Search Results (87)

Introduction: Immune dysfunction plays a significant role in Metabolic syndrome, contributing to both insulin resistance and chronic low-grade inflammation. This immune dysfunction is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and (MCP-1), whereas others such as interferon gamma (IFN-γ), IL-17A, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in Post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders following infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups—group 1 (individuals with newly diagnosed carbohydrate disorders after proven COVID-19 or Post-COVID group; n = 35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n = 33). They were further divided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as well as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar metabolic parameters including BMI and unadjusted lipid and uric acid levels (p > 0.05). After adjustment for age, sex, and BMI revealed significant differences, Post-COVID status independently predicted higher fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, triglycerides, uric acid, and insulin-resistance indices, indicating substantially impaired glycemic and metabolic control beyond traditional risk factors. Furthermore, the Post-COVID cohort demonstrated marked cytokine dysregulation, with significantly elevated levels of TNF-α, IFN-γ, IL-17A, and IL-10 after adjustment. Conclusions: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. Together, these findings indicate that Post-COVID metabolic dysfunction is characterized by inflammation-driven dyslipidemia, heightened oxidative stress, and persistent immune activation, distinguishing it from classical Metabolic syndrome. Full article

Background/Objectives: Identifying early and dynamic predictors of mortality in hospitalized COVID-19 patients is essential for improving prognosis and guiding therapy. Our aim is to evaluate clinical and laboratory predictors of in-hospital mortality among moderate and severe COVID-19 patients using multivariate Cox proportional hazards regression analysis. Methods: This retrospective cohort study included 168 adults (aged 18–64 years) with RT-PCR–confirmed COVID-19. Basic demographic data (age and sex) and laboratory parameters were collected on Day 1 and Day 7 of hospitalization. Stepwise Cox regression models were constructed for all patients and for the severe-disease subgroup. Results: Of 168 patients, 104 (61.9%) had severe and 64 (38.1%) moderate disease; 33 (19.6%) died, all with severe COVID-19. On Day 1, independent predictors of mortality in both the total cohort and the severe subgroup were older age (HR = 1.095, p = 0.003), male sex (HR = 0.324, p = 0.013), lower lymphocyte percentage (HR = 0.869, p = 0.041), and elevated procalcitonin (PCT) (HR = 10.972, p < 0.001). On Day 7, predictive significance shifted: in severe cases, mortality was independently associated with sex, PCT, eosinophil percentage, ferritin, vitamin D, and gamma-glutamyl transferase (GGT) (χ² = 69.47, p < 0.0001). In the total cohort, age, PCT, interleukin-6 (IL-6), and GGT were independent predictors (χ² = 86.24, p < 0.0001). Conclusions: Early mortality risk in COVID-19 was driven by demographic factors and inflammation markers, whereas by Day 7 biochemical indicators of systemic inflammation, oxidative stress and hepatic dysfunction became stronger determinants of outcome. Full article

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves not only cutaneous inflammation but also intestinal dysbiosis and oxidative stress (OxS). Monoclonal antibodies targeting interleukin (IL)-17 and IL-23 have demonstrated significant immunomodulatory effects; however, their impact on systemic parameters requires further investigation. We conducted a study on 33 patients with plaque psoriasis treated with anti-IL-17 or anti-IL-23 monoclonal antibodies. Dermatological parameters (Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI)), biomarkers of intestinal dysbiosis (trimethylamine-N-oxide (TMAO)) and OxS (reactive oxygen metabolites (d-ROMs) and oxidized LDL (oxLDL)) were evaluated. Anthropometric, metabolic, and adipose-derived hormonal parameters (adipokines) were also monitored. After 16 weeks of therapy, significant improvements were observed in PASI and DLQI scores (p < 0.001). TMAO levels were significantly reduced (p = 0.02), as were d-ROMs and oxLDL (p < 0.001). No significant changes were found in weight, body mass index, lipid profile, or adipokine levels (visfatin, leptin and adiponectin). Our data indicate that monoclonal antibody therapy not only improves psoriasis severity but also exerts beneficial effects on systemic biomarkers of dysbiosis and OxS, independent of metabolic or hormonal changes. These findings suggest a systemic mechanism of action, supporting a multifactorial therapeutic effect with potential implications for the prevention of cardiovascular risk. Full article

Post-traumatic stress disorder (PTSD) is associated with long-term disturbances in stress regulation, neuroinflammation, and oxidative stress and reduced psychological coping capacity. The aim of the study was to assess the relationship between selected neurobiological biomarkers (Insulin-like Growth Factor 1—IGF-1; Caspase-9—CASP-9; Neuronal Nitric Oxide Synthase—nNOS; and Interleukin-10—IL-10) and coping styles evaluated using the Brief Coping Orientation to Problems Experienced (Brief-COPE) questionnaire in men with trauma experience. Particular emphasis was placed on analyzing the effect of PTSD chronicity (≤5 years vs. >5 years) on these relationships. The study included 92 adult men with a history of life-threatening situations. Participants were divided into three groups: PTSD within the past ≤5 years (n = 33), PTSD within the past >5 years (n = 31), and a No PTSD group (n = 28). Biomarkers were measured in blood serum. Coping strategies were assessed using the Brief-COPE questionnaire, which includes four subscales: task-oriented, emotion-oriented, avoidant, and general coping. Due to the lack of normal distribution, the Kruskal–Wallis test and Dunn’s post hoc test were used. Correlations between biomarkers and Brief-COPE subscales were calculated using Spearman’s Rank Correlation Coefficient (Rho). Significant differences between groups were found in all four biomarkers (p < 0.001). IGF-1 and IL-10 reached the highest values in the No PTSD group and the lowest in the PTSD ≤ 5 years group, indicating neuroprotective and anti-inflammatory deficits in PTSD. Conversely, CASP-9 and nNOS levels (markers of apoptosis and oxidative stress) were highest in PTSD ≤ 5 years, with partial normalization in the PTSD > 5 years group. In terms of coping strategies, the No PTSD group displayed a highly adaptive profile (task-oriented: 30/32; emotion-oriented: 43/48; and avoidant: 12/32). Individuals with PTSD ≤ 5 years presented a maladaptive pattern (task-oriented: 13/32; avoidant: 26/32; and emotion-oriented: 27/48), while in PTSD > 5 years, a further decline in emotion-oriented (21/48) and general coping (59/112) was observed, suggesting progressive depletion of psychological resources. The strongest correlations between biomarkers and coping strategies occurred in PTSD groups. Low IGF-1 levels in PTSD ≤ 5 years correlated negatively with emotion-oriented coping (Rho = −0.39) and general coping (Rho = −0.35). High CASP-9 levels were associated with reduced task-oriented coping in PTSD > 5 years (Rho = −0.29). Similar trends were observed for nNOS and IL-10, indicating a disturbance in neurobiological balance that favors persistence of PTSD symptoms. PTSD, both in its acute and chronic phases, is associated with an abnormal profile of neuroprotective, apoptotic, and inflammatory biomarkers, which correlates with impaired adaptive coping capacity. Although partial normalization of biological parameters is observed in chronic PTSD, deficits in emotion-oriented and task-oriented coping persist. The Brief-COPE questionnaire, combined with biomarker analysis, may serve as a useful clinical tool for assessing psychophysiological balance and designing early interventions. These results highlight the potential of IGF-1, CASP-9, nNOS, and IL-10 as biomarkers of stress adaptation and therapeutic targets in PTSD. 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

