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Abstract: Co-inhibitory signals from the B7 superfamily have been demonstrated to induce T cell dysfunction in chronic HBV infection (CHB). However, the expression and function of Z39Ig, a new inhibitor of the B7 superfamily, is still unclear in CHB. Here immunohistochemical staining showed that Z39Ig was restricted to macrophages and that its level was decreased significantly in CHB patients compared to healthy controls. Moreover, reduced Z39Ig expression was positively correlated with plasma HBV load but was inversely related to serum alanine aminotransaminase levels. Further, Z39Ig mRNA had a negative relation to IFN-γ in vivo, and IFN-γ also down-regulated Z39Ig expression on monocyte-derived macrophages (MDMs) in a time- and dose-dependent manner in vitro. Interestingly, Z39Ig expression on MDMs was restored when IFN-γ neutralizing antibodies were added to the T cell/MDM co-culture system, indicating that the IFN-γ derived from activated-T cells may contribute to the reduction of Z39Ig in the CHB environment. Our results suggest that T cells can opposite T cell hyporesponsiveness through dampening Z39Ig inhibitory signals from macrophages and thus maintain their anti-viral function in CHB. Therefore, decreasing Z39Ig signals from macrophages could contribute to CHB clinical therapy. [Copyright &y& Elsevier]

Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group , Alloprevotella , and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group , Alloprevotella , and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis. • Sotagliflozin ameliorated cardiac function and depression-like behaviors induced by myocardial infarction (MI). • Sotagliflozin restored the altered composition of the gut microbiota in an animal model of MI. • Gut microbiota contributed to the beneficial effects of sotagliflozin on MI mice. • Sotagliflozin improved the condition of mice with MI through the gut-heart-brain axis. [ABSTRACT FROM AUTHOR]

Abstract: Increased lymphocyte apoptosis has been suggested to contribute to the development of systemic lupus erythematosus (SLE), but the critical factors involved in the apoptotic pathways are still unknown. By long serial analysis of gene expression (LongSAGE) profiles and microarray analyses, a novel apoptosis-related gene BclGL expression was found significantly increased in peripheral blood CD4+ T cells of SLE patients, which was correlated with the enhanced CD4+ T cells apoptosis, anti-nuclear antibody (ANA) titer and proteinuria. In vitro, BclGL expression could be specially upregulated by SLE serum stimulation and positively correlated with induced CD4+ T cell apoptosis. Enforcing BclGL overexpression by lentivirus could directly enhance CD4+ T cell apoptosis, but these apoptosis-inducing effects could be partially inhibited by knockdown of BclGL expression. Collectively, these results indicate that increased BclGL expression may contribute to the aberrant CD4+ T cell apoptosis which causes an inappropriate immune response and impaired homeostasis in SLE. [Copyright &y& Elsevier]