Project description:Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH.
Project description:Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH.
Project description:Patients with alcohol-associated liver cirrhosis (AC) may develop severe alcohol-associated hepatitis (sAH), but the mechanisms underlying the transition from AC to sAH still remain unclear. We performed single cell RNA (scRNA) sequencing analysis of livers and peripheral white blood cells (WBC) from sAH and AC patients. We found that the significant difference between sAH and AC was that sAH livers had a markedly higher number of neutrophil subsets than AC livers. Thus, we further focused on the neutrophil cluster and found two distinct sAH-specific liver neutrophils are notably characterized by heightened expression of CXCL8 (IL-8) defined as IL-8+ neutrophils blood. Our current study has demonstrated that sAH had self-sustaining IL-8+ neutrophil accumulation that likely drives inexorable liver inflammation and failure in sAH. Based on our study, we believe targeting IL-8+ neutrophils is a promising therapeutic strategy for sAH.
Project description:We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues. 12 HCC Samples
Project description:We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues.