Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer DOI Creative Commons

Chengmin Deng,

Lin Xiong, Yang Chen

et al.

BMC Pulmonary Medicine, Journal Year: 2023, Volume and Issue: 23(1)

Published: Sept. 25, 2023

Abstract Background Metformin is the most frequently prescribed medication for treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety cancer types. can inhibit growth many cells through various mechanisms, including ferroptosis. However, it still unclear whether metformin induce ferroptosis lung cancer. Methods This study evaluated effect by detecting levels oxidative stress factors, ferrous ions, expression ferroptosis-related genes A549 H1299 cell lines treated with or without metformin. Results The results showed that increased MDA, ROS iron while decreased GSH, T-SOD CAT. Meanwhile, reduced protein Gpx4 SLC7A11, Nrf2 HO-1, addition inhibitor ferrostatin-1 reversed reduction. Conclusions These demonstrated exerts effects inducing Nrf2/HO-1 signaling pathway cells, providing theoretical basis drug therapy patients.

Language: Английский

Ketone bodies: from enemy to friend and guardian angel DOI Creative Commons
Hubert Kolb, Kerstin Kempf, Martin Röhling

et al.

BMC Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: Dec. 9, 2021

Abstract During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and breakdown of fat becomes major source energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies generated from β-oxidation fatty acids secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma thus indicate dietary shortage carbohydrates. Ketone not only serve fuel but also promote resistance oxidative inflammatory stress, there decrease anabolic insulin-dependent expenditure. It has been suggested beneficial non-metabolic actions on organ functions mediated by them acting ligand specific cellular targets. We propose here role different pathway initiated induction stress mitochondria during increased ketolysis. Oxidative induced body long term because it initiates an adaptive (hormetic) response characterized activation master regulators cell-protective mechanism, nuclear factor erythroid 2-related 2 (Nrf2), sirtuins, AMP-activated kinase. results resolving upregulation anti-oxidative anti-inflammatory activities, improved mitochondrial function growth, DNA repair, autophagy. In heart, enhanced ketolysis improves damage after ischemic insults cardiotoxic doxorubicin. Sodium-dependent glucose co-transporter (SGLT2) inhibitors may exert their cardioprotective action via increasing conclude synthesis use periods deficient food supply low causes latter protective which allows cells cope with lower availability. Keywords Ketogenic diet, bodies, Beta hydroxybutyrate, Insulin, Obesity, Type diabetes, Inflammation, Cardiovascular disease, SGLT2, Hormesis

Language: Английский

Citations

235

The biological applications of DNA nanomaterials: current challenges and future directions DOI Creative Commons
Wenjuan Ma,

Yuxi Zhan,

Yuxin Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Oct. 8, 2021

Abstract DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With rapid progress nanotechnology, multitudinous nanomaterials have designed with shape size based on classic Watson–Crick base-pairing molecular self-assembly. Some materials could functionally change cell behaviors, such migration, proliferation, differentiation, autophagy, anti-inflammatory effects. single-stranded DNAs (ssDNAs) or RNAs secondary structures via self-pairing, named aptamer, possess ability of targeting, which are selected systematic evolution ligands exponential enrichment (SELEX) applied tumor targeted diagnosis treatment. three-dimensional (3D) nanostructures stable investigated carrier systems to delivery multiple medicine gene therapeutic agents. While functional promoted development innovative designs preparation strategies, also proved great potential medical use, there is still long way go eventual application real life. Here this review, we conducted comprehensive survey structural history nanomaterials, introduced principles summarized their fields, discussed current challenges further that help achieve future.

Language: Английский

Citations

224

ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways DOI Creative Commons
Arthur José Pontes Oliveira de Almeida, Júlio César Pinheiro Lúcio de Oliveira,

Larisse Virgolino da Silva Pontes

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 23

Published: Oct. 19, 2022

Reactive oxygen species (ROS) are bioproducts of cellular metabolism. There is a range molecules with oxidizing properties known as ROS. Despite those being implied negatively in aging and numerous diseases, their key role signaling evident. ROS control several biological processes such inflammation, proliferation, cell death. The redox underlying these events one characteristic the new generation scientists aimed at defining environment. potential, which includes balance sources antioxidant system, implies an important target for understanding cells’ fate derived from signaling. In this review, we summarized chemical, balance, signaling, implications aging.

