Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 180, С. 117513 - 117513
Опубликована: Сен. 27, 2024
Язык: Английский
Cardiovascular Drugs and Therapy, Год журнала: 2025, Номер unknown
Опубликована: Фев. 26, 2025
Язык: Английский
Процитировано
1
Redox Biology, Год журнала: 2024, Номер 75, С. 103293 - 103293
Опубликована: Июль 29, 2024
Doxorubicin (DOX)-induced cardiotoxicity limits the application of DOX in cancer patients. Currently, there is no effective prevention or treatment for DOX-induced cardiotoxicity. The cellular repressor E1A-stimulated genes (CREG1) a cardioprotective factor that plays an important role maintenance cardiomyocytes differentiation and homeostasis. However, mechanism CREG1 has not yet been elucidated.
Язык: Английский
Процитировано
6
Redox Biology, Год журнала: 2024, Номер 78, С. 103417 - 103417
Опубликована: Ноя. 7, 2024
Acute kidney injury (AKI) constitutes a significant public health issue. Sepsis accounts for over 50 % of AKI cases in the ICU. Recent findings from our research indicated that PRD1-BF1-RIZ1 homeodomain protein 16 (PRDM16) inhibited progression diabetic disease (DKD). However, its precise role and regulatory mechanism sepsis-induced remain obscure. This study reveals lipopolysaccharide (LPS) cecum ligation puncture (CLP) instigated PRDM16 expression Boston University mouse proximal tubule (BUMPT) cells kidneys, respectively. Functionally, curtailed LPS-induced ferroptosis. Mechanistically, associates with promoter regions nuclear factor-erythroid 2-related factor-2 (NRF2) augments expression, subsequently enhancing glutathione peroxidase 4 (GPX4) expression. Additionally, directly engages GPX4, stimulating Notably, these observations were corroborated human renal tubular epithelial (HK-2) cells. Furthermore, ablation tubules mice NRF2 GPX4 leading to decreased (GSH)/oxidized (GSSG) ratio, increased Fe2+ reactive oxygen species (ROS) production, exacerbated ferroptosis, progression. Conversely, knock-in exhibited opposite effects. Ultimately, adenovirus (ADV)-PRDM16 plasmid or poly (lactide-glycolide acid) (PLGA)-encapsulated formononetin not only mitigated but also alleviated liver, cardiac, lung injury. In summary, inhibits ferroptosis via NRF2/GPX4 axis prevent multi-organ injury, including AKI. PLGA-encapsulated presents promising therapeutic approach.
Язык: Английский
Процитировано
6
Antioxidants, Год журнала: 2024, Номер 13(8), С. 1015 - 1015
Опубликована: Авг. 20, 2024
The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that exert anti-tumor effects in HCC via inhibition of ferroptosis induction. Auraptene treatment induces total ROS lipid production to initiate ferroptosis. death or growth induced by be eliminated the scavenger NAC GSH inhibitor ferrostatin-1 Deferoxamine Mesylate (DFO). Mechanistically, key defense protein SLC7A11 targeted for ubiquitin–proteasomal degradation auraptene, resulting cells. Importantly, low doses sensitize RSL3 cystine deprivation. These findings demonstrate a critical mechanism which exhibits anti-HCC induction provides possible therapeutic strategy using combination with other inducers.
