Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117572 - 117572
Published: Oct. 19, 2024
Language: Английский
European Heart Journal, Journal Year: 2024, Volume and Issue: 45(37), P. 3871 - 3885
Published: July 8, 2024
Abstract Background and Aims Valve interstitial cells (VICs) undergo a transition to intermediate state before ultimately transforming into the osteogenic cell population, which is pivotal cellular process in calcific aortic valve disease (CAVD). Herein, this study successfully delineated stages of VIC transformation elucidated novel key regulatory role lumican (LUM) process. Methods Single-cell RNA-sequencing (scRNA-seq) from nine human valves was used characterize pathological switch identify factors. The vitro, ex vivo, double knockout mice were constructed further unravel calcification-promoting effect LUM. Moreover, multi-omic approaches employed analyse molecular mechanism LUM CAVD. Results ScRNA-seq highlighted significance as molecule pro-calcification confirmed on vivo level, ApoE−/−//LUM−/− mice. induces osteogenesis VICs via activation inflammatory pathways augmentation glycolysis, resulting accumulation lactate. Subsequent investigation has unveiled driving histone modification, lactylation, plays facilitating calcification. More importantly, identified two specific sites namely, H3K14la H3K9la, have been found facilitate confirmation these modification sites’ association with expression genes Runx2 BMP2 achieved through ChIP-PCR analysis. Conclusions presents findings, being first establish involvement mediating H3 thus development Consequently, would be promising therapeutic target for intervention treatment
Language: Английский
Citations
48
Advanced Science, Journal Year: 2024, Volume and Issue: 11(20)
Published: March 19, 2024
Abstract The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression calcific disease (CAVD). However, precise mechanisms underlying VICs remain unclear, demanding identification novel target to mitigate this process. Previous studies have highlighted anti‐aging potential morusin. Thus, study aimed explore therapeutic morusin CAVD. Cellular experiments reveal that effectively suppresses cellular and cause shift toward osteogenic differentiation vitro. Mechanistically, activate Nrf2‐mediated antiaging signaling pathway by downregulating CCND1 expression aiding Keap1 degradation through Trim 25. This activation lead upregulated antioxidant genes, thus reducing reactive oxygen species production thereby preventing VIC differentiation. In vivo ApoE −/− mice on high‐fat Western diet demonstrate positive effect mitigating calcification. These findings emphasize properties its as agent for
Language: Английский
Citations
11
Published: Jan. 1, 2025
1.Abstract Key pathological factors contributing to intervertebral disc degeneration (IVDD) include excessive production of reactive oxygen species (ROS), depletion the extracellular matrix (ECM), and an imbalance in M1/M2 macrophage ratio. To address these challenges, we developed a novel bioactive hydrogel (FUH@dECM) by integrating high-concentration fucoidan (FU) with decellularized (dECM). This is designed for situ injection, where it undergoes gelation at site administration, replenishing lost ECM nucleus pulposus cells while gradually releasing FU. In vitro, experiments demonstrated that controlled release FU effectively scavenges ROS, promotes polarization towards M2 phenotype, restores metabolic balance. RNA sequencing analysis revealed antioxidant effects FUH@dECM are primarily mediated through activation FOXO signaling pathway, inhibition NF-κB pathway mitigates inflammatory response. vivo rat model IVDD, this system strong mechanistic alignment physiological processes disc, significantly improving IVDD outcomes maintaining height preserving structural integrity tissue. These results underscore potential as promising therapeutic strategy treatment IVDD.
Language: Английский
Citations
0
Chemical and Biological Technologies in Agriculture, Journal Year: 2025, Volume and Issue: 12(1)
Published: Jan. 15, 2025
Mulberry twigs, a traditional Chinese medicinal and agricultural byproduct, contain bioactive compounds with anti-atherosclerotic potential. This study aims to identify evaluate the effects of key in mulberry twig extracts (MTEs) on oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs), focus understanding how these modulate oxidative stress related signaling pathways. Biospecific cell extraction ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) were employed screen compounds. Protective assessed by measuring viability, malondialdehyde (MDA), superoxide dismutase (SOD) levels, along detecting intracellular reactive oxygen species (ROS) using 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA) dihydroethidine (DHE) probes. Real-time qPCR Western blotting used for mRNA protein level analysis. Two novel active compounds, Kuwanon H Morusin, known G, identified. They significantly reduced MDA ROS levels while increasing SOD activity ox-LDL-treated HUVECs. was particularly effective, enhancing nuclear factor erythroid 2-related 2 (Nrf-2) upregulating its target genes Heme oxygenase-1 (HO-1) NAD(P)H: quinone oxidoreductase 1 (NQO-1). In conclusion, H, G effectively protected HUVECs from ox-LDL-induced injury, showing strongest protective via Nrf-2/HO-1 pathway. These hold potential treating atherosclerosis diseases.
Language: Английский
Citations
0
Medical Review, Journal Year: 2025, Volume and Issue: unknown
Published: March 5, 2025
Abstract Natural products, the most important chemical library with magical structures and unique functions, have long been playing significant roles in contributing to discovery of novel drugs. The complexity diversity natural products present great challenges regarding exploration their potential targets. Identifying targets not only enhances our understanding biological functions molecular mechanisms, but also paves way for discovering lead compounds disease treatment. Recent advances technologies like biology, structural artificial intelligence provided powerful tools pinpointing product target unraveling mechanisms. This review aims comprehensively summarize innovative strategies employed recent years identify targets, evaluate impact on pathways by modulating pharmacological effects. Moreover, we discuss encountered this field outline future research prospects, aiming offer guidance researchers biology.
