Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy

Biomaterials, Journal Year: 2021, Volume and Issue: 277, P. 121110 - 121110

Published: Aug. 30, 2021

Language: Английский

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Interplay of oxidative stress, cellular communication and signaling pathways in cancer

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 2, 2024

Abstract Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays critical role in development cancer affecting genomic stability signaling pathways cellular microenvironment. Elevated levels ROS disrupt homeostasis contribute to loss normal functions, which are associated initiation progression various types cancer. In this review, we have focused on elucidating downstream that influenced oxidative stress carcinogenesis. These include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, cell type transitions. Dysregulation these can lead uncontrolled growth, impaired DNA repair mechanisms, evasion death, all hallmark features development. Therapeutic strategies aimed at targeting emerged as area investigation for molecular biologists. The objective is limit response time cancer, including liver, breast, prostate, ovarian, lung cancers. By modulating redox balance restoring homeostasis, it may be possible mitigate damaging effects enhance efficacy treatments. targeted therapies interventions specifically address impact holds great promise improving patient outcomes. approaches antioxidant-based treatments, redox-modulating agents, restore function affected stress. summary, understanding carcinogenesis process through therapeutic utmost importance combating Further research needed unravel complex mechanisms underlying stress-related develop effective translated into clinical applications management treatment

Language: Английский

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Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2023, Volume and Issue: 19(5), P. 297 - 317

Published: May 4, 2023

Introduction Paracetamol is one of the most used medicines worldwide and common important poisoning in high-income countries. In overdose, paracetamol causes dose-dependent hepatotoxicity. Acetylcysteine an effective antidote, however despite its use hepatotoxicity many deaths still occur.Areas covered This review summarizes overdose toxicity (including mechanisms, risk factors, assessment, treatment). addition, we summarize epidemiology worldwide. A literature search on PubMed for mortality from 1 January 2017 to 26 October 2022 was performed estimate rates liver injury, worldwide.Expert opinion widely available yet substantially more toxic than other analgesics without prescription. Where data were available, that involved 6% poisonings, 56% severe acute injury failure, 7% drug-induced injury. These estimates are limited by lack countries, particularly Asia, South America, Africa. Harm reduction possible through better identification high-risk overdoses, treatment regimens. Large overdoses those involving modified-release can be targeted legislative change.

Language: Английский

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Introduction to Traditional Medicine and Their Role in Prevention and Treatment of Emerging and Re-Emerging Diseases

Biomolecules, Journal Year: 2022, Volume and Issue: 12(10), P. 1442 - 1442

Published: Oct. 9, 2022

Infectious diseases have been a threat to human health globally. The relentless efforts and research enabled us overcome most of the through use antiviral antibiotic agents discovered employed. Unfortunately, microorganisms capability adapt mutate over time resistance ensues. There are many challenges in treating infections such as failure respond therapeutic agents, which has led more chronic infections, complications, preventable loss life. Thus, multidisciplinary approach collaboration is warranted create potent, effective, versatile therapies prevent eradicate old newly emerging diseases. In recent past, natural medicine proven its effectiveness against various illnesses. Most pharmaceutical currently used can trace their origin products one way, shape, or form. full potential yet be realized, numerous resources not explored analyzed. This merits continuous support analysis ancient treatment systems explore employ them an alternative principal therapy.

Language: Английский

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Dysbiosis of Gut Microbiota from the Perspective of the Gut–Brain Axis: Role in the Provocation of Neurological Disorders

Metabolites, Journal Year: 2022, Volume and Issue: 12(11), P. 1064 - 1064

Published: Nov. 3, 2022

The gut-brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. keeps track of activities integrates them to connect gut health higher cognitive parts brain. Disruption in this connection may facilitate various neurological problems. Neurodegenerative diseases are characterized by progressive dysfunction specific populations neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity aid collapse proteostasis defining characteristic neurodegenerative proteinopathies. These disorders not only caused changes neural compartment but also due other factors non-neural origin. Mounting data reveal majority (GI) physiologies mechanics governed system (CNS). Furthermore, microbiota plays critical role regulation physiological function brain, although mechanism involved has yet been fully interpreted. One emerging explanations start progression many illnesses dysbiosis microbial makeup. present understanding literature surrounding relationship between intestinal emergence certain diseases, such as Alzheimer's disease, Parkinson's Huntington's multiple sclerosis, main emphasis review. potential entry pathway pathogen-associated secretions toxins into CNS explored article at outset neuropathology. We have included possible undelaying synergistic effect infections, their metabolites, interactions based on current understanding.

