocilizumab treatment is associated with a lower risk of mortality and mechanical ventilation requirement among COVID-19 patients. Tocilizumab may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases. This systematic review provides an up-to-date evidence of potential therapeutic role of tocilizumab in COVID-19 management.

Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke.

To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.

The Treg/Th17 paradigm in lung cancer.

Pathogenic mechanisms underlying the development of lung cancer are very complex and not yet entirely clarified. T lymphocytes and their immune-regulatory cytokines play a pivotal role in controlling tumor growth and metastasis. Following activation by unique cytokines, CD4+ T helper cells differentiate into Th1, Th2, Th17, and regulatory T cells (Tregs). Traditionally, research in lung cancer immunity has focused almost exclusively on Th1/Th2 cell balance. Recently, Th17 cells and Tregs represent an intriguing issue to be addressed in lung cancer pathogenesis. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against tumor cells. Th17 cells directly or via other proinflammatory cytokines modulate antitumor immune responses. Notably, there is a close relation between Tregs and Th17 cells. However, the possible interaction between these subsets in lung cancer remains to be elucidated. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent a useful tool for lung cancer treatment in the future. The purpose of this review is to discuss recent findings of the role of these novel populations in lung cancer immunity and to highlight the pleiotropic effects of these subsets on the development and regulation of lung cancer.

3-nitrotyrosine, a biomarker for cardiomyocyte apoptosis induced by diabetic cardiomyopathy in a rat model.

The aim of this study was to investigate whether 3-nitrotyrosine (3-NT) may serve as a predictive biomarker for cardiomyocyte apoptosis in a diabetic cardiomyopathic rat model. Using male Sprague-Dawley (SD) rats in a prospective, randomized, controlled study, a diabetic type II animal model was established by injection with streptozotocin. The diabetic group and the diabetic cardiomyopathy (DCM) group were administered valsartan. This study revealed the following: i) The ratio of heart/body weight increased in the DCM, diabetes administered with valsartan (D+V) and DCM+V groups compared with the N group. ii) The expression index (EI) of 3-NT correlated positively with the apoptotic index (AI) of the cardiomyocytes, whereas 3-NT in the serum did not reflect changes in the AI. iii) The AI of the DCM group was the highest of the assessed groups. The AI of the DCM group was higher than that in the D+V group, and the AI of the DCM+V group was higher than that of the N group. iv) The EI of 3-NT increased with a higher AI. The higher the EI of 3-NT, the higher the AI observed in rat cardiomyocytes. Both the EI of 3-NT and the AI of the DCM group were higher than in the other groups. However, both the EI of 3-NT and the AI in the DCM group markedly decreased for the DCM+V group. 3-NT in the myocardial tissue of rats was deemed to be a successful biomarker for predicting cardiomyocyte apoptosis in SD rats. 3-NT levels were significantly increased and related to cardiomyocyte apoptosis. Valsartan post-treatment reversed the increase of 3-NT and apoptosis in diabetic cardiomyopathy.