Search Results (533)

Retinol, a bioactive small molecule of the vitamin A family, contributes epidermal and dermal tissue repair through retinoic acid receptor γ (RARγ)/retinoid X receptor (RXR) receptor-mediated transcriptional regulation of keratinocyte differentiation, extracellular matrix (ECM) remodeling, and barrier restoration. However, the relationship between applied concentration, tissue-level regenerative outcomes, and tolerability remains incompletely characterized. This prospective, randomized, single-blind study compared biophysical effects and tolerance of two retinol concentrations in EU-compliant facial creams, high-performance liquid chromatography (HPLC)-verified as 0.104% and 0.247% (w/w). Thirty-eight women aged 40–61 years (Fitzpatrick phototypes II–III) participated across three independent sub-studies: 28 were randomized to either concentration for 12 weeks; 5 underwent split-face ultrasound imaging (0.247% versus retinol-free control) for 8 weeks; and 5 participated in a tape stripping sub-study quantifying stratum corneum interleukin-1 alpha (IL-1α) and interleukin-1 receptor antagonist (IL-1ra) by ELISA before and after 6 weeks of 0.247% retinol treatment. Main cohort assessments included transepidermal water loss (TEWL), hydration, melanin, erythema, pH, sebum, biomechanical parameters, and wrinkle grading. Both concentrations significantly improved barrier parameters—hydration, TEWL, brightness, pH, and sebum—with no inter-group differences. In the ultrasound sub-group, 0.247% retinol increased epidermal thickness (+12.4 μm), epidermal density (+3.84%), and dermal density (+1.81%) versus control, consistent with ECM reorganization and epidermal stratification. Biomechanical parameters showed no significant changes, consistent with retinol’s remodeling timeline. Consumer assessment indicated comparable efficacy; 0.247% demonstrated superior smoothing but higher erythema incidence. In the tape stripping sub-study, IL-1α decreased in all participants (median: 25.1 → 13.2 picograms per tape [pg/Tape]; 5/5 concordant), while IL-1ra increased in 4/5 participants (median: 352.8 → 1403.1 picograms per three sequential tapes [pg/3sT]), indicating a directionally consistent shift in the IL-1α/IL-1ra balance; these results are exploratory and require replication in larger cohorts. These findings collectively support clinically meaningful barrier restoration and structural remodeling within current EU safety limits (Commission Regulation EU 2024/996), with 0.104% offering a favorable efficacy-to-tolerability profile for initial therapy. Full article

GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Objectives: The purpose of the study is to study the safety, pharmacokinetics, and immunogenicity of the ustekinumab biosimilar GNR-068 and the reference drug Stelara^® after a single subcutaneous administration in healthy male volunteers. Methods: This was an open-label, randomized, comparative, parallel-group clinical trial of the safety, pharmacokinetics (PK), and immunogenicity of GNR-068 (JSC GENERIUM) and Stelara^® (Manufacturer: Silag AG, Switzerland; RU Holder: JOHNSON & JOHNSON) after a single subcutaneous administration of 45 mg in healthy volunteers. During the trial, 146 volunteers were screened, and 122 were randomized. Results: The results showed that PK similarity was established based on 90% confidence intervals (CIs) for the ratios of geometric means of the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUC_0–∞) and maximum observed serum concentration (Cmax) being contained within the pre-specified margin of 80.00–125.00%. The incidence of total ADA was lower in the GNR-068 group compared with the reference product group. Adverse events were similar between treatment groups and consistent with the safety profile of the ustekinumab RP. Conclusions: These results indicate that GNR-068 and the ustekinumab RP share similar PK and safety profiles. Full article