Posttraumatic Stress Disorder (PTSD) is characterized by disruptions in central nervous system functioning and existential crises, yet the mechanistic links between neurobiological processes and dimensions of life meaning and identity remain underexplored. The aim of this study was to examine the relationships between stress biomarkers (serotonin, cortisol, noradrenaline, and interleukin-12 [IL-12]) and existential attitudes (measured using the Life Attitude Profile (Revised) [LAP-R]) in mining rescuers, considering PTSD duration and participant age. This cross-sectional study included 92 men aged 18–50 years, divided into three groups: no PTSD (n = 28), PTSD ≤ 5 years (n = 33), and PTSD > 5 years (n = 31). Serum levels of four biomarkers and LAP-R scores across eight domains were evaluated. Statistical analyses employed nonparametric tests, including the Kruskal–Wallis test for overall group differences (with Wilcoxon r effect sizes for pairwise comparisons, Mann–Whitney U tests for post hoc pairwise comparisons, and Spearman’s rank correlations for biomarker–LAP-R associations. Age effects were assessed in two strata: 18–35 years and 36–50 years. Kruskal–Wallis tests revealed significant group differences (p < 0.001) for all biomarkers and most LAP-R domains, with very large effect sizes (r > 0.7) in pairwise comparisons for serotonin (control median: 225.2 ng/mL vs. PTSD ≤ 5y: 109.9 ng/mL, r = 0.86; vs. PTSD > 5y: 148.0 ng/mL, r = 0.86), IL-12 (control: ~8.0 pg/mL vs. PTSD ≤ 5y: 62.4 pg/mL, r = 0.86; vs. PTSD > 5y: ~21.0 pg/mL, r = 0.69), and LAP-R scales such as Life Purpose (control: 54.0 vs. PTSD ≤ 5y: 39.0, r = 0.78; vs. PTSD > 5y: 20.0, r = 0.86) and Coherence (control: 53.0 vs. PTSD ≤ 5y: 34.0, r = 0.85; vs. PTSD > 5y: 23.0, r = 0.86). The PTSD ≤ 5y group exhibited decreased serotonin, cortisol (median: 9.8 µg/dL), and noradrenaline (271.7 pg/mL) with elevated IL-12 (all p < 0.001 vs. control), alongside reduced LAP-R scores. The PTSD > 5y group showed elevated cortisol (median: ~50.0 µg/dL, p < 0.001 vs. control, r = 0.86) and normalized IL-12 but persistent LAP-R deficits. Older participants (36–50 years) in the PTSD ≤ 5y group displayed improved existential attitudes (e.g., Life Purpose: 47.0 vs. 27.5 in 18–35 years, p < 0.001), whereas in PTSD > 5y, age exacerbated biological stress (cortisol: 57.6 µg/dL vs. 36.1 µg/dL, p = 0.003). Spearman correlations revealed stage-specific patterns, such as negative associations between cortisol and Death Acceptance in PTSD > 5y (ρ = −0.49, p = 0.005). PTSD alters biomarker levels and their associations with existential dimensions, with duration and age modulating patient profiles. These findings underscore the necessity for integrated therapies addressing both biological and existential facets of PTSD. Full article

Background/Objectives: After the 2022 mpox outbreak also outside Africa, risk groups including people living with HIV (PLWH) were vaccinated with the Modified Vaccinia Ankara–Bavarian Nordic vaccine (MVA-BN). Previous data on PLWH showed that two vaccinations induced specific T cell responses in 64% of the patients and natural monkeypox virus (MPXV) infection in 100%. The initial T cell response assay took place at a median of approximately 100 days post-vaccination and 300 days post-infection. Methods: This study investigates the durability of T cell immunity in PLWH by retesting patients approximately two years after initial assessment. We were able to retest 27 of 33 vaccinated patients and 7 of 10 patients after MPXV infection. T cells were stimulated with the same orthopoxvirus-derived peptide pools as in the initial study, and interferon (IFN)-γ and interleukin (IL)-2 ELISpot assays were performed. Results: The ELISpot assays showed specific T cell responses in 59% and 86% of twice vaccinated and previously infected patients, respectively. Paired analysis revealed no significant differences between previous and current data (short- and long-term follow-up), with IL-2 ELISpot results showing positive correlations at both time points (r = 0.67, p = 0.0001). Long-term IFN-γ responses after MPXV infection were 4.3 times higher (p < 0.01), and IL-2 responses were 2.9 times higher (p = 0.05) than after vaccination. Conclusions: Our data indicates that T cell responses to Orthopoxviruses remain overall stable for 2–3 years in PLWH, with long-term immunity being stronger after natural MPXV infection than after two vaccinations. Full article

