Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles.

In this letter, we comment on the article by Xuan Yuan , published in the recent issue of the . Mixed lineage kinase domain-like protein (MLKL) exhibits cell-type-specific functions in liver parenchymal and non-parenchymal cells, playing dual roles in the pathogenesis of liver diseases. In hepatocytes, MLKL primarily mediates necroptosis and inhibits autophagy, thereby exacerbating liver injury.

Research progress on the roles of complement in liver injury.

The complement system is crucial for maintaining immunological homeostasis in the liver, playing a significant role in both innate and adaptive immune responses. Dysregulation of this system is closely linked to the pathogenesis of various liver diseases. Modulating the complement system can affect the progression of these conditions.

polysaccharides alleviate metabolic dysfunction-associated steatotic liver disease through enhancing hepatocyte RelA/ HNF1α signaling.

Background: polysaccharides (BSP) have antioxidant, immune regulation, and anti-fibrotic activities. However, the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease (MASLD) have not been fully understood.

Aim: To investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclear factor kappa B p65 (RelA)/hepatocyte nuclear factor-1 alpha (HNF1α) signaling.

Journey to diagnosis: An unfinished exploration of IgG4-related sclerosing cholangitis.

IgG4-related sclerosing cholangitis (IgG4-SC) is an inflammatory disease that leads to bile duct stricture, characterized by the infiltration of IgG4-positive plasma cells into the bile duct wall, thickening of the bile duct wall, and narrowing of the lumen. The differential diagnosis of IgG4-SC mainly includes primary sclerosing cholangitis, cholangiocarcinoma, and pancreatic cancer. IgG4-SC is often associated with autoimmune pancreatitis and can be accurately diagnosed based on clinical diagnostic criteria.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

Background: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear.

Aim: To determine the role and mechanism of UGT1A1 in liver damage progression.

Link between mutations in and genes and chronic intestinal ulcers: A case report and review of literature.

Background: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 () and phospholipase A2 group IVA () genes and review the available relevant literature.

Case Summary: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools.

The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury.

Aim: To investigate the effect of the gp130/STAT3-endoplasmic reticulum (ER) stress axis on hepatocyte necroptosis during acute liver injury.

Methods: ER stress and liver injury in LO2 cells were induced with thapsigargin, and in BALB/c mice with tunicamycin and carbon tetrachloride (CCl4). Glycoprotein 130 (gp130) expression, the degrees of ER stress, and hepatocyte necroptosis were assessed.

Postoperative jaundice related to and gene mutations: A case report and literature review.

Background: Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery. However, some patients may develop postoperative complications, liver failure, and other life-threatening situations. Here, we report a patient with mutations in the uridine 5'-diphospho-glucuronosyltransferase 1A1 () and bile salt export pump (adenosine triphosphate-binding cassette subfamily B member 11, ) genes who presented multiple intrahepatic bile duct stones and cholestasis, and the jaundice of the patient increased after partial hepatectomy.

Three-in-one incidence of hepatocellular carcinoma, cholangiocellular carcinoma, and neuroendocrine carcinoma: A case report.

Background: Primary hepatic neuroendocrine carcinoma (NEC) is rare, and a combination with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is extremely rare. To date, only four combination cases have been reported. The present paper describes the fifth patient.

Relationship of familial cytochrome P450 4V2 gene mutation with liver cirrhosis: A case report and review of the literature.

Background: Many genetic and metabolic diseases affect the liver, but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns. There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods.

Case Summary: We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema, abdominal distension, cirrhosis, and hypothyroidism.

Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

Background: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies.

Aim: To investigate whether and how AFP could regulate ER stress and hepatocyte injury.

Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model.

Background: Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor).

Inhibition of eIF2 Dephosphorylation Protects Hepatocytes from Apoptosis by Alleviating ER Stress in Acute Liver Injury.

Objectives: Protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2) is an important factor along the main pathways for endoplasmic reticulum (ER) stress-mediated apoptosis. In this study, we investigated the effects of eIF2 phosphorylation on hepatocyte apoptosis and the ER stress mechanisms in acute liver injury.

Methods: eIF2 phosphorylation and apoptosis under ER stress were monitored and measured in male BALB/c mice with acute liver injury and human hepatocyte line LO2 cells.

Phosphorylation of eIF2α mitigates endoplasmic reticulum stress and hepatocyte necroptosis in acute liver injury.

Introduction And Objectives: Necroptosis and endoplasmic reticulum (ER) stress has been implicated in acute and chronic liver injury. Activated eukaryotic initiation factor 2 alpha (eIF2α) attenuates protein synthesis and relieves the load of protein folding in the ER. In this study, we aimed to analyze the impact of eIF2α phosphorylation on hepatocyte necroptosis in acute liver injury.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection.

Background: Acute exacerbation in patients with chronic hepatitis B virus (HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation (HD) and acute-on-chronic liver failure (ACLF) in patients with severe acute exacerbation (SAE) of chronic HBV infection remain unknown.

Aim: To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.

Prostaglandin E1 protects hepatocytes against endoplasmic reticulum stress-induced apoptosis via protein kinase A-dependent induction of glucose-regulated protein 78 expression.

Aim: To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms.

Methods: Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment.