The Burden of Nonmalignant Metabolic Dysfunction-Associated Steatotic Liver Disease in the Western Pacific Region: A Systematic Analysis From 1990 to 2021.

The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, yet there is little understanding in the Western Pacific Region (WPR). This study aims to report the latest MASLD burden in the WPR from 1990 to 2021. This study obtained nonmalignant and total MASLD incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years of healthy life lost due to disability (YLDs) from the Global Burden of Disease (GBD) database, and calculated age-standardized ratios (ASRs) for each indicator.

Biliary YB-1/GLI2 axis facilitates ductular reaction and promotes HSC activation via SPP1/integrin αvβ1 signaling during liver fibrogenesis.

Background And Aims: Emerging evidence suggests that ductular reactive cells (DRCs)-mediated ductular reaction (DR) accelerates the activation of HSCs and contributes to liver fibrogenesis. Previous studies implicated Y-box binding protein 1 (YB-1) in promoting DRC expansion. This study aims to investigate the mechanisms underlying YB-1-mediated DR and its role in HSC activation.

YBX1/CD36 positive feedback loop-mediated lipid accumulation drives metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disorder mainly caused by an imbalance in lipid homeostasis. Y-box binding protein 1 (YBX1) participates in multiple pathophysiological processes, including embryonic development, tissue repair, liver disorders, and energy metabolism. The objective of this study is to investigate the mechanisms underlying MASLD and characterize the role of YBX1 in MASLD.

Hydronidone ameliorates liver fibrosis by inhibiting activation of hepatic stellate cells via Smad7-mediated degradation of TGFβRI.

Background And Purpose: Liver fibrosis is a wound-healing reaction that eventually leads to cirrhosis. Hydronidone is a new pyridine derivative with the potential to treat liver fibrosis. In this study, we explored the antifibrotic effects of hydronidone and its potential mode of action.

Escherichia coli Promotes Endothelial to Mesenchymal Transformation of Liver Sinusoidal Endothelial Cells and Exacerbates Nonalcoholic Fatty Liver Disease Via Its Flagellin.

Unlabelled: BACKGROUND＆AIMS: Gut bacteria translocate into the liver through a disrupted gut vascular barrier, which is an early and common event in the development of nonalcoholic fatty liver disease (NAFLD). Liver sinusoidal endothelial cells (LSECs) are directly exposed to translocated gut microbiota in portal vein blood. Escherichia coli, a commensal gut bacterium with flagella, is markedly enriched in the gut microbiota of patients with NAFLD.

FABP4 in LSECs promotes CXCL10-mediated macrophage recruitment and M1 polarization during NAFLD progression.

Background And Aims: Non-alcoholic liver disease (NAFLD) is emerging as the leading cause of end-stage liver disease with a serious threat to global health burden. Fatty acid-binding protein 4 (FABP4) is closely associated with metabolic syndromes. We aimed to explore the potential mechanisms of FABP4 in NAFLD progression.

NDH-1L with a truncated NdhM subunit is unstable under stress conditions in cyanobacteria.

Cyanobacterial NdhM, an oxygenic photosynthesis-specific NDH-1 subunit, has been found to be essential for the formation of a large complex of NDH-1 (NDH-1L). The cryo-electron microscopic (cryo-EM) structure of NdhM from showed that the N-terminus of NdhM contains three β-sheets, while two α-helixes are present in the middle and C-terminal part of NdhM. Here, we obtained a mutant of the unicellular cyanobacterium 6803 expressing a C-terminal truncated NdhM subunit designated NdhMΔC.

Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression.

Liver non-parenchymal cells (NPCs) play a critical role in the progression of non-alcoholic steatohepatitis (NASH). We aimed to explore the heterogeneity of NPCs and identify NASH-specific subpopulations contributing to NASH progression. Through single-cell RNA sequencing, we uncovered a proinflammatory subpopulation of Itgad/Fcrl5 macrophages with potential function of modulating macrophage accumulation and promoting NASH development.

Yes-associated protein promotes the proliferation and differentiation of liver progenitor cells during liver fibrosis.

Liver fibrosis is closely related to the proliferation and differentiation of liver progenitor cells (LPCs). Yes-associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood.

Identification of LBH and SPP1 involved in hepatic stellate cell activation during liver fibrogenesis.

Liver fibrosis is a pathological response driven by the activation of hepatic stellate cell (HSC). However, the mechanisms of liver fibrosis and HSC activation are complicated and far from being fully understood. We aimed to explore the candidate genes involved in HSC activation during liver fibrogenesis.

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis.

Liver fibrosis is a common outcome of the pathological progression of chronic liver disease; however, no specific and effective therapeutic agent has been approved for its treatment. We investigated the effects of Kuhuang on liver fibrosis and the underlying mechanisms of action. To induce hepatic fibrosis, either 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet was administered, or bile duct ligation (BDL) surgery was performed on C57BL/6 mice.

YAP affects the efficacy of liver progenitor cells transplantation in CCl-induced acute liver injury.

The liver is a highly regenerative organ. During acute liver injury, the remaining hepatocytes rapidly proliferate to restore liver parenchyma and liver function. However, hepatocytes-driven regeneration is compromised in severe liver injury; instead, liver progenitor cells (LPCs) proliferate and differentiate into hepatocytes or cholangiocytes to restore mass and function of liver.

Loss of YB-1 alleviates liver fibrosis by suppressing epithelial-mesenchymal transition in hepatic progenitor cells.

Previously, we reported that the nuclear translocation of Y-box binding protein 1 (YB-1) is induced by transforming growth factor-β (TGF-β) and promotes hepatic progenitor cells (HPCs) expansion. Here, we explored the mechanisms underlying YB-1 translocation and the impact of YB-1 on the epithelial-mesenchymal transition (EMT) in HPCs. YB-1cre (YB-1cre) mice and YB-1cre mice were fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or a choline-deficient, ethionine-supplemented (CDE) diet.

Specific knockdown of Y-box binding protein 1 in hepatic progenitor cells inhibits proliferation and alleviates liver fibrosis.

The proliferation of hepatic progenitor cells (HPCs) contributes to liver regeneration and fibrogenesis during chronic liver injury; however, the mechanism modulating HPC proliferation remains unknown. Y-box binding protein-1 (YB-1) is a transcription factor that regulates the transcription of several genes and is highly expressed in liver injury. We explored the role of YB-1 in HPC proliferation and liver fibrosis.

Dextran Sulfate Sodium Salt-Induced Colitis Aggravates Gut Microbiota Dysbiosis and Liver Injury in Mice With Non-alcoholic Steatohepatitis.

Inflammatory bowel disease (IBD) is characterized by gut microbiota dysbiosis, which is also frequently observed in patients with non-alcoholic fatty liver disease. Whether gut microbiota dysbiosis in IBD patients promotes the development of non-alcoholic steatohepatitis (NASH) remains unclear. We aimed to explore the role of gut microbiota dysbiosis in the development of NASH in mice with dextran sulfate sodium salt (DSS) induced colitis.

TGF-β/YB-1/Atg7 axis promotes the proliferation of hepatic progenitor cells and liver fibrogenesis.

Hepatic fibrosis is characterized by excessive extracellular matrix deposition and ductular reactions, manifested as the expansion of hepatic progenitor cells (HPCs). We previously reported that the Y-box binding protein 1 (YB-1) in HPCs is involved in chronic liver injury. In this study, we constructed YB-1 Foxl1-Cre mice and investigated the role of YB-1 in HPC expansion in murine choline-deficient, ethionine-supplemented (CDE), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) models.

miR-30c inhibits angiogenesis by targeting delta-like ligand 4 in liver sinusoidal endothelial cell to attenuate liver fibrosis.

Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR-30c in attenuating liver fibrosis.

Antihepatic Fibrosis Drugs in Clinical Trials.

Liver fibrosis is not an independent disease. It refers to the abnormal proliferation of connective tissues in the liver caused by various pathogenic factors. Thus far, liver fibrosis has been considered to be associated with a set of factors, such as viral infection, alcohol abuse, non-alcoholic fatty liver disease, and autoimmune hepatitis, as well as genetic diseases.

Rapamycin Alleviates Hypertriglyceridemia-Related Acute Pancreatitis via Restoring Autophagy Flux and Inhibiting Endoplasmic Reticulum Stress.

Hypertriglyceridemia (HTG) can aggravate acute pancreatitis (AP), but its pathogenesis remains unclear. As autophagic activity is closely related to lipid metabolism and AP, we investigated the autophagic response in models of AP aggravated by HTG and explored whether rapamycin has a protective effect against HTG-related pancreatitis. HTG-associated AP models were established in vivo in rats and in vitro.

Paneth Cell Ablation Aggravates Pancreatic and Intestinal Injuries in a Rat Model of Acute Necrotizing Pancreatitis after Normal and High-Fat Diet.

We previously reported that acute necrotizing pancreatitis (ANP) after normal or high-fat diet is associated with a decreased number of Paneth cells in ileal crypts. Here, we ablated Paneth cells in a rat model of ANP after normal and high-fat diet to investigate the effects on disease symptoms. Adult male Sprague-Dawley rats received standard rat chow or a high-fat diet for 2 weeks, after which they were treated with dithizone to deplete Paneth cells.

Paneth cell ablation increases the small intestinal injury during acute necrotizing pancreatitis in rats.

The present work aimed to investigate the role of Paneth cells in small intestinal injury during acute necrotizing pancreatitis (ANP) using rat models established by injection of dithizone, a metal chelator of zinc with the ability to selectively ablate Paneth cells. Sprague‑Dawley rats were randomly divided into four groups: Sham‑operated group, ANP group (3.5% sodium taurocholate solution, 1 ml/kg body weight), dithizone group (100 mg/kg of body weight) and ANP + dithizone group (sodium taurocholate solution was administered 6 h after dithizone injection).

Commensal Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells.

An increase of was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether MG1655, an commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.