Mechanistic study of dual‐function inhibitors targeting topoisomerase II and Rad51‐mediated DNA repair pathway against castration‐resistant prostate cancer DOI Open Access

Yi‐Chang Chiang,

Wohn‐Jenn Leu,

Yi‐Chin Chen

et al.

The Prostate, Journal Year: 2023, Volume and Issue: 83(16), P. 1549 - 1563

Published: Aug. 15, 2023

Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment and the therapeutic options are continuously advancing. This study aims discover anti-CRPC effects underlying mechanisms of small-molecule compounds targeting topoisomerase (TOP) II cellular components DNA damage repair.Cell proliferation was determined in CRPC PC-3 DU-145 cells using anchorage-dependent colony formation, sulforhodamine B assay flow cytometric analysis CFSE staining. Flow analyses propidium iodide staining JC-1 were used examine population cell-cycle phases mitochondrial membrane potential, respectively. Nuclear extraction performed detect nuclear localization repair pathways. Protein expressions Western blot analysis.A series azathioxanthone-based derivatives synthesized examined for bioactivities which WC-A13, WC-A14, WC-A15, WC-A16 displayed potent activities both cell models. These WC-A selectively downregulated TOP IIα IIβ but not I protein expression. WC-A15 more than on inhibition, dysfunction, induction caspase cascades indicating key role amine-containing side chain determining activities. Furthermore, induced an increase γH2AX activated ATR-Chk1 ATM-Chk2 signaling P21 expression also upregulated by showed least activity. Notably, exhibited different regulation Rad51, a major homologous recombination double-stranded break repair. inhibited, whereas induced, translocation Rad51.The data suggest that exhibit through inhibition activities, leading stress-involved activation apoptosis. Moreover, display inhibitory Rad51-mediated pathway may apoptotic effect cells.

Language: Английский

Alcohol and the mechanisms of liver disease DOI Creative Commons
Mo Chen, Wanglei Zhong, Weiqi Xu

et al.

Journal of Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 38(8), P. 1233 - 1240

Published: July 9, 2023

Abstract Alcoholic liver disease (ALD), which is a leading cause of morbidity and mortality worldwide, covers large spectrum injuries ranging from simple steatosis to steatohepatitis, advanced fibrosis, cirrhosis, hepatocellular carcinoma. The pathogenesis ALD includes genetic epigenetic alterations, oxidative stress, acetaldehyde‐mediated toxicity cytokine chemokine‐induced inflammation, metabolic reprogramming, immune damage, dysbiosis the gut microbiota. This review discusses progress in molecular mechanism ALD, could provide evidence for further research on potential therapeutic strategies targeting these pathways.

Language: Английский

Citations

24
CXCR4/CXCL12 axis: “old” pathway as “novel” target for anti‐inflammatory drug discovery DOI

Liuxin Lu,

Junjie Li, Xiaoying Jiang

et al.

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(3), P. 1189 - 1220

Published: Jan. 4, 2024

Inflammation is the body's defense response to exogenous or endogenous stimuli, involving complex regulatory mechanisms. Discovering anti-inflammatory drugs with both effectiveness and long-term use safety still direction of researchers' efforts. The inflammatory pathway was initially identified be involved in tumor metastasis HIV infection. However, research recent years has proved that CXC chemokine receptor type 4 (CXCR4)/CXC motif ligand 12 (CXCL12) axis plays a critical role upstream due its chemotaxis cells. Blocking cells by CXCL12 at site may block alleviate response. Therefore, developing CXCR4 antagonists become novel strategy for therapy. This review aimed systematically summarize analyze mechanisms action CXCR4/CXCL12 more than 20 diseases, highlighting crucial inflammation. Additionally, activities were discussed. findings might help generate new perspectives targeting axis.

Language: Английский

Citations

15
OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage DOI Creative Commons

Yunxiao Zhong,

Xinya Zhang, Ruibing Feng

et al.

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(6), P. 2825 - 2848

Published: Aug. 9, 2024

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms limitations identifying effective treatment targets. Recently, 8-oxoguanine glycosylase 1 (OGG1) has emerged a promising multifunctional therapeutic target for the of these challenging diseases. In this review, we systematically summarize multiple functions OGG1, including pro-inflammatory, tumorigenic, aging regulatory mechanisms. We also highlight potential OGG1 inhibitors activators potent agents aforementioned life-limiting conclude that serves hub; inhibition may provide novel approach preventing treating inflammation cancer, activation could be strategy disorders. Furthermore, an extensive overview successful applications regulation inflammatory, cancerous, aging-related Finally, discuss current future directions emerging marker The aim review is robust reference scientific researchers clinical drug developers development targeted drugs especially

Language: Английский

Citations

9
Glyphosate-triggered hepatocyte ferroptosis via suppressing Nrf2/GSH/GPX4 axis exacerbates hepatotoxicity DOI
Jingbo Liu,

Guangcheng Yang,

Hongna Zhang

et al.

