Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.
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http://dx.doi.org/10.1002/advs.202403095 | DOI Listing |
Arch Toxicol
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Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic and Polyclinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.
The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).
View Article and Find Full Text PDFBest Pract Res Clin Gastroenterol
December 2024
Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Acute liver failure (ALF) is defined as the loss of hepatic function in conjunction with hepatic encephalopathy and coagulopathy. There is histological evidence of profound hepatocyte damage. If it is not aggressively managed, ALF can be fatal within a few days.
View Article and Find Full Text PDFCell Biol Toxicol
December 2024
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 13850 E. Montview Blvd, Box C238/V20-3128, Aurora, CO, 80045, USA.
Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease.
View Article and Find Full Text PDFImmunobiology
December 2024
Department of Clinical Laboratory, Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei 230601, Anhui, China. Electronic address:
Background & Aims: HBV-related acute-on-chronic liver failure (HBV-ACLF) is a severe acute liver injury secondary to HBV-related chronic liver disease (with or without cirrhosis) and is characterized by a high short-term mortality rate. Presently, there is a paucity of experimental models that specifically focus on HBV-ACLF based on chronic hepatitis B. Therefore, this study aimed to establish an experimental mouse model of HBV-ACLF using chronic hepatitis B (CHB) as a basis and investigate the impact of STING activation on the disease.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2024
The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China; Shanghai Key Laboratory of Birth Defect, Shanghai 201102, China. Electronic address:
Background: Ubiquitin-specific protease 53 (USP53) deficiency is associated with familial intrahepatic cholestasis in which serum gamma-glutamyl transferase (GGT) activity is relatively low. However, how USP53 deficiency contributes to cholestasis is obscure. No animal model has been reported.
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