Precise modulation and use of reactive oxygen species for immunotherapy

Science Advances, Год журнала: 2024, Номер 10(20)

Опубликована: Май 15, 2024

Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and cells. Recent advances biomaterials have leveraged this mechanism to precisely modulate ROS levels target tissues for improving effectiveness of immunotherapies infectious diseases, cancer, autoimmune diseases. Moreover, ROS-responsive can trigger release immunotherapeutics provide tunable kinetics, which further boost their efficacy. This review will discuss latest biomaterial-based approaches both precise modulation using as a stimulus control kinetics immunotherapeutics. Finally, we existing challenges potential solutions clinical translation ROS-modulating immunotherapy, outlook future research.

Язык: Английский

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Exploring Natural Products as Radioprotective Agents for Cancer Therapy: Mechanisms, Challenges, and Opportunities

Cancers, Год журнала: 2023, Номер 15(14), С. 3585 - 3585

Опубликована: Июль 12, 2023

Radiotherapy is an important cancer treatment. However, in addition to killing tumor cells, radiotherapy causes damage the surrounding cells and toxic normal tissues. Therefore, effective radioprotective agent that prevents deleterious effects of ionizing radiation required. Numerous synthetic substances have been shown clear effects. most these not translated for use clinical applications due their high toxicity side Many medicinal plants exhibit various biological activities, including antioxidant, anti-inflammatory, anticancer activities. In recent years, new agents obtained from natural products investigated by radioprotection researchers, abundance sources, efficiency, low toxicity. this review, we summarize mechanisms underlying products, ROS scavenging, promotion DNA repair, anti-inflammatory effects, inhibition cell death signaling pathways. addition, systematically review with properties, polyphenols, polysaccharides, alkaloids, saponins. Specifically, discuss polyphenols apigenin, genistein, epigallocatechin gallate, quercetin, resveratrol, curcumin; polysaccharides astragalus, schisandra, Hohenbuehelia serotina; saponins ginsenosides acanthopanax senticosus; alkaloids matrine, ligustrazine, β-carboline. further optimization through structural modification, improved extraction purification methods, trials are needed before translation. With a deeper understanding involved development high-throughput screening could become promising novel agents.

Язык: Английский

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Redox mechanisms in autoimmune thyroid eye disease

Autoimmunity Reviews, Год журнала: 2024, Номер 23(5), С. 103534 - 103534

Опубликована: Март 26, 2024

Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and with its adnexa, often occurring as extrathyroidal complication of Graves' (GD). Orbital inflammatory infiltration stimulation orbital fibroblasts, triggering de novo adipogenesis, overproduction hyaluronan, myofibroblast differentiation, eventual tissue fibrosis are hallmarks disease. Notably, several redox signaling pathways have been shown to intensify inflammation promote fibrogenesis by upregulating potent cytokines, such interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β. While existing treatment options can manage symptoms potentially halt progression, they come drawbacks relapses, side effects, chronic adverse effects on optic nerve. Currently, studies shed light pathogenetic contributions emerging factors within immunological cascades oxidative stress. This review article provides overview latest advancements in understanding pathophysiology TED, a special focus interplay between stress, mechanisms environmental factors. Furthermore, cutting-edge therapeutic approaches targeting will be presented discussed.

Язык: Английский

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IFNγ causes mitochondrial dysfunction and oxidative stress in myositis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 26, 2024

Abstract Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of interferon γ (IFNγ) using NOD female mice deficient in inducible T cell co-stimulator ( Icos ), which have previously been shown to develop spontaneous IFNγ-driven myositis mimicking human disease. Using muscle proteomic spatial transcriptomic analyses reveal profound myofiber metabolic dysregulation these mice. In addition, report mitochondrial abnormalities oxidative stress diseased Supporting a pathogenic for stress, treatment reactive oxygen species (ROS) buffer compound alleviated myositis, preserved ultrastructure respiration, reduced inflammation. Mitochondrial anomalies were diminished following anti-IFNγ treatment. Further analysis IIMs patients myoblast vitro studies supported link between IFNγ dysfunction observed These results suggest that dysfunction, ROS inflammation interconnected self-maintenance loop, opening perspectives mitochondria therapy and/or targeting drugs myositis.

Язык: Английский

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

Medicinal Research Reviews, Год журнала: 2024, Номер 44(6), С. 2825 - 2848

Опубликована: Авг. 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

Язык: Английский

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Mitochondrial Oxidative Stress Related Diagnostic Model Accurately Assesses Rheumatoid Arthritis Risk Stratification and Immune Infiltration Characterization

Biotechnology Journal, Год журнала: 2025, Номер 20(2)

Опубликована: Фев. 1, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects synovial joints, leading to joint destruction, impaired physical function, and reduced quality of life. However, no accurate method for assessing RA risk currently exists. Given the critical role early detection intervention in management, further comprehensive assessments are essential. Mitochondrial oxidative stress (MOS) key factor initiation progression RA. The bidirectional interaction between MOS supports feasibility MOS-based stratification Using public databases, we first applied weighted gene co-expression network analysis (WGCNA) model identify genes involved among MOS-related genes. Differential expression patterns were then analyzed using various machine learning algorithms potential biomarkers. A nomogram was established CDKN1A, GADD45B, MAFF predict risk, followed by an evaluation its reliability stability. Additionally, MOS-associated molecular subtypes immune infiltration characteristics. Our findings highlight significant development underscore clinical value personalized treatment strategies.

