Search Results (223)

Background/Objectives: Anemia of inflammation (AI) is a prevalent condition linked to systemic inflammation in several chronic diseases, including chronic liver diseases. Hypovitaminosis D is frequently identified in patients with chronic diseases, and its pathogenic role in anemia is currently under investigation. The aim of this study was to prospectively investigate changes in hemoglobin concentration and inflammatory markers in vitamin D-deficient/-insufficient patients with decompensated cirrhosis after initiating vitamin D supplementation, in addition to the supplementation of other micronutrients if needed. Methods: Patients with cirrhosis discharged from decompensation were assessed at baseline and 3 months after vitamin D supplementation. Laboratory parameters of red cell series, nutrition, and micronutrients were assessed in both visits, together with markers of systemic inflammation. Results: Thirty-nine patients were included in the study, of whom 33 completed the 3-month evaluation and were analyzed [age: 62.7 ± 10.7 years; gender: n = 29 (87.9%) males; Charlson index: 5.9 ± 1.6; Model for End-Stage Liver Disease (MELD): 12.4 ± 4.5; baseline hemoglobin (Hb): 11.7 ± 1.8 g/dL (anemia n = 24 (72.7%)); mean 25-hydroxyvitamin D (25OHD) plasma level: 15.5 ± 8.6 µg/L]. A significant increase in plasma 25OHD (40.1 ± 17.8, p < 0.001) and in Hb (12.4 ± 2.0, p = 0.01) was observed at 3 months with a decrease in the prevalence of anemia (n = 17, p = 0.015) and of Interleukin 6 in plasma levels [IL-6, 10.7 (5.8–23.3) vs. 6.5 (4.1–11.8), p = 0.016]. A greater rise in hemoglobin was correlated with higher plasma IL-6 concentration at baseline. Milder anemia and indexes of hypoferremia at baseline, along with optimal renal function and plasma levels of 25OHD at 3 months, were linked to resolution of anemia. Conclusions: Treating vitamin D deficiency together with other micronutrient deficits is associated with inflammation amelioration and improvement in anemia in patients with cirrhosis following discharge from acute decompensation. This paper supports the potential role of vitamin D in the management of anemia in patients with decompensated cirrhosis by modulating systemic inflammation. Full article

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease characterized by hypergammaglobulinemia, circulating antibodies, and distinctive histological features, with a higher prevalence in females. Immune responses targeting hepatic antigens are considered the main mechanism behind AIH. Many cytokines are involved in the inflammatory response typical of this disease. Interleukin 17 (IL-17) is a powerful pro-inflammatory protein that serves as a key link between the innate and adaptive immune systems. It plays an important role in regulating the inflammatory response in various tissues, including the liver. Several studies have shown that increased IL-17 levels are associated with the severity and progression of AIH. This review explores IL-17’s role in the AIH inflammatory pathway and summarizes existing evidence linking it to liver damage. We also highlight the potential of future therapies targeting this cytokine. Full article

The aim of this preliminary study was to determine the effect of taurine on the expression of genes involved in glycolysis, oxidative phosphorylation, inflammation, autophagy, and regenerative activity in cultured peripheral blood mononuclear cells (PBMCs) and articular cartilage explants from patients with end-stage rheumatoid arthritis (RA). PBMCs and knee articular cartilage were obtained from 20 patients with RA (3 men and 17 women) aged 62.2 ± 10.9 years, with a mean disease duration of 17.5 years (range: 2–43), prior to arthroplasty. PBMCs and cartilage explants were cultured in the presence of 50 µM taurine. Gene expression was determined using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Protein expression of the examined genes in PBMCs was quantified using ELISA. In the presence of 50 µM taurine PBMCs from patients with RA demonstrated a significant increase in the expression of genes encoding pyruvate kinase (PKM2), succinate dehydrogenase (SDHB), uncoupler of oxidation and phosphorylation (UCP2), ATP synthase (ATP5B), and unc-51-like kinase 1 (ULK1). At the same time a significant decrease in tumor necrosis factor (TNF)α and interleukin (IL)-1β expression was noted. In cartilage explants, taurine upregulated SDHB, UCP2, ULK1, and type 2 collagen gene (COL2A1), and decreased TNFα expression. We concluded that, under in vitro conditions, taurine can influence the expression of genes involved in glycolysis, oxidative phosphorylation, inflammation, autophagy, and regenerative processes in PBMCs and articular chondrocytes from patients with end-stage RA. Full article

