Search Results (808)

Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review critically analyzes the efficacy, limitations, and clinical utility of currently available diagnostic tests for food allergy, with particular emphasis on their ability to predict true clinical reactivity. A comprehensive literature review was conducted to evaluate the sensitivity, specificity, and predictive values of both traditional and emerging diagnostic modalities. English-language guidelines, systematic reviews, and key clinical studies published primarily within the past 15 years (up to 2025) were identified through PubMed and Google Scholar. Classic diagnostic tools, including skin prick testing (SPT) and serum-specific IgE (sIgE), were assessed alongside novel approaches such as component-resolved diagnostics (CRD), basophil activation test (BAT), mast cell activation test (MAT), atopy patch testing (APT), cytokine profiling, and omics-based diagnostics. Particular attention was given to how these tests compare with the oral food challenge (OFC), which remains the diagnostic gold standard. The findings demonstrate that while conventional tests offer high sensitivity and are valuable for initial risk assessment, their limited specificity often leads to overdiagnosis. Emerging molecular and cellular assays show improved specificity and functional relevance, especially in complex cases involving polysensitization or unclear clinical histories and may reduce reliance on OFCs in the future. However, accessibility, cost, and lack of standardization currently limit their widespread clinical application. Advances in artificial intelligence and data integration hold promise for improving diagnostic accuracy through enhanced interpretation of complex immunological data. Based on the synthesized evidence, this review proposes an evidence-based, stepwise, and individualized diagnostic algorithm for food allergy. Integrating clinical history, targeted testing, and selective use of OFCs can improve diagnostic certainty, enhance food safety, minimize unnecessary dietary avoidance, and optimize patient outcomes. The review underscores the need for continued research, standardization, and validation of novel diagnostic tools to support personalized and precise food allergy management. Full article

Cytokines IL-17A and TNF-α have been implicated in the dysregulated immune responses that characterize SLE, with potential relevance to specific organ involvement. This study aimed to assess their serum levels in SLE patients and to explore potential correlations with clinical, biological, and immunological features, as well as with disease activity and damage scores. We conducted a cross-sectional analysis of 88 SLE patients diagnosed according to the 2012 SLICC classification criteria and 87 controls matched by sex and age. Serum IL-17A and TNF-α levels were quantified using ELISA. Clinical and laboratory data were collected, including SLEDAI for disease activity and the SLICC/ACR Damage Index for cumulative organ damage. No significant differences were observed in serum IL-17A levels between SLE patients and healthy controls, whereas serum TNF-α levels differed significantly between the two groups. Serum IL-17A levels were significantly associated with cutaneous involvement (p = 0.036) and the inflammatory syndrome (p = 0.049). TNF-α levels were also significantly elevated in patients with cutaneous manifestations (p = 0.050). A positive correlation was observed between TNF-α levels and cumulative organ damage, as assessed by the SLICC/ACR Damage Index (r = 0.36, p < 0.001; R² = 0.13), and levels were particularly higher in patients with malignancies (p = 0.032). A positive correlation was observed between IL-17A and TNF-α levels. No significant associations were found between serum levels of IL-17A or TNF-α and demographic factors, disease activity (SLEDAI), immunological and biological markers. Both IL-17A and TNF-α were significantly associated with cutaneous involvement in SLE patients, supporting their implication in skin-related inflammatory processes. IL-17A was additionally linked to the presence of an inflammatory syndrome. TNF-α levels correlated with cumulative organ damage and were elevated in patients with malignancies, suggesting that patients with higher TNF-α accumulated significantly more irreversible organ damage over time. No meaningful associations were observed between cytokine levels and demographic characteristics, disease duration, treatment or global SLE activity. Full article