Language: Английский

Citations

169

Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders DOI Creative Commons
Stefan W. Ryter

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 555 - 555

Published: March 15, 2022

The heme oxygenase (HO) enzyme system catabolizes to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity represented two distinct isozymes, the inducible form, HO-1, a constitutive HO-2, encoded genes (HMOX1, HMOX2, respectively). HO-1 responds transcriptional activation in response wide variety of chemical physical stimuli, including its natural substrate heme, oxidants, phytochemical antioxidants. expression regulated NF-E2-related factor-2 counter-regulated Bach-1, heme-sensitive manner. Additionally, HMOX1 promoter polymorphisms have been associated with human disease. induction can confer protection inflammatory conditions through removal pro-oxidant potential catalyst lipid peroxidation, whereas iron released from may trigger ferritin synthesis or ferroptosis. production heme-derived reaction products (i.e., BV, BR) contribute HO-dependent cytoprotection via antioxidant immunomodulatory effects. BVR BR newly recognized roles regulation. CO alter mitochondrial function leading modulation downstream signaling pathways that culminate anti-apoptotic, anti-inflammatory, anti-proliferative This review will present evidence for beneficial effects diseases, cardiovascular disease (CVD), metabolic conditions, diabetes obesity, as well acute chronic diseases liver, kidney, lung. Strategies targeting pathway, genetic expression, application BR, gas, donor compounds show therapeutic organ ischemia/reperfusion injury. Evidence studies indicate represent biomarker oxidative stress various clinical while increases serum levels correlated inversely risk CVD Ongoing trials investigate

Language: Английский

Citations

152

Electrochemical biosensors represent promising detection tools in medical field DOI Creative Commons
Li Zhang, Wenqiang Guo,

Chenrui Lv

et al.

Advanced Sensor and Energy Materials, Journal Year: 2023, Volume and Issue: 2(4), P. 100081 - 100081

Published: Oct. 29, 2023

In recent years, there has been a growing demand for rapid detection methods, leading to the proliferation of biosensors, particularly electrochemical which have garnered substantial attention from researchers. The fusion biosensors with advanced sensing technology given rise diverse array characterized by their capabilities and heightened sensitivity. Consequently, an imperative exists comprehensively recapitulate advances in especially within realm clinical medicine. This review aims elucidate applications delineate future development prospects, facilitating more profound comprehension further progression this field. Specifically, we will examine utilization medicine, encompassing roles point-of-care testing, disease diagnosis, therapeutic monitoring. Moreover, spotlight emerging trends prospective innovations, such as evolution nanostructured sensors portable devices. By providing comprehensive overview potential significantly contribute advancement field serve catalyst research into innovative tools.

Language: Английский

Citations

51

Oxidative Stress in Ischemic Heart Disease DOI Open Access
Aleksandar Kibel, Ana Marija Lukinac, Vedran Đambić

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 30

Published: Dec. 29, 2020

One of the novel interesting topics in study cardiovascular disease is role oxidation system, since inflammation and oxidative stress are known to lead diseases, their progression complications. During decades research, many complex interactions between agents stress, oxidation, antioxidant systems have been elucidated, numerous important pathophysiological links na number disorders diseases established. This review article will present most relevant knowledge linking vascular dysfunction disease. The focus on endotheleial dysfunction, atherosclerosis, other pathogenetic processes mechanisms that contribute development ischemic heart

Language: Английский

Citations

102

Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells DOI Creative Commons
Qingxin Song, Shanxin Peng, Zhiqing Sun

et al.