This study investigated the effects of noni fruit flavonoids (NFF) on antioxidant status and anti-inflammatory responses in cashmere goats and explored the underlying mechanisms based on liver transcriptomics and metabolomics. Sixteen male Albas cashmere goats were randomly assigned to two groups: a control (CON) group and a group supplemented with 0.1% NFF. The adaptation and trial periods were 2 and 12 weeks, respectively. The results showed that NFF significantly enhanced antioxidant capacity, with mean increases of 32.9%, 20.7%, and 35.5% for total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activities, respectively, across serum, liver, spleen, and thymus (p < 0.05). NFF also modulated the inflammatory profile, with a mean increase of 18.0% for interleukin (IL)-10 and mean reductions of 18.6%, 19.4%, and 16.7% for IL-1β, IL-2, and tumor necrosis factor (TNF)-α, respectively, across the serum, liver, and thymus (p < 0.05). Integrative transcriptomic and metabolomic analyses suggested that the AMPK signaling pathway, glutathione metabolism, and TGF-β signaling pathway may be critically involved in mediating these effects. GPX3, GPX8, GCLM, NFKB1, and IL1B were identified as key candidate genes, while adenosine-5′-monophosphate (AMP), cysteinylglycine, and pyroglutamic acid were key differential metabolites. Dietary supplementation with 0.1% NFF enhanced the antioxidant levels and anti-inflammatory response in cashmere goats. Full article

This study evaluated the impact of fermented palm kernel meal (FPKM) on the lactation performance, blood biochemical indices, rumen microbiota, and metabolic functions of Holstein dairy cows, aiming to enhance the nutritional value of palm kernel meal (PKM) through solid-state fermentation. A 3 × 3 Latin square design was used, involving 12 multiparous Holstein cows (parity = 3; body weight = 625 ± 25.8 kg; days in milk = 103 ± 19.6 day(s); milk yield = 32.6 ± 1.58 kg/d) over three 28-day periods. Cows were randomly assigned to three isocaloric and isonitrogenous diets: a basal diet with wheat bran (WB group), a diet with wheat bran replaced by PKM (PKM group), and a diet with wheat bran replaced by FPKM (FPKM group). Solid-state fermentation improved PKM’s nutritional profile by reducing fiber and β-mannan content while increasing protein availability and ruminal degradability. Compared to the WB group, the PKM group showed lower dry matter intake, milk yield, and nutrient digestibility. In contrast, the FPKM group had higher DMI and milk yield than the PKM group, improved nutrient digestibility, and the highest energy-corrected milk yield due to increased milk protein and lactose production. The FPKM group also had higher concentrations of total volatile fatty acids, propionate, acetate, and microbial protein synthesis than the PKM group. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-8) were elevated in the PKM group but were reduced to levels similar to the WB group in the FPKM group. Plasma immunoglobulin G levels were higher in both the FPKM and WB groups compared to the PKM group. The FPKM group also showed increased relative abundances of Prevotella, Fibrobacterota, and Verrucomicrobiota, while Bacillota and Ruminococcus were reduced compared to the WB group. Metabolomic profiling revealed that FPKM upregulated energy metabolism and inflammation-related pathways, increasing metabolites such as riboflavin and adenine and decreasing succinic acid and guanine compared to the PKM group. In conclusion, FPKM improved the feeding value of PKM-based material and showed more favorable responses than PKM, with generally comparable responses to WB, supporting its potential as an alternative feed ingredient for lactating dairy cows. Full article

