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Introduction: Endometriosis is a prevalent and recurrent medical condition associated with symptoms such as pelvic discomfort, dysmenorrhea, and reproductive challenges. Furthermore, it has the potential to progress into a malignant state, significantly impacting the quality of life for affected individuals. Despite its significance, there is currently a lack of precise and non-invasive diagnostic techniques for this condition.Methods: In this study, we leveraged microarray datasets and employed a multifaceted approach. We conducted differential gene analysis, implemented weighted gene co-expression network analysis (WGCNA), and utilized machine learning algorithms, including random forest, support vector machine, and LASSO analysis, to comprehensively explore senescence-related genes (SRGs) associated with endometriosis.Discussion: Our comprehensive analysis, which also encompassed profiling of immune cell infiltration and single-cell analysis, highlights the therapeutic potential of this gene assemblage as promising targets for alleviating endometriosis. Furthermore, the integration of these biomarkers into diagnostic protocols promises to enhance diagnostic precision, offering a more effective diagnostic journey for future endometriosis patients in clinical settings.Results: Our meticulous investigation led to the identification of a cluster of genes, namely BAK1, LMNA, and FLT1, which emerged as potential discerning biomarkers for endometriosis. These biomarkers were subsequently utilized to construct an artificial neural network classifier model and were graphically represented in the form of a Nomogram.

Abstract The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

A defining unique characteristic of the gut immune system is its ability to respond effectively to foreign pathogens while mitigating unnecessary inflammation. Intestinal macrophages serve as the cornerstone of this balancing act, acting uniquely as both the sword and shield in the gut microenvironment. The GI tract is densely innervated by the enteric nervous system (ENS), the intrinsic nervous system of the gut. Recent advances in sequencing technology have increasingly suggested neuroimmune crosstalk as a critical component for homeostasis both within the gut and in other tissues. Here, we systematically review the ENS–macrophage axis. We focus on the pertinent molecules produced by the ENS, spotlight the mechanistic contributions of intestinal macrophages to gut homeostasis and inflammation, and discuss both existing and potential strategies that intestinal macrophages use to integrate signals from the ENS. This review aims to elucidate the complex molecular basis governing ENS–macrophage signaling, highlighting their cooperative roles in sustaining intestinal health and immune equilibrium. [ABSTRACT FROM AUTHOR]

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP–AMP synthase (cGAS)‐stimulator of interferon gene (STING) signaling pathway has been identified as a DNA‐sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS‐STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING‐induced Interferon beta production remain unknown. We report that HPV18 E7 selectively antagonizes STING‐triggered nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF‐κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING‐triggered NF‐κB activation is related to HPV pathogenicity but not E7–Rb binding. HPV18 E7, severe acute respiratory syndrome coronavirus‐2 open reading frame 3a, human immunodeficiency virus‐2 viral protein X, and Kaposi's sarcoma‐associated herpesvirus KSHV viral interferon regulatory factor 1 selectively inhibited STING‐triggered NF‐κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS‐STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus‐induced tumor diseases. [ABSTRACT FROM AUTHOR]