Journal of Hazardous Materials, Год журнала: 2024, Номер 466, С. 133590 - 133590
Опубликована: Янв. 23, 2024
Язык: Английский
Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)
Опубликована: Июль 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.
Язык: Английский
Процитировано
170
Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(3), С. 137 - 149
Опубликована: Янв. 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.
Язык: Английский
Процитировано
146
Nature, Год журнала: 2023, Номер 615(7952), С. 490 - 498
Опубликована: Март 8, 2023
Язык: Английский
Процитировано
137
Free Radical Biology and Medicine, Год журнала: 2022, Номер 189, С. 136 - 153
Опубликована: Июль 31, 2022
Язык: Английский
Процитировано
105
Cell, Год журнала: 2023, Номер 186(17), С. 3706 - 3725.e29
Опубликована: Авг. 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.
Язык: Английский
Процитировано
77
Frontiers in Immunology, Год журнала: 2024, Номер 14
Опубликована: Янв. 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.
Язык: Английский
Процитировано
55
British Journal of Pharmacology, Год журнала: 2023, Номер unknown
Опубликована: Сен. 16, 2023
The KEAP1 ‐ NRF2 system plays a central role in cytoprotection defence mechanisms against oxidative stress. KEAP1‐NRF2 has been regarded as sulfur‐utilizing cytoprotective mechanism, because serves biosensor for electrophiles by using its reactive thiols and is transcriptional factor regulating genes involved sulfur‐mediated redox reactions. key regulator of genes, such antioxidant detoxification also possesses potent anti‐inflammatory activity. Recently the focus attention cellular metabolism mitochondrial function. NRF2‐mediated regulatory metabolites mitochondria have considered diverse, but not yet fully clarified. This review article provides an overview molecular that regulate signalling roles, highlights contribution to metabolism, particularly context function newly‐found sulfur metabolism.
Язык: Английский
Процитировано
45
Redox Biology, Год журнала: 2024, Номер 70, С. 103077 - 103077
Опубликована: Фев. 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.
Язык: Английский
Процитировано
30
Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)
Опубликована: Март 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.
Язык: Английский
Процитировано
19
Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown
Опубликована: Март 4, 2025
Язык: Английский
Процитировано
11