Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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The multi-faceted immune modulatory role of S100A4 in cancer and chronic inflammatory disease

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

Published: Feb. 26, 2025

S100A4 is a Ca2+-binding protein involved in multiple chronic inflammatory and neoplastic conditions. This review focuses on recent advances the understanding of function immune cells, comparing contrasting regulation responses cancer diseases. We provide evidence that cell has profound role promoting pathogenesis pro-inflammatory Finally, we discuss relevant future directions to target therapeutically different disease states.

Language: Английский

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Special correlation between diet and MASLD: positive or negative?

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic and systemic metabolic characterized by the presence of hepatic steatosis at least one cardiometabolic risk factor (CMRF). The pathogenesis MASLD involves multiple mechanisms, including lipid metabolism disorders, insulin resistance, inflammatory responses, hepato-intestinal axis dysfunction. Among these factors, diet serves as both an inducement potential remedy in disease's development. Notably, high-lipid exacerbates fat accumulation, oxidative stress, thereby promoting progression MASLD. Consequently, dietary induction models have become vital tools for studying pathological mechanisms MASLD, providing foundation identifying therapeutic targets. Additionally, we summarize effects optimization on elucidate role specific components regulating axis, metabolism, inhibiting responses. In conclusion, studies utilizing animal offer significant insights into therapy, particularly concerning regulation metabolism-related hepatoenteric axis-related signaling pathways well beneficial mechanism probiotics regulation. By understanding which different patterns affect can assess clinical applicability current strategies provide new directions research treatment aimed modification.

Language: Английский

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m6A epitranscriptomic modification in hepatocellular carcinoma: implications for the tumor microenvironment and immunotherapy

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

Published: Feb. 17, 2025

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and a leading cause of cancer-related deaths globally. The asymptomatic progression early-stage HCC often results in diagnosis at advanced stages, significantly limiting therapeutic options worsening prognosis. Immunotherapy, with immune checkpoint inhibitors (ICIs) forefront, has revolutionized treatment. Nevertheless, tumor heterogeneity, evasion, presence immunosuppressive components within microenvironment (TIME) continue to compromise its efficacy. Furthermore, resistance or non-responsiveness ICIs some patients underscores urgent need unravel complexities TIME design innovative strategies that enhance immunotherapeutic outcomes. Emerging evidence revealed pivotal role N6-methyladenosine (m6A), prominent RNA methylation modification, shaping HCC. By regulating stability translation, m6A influences immune-related factors, including cytokines molecules. This modification governs PD-L1 expression, facilitating escape contributing against ICIs. Advances this field have also identified m6A-related regulators as promising biomarkers for predicting immunotherapy response potential targets optimizing treatment review examines regulatory mechanisms HCC, focus on impact cells cytokine dynamics. It explores targeting pathways improve efficacy outlines emerging directions future research. These insights aim provide foundation developing novel overcome advance

Language: Английский

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Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment

Food Research International, Journal Year: 2025, Volume and Issue: unknown, P. 116207 - 116207

Published: March 1, 2025

Language: Английский

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RNA Methylation and Transcriptome Analysis Reveal Key Regulatory Pathways Related to Cadmium-Induced Liver Damage

Chemical Research in Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Cadmium (Cd) is a prevalent environmental and industrial contaminant that causes significant damage to liver function. However, the role of m6A methylation─a critical epigenetic modification─in Cd-induced injury remains poorly understood. This study aimed investigate effects methylation in damage. A mouse model was established, exposure CdCl2 (20 mg/kg) for 90 days resulted reduced levels. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) (RNA-Seq), we characterized profiles both control Cd-exposed groups. total 8355 unique peaks 1,101 m6A-modified genes were identified. Among these, 673 exhibited differential modifications, including 463 hyper-methylated 210 hypo-methylated genes. Conjoint analysis MeRIP-seq RNA-Seq data unveiled showed expression. These significantly enriched AGE-RAGE PI3K-Akt signaling pathway. Through bioinformatics screening, five key (Il-1β, Ccl2, Tlr2, Itgax, Ccr2) identified, expression validation indicated Itgax Ccr2 may play pivotal roles injury. Notably, elevated methyltransferase-like 14 (METTL14) observed vivo vitro models. Inhibition Mettl14 can regulate inflammation through m6A-dependent regulation Collectively, our findings highlight crucial injury, providing novel insights into mechanisms underlying diseases potential biomarkers diagnosis therapy.

Language: Английский

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TJ0113 attenuates fibrosis in metabolic dysfunction-associated steatohepatitis by inducing mitophagy

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114678 - 114678

Published: April 18, 2025

Language: Английский

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Targeting hepatic macrophages for non-alcoholic fatty liver disease therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 5, 2024

Non-alcoholic fatty liver disease (NAFLD) and its more advanced form, non-alcoholic steatohepatitis (NASH), have become global health challenges with significant morbidity mortality rates. NAFLD encompasses several diseases, ranging from simple steatosis to severe inflammatory fibrotic forms. Ultimately, this can lead cirrhosis hepatocellular carcinoma. The intricate role of hepatic macrophages, particularly Kupffer cells (KCs) monocyte-derived macrophages (MoMFs), in the pathogenesis NASH, has received increasing attention. Hepatic interact hepatocytes, stellate cells, endothelial playing a crucial maintaining homeostasis. Paradoxically, they also participate some diseases. This review highlights fundamental emphasizing their plasticity contribution inflammation fibrosis, hopes provide ideas for subsequent experimental research clinical treatment.

Language: Английский

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Unraveling the role of METTL14 in metabolic dysfunction-associated fatty liver disease: insights and therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 29, 2024

Language: Английский

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A Tetrahedral Framework DNA-Based Bioswitchable miR-150 Delivery System for Sepsis

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(43), P. 58477 - 58488

Published: Oct. 18, 2024

Sepsis is a disease with high morbidity and mortality, for which effective treatments are lacking. In recent years, microRNAs (miRs) have been shown to regulate numerous biological processes can function as therapeutic options various diseases. However, the poor stability cell entry properties of miRs greatly limited their clinical application. this study, we developed tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) deliver miR-150 treatment sepsis. BiRDS showed anti-inflammatory effects both in vitro vivo by regulating NF-κB Notch1 pathways. Therefore, holds promise an ideal candidate tackling systemic inflammation multiorgan dysfunction septic patients future.

Language: Английский

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