Background: This study examined associations between C-reactive protein (CRP), interleukin-6 (IL-6), ordinal procalcitonin (PCT) categories, and delirium severity in critically ill adults. Secondary exploratory analyses evaluated whether baseline CRP and IL-6 discriminated subsequent incident delirium and remained associated with this outcome after adjustment. Methods: This prospective observational cohort included 267 adults treated in a general intensive care unit. Delirium severity was assessed using CAM-ICU-7 at 12 h after admission and on days 2, 4, 7, and 14. CRP and IL-6 were analyzed as continuous variables, whereas PCT was analyzed as a three-level ordinal variable across all five assessment times. Associations with delirium severity and intensive care unit length of stay were evaluated using Spearman rank correlations. Among patients without delirium at 12 h, bootstrap receiver operating characteristic analysis and Firth-penalized logistic regression adjusted for age and sex were performed as secondary exploratory analyses. PCT was not included in these prospective analyses because only ordinal PCT categories were available. Results: Delirium was recorded at least once in 38 of 267 patients (14.2%). Thirteen patients had delirium at 12 h, and 25 additional patients subsequently developed incident delirium. Concurrent correlations with CAM-ICU-7 severity ranged from 0.271 to 0.898 for CRP and from 0.312 to 0.735 for IL-6. Concurrent correlations for ordinal PCT categories were 0.304, 0.666, 0.711, 0.720, and 0.329 at the five respective assessment times. All concurrent associations were positive and statistically significant at p < 0.001. PCT categories also showed weak positive correlations with intensive care unit length of stay, with coefficients ranging from 0.151 to 0.281. Among 254 patients without delirium at 12 h, baseline CRP showed an AUC of 0.969 (95% bootstrap CI, 0.923 to 0.997), compared with an AUC of 0.653 (95% bootstrap CI, 0.569 to 0.750) for IL-6. Both baseline CRP concentrations and incident delirium were concentrated at floor values in most patients, and this discrimination should be read accordingly as a largely binary separation between floored and elevated CRP rather than a graded biomarker-severity gradient. In the joint Firth model, CRP remained associated with incident delirium, with an adjusted odds ratio of 10.75 per 5 mg/L increase, 95% confidence interval 4.50 to 33.18, p < 0.001. IL-6 was not associated with incident delirium after adjustment for CRP, age, and sex, with an adjusted odds ratio of 0.81 per 5 pg/mL increase, 95% confidence interval 0.42 to 2.04, p = 0.510. Conclusions: CRP, IL-6, and ordinal PCT categories were positively associated with concurrent delirium severity, although no consistent biomarker hierarchy was observed across assessment times. In secondary exploratory analyses, baseline CRP showed high apparent within-sample discrimination for subsequent incident delirium and remained associated with the outcome after adjustment for IL-6, age, and sex. However, the cutoff, discrimination, and effect estimates were derived from a single-center cohort with only 25 incident events. Model calibration, optimism-corrected performance, net clinical benefit, and clinical utility were not evaluated. These findings should not be interpreted as establishing a diagnostic test or clinical prediction tool and require validation in independent external cohorts before any clinical application. Full article

Background: Green tea (Camellia sinensis) is widely consumed around the world, particularly in East Asia, and has traditionally been used to support cardiovascular and metabolic health. Rich in catechins—most notably epigallocatechin-3-gallate (EGCG)—green tea is recognized for its potential immunomodulatory and anti-inflammatory effects. However, evidence from human studies remains inconsistent, and the distinction between functional immune outcomes and systemic inflammatory markers has not been systematically evaluated. Methods: We conducted a systematic review in accordance with PRISMA guidelines, searching PubMed, Google Scholar, Cochrane Library, and EBSCO from inception to the most recent date. Eligible studies included human investigations evaluating green tea or catechin intake and reporting either immune response outcomes (e.g., natural killer cell activity, T cell responses) or systemic inflammatory markers (e.g., C-reactive protein, cytokines). Randomized controlled trials (RCTs), non-randomized interventional studies, and observational analyses were included. Data were synthesized narratively due to heterogeneity. Results: Nineteen studies (≈6800 participants) were included, comprising 12 RCTs, three non-randomized interventions, and five observational studies. Eight studies assessed immune responses and consistently demonstrated enhanced immune activity, including increased natural killer cell function and augmented γδ T cell responses. Eleven studies evaluated inflammatory markers and showed heterogeneous results: several trials reported reductions in C-reactive protein and related biomarkers, particularly in high-risk populations, whereas others found no significant changes in cytokines such as interleukin-6 or tumor necrosis factor-α. Observational studies generally reported inverse associations between tea consumption and inflammation. Green tea was well tolerated across studies. Conclusions: Green tea consumption appears to enhance functional immune responses while exerting modest, context-dependent anti-inflammatory effects. These findings support a dual immunomodulatory role and highlight the importance of distinguishing between immune function and systemic inflammation in nutritional research. Full article

