A novel coronavirus disease 2019 (COVID-19) emerged around December 2019 in Wuhan, China and has spread rapidly worldwide ( Lu et al., 2020). Until March 27, 2020, the Chinese health authorities had reported 82082 confirmed COVID-19 cases in China with 3298 deaths and 381443 confirmed cases with 20787 deaths outside China. The World Health Organization (WHO) named the virus SARS-CoV-2, which belongs to a distinct clade from the human severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) ( Zhu et al., 2020). At present, there is no effective therapy against this new virus. Identifying effective antiviral agents to treat the COVID-19 is of most urgency.

Background: Previous studies have linked gut microbiota with cancer etiology, but the associations for specific gut microbiota are causal or owing to bias remain to be elucidated.Methods: We performed a two‐sample Mendelian randomization (MR) analysis to assess the causal effect of gut microbiota on cancer risk. Five common cancers, including breast, endometrial, lung, ovarian, and prostate cancer as well as their subtypes (sample sizes ranging from 27,209 to 228,951) were included as the outcomes. Genetic information for gut microbiota was obtained from a genome‐wide association study (GWAS) comprising 18,340 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the robust adjusted profile scores, weighted median, and MR Egger used as supplementary methods for causal inference. Sensitivity analyses including the Cochran Q test, Egger intercept test, and leave‐one‐out analysis were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was performed to evaluate the direct causal effects of gut microbiota on the risk of cancers.Results: UVMR detected a higher abundance of genus Sellimonas predicted a higher risk of estrogen receptor‐positive breast cancer (OR = 1.09, 95% CI 1.05–1.14, p = 2.01 × 10⁻⁵), and a higher abundance of class Alphaproteobacteria was associated with a lower risk of prostate cancer (OR = 0.84, 95% CI 0.75–0.93, p = 1.11 × 10⁻³). Sensitivity analysis found little evidence of bias in the current study. MVMR further confirmed that genus Sellimonas exerted a direct effect on breast cancer, while the effect of class Alphaproteobacteria on prostate cancer was driven by the common risk factors of prostate cancer.Conclusion: Our study implies the involvement of gut microbiota in cancer development, which provides a novel potential target for cancer screening and prevention, and might have an implication for future functional analysis.

Obesity increases the morbidity and severity of asthma, with poor sensitivity to corticosteroid treatment. Metformin has potential effects on improving asthma airway inflammation. Regulatory T cells (Tregs) play a key role in suppressing the immunoreaction to allergens. We built an obese asthmatic mouse model by administering a high‐fat diet (HFD) and ovalbumin (OVA) sensitization, with daily metformin treatment. We measured the body weight and airway inflammatory status by histological analysis, qRT‐PCR, and ELISA. The percentage of Tregs was measured by flow cytometry. Obese asthmatic mice displayed more severe airway inflammation and more significant changes in inflammatory cytokines. Metformin reversed the obese situation and alleviated the airway inflammation and remodelling with increased Tregs and related transcript factors. The anti‐inflammatory function of metformin may be mediated by increasing Tregs.

Background:Asthma is a complex respiratory disease characterized by airway inflammation and remodeling. MicroRNAs (miRNAs) mediate various cellular processes including macrophage polarization and play an important role in the pathogenesis of asthma. In present study, we aimed to screen miRNA profiling involved in macrophage polarization and investigate its possible functions and mechanisms.Methods:An OVA-sensitized mouse model was established and 2-chloroadenosine (2-CA) was used to interfere with macrophages. The airway inflammation and remodeling were assessed. The identification and function of M2 alveolar macrophages were assessed by flow cytometry, RT-qPCR, arginase activity and co-culture experiment. Microarray screening was used to select miRNAs which were related to macrophage polarization and RNA interference (RNAi) technique was performed to confirm the function of the selected miRNA and its target gene.Results:Alveolar macrophages of asthmatic mice showed significant M2 polarization. 2-CA alleviated airway inflammation and remodeling as well as M2 polarization.In vitro, IL-4-induced M2 macrophages promoted the proliferation of α-SMA-positive cells. And miRNA profiling showed a remarkable increased expression of miR-378a-3p in IL-4 induced M2 macrophages. Dual luciferase reporter assay confirmed growth factor receptor binding protein 2 (GRB2) was a target gene of miR-378a-3p. A miR-378a-3p inhibitor and knockdown of GRB2 repolarized alveolar macrophages from M1 to M2 phenotype.Conclusion:Our findings suggest that miR-378a-3p/GRB2 pathway regulates the polarization of alveolar macrophages which acts as a potential therapeutic target for airway inflammation and remodeling in asthma.

Exosomes derived from Mesenchymal Stem Cells (MSCs) possesses similar immunomodulatory effect as MSCs. It had been suggested that MSCs exosomes contain higher level of miR-1470 compared to exosomes derived from fibroblast. Here, we show that MSCs exosomal miR-1470 can elevate the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in asthmatic patients. Moreover, mechanistic studies revealed that miR-1470 can promote the upregulation of P27KIP1 by directly targeting the 3' region of c-Jun mRNA. Furthermore, miR-1470 mimic transfection could significantly upregulate the proportion of CD4+CD25+FOXP3+ Tregs in CD4+ T cells. P27KIP1 knockdown via siRNA silencing significantly inhibited the proportion of CD4+CD25+FOXP3+ Tregs with over-expression of miR-1470, which indicates that miR-1470 induces the differentiation of CD4+CD25+FOXP3+ Tregs through P27KIP1.