OTULIN confers cisplatin resistance in osteosarcoma by mediating GPX4 protein homeostasis to evade the mitochondrial apoptotic pathway DOI Creative Commons

Zehang Zheng,

Yunhao Zeng,

Xing Bao

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Дек. 26, 2024

Abstract Background Osteosarcoma (OS), the most prevalent primary malignant bone tumor in children and adolescents, arises from bone-forming mesenchymal cells. Despite advancements surgical resection neoadjuvant chemotherapy (cisplatin, doxorubicin, methotrexate), resistance remains a significant challenge, leading to poor survival rates patients with metastatic or recurrent OS. Methods In this study, we focused on role of OTULIN, key linear deubiquitinating enzyme, OS chemoresistance. addition, mechanistic investigations were carried out identify potential downstream targets OTULIN involved cisplatin resistance. Results Our results demonstrated that expression was significantly upregulated tissues cell lines following treatment but not response doxorubicin methotrexate. High associated reduced sarcoma patients. Furthermore, immunohistochemical analysis prechemotherapy postchemotherapy revealed increased samples. vitro plays critical mediating Mechanistically, GPX4 could be target conferring by blocking mitochondrial apoptotic pathway ferroptosis. Specifically, prevents proteasomal degradation reducing its ubiquitin level, thereby Conclusion This study highlights importance chemoresistance provides promising approach for targeting OTULIN-GPX4 axis improve prognosis findings offer new insights into molecular mechanisms underlying suggest therapeutic future clinical interventions.

Язык: Английский

The role of polyphenols in modulating mitophagy: Implications for therapeutic interventions DOI Creative Commons
Xinyu Lin, Wenkai Liu, Xizhuo Hu

и другие.

Pharmacological Research, Год журнала: 2024, Номер 207, С. 107324 - 107324

Опубликована: Июль 24, 2024

This review rigorously assesses the burgeoning research into role of polyphenols in modulating mitophagy, an essential cellular mechanism for targeted removal impaired mitochondria. These natural compounds, known their low toxicity, are underscored potential therapeutic strategies against a diverse array diseases, such as neurodegenerative, cardiovascular, and musculoskeletal disorders. The analysis penetrates deeply molecular mechanisms whereby promote particularly by influencing crucial signaling pathways transcriptional regulators, including phosphatase tensin homolog (PTEN) induced putative kinase 1 (PINK1)/parkin forkhead box O3 (FOXO3a) pathways. Noteworthy discoveries include neuroprotective properties resveratrol curcumin, which affect both autophagic mitochondrial dynamics, pioneering integration with other substances to amplify effectiveness. Furthermore, confronts issue polyphenol bioavailability emphasizes imperative clinical trials corroborate viability. By delivering exhaustive synthesis contemporary insights recent advancements mitophagy research, this endeavors catalyze additional foster creation innovative modalities that exploit distinctive attributes manage prevent disease.

Язык: Английский

Процитировано

5
Recent advances in ruthenium（III） complex-loaded nanomaterial for enhanced cancer therapy efficacy DOI

Xuemei Zhong,

Ye Zhang, Jian-Hua Wei

и другие.

Drug Development and Industrial Pharmacy, Год журнала: 2025, Номер unknown, С. 1 - 18

Опубликована: Янв. 21, 2025

Objective Amid the escalating global cancer incidence, development of effective and safe anticancer drugs is a critical priority in medical research. Addressing clinical shortcomings ruthenium-based are currently prominent focus

Язык: Английский

Процитировано

0
Ethanol precipitation process affects the pharmacokinetic characteristics of major active glycosides of Qiong-Yu-Gao: evidences in normal and cisplatin-induced acute kidney injury rats DOI

Lin-Xia Chen,

Yao Wang, Rongrong Zhu

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119809 - 119809

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Enhancing chemotherapeutic efficacy: Niosome‐encapsulated Dox‐Cis with MUC‐1 aptamer DOI Creative Commons
Fırat Barış Barlas,

Bilge Olceroglu,

Didem Ag Seleci

и другие.

Cancer Medicine, Год журнала: 2024, Номер 13(15)

Опубликована: Авг. 1, 2024

Abstract Background Cancer remains a formidable global health challenge, currently affecting nearly 20 million individuals worldwide. Due to the absence of universally effective treatments, ongoing research explores diverse strategies combat this disease. Recent efforts have concentrated on developing combined drug regimens and targeted therapeutic approaches. Objective This study aimed investigate anticancer efficacy conjugated system, consisting doxorubicin cisplatin (Dox‐Cis), encapsulated within niosomes modified with MUC‐1 aptamers enhance biocompatibility target specific cancer cells. Methods The chemical structure Dox‐Cis conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR) Liquid Chromatography Quadrupole Time‐of‐Flight Mass Spectrometry (LC‐Q‐TOF/MS). zeta potential morphological parameters niosomal vesicles were determined through Dynamic Light Scattering (DLS) Transmission Electron Microscopy (TEM). In vitro assessments cell viability apoptosis conducted positive HeLa cells negative U87 Results findings confirmed successful conjugation Dox Cis niosomes. Nio/Dox‐Cis/MUC‐1 formulation demonstrated enhanced compared individual drugs their unencapsulated combination in both lines. Notably, exhibited greater effectiveness (38.503 ± 1.407) than (46.653 1.297). Conclusion underscores as promising strategy for treatment, particularly platforms that facilitate delivery approach could lead more personalized therapies.

