Effect of metformin combined with clomiphene on insulin resistance, oxidative stress response and T cell immune response in patients with PCOS

Objective: To study the effect of metformin combined with clomiphene on insulin resistance, oxidative stress response and T cell immune response in patients with polycystic ovarian syndrome (PCOS). Methods: A total of 94 patients who were diagnosed with PCOS in Jingzhou Second People's Hospital between September 2014 and October 2016 were selected and randomly divided into the combined group who received the metformin combined with clomiphene therapy and the control group who received clomiphene therapy. The insulin resistance, oxidative stress response and T cell immune response were evaluated before treatment and 3 menstrual cycles after treatment. Results: 3 menstrual cycles after treatment, HOMA-IR level, serum F-Ins, F-CP, TOS, MDA, AOPP and IL-17 contents as well as peripheral blood RORγt mRNA expression of combined group were significantly lower than those before treatment while HOMA-β level, serum TAS, SOD, GSH-Px, VitC, VitE, IL-10 and TGF-β1 contents as well as peripheral blood Foxp3 mRNA expression were significantly higher than those before treatment;HOMA-IR and HOMA-β levels, serum F-Ins, F-CP, TOS, MDA, AOPP, IL-17, TAS, SOD, GSH-Px, VitC, VitE, IL-10 and TGF-β1 contents as well as peripheral blood Foxp3 and RORγt mRNA expression of control group were not different from those before treatment. Conclusion: Metformin combined with clomiphene can significantly improve the insulin resistance, oxidative stress response and T cell immune response in patients with PCOS.

Lnc-EST12,which is negatively regulated by mycobacterial EST12,suppresses antimycobacterial innate immunity through its interaction with FUBP3

Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of intracellular pathogens. However, the role andmechanism of the important lncRNAs in Mycobacterium tuberculosis (M.tb) infection remain largely unexplored. Recently, we foundthat a secreted M.tb Rv1579c (an early secreted target with a molecular weight of 12 kDa, named EST12) protein activates NLRP3-gasdermin D (GSDMD)-mediated pyroptosis and plays a pivotal role in M.tb-induced immunity. In the present study, M.tb and theEST12 protein negatively regulated the expression of a key lncRNA (named lnc-EST12) in mouse macrophages by activating theJAK2-STAT5a signaling pathway. Lnc-EST12, with a size of 1583 bp, is mainly expressed in immune-related organs (liver, lung andspleen). Lnc-EST12 not only reduces the expression of the proinflammatory cytokines IL-1β, IL-6, and CCL5/8 but also suppressesthe NLRP3 inflammasome and GSDMD pyroptosis-IL-1β immune pathway through its interaction with the transcription factor farupstream element-binding protein 3 (FUBP3). The KH3 and KH4 domains of FUBP3 are the critical sites for binding to lnc-EST12.Deficiency of mouse lnc-EST12 or FUBP3 in macrophages increased M.tb clearance and inflammation in mouse macrophages ormice. In conclusion, we report a new immunoregulatory mechanism in which mouse lnc-EST12 negatively regulates anti-M.tbinnate immunity through FUBP3.

Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

Human ficolin-2 is an important lectin complement pathway activator that is secreted from liver cells and has been implicated as an anti-infection innate immune molecule. However, the role of ficolin-2 protein and its dynamic changes over the course of and in the prognosis of chronic hepatitis B(CHB) and hepatocellular carcinoma(HCC) remain unclear. In this study, we analyzed ficolin-2 protein expression in a cohort of individuals with CHB infection, HCC and cirrhosis. A sandwich enzyme-linked immunosorbent assay(ELISA) method was used to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues was detected by immunohistochemical staining. Serum ficolin-2 concentrations in CHB patients were significantly higher than in healthy controls and HBV carriers. After 48 weeks of routine amelioration liver function treatment, serum ficolin-2 concentrations decreased and were positively correlated with favorable alanine aminotransferase(ALT), HBV DNA and HBe Ag-seroconversion outcomes. Interestingly, we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and cirrhosis compared with healthy controls. Our findings suggest that serum and intrahepatic ficolin-2 levels may be considered one of the indicators for the response of chronic HBV infection, HCC and cirrhosis.

Neamine-heterocycle conjugates as potential anti-HIV agents

A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV activity than neomycin B. The results suggested that it might be a promising approach to modify neamine for the discovery of new anti-HIV agents.