The Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis in Inflammatory Bowel Disease, Colorectal Cancer, and Intestinal Injury DOI Creative Commons
Ping Zhou, Shun Zhang,

Maohua Wang

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 820 - 820

Published: May 11, 2023

Cell death includes programmed and nonprogrammed cell death. The former mainly ferroptosis, necroptosis, pyroptosis, autophagy, apoptosis, while the latter refers to necrosis. Accumulating evidence shows that pyroptosis play essential regulatory roles in development of intestinal diseases. In recent years, incidence inflammatory bowel disease (IBD), colorectal cancer (CRC), injury induced by ischemia-reperfusion (I/R), sepsis, radiation have gradually increased, posing a significant threat human health. advancement targeted therapies for diseases based on provides new strategies treating Herein, we review with respect regulation highlight underlying molecular mechanisms potential therapeutic applications.

Language: Английский

Hyperoxia-activated Nrf2 regulates ferroptosis in intestinal epithelial cells and intervenes in inflammatory reaction through COX-2/PGE2/EP2 pathway DOI Creative Commons
Yanping Liu,

Tianming Li,

Changping Niu

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 3, 2025

Language: Английский

Citations

2
Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation DOI Creative Commons
Xiang Yu, Xiaying Chen, Wengang Wang

et al.

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 29, 2021

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl , has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin bladder cancer cells remain unexplored. In this study, we found that triggered cell death cycle arrest cells. Then demonstrated could promote accumulation lethal lipid-based reactive oxygen species (ROS) depletion glutathione (GSH), suggesting induction ferroptosis. further ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused death, showing played major role death. vivo also showed suppressed tumor growth by inducing Mechanistically, nuclear factor E2-related 2 (NRF2) inactivation was key determinant caused erianin. cells, compound tert-butylhydro-quinone (TBHQ), an activator NRF2, erianin-induced Whereas, NRF2 inhibition used shRNA augmented response induced treatment. conclusion, our data provide first evidence can initiate ferroptosis-like lipid peroxidation cancer, which will hopefully become promising anticancer for treatment cancer.

Language: Английский

Citations

71
Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis DOI Creative Commons
Bufu Tang, Jinyu Zhu,

Shiji Fang

et al.

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 172, P. 312 - 329

Published: June 16, 2021

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's (CD), is a group of chronic recurrent incurable gastrointestinal diseases with an unknown etiology that leads to high risk developing colitis-associated colorectal cancer (CRC). In this study, we measured the expression characteristics MELK in IBD CRC tissues explored regulatory effect OTSSP167 (a MELK-selective inhibitor) on mice models carcinogenesis analyzed specific molecular mechanisms. DSS-induced (CAC) model were treated inhibitor then fight against clinical symptoms CAC was measured. addition, underlying mechanism treatment vitro vivo anti-ferroptosis anti-inflammatory response further explored. We found pharmacological inhibition indicated significantly alleviate inflammatory colitis, reduce intestinal damage, effectively inhibit occurrence progression colitis-propelled carcinogenesis, which closely related regulation gut microbial composition, OTSSP167-mediated fecal microbiota transplantation alleviated colitis. obviously inhibited ferroptosis tissue suppressed macrophage infiltration M1 polarization, reduced secretion pro-inflammatory factors. Further exploration revealed AKT/IKK/P65 ERK/IKK/P65 signaling cascades both vitro, may help inflammation control cancer. Our findings lay theoretical foundation for use as its carcinogenesis; additionally, be potentially effective target molecule, thus providing more options treatment.

Language: Английский

Citations

66
Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells DOI
Jun Guo, Rong Wang,

Min Fei

et al.

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(5), P. 1065 - 1077

Published: June 30, 2022

Acute kidney injury (AKI) represents a prevailing complication of sepsis, and its onset involves ferroptosis. Ginsenoside Rg1 exerts positive effect on diseases. This study explored the action ginsenoside in sepsis-induced AKI (SI-AKI) by regulating ferroptosis renal tubular epithelial cells (TECs). Sepsis rat models were established using cecal ligation puncture (CLP) cell treating human TECs (HK-2) with LPS to induce Serum creatinine (SCr) blood urea nitrogen (BUN) urine KIM1 contents rats determined ELISA kits. Kidney tissues subjected immunohistochemical H&E stainings. Iron concentration, malondialdehyde (MDA), glutathione (GSH), ferroptosis-related protein (ferritin light chain [FTL], ferritin heavy [FTH], GSH peroxidase 4 [GPX4], Ferroptosis suppressor 1 [FSP1]) levels HK-2 measured kits Western blotting. viability was detected counting kit-8, death observed via propidium iodide staining. Reactive oxygen species accumulation C11 BODIPY 581/591 as molecular probe. In CLP rats, reduced SCr, BUN, KIM1, NGAL levels, thus palliating SI-AKI. Additionally, decreased iron content, FTL, FTH, MDA elevated GPX4, FSP1, thereby inhibiting lipid peroxidation Moreover, FSP1 knockdown annulled inhibition vitro experiments, raised lowered during ferroptosis, antiferroptosis activity dependent FSP1. alleviates SI-AKI, possibly resulting from through

