Search Results (3,518)

Purpose: Preclinical studies suggest that interleukin-1β (IL-1β) influences tumor behavior in non-small cell lung cancer (NSCLC). While the CANTOS trial demonstrated reduced lung cancer incidence with IL-1β inhibition, the CANOPY trials failed to show survival benefit when combined with chemoimmunotherapy. The role of IL-1β in NSCLC with oncogenic mutations remains unclear. We evaluated the prognostic and predictive significance of IL-1β expression across NSCLC subtypes. Methods: We analyzed 21,698 NSCLC tumors profiled by Caris Life Sciences using DNA and RNA next-generation sequencing. IL-1β expression was stratified into quartiles (Q1: lowest 25%, Q4: highest 25%). Real-world overall survival (OS) and time on treatment (TOT) were obtained from insurance claims. Statistical comparisons used Chi-square, Fisher’s exact, or Mann–Whitney U tests. Survival outcomes were assessed with Cox models. Results: Across unselected NSCLC patients, low IL-1β expression (Q1) was associated with modestly longer OS versus high expression (Q4) (median OS 19.5 vs. 17.4 months; HR 0.94; p < 0.0001). This effect was more pronounced in EGFR-mutant adenocarcinoma (36.7 vs. 27.2 months; HR 0.76; p < 0.001) and ALK fusion-positive NSCLC (53.0 vs. 35.2 months; HR 0.62; p = 0.002). In NSCLC without targetable mutations, IL-1β expression was not prognostic. In KRAS-mutant adenocarcinoma, high IL-1β expression was associated with modestly longer TOT on immunotherapy (7.4 vs. 6.4 months; HR 1.15; p = 0.041), but not OS. High IL-1β expression correlated positively with TP53 mutation, TMB-high, and PD-L1 expression and inversely with EGFR, KRAS, BRAF, ERBB2, KEAP1, and STK11 mutations. Conclusions: IL-1β expression is a potential prognostic and predictive biomarker in NSCLC, associated with survival outcomes in defined molecular subsets. These findings suggest that IL-1β-targeted strategies may be particularly relevant in EGFR- or ALK-altered tumors. Full article

Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation against cisplatin-induced ovarian damage in a rat model, with a focus on oxidative stress, inflammation, follicular dynamics, and stromal fibrosis. Twenty-one adult female Wistar albino rats were randomized into three groups: control, cisplatin-treated, and cisplatin + krill oil-treated. Ovarian toxicity was induced via intraperitoneal injection of cisplatin (2.5 mg/kg, twice weekly for four weeks). Krill oil (4 mL/kg/day) was administered orally during the same period. Ovarian histopathology, follicle counts (primordial, primary, secondary, tertiary), stromal fibrosis, and biochemical markers, including plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and ovarian levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Toll-like receptor 4 (TLR4), TNF-α, NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-1β were evaluated. Cisplatin significantly reduced primordial, primary, secondary, and tertiary follicle counts while increasing stromal fibrosis (p < 0.001). Krill oil co-treatment notably ameliorated follicular depletion—improving follicle counts by 38.16%, 54.74%, 62.5%, 40.43%, respectively—and reduced fibrosis (p = 0.017). Biochemically, cisplatin decreased AMH levels and Nrf2 expression while elevating MDA, TNF-α, TLR4, NLRP3, and IL-1β levels (p < 0.001). Krill oil supplementation restored AMH (p = 0.002) and Nrf2 (p = 0.003) levels, while reducing MDA (p = 0.009), NLRP3 (p < 0.001), ovarian IL-1β (p = 0.005), plasma IL-1β (p < 0.001), TLR4 (p = 0.001), plasma TNF-α (p = 0.001), and ovarian TNF-α (p < 0.001), compared to the cisplatin group. Krill oil exerts significant antioxidant and anti-inflammatory effects, offering a promising strategy to mitigate cisplatin-induced ovarian damage and preserve fertility in young cancer patients. Full article

