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Phytosphingosine, a type of sphingolipids, has gained significant attention due to their diverse biological activities, including anti-inflammatory, anticancer, and immunomodulatory properties. These bioactive lipids, predominantly found in plant sources, play crucial roles in cellular signaling and membrane structure. In recent years, the chemical synthesis of phytosphingosine and other sphingolipids have become a major focus in organic chemistry due to the increasing demand for these molecules in pharmacological research and drug development. The synthesis of sphingosine has been extensively reported and is relatively straightforward to implement. However, the synthesis of phytosphingosine is more complex due to the presence of additional chiral centers, leading to a greater diversity of synthetic methods. This review provides a comprehensive overview of the recent advancements in synthetic methodologies for phytosphingosine and its analogs, including asymmetric synthesis and total synthesis using chiral auxiliaries and catalysts. By summarizing recent chemical synthesis advancements, this review serves as a valuable resource for researchers interested in the biological activities and synthetic aspects of phytosphingosine and other sphingolipids.
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http://dx.doi.org/10.1007/s41061-025-00518-8 | DOI Listing |
JCI Insight
September 2025
Division of Nephrology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States of America.
Background: Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects that attenuate acute kidney injury (AKI) in animal models.
Methods: We conducted a phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among 150 critically ill adult patients at high-risk of moderate-to-severe AKI. The primary endpoint was a hierarchical composite of death, kidney replacement therapy (KRT), and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure.
JCI Insight
September 2025
Department of Pharmacology, University of Michigan, Ann Arbor, United States of America.
Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes.
View Article and Find Full Text PDFJCI Insight
September 2025
Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, United States of America.
Impaired muscle regrowth in aging is underpinned by reduced pro-inflammatory macrophage function and subsequently impaired muscle cellular remodeling. Macrophage phenotype is metabolically controlled through TCA intermediate accumulation and activation of HIF1A. We hypothesized that transient hypoxia following disuse in old mice would enhance macrophage metabolic inflammatory function thereby improving muscle cellular remodeling and recovery.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America.
B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof.
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