Biochemical Pharmacology, Год журнала: 2024, Номер unknown, С. 116669 - 116669
Опубликована: Ноя. 1, 2024
Язык: Английский
Redox Biology, Год журнала: 2024, Номер 74, С. 103224 - 103224
Опубликована: Июнь 8, 2024
Silicosis, characterized by interstitial lung inflammation and fibrosis, poses a significant health threat. ATII cells play crucial role in alveolar epithelial repair structural integrity maintenance. Inhibiting cell senescence has shown promise silicosis treatment. However, the mechanism behind silica-induced remains elusive. The study employed male C57BL/6 N mice A549 human to investigate its potential Silicosis was induced via intratracheal instillation of crystalline silica particles, with honokiol administered intraperitoneally for 14 days. Silica-induced confirmed, SIRT3 knockout overexpression lines were generated. Various analyses conducted, including immunoblotting, qRT-PCR, histology, transmission electron microscopy. Statistical significance determined using one-way ANOVA Tukey's post-hoc test. This elucidates how induces senescence, emphasizing mtDNA damage. Notably, (HKL) emerges as promising anti-senescence anti-fibrosis agent, acting through sirt3. effectively attenuated cells, dependent on sirt3 expression, while mitigating Sirt3, class III histone deacetylase, regulates mitochondrial stress. HKL activates sirt3, protecting against pulmonary fibrosis Additionally, downregulated cGAS expression senescent silica, suggesting sirt3's an upstream regulator cGAS/STING signaling pathway. Moreover, treatment inhibited activation NF-κB pathway, associated reduced oxidative stress enhanced activity SOD2, function, sirt3-mediated deacetylation. promoted deacetylation further safeguarding integrity. uncovers natural compound, HKL, anti-fibrotic properties activating shedding light pathogenesis avenues.
Язык: Английский
Процитировано
11
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10222 - 10222
Опубликована: Сен. 23, 2024
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third type 1 and nearly half 2 patients. As the leading cause end-stage renal (ESRD) globally, DKD develops through complex interplay chronic hyperglycemia, oxidative stress, inflammation. Early detection crucial, with diagnosis based on persistent albuminuria reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, use nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) glucagon-like peptide-1 (GLP-1) agonists. Ongoing research explores novel therapies targeting molecular pathways non-coding RNAs. Preventive measures focus rigorous control hyperglycemia hypertension, aiming to mitigate progression. Despite therapeutic advances, remains ESRD, highlighting need for continued identify new biomarkers innovative treatments.
Язык: Английский
Процитировано
11
Aging Cell, Год журнала: 2025, Номер unknown
Опубликована: Фев. 4, 2025
ABSTRACT Recent studies have shown that disruptions in the nicotinamide adenine dinucleotide (NAD + ) de novo synthesis pathway accelerate ovarian aging, yet its role spermatogenesis remains largely unknown. In this study, we investigated impact of NAD on by generating Qprt ‐deficient mice using CRISPR‐Cas9 to target quinolinate phosphoribosyl transferase ( ), a key enzyme predominantly expressed spermatocytes. Our results revealed deletion did not affect levels or testes 3‐month‐old mice. However, from 6 months age onward, exhibited significantly reduced compared wild‐type (WT) controls, along with notable decrease germ cell numbers and increased apoptosis. Additionally, these demonstrated mitochondrial dysfunction spermatocytes, impaired progression through prophase I meiosis, defective double‐strand break (DSB) repair, abnormal meiotic sex chromosome inactivation. Importantly, supplementation precursor riboside (NR) restored rescued spermatogenic defects. These findings underscore critical maintaining homeostasis highlight importance recombination inactivation spermatogenesis.
Язык: Английский
Процитировано
1
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 6936 - 6936
Опубликована: Июнь 25, 2024
Kidney diseases, including chronic kidney disease (CKD), diabetic nephropathy, and acute injury (AKI), represent a significant global health burden. The kidneys are metabolically very active organs demanding large amount of ATP. They composed highly specialized cell types in the glomerulus subsequent tubular compartments which fine-tune metabolism to meet their numerous diverse functions. Defective renal metabolism, altered fatty acid oxidation or glycolysis, has been linked both AKI CKD. Mitochondria play vital role emerging research identified mitochondrial sirtuins (SIRT3, SIRT4 SIRT5) as key regulators metabolic adaptation, especially SIRT3. Sirtuins belong an evolutionarily conserved family mainly NAD
Язык: Английский
Процитировано
5
Clinical Journal of the American Society of Nephrology, Год журнала: 2025, Номер 20(3), С. 346 - 357
Опубликована: Янв. 23, 2025
Key Points Nicotinamide riboside and coenzyme Q10 supplementation showed distinct beneficial effects on whole-blood transcriptome, inflammatory cytokines, oxidative stress. treatment altered the expression of genes associated with metabolism immune response coinciding a decrease in markers Coenzyme lipid reductions stress cytokines. Background Mitochondria-driven oxidative/redox inflammation play major role CKD pathophysiology. Compounds targeting mitochondrial may improve function, inflammation, redox stress; however, there is limited evidence their efficacy CKD. Methods We conducted pilot, randomized, double-blind, placebo-controlled crossover trial comparing 1200 mg/d (CoQ10) or 1000 nicotinamide (NR) placebo 25 patients moderate-to-severe (eGFR <60 ml/min per 1.73 m 2 ). assessed changes blood transcriptome using 3′-Tag-Seq gene profiling prespecified secondary outcomes biomarkers. For subsample participants ( n =14), we lymphocyte monocyte bioenergetics an extracellular flux analyzer. Results The (mean±SD) age, eGFR, body mass index were 61±11 years, 37±9 , 28±5 kg/m respectively. Of participants, 16% had diabetes 40% female. Compared placebo, NR-mediated transcriptomic enriched ontology terms carbohydrate/lipid signaling, whereas CoQ10 immune/stress terms. NR increased plasma IL-2 (estimated difference, 0.32; 95% confidence interval [CI], 0.14 to 0.49 pg/ml), decreased both IL-13 −0.12; CI, −0.24 −0.01 pg/ml) C-reactive protein −0.11; −0.22 0.00 mg/dl) compared placebo. Both reduced five-series F2-isoprostanes −0.16 −0.11 pg/ml, respectively; P < 0.05 for both). NR, but not CoQ10, Bioenergetic Health Index 0.29; 0.06 0.53) spare respiratory capacity 3.52; 0.04 7 pmol/min 10,000 cells) monocytes. Conclusions Six weeks improved stress, cell Clinical Trial registry name registration number: NCT03579693.