In exerting its actions on the utilization and storage of nutrients, the hormonal effects of insulin (INS) on target cells include important changes in terms of cell morphology involving cytoskeletal actin. Sensitivity to INS affects intestinal epithelial cells, which express receptors through which tight junctions and barrier permeability are also modulated. Nevertheless, the impact of INS on physiological rather than pathophysiological processes along gastrointestinal epithelia is not fully established. Here, we investigate INS effects on differentiated Caco-2 monolayers challenged by inflammatory stimuli, i.e., interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ), aiming to identify morpho-functional variations potentially associated with INS-dependent responses in intestinal epithelia differentially driven by different inflammation mediators. By observing the actin cytoskeleton, we characterized the impact of INS on actin structures’ organization, both in the absence and presence of pro-inflammatory treatments. Coherently, we observed altered expression of proteins interrelated to cytoskeletal dynamics (FAK, ITGB1), particularly evident in the synergistic action of IFN-γ and INS, also confirmed by the impact on INS-mediated regulation of the MAPK signalling pathway. Overall, the results describe a modular responsiveness of enterocyte-like monolayers to INS, depending on different inflammatory mediators, hinting at the interplay between INS signalling and morpho-functional remodelling in intestinal epithelial cells. Full article

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients. Full article

Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration. Full article

Background: Oxidative stress (OS) and inflammation are interconnected processes with significant roles in various chronic diseases, particularly those associated with aging, such as metabolic syndrome (MetS). Recent evidence suggests that walnuts (from Juglans regia L.), due to their rich content of phytochemicals, have antiaging potential by attenuating OS and chronic low-grade inflammation, known as inflammaging. Objectives: We aimed to assess the impact of daily walnut consumption for 4 weeks on biomarkers of OS and inflammation in a cohort of middle-aged individuals at risk of developing MetS. Methods: In this crossover randomized controlled trial (RCT), 22 participants (mean age: 48.81 ± 4.3 years) underwent two 28-day dietary interventions separated by a one-month washout period. One intervention period included daily consumption of 45 g of walnuts, while the other (control period) involved a normal-calorie diet without walnuts. Catalase (CAT) and glutathione peroxidase (GPx) activities, total antioxidant capacity (TAC), and interleukin (IL-1β, IL-6, IL-8) and tumor necrosis factor alpha (TNF-α) levels were determined from serum before and after each intervention period. Results: Assessment of changes obtained for the selected biomarkers following the walnut and control-diet periods (final-baseline) showed slight changes, but without any statistical significance, among the 20 participants included in the analysis. Conclusions: This first RCT targeting a group of middle-aged adults at risk of developing MetS shows that short-term (4 weeks) daily walnut consumption did not significantly alter oxidative stress and inflammation parameters, thus potentially contributing to the maintenance of cellular homeostasis. Further research is needed to investigate the impact of daily walnut consumption over a longer period (>3 months) on oxidative and inflammatory status in the middle-aged population and its potential to positively impact MetS biomarkers. Full article

Current acne therapies face major limitations, including antibiotic resistance and skin irritancy. In this study, a synergistic strategy combining cryptotanshinone and madecassoside was developed through functional complementarity. Antibacterial activity against Cutibacterium acnes was evaluated using minimum inhibitory concentration (MIC) and inhibition zone assays, while cytotoxicity was assessed using human keratinocytes (HaCaTs). Anti-inflammatory efficacy was quantified by measuring tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and prostaglandin E₂ (PGE₂) in lipopolysaccharide-stimulated macrophages and a copper sulfate-induced zebrafish inflammatory model. Systemic safety was examined in zebrafish models (developmental toxicity and sodium dodecyl sulfate-induced irritation). Finally, macroscopic severity, histopathology, and serum cytokines were used to assess an oleic acid-induced rat acne model. Cryptotanshinone inhibited Cutibacterium acnes (minimum inhibitory concentration = 62.5 μg/mL) but exhibited cytotoxicity (>5 μg/mL) and irritancy (≥1000 μg/mL). Madecassoside eliminated cryptotanshinone-induced cytotoxicity and reduced irritation. Importantly, the combination maintained antibacterial efficacy while synergistically enhancing anti-inflammatory effects, achieving a 94% reduction in follicular hyperkeratosis compared with 39% for cryptotanshinone alone (p < 0.01), alongside normalization of histopathology and cytokine levels. In conclusion, madecassoside functionally complements cryptotanshinone by neutralizing its cytotoxicity and irritancy, enabling a safe, synergistic therapy that concurrently targets antibacterial and anti-inflammatory pathways in acne pathogenesis. Full article

