Metabolism, metabolites, and macrophages in cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: July 25, 2023

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in development drug resistance by creating an immunosuppressive microenvironment. Macrophages essential both innate adaptive immune systems contribute to pathogen regulation organism homeostasis. Macrophage function polarization closely linked altered metabolism. Generally, M1 rely primarily on aerobic glycolysis, whereas M2 depend oxidative Metabolic studies have revealed that metabolic signature TAMs metabolites regulate TAMs. However, precise effects reprogramming tumours remain incompletely understood. In this review, we discuss impact pathways macrophage as well potential strategies for metabolism cancer treatment.

Language: Английский

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Advances and challenges in therapeutic targeting of NRF2

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(3), P. 137 - 149

Published: Jan. 9, 2023

Activation of the transcription factor nuclear erythroid 2-related 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet needs, including neurodegenerative disorders diseases. As NRF2 field transitions into clinical phase its evolution, need for understanding factors influencing pharmacology has never been greater. In this opinion article we describe rationale targeting NRF2, summarise recent advances in drug development modulators, reflect on remaining challenges realising full potential a target.

Language: Английский

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Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Nature, Journal Year: 2023, Volume and Issue: 615(7952), P. 490 - 498

Published: March 8, 2023

Language: Английский

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Nrf2 as a regulator of mitochondrial function: Energy metabolism and beyond

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 189, P. 136 - 153

Published: July 31, 2022

Language: Английский

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Distinct molecular profiles of skull bone marrow in health and neurological disorders

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3706 - 3725.e29

Published: Aug. 1, 2023

The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates structural cellular details skull-meninges connections (SMCs) veins. Last, using translocator positron emission tomography (TSPO-PET) imaging, reflects inflammatory disease-specific spatial distribution patients various neurological disorders. anatomical functional potential as site diagnosing, monitoring, treating diseases.

Language: Английский

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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

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Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103077 - 103077

Published: Feb. 11, 2024

Inflammatory diseases present a serious health challenge due to their widespread prevalence and the severe impact on patients' lives. In quest alleviate burden of these diseases, nuclear factor erythroid 2-related 2 (Nrf2) has emerged as pivotal player. As transcription intimately involved in cellular defense against metabolic oxidative stress, Nrf2's role modulating inflammatory responses immune cells garnered significant attention. Recent findings suggest that ability alter redox status underlies its regulatory effects responses. Our review delves into preclinical clinical evidence underscores complex influence Nrf2 activators cell phenotypes, particularly milieu. By offering detailed analysis different populations, we cast light potential shaping response towards more regulated state, mitigating adverse inflammation through modeling cells. Furthermore, explore innovative use nanoencapsulation techniques enhance delivery efficacy activators, potentially advancing treatment strategies for ailments. We hope this will stimulate development expansion Nrf2-targeted treatments could substantially improve outcomes patients suffering from broad range diseases.

Language: Английский

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Anti-inflammatory and anti-oxidative electrospun nanofiber membrane promotes diabetic wound healing via macrophage modulation

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 16, 2024

Abstract Background In the inflammatory milieu of diabetic chronic wounds, macrophages undergo substantial metabolic reprogramming and play a pivotal role in orchestrating immune responses. Itaconic acid, primarily synthesized by as byproduct tricarboxylic acid cycle, has recently gained increasing attention an immunomodulator. This study aims to assess immunomodulatory capacity itaconic derivative, 4-Octyl itaconate (OI), which was covalently conjugated electrospun nanofibers investigated through vitro studies full-thickness wound model mice. Results OI feasibly onto chitosan (CS), then grafted polycaprolactone/gelatin (PG) obtain P/G-CS-OI membranes. The membrane exhibited good mechanical strength, compliance, biocompatibility. addition, sustained release endowed nanofiber with great antioxidative anti-inflammatory activities revealed vivo studies. Specifically, activated nuclear factor-erythroid-2-related factor 2 (NRF2) alkylating Kelch-like ECH-associated protein 1 (KEAP1). response modulates macrophage polarization, leading mitigated responses, enhanced angiogenesis, recovered re-epithelization, finally contributing improved healing mouse wounds. Conclusions shows modulation might be promising for treatment.

Language: Английский

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Thirty years of NRF2: advances and therapeutic challenges

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

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Nonalcoholic steatohepatitis and mechanisms by which it is ameliorated by activation of the CNC-bZIP transcription factor Nrf2

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 188, P. 221 - 261

Published: June 18, 2022

Non-alcoholic steatohepatitis (NASH) represents a global health concern. It is characterised by fatty liver, hepatocyte cell death and inflammation, which are associated with lipotoxicity, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron overload oxidative stress. NF-E2 p45-related factor 2 (Nrf2) transcription that combats Remarkably, Nrf2 downregulated during the development of NASH, probably accelerates disease, whereas in pre-clinical studies upregulation inhibits NASH. We now review scientific literature proposes downregulation NASH involves its increased ubiquitylation proteasomal degradation, mediated Kelch-like ECH-associated protein 1 (Keap1) and/or β-transducin repeat-containing (β-TrCP) HMG-CoA reductase degradation (Hrd1, also called synoviolin (SYVN1)). Additionally, Nrf2-mediated may involve diminished recruitment coactivators Nrf2, due to levels activating 3 (ATF3) nuclear factor-kappaB (NF-κB) p65, or competition for promoter binding BTB CNC homology (Bach1). Many processes downregulate triggered transforming growth factor-beta (TGF-β), stress amplifying signalling. Oxidative increase suppression β-TrCP through facilitating formation DSGIS-containing phosphodegron glycogen synthase kinase-3. In animal models, knockout increases susceptibility while pharmacological activation inducing agents target Keap1 These counter affected β-TrCP, Hrd1/SYVN1, ATF3, NF-κB p65 Bach1, suppressing Activation likely inhibit ameliorating ER overload. Crucially, mice has already been established supresses liver steatosis inflammation. There therefore compelling evidence provides comprehensive multipronged strategy treat

Language: Английский

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