MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells.

Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen-specific T cells due to a breach of immune tolerance. Studies in immunometabolism demonstrate that activated T cells harbor increased levels of reactive oxygen species that cause oxidative DNA damage. In this study, we assessed the potential of DNA damage repair enzyme MutT homolog 1 (MTH1) as a therapeutic target in AIH and karonudib as a novel drug for patients with AIH.

Case Report: Response With Immunotherapy in a Patient With Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder.

Background: Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 2% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are sporadic.

Case Presentation: A 56-year-old woman admitted to our hospital due to right upper abdominal pain of 3 days duration.

XRCC2 repairs mitochondrial DNA damage and fuels malignant behavior in hepatocellular carcinoma.

The effects of DNA damage repair (DDR) and mitochondrial dysfunction associated with HCC have been investigated, but the functional role of mitochondrial DDR in HCC remains elusive. We studied the DDR genes and identified XRCC2 as a potential prognostic marker for HCC. XRCC2 overexpression was detected in HCC cells and shown to promote the malignant behavior of cancer cells.

Karonudib is a promising anticancer therapy in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent.

Inhibition of glycogen synthase kinase 3β protects liver against ischemia/reperfusion injury by activating 5' adenosine monophosphate-activated protein kinase-mediated autophagy.

Aim: Autophagy has been found to play an important role in hepatic ischemia/reperfusion (I/R) injury. Our previous study has also clarified that rictor deficiency aggravated hepatic I/R injury by suppressing autophagy. Here, we explore whether autophagy participates in glycogen synthase kinase 3β (GSK3β)-mediated cytoprotection in liver I/R.

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling.

Background/aims: The role of Rictor in hepatic ischemia/reperfusion (I/R) injury remains unknown. Here, we comprehensively examined the role of Rictor in hepatic I/R injury.

Methods: We studied the expression of Rictor during hepatic I/R injury.

Inhibition of GSK-3β induces AP-1-mediated osteopontin expression to promote cholestatic liver fibrosis.

The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs.

Hypoxia-inducible factor-2α promotes hepatocyte apoptosis during cholestasis.

Aim: Hypoxia-inducible factor-2α (HIF-2α) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF-2α in cholestasis-mediated hepatocyte apoptosis.

Methods: Hypoxia-inducible factor-2α expression was measured by immunohistochemistry and confocal microscopy.

Contrast-enhanced micro-computed tomography using ExiTron nano6000 for assessment of liver injury.

Aim: To explore the potential of contrast-enhanced computed tomography (CECT) using ExiTron nano6000 for assessment of liver lesions in mouse models.

Methods: Three mouse models of liver lesions were used: bile duct ligation (BDL), lipopolysaccharide (LPS)/D-galactosamine (D-GalN), and alcohol. After injection with the contrast agent ExiTron nano6000, the mice were scanned with micro-CT.

Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis.

Aim: To determine the risk factors for new-onset diabetes mellitus (NODM) after liver transplantation by conducting a systematic review and meta-analysis.

Methods: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data.

A Potential Profibrogenic Role of Biliary Epithelium-Derived Cardiotrophin-1 in Pediatric Cholestatic Liver Disease.

As a cytokine of the interleukin-6 family, cardiotrophin-1 (CT-1) has been shown to be an important endogenous protector in liver injury. Our study aimed to investigate the role of CT-1 in liver fibrosis in pediatric cholestatic liver disease (PCLD). CT-1 mRNA and protein expression levels were upregulated in PCLD liver biopsy tissues compared with controls.