Yonsei Medical Journal, Journal Year: 2021, Volume and Issue: 62(9), P. 843 - 843

Published: Jan. 1, 2021

PURPOSE Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide common glioma patients. In addition, mechanisms the anti-tumor effects of are largely unknown. Ferroptosis a form programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed elucidate involvement ferroptosis temozolomide. MATERIALS AND METHODS We utilized CCK8 assay evaluate cytotoxicity. Levels lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH) were measured. Flow cytometry fluorescence microscope detect production reactive oxygen species (ROS). Western blotting, RT-PCR siRNA transfection investigate molecular mechanisms. RESULTS levels LDH, MDA, iron reduced GSH TG905 cells. Furthermore, we found that ROS DMT1 expression elevated cells treated with accompanied decrease peroxidase 4, indicating an iron-dependent death, ferroptosis. Our results also showed temozolomide-induced associated regulation Nrf2/HO-1 pathway. Conversely, knockdown evidently blocked CONCLUSION Taken together, our findings indicate may suppress growth partly inducing targeting glioblastoma

Language: Английский

Citations

80

Etomidate Attenuates the Ferroptosis in Myocardial Ischemia/Reperfusion Rat Model via Nrf2/HO-1 Pathway DOI Open Access

Zhenqian Lv,

Feng’e Wang,

Xingfeng Zhang

et al.

Shock, Journal Year: 2021, Volume and Issue: 56(3), P. 440 - 449

Published: June 4, 2021

Ferroptosis has been found to play an important role in myocardial ischemia reperfusion (MIR) injury (MIRI). This study aimed explore whether the improvement effect of Etomidate (Eto) on MIRI was related ferroptosis.The rats were constructed using left anterior descending artery occlusion for 30 min followed by 3 h. The Eto post-conditioning performed administration at beginning reperfusion. For rescue experiments, pretreated with ferroptosis inducer erastin or Nrf2 inhibitor ML385 intraperitoneally 1 h prior MIR surgery.Eto mitigated cardiac dysfunction and myocardium damage, as well release creatine kinase lactate dehydrogenase caused ischemia/reperfusion (IR). Additionally, reduced expression fibrosis-related proteins (collagen II α-smooth muscle actin) secretion inflammatory factors (IL-6, IL-1β, TNF-α) rats. Also, inhibited IR-induced myocardium, including reducing superoxide dismutase content, glutathione activity, peroxidase 4 expression, while increasing levels malondialdehyde iron Acyl-CoA synthetase long-chain family member 4. Moreover, inhibition fibrosis inflammation could be eliminated erastin. up-regulation HO-1 protein nuclear translocation induced tissues rats, prevented Besides, MIR.Eto attenuated inhibiting via pathway, which may provide a new idea clinical therapy.

Language: Английский

Citations

67

The heart as a target for deltamethrin toxicity: Inhibition of Nrf2/HO-1 pathway induces oxidative stress and results in inflammation and apoptosis DOI
Xue Yang,

Yi Fang,

Jianbo Hou

et al.

Chemosphere, Journal Year: 2022, Volume and Issue: 300, P. 134479 - 134479

Published: March 31, 2022

Language: Английский

Citations

63

Natural antioxidants in diabetes treatment and management: prospects of astaxanthin DOI
Osman N. Kanwugu, Т. В. Глухарева, Irina Danilova

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2021, Volume and Issue: 62(18), P. 5005 - 5028

Published: Feb. 16, 2021

Diabetes remains a major health emergency in our entire world, affecting hundreds of millions people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality life, increases mortality as well economic burden among patients. Over years, oxidative stress and inflammation have been highlighted key players development progression diabetes associated complications. Much research has devoted, such, to role antioxidants diabetes. Astaxanthin is powerful antioxidant found mostly marine organisms. past several studies demonstrated that astaxanthin could be useful treatment management It shown protect β-cells, neurons organs including eyes, kidney, liver, etc. against injuries experienced during Furthermore, improves glucose lipid metabolism along health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these fact foods natural products biological pharmacological activities much interest 21st-century food drug industry, bright prospect

Language: Английский

Citations

62