👤 Amina El Ayadi

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a lack of targeted therapies and poor prognosis. The tumor microenvironment (TME) plays a pivotal role in TNBC progression, with immune mediators such as cytokines, chemokines, growth factors, and immune checkpoints driving inflammation, angiogenesis, and immune evasion. We conducted a comparative analysis of 81 immune-related proteins in serum samples from 137 participants: 49 healthy controls (HC), 63 non-TNBC (NTNBC) patients, and 25 TNBC patients. Protein expression was quantified using multiplex immunoassays (ProcartaPlex and MILLIPLEX MAP® panels). Statistical analyses included principal component analysis (PCA), hierarchical clustering, receive operating curves (ROC), and pathway enrichment to identify diagnostic biomarkers and molecular networks associated with TNBC aggressiveness. Ou results revealed distinct immune dysregulation in TNBC, characterized by significant overexpression of pro-inflammatory cytokines (IFN-γ, IL-12p70, IL-8), chemokines (MIP-1α, Fractalkine), growth factors (VEGF-A, SCF), and immune checkpoints (LAG-3, PD-L1). ROC curve analyses identified LAG-3, Fractalkine, and VEGF-A as the top biomarkers distinguishing healthy controls from TNBC, while IL-5, IL-27, and TNF-β effectively discriminated TNBC from NTNBC. Cytokine network analysis highlighted TSLP, IL-12p70, and IL-17 A as central hubs coordinating Th1/Th17 inflammatory responses, stromal remodeling, and immune evasion, with strong interactions between IL-17 A-ENA-78-SCF and IL-3-IL-21 axes driving TNBC aggressiveness. Stratified analyses further demonstrated stage, grade, and metastasis revealed that IL-12p70, MIP-1α, and IL-18 were elevated in late-stage TNBC; IL-17 A, IL-5, and TWEAK were significantly overexpressed in high-grade tumors; and IFN-γ, IL-8, CTLA-4 and TSLP peaked in metastatic TNBC. Our findings identify immune mediator panels as promising diagnostic and prognostic biomarkers for TNBC. Show less

Severe burn injuries can cause long-term cognitive impairments, potentially driven by lipid-mediated neuroinflammation in the central nervous system (CNS). The disruption of lipid homeostasis may contribute to neuroinflammatory responses, exacerbating neuronal damage. This study investigates whether acipimox, an anti-lipolytic agent, modulates lipid accumulation and neuroinflammation in the prefrontal cortex following severe burns. Sprague Dawley rats were randomized into four groups: sham vehicle, sham acipimox, burn vehicle, and burn acipimox. A scald injury covering 40-60% of total body surface area was induced, and rats were treated with acipimox (50 mg/kg/day, intraperitoneally) or vehicle for seven days. Lipidomic analysis assessed alterations in lipid profiles, while machine learning (XGBoost) identified key lipid drivers of burn-induced neuroinflammation. Additionally, mRNA expression of inflammatory markers, including interleukin-1β (IL-1β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and toll-like receptor 4 (TLR4), was quantified to evaluate neuroinflammatory responses. Cytokine-lipid correlations were also examined using Spearman analysis. Lipidomic analysis identified significant alterations in a subset of the 21 lipid classes analyzed, particularly long-chain and very-long-chain fatty acids, including lysophosphatidylethanolamines, lysophosphatidylcholines, phosphatidylglycerols, phosphatidylethanolamines, and triacylglycerols ( These findings suggest that severe burns induce significant lipid dysregulation in the CNS, contributing to neuroinflammation and potential cognitive impairment. By targeting lipolysis, acipimox mitigates lipid accumulation, suppresses inflammatory pathways, and normalizes lipid levels, highlighting a potential therapeutic mechanism. This study establishes a mechanistic link between elevated lipolysis and CNS inflammation following severe burns. Acipimox effectively modulates lipid profiles and reduces neuroinflammation, underscoring its potential for managing burn-induced neurological complications. Further studies are needed to validate these findings and explore clinical applications. Show less

Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non-smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G-A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies. Show less