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The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression. Consequently, elucidating the specific roles of the STING signaling pathway and ferroptosis in vivo is vital for targeted disease intervention. This review systematically examines the interactions between the cGAS-STING signaling pathway and ferroptosis, highlighting their influence on disease progression in the contexts of inflammation, injury, and cancerous cell dynamics. Understanding these interactions may provide novel therapeutic strategies. The STING pathway has been implicated in the regulation of various cell death mechanisms, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Our focus primarily addresses the role and mechanism of the cGAS-STING signaling pathway and ferroptosis in diseases, limiting discussion of other cell death modalities and precluding a comprehensive overview of the pathway's additional functions.
BACKGROUND The study aimed to investigate the effects of accident pregnancy CHB ([Chronic Hepatitis](http://www.baidu.com/link?url=bHvatnxYLAbcjw_Xc6Po2pWn-j8Cw8-V01IB9mGZLaFAS63z43BHW-ZECROGrZEeOOjAJDQ1ICVf3GKfmBN7GfifgilBQbCFlMWNkzl8Daa0vxsvMG9VXI7dE_T8X4Tf) B) patients’ reproductive age on their offspring during entecavir (ETV) antiviral therapy due to lacking related data. METHODS 112 couples were divided into case and control groups. 53 couples who had accident pregnancies while receiving long-term ETV antiviral medication were recruited for the case group. 53 of them, including HBsAg-positive dads (11/53, 20.7%). The control group comprised 59 couples who became pregnant accidentally while receiving long-term TDF antiviral treatment. Of them,59 couples, including HBsAg-positive dads (25.4%, 15/59), All mothers persisted in their pregnancies in the case group, and ETV was promptly replaced with TDF. Every mother remained pregnant and continued to use TDF in the control group. All newborns received immunoprophylaxis. RESULTS The maternal and baby safety profiles, including the prevalence of congenital disabilities, were comparable across the case and control groups at delivery. In addition, no unusual indications or symptoms of the newborns were noted during the follow-up intervals of 28, 48, and 96 weeks postpartum. The current study had a 100% success rate in preventing mother-to-child transmission. CONCLUSIONS Initiating ETV or TDF in early and middle pregnancy seems to be safe for both mothers and infants and is effective. Important data from our investigation support using ETV in early-mid gestational accident pregnancies and the prompt substitution of TDF antiviral medication for ETV. The pregnancy was not needed to be terminated.
Abstract In recent years, hepatitis B virus (HBV) core protein allosteric modulators (CpAMs) have become a hot spot to develop new anti‐HBV drugs. Sulfonamide analogues are a new class of CpAMs targeting HBV core protein (Cp), while their biological activity is still needed to be improved and the binding mechanism is unclear still. In this study, we utilized molecular docking and molecular dynamics simulation to explore the binding mode between the novel compounds and HBV Cp. Combining with binding free energy calculation and decomposition, we inferred that TyrE132, ValE124, ThrE128, ThrD109, and IleD105 were key residues during the binding process, and especially, the conformational change of TryE132 was responsible for the stable binding. Besides, reasonable CoMFA ( q 2 = 0.515, r 2 ncv = 0.994, and r 2 pred = 0.628) and CoMSIA ( q 2 = 0.602, r 2 ncv = 0.988, and r 2 pred = 0.681) models were constructed to explore the 3D structure‐activity relationship of the novel compounds. The results suggested that it was favorable to increase the biological activity of sulfonamide analogues when introducing hydrophobic groups to R 1 and electronegative groups to R 2 . In conclusion, we explored the binding mode and structure‐activity relationship between sulfonamides and HBV Cp and provided a theoretical basis for the optimization of this series of compounds.
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