Molecular Therapy — Nucleic Acids, Год журнала: 2024, Номер 36(1), С. 102433 - 102433
Опубликована: Дек. 21, 2024
Язык: Английский
Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)
Опубликована: Дек. 4, 2024
The pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism ferroptosis in various diseases, including DCM, has attracted widespread attention. Here, we explored role PACS2 DCM through downregulation expression. Cardiomyocytes were treated with high glucose and palmitic acid (HGPA), detection cardiomyocyte iron ions, lipid peroxides, reactive oxygen species (ROS) revealed clear during these treatments. Silencing downregulated CPT1A expression upregulated DHODH significantly, reversing HGPA-induced ferroptosis. Further silencing agonist exacerbated while promoting mitochondrial damage cardiomyocytes. Using mouse model type 2 diabetes induced by streptozotocin (STZ) high-fat diet (HFD), found that deletion reversed treatment-induced increases cellular impaired cardiac function, muscle tissues. PACS2/CPT1A/DHODH signalling pathway may be involved regulating function.
Язык: Английский
Процитировано
3
Cell Biochemistry and Function, Год журнала: 2024, Номер 42(1)
Опубликована: Янв. 1, 2024
Abstract Photodynamic therapy (PDT) is nowadays widely employed in cancer treatment. We sought to assess the efficacy of combining PDT with anti‐programmed cell death protein 1 (PD1) and investigate associated mechanisms nonsmall lung (NSCLC). established a xenograft tumor model C57BL/6J mice using Lewis carcinoma (LLC) cells, recorded growth, quantified reactive oxygen species (ROS) levels ROS detection kit. Pathological changes were assessed through H&E staining, while immunofluorescence (IF) was used determine expression CD8 Foxp3. Transcriptomic analysis conducted, analyzing differential expressed genes (DEGs) among control, PDT, combined anti‐PD1 (PDT+anti‐PD1) groups. Functional enrichment via Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) performed. The Cancer Genome Atlas (TCGA) database utilized analyze aminolevulinate synthase gene (ALAS2), integrin alpha10 (ITGA10), ATP1A2, disintegrin metalloprotease 12 (ADAM12), Lox1 adenocarcinoma adjacent tissues, concurrent immune infiltration analysis. Quantitative real‐time polymerase chain reaction western blot measure mRNA levels. Treatment significantly inhibited growth increased number + cells decreasing Foxp3 cells. Immune results presented ALAS2, ADAM12, ITGA10 various types T or macrophages. Additionally, EGFR, ERK, PI3K/Akt suppressed after Our findings collectively suggest that treatment could enhance suppressing this effect ITGA10, ADAM12. underlying mechanism might be linked signaling. Overall, study provides valuable insights into application NSCLC.
Язык: Английский
Процитировано
2
Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(7)
Опубликована: Июль 24, 2024
Background: Heart failure (HF) is a clinical syndrome that seriously endangers human health and quality of life as the terminal stage cardiovascular diseases. Ferroptosis new iron-dependent programmed cell death mode closely related to occurrence development Dihydroorotate dehydrogenase (DHODH) has been found play crucial role in inhibiting ferroptosis improving mitochondrial function, its expression can be upregulated by estradiol (E2). Recent studies have DHODH inhibit reducing coenzyme Q (CoQ) CoQH2. Therefore, this study aims explore effect up-regulation on pathological hypertrophy fibrosis heart mechanisms. Methods: The mouse model was established transverse aortic constriction (TAC), surgery mice. Two days after operation, subcutaneous injection E2 or same volume sesame oil given for 8 weeks. Then, left ventricular systolic function indicators mice were measured echocardiography, degree myocardial detected histological analysis; levels markers quantitative polymerase chain reaction (q-PCR) western blot (WB) morphological changes mitochondria cardiac cells observed transmission electron microscopy. Cell stimulating with phenylephrine 96 hours. kits WB analysis. Mitochondrial verified JC-1 fluorescent probe, 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining. knockdown results analysis transfection small interfering RNA (siRNA) CoQ. Fer-1 added positive control verify ferroptosis-related cells. Results: In animal model, we treatment alleviates TAC-induced suppresses cardiomyocyte promotes upregulation murine cardiomyocytes. protects against phenylephrine-induced cardiomyocytes failure. However, up-regulating inhibited down-regulate CoQ expression. Conclusions: could effectively ameliorate manifestations such TAC surgery, myocytes, function. mechanism involves CoQ-related biological processes.
