Search Results (2,022)

Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular risk characterized by low-grade inflammation. The aim of this systematic review and meta-analysis was to assess the effects of resistance exercise training (RET) predominantly on cytokines, along with changes in glucose profile and body composition in T2DM patients. The present systematic review and meta-analysis was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library databases from their inception up to July 2024 (PROSPERO; registration number CRD420251149352). We screened only for randomized controlled trials investigating the effects of systematic, supervised RET on C-reactive protein (CRP) and adipokines: adiponectin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls. Sixteen studies involving a total of 668 T2DM patients were retrieved from the databases for meta-analysis. We used the GRADE framework for assessing the certainty of evidence. Cochran Q-score (I²) was used to estimate heterogeneity among studies (level of significance p < 0.10) and risk of bias analysis was also performed. The cumulative results showed that post-RET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L) (WMD: −0.63; 95%CIs: −1.05, −0.20; p < 0.001); adiponectin (μg/mL) (WMD: −0.94; 95%CIs: −1.49, −0.38; p < 0.001). The results from adiponectin are quite conflicting since they derived from only three studies, where one of them had the greater impact. In parallel, we noticed significant amelioration of fasting glucose and HbA1c (p < 0.001), while body weight remained unaltered. Our meta-analysis demonstrated non-significantly lower levels of IL-6 and TNF-α in RET vs. control group. RET can merely reduce the inflammatory burden in T2DM patients by ameliorating the circulating levels of CRP and adiponectin, while in the rest of the biomarkers, non-significant results were obtained. Hence, the overall clinical impact of those anti-inflammatory effects of RET needs to be determined. Full article

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with subtypes ranging from patchy alopecia (AAP) to alopecia totalis and universalis (AT/AU). The aim of this research is to investigate molecular features across AA severity by performing an integrated analysis of scalp transcriptomic datasets (GSE148346, GSE68801, GSE45512, GSE111061) and matched serum proteomic data from GSE148346. Differential expression analysis indicated that, relative to normal scalp, non-lesional AA tissue shows early immune activation—including Type 1 (C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CD8a molecule (CD8A), C-C motif chemokine ligand 5 (CCL5)) and Type 2 (CCL13, CCL18) signatures—together with reduced expression of hair-follicle structural genes (keratin 32(KRT32)–35, homeobox C13 (HOXC13)) (FDR < 0.05, |fold change| > 1.5). Lesional AAP and AT/AU scalp showed stronger pro-inflammatory upregulation and greater loss of keratins and keratin-associated proteins (KRT81, KRT83, desmoglein 4 (DSG4), KRTAP12/15) compared with non-lesional scalp (FDR < 0.05, |fold change| > 1.5). Ferroptosis-associated genes (cAMP responsive element binding protein 5 (CREB5), solute carrier family 40 member 1 (SLC40A1), (lipocalin 2) LCN2, SLC7A11) and IRS (inner root sheath) differentiation genes (KRT25, KRT27, KRT28, KRT71–KRT75, KRT81, KRT83, KRT85–86, trichohyalin (TCHH)) were consistently repressed across subtypes, with the strongest reductions in AT/AU lesions versus AAP lesions, suggesting that oxidative-stress pathways and follicular structural integrity may contribute to subtype-specific pathology. Pathway analysis of lesional versus non-lesional scalp highlighted enrichment of IFN-α/γ, cytotoxic, and IL-15 signaling. Serum proteomic profiling, contrasting AA vs. healthy controls, corroborated scalp findings, revealing parallel alterations in immune-related proteins (CXCL9–CXCL10, CD163, interleukin-16 (IL16)) and structural markers (angiopoietin 1 (ANGPT1), decorin (DCN), chitinase-3-like protein 1 (CHI3L1)) across AA subtypes. Together, these data offer an integrated view of immune, oxidative, and structural changes in AA and found ferroptosis-related and IRS genes, along with immune signatures, as potential molecular indicators to support future studies on disease subtypes and therapeutic strategies. Full article

Gout is a form of sterile inflammatory arthritis in which monosodium urate (MSU) crystals deposit and provoke a neutrophil-predominant response, primarily driven by activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Here, we show that auranofin, a Food and Drug Administration (FDA)-approved anti-rheumatic agent, exerts anti-inflammatory effects in both in vitro and in vivo models of gout. Auranofin inhibited NLRP3 inflammasome activation in human THP-1 cells and murine macrophages, leading to reduced cleavage of caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). In MSU crystal-induced mouse models, auranofin treatment reduced paw swelling, serum cytokine levels, and tissue inflammation. Notably, auranofin suppressed neutrophil migration and decreased expression of C-X-C motif chemokine ligand 1 (CXCL1) in inflamed foot tissue and air-pouch exudates. Mechanistically, auranofin disrupted the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis, a key signaling pathway promoting neutrophil recruitment. Overexpression of IL-33 abolished the anti-inflammatory effects of auranofin, highlighting the central role of IL-33 in gout pathogenesis. Together, our findings suggest that auranofin alleviates MSU-induced inflammation by concurrently inhibiting NLRP3 inflammasome activation and IL-33-mediated neutrophil recruitment, supporting its potential as a dual-action therapeutic candidate for gout. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients. Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance. Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L, p = 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L. Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms. Full article

Under intensive farming systems and the global ban on antibiotic growth promoters (AGPs), early-weaned piglets exhibit incomplete physiological development, increasing their susceptibility to stress-related liver dysfunction and growth performance impairments. This study first investigated the effects of dietary supplementation with 0.2% tributyrin on the growth performance of 21-day-old weaned piglets over a 28-day period. Subsequently, on the final day, we examined its influence on antioxidant capacity, immune responses, and liver macrophage polarization using a 2 × 2 factorial challenge model, with the factors being diet (basal or tributyrin-supplemented) and immunological challenge (saline or lipopolysaccharide). The experimental results indicated that tributyrin had a significant enhancement on the average daily gain (ADG) of weaned piglets within the 0–14-day period (p < 0.05). Under lipopolysaccharide (LPS) challenge, tributyrin significantly increased the levels of catalase (CAT) and interleukin-10 (IL-10) while reducing the levels of malondialdehyde (MDA) and interleukin-6 (IL-6) in both serum and liver. Additionally, it significantly increased glutathione peroxidase (GSH-pX) activity in the serum and reduced glutathione (GSH) levels in the liver, and also decreased the serum level of interleukin-1β (IL-1β). Tributyrin downregulated pro-inflammatory cytokine gene expression while upregulating anti-inflammatory cytokine expression (p < 0.05). Furthermore, tributyrin significantly inhibited the expression of M1 macrophage polarization markers while enhancing those of M2 polarization (p < 0.05). Additionally, tributyrin suppressed SIRT1/NF-κB signaling pathway activation and promoted JAK2/STAT6 signaling pathway activation (p < 0.05). These findings exhibit that tributyrin alters the polarization of liver macrophages by regulating the SIRT1/NF-κB and JAK2/STAT6 signaling pathways, enhances antioxidant and immune functions, reduces LPS-induced liver inflammatory damage, and improves the growth performance of weaned piglets. Full article

Tyrosine kinase 2 (TYK2) mediates the signaling pathways of proinflammatory cytokines such as interleukin (IL)-12, IL-23, and type I interferons (IFNs) and plays a pivotal role in the pathogenesis of psoriasis and various other immune-mediated diseases. Deucravacitinib, a selective oral TYK2 inhibitor, has been approved for the treatment of psoriasis and demonstrated high efficacy and a favorable safety profile. This review summarizes the potential for expanding deucravacitinib indications based on case reports, clinical trials, and preclinical studies. Diseases in which TYK2 pathway has been demonstrated to be involved and for which clinical benefit of deucravacitinib has been reported include discoid lupus erythematosus, systemic lupus erythematosus, alopecia areata, lichen planus, palmoplantar pustulosis, psoriatic arthritis, systemic sclerosis, interstitial pneumonia, inflammatory bowel disease, and chronic recurrent multifocal osteomyelitis. Furthermore, emerging research suggests potential therapeutic applications in neurodegenerative diseases such as Alzheimer’s disease, and malignancies such as type 1 diabetes, vascular calcification in chronic kidney disease, T-cell acute lymphoblastic leukemia, and multiple sclerosis. Deucravacitinib may exert therapeutic effects by broadly suppressing cytokine signaling in a diverse range of inflammatory disorders. Ongoing clinical trials and mechanistic studies are required to clarify the efficacy and support its future indications. Full article

Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) and 2,3-indoleamine dioxygenase (IDO1) levels, and (3) peripheral inflammatory markers in a streptozotocin (STZ)-induced rat model of sporadic Alzheimer’s disease (sAD). After repeated treatment with a dose of 35 mg/kg MINO for seven consecutive days, male Wistar rats with sAD showed (1) improvements in early (29 days after injection, probe test) reference memory (decreased latency to reach the platform, increased time in the critical quadrant of the Morris water maze) and anxiety disorders (increased time in the open arms of the elevated plus maze; increased exploration and entrances in the center of the white–light illuminated open field) 45–46 and 90–91 days after STZ injection; (2) reduced APP and IDO1 levels in the hippocampus and prefrontal cortex; and (3) induction of anti-inflammatory response in blood (increased TCD4⁺ lymphocyte number and interleukin-10 production). This suggests that MINO, due to its anti-inflammatory action, improves memory and anxiety behavior related to sAD, indicating its neuroprotective and psychotropic properties. Full article

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1β-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1/AKT pathways. The experimental results show that IL-1β stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK/JNK activation, restored IRS-1/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1β. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR. Full article

Liver steatosis, the hallmark component of metabolic dysfunction-associated steatotic liver disease (MASLD), is particularly common among individuals with type 2 diabetes mellitus (T2DM). Shared mechanisms such as insulin resistance, oxidative stress, and chronic inflammation contribute to the coexistence of these conditions and accelerate disease progression, emphasizing the need for effective therapeutic strategies. In this 12-month, randomized, double-blind, placebo-controlled trial, 227 obese individuals with T2DM were assigned to receive either 1500 mg of curcumin daily or placebo. Curcumin significantly reduced liver fat content, liver stiffness, and glycated hemoglobin (HbA1c) compared with placebo (all p < 0.001). Improvements were also noted in inflammatory mediators, including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) (all p < 0.001), reflecting curcumin’s anti-inflammatory effects. Antioxidant benefits were evident, as total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) increased, while malondialdehyde levels decreased (all p < 0.001). Systematic safety assessments, including liver and kidney function tests, revealed no clinically significant abnormalities. Mild gastrointestinal discomfort was the most common non-serious adverse event. Overall, these findings support curcumin as a safe and effective adjunctive therapy for improving liver steatosis in obese patients with T2DM. Full article

Background: Despite anatomically successful surgical correction, postoperative hypertension remains a significant concern in patients with coarctation of the aorta, even when repair is performed during infancy. Inflammation and neurohormonal activation have been proposed as contributing mechanisms. Objective: To investigate the association between preoperative inflammatory biomarkers—specifically the interleukin-6 (IL-6) to tumor necrosis factor-alpha (TNF-α) ratio—and the development of hypertension in patients with successful isolated coarctation of the aorta repair under one year of age. Methods: This observational study included 42 infants with isolated CoA. Clinical, echocardiographic, and biochemical parameters were analyzed. Preoperative plasma levels of IL-6, TNF-α, von Willebrand factor (vWF), and renin were measured. Patients were classified based on hypertensive status at 2-year follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of postoperative hypertension. Results: Hypertension was diagnosed in 16 out of 41 patients (39%) at follow-up. A preoperative IL-6/TNF-α ratio > 2 was an independent predictor in multivariate analysis for postoperative HT (OR = 6.1, 95% CI = 6.23–9.31, p = 0.02). Conclusions: In this small single-center cohort, an elevated IL-6/TNF-α ratio was associated with postoperative hypertension after coarctation repair. These exploratory findings should be considered hypothesis-generating and warrant confirmation in larger, multicenter studies. Full article

Background/Objectives: The consumption of ultra-processed foods (UPF) has increased worldwide and has been hypothesized to contribute to chronic diseases, including conditions characterized by inflammatory dysregulation. We conducted a scoping review to map the human evidence on the relationship between UPF consumption and systemic inflammatory biomarkers. Methods: We developed a search strategy combining terms for UPF with terms for circulating inflammatory biomarkers, including C-reactive protein (CRP/hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and leptin. Findings were synthesized separately for children/adolescents and adults. Results: A total of 24 studies were included. CRP/hs-CRP was assessed in 21; IL-6 in 9; TNF-α in 8; IL-1β in 5; leptin in 5; MCP-1 in 5; PAI-1 in 5; and IL-8 in 2. In children/adolescents, CRP/hs-CRP tended to be higher with greater UPF intake in large cohorts and in preterm infants, whereas smaller or clinically selected samples did not show an association. For other biomarkers, IL-6 generally did not vary with UPF, TNF-α and IL-1β showed no association across studies, and the two IL-8 analyses yielded mixed results. In adults, 11/17 analyses reported higher CRP/hs-CRP levels with greater UPF intake, 5/17 reported no association, and 1/17 reported an association limited to women. IL-6 was predominantly higher with greater UPF intake; TNF-α likewise tended to be higher with UPF across several settings; IL-1β showed no association; MCP-1 and PAI-1 provided limited, inconsistent signals; leptin results were mixed. Conclusions: Higher UPF consumption is frequently associated with elevated systemic inflammatory biomarkers—most consistently CRP/hs-CRP—across adults and selected pediatric contexts. Signals for IL-6 and TNF-α appear in specific populations, whereas IL-1β, MCP-1, PAI-1, and leptin show inconsistent patterns. Full article

Background/Objectives: Most genes involved in the pathogenesis of Metabolic Syndrome (MS) and Type 2 Diabetes Mellitus (T2DM) are regulated by peroxisome proliferator-activated receptors (PPARs), which modulate the production of pro-inflammatory cytokines, with interleukin-6 (IL-6) playing a crucial role. The associations of single-nucleotide polymorphisms (SNPs) with MS and T2DM remain uncertain across populations. Therefore, we aimed to investigate the associations of PPAR-related SNPs in IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 with MS and T2DM clinical features. Methods: Polymorphism analysis of IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 genes was performed on isolated DNA from individuals diagnosed with T2DM and from healthy controls using real-time polymerase chain reaction (qPCR). Results: The IL-6-174G/C polymorphism shows that the CC genotype is associated with higher MS risk, whereas the GG genotype appears protective against metabolic disturbances. When the IL6 CC genotype is combined with ADIPOR2 GA or ADIPOR2 219 A/T, hyperglycemia is 1.3 times more frequent than with other IL6/ADIPOR2 genotype combinations. Conclusions: To develop informative genetic risk scores, future studies should include additional polymorphisms in key immune–metabolic pathway genes, such as AP-1, NF-κB, and FFAs. Full article

Cardiac allograft rejection remains a major cause of graft dysfunction post-transplant. While histology is the current diagnostic standard, it may miss early immune and inflammatory events. This study evaluated the immunohistochemical expression of matrix metalloproteinases 2 (MMP2), 9 (MMP9), and interleukin-1 beta (IL-1β) in cardiac transplant patients, correlating their expression with acute cellular rejection (ACR), antibody-mediated rejection (AMR), inflammation, vasculitis, the Quilty effect, and immune markers. Fifty-nine endomyocardial biopsy specimens were retrospectively analyzed. Immunohistochemical staining for MMP2, MMP9, and IL-1β was assessed based on nuclear, cytoplasmic, and membranous expression. Correlations were evaluated using Fisher’s exact test and odds ratios (ORs) with 95% confidence intervals (CIs). IL-1β nuclear expression showed strong associations with ACR (p = 0.0001), inflammation, vasculitis, and immune/endothelial markers (all p < 0.003). Nuclear MMP9 expression correlated with ACR and immune cell markers and was borderline significant for AMR (p ≈ 0.05). Cytoplasmic MMP2 (>50%) was significantly associated with AMR (OR = 7.47, p = 0.0002). No marker correlated with the Quilty effect. The immunohistochemical profiles of IL-1β and MMP9 support their involvement in immune-mediated injury in cardiac allograft rejection, with IL-1β emerging as a sensitive marker of early inflammation. MMP2 appears to be more relevant to humoral rejection processes. These findings suggest that selected tissue biomarkers may enhance diagnostic precision and support early detection of graft injury when integrated with conventional histology. Full article

