Current Opinion in Endocrinology Diabetes and Obesity, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 20, 2024
This review highlights emerging evidence supporting the premise of precision diabetes care including but not limited to monogenic and discuss potential opportunities, challenges, limitations for clinical adoption.
Language: Английский
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102480 - 102480
Published: Sept. 3, 2024
Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.
Language: Английский
Citations
14
Kidney International Reports, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Citations
1
Science Advances, Journal Year: 2024, Volume and Issue: 10(49)
Published: Dec. 4, 2024
Angiopoietin-like 4 (ANGPTL4), a key protein involved in lipoprotein metabolism, has diverse effects. There is an association between Angptl4 and diabetic kidney disease; however, this not been well investigated. We show that both podocyte- tubule-specific ANGPTL4 are crucial fibrogenic molecules diabetes. Diabetes accelerates the phenotype control mice but mutant mice. The protective effect observed correlated with reduction stimulator of interferon genes pathway activation, expression pro-inflammatory cytokines, reduced epithelial-to-mesenchymal transition endothelial-to-mesenchymal transition, lessened mitochondrial damage, increased fatty acid oxidation. Mechanistically, we demonstrate or tubule-secreted interacts Integrin β1 influences dipeptidyl-4 β1. utility targeted pharmacologic therapy specifically inhibits gene kidneys protects from proteinuria fibrosis. Together, these data tubule-derived kidneys.
Language: Английский
Citations
6
Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 405, P. 111310 - 111310
Published: Nov. 15, 2024
Language: Английский
Citations
4
Nature Reviews Nephrology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 6, 2025
Language: Английский
Citations
0
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167656 - 167656
Published: Jan. 6, 2025
Language: Английский
Citations
0
Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119398 - 119398
Published: Jan. 1, 2025
Language: Английский
Citations
0
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114265 - 114265
Published: Feb. 16, 2025
Macrophage-mediated inflammation is closely linked to the pathogenesis of acute kidney injury (AKI) and shift macrophages a pro-inflammatory phenotype being reliant on glycolytic metabolism. Galloflavin, polyphenol derived from tea, functions as lactate dehydrogenase A (LDHA) inhibitor, effectively obstructing metabolic pathways. However, specific immunometabolic regulatory galloflavin in remain unclear. Here, we observed that drives alleviation metabolism levels lipopolysaccharide (LPS)-induced (RAW264.7 cells human peripheral blood mononuclear cells-derived macrophages) through downregulation LDHA expression, thereby inhibiting macrophage conversion reducing release inflammatory cytokines. overexpression counteracts effects macrophages. In addition, vivo experiments protective effect against cecal ligation puncture (CLP) cisplatin-induced renal injury. The ability inhibit glycolysis macrophages, regulating their phenotypic transition during AKI was further validated isolation primary This intervention ultimately ameliorated response decelerated progression AKI. Collectively, confers protection by suppressing LDHA-dependent mechanism, positioning it potential therapeutic option for future.
Language: Английский
Citations
0
Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156582 - 156582
Published: Feb. 26, 2025
The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role CsA nephrotoxicity not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza (HD) ameliorating the CsA, mechanisms still need be fully clarified. This study innovatively aimed analyse coexpression proteins serum metabolites for identification key pathways targets. provides novel insight into mechanism by which HD ameliorates CsA-induced We utilized intervene both vivo vitro models induced CsA. For experiments, we constructed a network metabolites, was used screen pathways. To validate these findings, knocked down vivo. studies, employed MTT, Transwell, flow cytometry, immunofluorescence assays monitor epithelial-mesenchymal transition (EMT) HK-2 cells. Additionally, electron microscopy Seahorse examine effects on mitochondrial structure function. Furthermore, overexpressed Ppara further confirm improves can improve pathological damage function; regulate blood lipids, inflammation oxidative stress indicators; reduce apoptosis tissues. Joint protein metabolomics analyses revealed that two lipid metabolism-related (the PPAR signalling pathway linoleic acid pathway) were coenriched, involving six differential (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, Pck1) differentially abundant (alpha-Dimorphecolic 12,13-EpOME). Western blot verify expressed proteins. improved accumulation, as demonstrated transmission (TEM) analysis Oil Red O staining. Knockdown affected expression ACOX1 exacerbated RF. In verification significantly inhibited EMT cells overexpression promoted HD-mediated regulation function, reduced apoptosis, ameliorate through protein-serum coexpression, pathway, metabolism. HD-induced upregulation metabolism, function are mechanisms. Ppara/ACOX1/TGF-β1 axis may an this process. These findings offer potential targets future development therapeutic strategies drugs.
Language: Английский
Citations
0
Metabolism Open, Journal Year: 2025, Volume and Issue: 25, P. 100354 - 100354
Published: March 1, 2025
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, affecting over 30 % diabetes mellitus (DM) patients. Early detection DKD in DM patients can enable timely preventive therapies, and potentially delay progression. Since relies on fatty acid oxidation for energy, dysregulated lipid metabolism has been implicated proximal tubular cell damage pathogenesis. This study aimed to identify alterations during development potential biomarkers differentiating from DM. lipidomics analysis was performed serum collected 55 with DM, 21 early stage 32 advanced DKD, 22 healthy subjects. Associations between lipids risk were evaluated by logistic regression. Lipid profiling revealed elevated levels certain lysophosphatidylethanolamines (LPEs), phosphatidylethanolamines (PEs), ceramides (Cers), diacylglycerols (DAGs) DM-DKD transition, while most LPEs, lysophosphatidylcholines (LPCs), along several monoacylglycerol (MAG) triacylglycerols (TAGs), increased further DKD-E DKD-A. Logistic regression indicated positive associations LPCs, PEs, DAGs risk, LPEs correlating significantly urinary albumin-to-creatinine ratio (UACR) inversely estimated glomerular filtration rate (eGFR). A machine-learning-derived biomarker panel, Lipid9, consisting LPC(18:2), LPC(20:5), LPE (16:0), (18:0), (18:1), (24:0), PE (34:1), (34:2), (36:2), accurately distinguished (AUC: 0.78, 95 CI 0.68-0.86) Incorporating two clinical indexes, creatinine blood urea nitrogen, Lipid9-SCB model improved 0.83, 0.75-0.90) notably more sensitive identifying 0.79, 0.67-0.91). deciphers signature progression, suggests panel as a promising tool
Language: Английский
Citations
0