Background and Objectives: Immunosenescence is a complex biological process associated with aging, characterized by a progressive decline in immune function and increased chronic inflammation (“inflammaging”), with clinical implications such as frailty, functional decline, multimorbidity, and a higher risk of adverse events in older adults. Nurses in community and primary care settings play a central role in preventive and health promotion interventions that may indirectly influence these processes. However, the available literature remains fragmented. Therefore, this scoping review aims to map and synthesise nursing interventions targeting older adults (≥60 years) that may indirectly influence immunosenescence by acting on its clinical correlates and modifiable determinants, organising the evidence within a four-pillar conceptual framework. Materials and Methods: A scoping review was conducted following JBI methodology and the PRISMA-ScR checklist. We included primary studies on nurse-led interventions in community, home care, primary care, territorial, or long-term care settings. PubMed, Scopus, and Web of Science were searched (English; last 10 years). Interventions were classified into four pillars: nursing nutrition and immunonutrition support, physical activity and exercise support, nursing vaccination coaching, and frailty monitoring and prevention of functional decline. Results: Twenty-five primary studies were included, mostly randomised or cluster-randomised trials in community, primary care, home care, and transitional care settings. Interventions mapped mainly to Pillar 4 and Pillar 2, while Pillar 1 was less frequent and usually part of multicomponent programmes; no primary studies targeted Pillar 3. Overall, effectiveness appeared driven more by intervention intensity and integration than by frailty identification alone: structured, multicomponent nurse-led programmes combining exercise with nutritional and psychosocial components showed the most consistent benefits on frailty, functional outcomes, and well-being, whereas low-intensity preventive consultations and Comprehensive Geriatric Assessment (CGA)-based models often showed limited improvements over usual care. Conclusions: This scoping review highlights the key role of community and primary care nurses in preventive interventions targeting clinical correlates of immunosenescence. Multicomponent nurse-led programmes integrating physical activity, nutrition, and psychosocial support appear most promising for frailty and functional outcomes, while low-intensity interventions show limited effectiveness. No primary studies addressed nurse-led vaccination coaching, representing an evidence gap. Future research should include biological/immunological markers alongside clinical outcomes. Full article

Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presents with a heterogeneous clinical spectrum, whereas multisystem inflammatory syndrome in children (MIS-C) is a distinct immunological entity characterized by a hyperinflammatory phenotype and a distinct biological architecture. Identifying routine biomarkers with early discriminatory utility is essential for rapid differentiation between MIS-C and coronavirus disease 2019 (COVID-19). Methods: We conducted a retrospective comparative study of 144 pediatric patients with COVID-19 or MIS-C admitted to a single specialized medical center. The analyses integrated classical statistical methods, Benjamini–Hochberg false discovery rate correction (FDR), penalized regression models, and machine learning algorithms to identify biomarkers with discriminative value, using only routine laboratory tests. Results: MIS-C was associated with an intense inflammatory profile, characterized by increases in C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), lymphopenia, and selective electrolyte disturbances, highlighting a coherent biological architecture. In contrast, COVID-19 showed limited associations with traditional inflammatory markers. Predictive models identified a stable core of biomarkers with excellent performance in Random Forest analysis (area under the curve, AUC = 0.95), and reproducible thresholds (CRP ~3.7 mg/dL, NLR ~3.3, PLR ~376; potassium ~4.2 mmol/L). These findings were independently confirmed using penalized Ridge regression, where the reduced model achieved superior discrimination compared to the full 13-variable model (AUC = 0.93 vs. 0.89) and maintained stable performance under internal cross-validation, reinforcing the clinical relevance of this compact biomarker panel. Conclusions: MIS-C is clearly distinguished from COVID-19 by a specific and reproducible immunological signature. The identified biomarkers may represent a potential foundation for the development of simple clinical algorithms for pediatric triage and risk stratification, opening the prospect of a simplified scoring tool applicable in emergency settings. Full article

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (MMP1, MMP9) and vascular homeostasis (NOS3) genes with JS risk and immunological phenotypes. A case–control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (MMP1 rs1799750, MMP9 rs3918242, NOS3 rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. The MMP9 (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14–4.37, p = 0.022), showing a trend in linear facial forms. The NOS3 (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92–7.37, p = 0.065). No significant associations were found for rs1799750 MMP1 and risk of disease development. The MMP9 risk genotype did not correlate with scleroderma-specific autoantibodies, while the NOS3 GG genotype was associated with lower serum levels of anti-collagen IV antibodies (p = 0.039). Genetic associations differ for JS subtypes: MMP9 with JLSd and NOS3 with JSSc. Children with CT polymorphism MMP9 (rs3918242) and with NOS3 (rs1799983) GG genotype were found to be genetically predisposed for the development of JS. Full article

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6–8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite’s discrete typing unit (DTU). This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox. This study provides a comprehensive, kinetic, multifaceted characterization of the acute infection using the highly virulent T. cruzi Y strain (TcII) in outbred Swiss mice. Here, crucial infection parameters are presented, including the optimal infective dose, the parasitemia dynamics, tissue damage markers, hematological profiles, cytokine production (Th1/Th2/Th17/Th22), and molecular parasite identification in target organs (heart, colon, esophagus, spleen, and liver) across the span of the infection. The novelty of this study lies in the kinetic integration of these parameters within a defined model; rather than presenting isolated data points, we demonstrate how the biochemical, physiological, and clinical signs and immunological responses, with the resulting organ involvement, evolve and interact over time. To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents. Full article

