Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation DOI Creative Commons
Z. Zhang, Jiawei Guo

Antioxidants, Год журнала: 2024, Номер 14(1), С. 38 - 38

Опубликована: Дек. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Язык: Английский

Dapagliflozin in Chronic Kidney Disease: Insights from Network Pharmacology and Molecular Docking Simulation DOI Creative Commons
Atthaphong Phongphithakchai, Aman Tedasen,

Ratana Netphakdee

и другие.

Life, Год журнала: 2025, Номер 15(3), С. 437 - 437

Опубликована: Март 11, 2025

Chronic kidney disease (CKD) involves inflammation, oxidative stress, and fibrosis, leading to renal dysfunction. Dapagliflozin, an SGLT2 inhibitor, shows renoprotective effects beyond glucose control, but its precise molecular mechanisms remain unclear. This study utilizes network pharmacology docking elucidate multi-target in CKD. Dapagliflozin’s SMILES structure was analyzed for ADMET properties. Potential targets were identified via SwissTargetPrediction, GeneCards, SEA, common CKD-related determined. A protein–protein interaction (PPI) constructed, key pathways using GO KEGG enrichment analyses. Molecular conducted validate dapagliflozin’s binding affinities with hub proteins. total of 208 identified, including EGFR, GSK3β, IL-6. analyses highlighted pathways, such as PI3K-Akt, MAPK, AGE-RAGE, involved metabolic regulation. confirmed strong EGFR (−8.42 kcal/mol), GSK3β (−7.70 IL-6 (−6.83 kcal/mol). Dapagliflozin exhibits therapeutic potential CKD by modulating pathways. integrative approach enhances the understanding mechanisms, supporting future experimental validation clinical application management.

Язык: Английский

Процитировано

2
Targeting Zfp36 to combat cardiac hypertrophy: Insights into ferroptosis pathways DOI Creative Commons
Mingyu Zhang, Xiaoxiang Guan, Zheng Dong

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(3)

Опубликована: Фев. 25, 2025

Cardiac hypertrophy is a precursor to heart failure and represents significant global cause of mortality, thereby necessitating timely effective therapeutic interventions. Zinc finger protein 36 (Zfp36) recognised as critical regulator ferroptosis; however, its role underlying mechanisms in cardiac remain largely unexplored. This study aims investigate the regulatory function Zfp36 ferroptosis within context hypertrophy. Single-cell sequencing analysis demonstrated reduction expression associated with was observed mitigate reduce hypertrophic phenotypes cardiomyocytes subjected Angiotensin II (Ang II) myocardial tissues induced by transverse aortic constriction. The inhibitor Ferrostatin-1 shown alleviate when co-incubated si-Zfp36 Ang II. Mechanistically, binds 3' untranslated region (3'UTR) Ythdc2 mRNA, facilitating degradation. subsequently SLC7A11 enhancing decay, which leads glutathione (GSH) levels, exacerbating Furthermore, overexpression reversed protective effects conferred Zfp36, while silencing counteracted knockdown. elucidates hypertrophy, specifically detailing modulatory mechanism via Ythdc2/SLC7A11/GSH pathway. These insights lay groundwork for innovative approaches understanding pathological clinical initially attenuate through inhibition cardiomyocytes, providing new target strategies targeting ferroptosis. facilitated degradation mRNA binding it, inhibiting Ythdc2-mediated maintaining GSH levels. previously unrecognized pathway

Язык: Английский

Процитировано

1
Animal experiments and network pharmacology to explore the anti-inflammatory mechanism of dapagliflozin in the treatment of polycystic ovary syndrome DOI Creative Commons
Liu Y,

He Bai,

Huilin Guan

и другие.

Gynecological Endocrinology, Год журнала: 2025, Номер 41(1)

Опубликована: Янв. 18, 2025

Background Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic low-grade inflammation of the ovary. Sodium glucose co-transporter 2 (SGLT2) inhibitors are class antidiabetic drugs that can reduce weight hyperglycemia type diabetes patients. Dapagliflozin highly selective, orally active reversible inhibitor human SGLT2. However, role dapagliflozin in regulating PCOS remains unclear.

Язык: Английский

Процитировано

0
Exploring the effect of dapagliflozin on coronary inflammation in type 2 diabetes patients based on the coronary artery perivascular fat attenuation index DOI Creative Commons

Xuehua Liu,

Tian Zhang,

Rongguo Fu

и другие.

Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 18, 2025

The pericoronary fat attenuation index (FAI) is a novel biomarker that serves as an indicator of coronary artery inflammation. Dapagliflozin has become important component standard treatment for type 2 diabetes because its cardioprotective and renoprotective effects. objective this research was to explore how dapagliflozin impacts inflammation in T2DM patients establish theoretical framework the protective role cardiovascular system. This retrospectively included 271 treated with computed tomography angiography (CCTA) at Hebei Provincial People's Hospital from January 2021 November 2024, 103 receiving therapy (dapagliflozin+) 168 not (dapagliflozin-) (oral 10 mg/day no less than 6 months). Baseline clinical information, laboratory markers, CCTA-related metrics were collected analysed across both groups. relationship between FAI using multiple linear regression control confounding variables, correlation two variables further examined various subgroups. Compared those dapagliflozin- group, dapagliflozin+ group younger (P<0.001), proportion men higher (P<0.05). There between-group differences baseline data, such course, BMI, blood lipid status (P>0.05). LAD RCA lower other groups, average three arteries also significantly lower, while there significant difference LCX (LAD: group: -85.50 (-90.43, -78.27)，dapagliflozin+ group：-86.94 (-92.81, -81.57)，P= 0.044；RCA：dapagliflozin- group：-86.31 (-92.12, -80.09), group：-88.79 (-94.59, -83.31), P= 0.019; Mean: -84.05 (-87.73, -77.45), -84.88 (-89.82, -79.67), 0.022; LCX: group：-77.81 (-82.57, -71.75), -78.25 (-84.56, -72.15), P = 0.260). Multiple analyses revealed independent association decreased β=-2.449; RCA: β=-3.897; values are all 0.05). different subsets patients. associated reduction patients, which may partly explain beneficial effects on reducing risk.

Язык: Английский

Процитировано

0
Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila DOI Creative Commons
Jinhua Yan,

Chenxi Feng,

H Zhang

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 23, 2025

Introduction Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading diminished regeneration an increased risk of age-associated diseases. Methods This study investigates effects Dapagliflozin (DAPA), a novel insulin sensitizer SGLT2 inhibitor, on aging ISCs using Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit MAPK signaling pathway, as confirmed by network pharmacology analysis molecular docking experiments. Results ameliorates ISC aging, improves function (including enhanced fecal excretion, restored barrier integrity acid-base balance), enhances healthspan. These results highlight potential anti-aging therapeutic agent. Discussion provides new evidence application treatment.

Язык: Английский

Процитировано

0
Dapagliflozin activates the RAP1B/NRF2/GPX4 signaling and promotes mitochondrial biogenesis to alleviate vascular endothelial ferroptosis DOI
Yi Zhu, Jin Yang, Jiali Zhang

и другие.

Cellular Signalling, Год журнала: 2025, Номер unknown, С. 111824 - 111824

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
The cardio‐renal‐metabolic role of the nod‐like receptor protein‐3 and senescence‐associated secretory phenotype in early sodium/glucose cotransporter‐2 inhibitor therapy in people with diabetes who have had a myocardial infarction DOI Creative Commons
Muhammad Usman Shah, Chelsy L. Cliff, Paul E. Squires

и другие.

Diabetic Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Abstract Aims Following an acute myocardial infarction (AMI), individuals with type 2 diabetes (T2DM) have a 2‐to‐3 fold increased risk of mortality compared to those without diabetes, and globally cardiorenal complications account for 50% diabetes‐related deaths. The use sodium/glucose cotransporter‐2 inhibitors (SGLT2i) in people T2DM‐AMI is associated decreased inflammatory burden improved outcomes. mechanisms behind this protection are unclear form the basis study. Methods This single centre, prospective study randomisation will utilise plasma monocyte‐derived macrophages from patients T2DM who recently had AMI prescribed Empagliflozin either immediately following cardiac event or at 3 months post‐AMI. Results test hypothesis that provides anti‐inflammatory by suppressing systemic NOD‐like receptor protein‐3 (NLRP3) inflammasome activation pro‐inflammatory senescence‐associated secretory phenotype (SASP), perpetrators sterile (non‐pathogen evoked) inflammation linked poor clinical outcomes patients. also assess benefits early intervention on these parameters. Conclusions Elucidating role SGLT2i enhance understanding how they can be used effectively treat identify novel pathways future intervention. Furthermore, optimal timing when initiate therapy post‐AMI unclear. Correlating level onset T2DM, cardiovascular establish if greater benefit initiated earlier.

Язык: Английский

Процитировано

0
Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation DOI Creative Commons
Z. Zhang, Jiawei Guo

Antioxidants, Год журнала: 2024, Номер 14(1), С. 38 - 38

Опубликована: Дек. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Язык: Английский

Процитировано

3