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Structure-activity relationship expansion and microsomal stability assessment of the 2-morpholinobenzoic acid scaffold as antiproliferative phosphatidylcholine-specific phospholipase C inhibitors.
RSC Med Chem
January 2025
School of Chemical Sciences, University of Auckland Auckland 1010 New Zealand
Dysregulation of choline phospholipid metabolism and overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in various cancers. Current known enzyme inhibitors include compounds based on a 2-morpholino-5--benzylamino benzoic acid, or hydroxamic acid, scaffold. In this work, 81 compounds were made by modifying this core structure to explore the pharmacophore.
View Article and Find Full Text PDFis overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression.
Burns Trauma
January 2025
Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Background: Keloids are disfiguring, fibrotic scar-like lesions that are challenging to treat and commonly recur after therapy. A deeper understanding of the mechanisms driving keloid formation is necessary for the development of more effective therapies. Reduced vitamin D receptor (VDR) expression has been observed in keloids, implicating vitamin D signaling in keloid pathology.
View Article and Find Full Text PDFmiR-129-5p targets HOXC10 to control BMSC adipogenesis and osteogenesis in a model of steroid-induced osteonecrosis of the femoral head.
Am J Transl Res
December 2024
Department of Orthopedics, Huai'an Hospital of Huai'an City Huai'an 223200, Jiangsu, China.
Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a pathological condition primarily driven by an impaired balance in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into adipogenic and osteogenic lineages. This study aimed to explore the role of miR-129-5p as a regulator of SONFH progression and associated mechanisms.
Methods: BMSCs were harvested from a rat SONFH model.
NOTCH1 regulates the DNA damage response and sorafenib resistance by activating ATM in hepatocellular carcinoma.
Am J Transl Res
December 2024
Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University 801 Heqing Road, Shanghai 200240, China.
Objective: This study investigates the mechanism underlying sorafenib resistance in hepatocellular carcinoma cells (HCC), focusing on DNA damage repair (DDR) pathways to develop targeted therapeutic strategies.
Methods: Bioinformatics analysis was used to screen genes associated with sorafenib resistance, which was further demonstrated by western blotting. Cell proliferation was determined using the EdU assay.
The High-Affinity IL-2 Receptor Affects White Matter Damage after Cerebral Ischemia by Regulating CD8 + T Lymphocyte Differentiation.
J Neuroimmune Pharmacol
January 2025
Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencing data of ischemic brain tissue revealed that most of the high-affinity IL-2R would be expressed by CD8 + T cells, especially by a highly-proliferative subset. Interestingly, only the CD8 + T cells with high-affinity IL-2R infiltrated ischemic brain tissues, highly expressing 32 genes (including Cdc20, Cdca3/5, and Asns) and activating 7 signaling pathways (including the interferon-alpha response pathway, a key mediator in the proliferation, migration, and cytotoxicity of CD8 + T cells).
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