Язык: Английский
Процитировано
5
BMC Cardiovascular Disorders, Год журнала: 2024, Номер 24(1)
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
5
Neuroscience and Behavioral Physiology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 9, 2024
Язык: Английский
Процитировано
4
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Ноя. 12, 2024
Background Heart failure is primarily characterized by damage to the structure and function of heart. Ferroptosis represents a form programmed cell death, studies indicate that it constitutes one primary mechanisms underlying cardiomyocyte death in heart failure. Calycosin, natural compound derived from astragalus, exhibits various pharmacological properties, including anti-ferroptosis, antioxidant effects, cardiovascular protection. Nonetheless, specific role Calycosin treatment ferroptosis remains poorly understood. Objective This study aims elucidate regulatory effect on its influence through vivo vitro experiments. Methods A rat model was induced using doxorubicin, cardiac evaluated ultrasound examination NT-Pro BNP detection. Myocardial injury assessed H&E staining Masson staining. The extent mitochondrial transmission electron microscopy. Concurrently, level analyzed measuring markers, MDA, ferrous ions, GSH/GSSG ratio, GPX4 activity. Subsequently, molecular mechanism which exerts therapeutic effects investigated immunofluorescence Western blotting. Finally, H9c2 cardiomyocytes were treated with doxorubicin simulate myocardial injury, mediates further verified Nrf2 gene silencing. Results significantly improves rats, reduces serum levels, alleviates damage. Additionally, decreases levels tissue, as confirmed microscopy assessment GSH, At level, activating Nrf2/SLC7A11/GPX4 signaling pathway, evidenced upregulation Nrf2, SLC7A11, GPX4, GSS, GCL protein expression. process substantially enhances capacity tissue effectively suppresses cells. results obtained both experiments are consistent. Notably, when silenced, protective myocardium markedly diminished. Conclusion treats doxorubicin-induced likely closely associated activation pathway inhibition Consequently, promising against cardiotoxicity, warrants investigation.
Язык: Английский
Процитировано
4
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Фев. 28, 2025
Abstract Abdominal aortic aneurysm (AAA) is a high‐risk inflammatory disorder. SENP3, SUMO2/3‐specific protease, closely involved in the development of cancer. In this study, aim to explore role SENP3 macrophages AAA. It found that protein expression significantly upregulated both human and murine AAA specimens. negatively regulated by E3 ubiquitin ligase STUB1/CHIP. Furthermore, myeloid‐specific knockout inhibited formation AngII‐ CaCl 2 ‐induced mouse models. deficiency repressed lesion macrophage infiltration response. Mechanistic studies identified Cystathionine Gamma–Lyase (CTH), critical enzyme hydrogen sulfide production, as target mediated exacerbating effects on ferroptosis programs macrophages. SUMO‐3 modification at Lysine 361 promoted CTH stability, whereas de‐SUMOylation facilitated its proteasome‐dependent degradation. Most importantly, it inhibitor counteracted protective effect Additionally, supplementation with ATB346, novel H S‐donating naproxen derivative, prevented mice. These suggest SENP3‐mediated deSUMOylation regulates development. The SENP3/CTH axis therefore an important therapeutic for aneurysmal diseases.
Язык: Английский
Процитировано
0
Redox Biology, Год журнала: 2025, Номер unknown, С. 103631 - 103631
Опубликована: Апрель 1, 2025
Hydrogen sulfide (H2S) is a vital signaling molecule involved in various physiological processes; however, the mechanisms underlying its systemic remain poorly understood. We hypothesized that albumin, predominant plasma protein and sulfhydryl carrier, mediated H2S signaling, which could potentially treat H2S-deficient diseases. This study aimed to investigate this hypothesis. Our results showed presence of sulfhydrated proteins normal mouse serum, with albumin being particularly enriched. The level sulfhydration was influenced by availability redox environment. In vitro incubation NaHS resulted an increased number groups. Under reductive conditions, (-SSH-Alb) released substantial amounts H2S. When -SSH-Alb added cultured endothelial cells, it activated cAMP pathway, upregulated cystathionine γ-lyase (CSE) expression, enhanced intracellular levels. inflammatory model involving macrophages inhibited macrophage adhesion, reduced LPS-induced expression adhesion molecules, suppressed cytokine production inflammasome activation. These effects correlated improved cellular status. Furthermore, vivo administration protected mice from doxorubicin (DOX)-induced cardiotoxicity intestinal damage. It mortality, alleviated ferroptotic cardiac injury gut barrier dysfunction. therapeutic benefits were associated rebalanced local summary, our reveals reserves, transmits, amplifies signals exhibits significant anti-inflammatory antioxidant properties. characteristic holds promise for preventing treating wide range
Язык: Английский
Процитировано
0
Phytomedicine, Год журнала: 2025, Номер 142, С. 156799 - 156799
Опубликована: Апрель 22, 2025
Язык: Английский
Процитировано
0