Background and Objectives: The pathogenesis of liver steatosis is associated with obesity and systemic inflammation, particularly in subjects with body mass index (BMI) above 40 kg/m² and altered serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). Recent evidence suggests that disruption of the blood–brain barrier (BBB) may be associated with the development of steatosis, although limited data are available in humans. Thus, we assessed serum levels of neuron-specific enolase (NSE), transglutaminase 2 (TGM2), and glial fibrillary acidic protein (GFAP) as indirect markers of BBB dysfunction and examined their associations with steatosis severity, TNF-α and IL-10 in patients with morbid obesity. Materials and Methods: We biopsied the liver during bariatric surgery to assess steatosis by histology and serum markers by ELISA. Results: Most study subjects were women aged 38.7 ± 9.9 years with an average BMI of 42.3 ± 7.9 kg/m² and a steatosis prevalence of 78.9%. After grading steatosis as none (n = 8), mild (n = 17), moderate (n = 8), or severe (n = 5), we found no differences in sex, age, BMI, comorbidities, or laboratory variables, including liver enzymes. One-way ANOVA showed that serum IL-10 was 4-fold less in severe steatosis than in mild steatosis (p = 0.038), whereas TNF-α levels increased twice in severe steatosis compared to no steatosis (p = 0.029). NSE and GFAP serum levels, but not TGM2, increased proportionally to steatosis stage, showing differences between severe steatosis and no steatosis (p = 0.012 and p = 0.0002, respectively). Pearson correlation coefficients showed that NSE and GFAP were significantly associated with TNF-α (r = 0.600 and r = 0.402, respectively), but not with IL-10. Conclusions: Steatosis severity is significantly associated with markers of BBB disruption and systemic inflammation in patients with morbid obesity, suggesting a link between the BBB and liver steatosis. Full article

Type 17 immune responses are primarily mediated by Th17 cells and their effector cytokine interleukin-17 (IL-17), exerting a dual influence on wound healing. IL-17 plays a protective role during the initial stages of acute injury by facilitating rapid neutrophil recruitment, inducing antimicrobial peptide production and reinforcing pro-inflammatory signaling. However, sustained high signal of IL-17 results in a persistent inflammatory response that impairs keratinocyte proliferation and migration, angiogenesis, and nerve regeneration. This review elucidates the IL-17 signal effects and Th17 subset plasticity, which determines wound healing and skin barrier repair through their interactions with microbiota–immune, neuro–immune and metabolic reprogramming systems. Finally, we propose that the new therapeutic methods focus on IL-17 targets through precise spatiotemporal modulation and microenvironmental remodeling to create effective treatments for chronic non-healing wounds. Full article

Background and Objectives: Biological therapies improve disease severity and quality of life in patients with psoriasis, but data on Romanian patients remain limited. Our study aimed to characterize patients with psoriasis from Transylvania and to evaluate the impact of biologics on disease severity, treatment switching, affected special areas response, quality of life, and laboratory biomarkers. Materials and Methods: We conducted a retrospective exploratory study at two centers in Cluj-Napoca, Romania, using routinely collected medical data. Results: One-hundred and fifteen patients (aged 2–72 years) were evaluated; 45 patients received anti-TNF, 43 received anti-IL-17, and 27 received anti-IL-23. Patients treated with anti-IL-17 or anti-IL-23 were older at diagnosis than those treated with anti-TNF (p = 0.0001). Psoriatic lesions were prevalent in the scalp (58.3%) and nails (36.5%). Methotrexate was the most common prior systemic therapy (87.8%), with no difference between the groups (p = 0.7668). Patients receiving anti-TNF therapy (46.7%) or anti-IL-17 therapy (20.9%) also most frequently received prior treatment with systemic retinoids. Cardiometabolic comorbidities, including hypertension (40.9%) and diabetes mellitus (20.9%), were prevalent. Anti-IL-17 therapies were used more frequently in patients with hypertension (46.5%), diabetes mellitus (34.9%), and psoriatic arthritis (34.9%). Baseline severity scores were comparable across the groups (p > 0.10). A therapeutic switch occurred in approximately one-quarter of the patients, most frequently in the anti-TNF group (57.8%), which also showed higher PASI and DLQI scores at switching (p < 0.0001). At 36 weeks, anti-IL-17 and anti-IL-23 therapies demonstrated superior outcomes compared to anti-TNF therapy (p = 0.045). All patients receiving anti-IL-23 therapy achieved a PASI 100 at the 60-week follow-up. Significant improvements in PASI and DLQI were observed for all biologics (p < 0.0001). Conclusions: Biological therapies were associated with significant improvements in disease severity and quality of life. Anti-TNF therapies were switched more frequently due to reduced efficacy, while clinical improvement was observed regardless of lesion localization. Full article

