Rheumatoid arthritis (RA) is a systematical autoimmune disease, characterized by chronic synovial joint inflammation and hurt. Porphyromonas gingivalis(P. gingivalis) can cause life-threatening inflammatory immune responses in humans when the host pathogenic clearance machinery is disordered. Some epidemiological studies have reported that P. gingivalis exposure would increase the prevalence of RA. However, the results remain inconsistent. Therefore, a meta-analysis was done to systematically analyze the relationship between P. gingivalis exposure and the prevalence of rheumatoid arthritis. Database including Cochrane Library, Web of Science, PubMed, and EMBASE were searched for published epidemiological articles assessed the relationship between P. gingivalis and RA. Obtained studies were screened based on the predefined inclusion and exclusion criteria. The overall Odds Ratios (ORs) of incorporated articles were pooled by random-effect model with STATA 15.1 software. The literature search returned a total of 2057 studies. After exclusion, 28 articles were included and analyzed. The pooled ORs showed a significant increase in the risk of RA in individuals with P. gingivalis exposure (OR = 1.86; 95% CI: 1.43-2.43). Subgroup analysis revealed that pooled ORs from populations located in Europe (OR = 2.17; 95% CI: 1.46-3.22) and North America (OR = 2.50; 95% CI: 1.23-5.08) were significantly higher than that from population in Asia (OR = 1.11; 95% CI: 1.03-1.20). Substantial heterogeneity was observed but did not significantly influence the overall outcome. In conclusion, our results indicated P. gingivalis exposure was a risk factor in RA. Prompt diagnosis and management decisions on P. gingivalis antimicrobial therapy would prevent rheumatoid arthritis development and progression.

Destructions in the intestinal ecosystem are implicated with changes in slow transit constipation (STC), which is a kind of intractable constipation characterized by colonic motility disorder. In order to deepen the understanding of the structure of the STC gut microbiota and the relationship between the gut microbiota and fecal metabolites, we first used 16S rRNA amplicon sequencing to evaluate the gut microbiota in 30 STC patients and 30 healthy subjects. The α-diversity of the STC group was changed to a certain degree, and the β-diversity was significantly different, which indicated that the composition of the gut microbiota of STC patients was inconsistent with healthy subjects. Among them, Bacteroides, Parabacteroides, Desulfovibrionaceae, and Ruminiclostridium were significantly upregulated, while Subdoligranulum was significantly downregulated. The metabolomics showed that different metabolites between the STC and the control group were involved in the process of bile acids and lipid metabolism, including taurocholate, taurochenodeoxycholate, taurine, deoxycholic acid, cyclohexylsulfamate, cholic acid, chenodeoxycholate, arachidonic acid, and 4-pyridoxic acid. We found that the colon histomorphology of STC patients was significantly disrupted, and TGR5 and FXR were significantly downregulated. The differences in metabolites were related to changes in the abundance of specific bacteria and patients’ intestinal dysfunction. Analysis of the fecal genomics and metabolomics enabled separation of the STC from controls based on random forest model prediction [STC vs. control (14 gut microbiota and metabolite biomarkers)—Sensitivity: 1, Specificity: 0.877]. This study provided a perspective for the diagnosis and intervention of STC related with abnormal bile acid metabolism.

Various studies are being conducted on oncolytic virotherapy which one of the mechanisms is mediating interferon (IFN) production by it exerts antitumor effects. The antiviral effect of IFN itself has a negative impact on the inhibition of oncolytic virus or tumor eradication. Therefore, it is very critical to understand the mechanism of IFN regulation by oncolytic viruses, and to define its mechanism is of great significance for improving the antitumor effect of oncolytic viruses. This review focuses on the regulatory mechanisms of IFNs by various oncolytic viruses and their combination therapies. In addition, the exerting and the producing pathways of IFNs are briefly summarized, and some current issues are put forward.

Novel coronavirus pneumonia (COVID-19) is spreading worldwide, causing great harm and stress to humans. Since patients with novel coronavirus (SARS-CoV-2) have a high probability of developing acute respiratory distress syndrome (ARDS) in severe cases, the pathways through which SARS-CoV-2 causes lung injury have become a major concern in the scientific field. In this paper, we investigate the relationship between SARS-CoV-2 and lung injury and explore the possible mechanisms of COVID-19 in ARDS from the perspectives of angiotensin-converting enzyme 2 protein, cytokine storm, activation of the immune response, triggering of Fas/FasL signaling pathway to promote apoptosis, JAK/STAT pathway, NF-κB pathway, type I interferon, vitamin D, and explore the possibility of prevention and treatment of COVID-19. To explore the possibility of SARS-CoV-2, and to provide new ideas to stop the development of ARDS in COVID-19 patients.

Macrophages are involved in hepatocyte steatosis and necroinflammation and play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Impaired autophagy function (decreased autophagy or blocked autophagic flow) leads to cell damage and death and promotes NAFLD progression. The experimental and clinical research of glycyrrhetinic acid (GA) in the treatment of NAFLD has gradually attracted attention with clear pharmacological activities such as immune regulation, antiviral, antitumor, antioxidant, liver protection, and anti-inflammatory. However, the effects of GA on the STAT3-HIF-1α pathway and autophagy in macrophages are still unclear, and its mechanism of action in the treatment of NAFLD remains to be further elucidated. We constructed a NAFLD mouse model through a high-fat and high-sugar diet to investigate the therapeutic effects of GA. The results showed that GA reduced weight, improved the pathological changes and hepatic lipid deposition of liver, and abnormally elevated the levels of serum biochemical (AST, ALT, TG, T-CHO, LDL-C, and HDL-C) and inflammatory indexes (IL-1β, IL-4, IL-6, MCP-1, and TNF-α) in NAFLD mice. Further examination revealed that GA ameliorates excessive hepatic macrophage infiltration and hepatocyte apoptosis. The results of the cell experiments further elaborated that GA modulated the PA-induced macrophage STAT3-HIF-1α pathway and ameliorated impaired autophagic flux (blockade of autophagosome–lysosome fusion) and overactivation of inflammation. Excessive hepatocyte apoptosis caused by the uncontrolled release of inflammatory cytokines was also suppressed by GA.Conclusion: This study demonstrated that GA could regulate the STAT3-HIF-1α pathway of macrophages, ameliorate the impaired autophagy flux, and reduce the excessive production of inflammatory cytokines to improve the excessive apoptosis of liver cells, thus playing a therapeutic role on NAFLD.