Small mammals in temperate areas frequently face fluctuations in food resources, and food shortage is a key factor affecting their immune function. In order to understand whether immune function and gut microbiota change under food shortage, adult male Brandt’s voles (Lasiopodomys brandtii) were used and divided into Fed (Fed, n = 8), 80% food restriction (80% FR, n = 10) and 60% food restriction (60% FR, n = 9) groups. The experimental course lasted for 35 days. Food restriction reduced body mass (p < 0.001) but did not affect total fat mass (p = 0.532) or blood glucose levels (p = 0.777) compared with the Fed voles. Immunological parameters—including wet masses of thymus and spleen, phytohemagglutinin (PHA) responses at 6 h, 12 h, 24 h, and 48 h post PHA injection, interleukin-4 (IL-4) levels (p = 0.700), the counts of white blood cells (p = 0.864), lymphocytes (p = 0.692), and neutrophils (p = 0.729)—were not influenced by food restriction, indicating that voles could maintain stable immune function under food shortage. Similarly, leptin (p = 0.219) and corticosterone (CORT) (p = 0.282) levels were also not impacted by food restriction, and no correlation existed between these two hormones and the above immunological indices. However, interferon-γ (IFN-γ) (p < 0.001) levels in the 80% FR group were the highest among the three groups. Food restriction had no effect on alpha (α)-diversity of the gut microbiota, indicating that food restriction does not affect their diversity or richness. Food restriction did not affect relative abundance at the phylum or genus levels, nor at most family levels, but reduced Erysipelotrichaceae at the family level. In summary, Brandt’s voles could maintain stable energy status, leptin and corticosterone levels, and the diversity and richness of the gut microbiota under food restriction, which may help us to understand this species’ ability to survive well in times of food shortage. Full article

Background: Evidence regarding the impacts of magnesium (Mg) supplementation on cardiometabolic risk factors (CMRFs) remains inconsistent. Objectives: This systematic review and dose–response meta-analysis evaluated effects of Mg supplementation on anthropometric indices, liver and kidney function, lipid and glycemic profiles, blood pressure, and inflammatory biomarkers. Methods: A systematic search of electronic databases up to May 2026 identified 78 eligible randomized controlled trials. Results: Mg supplementation significantly reduced body weight (weighted mean difference [WMD]: −0.70 kg; 95% confidence interval [CI]: −1.30, −0.09), diastolic blood pressure (WMD: −1.58 mmHg; 95% CI: −2.50, −0.65), homeostasis model assessment of insulin resistance (WMD: −0.48; 95% CI: −0.79, −0.18), low-density lipoprotein cholesterol (WMD: −3.21 mg/dL; 95% CI: −5.27, −1.15), fasting blood glucose (WMD: −3.60 mg/dL; 95% CI: −6.13, −1.06), systolic blood pressure (WMD: −2.50 mmHg; 95% CI: −4.08, −0.91), glycated hemoglobin (WMD: −0.15%; 95% CI: −0.26, −0.03), triglycerides (WMD: −9.24 mg/dL; 95% CI: −16.87, −1.61), and interleukin-6 levels (WMD: −1.10 pg/mL; 95% CI: −1.93, −0.27) compared with controls. High-density lipoprotein cholesterol concentrations significantly increased (WMD: 1.45 mg/dL; 95% CI: 0.37, 2.54). No significant effects were identified on hip circumference, alanine aminotransferase, waist circumference, tumor necrosis factor-α, creatinine, C-reactive protein, body mass index, total cholesterol, fasting insulin, body fat percentage, and aspartate aminotransferase. Most RCTs (79.5%) administered Mg doses ≥ 300 mg/day, and 66.7% had intervention durations ≥ 12 weeks; however, evidence from higher-dose (≥500 mg/day) and longer-term (≥25 weeks) interventions remained limited. Conclusions: Mg supplementation was associated with significant improvements in several CMRFs, including body weight, lipid and glycemic profiles, blood pressure, and interleukin-6 levels. However, these effects were generally modest, and their clinical relevance remains uncertain given the variable certainty of evidence across outcomes. Full article

