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Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.
Hepatol Commun
December 2024
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.
View Article and Find Full Text PDFWeight cycling exacerbates glucose intolerance and hepatic triglyceride storage in mice with a history of chronic high fat diet exposure.
J Transl Med
January 2025
Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Background: Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.
View Article and Find Full Text PDFContribution of extracellular vesicles to neuroinflammation and cognitive and motor deficits in hyperammonemia and hepatic encephalopathy.
Extracell Vesicles Circ Nucl Acids
January 2024
Laboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia 46012, Spain.
Cirrhotic patients can present hepatic encephalopathy (HE), showing motor and cognitive deficits. Hyperammonemia and peripheral inflammation are known to induce neuroinflammation and alter neurotransmission, which finally induces neurological impairment in HE. However, the mechanisms by which the deleterious effects of peripheral inflammation are transmitted to the brain are not well understood.
View Article and Find Full Text PDFExtracellular vesicles from mesenchymal stem cells improve neuroinflammation and neurotransmission in hippocampus and cognitive impairment in rats with mild liver damage and minimal hepatic encephalopathy.
Stem Cell Res Ther
December 2024
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, 46012, Valencia, Spain.
Background: Patients with steatotic liver disease may show mild cognitive impairment. Rats with mild liver damage reproduce this cognitive impairment, which is mediated by neuroinflammation that alters glutamate neurotransmission in the hippocampus. Treatment with extracellular vesicles (EV) from mesenchymal stem cells (MSC) reduces neuroinflammation and improves cognitive impairment in different animal models of neurological diseases.
View Article and Find Full Text PDFSingle-dose tolerability and pharmacokinetics of leritrelvir in Chinese patients with hepatic impairment and healthy matched controls.
Antimicrob Agents Chemother
December 2024
Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child-Pugh A) hepatic impairment, eight with moderate (Child-Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups.
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