The p38 family of mitogen-activated protein kinases includes p38 alpha (SAPK2a, CSBP), p38 beta (SAPK2b), p38 delta (SAPK4), and p38 gamma (SAPK3/ERK6). p38 alpha and p38 beta are widely expressed p38 isoforms that are involved in regulation of cell proliferation, differentiation, development, and response to stress. Relatively less is known regarding the function of the p38 delta isoform. In this review, we discuss the role of the p38 alpha, p38 beta, and p38 gamma isoforms and then present recent findings that define a role for p38 delta as a regulator of differentiation-dependent gene expression in keratinocytes.
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http://dx.doi.org/10.1046/j.1523-1747.2003.12120.x | DOI Listing |
Eur J Pharmacol
January 2025
College of Korean Medicine, Gachon University, Seongnam 13120, Korea. Electronic address:
Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.
View Article and Find Full Text PDFMol Nutr Food Res
December 2024
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
The objective of this omega-3 feeding study was to elucidate the independent effects of α-linolenic acid (ALA) versus eicosapentaenoic (EPA)/docosahexaenoic acid (DHA) on visceral adiposity and inflammatory signaling in diet-induced obese delta-6 desaturase (Fads2) knockout (KO) mice. Male wildtype (WT) and Fads2 KO mice were fed a high-fat diet (45% kcal from fat) containing either lard (no omega-3s), flaxseed (ALA), or menhaden (EPA/DHA) for 21 weeks. Epididymal white adipose tissue (eWAT) was analyzed for changes in tissue weight, adipocyte size, triacylglycerol (TAG) and fatty acid content, and inflammatory markers.
View Article and Find Full Text PDFJ Med Chem
January 2025
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
Acute lung injury (ALI) is a disease characterized by pulmonary inflammation, blood barrier functional disorder, and hypoxemia. Herein, a series of 2-aminopyrimidine derivatives were synthesized. Most of them exhibited inhibitory effects on inflammatory cytokines IL-6 and IL-8 in human bronchial epithelial (HBE) cells at a concentration of 5 μM without significant cytotoxicity.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, India. Electronic address:
Dorzolamide (DZD), a Carbonic anhydrase (CA) inhibitor clinically used to lower intraocular pressure, exhibits anti-inflammatory effects owing to the drug's ability to inhibit the TIR domain-containing adaptor protein (TIRAP)-mediated signalling in macrophages. Here, we investigated whether DZD intermediates also demonstrate any anti-inflammatory property like DZD but with a reduced inhibition of CA. We found that several intermediates of DZD show increased binding to TIRAP at the common interface of kinases, such as Protein kinase C-delta (PKCδ) and Bruton's tyrosine kinase (BTK).
View Article and Find Full Text PDFJ Clin Endocrinol Metab
November 2024
Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.
Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n=3460; discovery cohort) and Rotterdam Study (RS; n=1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23,571 serum metabolomic spectral variables and incident T2DM.
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