Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective

Antioxidants, Journal Year: 2022, Volume and Issue: 11(7), P. 1394 - 1394

Published: July 19, 2022

Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects progression of inflammatory disorders. Here, we review how redox signals regulate macrophage and reprogramming during acute inflammation. In M1, augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), tumor necrosis factor receptor-associated 6 increase oxygen nitrogen reactive species, triggers response, phagocytosis, cytotoxicity. M2, down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase superoxide dismutase type 1, counteract oxidative nitrosative stress, favor anti-inflammatory tissue repair responses. M2 exhibit different metabolic profiles, are tightly regulated mechanisms. Oxidative stress sustain phenotype activating glycolysis lipid biosynthesis, but inhibiting tricarboxylic acid cycle phosphorylation. This profile is reversed in because changes state. Therefore, new therapies based on mechanisms have emerged treat inflammation with positive results, highlights relevance signaling as a master regulator reprogramming.

Language: Английский

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Targeting ROS in cancer: rationale and strategies

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(8), P. 583 - 606

Published: July 9, 2024

Language: Английский

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Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Language: Английский

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Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(4), P. 741 - 763

Published: April 25, 2024

Language: Английский

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Anchang Yuyang Decoction inhibits experimental colitis-related carcinogenesis by regulating PPAR signaling pathway and affecting metabolic homeostasis of host and microbiota

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117995 - 117995

Published: Feb. 28, 2024

Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration IBD. Persistent histological inflammation is considered to be driving factor colitis carcinogenesis. Effective control helpful prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), traditional Chinese medicine (TCM) formula, originated from ancient prescription TCM for treating cancer. AYD has demonstrated efficacy in IBD potential anti-carcinogenic properties.

Language: Английский

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Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling

Science, Journal Year: 2025, Volume and Issue: 387(6739)

Published: March 13, 2025

Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose amino acids are well characterized, less is known about lipids. We defined a nutrient signaling mechanism involving fatty acid–binding protein 5 (FABP5) mechanistic target rapamycin complex 1 (mTORC1) that activated by the essential polyunsaturated acid (PUFA) ω-6 linoleic (LA). FABP5 directly bound regulatory-associated mTOR (Raptor) enhance formation functional mTORC1 substrate binding, ultimately converging on increased proliferation. The amounts were in tumors serum from triple-negative compared with those receptor-positive breast cancer patients, which highlights its potential role as biomarker mediates cellular responses LA intake this disease subtype.

Language: Английский

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Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling

Circulation, Journal Year: 2022, Volume and Issue: 147(5), P. 388 - 408

Published: Nov. 23, 2022

Background: Cross-talk between sterol metabolism and inflammatory pathways has been demonstrated to significantly affect the development of atherosclerosis. Cholesterol biosynthetic intermediates derivatives are increasingly recognized as key immune regulators macrophages in response innate activation lipid overloading. 25-Hydroxycholesterol (25-HC) is produced an oxidation product cholesterol by enzyme 25-hydroxylase (CH25H) belongs a family bioactive cells fluctuating levels activation. Despite major role 25-HC mediator adaptive responses, its contribution during progression atherosclerosis remains unclear. Methods: The were analyzed liquid chromatography-mass spectrometry, expression CH25H different macrophage populations human or mouse atherosclerotic plaques, respectively. effect on was bone marrow adoptive transfer from wild-type Ch25h –/– mice lethally irradiated Ldlr mice, followed Western diet feeding for 12 weeks. Lipidomic, transcriptomic analysis effects function signaling vitro lipid-loaded isolated Ch25h–/–;Ldlr–/– . secreted fibrous cap formation using smooth muscle cell lineage–tracing model, Myh11 ERT2CRE mT/mG;Ldlr , adoptively transferred with weeks feeding. Results: We found that accumulated coronary lesions macrophage-derived accelerated progression, promoting plaque instability through autocrine paracrine actions. amplified inhibited migration within plaque. intensified responses lipid-laden modifying pool accessible plasma membrane, which altered Toll-like receptor 4 signaling, promoted nuclear factor-κB–mediated proinflammatory gene expression, increased apoptosis susceptibility. These independent 25-HC–mediated modulation liver X SREBP (sterol regulatory element–binding protein) transcriptional activity. Conclusions: Production activated amplifies their phenotype, thus atherogenesis.

Language: Английский

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NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5125 - 5125

Published: March 7, 2023

Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, mechanisms which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated NETs and underlying mechanism involved acute lung injury (ALI). found higher expression cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) airways, was reduced Deoxyribonuclease I (DNase I) ALI. The administration STING inhibitor H-151 also significantly relieved injury, but failed to affect high isolated murine from bone marrow acquired human inducing HL-60 differentiate. After PMA interventions, exogenous were obtained such extracted neutrophils. Exogenous intervention vitro vivo resulted airway reversed upon degrading with or inhibiting cGAS-STING as well siRNA STING. In conclusion, participates regulating NETs-mediated pulmonary is expected be new therapeutic target for ARDS/ALI.

Language: Английский

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Role of Mitophagy in Regulating Intestinal Oxidative Damage

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 480 - 480

Published: Feb. 14, 2023

The mitochondrion is also a major site for maintaining redox homeostasis between reactive oxygen species (ROS) generation and scavenging. quantity, quality, functional integrity of mitochondria are crucial regulating intracellular the normal physiological function cells. role oxidative stress in human disease well established, particularly inflammatory bowel gastrointestinal mucosal diseases. Oxidative could result from an imbalance ROS antioxidative system. Mitochondria both main sites production target ROS. It vicious cycle which initial ROS-induced mitochondrial damage enhanced that, turn, leads to further eventually massive intestinal cell death. can be significantly mitigated by mitophagy, clears damaged mitochondria. In this review, we aimed review molecular mechanisms involved regulation mitophagy their relationship some We believe reviews provide new ideas scientific basis researching antioxidants preventing diseases related damage.

Language: Английский

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C1q⁺tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(8), P. e007441 - e007441

Published: Aug. 1, 2023

Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as dominant population, impede antitumor response; however, underlying mechanisms have not been fully elucidated yet.Single-cell RNA sequencing analysis was performed portray macrophage landscape and revealed mechanism component 1q (C1q)+ TAMs. Malignant pleural effusion (MPE) human mouse used explore phenotypes functions C1q+ TAMs.C1q+ TAMs highly expressed multiple inhibitory molecules their high infiltration significantly correlated poor prognosis. promote MPE immunosuppression through impairing effects CD8+ T Mechanistically, enhance fatty acid binding protein 5 (FABP5)-mediated metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing gene expression molecules. A high-fat diet increases microenvironment, whereas low-fat ameliorates these effects. Moreover, FABP5 inhibition represses tumor progression, while enhancing efficacy ICB lung cancer.C1q+ cells promoting immunosuppression. Targeting effectively alleviates enhances therapy. great potential be therapeutic target for immunotherapy.

Language: Английский

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