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary sarcoidosis with extrapulmonary lesions (EPL) confers poor prognoses. The transcriptomic features of peripheral blood mononuclear cells (PBMCs) could be crucial in sarcoidosis pathogenesis. However, the gene expression characteristics associated with EPL development remain unknown. Methods: Bulk PBMCs were collected from 26 healthy controls and 14 patients with pulmonary sarcoidosis stratified into those with (n = 9) or without (n = 5) EPL. None of the participants were receiving immunosuppressive agents. PBMC transcriptomic analysis was conducted using RNA sequencing. Results: Principal component analysis (PCA) revealed a clear distinction between pulmonary sarcoidosis and healthy control groups, with 227 differentially expressed genes (88 upregulated, 139 downregulated), including upregulated (CLEC7A, GBP5, JAK2, IL15, IL1B, CXCL8, and CXCL10) and downregulated (TNFRSF13C, CD40LG, CD28, and ID3) genes in pulmonary sarcoidosis group. Enrichment analysis revealed upregulated immunological pathways related to granuloma formation in pulmonary sarcoidosis PBMCs, including T helper 17 and tumor necrosis factor-alpha signaling pathways, IL-1B, IL-6, and IL-17 production, and response to external stimuli. Furthermore, patients with and without EPL showed 206 differentially expressed genes (131 upregulated, 75 downregulated), including upregulated (IFNG and IFNLR1) and downregulated (SOCS3, MMP9, and CXCL10) genes. Gene ontology (GO) analysis revealed that interleukin 6 (IL-6) and IL-23 production were upregulated in patients with EPL. Conclusions: These findings elucidate the mechanisms underlying granuloma formation in sarcoidosis and demonstrate the differential transcriptomic features of PBMCs in patients with and without EPL. The upregulation of IFNG and IFNLR1 may be related to EPL development and could serve as potential therapeutic targets for sarcoidosis. Full article

The absent in melanoma 2 (AIM2) inflammasome is a cytosolic DNA sensor that links genomic instability, mitochondrial dysfunction, and chronic inflammation. Unlike the nucleotide-binding domain, leucine-rich repeat (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome, AIM2 is activated directly by double-stranded Deoxyribonucleic Acid (dsDNA), including mitochondrial DNA (mtDNA) released under stress conditions. This positions AIM2 at the intersection of oxidative stress, impaired mitophagy, and innate immune dysregulation. Current therapies for ankylosis spondylitis (AS), such as anti-tumor necrosis factor (TNF), anti-interleukin 17 (IL-17), and Janus kinase (JAK) inhibitors, improve clinical outcomes; however, they do not address upstream mitochondrial dysfunction or DNA-driven inflammasome activation. By contrast, other inflammasomes, such as AIM2, remain comparatively less studied. Since autoimmune diseases, including AS, are frequently accompanied by uncontrolled innate immune responses to self-DNA, these findings provide a framework for comprehending the mechanisms of AIM2 activation and its interaction with inflammation, mitophagy, and oxidative stress. Here, we review the current evidence on AIM2 inflammasome involvement in AS pathogenesis and its potential as a therapeutic target. This approach offers new insight into disease control through re-establishing the balance between mitochondrial dysfunction and autoimmunity. Full article

Interleukin 17 (IL-17) is a crucial mediator at the interface of periodontal dysbiosis and host immunity. This review synthesizes current evidence on IL-17 in periodontitis (PD), its systemic connections, and the role of IL-17 gene variants. Clinical and experimental studies show that IL-17 rises in periodontal disease and is associated with the severity of PD via action on epithelial, stromal and osteoblastic cells to promote chemokine release, neutrophil recruitment, cyclooxygenase 2 and prostaglandin E2 synthesis, RANKL expression, osteoclastogenesis, and matrix metalloproteinase activity. Periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans pre-activate the local inflammation-maintaining Th17 response. There is converging evidence linking IL-17-centered signaling with rheumatoid arthritis, diabetes mellitus, and psoriasis in favor of a shared inflammatory network in barrier tissues and synovium. Despite these associations, IL-17 biology is contextually determined with mucosal defense and bone homeostatic roles that caution against unidimensional explanations. Evidence on IL-17A and IL-17F polymorphisms is still heterogeneous across populations with modest and variable risk associations with PD. Clinically, IL-17 in gingival crevicular fluid, saliva, or serum is a potential monitoring biomarker when utilized along with conventional indices. Therapeutically, periodontal therapy that reduces microbial burden may inhibit IL-17 function, and IL-17-targeted therapy has to balance potential benefit to inflammation and bone resorption against safety in oral tissues. The following research must utilize harmonized case definitions, standardized sampling, and multiethnic cohorts, and it must include multiomics to be able to differentiate between causal and compensatory IL-17 signals. Full article

