Publications by authors named "Satoshi Shigeno"
Intrahepatic Exhausted Antiviral Immunity in an Immunocompetent Mouse Model of Chronic Hepatitis B.
Cell Mol Gastroenterol Hepatol
December 2024
Article Synopsis
- Researchers developed a new mouse model to study chronic hepatitis B (CHB) by delivering the HBV genome and a key enzyme, allowing for detailed immune profiling in a lab setting.
- The CHB mice showed ongoing HBV infection and had signs of exhausted immune cells, with treatments using IFNα and a TLR7 agonist leading to viral suppression and immune enhancement.
- This study's mouse model mimics immune exhaustion seen in CHB patients and suggests that targeted treatments could help restore immune function against HBV.
Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.
Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.
Article Synopsis
- Approximately 250 million people globally are chronically infected with hepatitis B virus (HBV), which is linked to liver cancer but its integration into cancer cells isn't fully understood.
- Researchers aimed to find vulnerability factors related to HBV-infected liver cancer using CRISPR technology, focusing on the differences between normal and HBV-integrated liver cells.
- Four key genes were identified as potential vulnerability factors, with INSIG2 playing a significant role in inhibiting cell growth specifically in HBV-integrated liver cells by causing cell cycle arrest through a CDK2-dependent mechanism.
Background: Pancreatitis is known to be an important risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the exact molecular mechanisms of how inflammation promotes PDAC are still not fully understood. Regnase-1, an endoribonuclease, regulates immune responses by degrading mRNAs of inflammation-related genes.
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- - Current treatments for hepatitis B virus (HBV) do not effectively remove its DNA form (cccDNA), but researchers are exploring the use of the CRISPR/Cas9 system to target and reduce cccDNA levels.
- - The study found that inhibiting DNA repair processes, particularly those handled by PARP2 and DNA Ligase 4, can enhance the effectiveness of CRISPR in reducing HBV replication markers in infected liver cells.
- - Additionally, using the PARP inhibitor olaparib further boosted the effectiveness of CRISPR by lowering levels of HBV-related RNA and cccDNA, highlighting a potential new combination therapy for HBV.
Background And Aims: Intrahepatic cholangiocarcinoma (ICC) is a deadly but poorly understood disease, and its treatment options are very limited. The aim of this study was to identify the molecular drivers of ICC and search for therapeutic targets.
Approach And Results: We performed a Sleeping Beauty transposon-based in vivo insertional mutagenesis screen in liver-specific Pten -deficient mice and identified TNF receptor-related factor 3 ( Traf3 ) as the most significantly mutated gene in murine ICCs in a loss-of-function manner.