Comprehensive Analysis of Immune Characteristics of Fluorosis and Cuprotosis-Related Genes in Fluorosis Targeted Drugs

Biological Trace Element Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Язык: Английский

Single-cell RNA sequencing reveals SLC31A1-mediated M2 polarization of macrophages promotes malignant progression in triple-negative breast cancer

Journal of Cancer Research and Clinical Oncology, Год журнала: 2025, Номер 151(5)

Опубликована: Май 14, 2025

Among the various types of breast cancer that endanger women's lives, triple-negative (TNBC) stands out due to its extreme heterogeneity, aggressive nature, and high likelihood recurrence. The absence unique targets targeted drugs is a major factor contributing failure treatments eventual death patients. Single-cell RNA sequencing (scRNA-seq) was applied investigate immune microenvironment TNBC, facilitating detection key cell subpopulations regulatory genes. mRNA expression SLC31A1 in macrophages measured by qPCR. Flow cytometry utilized ascertain M2 macrophage proportion apoptosis. Transwell scratch assays were conducted gauge migration invasion. Copper ion H2O2 kits employed evaluate copper content oxidative stress levels macrophages. overexpression TNBC myeloid cells, particularly subpopulations, identified through scRNA-seq analysis. Cluster pseudotime analyses showed with are often advanced stages growth, accompanied notable changes stress. Functional studies revealed knocking down significantly reduced M2-type polarization. conditioned medium from these markedly inhibited invasion, while promoting Furthermore, knockdown resulted decreased enhances malignant phenotype cells inducing polarization

Язык: Английский

Role of cuproptosis in mediating the severity of experimental malaria-associated acute lung injury/acute respiratory distress syndrome

Parasites & Vectors, Год журнала: 2024, Номер 17(1)

Опубликована: Окт. 19, 2024

Abstract Background Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk malaria infection, accumulation-induced cuproptosis triggers M1 It thus hypothesized could act as critical mediator in pathogenesis MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore role severity murine MA-ALI/ARDS. Methods We utilized an experimental model MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA treated these animals potent ion carrier disulfiram (DSF) or chelator tetrathiomolybdate (TTM). RAW 264.7 macrophages, which were stimulated infected red blood cells (iRBCs) vitro, also targeted DSF-CuCl 2 TTM-CuCl further investigate mechanism. Results Our findings showed dramatic elevation amount expression SLC31A1 (a influx transporter) FDX1 key positive regulator cuproptosis) displayed notable reduction ATP7A efflux tissue mice. Compared ANKA-infected control group, administered DSF exhibited remarkable increase parasitemia/lung parasite burden, total protein concentrations bronchoalveolar lavage fluid (BALF), wet/dry weight ratio, vascular leakage, pathological changes tissue. Strikingly, treatment demonstrated dramatically elevated levels, FDX1, numbers CD86 + , CD68 -CD68 messenger RNA (mRNA) levels pro-inflammatory cytokines (tumor necrosis factor [TNF-α] inducible nitric oxide synthase [iNOS]) tissue, decrease body weight, survival time, ATP7A, number CD206 mRNA anti-inflammatory (transforming growth beta [TGF-β] interleukin 10 [IL-10]). In contrast, TTM reversed Similarly, vitro experiment SLC31A1, CD86, TNF-α, iNOS iRBC-stimulated decline CD206, TGF-β, IL-10. trends cells. Conclusions data demonstrate activation aggravated inducing polarization pulmonary while inhibition contrarily ameliorated promoting M2 suggest blockage be potential therapeutic strategy for Graphical

Язык: Английский