Statins, primarily prescribed for their lipid-lowering effects, have garnered significant attention for their potent anti-inflammatory effects. This review explores the underlying molecular pathways and clinical relevance of statins’ anti-inflammatory actions, extending beyond cardiovascular disease management to chronic inflammatory conditions and oncological applications. The lipid-lowering effect of statins stems from their ability to suppress HMG-CoA reductase, a crucial enzyme in cholesterol synthesis; however, their pleiotropic effects include modulation of critical inflammatory pathways such as the inhibition of NF-κB signalling, a reduction in pro-inflammatory cytokine production, and enhancement of endothelial function. We delve into the molecular pathways influenced by statins, including their effects on inflammatory mediators like C-reactive protein (CRP), interleukins (IL-6, IL-1β), and tumour necrosis factor-alpha (TNF-α). Clinical evidence supporting the efficacy of statins in managing chronic inflammatory diseases, such as rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, and osteoarthritis, is critically reviewed. Additionally, we investigate the emerging role of statins in oncology, examining their impact on inflammation-driven carcinogenesis, tumour microenvironment modulation, and cancer progression. Despite their broad therapeutic potential, the safety profile of statins, particularly concerning adverse effects such as myopathy, hepatotoxicity, and potential diabetes risk, is discussed. Controversies surrounding the extent of their anti-inflammatory benefits and the variability in patient responses are also addressed. This review consolidates the current literature, elucidating the biochemical mechanisms underlying the anti-inflammatory properties of statins and evaluating their clinical applications and associated controversies. Future research directions are identified, including the development of novel statin analogues with enhanced anti-inflammatory effects and the investigation of new therapeutic indications in inflammatory diseases and cancer. By providing an in-depth analysis, this review underscores the expanding therapeutic scope of statins and advocates for their integration into broader clinical strategies for the management of inflammation and cancer. Full article

Objectives: Skin aging, often accelerated by dietary advanced glycation end products (AGEs), poses both cosmetic and health challenges. This study explores the protective effects of hydroxytyrosol (HT), a potent antioxidant found in olives, against AGEs-induced skin aging in mice. Methods: A total of forty-eight 8-month-old specific pathogen-free (SPF) male C57BL/6J mice were randomly assigned to one of four groups: control, model, low-dose hydroxytyrosol (HT25), and high-dose hydroxytyrosol (HT50). An additional group of six 6-week-old SPF male C57BL/6J mice served as the youth group. The experimental period lasted 16 weeks. Following the intervention, skin, serum, and ileum samples were collected. Results: The results demonstrated that HT50 significantly increased skin moisture, epidermal thickness, and dermal thickness (p < 0.05). HT50 also significantly elevated hydroxyproline levels as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the skin while reducing malondialdehyde (MDA) content (p < 0.05). Furthermore, HT50 significantly reduced the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) (p < 0.05). Regarding intestinal integrity, hydroxytyrosol intervention (either HT25 or HT50) significantly increased the positive staining ratios of zonula occludens-1 (ZO-1) and occludin in the ileum (p < 0.05). Conclusions: HT improves skin hydration, thickness, and collagen levels while reducing oxidative stress and inflammation. Notably, HT also enhances intestinal barrier function, suggesting a role for the gut–skin axis. These findings highlight HT’s potential as a natural intervention for skin aging. Full article

With the global aging population, skeletal muscle aging has threatened to elderly health, making dietary interventions for age-related muscle decline a research priority. Lycium barbarum, a traditional food and medicinal herb, was used in the study to prepare Lycium barbarum water (LBW). This experiment was conducted in animals and included four groups: young control (C-Young), aged control (C-Aged), young LBW-drinking (G-Young), and aged LBW-drinking (G-Aged). Assessments covered skeletal muscle mass, cross-sectional area, and exercise ability to compare health status. The study measured mRNA expression of Atrogin-1 and MuRF-1 from the Forkhead Box O (FOXO) pathway, advanced glycation end products (AGEs) and senescence-associated β-galactosidase (SA-β-gal), oxidative stress levels via superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH), inflammatory levels through interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α), and applied untargeted metabolomics to profile metabolic alterations. Optimal LBW was achieved at 80 °C with a 1:10 (w/v) solid-liquid ratio. In aged mice, long-term LBW administration improved exercise capacity, reduced muscle atrophy, and increased muscle mass, alongside decreased aging-related markers, alleviated oxidative stress, and modulated inflammatory levels. Additionally, metabolomics confirmed age-related oxidative stress and inflammation. Long-term LBW consumption alleviates age-related skeletal muscle dysfunction via multi-target regulation, holding promise as a natural nutritional intervention for mitigating skeletal muscle aging. Full article

