Pharmacologic inhibition of eIF4A blocks NRF2 synthesis to prevent osteosarcoma metastasis

Clinical Cancer Research, Год журнала: 2024, Номер 30(19), С. 4464 - 4481

Опубликована: Июль 30, 2024

Effective therapies for metastatic osteosarcoma (OS) remain a critical unmet need. Targeting mRNA translation in OS offers promising option, as selective drives the synthesis of cytoprotective proteins under harsh microenvironmental conditions to facilitate competence.

Язык: Английский

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Salinomycin, a potent inhibitor of XOD and URAT1, ameliorates hyperuricemic nephropathy by activating NRF2, modulating the gut microbiota, and promoting SCFA production

Chemico-Biological Interactions, Год журнала: 2024, Номер 403, С. 111220 - 111220

Опубликована: Авг. 31, 2024

Язык: Английский

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Artemisinin conferred cytoprotection to human retinal pigment epithelial cells exposed to amiodarone-induced oxidative insult by activating the CaMKK2/AMPK/Nrf2 pathway

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 16, 2024

Abstract Background Ocular toxicity is a severe adverse effect that limits the chronic clinical use of antiarrhythmic drug amiodarone. Here, we aimed to evaluate cytoprotective artemisinin and explore potential signalling pathways in human retinal pigment epithelial (RPE) cell cultures. Methods D407 cultures were exposed amiodarone impact was evaluated. The key parameters included lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) generation, mitochondrial membrane (MMP). We also assessed protein levels cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), phosphorylated adenosine monophosphate-activated kinase (AMPK)ɑ (p-AMPK), calcium/calmodulin-dependent 2 (CaMKK2), nuclear factor erythroid 2-related (Nrf2). Results Artemisinin reduced cytotoxicity induced by amiodarone, as reflected decreased LDH ROS MMP disruption. Additionally, increased p-AMPK, CaMKK2, Nrf2 levels. Inhibition AMPK, or abolished artemisinin. AMPK activation knockdown further supported its protective role. Conclusions protected RPE cells from amiodarone-induced damage via CaMKK2/AMPK/Nrf2 pathway. vivo experiments mice confirmed efficacy preventing injury caused These results suggest an artemisinin-based eye formulation could be repurposed for treating ocular toxicity.

Язык: Английский

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Redox Regulation of Proteostasis

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(12), С. 107977 - 107977

Опубликована: Ноя. 8, 2024

Язык: Английский

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Mercapto-NSAIDs Generate a Non-Steroidal Anti-Inflammatory Drug (NSAID) and Hydrogen Sulfide

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A new class of mercapto-NSAIDs that generate persulfide, H 2 S, and the NSAID is reported.

Язык: Английский

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Nrf2/Nlrp3 Signaling in Aging Bmscs: Traf6 Intervention as a Novel Approach to Osteoporosis Treatment

Опубликована: Янв. 1, 2025

Язык: Английский

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Keap1-independent Nrf2 regulation: a novel therapeutic target for treating kidney disease

Redox Biology, Год журнала: 2025, Номер 82, С. 103593 - 103593

Опубликована: Март 12, 2025

Язык: Английский

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The clinical-grade CBP/ p300 inhibitor CCS1477 represses the global NRF2-dependent cytoprotective transcription program and re-sensitizes cancer cells to chemotherapeutic drugs

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Sphaeropsidin A covalently binds to Cys 151 of Keap1 to attenuate LPS-induced acute pneumonia in mice

Redox Biology, Год журнала: 2025, Номер unknown, С. 103621 - 103621

Опубликована: Март 1, 2025

Kelch ECH-associating protein 1 (Keap1)-Nuclear factor erythroid 2-related 2 (Nrf2) axis is crucial for regulating oxidative stress and inflammatory responses in acute pneumonia. Sphaeropsidin A (SA) a antioxidant diterpenoid isolated from Sphaeropsis sapinea f. sp. cupressi, discovered as novel Nrf2 agonist by our research group previously. However, the accurate function mechanism of SA treating pneumonia are still unknown. The therapeutic effect was evaluated LPS-induced mice. underlying action then analyzed transcriptomics. direct target identified through synthesis SA-biotin probe, binding amino acid residues were found verified LC-MS/MS analysis site-specific mutation. Finally, knockout mice employed to verify SA. Our data indicated that significantly inhibited via up-regulating Nrf2, inhibiting NLRP3 inflammasome NF-κB activation, Keap1 Specifically, effective dose only mg/kg. selectively covalent bound cysteine 151 residue (Cys151). mediated activation reduced level ROS, thereby inflammasome. Besides, formed hydrogen bond with ASP48 ASC, blocking its oligomerization This study indicates might be new molecule activate promising drug candidate or lead therapy Nrf2/NF-κB/NLRP3 axis.

Язык: Английский

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Rhodotorula Yeast Culture Improved the Antioxidant Capacity, Lipid Metabolism, and Immunity of Sheep Livers

Veterinary Sciences, Год журнала: 2025, Номер 12(4), С. 314 - 314

Опубликована: Март 30, 2025

There is currently no research on the application evaluation of R. mucilaginosa yeast culture (RYC) in animal production. Therefore, this study investigated effects RYC antioxidant capacity, lipid metabolism, and immunity sheep livers. Twenty-four 3-month-old Duhan male (36 ± 4 kg) were divided into four groups. The control group received a basal diet, L diet + 10 g/sheep/day RYC, M 20 H 40 RYC. trial lasted for 75 days. results showed that content glutathione peroxidase livers was significantly increased by 26.6%, malondialdehyde decreased 38% (p < 0.05). Additionally, serum levels total cholesterol, triglycerides, high-density lipoprotein low-density cholesterol decreased; liver C16:0 C18:2n6C C20:1 Furthermore, contents cytokines TNF-α IFN-γ from also 20% 24.8%, respectively These findings suggest supplementation with can enhance improve reduce inflammation livers, which advantageous farming healthy sheep.

Язык: Английский

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