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 role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target.

Liver disease is a common and serious threat to human health. The progression of liver diseases is influenced by many physiologic processes, including oxidative stress, inflammation, bile acid metabolism, and autophagy. Various factors lead to the dysfunction of these processes and basing on the different pathogeny, pathology, clinical manifestation, and pathogenesis, liver diseases are grouped into different categories.

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.

Pharmacological targeting of gastric mucosal barrier with traditional Chinese medications for repairing gastric mucosal injury.

The gastric mucosa (GM) is the first barrier and vital interface in the stomach that protects the host from hydrochloric acid in gastric juice and defends against exogenous insults to gastric tissues. The use of traditional Chinese medications (TCMs) for the treatment of gastric mucosal injury (GMI) has long-standing history and a good curative effect. Whereas there are poor overall reports on the intrinsic mechanisms of these TCM preparations that pharmacology uses to protect body from GMI, which is crucial to treating this disease.

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.

Effects of Naltrexone on Expression of Lipid Metabolism-Related Proteins in Liver Steatosis Induced by Endoplasmic Reticulum Stress in Mice.

This study aimed to explore the effect of naltrexone on the expression of lipid metabolism-related proteins in liver steatosis induced by endoplasmic reticulum stress in mice. Thirty inbred mice (C57BL/6J) were divided into three groups: group A (normal control group), group B (model control), and group C (naltrexone group). The male mice in group A were fed a regular diet, and the mice in groups B and C were fed a high-fat diet.

Mechanisms by Which Traditional Chinese Medicines Influence the Intestinal Flora and Intestinal Barrier.

The effect of a drug on the intestinal flora and the intestinal barrier is an important evaluation index for drug safety and efficacy. Chemical synthetic drugs are widely used due to their advantages of fast efficacy and low doses, but they are prone to cause drug resistance and inhibit proton pumps, which may harm intestinal health. Traditional Chinese medicine (TCM) has been applied clinically for thousands of years, and how TCMs regulate intestinal health to achieve their effects of disease treatment has become a hot research topic that needs to be resolved.

Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice.

Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis.

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.

Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury.

Aim: To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration.

Methods: Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsigargin to induce endoplasmic reticulum (ER) stress.

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.

Development and validation of a scoring system to predict progression to acute-on-chronic liver failure in patients with acute exacerbation of chronic hepatitis B.

Aim: The aim of this study was to develop and validate a scoring system to predict the progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) of chronic hepatitis B (CHB).

Methods: The baseline characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280 and 194 patients were randomly assigned to the derivation and validation cohorts, respectively. Univariate risk factors associated with ACLF development were entered into a multivariate logistic regression.

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.