Hidradenitis suppurativa (HS) is a chronic auto‐inflammatory skin disorder characterised by recurrent, painful nodules, abscesses and tunnels, often leading to tissue destruction with a significant impairment in quality of life. Despite advancements in understanding, HS remains a complex disease, whose exact pathogenesis is yet to be revealed. Nevertheless, the role of a dysregulated innate immune response has been established, potentially contributing to the persistent and chronic inflammation. Recent advances in immunology have highlighted the concept of trained immunity, a form of innate immune memory that may provide new insights into HS pathophysiology. Trained immunity is mediated by epigenetic and metabolic reprogramming of innate immune cells, enabling them to mount a heightened and prolonged inflammatory response upon subsequent stimuli, even in the absence of the original trigger. We hypothesize that trained immunity could contribute to the persistent inflammatory state, influencing HS progression and severity. Environmental and microbial factors may act as persistent stimuli, leading to activation of innate immune pathways. From a mechanistic perspective, trained immunity in HS might involve increased cytokine production, altered myeloid cell differentiation and persistent epigenetic modifications favouring a pro‐inflammatory phenotype. Identifying specific molecular markers associated with trained immunity in HS could provide new diagnostic and prognostic tools and may open novel therapeutic avenues. By exploring the potential role of trained immunity in HS, we provide a new perspective on chronic inflammation, thus hypothesizing another actor involved in the aetiology/pathogenesis of this complex disease.

Colorectal cancer (CRC) remains a major clinical challenge due to resistance to conventional cell death-inducing therapies. TRAIL selectively induces apoptosis in cancer cells via death receptors, but its effectiveness in preclinical models is limited by tumor resistance mechanisms. Curcumin, a natural polyphenol, modulates multiple survival and apoptotic pathways and has been proposed as a sensitizing agent to overcome TRAIL resistance. Here, we investigated the combinatorial effects of TRAIL and curcumin in the HCT116 colorectal cancer cell model. Cells were treated with TRAIL, curcumin, or their combination for 24 and 48 h, evaluating apoptosis, viability, and underlying mechanisms. Curcumin significantly enhanced TRAIL-induced apoptosis (p < 0.0001) and further reduced MTT-derived metabolic activity (p < 0.01) compared with TRAIL treatment alone. This effect remained evident after 48 h, although the stability and persistence of TRAIL activity were not directly assessed. Mechanistically, combined treatment enhanced PARP cleavage, γ-H2AX phosphorylation, and BAX and Caspase-3 cleavage, while downregulating anti-apoptotic IAP family members. Notably, cotreatment also promoted pyroptosis, shown by characteristic morphological changes (p < 0.0001) and increased Gasdermin-E cleavage. These findings indicate that curcumin sensitizes CRC cells to TRAIL by engaging both apoptotic and pyroptotic pathways, suggesting a potential approach to counteract both TRAIL and multidrug resistance in colorectal cancer.

Inflammation is associated with metabolic alterations that can lead to the release of volatile organic compounds (VOCs) reflecting cellular biochemical activity. Profiling these volatile metabolites may provide insight into cellular responses to inflammatory stimuli, although their characterization in skin-derived cells remains limited. In this exploratory proof-of-concept study, we investigated the volatile metabolite profiles of human skin fibroblasts exposed to different inflammatory stimuli. Fibroblast cell lines were stimulated with polyinosinic:polycytidylic acid (Poly I:C), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS) to model viral-, cytokine-, and bacterial-associated stress conditions. Headspace solid-phase microextraction coupled with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was applied to analyze volatile metabolites released from the cell cultures, enabling exploratory profiling of the fibroblast volatilome. A data-processing workflow including pairwise comparisons between experimental groups and statistical filtering was implemented to identify volatile features associated with the different conditions. Several VOCs were tentatively identified, mainly belonging to alcohol, ester, and hydrocarbon classes, and showed differential abundance patterns between stimulated and control samples. Multivariate analysis indicated a separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the volatile profiles of fibroblast cultures. While these observations may reflect metabolic responses occurring under inflammatory stimulation, the chemical identity and biochemical origins of several detected features remain to be confirmed. All in all, this study demonstrates the feasibility of applying HS-SPME-GC×GC-TOFMS-based volatilome profiling to investigate stimulus-associated changes in fibroblast cultures. The detected VOC patterns should therefore be considered preliminary observations requiring further chemical characterization and independent validation. Future studies including larger sample numbers, complementary biological verification of the inflammatory response, and more physiologically relevant experimental models will be necessary to further assess the robustness and potential relevance of these volatile signatures in the context of inflammatory processes.