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

TRIMming down Flavivirus Infections

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1262 - 1262

Published: Aug. 6, 2024

Flaviviruses comprise a large number of arthropod-borne viruses, some which are associated with life-threatening diseases. Flavivirus infections rising worldwide, mainly due to the proliferation and geographical expansion their vectors. The main human pathogens mosquito-borne flaviviruses, including dengue virus, Zika West Nile but tick-borne flaviviruses also emerging. As any viral infection, body's first line defense against flavivirus is innate immune defense, type I interferon armed wing. This cytokine exerts its antiviral activity by triggering synthesis hundreds interferon-induced genes (ISGs), whose products can prevent infection. Among ISGs that inhibit replication, certain tripartite motif (TRIM) proteins have been identified. Although involved in other biological processes, TRIMs constitute family active on wide range viruses. Furthermore, whereas TRIM directly block others positive regulators IFN response. Therefore, viruses developed strategies evade or counteract proteins, even hijack advantage. In this review, we summarize current state knowledge interactions between covering both direct indirect mechanisms.

Language: Английский

Exploring necroptosis-associated genes: implications for immune responses and therapeutic strategies in diabetic foot ulcers

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Diabetic foot ulcers (DFUs) are among the most severe and debilitating diabetic complications, often leading to extremely high morbidity mortality. Recently, increasing evidence has highlighted role of necroptosis, a distinct type programmed cell death from apoptosis, in progression severity DFUs. Understanding necroptosis-associated genes DFUs could open new therapeutic avenues aimed at modulating this form death, potentially improving outcomes for patients suffering serious complication. This study focuses on discovering confirming potential necroptosis biomarkers linked DFU through application machine learning bioinformatics approaches. We obtained three microarray datasets associated with individuals Gene Expression Omnibus (GEO) database: GSE68183, GSE134431, GSE80178. In we identified (NRGs) differential expression between healthy controls, totaling 37 NRGs. Additionally, observed an activated immune response both groups. Moreover, clustering analysis revealed two clusters within samples, showcasing heterogeneity. Subsequently, constructed Random Forest (RF) model utilizing 5 (CENPB, TRIM56, ZNF768, PLIN4, ATP1A1). Notably, demonstrated outstanding performance external validation GSE68183 (AUC = 1.000). The pinpointed five context DFU, unveiling targets therapy. Bioinformatics elucidated that CENPB, ATP1A1 serve as future research.

Language: Английский