Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-β), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.
Introduction: Grasslands harbor complex bacterial communities, whose dynamic interactions are considered critical for organic matter and nutrient cycling. However, less is known about how changes in precipitation impact bacterial interactions.Methods: We conducted precipitation manipulation experiments in the Eastern Eurasian Steppe in China and constructed co-occurrence networks for bacterial communities.Results: The network topological features of the bacterial communities exhibited considerable differences among increased precipitation, control, and decreased precipitation gradients. The bacterial co-occurrence pattern in the increased precipitation gradient was the most complex and stable, with a large network size, followed by those of the control and decreased precipitation gradients. Soil moisture (SM) was the primary factor influencing the complexity, size, and stability of bacterial networks across different precipitation gradients, followed by total nitrogen (TN), belowground biomass, aboveground biomass, and total carbon (TC).Discussion: Our results indicate that drought conditions reduce the complexity and stability of the bacterial community, and future changes in precipitation will greatly reshape bacterial interactions in semiarid grasslands. Overall, these findings could enhance our understanding of how microbes respond to changing precipitation patterns by regulating their interactions in water-limited ecosystems and will improve our ability to predict the impacts of precipitation regime change on ecosystem nutrient cycling and feedback between ecosystem processes and global climate change.