Immunogenic cell death (ICD) is a programmed pathway leading to cell death and promotion of immunological responses. Melanoma is resistant to chemotherapy and radiotherapy (RT). Disulfiram (DSF), which forms complexes with copper (Cu), has been shown to induce ICD of many tumor types. Here, we aim to investigate whether DSF/Cu combined with irradiation (IR) can induce ICD and exert anti-cancer effects in melanoma. In vitro experiments, treatment of MV3 and B16F10 melanoma cells with DSF/Cu + IR significantly increased the cellular apoptosis and increased ICD markers: damage-associated molecular pattern molecule (DAMP) exposure and release, including calreticulin cell surface expression, high-mobility group box 1 (HMGB1) release, and decreased intracellular ATP levels. In addition, DSF/Cu combined with IR treatment inhibited tumor growth and enhanced tumor-infiltrating immune cells in the B16F10-bearing C57BL/6 model. Our findings reveal that combining IR with DSF/Cu induces ICD and inhibits tumor growth in melanoma, providing a promising strategy to overcome the inherent resistance of RT in melanoma. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

Background/Objectives: This systematic review aimed to evaluate the clinical and immunological outcomes of non-surgical periodontal therapy (NSPT) in HIV-positive patients with periodontitis. Methods: Systematic search on four databases (PubMed, Scopus, Web of Science, Cochrane Library) and the gray literature was completed through December 2025. A comprehensive set of clinical parameters and immunological markers were assessed. Three studies met the inclusion criteria and were included in the final synthesis and qualitative analysis. Extracted outcomes included clinical periodontal parameters (PPD, CAL, BoP, PI, GBI, BI) and immunological markers (viral load, CD4+ lymphocyte count, CD4/CD8 ratio, salivary LF, salivary HST, GCF LF, GCF HST). Results: With a very low level of certainty, NSPT was generally associated with significant improvements in clinical periodontal parameters compared to before treatment measurements and HIV-negative individuals. Improvements in immunological status were also reported. Heterogeneity of study designs and reporting standards limited this study’s quantitative analysis. Conclusions: NSPT demonstrates beneficial clinical and immunological outcomes in people living with HIV. However, the very low level of certainty in the available data limits confidence in changes in periodontal status and immune system reconstitution following NSPT in this population; therefore, the findings remain inconclusive and should be interpreted with caution. Full article

Background: Chronic urticaria (CU) is characterized by recurrent wheals and/or angioedema persisting for more than six weeks. While disease triggers are often unidentified, seasonal and environmental factors may modulate disease activity; however, evidence regarding their clinical impact remains limited. Objective: This study aimed to evaluate the effects of seasonal, meteorological, and pollutant-specific environmental factors on urticaria control using the Urticaria Control Test (UCT), and to compare these effects between chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIU) in relation to inflammatory serum biomarkers. Materials and Methods: This prospective observational study was conducted at the Allergy and Clinical Immunology outpatient clinic of Kirikkale University Faculty of Medicine between 1 June 2023 and 1 April 2024. Patients with CU were classified as CSU or CIU according to international guidelines. Each participant was evaluated during summer and winter seasons. Area-level air pollution data and meteorological parameters were obtained from national monitoring systems. Disease control was assessed using the UCT, and inflammatory biomarkers were analyzed. Results: Urticaria control showed significant seasonal variation, with lower UCT scores during summer and higher scores during winter in both CSU and CIU patients. Among environmental factors, ozone (O₃) was the only pollutant consistently associated with poorer urticaria control, whereas particulate matter and traffic-related pollutants, despite being higher in winter, showed no clinically relevant association. Summer months were characterized by increased inflammatory activity, including elevated leukocyte counts, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and D-dimer levels, particularly in CSU patients. D-dimer emerged as an independent marker associated with poor disease control during summer. Conclusions: CU demonstrates marked seasonal variation, with disease worsening during summer months. Pollutant-specific effects, particularly O₃ exposure, rather than overall air pollution burden, appear to be clinically relevant in urticaria control. Inflammatory and coagulation-related biomarkers may provide additional insight into disease activity. These findings support a season-aware and individualized management approach and highlight the need for future studies incorporating individual-level exposure assessment and biomarker-guided strategies. Full article