Neuroimmune dysregulation and altered pro- and anti-inflammatory signaling have been implicated in selected phenotypes of depressive and anxiety disorders. Interleukin-37 (IL-37), a member of the IL-1 family, exerts anti-inflammatory effects through extracellular signaling involving IL-18Rα and IL-1R8 and intracellular interactions with SMAD3. This scoping review mapped direct and indirect evidence concerning the relevance of IL-37 to depressive and anxiety disorders. PubMed/MEDLINE was searched through 12 July 2026, supplemented by backward citation searching and reference-list checking; evidence was charted by study type, population or model, IL-37 assessment, principal findings, and level of psychiatric relevance. Thirty-two IL-37-related sources were included. Direct psychiatric evidence comprised one small cross-sectional human study and two rodent stress-model studies, in which IL-37 was assessed as one component of broader inflammatory profiles rather than as a prespecified primary biomarker or intervention target. The remaining evidence was derived from non-psychiatric inflammatory conditions, central nervous system disease models, or mechanistic studies. These findings provide hypothesis-generating biological context but do not establish psychiatric specificity, causality, biomarker validity, or therapeutic efficacy. IL-37 should therefore be considered an exploratory research variable requiring validation in well-characterized longitudinal psychiatric cohorts using standardized assays and integrated immune profiling. Full article

Background and Objectives: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is characterized by type 2 inflammation, marked eosinophil infiltration, and enhanced epithelial–mesenchymal transition (EMT). Although interleukin-5 (IL-5) is central to eosinophil differentiation and activation, its role in EMT in human nasal epithelial cells (HNECs) remains unclear. This study aimed to elucidate the contribution of IL-5Rα/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signaling in eosinophils in EMT in ECRSwNP. Materials and Methods: Nasal mucosal tissues from control and ECRSwNP or non-ECRSwNP group patients (n = 12 each) were analyzed for type 2 cytokine, EMT marker, and IL-5Rα/JAK2/STAT5 axis component levels using Western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. HL-60 cells were differentiated into eosinophil-like cells using butyric acid and stimulated with IL-5, and HNECs were co-cultured with undifferentiated, differentiated, or IL-5-activated differentiated HL-60 cells. EMT induction and migration were assessed using immunofluorescence, wound-healing assays, and Western blotting. IL-5RA, JAK2, or STAT5 was silenced using small interfering RNA to determine pathway dependency. Results: ECRSwNP tissues showed elevated type 2 cytokine and EMT marker expression and enhanced IL-5Rα/JAK2/STAT5 pathway activation. Co-culture with IL-5-activated differentiated HL-60 cells induced EMT in HNECs, evidenced by decreased E-cadherin and zonula occludens-1, increased N-cadherin and vimentin levels, and enhanced migration. Moreover, silencing IL-5RA, JAK2, or STAT5 significantly attenuated these effects. Conclusions: IL-5-activated IL-5Rα/JAK2/STAT5 signaling in eosinophils may contribute to EMT in HNECs. Thus, this pathway could be a potential therapeutic target for tissue remodeling and polyp formation in type 2 chronic rhinosinusitis. Full article

Background/Objectives: Intensified training in adolescent soccer players increases oxidative stress, muscle damage, inflammation, and immune suppression, but direct comparisons of nutritional countermeasures are lacking. This randomised, double-blind, placebo-controlled trial compared the effects of 14-day coenzyme Q10 (CoQ10) versus taurine supplementation on haematological, oxidative, muscle damage, inflammatory, hormonal, and immune biomarkers in under-19 soccer players undergoing three repeated 90 min Soccer Match Simulation (SMS) sessions. Methods: Twenty-four male players (age 17.9 ± 0.7 years) received placebo (n = 8), CoQ10 (300 mg/day, n = 8), or taurine (4 g/day plus 4 g pre-session, n = 8). Blood was collected at baseline (T0), post-first session (T1), post-third session (T2), and 24 h post-third session (T3). Biomarkers included creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capacity (TAC), interleukins (IL-6, IL-10, TNF-α), cortisol, testosterone, CD4/CD8 ratio, immunoglobulins (IgA, IgG), and plasma volume (Dill–Costill). Data were analysed by two-way repeated-measures ANOVA. Results: CoQ10 was superior in reducing MDA (T2: 0.83 ± 0.02 vs. 1.24 ± 0.03 μmol/L, p < 0.001), LDH (434 ± 9 vs. 684 ± 12 U/L, p < 0.001), and cortisol (20.2 ± 0.6 vs. 30.4 ± 0.8 μg/dL, p < 0.001), and preserved the testosterone:cortisol ratio (24.5 ± 1.1 vs. 13.6 ± 1.0 × 10⁻³, p < 0.001). CoQ10 was more effective than taurine in lowering IL-6 at T2 (3.5 ± 0.2 vs. 3.9 ± 0.2 pg/mL, p = 0.03), whereas taurine was more effective in increasing IL-10 (7.5 ± 0.2 vs. 5.7 ± 0.2 pg/mL, p = 0.005). Both supplements preserved CD4 counts (CoQ10: 790 ± 13, taurine: 795 ± 14 vs. placebo: 680 ± 15 cells/μL, p < 0.01) and the CD4/CD8 ratio, as well as IgA and IgG levels, with no between-supplement differences for immune outcomes (p > 0.05). No adverse events occurred. Conclusions: For adolescent soccer players undergoing intensified training, CoQ10 may be preferred when the goal is reducing oxidative stress, muscle damage, and catabolic load; taurine may be preferred for targeted anti-inflammatory support (IL-10 elevation). Either supplement effectively attenuated changes in circulating immune biomarkers. These preliminary findings provide evidence-based guidance for targeted sports nutrition, pending confirmation in larger trials. Full article