Language: Английский

Citations

66
Ferroptosis and Its Role in Chronic Diseases DOI Creative Commons
Wenli Hu, Kehong Liang, Hong Zhu

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2040 - 2040

Published: June 27, 2022

Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of death. The course ferroptosis can be accurately the metabolism iron, lipids, amino acids, various signal pathways. In this review, we summarize basic ferroptosis, its regulation, as well relationship between chronic diseases such cancer, nervous system metabolic inflammatory bowel diseases. Finally, describe regulatory effects food-borne active ingredients on ferroptosis.

Language: Английский

Citations

65
Emerging Pathological Engagement of Ferroptosis in Gut Diseases DOI Creative Commons
Weihua Gao, Ting Zhang, Hao Wu

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is mainly characterized by chronic progressive inflammation that damages the gastrointestinal mucosa. Increasing studies have enlightened dysregulated cell death occurs in inflamed sites, leading to disruption of intestinal barrier aggravating inflammatory response. Ferroptosis, a newly form regulated death, driven lethal accumulation lipid peroxides catalyzed cellular free iron. It has been widely documented fundamental features ferroptosis, iron deposition, GSH exhaustion, GPX4 inactivation, peroxidation, are manifested injured tract IBD patients. Furthermore, manipulation critical ferroptotic genes could alter progression, severity, or even morbidity experimental colitis. Herein, we critically summarize recent advances field focusing on interpreting potential engagement ferroptosis pathogenesis IBD. Moreover, attempting shed light perspective insight into possibility targeting as novel therapeutic designs for clinical intervention these diseases.

Language: Английский

Citations

61
Furin inhibits epithelial cell injury and alleviates experimental colitis by activating the Nrf2-Gpx4 signaling pathway DOI

Shouquan Dong,

Yuanyuan Lu,

Ganjing Peng

et al.

Digestive and Liver Disease, Journal Year: 2021, Volume and Issue: 53(10), P. 1276 - 1285

Published: Feb. 25, 2021

Language: Английский

Citations

60
Inhibiting Ferroptosis: A Novel Approach for Ulcerative Colitis Therapeutics DOI Creative Commons
Jinke Huang, Jiaqi Zhang, Jinxin Ma

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 9

Published: March 26, 2022

Ulcerative colitis (UC) is a recurrent and persistent nonspecific inflammatory bowel disease (IBD) that greatly affects human survival social wealth. Despite the advances in treatment of UC, there still high demand for novel therapeutic strategies UC patients. Cell death critical to development progression UC. Understanding how intestinal cells die prevent damage great interest diagnosis early Ferroptosis, form regulated cell (RCD) manifested by iron accumulation, lipid peroxidation, excessive reactive oxygen species (ROS) production, has been shown contribute Inhibitors ferroptosis have validated models Here, we reviewed mechanisms initiation control summarize activity inhibitors We further discussed possibility inhibiting as target These findings revealed protect colonic mucosa highlighted importance process.

Language: Английский

Citations

50
Zero‐Valence Selenium‐Enriched Prussian Blue Nanozymes Reconstruct Intestinal Barrier against Inflammatory Bowel Disease via Inhibiting Ferroptosis and T Cells Differentiation DOI
Dongdong Zhu, Haitao Wu, Kai Jiang

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(12)

Published: Jan. 18, 2023

Abstract The structural disruption of mechanical barrier and dysfunction immune in intestinal, are important factors, that aggravate inflammatory bowel disease (IBD). To tackle this challenge, a multifunctional nanozyme capable scavenging reactive oxygen species (ROS) inhibiting ferroptosis or T cells differentiation for IBD therapy is here reported. In work, zero‐valence selenium‐enriched Prussian blue nanozymes (Se‐HMPB nanozymes) prepared via the hard template method. PB with multi‐enzyme activities can effectively scavenge various ROS tissues. Meanwhile, presence selenium element endows glutathione peroxidase activity Se‐HMPB nanozymes, which inhibit reverse lipid peroxidation intestinal epithelial to protect ulcerative colitis (UC) model. addition, supplementation realize efficient inhibition on Crohn's (CD) model, regulating barrier. Thus, reconstructed UC CD models, depicting great potential alleviate IBD.

Language: Английский

Citations

41
Iron overload induces colitis by modulating ferroptosis and interfering gut microbiota in mice DOI

Ke Gu,

Aimin Wu, Bing Yu

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 905, P. 167043 - 167043

Published: Sept. 17, 2023

Language: Английский

Citations

36