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 862, P. 160839 - 160839

Published: Dec. 12, 2022

Language: Английский

Citations

33
Parishin A-loaded mesoporous silica nanoparticles modulate macrophage polarization to attenuate tendinopathy DOI Creative Commons
Lisha Zhu, Yu Wang, Shanshan Jin

et al.

npj Regenerative Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 10, 2023

Macrophages are involved mainly in the balance between inflammation and tenogenesis during healing process of tendinopathy. However, etiological therapeutic strategies to efficiently treat tendinopathy by modulating macrophage state still lacking. In this study, we find that a small molecule compound Parishin-A (PA) isolated from Gastrodia elata could promote anti-inflammatory M2 polarization inhibiting gene transcription protein phosphorylation signal transducers activators 1. Local injection or sustained delivery PA mesoporous silica nanoparticles (MSNs) almost recover native tendon's dense parallel-aligned collagen matrix collagenase-induced macrophage-mediated immune microenvironment preventing heterotopic ossification. Especially, MSNs decrease doses PA, frequency yield preferable effects. Mechanistically, intervention with indirectly inhibit activation mammalian target rapamycin repress chondrogenic osteogenic differentiation tendon stem/progenitor cells influencing inflammatory cytokine secretion. Together, pharmacological natural small-molecule modulate status appears be promising strategy for treatment.

Language: Английский

Citations

18
Quercetin-primed BMSC-derived extracellular vesicles ameliorate chronic liver damage through miR-136-5p and GNAS/STAT3 signaling pathways DOI

Xiaodan Jiang,

Zhejun Liu,

Hongjie You

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113162 - 113162

Published: Sept. 27, 2024

Language: Английский

Citations

5
Research Progress of Pyroptosis in Fatty Liver Disease DOI Open Access

Rongxuan Li,

Weiyue Xue,

Huiting Wei

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13065 - 13065

Published: Aug. 22, 2023

Fatty liver disease (FLD) is a clinical and pathological syndrome characterized by excessive fat deposition even steatosis in hepatocytes. It has been proven that inflammation induced its derivatives are involved the pathogenesis of FLD, while precise mechanism still remains poorly understood. Pyroptosis programmed inflammatory cell death driving swelling membrane rupture. initiated activation inflammasomes caspases, which further cleaves activates various gasdermins, leading to pores forming on release pro-inflammatory factors such as interleukin (IL)-1β IL-18. Recent studies demonstrate pyroptosis occurs hepatocytes, inhibiting could effectively reduce ameliorate from attracting our prime focus role FLD. In this manuscript, we reviewed current understanding FLD development, aiming provide new insights potential research targets for diagnosis intervention

Language: Английский

Citations

13
Baicalin nanoemulsion mitigates cisplatin-induced hepatotoxicity by alleviating oxidative stress, inflammation, and restoring cellular integrity DOI

Hadir Farouk,

Maha Nasr, Marawan A. Elbaset

et al.

Toxicology and Applied Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 117231 - 117231

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Anticancer Effects of the Garlic Organosulfide Diallyl Trisulfide through the Attenuation of B[a]P-Induced Oxidative Stress, AhR Expression, and DNA Damage in Human Premalignant Breast Epithelial (MCF-10AT1) Cells DOI Open Access
Dominique T. Ferguson,

Equar Taka,

Syreeta L. Tilghman

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 923 - 923

Published: Jan. 11, 2024

Benzo[a]pyrene (B[a]P) is the most characterized polycyclic aromatic hydrocarbon associated with breast cancer. Our lab previously reported that organosulfur compound (OSC), diallyl trisulfide (DATS), chemoprevention mechanism works through induction of cell cycle arrest and a reduction in oxidative stress DNA damage normal epithelial cells. We hypothesize DATS will inhibit B[a]P-induced cancer initiation premalignant (MCF-10AT1) In this study, we evaluated ability to attenuate neoplastic transformation MCF-10AT1 cells by measuring biological endpoints such as proliferation, clonogenicity, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, well repair antioxidant proteins. The results indicate B[a]P induced clonogenic ROS 8-OHdG increasing AhR, ARNT/HIF-1β, CYP1A1 protein expression compared control B[a]P/DATS’s co-treatment (CoTx) inhibited AhR expression, levels alone attenuated all above-mentioned changes causing chemopreventive effect. This study demonstrates, for first time, prevents from undergoing transformation, thus providing more evidence its effects

Language: Английский

Citations

3
OGG1 prevents atherosclerosis-induced vascular endothelial cell injury through mediating DNA damage repair DOI
Yiming Zhang, Guohua Wang, Miaojun Xu

et al.

Clinical Hemorheology and Microcirculation, Journal Year: 2024, Volume and Issue: 87(2), P. 249 - 261

Published: Feb. 16, 2024

This study was designed to investigate the role of 8-oxoguanine DNA glycosylase 1 (OGG1) in preventing atherosclerosis-induced vascular EC injury, thereby providing a theoretical basis for exploration drug targets and treatment methods atherosclerosis.

Language: Английский

Citations

3