Language: Английский

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Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes

Metabolites, Journal Year: 2023, Volume and Issue: 13(1), P. 86 - 86

Published: Jan. 5, 2023

Obesity is defined as abnormal and excessive fat accumulation, it a risk factor for developing metabolic neurodegenerative diseases cognitive deficits. caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with sedentary lifestyle. However, the entire physiopathology linking obesity neurodegeneration decline has not yet been elucidated. During progression of obesity, adipose tissue undergoes immune, metabolic, functional changes that induce chronic low-grade inflammation. It proposed inflammatory processes may participate both peripheral disorders brain including development In addition, mitochondrial dysfunction related to inflammation oxidative stress, causing cellular damage. Preclinical clinical studies have demonstrated dysfunction. Since neuronal cells high demand mitochondria play important role maintaining constant supply, impairments activity lead damage and, consequently, neurotoxicity. this review, we highlight effect high-fat diet consumption on neuroinflammation link between decline.

Language: Английский

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Polycystic Ovary Syndrome and Oxidative Stress—From Bench to Bedside

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14126 - 14126

Published: Sept. 15, 2023

Oxidative stress (OS) is a condition that occurs as result of an imbalance between the production reactive oxygen species (ROS) and body's ability to detoxify neutralize them. It can play role in variety reproductive system conditions, including polycystic ovary syndrome (PCOS), endometriosis, preeclampsia, infertility. In this review, we briefly discuss links oxidative PCOS. Mitochondrial mutations may lead impaired phosphorylation (OXPHOS), decreased adenosine triphosphate (ATP) production, increased ROS. These functional consequences contribute metabolic hormonal dysregulation observed Studies have shown OS negatively affects ovarian follicles disrupts normal follicular development maturation. Excessive ROS damage oocytes granulosa cells within follicles, impairing their quality compromising fertility. Impaired OXPHOS mitochondrial dysfunction insulin resistance (IR) by disrupting signaling pathways glucose metabolism. Due dysfunctional OXPHOS, reduced ATP hinder insulin-stimulated uptake, leading IR. Hyperandrogenism promotes inflammation IR, both which increase OS. A detrimental feedback loop ensues IR escalates, causing elevated levels exacerbate Exploring relations PCOS crucial fully understand pathophysiology develop effective treatment strategies improve life women affected condition. The antioxidants potential therapies also discussed.

Language: Английский

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Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(5), P. 784 - 784

Published: May 11, 2023

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development new therapeutic strategies against could be beneficial. Oxidative stress mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation increasingly understood contribute pathogenesis Mitochondrial also recognized for its contributions neuronal excitability apoptosis, which can lead loss This review focuses on roles oxidative damage, dysfunction, NAPDH oxidase, blood–brain barrier, excitotoxicity, We therapies used treat prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, antioxidant therapies. In addition, we use neuromodulation surgery treatment Finally, present role dietary nutritional management epilepsy, ketogenic diet intake vitamins, polyphenols, flavonoids. By reviewing available interventions research pathophysiology this points areas further manage

Language: Английский

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Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: March 6, 2024

Sepsis is a potentially fatal condition characterized by organ dysfunction caused an imbalanced immune response to infection. Although increased inflammatory significantly contributes the pathogenesis of sepsis, several molecular mechanisms underlying progression sepsis are associated with cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides comprehensive overview involvement ROS in pathophysiology potential application antioxidants antimicrobial properties as adjunct primary therapies (fluid antibiotic therapies) against sepsis. delves into advantages disadvantages utilization therapeutic approach which has been explored variety animal models clinical trials. While suggested therapy suppress cases where intensified reaction occurs, use multiple agents can be beneficial they act additively or synergistically on different pathways, thereby enhancing defense. Furthermore, immunoadjuvant therapy, specifically septic patients displaying immunosuppressive tendencies, represents promising advancement therapy.

Language: Английский

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Lipid droplet‐targeted NIR AIE photosensitizer evoking concurrent ferroptosis and apoptosis

Aggregate, Journal Year: 2024, Volume and Issue: 5(3)

Published: Feb. 1, 2024

Abstract Lipid droplets (LDs), which are the hubs of lipid metabolism, play a critical role in maintaining cellular energy homeostasis. The construction advanced photosensitizers (PSs) capable manipulating LD‐mediated cell fate regulation is highly desirable though rarely reported. In this study, near‐infrared emissive PS (DPCMP) with LDs specificity was synthesized and successfully applied to induce ferroptosis apoptosis. DPCMP exhibited typical aggregation‐induced emission characteristics owing its twisted molecular conformation. Excellent biocompatibility suitable lipophilicity allowed specifically stain living cells. Under white light illumination, displayed potent reactive oxygen species (ROS) generation capacity through both type I II photochemistry. massive accumulation lethal ROS generated by DPCMP‐mediated photosensitization initiated peroxidation, impaired redox homeostasis, led endoplasmic reticulum oxidative stress, ultimately inhibiting proliferation via concurrent apoptosis cancer cells multicellular tumor spheroids.

Language: Английский

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