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| http://dx.doi.org/10.1186/s12943-022-01673-y | DOI Listing |
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AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.
J Hepatol
January 2025
MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA.
Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.
View Article and Find Full Text PDFKi-67 and CDK1 Control the Dynamic Association of Nuclear Lipids with Mitotic Chromosomes.
J Lipid Res
December 2024
Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan. Electronic address:
Nuclear lipids play roles in regulatory processes such as signaling, transcriptional regulation, and DNA repair. In this report, we demonstrate that nuclear lipids may contribute to Ki-67-regulated chromosome integrity during mitosis. In COS-7 cells, nuclear lipids are enriched at the perichromosomal layer and excluded from intrachromosomal regions during early mitosis, but are then detected in intrachromosomal regions during late mitosis, as revealed by TT-ExM, an improved expansion microscopy technique that enables high-sensitivity, super-resolution imaging of proteins, lipids, and nuclear DNA.
View Article and Find Full Text PDFMolecular profiling unveils pyroptosis markers in preterm birth.
FASEB J
December 2024
Department of Clinical Laboratory, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China.
Through a comprehensive examination of pyroptosis-related differential expressed genes (PRDEGs), this work investigates the molecular complexities of spontaneous preterm birth (SPTB), also known as premature delivery, before the due date. Through the process of merging and correcting batch effects in the GSE120480 and GSE73714 datasets, we were able to identify 36 PRDEGs that exhibited significant expression differentiation in SPTB. Through functional enrichment and pathway analysis, their importance in amino acid transport and cytokine receptor interaction has been highlighted.
View Article and Find Full Text PDFCD36 inhibition corrects lipid-FetuinA mediated insulin secretory defects by preventing intracellular lipid accumulation and inflammation in the pancreatic beta cells.
Biochim Biophys Acta Mol Basis Dis
February 2025
Cell Signaling Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati University, Santiniketan 731235, India. Electronic address:
Article Synopsis
- CD36 is a protein that helps with fat uptake and immune response, and it's found to be more active in the pancreatic islets of obese diabetic people, which can lead to issues with insulin secretion.
- The study found that when beta cells were exposed to a combination of palmitate (a fatty acid) and fetuinA (a protein linked to inflammation), it triggered an inflammatory response that worsened lipid buildup and insulin secretion problems.
- Inhibiting CD36 or the inflammatory receptor TLR4 helped reduce this lipid accumulation and restored insulin secretion in beta cells, indicating that targeting CD36 could be a potential treatment for obesity-related beta cell dysfunction.
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