Язык: Английский
Процитировано
2
Molecular Neurobiology, Год журнала: 2024, Номер unknown
Опубликована: Авг. 24, 2024
Язык: Английский
Процитировано
2
Free Radical Biology and Medicine, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
2
Antioxidants, Год журнала: 2023, Номер 12(12), С. 2100 - 2100
Опубликована: Дек. 12, 2023
Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and the potential to protect mitochondrial function alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E2) intervention developed NAFLD, whereas E2 supplementation was effective preventing NAFLD rats. The altered pathways cellular events from both comparison pairs, namely, OVX vs. sham group group, were assessed using transcriptomic analysis. KEGG enriched by metabolomic analyses strongly suggest that oxidative phosphorylation a vital pathway changes during development remains unchanged when applied. Liver tissue OVX-induced exhibited lipid peroxidation, impaired mitochondria, downregulated ERα/SIRT1/PGC-1α expression. An vitro study indicated protective effect treatment on hepatic steatosis could be abolished ERα or SIRT1 selectively inhibited. This damage accompanied reduced complex activity peroxidation. current research indicates upregulates signaling protects prevent
Язык: Английский
Процитировано
5
Animals, Год журнала: 2023, Номер 13(24), С. 3832 - 3832
Опубликована: Дек. 13, 2023
Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme of de novo biosynthesis pyrimidine. Although the involvement DHODH in resisting ferroptosis has been successively reported recent years, which greatly advanced understanding mechanism programmed cell death (PCD), genetic sequence yak gene and its roles are still unknown. For this purpose, we firstly cloned coding region (1188 bp) from liver conducted characterization analysis predictive protein that consists 395 amino acids. We found presented high conservation among species. Second, expression profile various tissues was investigated using RT-qPCR. The results demonstrated widely expressed different tissues, with particularly levels spleen, heart, liver. Third, to investigate regulating cells, skin fibroblasts (YSFs) were isolated fetuses. And then, bisphenol S (BPS) used induce vitro model YSFs. observed BPS decreased viability (CCK8) membrane potential (JC-1) YSFs dose-dependent manner induced oxidative stress by elevating reactive oxygen species (ROS). Simultaneously, it evident effectively augmented indicators associated (MDA BODIPY staining) reduced GSH levels. Importantly, co-administration Ferrostatin-1 (Fer), potent inhibitor ferroptosis, significantly alleviated aforementioned markers, thereby confirming successful induction BPS. Finally, overexpression plasmids siRNAs designed transfected respectively into BPS-cultured modulate expression. findings revealed occurrence BPS-induced while interference intensified process In summary, successfully gene, demonstrating remarkable across Moreover, as model, study confirmed role yaks. These offer valuable theoretical foundations for future investigations functionality underlying mechanisms
Язык: Английский
Процитировано
3
Phytotherapy Research, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 8, 2024
Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to pathogenesis DBJDs, targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti-inflammatory antioxidant properties, have shown unique advantages preventing potentially through modulating ferroptosis. This article provides an overview latest research on ferroptosis, with focus role DBJDs therapeutic potential natural products this pathway, offering novel insights prevention treatment DBJDs.
Язык: Английский
Процитировано
0
Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0
Molecular Therapy — Nucleic Acids, Год журнала: 2024, Номер 36(1), С. 102433 - 102433
Опубликована: Дек. 21, 2024
Язык: Английский
Процитировано
0