Introduction: Expanded hemodialysis using medium cut-off (MCO) dialyzers effectively removes middle-molecule uremic toxins, comparable to hemodiafiltration, but their single-use designation increases the dialysis costs. This study evaluated the efficacy and safety of reusing two MCO dialyzers available in Thailand. Methods: In this randomized controlled trial, hemodialysis patients were assigned to receive treatment with either Theranova^® 500 or Elisio^® 21HX dialyzers. Each dialyzer was reprocessed using peracetic acid and reused for up to 15 sessions. Dialyzer performance was assessed by the reduction ratios (RRs) of solutes, including β2-microglobulin (β2-MG), kappa and lambda free light chains (κ-FLC, λ-FLC), and interleukin-6 (IL-6), at baseline and the 2nd, 5th, 10th, and 15th sessions. Results: Forty-eight patients were enrolled (mean age 63.6 ± 13.7 years; 62.5% male) and randomized into 2 groups with comparable baseline characteristics. RRs for β2-MG, κ-FLC, and λ-FLC were similar between the groups and declined modestly over time after dialyzer reused (β2-MG: 78.2% to 72.5% vs. 77.2% to 74.5%, κ-FLC: 64.6% to 51.3% vs. 58.9% to 49.5%, and λ-FLC: 51.2% to 46.4% vs. 49.4% to 39.2% in the Theranova^® 500 and Elisio^® 21HX groups, respectively). Theranova^® 500 demonstrated significantly higher IL-6 clearance in the 2nd (29.9% vs. 16.0%; p = 0.018) and 5th (23.8% vs. 7.7%, p = 0.031) sessions. It also showed a non-significant trend toward lower dialyzer survival (HR 3.98; p = 0.085) and higher, though clinically acceptable, albumin loss (mean difference 0.56 g/session; p < 0.001), which decreased with reuse. Conclusions: Both MCO dialyzers demonstrated comparable overall performance during reuse. Theranova^® 500 provided better IL-6 clearance with manageable albumin loss. Implementation of high-quality dialyzer reuse protocols may optimize clinical efficacy and patient outcomes while balancing cost, accessibility, and environmental considerations. Full article

Background/Objectives: Inflammation is a hallmark of diabetes, with interleukin-6 (IL-6) emerging as a key mediator linking immune activation with metabolic regulation. Although IL-6 has been studied in both type 1 (T1D) and type 2 diabetes (T2D), its relationship with glycemic control across diabetes subtypes remains unexplored. Methods: We conducted a cross-sectional pilot study including 82 participants divided into the following subgroups: healthy controls (n = 14), individuals with T1D [n = 11 with glycated hemoglobin (HbA1c) < 7%; n = 11 with HbA1c ≥ 7%] and T2D (n = 21 with HbA1c < 7%; n = 25 with HbA1c ≥ 7%). Demographic, anthropometric, and laboratory parameters were collected. Group comparisons were performed, adjusted for age and body mass index (BMI) to account for significant demographic differences between groups. Correlations between IL-6, high-sensitivity C-reactive protein (hs-CRP), ferritin, and presepsin were evaluated using Spearman’s rank correlation. Results: IL-6 levels were approximately four-fold higher in T1D individuals with HbA1c ≥ 7% compared with controls [fold-change 4.06 (95% CI: 1.36–12.1), p = 0.013], with optimally managed T1D showing a non-significant trend (p = 0.079). No significant differences were observed in T2D groups. Advancing age demonstrated a borderline association with IL-6 (p = 0.068), whereas BMI was not significantly related. IL-6 correlated positively with hs-CRP (ρ = 0.463, p < 0.001), but not with ferritin or presepsin. Conclusions: IL-6 concentrations were significantly elevated in individuals with suboptimally managed T1D compared with controls, independent of age and BMI, suggesting that poor metabolic control amplifies systemic inflammation in autoimmune diabetes. These findings support IL-6 as a biomarker of inflammatory burden in T1D and provide a rationale for larger, longitudinal studies to determine its clinical utility. Full article