In recent years, monoclonal antibodies targeting key cytokines underlying the occurrence of psoriatic skin lesions and joint involvement, i.e., Tumor Necrosis Factor-alpha (TNF-α), Interleukin 17 (IL-17), Interleukin 12 (IL-12), and Interleukin 23 (IL-23), have become more commonly used in the therapy of psoriasis. Due to the high effectiveness, a favorable safety profile, and growing availability of biological treatment methods, the number of patients receiving chronic monoclonal antibody therapy is increasing each year. However, the factors affecting the effectiveness of biological drugs are not fully recognized. The study aimed at analyzing the clinical profile of patients and non-specific inflammatory markers in terms of the response to the psoriasis treatment with IL-17, IL-23, IL-12/23, and TNF-α inhibitors. The analysis involved 185 patients receiving biological therapy in the Department of Dermatology and Venereology at the Medical University of Lodz, which resulted in a total of 222 treatment cycles (TC). The super-response was defined as 100% reduction in the Psoriasis Area and Severity Index (PASI 100), at week 16 (±4 weeks) of therapy. Our study indicates that the chance of achieving a super-response was higher among younger patients with no psoriatic lesions on palms and soles, not suffering from non-alcoholic fatty liver disease, previously treated with methotrexate, and characterized by a higher level of derived Neutrophil-to-Lymphocyte Ratio (dNLR) at the beginning of treatment. Full article

Background/Objectives: The association between plasma metabolites derived from dietary substrates and inflammatory processes remains underexplored, despite its potential relevance in the prevention of non-communicable diseases. This systematic review aimed to examine the relationship between blood metabolites and the modulation of inflammatory biomarkers. Methods: A total of 25 randomized controlled trials, published between 2019 and 2024, were included from an initial pool of 111 records. These studies investigated the effects of dietary patterns, specific food groups, or nutritional supplements on the human metabolome and their potential links to inflammation. Results: Metabolomic analyses were predominantly performed using mass spectrometry (MS)-based platforms (17 out of 25), with liquid chromatography–mass spectrometry as the most frequently employed method. Both targeted (n = 14) and untargeted (n = 11) approaches were represented, and samples were drawn from plasma, urine, and feces. Across the interventions, 64 metabolites were modulated, including fatty acyls, glycerolipids, benzenoids, and organic acids, reflecting potential changes in pathways related to oxidative stress, lipid and carbohydrate metabolism, and inflammatory signaling. Several studies also assessed classical inflammatory biomarkers such as C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Interventions involving healthy traditional dietary patterns, improvements in dietary fat quality, or the use of specific probiotic strains were often associated with favorable immunometabolic outcomes. In contrast, some interventions, such as Mohana Choorna, elicited upregulation of immune-related gene expression in adipose tissue without improvements in glucose or lipid metabolism. Conclusions: While metabolomic responses varied across studies, the evidence highlights the value of dietary interventions in modulating systemic metabolism and inflammation. These findings support the integration of metabolomics into clinical nutrition to define more personalized and effective dietary strategies for inflammation-related chronic disease prevention. Full article

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, Candida albicans and C. albicans-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific C. albicans antigens that activate Th17 cells during this disease are unknown. The C. albicans 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of C. albicans, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; R = 0.33, p = 0.0092), alanine aminotransferase (ALT; R = 0.27, p = 0.037), gamma-glutamyl transferase (GGT; R = 0.35, p = 0.0055) and alkaline phosphatase (R = 0.36, p = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; R = 0.51, p = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (p = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2–F4 as compared with patients with no or minimal fibrosis F0–F1 (p = 0.0082). The area under the curve (AUC) for detecting F2–F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder. Full article