Background/Objectives: Chronic exercise training reduces markers of systemic inflammation; however, less is known about how to optimize this adaptation using nutrition. Dairy products, especially fermented ones, like Greek yogurt (GY), contain anti-inflammatory constituents. This secondary analysis aimed to examine the influence of post-exercise GY consumption vs. an isoenergetic carbohydrate pudding (CP; control) on markers of systemic inflammation during an exercise training intervention. Methods: Thirty healthy young males completed 12 weeks of resistance and plyometric exercise training and were randomized to consume GY (n = 15) or CP (n = 15). Rested/fasted blood samples were acquired at baseline, and weeks 1 and 12, and inflammatory biomarkers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, IL-1 receptor antagonist [IL-1ra], IL-1Beta [IL-1β], IL-10, and C-reactive protein [CRP]) were measured. Linear mixed models were run on the absolute concentrations, and linear regressions were performed on the absolute change (baseline to week 12), allowing us to account for important covariates. Results: In both groups, CRP (pro) and IL-1ra (anti) increased at week 1 vs. baseline and week 12, while IL-1β (pro) decreased at week 12 vs. baseline (main time effects). We observed significant interactions for IL-6, TNF-α, and the TNF-α/IL-10 ratio, indicating that at week 12, IL-6 (pro) was lower in GY, whereas TNF-α and TNF-α/IL-10 (both pro-inflammatory) were higher in CP vs. week 1 and baseline, respectively. Additionally, within our linear regression models, higher baseline concentrations of IL-1ra (anti), IL-10 (anti) and CRP (pro) predicted greater change over the intervention. Conclusions: These results indicate that our intervention benefited circulating inflammatory markers, and GY supplementation may enhance these effects. Full article

Objectives: The current study focused on the kidney protection and antioxidant properties along with the potential anti-ferroptotic activity of Geranium macrorrhizum L. (G. macrorrhizum) oil to ameliorate the acute renal oxidative tissue damage and toxicity of the aminoglycoside antibiotic gentamicin (GM) in an experimental murine model. Methods: The research was carried out with mature Balb/c mice distributed into four groups (n = 6). Application of GM (200 mg kg⁻¹ intraperitoneal injection for 10 days) was performed to induce kidney injury. Only saline was administered to the controls. The remaining groups were administered G. macrorrhizum oil (50 mg kg⁻¹ per dose) either used alone or in combination with GM. To assess the renal antioxidant status, the activities of specific antioxidant enzymes, indicators of lipid and DNA peroxidation and renal functional damage were examined using standard commercial kits, ELISA and EPR spectroscopy. Results: G. macrorrhizum oil analysis revealed 20 organic components belonging to mono- and sesquiterpenoids and long-chain hydrocarbons. The antioxidant and anti-inflammatory effects of G. macrorrhizum oil were demonstrated by reduced malondialdehyde, ROS, 8-hydroxy-2′-deoxyguanosine and cytokine levels (especially interleukin-1β) compared with GM. Furthermore, increased activation of superoxide dismutase, catalase and glutathione (GSH) were observed in the kidney homogenates of the animals which received GM in combination with G. macrorrhizum oil compared with the GM group. Additional changes in the GSH/glutathione peroxidase-4 axis were detected, suggesting the possible anti-ferroptotic potential of the oil. Nephroprotection was also demonstrated by elevated PGC-1α expression (peroxisome proliferator-activated receptor γ coactivator 1-alpha) and reduced KIM-1 levels (kidney injury molecule-1) following application of the oil. Conclusions: The preserved kidney antioxidant and functional properties in the groups treated with oil suggest that Geranium macrorrhizum L. could be utilized clinically to mitigate the toxic effects of GM application. Full article