Vitamin D is believed to exert an immunomodulatory effect in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and may influence the intensity of inflammatory processes. Therefore, this study aimed to assess serum vitamin D levels in relation to selected cytokines in patients with CRSwNP and without nasal polyps (CRSsNP). This prospective study included patients with clinically and radiologically confirmed diseases. In total, 39 patients were included in three phenotypic groups: CRSwNP (n = 17), CRSsNP (n = 10), and controls (n = 12). Serum concentrations of vitamin D (25(OH)D3), interleukins 4, 5, 17A, interferon-γ (IFN-γ), and immunoglobulin E were assessed preoperatively. The extent of subjective and objective mucosal disease was evaluated using endoscopic and radiological staging, based on the Lund–Kennedy and Lund–Mackay scoring systems in accordance with the Sino-Nasal Outcome Test-22 (SNOT-22), respectively. Patients with CRSwNP demonstrated higher serum IL-4 and IL-5 concentrations, consistent with a Th2-skewed inflammatory profile, whereas patients with CRSsNP showed higher IL-17A and IFN-γ levels, suggesting a mixed Th17/Th1 inflammatory pattern. IL-5 was positively associated with radiological disease severity. Serum vitamin D levels tended to be inversely associated with IL-5 concentration and disease severity; however, these associations did not reach statistical significance.: The findings of this study support differences in inflammatory profiles between CRSwNP and CRSsNP and confirm an association between IL-5 and radiological disease severity. Although lower vitamin D levels showed a trend toward greater inflammatory activity and disease severity, no statistically significant associations were demonstrated in this cohort. Further studies with larger populations are warranted to clarify the role of vitamin D in CRS endotypes. Full article

Diabetic wounds are a common complication of diabetes mellitus (DM), with healing often impaired by ferroptosis and persistent inflammation. This study investigated the effects of Ginkgo biloba flower extract (GBF) on diabetic wound healing by focusing on inflammation and ferroptosis. Chemical composition analysis identified 123 compounds in GBF containing 73 active ingredients of flavonoids and 12 terpenoids. In vivo, GBF treatment significantly accelerated the wound healing process in diabetic rats, and GBF promoted epithelial regeneration and collagen deposition by increasing the expression of CD31 and VEGF. It also enhanced the formation of new blood vessels. Mechanistically, GBF could inhibit the inflammatory response by reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and inhibit the oxidative stress-induced ferroptosis by increasing the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4). Proteomics analysis further confirmed its regulatory effects on inflammation and iron metabolism pathways. In vitro, GBF promoted the survival and migration of rat skin fibroblasts (RS1) while reducing the levels of reactive oxygen species (ROS) and Fe²⁺ in erastin-induced ferroptosis cells. In conclusion, GBF promotes diabetic wound healing by inhibiting ferroptosis and inflammation. Full article