Язык: Английский

Процитировано

3
Ginseng Radix et Rhizoma enhanced the effect of metoprolol in chronic heart failure by inhibiting autophagy in male C57BL/6J mice DOI Creative Commons

Niu Zi‐Chang,

Xiaoling Han, Jin Qi

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(8), С. e0301875 - e0301875

Опубликована: Авг. 14, 2024

Background Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol widely in HF. However, there no report on the combined effects of GS and metoprolol Objective This study investigated male C57BL/6J mice HF underlying mechanisms. Materials methods We utilized a mouse myocardial model to measure serum levels creatine kinase (CK) kinase-MB form (CK-MB) using automated biochemical analyzer. Lactate dehydrogenase (LDH) cardiac troponin (cTnT) were determined enzyme-linked immunosorbent assays. Autophagy cells was evaluated transmission electron microscopy, changes signal pathway proteins related autophagy analyzed by Western blotting. Results improved function, reduced damage, decreased CK, CK-MB, LDH, cTnT. The combination reducing autophagy-related (LC3, p62, Beclin1, Atg5) increasing ratios p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR. Conclusion enhanced anti-heart effect metoprolol. Its mechanism action might be inhibition mediated activation PI3K/Akt/mTOR pathway.

Язык: Английский

Процитировано

1
APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway DOI Open Access
Xingyue He,

Mingdian Wu,

Li-kun Chen

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 180, С. 117506 - 117506

Опубликована: Окт. 4, 2024

Язык: Английский

Процитировано

1
Enhancing Cisplatin Efficacy in Hepatocellular Carcinoma with Selenocystine: The Suppression of DNA Repair and Inhibition of Proliferation in Hepatoma Cells DOI
Pei‐Yi Wu, Uswatun Hasanah,

Sheng‐Hua Yang

и другие.

Chemico-Biological Interactions, Год журнала: 2024, Номер unknown, С. 111291 - 111291

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0
Yi-Qi-Jian-Pi-Xiao-Yu Formula Inhibits Cisplatin-Induced Acute Kidney Injury Through Suppressing Ferroptosis via STING-NCOA4-mediated Ferritinophagy DOI
Ji Zhu,

Aini Yuan,

Yifei Le

и другие.

Phytomedicine, Год журнала: 2024, Номер 135, С. 156189 - 156189

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

0
ALKBH5 insufficiency protects against ferroptosis-driven cisplatin-induced renal cytotoxicity DOI Creative Commons
Yu Zhu, Yanyan Jin, Xue He

и другие.

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Ноя. 18, 2024

In the clinical setting, cisplatin-induced nephrotoxicity primarily manifests as acute kidney injury (AKI). Recent studies have indicated that ferroptosis, a type of iron-dependent cell death, is closely involved in cisplatin nephrotoxicity. AlkB homologue 5 (ALKBH5), an N6-methyladenosine (m6A) eraser protein expressed various tissues, including kidneys, has been implicated this process. However, specific role ALKBH5 remains unknown. Our findings was upregulated AKI, and vivo study results were consistent with vitro study. Additionally, knockout transgenic animals found to mitigate renal dysfunction, whereas its knock-in exacerbated effects. revealed controls traditional ferroptosis metabolic pathway, leading worsening AKI experiments conducted both vitro. The efficacy pharmacological intervention targeting animal models demonstrated, ALKBH5-based gene therapy confirmed these displayed renoprotective effects against AKI. conclusion, highlighted crucial key regulator Overall, our research demonstrates significant impact controlling suggesting focusing on could be promising approach for treating cisplatin-related damage.

Язык: Английский

Процитировано

0
OTULIN confers cisplatin resistance in osteosarcoma by mediating GPX4 protein homeostasis to evade the mitochondrial apoptotic pathway DOI Creative Commons

Zehang Zheng,

Yunhao Zeng,

Xing Bao

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Дек. 26, 2024

Abstract Background Osteosarcoma (OS), the most prevalent primary malignant bone tumor in children and adolescents, arises from bone-forming mesenchymal cells. Despite advancements surgical resection neoadjuvant chemotherapy (cisplatin, doxorubicin, methotrexate), resistance remains a significant challenge, leading to poor survival rates patients with metastatic or recurrent OS. Methods In this study, we focused on role of OTULIN, key linear deubiquitinating enzyme, OS chemoresistance. addition, mechanistic investigations were carried out identify potential downstream targets OTULIN involved cisplatin resistance. Results Our results demonstrated that expression was significantly upregulated tissues cell lines following treatment but not response doxorubicin methotrexate. High associated reduced sarcoma patients. Furthermore, immunohistochemical analysis prechemotherapy postchemotherapy revealed increased samples. vitro plays critical mediating Mechanistically, GPX4 could be target conferring by blocking mitochondrial apoptotic pathway ferroptosis. Specifically, prevents proteasomal degradation reducing its ubiquitin level, thereby Conclusion This study highlights importance chemoresistance provides promising approach for targeting OTULIN-GPX4 axis improve prognosis findings offer new insights into molecular mechanisms underlying suggest therapeutic future clinical interventions.

Язык: Английский

Процитировано

0