Язык: Английский

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Ferroptosis as an emerging target in rheumatoid arthritis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 19, 2023

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. Due to the rise in incidence rate RA and limitations existing therapies, search for new treatment strategies has become a global focus. Ferroptosis novel programmed cell death characterized by iron-dependent lipid peroxidation, with distinct differences from apoptosis, autophagy, necrosis. Under conditions iron accumulation glutathione peroxidase 4 (GPX4) activity loss, lethal peroxide direct cause ferroptosis. mediates inflammation, oxidative stress, damage processes, also participates occurrence pathological progression inflammatory joint diseases including RA. This review provides insight into role mechanism ferroptosis discusses potential challenges as therapeutic strategy RA, effort provide targets prevention treatment.

Язык: Английский

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A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 1, 2023

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the system mistakenly attacks damages body’s tissues organs. This excessive response leads to inflammation, tissue damage, functional impairment. Therapeutic approaches typically involve medications that regulate responses, reduce alleviate symptoms, target specific damaged Tripterygium wilfordii Hook. f., traditional Chinese medicinal plant, has been widely studied in recent years for its application treatment diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Numerous studies have shown preparations anti-inflammatory, immunomodulatory, immunosuppressive effects, which effectively improve symptoms quality life patients with whereas active metabolites T. demonstrated inhibit cell activation, production inflammatory factors, modulate system. However, although these effects contribute reductions responses suppression reactions, as well minimize organ underlying mechanisms action require further investigation. Moreover, despite efficacy toxicity side potential hepatotoxicity nephrotoxicity, warrant thorough assessment. Furthermore, maximize therapeutic benefits this plant enable more utilize benefits, efforts should be made strengthen regulation standardized use wilfordii.

Язык: Английский

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Exploring the effect of LncRNA DANCR to regulate the Keap1‐Nrf2/ARE pathway on oxidative stress in rheumatoid arthritis

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(1)

Опубликована: Янв. 1, 2024

Abstract Introduction Aberrant expression of long noncoding RNAs (LncRNAs) can regulate oxidative stress in rheumatoid arthritis (RA). This study focused on investigating the effects LncRNA differentiation antagonizing nonprotein coding RNA (DANCR) regulation Keap1‐Nrf2/ARE pathway inflammation and RA. Methods The levels DANCR/miR‐486‐3p/Keap1 peripheral blood 30 RA groups normal subjects were examined, association DANCR with inflammatory indicators was investigated. We stimulated fibroblast‐like synoviocytes (FLS) from patients tumor necrosis factor α subsequently performed vitro cellular assays to construct overexpression plasmids small interfering investigate relationship between FLSs viability migration RA, as well factors pathway; molecular biology analysis used predict microRNAs that bind DANCR, luciferase verified binding sites Keap1 miR‐486‐3p; further refine gene protein results, we reverse transcription‐quantitative polymerase chain reaction immunoblotting assays. Results In both mononuclear cells, messenger higher group than control group, opposite true for positively correlated total antioxidant capacity (TAOC), IL6, IL17, malondialdehyde (MDA), but not IL11, factor, cyclic citrullinated peptide, superoxide dismutase (SOD), 28‐joint disease activity score, reactive oxygen species, C‐reactive protein, erythrocyte sedimentation rate negatively correlated; pathway, decreased IL10, SOD, TAOC, increased MDA, IL‐17, PD‐L1, silencing opposite, knockdown miR‐486‐3p or keap1 reversed above‐mentioned factors. addition, pcDNA‐DANCR clearly showed stronger cell invasion ability exacerbated its response, which may be related regulatory role signaling their targeting using dual luciferase, showing could through modulates affects responses patients. Conclusion low‐expressed suppress

Язык: Английский

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A dual dynamically cross-linked hydrogel promotes rheumatoid arthritis repair through ROS initiative regulation and microenvironment modulation-independent triptolide release

Materials Today Bio, Год журнала: 2024, Номер 26, С. 101042 - 101042

Опубликована: Апрель 3, 2024

High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory anti-inflammatory effects. However, sudden accumulation caused by binding "stimulus-response" "drug release" general smart delivery system is meet shortcoming extreme toxicity demand for long-term administration TPL. Herein, we developed dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation modulation-independent TPL release 30 days. The abundant borate ester/tea polyphenol units SPT@TPL possessed capability respond regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on dense crosslinked structure as well spontaneous healing behavior numerous intermolecular hydrogen bonds formed after breakage ester, could remain stable slowly under ROS environments RA, dramatically reduced risk exerting while maximized efficacy. Through effects sustained-release, alleviated reprogrammed macrophages into M2 phenotype, showing marked inhibition inflammation optimal articular cartilage rat model. In conclusion, this platform with both initiative sustained provides potential scheme arthritis.

Язык: Английский

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