High-glucose exposure impairs intestinal metabolic homeostasis and barrier integrity in fish, but the transcriptional responses associated with high-glucose adaptation in fish intestinal epithelial cells remain incompletely understood. This study investigated whether exogenous 5-methylcytosine (5MC) alleviates high-glucose-induced metabolic and epithelial stress in grass carp (Ctenopharyngodon Idella) intestinal epithelial cells and whether these responses are associated with changes in DNA methyltransferase 3 beta (dnmt3b) expression and Caudal type homeobox 1b (cdx1b)/Sodium-glucose cotransporter 1 (sglt1)-related transcriptional responses. As exploratory in silico information, molecular docking predicted candidate complex conformations of DNMT3B with CDX1B and SGLT1, with binding energies of −37.2 and −25.9 kcal/mol, respectively. Functionally, dnmt3b knockdown significantly reduced dnmt3b, Interleukin 6 (il6), and Nuclear factor kappa B (nfκb) expression, while increasing cdx1b, sglt1, Solute carrier family 2 member 3a (slc2a3a), 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4a (pfkfb4a), and Amine oxidase copper containing 1 (aoc1) expression (p < 0.05). CDX2/CDX1B-like immunoreactive protein and SGLT1 protein levels were also increased after dnmt3b knockdown (p < 0.05). Under high-glucose stress, exogenous 5MC exerted concentration-dependent effects. Specifically, 6 mM 5MC significantly reduced residual extracellular glucose, lactate dehydrogenase and diamine oxidase activities, and malondialdehyde content, while increasing glutathione content, cell viability, and cell migration (p < 0.05). These effects remained detectable after replacement with high-glucose medium for an additional 12 h. By contrast, 24 mM 5MC markedly increased lactate dehydrogenase activity and reduced cell viability, suggesting potential cytotoxicity (p < 0.05). S-adenosylmethionine (SAM) levels were significantly lower in the NC and 6 mM groups than in the HG, 12 mM, and 24 mM groups, suggesting changes in SAM-related one-carbon metabolic status rather than direct evidence of altered DNA methylation (p < 0.05). Exogenous 5MC, particularly at 6 mM, alleviated high-glucose-induced metabolic and epithelial stress in grass carp intestinal epithelial cells. These effects were accompanied by changes in several glucose metabolism- and inflammation-related genes. However, the cellular uptake, metabolic fate, DNA incorporation, methylation consequences, and causal roles of these gene-expression changes remain to be further verified. Full article

Background/Objectives: Obesity-related insulin resistance is accompanied by chronic low-grade inflammation, but the extent to which weight loss modifies circulating cytokines in a sex-specific manner remains insufficiently understood. The aim of this study was to assess sex-specific cytokine responses and metabolic adaptation in adults with obesity and insulin resistance following a six-month weight-reduction program (WRP). Methods: Thirty-six participants (24 women and 12 men) with a value of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2 underwent an individualized low-calorie diet combined with moderate physical activity and health education. Anthropometric, body composition, biochemical, oxidative stress, and cytokine parameters were evaluated before and after the intervention. Results: Both women and men showed significant reductions in body mass, Body Mass Index (BMI), waist circumference, visceral fat area (VFA), body fat mass (BFM), fasting glucose, HOMA-IR, modified Atherogenic Index of Plasma (new-AIP), malondialdehyde (MDA), and Oxidative Stress Index (OSI). Women additionally showed significant decreases in fat-free mass (FFM), skeletal-muscle mass (SMM), total body water (TBW), glycated hemoglobin A_1c (HbA1c), and triacylglycerols, whereas cholesterol in high-density lipoproteins (HDL-C) increased significantly in men. Cytokine changes were selective rather than uniform. Interleukin-1 receptor antagonist (IL-1ra), Interleukin 6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α) decreased in both women and men. In sex-stratified analyses, IL-1β decreased significantly only in women, whereas IL-7 decreased significantly only in men. ClinicalTrials.gov Registration: [NCT07645105] (retrospectively registered on [11 June 2026]). Conclusions: A 6-month lifestyle-based weight-reduction program in adults with overweight or obesity and insulin resistance was associated with metabolic improvement, reduced oxidative stress, and partial attenuation of obesity-related low-grade inflammation. The observed cytokine and metabolic changes suggest sex-related patterns of immunometabolic adaptation to weight reduction. However, these findings should be interpreted cautiously because of the relatively small sex-stratified subgroups and the number of cytokine endpoints analyzed, and they require confirmation in larger, sex-balanced studies. Full article