Inhibition of Glutaminase 1 Reduces M1 Macrophage Polarization to Protect Against Monocrotaline-Induced Pulmonary Arterial Hypertension

Immunology Letters, Journal Year: 2025, Volume and Issue: 272, P. 106974 - 106974

Published: Jan. 5, 2025

(1) BACKGROUND: Metabolic abnormalities and immune inflammation are key elements within pathogenesis of pulmonary arterial hypertension (PAH). And in PAH patients, aberrant glutamine metabolism has been observed; however, the function glutaminase 1 (GLS1) macrophage is still unknown. So we aims to investigate GLS1's impact upon macrophages PAH. (2) METHODS: We firstly constructed an monocrotaline (MCT)-induced rat model. Briefly, rats were treated with GLS1 inhibitor BPTES, various index evaluated, including hemodynamics, right ventricular function, vascular remodeling, markers, metabolism. After that, polarized bone marrow-derived (BMDMs) into M1 phenotype then subjected BPTES intervention. Finally, assessed phenotype, inflammatory indicators, along BMDM supernatant on behavior smooth muscle cells (PASMCs). (3) RESULTS: was significantly upregulated both patients rats. Treatment markedly improved pressure, remodeling rats, while inhibiting polarization, NLRP3 activation, release pro-inflammatory cytokines. This, turn, alleviated proliferation migration PASMCs induced by stimuli. (4) CONCLUSION: propose that targeting reduce polarization responses may represent a promising therapeutic approach for

Language: Английский

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Electroacupuncture normalized tumor vasculature by downregulating glyoxalase-1 to polarize tumor-associated macrophage to M1 phenotype in triple-negative breast cancer

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113988 - 113988

Published: Jan. 7, 2025

Language: Английский

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Antitumor Research Based on Drug Delivery Carriers: Reversing the Polarization of Tumor-Associated Macrophages

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as key mechanism through which cells evade immune detection and play crucial role in progression metastasis. This impedes optimal effectiveness immunotherapeutic approaches, including cytokines, checkpoint inhibitors, vaccines. Tumor-associated macrophages (TAMs), major component tumor-infiltrating cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like promote growth Consequently, various nanocarriers aimed at polarizing phenotypes distinct mechanisms has emerged promising therapeutic strategy inhibit escape enhance antitumor responses. Review covers origin types TAMs, common pathways regulating macrophage polarization, progression, strategies targeting aiming provide comprehensive understanding guidance for future research clinical applications.

Language: Английский

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Mitochondrial-related drug resistance lncRNAs as prognostic biomarkers in laryngeal squamous cell carcinoma

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck that significantly impacts patients' quality life, with chemotherapy resistance notably affecting prognosis. This study aims to identify prognostic biomarkers optimize treatment strategies for LSCC. Using data from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO), combined mitochondrial gene database analysis, we identified lncRNAs associated drug genes. Key long non-coding RNAs (lncRNAs) were selected through univariate Cox regression Lasso regression, multivariate model was constructed predict We further analyzed differences in immune function biological pathway enrichment between high- low-risk groups, developed nomogram, compared sensitivity. Results showed based on seven could serve as an independent factor, Area Under Curve (AUC) values 0.746, 0.827, 0.771 at 1, 3, 5 years, respectively, outperforming some existing models, demonstrating high predictive performance. Significant observed sensitivity groups. risk prediction incorporating resistance-related can accurately independently prognosis LSCC patients.

Language: Английский

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Myeloid-derived suppressor cells in metabolic and cardiovascular disorders

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Harnessing myeloid cells in cancer

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 6, 2025

Cancer-associated myeloid cells due to their plasticity play dual roles in both promoting and inhibiting tumor progression. Myeloid with immunosuppressive properties a critical role anti-cancer immune regulation. Cells of different origin, such as associated macrophages (TAMs), neutrophils (TANs), derived suppressor (also called MDSCs) eosinophils are often expanded cancer patients significantly influence survival, but also the outcome therapies. For this reason, variety preclinical clinical studies modulate activity these have been conducted, however without successful date. In review, pro-tumor cells, cell-specific therapeutic targets, vivo on cell re-polarization impact immunotherapies/genetic engineering addressed. This paper summarizes ongoing trials concept chimeric antigen receptor macrophage (CAR-M) therapies, suggests future research perspectives, offering new opportunities development novel treatment strategies.

Language: Английский

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Enhanced Delivery of Photothermal Gelatin Nanoparticle for Redox Balanced Nanocatalytic Tumor Chemotherapy

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Abstract Nanocatalytic platforms are promising in cancer therapeutics via combining multiple treatments, which can be leveraged through the metabolic dysfunction progression. However, lack of effective tumor delivery hampers this approach. Here, a gelatin‐based platform is designed that preloaded with gold nanoparticles and photothermal polypyrrole (GNPs@AuNPs‐PPy) an acid‐induced doping enhancement. Benefiting from associated overexpression H 2 O , peroxidase‐like Au induce burst oxidative reactive oxygen species local microenvironment (TME). Subsequent orchestration redox surroundings recruits immune cells, showcasing antineoplastic pathway. Under near infrared light (NIR) irradiation, nanohybrids exhibit dual pH/NIR enhanced drug release within TME, while allowing for multimodal imaging‐guided theranostics. Leveraging modality, GNPs@AuNPs‐PPy delivers quercetin (a natural antitumor mediator) boosting anti‐tumor therapy. The gelatin‐mediated nanomedicine provides alternative combinatorial dynamic treatment.

Language: Английский

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The mechanism of action and therapeutic potential of tumor-associated macrophages in tumor immune evasion

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 22, 2025

Tumor-associated macrophages (TAMs) play a multifaceted role in tumor progression. As specialized immune cells, are capable of phagocytosis and digesting foreign substances, as well removing harmful substances including cellular debris cells. Under specific pathological conditions, circulating monocytes can be recruited into the microenvironment differentiate TAMs. Macrophages generally polarized two distinct subpopulations: classically activated (M1) alternatively (M2). TAMs constitute significant proportion mononuclear leukocyte population solid tumors, exhibiting complex dualistic relationship with Substantial evidence indicates that interact facilitating their evasion while promoting invasion metastasis. This review focuses on mechanism regulation response to various macrophage-based tumor-targeted therapeutic strategies. It will provide reference for research macrophage-centered therapy strategies application clinical practice.

Language: Английский

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Glioblastoma-associated macrophages in glioblastoma: from their function and mechanism to therapeutic advances

Cancer Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Language: Английский

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Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 10, 2024

HBV infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC), highly invasive tumor, characterized by its persistent immunosuppressive microenvironment. This review provides an in-depth analysis HBV-related HCC explores interactions between neutrophils, natural killer cells, dendritic examining their roles in regulating tumor-associated macrophages CD8+ T cells shaping tumor Two critical players milieu are (TAMs). The study how TAMs, initially recruited to combat infection, transform, adopting tumor-promoting phenotype, turning against body, promoting cell proliferation, suppressing anti-tumor immunity, assisting spread cancer. Meanwhile, crucial controlling become dysfunctional exhausted response chronic viral inflammation. then dissects TAMs manipulate this immune response, further depleting functions through mechanisms like arginine deprivation creating hypoxic environments that lead exhaustion. Finally, it challenges promising therapeutic avenues target either separately or combination with antiviral therapy personalized medicine approaches, offering hope improved outcomes HCC.

Language: Английский

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