Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Characterization of the Intestinal Microbiome in Healthy Adults over Sars-Cov-2 Vaccination.

BACKGROUND: In response to the outbreak of coronavirus disease 2019 (COVID-19) worldwide, inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are implemented. Dysbiosic gut microbiota is implicated in the COVID-19 patients. Whereas, how intestinal microbiota are affected by vaccination remains elusive, and it is important to investigate the microbial shifts during vaccines treatment. METHODS: In the present study, we assessed the gut microbial composition in healthy adults, and performed comparison before and post an inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV vaccination. RESULTS: Microbial diversity in shannon, pielou evenness, simpson and invsimpson index was remarkably suppressed by vaccination. Ruminococcus and Actinomyces were observed to be strikingly deficient, and Faecalibacterium was dramatically augmented after BBIBP-CorV treatment. Potential functional profiles of gut microbiome in amino acid metabolism, lipid biosynthesis proteins and steroid biosynthesis were remarkably increased, while the capacity in renin-angiotensin system was remarkably decreased following vaccines. CONCLUSIONS: Our study suggests that inactivated BBIBP-CorV against SARS-CoV-2 could elicit modulations on gut microbial composition and functions, which might favor host immune response and protect from COVID-19.

Cardiovascular complications of SARS-CoV-2 infection (COVID-19): a systematic review and meta-analysis.

Coronavirus Disease 2019 (COVID-19) originated in Wuhan, China in December 2019 and rapidly spread worldwide. Herein, we conducted a systematic review and meta-analysis to find the association between COVID-19 and cardiovascular complications. We conducted a systematic literature search of the PubMed and Embase databases from 01 December 2019 to 30 November 2020. We then statistically analyzed the incidence of cardiovascular complications in COVID-19 patients. We included 3044 confirmed COVID-19 cases from 12 studies. The most common cardiovascular complications in COVID-19 patients were myocardial injury (21.2%, 95% CI 12.3-30.0%) and arrhythmia (15.3%, 95% CI 8.4-22.3%), followed by heart failure (14.4%, 95% CI 5.7-23.1%) and acute coronary syndrome (1.0%, 95% CI 0.5-1.5%). The pooled incidence of heart failure, arrhythmia and myocardial injury in non-survivors were 47.8% (95% CI 41.4-54.2%), 40.3% (95% CI 1.6-78.9%) and 61.7% (95% CI 46.8-76.6%), respectively. Also, the data separately showed significantly higher incidence of heart failure and cardiac injury in non-survivors (relative risks = 5.13, 95% CI 2.46-10.7, Z = 4.36, P = 0.017) and (relative risks = 6.91, 95% CI 3.19-14.95, Z = 4.91, P = 0.009). Myocardial injury and arrhythmia were the most common complications in COVID-19 patients. Myocardial injury and heart failure were more common in patients who died, regardless of a history of cardiovascular disease. The incidence of heart failure and myocardial injury were higher in non-survivors compared to the survivors. Accordingly, in addition to basic support, cardiac reactions of patients with confirmed COVID-19 with or without underlying cardiovascular diseases should be closely monitored.

The Elabela-APJ axis: a promising therapeutic target for heart failure.

Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin-APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA-APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA-APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA-APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA-apelin-APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.