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Spatial multi-omics characterizes GPR35-relevant lipid metabolism signatures across liver zonation in MASLD.
Life Metab
December 2024
Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and cancer. The zonal distribution of biomolecules in the liver is implicated in mediating the disease progression. Recently, G-protein-coupled receptor 35 (GPR35) has been highlighted to play a role in MASLD, but the precise mechanism is not fully understood, particularly, in a liver-zonal manner.
View Article and Find Full Text PDFPreviously, our metabolomic, transcriptomic, and genomic studies characterized the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease, and we demonstrated that FTY720, a sphingosine-1-phospahate receptor modulator approved for treatment of multiple sclerosis, recovers synaptic plasticity and memory in APP/PS1 mice. To further investigate how FTY720 rescues the pathology, we performed metabolomic analysis in brain, plasma, and liver of trained APP/PS1 and wild-type mice. APP/PS1 mice showed area-specific brain disturbances in polyamines, phospholipids, and sphingolipids.
View Article and Find Full Text PDFBlockade of TIPE2-Mediated Ferroptosis of Myeloid-Derived Suppressor Cells Achieves the Full Potential of Combinatory Ferroptosis and Anti-PD-L1 Cancer Immunotherapy.
Cells
January 2025
Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Although immune checkpoint blockade (ICB) therapy has attained unprecedented clinical success, the tolerance and immune suppression mechanisms evolved by tumor cells and their tumor microenvironment (TME) hinder its maximum anti-cancer potential. Ferroptosis therapy can partially improve the efficacy of ICB, but it is still subject to immune suppression by myeloid-derived suppressor cells (MDSCs) in the TME. Recent research suggests that an MDSC blockade can unleash the full therapeutic potential of the combined therapy of ferroptosis and ICB in liver cancer treatment.
View Article and Find Full Text PDFVCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8T cells function in the HCC microenvironment.
Signal Transduct Target Ther
January 2025
Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
CD8T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8T cells suppression in hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFHepatotoxic effects of environmentally relevant concentrations of polystyrene microplastics on senescent Zebrafish (Danio rerio): Patterns of stress response and metabolomic alterations.
Aquat Toxicol
January 2025
College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China. Electronic address:
The hepatotoxicity of microplastics (MPs) has garnered increasing attention, but their effects on elderly organisms remain inadequately characterized, particularly concerning hepatic stress response patterns in environmental conditions. In this study, a 10-day exposure period of elderly zebrafish to polystyrene microplastics (PS-MPs, 1 µm) was conducted, with exposure concentrations set at 5.6 × 10 µg/L, 5.
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