Major depressive disorder (MDD) is a severe mental disorder associated with significant functional impairment and decreased quality of life. Growing evidence suggests that immune-inflammatory mechanisms, particularly cytokine dysregulation, take part in its development and course. This systematic review and meta-analysis aimed to evaluate whether cytokine alterations are present in early stages of MDD, specifically in first-episode (FE) and drug-naïve (DN) patients. Following PRISMA guidelines a comprehensive search of PubMed, Scopus, and Web of Science was conducted in March 2025. Studies were eligible if they compared levels of inflammatory cytokines between adult FE or DN MDD patients and healthy controls (HCs). Meta-analyses using random-effects models were performed, including subanalyses depending on the source of the sample and the quality of the studies. In total, 17 eligible studies involving 1371 MDD patients were included. The meta-analysis showed significantly elevated levels of interleukin 6 (IL-6), interleukin 2 (IL-2), and tumor necrosis factor alfa (TNF-α) in FE patients compared to HCs. DN patients’ quantitative analysis showed increased levels of IL-6, IL-2, interleukin 4 (IL-4), interleukin 10 (IL-10), TNF-α, and interferon gamma (IFN-γ) compared to healthy individuals. Moreover, in the case of TNF-α, IL-2, interleukin 1 beta (IL-1β), and IL-4, there was a difference in results depending on the sample source (plasma/serum). Cytokine dysregulation is present in first-episode and drug-naïve MDD individuals. These findings highlight that the immune–inflammatory response exists in the early stages of this disorder. Moreover, since more cytokines were elevated in DN patients, pharmacological antidepressant treatment might be a significant factor involved in inflammatory regulation in MDD. Nonetheless, future prospective studies with standardized protocols and division by clinical subtypes are needed to better understand the dynamics and clinical relevance of cytokine alterations in depression. Full article

Background: Early childhood caries (ECC) is a common chronic disease in young children, influenced by multiple factors, including the activity of bacteria and other microorganisms, diet, and immune response. Pro-inflammatory cytokines like interleukin-8 (IL-8) and anti-inflammatory cytokines like interleukin-10 (IL-10) play crucial roles in the inflammatory process of caries. However, their relationship with ECC severity remains unclear. This study aimed to compare salivary IL-8 and IL-10 levels in children with and without ECC and analyze their association with caries severity using the International Caries Detection and Assessment System (ICDAS). Children with and without central obesity were included to evaluate the potential influence of nutritional status on cytokine expression. Methods: A cross-sectional study was conducted from March 2022 to December 2023 in San Luis Potosí, México, including 76 children aged 3 to 5 years (40 with ECC and 36 caries-free). Anthropometric measurements were taken to classify children as centrally obese or non-centrally obese. Unstimulated saliva samples were collected, and IL-8 and IL-10 levels were measured using ELISA. Statistical analysis included the Mann–Whitney U test, Spearman’s rank correlation coefficient, and binary logistic regression analysis, considering p < 0.05 as statistically significant. Results: IL-8 levels were higher in the ECC group (85 ± 119 pg/mL) than in the control group (45 ± 74 pg/mL), but this difference was not significant (p = 0.3613). IL-10 levels were lower in the ECC group (3 ± 2 pg/mL) than in the control group (11 ± 44 pg/mL; p = 0.6481). The difference between IL-8 and IL-10 levels was greater in the ECC group (27 ± 41 pg/mL) than in the control group (17 ± 33 pg/mL; p = 0.1709). No significant correlation was found between cytokine levels and ICDAS scores (p > 0.05), and binary logistic regression did not show an association between IL-8, IL-10, WHtR, and cavitated caries lesions. Conclusions: Although IL-8 tended to be elevated and IL-10 reduced in children with ECC, the differences were not statistically significant. The observed trend suggests a possible local immunological imbalance in children with caries, which may contribute to disease progression independently of bacterial activity or behavioral influences. Full article

Background: Artificial sweeteners, widely used as non-nutritive sugar substitutes, are increasingly prevalent in ultra-processed products. Although promoted for weight management due to their minimal caloric content, their impact on systemic inflammation remains uncertain. This systematic review of animal studies aims to evaluate the association between artificial sweetener consumption and inflammatory biomarkers. Methods: A systematic literature search was conducted up to May 2025 across PubMed, Web of Science, and Scopus, following PRISMA guidelines and registered in PROSPERO (CRD420251084004). Risk of bias was assessed using the ARRIVE guidelines and SCYRCLE’s risk of bias tool. Results: Thirty-seven animal studies were included: aspartame (n = 17), sucralose (n = 16), acesulfame potassium (n = 5), and saccharin (n = 4). Protocols varied in terms of dosage, exposure duration, animal models, and assessment of inflammatory outcomes, including C-reactive protein, interleukins (IL-6 and IL-1β), and tumor necrosis factor alpha. Aspartame and sucralose could elevate inflammatory markers, with sucralose also disrupting gut integrity and microbiota. Acesulfame K and saccharin showed variable, dose-dependent effects. Conclusions: This systematic review of animal studies suggests a possible mechanistic association between the consumption of certain artificial sweeteners and systemic inflammation. However, this relationship remains to be clarified and warrants exploration through well-designed, large-scale randomized controlled trials. Full article