Background and Objectives: Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) commonly occur after coronary artery bypass grafting (CABG) surgery, with frequent ectopics linked to atrial fibrillation risk and reduced heart function. While CABG-induced inflammation causes arrhythmogenic changes, the connection between preoperative inflammatory markers and postoperative ectopic burden has not been studied. Therefore, the aim of the present study is to evaluate the association between preoperative inflammatory biomarkers and postoperative atrial and ventricular ectopic burden, and to determine their influence on clinical outcomes following elective CABG procedures. Materials and methods: This study assessed preoperative plasma levels of highly sensitive C-reactive protein (hs-CRP), von Willebrand factor (vWF), transforming growth factor-β (TGF-β), interleukin (IL)-2, IL-1β, IL-6, IL-8, and vascular endothelial growth factor (VEGF) using the Multiplex technique in patients undergoing elective CABG. A continuous 24-h ECG Holter monitoring was performed one day before CABG, as well as on days 2, 3, and 4 post-CABG. The PACs and PVCs burdens were quantified, and correlations with clinical parameters were analyzed. Results: Preoperative plasma concentrations of vWF, TGF-β, and IL-8 exhibited significant positive correlations with postoperative PACs (p < 0.001, p = 0.03, and p < 0.001, respectively). Preprocedural hs-CRP, TGF-β, IL-6, and IL-8 levels showed significant positive associations with PVCs (p < 0.0001, p < 0.0001, p = 0.02, and p < 0.0001, respectively). However, none of the tested biomarkers could predict other postoperative outcomes, such as acute kidney injury, acute liver failure, duration of inotropic support, and days of hospitalization. Conclusions: Preoperative inflammatory biomarkers may serve as predictive tools for postoperative ectopic activity following CABG. Early identification of high-risk patients could enable prophylactic strategies and improve post-CABG outcomes. Full article

Glycosaminoglycans (GAGs) are linear, high molecular weight polydisperse heteropolysaccharides consisting of repeating disaccharide units, which always contain a uronic acid building block (e.g., d-glucuronic acid or l-iduronic acid). Their analogues containing d-mannuronic acid were not known until now. Another important class of the linear negatively charged polisaccharides are alginates, which are also present in the cell surface in the cell wall. They are composed of blocks of 1,4-linked β-d-mannuronic acid and its C-5 epimer α-l-guluronic acid in alternating or random order. Both groups of molecules have significant biological activity (e.g., cell growth inhibitory activity, anti-inflammatory effect, etc.). In the course of our research, we combined the structural characteristics of these two groups of molecules and produced a series of heparan sulphate analogue trisaccharides containing d-mannuronic acid, with a simplified structure, in which α- and β-mannosidic bonds are also found. Since trisaccharides may exert diverse biological effects and alginate derivatives can influence wound healing processes, we investigated the effects of the synthesized compounds on primary human dermal fibroblasts. We found that, when applied at 10 μM, none of the compounds influenced viability or spontaneous collagen production; however, some derivatives exhibited anti-inflammatory activity and suppressed the poly(I:C)-induced release of interleukin 6. Full article

Iron is essential for cellular respiration, oxidative defense, and host immunity, but its dysregulation is increasingly associated with metabolic disorders, such as obesity and type 2 diabetes. In these diseases, regional iron accumulation occurs in adipose tissue, independent of systemic overload. This process disrupts the mitochondrial redox balance, induces ferroptotic stress, and activates the innate immune pathways. Recent studies have highlighted the NLRP3 (nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing protein 3) inflammasome and its effector cytokine interleukin-1β (IL-1β) as important mediators of the interface between iron and inflammation. In both adipocytes and macrophages, labile iron increased reactive oxygen species (ROS) production and promoted inflammasome formation. Simultaneously, metabolic stress factors upregulate hepcidin expression, suppress ferroportin activity and exacerbate intracellular iron retention. These molecular events converge to maintain low-grade inflammation and impair insulin signaling. Despite these compelling associations, direct mechanistic evidence remains limited, particularly with respect to depot-specific responses and cell type resolution. In this review, I examine the current evidence linking iron handling and inflammasome biology in adipose tissue, focusing on ferroptosis, thioredoxin-interacting protein (TXNIP) signaling, and spatial mapping of iron–cytokine networks. I also discuss novel therapeutic strategies targeting iron overload and inflammasome activation, including chelation, hepcidin modulation, and inflammasome inhibition in the context of metabolic diseases. Full article