Язык: Английский
Процитировано
0
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 4, 2025
Diabetic nephropathy (DN) is one of the major causes end-stage renal disease. This study aimed to explore internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics Olink proteomics. The serum 10 who were diagnosed healthy individuals Animal models used validate characterized genes. Correlation analysis differentially abundant metabolites expressed proteins revealed that SIRT2 might be a key hub linking energy metabolism innate immune responses. KEGG enrichment showed HIF-1 signaling pathway cell carcinoma co-enriched pathways inflammatory response. VEGFA plays vital role these two pathways. ability regulate expression has been demonstrated. In vivo experiments SIRT2, VEGFA, HIF-1α highly kidneys mice diabetic nephropathy. conclusion, our combines proteomics provide valuable insights into synergistic roles disorders DN. data suggest may target affecting processes.
Язык: Английский
Процитировано
0
Antioxidants, Год журнала: 2025, Номер 14(3), С. 267 - 267
Опубликована: Фев. 25, 2025
Diabetic nephropathy (DN), one of the most common and severe microvascular complications diabetes, significantly increases risk renal failure cardiovascular events. A high-glucose environment can lead to mitochondrial dysfunction in macrophages, which, through remodeling energy metabolism, mediates polarization a pro-inflammatory phenotype contributes formation chronic inflammatory microenvironment. Recent studies have found that stimulation induces dysregulation nuclear factor erythroid 2-related 2 (NRF2) redox pathway leading generation oxidative stress (OS) further drives inflammation. Therefore, it is crucial fully understand how OS affects macrophage phenotypes functions following NRF2 inhibition. This review analyzes role induced by inflammation DN explores relationship between metabolism NAD⁺/NADH-SIRT3 axis, providing new therapeutic targets for targeting improve microenvironment vascular damage DN.
Язык: Английский
Процитировано
0
JCI Insight, Год журнала: 2025, Номер 10(5)
Опубликована: Март 9, 2025
Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased CKD, and supplementation protective. However, both the mechanism how protects from as well cell types involved, poorly understood. Using mouse model Alport syndrome, we show nicotinamide riboside (NR), an precursor, stimulated PPARα signaling restored FAO proximal tubules, thereby protecting CKD sexes. Bulk RNA-sequencing showed pathways were mice activated by NR These transcriptional changes confirmed orthogonal imaging techniques biochemical assays. Single-nuclei RNA sequencing spatial transcriptomics, first their kind to our knowledge mice, tubule cells. Finally, also report, for time knowledge, sex differences at level this model. In summary, data herein identify nephroprotective they demonstrate benefit localizes
Язык: Английский
Процитировано
0
Chinese Medical Journal, Год журнала: 2024, Номер 137(9), С. 1044 - 1053
Опубликована: Март 6, 2024
Abstract Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, precise molecular mechanisms linking damage disease remain elusive. The recent insights into cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One these findings is that DNA (mtDNA) induces inflammatory responses via cGAS-STING pathway. Herein, we provide an overview underlying mtDNA release following damage, focusing specifically on association between release-activated development Furthermore, summarize latest cell, with particular emphasis downstream related This review intends enhance our understanding intricate relationship among pathway, diseases, dysfunction.
Язык: Английский
Процитировано
3
Biomolecules, Год журнала: 2024, Номер 14(6), С. 733 - 733
Опубликована: Июнь 20, 2024
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause end-stage renal around world. Mitochondria are organelles responsible for producing energy in cells closely involved maintaining normal organ function. Studies have found that high-sugar environment can damage glomeruli tubules trigger mitochondrial dysfunction. Meanwhile, animal experiments shown DKD symptoms alleviated when targeted, suggesting dysfunction inextricably linked to development DKD. This article describes mechanisms progression onset The relationship between discussed. At same time, progress treatment targeting summarized. We hope provide new insights into
Язык: Английский
Процитировано
3