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention. Full article

Background: In melanoma diagnostics key molecular markers, such as BRAF, NRAS, and KIT mutations also paved the way for targeted therapies. Immunotherapies, including immune checkpoint inhibitors like anti-CTLA-4 and anti-PD-1/PD-L1, have revolutionized treatment, improving survival outcomes for advanced-stage melanoma patients. Despite these advances, challenges such as resistance to targeted therapies and variability in patient responses to immunotherapy remain critical issues. The purpose of the project is to characterize the molecular landscape of a set of 28 malignant melanomas using next-generation sequencing, identify the prevalence and nature of class 3–5 variants (e.g., NRAS, BRAF, KIT, TP53), assess the genetic complexity and molecular patterns, and use these insights to inform personalized therapies and optimize patient stratification for potential combination strategies (targeted therapy followed by immunotherapy). Methods: We analyzed a set of malignant melanoma of the skin of 17 women (61%) and 11 men (39%) at the age of 23 to 85 years (median: 63 years) by tumor-only next generation sequencing. Results: 22/28 cases (79%) present a pathogenic or likely pathogenic variant with an allelic frequency of ≥5%. In total 42 distinct somatic pathogenic or likely pathogenic variants with an allelic frequency of ≥5% could be detected. The most frequent pathogenic molecular alteration in these melanomas were found in NRAS (25%) and BRAF (25%). The most frequent molecular alteration of unknown significance was found in FANDC2 (46%), NOTCH3 (39%), ARID1A (32%), PMS2 (32%), POLE (29%), NOTCH1 (29%), TSC2 (25%), SMARCA4 (25%), ATR (25%) and TERT (21%). Conclusions: While NRAS and BRAF were the most frequent actionable alterations (each 25%), a broad spectrum of variants of unknown significance (e.g., FANDC2, NOTCH3, ARID1A, PMS2, POLE, NOTCH1, TSC2, SMARCA4, ATR and TERT) also predominates, underscoring the genetic complexity of melanoma. These variants complicate clinical decision-making because their contribution to tumorigenesis, therapeutic response, and prognosis remains uncertain. Nevertheless, these variants also offer a valuable resource for future research, as they may uncover novel pathogenic mechanisms or therapeutic targets once their significance is elucidated. Integrating comprehensive genetic profiling with immunologic markers can enhance patient stratification and support rational, potentially synergistic strategies, such as combining targeted therapies with immunotherapy, to optimize clinical outcomes. This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma. Full article

Background/Objectives: This study examined the metabolic, oxidative, immunological, and histomorphological effects of the multicomponent fermented biological product derived from camel milk, Inullact-Fito, in comparison to metformin in a rat model of alloxan-induced diabetes resulting from insulin insufficiency. The model was chosen as an experimental system that replicates pancreatic β-cell damage induced by oxidative stress rather than insulin resistance. Methods: Alloxan-induced diabetes was used to evaluate metabolic, oxidative, immunological, and histomorphological alterations. Metformin was utilized as a pharmacological comparator. Blood glucose levels, circulating insulin concentrations, markers of oxidative stress and lipid peroxidation, immunoglobulin levels, CD4⁺/CD8⁺ T cell balance, and pancreatic histostructure were assessed. Results: Alloxan administration led to substantial hyperglycemia, oxidative stress, immunological imbalance, and structural damage to pancreatic tissue. Following therapy with Inullact-Fito, blood glucose levels reduced dramatically (from 21.9 ± 0.22 to 9.85 ± 0.10 mmol/L, p < 0.05), circulating insulin concentrations were largely corrected, oxidative stress and lipid peroxidation markers decreased. Immunological evaluation revealed decreased serum immunoglobulin M and IgG levels (p < 0.05) and partial normalization of the CD4⁺/CD8⁺ T cell balance. Metformin showed comparative effects; however, its activity in this model is limited by its primary mechanism related to insulin resistance. Conclusions: Overall, the data reveal that Inullact-Fito combines metabolic, antioxidant, and immunomodulatory actions under experimental oxidative and metabolic stress conditions. Further research using models of insulin resistance and type 2 diabetes, as well as long-term clinical trials, is needed to fully evaluate the therapeutic potential, safety profile, and translational importance of this fermented dairy product as a functional nutritional intervention. Full article