Language: Английский
Citations
0
PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0318574 - e0318574
Published: March 10, 2025
Objective Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative characterized by the accumulation of calcium deposits in valve. We aim to screen key genes associated with cellular senescence (CS) CAVD. Methods The GSE12644 and GSE51472 datasets from GEO database was utilized this study, differentially expressed (DEGs) were identified using “ limma ” R package. CS-related DEGs (CS-DEGs) determined through CellAge database. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses performed on CS-DEGs. A protein–protein interaction (PPI) network constructed STRING cytoHubba plug-in Cytoscape used identify hub genes. noncoding-RNA-mRNA regulatory established. DSigDB drugs potentially be useful for treating Results total 16 CS-DEGs identified. These primarily collagen metabolic process, catabolic process external side plasma membrane. 10 as regulators CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A. Noncoding RNA-mRNA indicated that may regulated noncoding RNAs. β-Carotene, naturally occurring carotenoid antioxidant properties, potential therapeutic agents interacting MMP9, CTSB. Conclusion This study provides insights into pathways related CAVD (MMP9, CTSB) highlights role β-Carotene treatment
Language: Английский
Citations
0
Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 620 - 620
Published: April 25, 2025
Renal cell carcinoma (RCC) is the most lethal malignancy of urinary system, with limited treatment options due to drug resistance and adverse effects associated current therapies. This review aims systematically examine therapeutic potential flavonoids, which are natural polyphenolic compounds possessing anti-inflammatory, antioxidant, anticancer properties, in context RCC treatment. We summarize activities 26 classified into six subclasses, explore their mechanisms action, including inhibition tumor proliferation, migration, invasion, as well induction apoptosis, autophagy, ferroptosis. Particular attention paid modulation key signaling pathways such JAK/STAT3, PI3K/Akt/mTOR, miRNA-related axes, miR-21/YAP1 miR-324-3p/GPX4, providing a molecular basis for anti-RCC activity. also address several pharmacological challenges that limit clinical application poor bioavailability, metabolic instability, toxicity. Emerging solutions novel flavonoid derivatives, advanced delivery systems, rational combination therapy strategies discussed. Current evidence, phase II trial flavopiridol RCC, highlights but need further validation. In conclusion, flavonoids offer promising approach improving Future research should focus on optimizing efficacy ensuring safe translation, goal achieving personalized minimally invasive cancer
Language: Английский
Citations
0
GeroScience, Journal Year: 2025, Volume and Issue: unknown
Published: May 8, 2025
Abstract Calcific aortic valve disease (CAVD) is a cardiovascular prevalent in the aging population, resulting high morbidity and mortality rates. However, molecular mechanisms underlying CAVD remain unclear. We initially conducted an RNA sequencing analysis of leaflets from rats different ages to identify key genes involved valvular calcification. Bioinformatics demonstrated that methionine sulfoxide reductase A (MSRA) was crucial calcification senescence. To further investigate whether how MSRA influences pathogenesis, we utilized two vitro models: human interstitial cell (VIC) model induced by osteogenic medium, VIC senescence hydrogen peroxide. Western blotting, immunofluorescence, flow cytometry, alkaline phosphatase staining were evaluate changes calcific nodule formation senescent markers. In vivo, ApoE −/− mice treated either normal chow or high-cholesterol determine effects overexpression on silencing increased differentiation VIC, whereas its produced opposite effects. Similarly, found reduced calcium deposition decreased levels markers mice. Further mechanism experiments showed suppressed osteoblastic via inhibiting toll-like receptor (TLR2)/nuclear factor-κB (NF-κB) pathway. Our findings demonstrate ameliorates TLR2/NF-κB pathway, highlighting as promising target for treating age-associated CAVD.
Language: Английский
Citations
0
Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103215 - 103215
Published: May 27, 2024
The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) known to be involved in the pathogenesis cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role elucidated. In this study, we identified FOXO1 significantly down-regulated interstitial cells (VICs) calcified valves by investigating clinical specimens GEO database analysis. silencing or inhibition promoted VICs osteogenic differentiation vitro Apoe
Language: Английский
Citations
1
PubMed, Journal Year: 2024, Volume and Issue: 28(6), P. 440 - 440
Published: Dec. 1, 2024
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiac disorder characterized by ventricular hypertrophy resulting from the disordered arrangement of myocardial cells, which leads to impaired function or death. Autophagy (AT) a biochemical process through lysosomes degrade and recycle damaged discarded intracellular components protect cells against external environmental conditions, such as hypoxia oxidative stress. AT closely related HCM, thus, serves important role in hypertrophy. However, precise mechanism underlying regulation remains elusive. The present study aimed examine mechanisms AT-related genes (ARGs) HCM bioinformatics analysis experimental validation identify potential targeted drugs for HCM. In this study, samples were obtained healthy individuals patients with GEO database, screened differentially expressed ARGs further investigate their interactions functional pathways. These subjected enrichment crosstalk involved Based on protein-protein interaction network, EIF4EBP1, MCL1, PIK3R1, CCND1 PPARG identified biomarkers diagnosis treatment Furthermore, 10 therapeutic predicted based aforementioned hub genes. results validated using H9c2 stimulated angiotensin II, represented
Language: Английский
Citations
0