Background/Objectives: Chronic inflammation is a key driver of cancer. Interleukin 33 (IL-33) has emerged as a crucial factor involved in the pathogenesis of cancer-prone chronic inflammation. IL-33 functions as a cytokine and a nuclear protein to initiate chronic inflammation and cancer. However, small molecules capable of suppressing IL-33 expression to block its cytokine and nuclear functions are underexplored. Methods: The impact of tropisetron on IL-33 expression and its role in suppressing pancreatitis and pancreatitis-mediated pancreatic cancer were examined. Results: We demonstrate that tropisetron suppresses IL-33 expression, with high potential to serve as a novel therapeutic strategy for preventing chronic inflammation and its cancer sequela. Through screening 1018 Food and Drug Administration (FDA)-approved drugs, we discovered that tropisetron, a 5-hydroxytryptamine type 3 (5-HT3) antagonist commonly used to prevent and treat nausea and vomiting, effectively blocked IL-33 expression by suppressing IRF3 activation. Tropisetron inhibited pancreatitis and its progression to pancreatic cancer in mice. Conclusions: Tropisetron is an IL-33 inhibitor and can provide a novel therapeutic strategy to prevent and treat chronic pancreatitis and its associated cancer. Full article

Inflammation contributes to myocardial injury in ST-elevation myocardial infarction (STEMI). Interleukin-6 receptor (IL-6R) inhibition has been shown to mitigate myocardial injury and reduce levels of the prothrombotic and inflammatory mediator, neutrophil extracellular traps (NETs). The enzyme peptidylarginine deiminase 4 (PAD4) is central in NET formation. We hypothesized that PAD4 links IL-6R activation and NET formation. Methods: We conducted thrombus aspiration and peripheral blood sampling in 33 STEMI patients. In thrombi and leukocytes, we quantified the mRNA of IL-6, IL-6R, and PAD4. In peripheral blood, the protein levels of IL-6, IL-6R, PAD4, dsDNA, H3Cit, MPO-DNA, and troponin T were quantified. Results: In thrombi and circulating leukocytes, PAD4 mRNA was associated with IL-6R mRNA (thrombi: β = 0.34, 95% CI [0.16–0.53], p = 0.001, circulating leukocytes: β = 0.92, 95% CI [0.07–1.77], p = 0.036). There were no correlations between PAD4 and IL-6 in thrombi and leukocytes. The protein levels of IL-6R were associated with the NET marker H3Cit (r_s = 0.40, p = 0.02). In thrombi, PAD4 mRNA was associated with high levels of troponin T (β = 1.15 95% CI [0.27–2.04], p = 0.013). Conclusion: We demonstrate an association between PAD4, IL-6R, and troponin release in STEMI patients. Our findings indicate a PAD4-mediated connection between IL-6R and NET formation and highlight PAD4 as a potential treatment target for mitigating inflammation and myocardial injury in STEMI. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

Background/Objectives: This study aims to identify genetic variants associated with early-onset inflammatory bowel disease (IBD) and to improve diagnostic and therapeutic approaches. In selected monogenic IBD cases, treatment included colchicine, interleukin-1 inhibitors, and hematopoietic stem cell transplantation. Methods: This study included patients with early-onset IBD, defined as IBD diagnosed before the age of 10, who were under follow-up at the Department of Pediatric Gastroenterology, Hacettepe University, and agreed to participate between December 2018 and April 2021. Whole-exome sequencing (WES) was performed prospectively in patients without a prior diagnosis of monogenic disease, while clinical and laboratory data were reviewed retrospectively. Identified variants were evaluated for pathogenicity using standard bioinformatics tools. Results: A total of 47 patients were enrolled, including 33 boys (70.2%) and 14 girls (29.8%). The median age at symptom onset was 36 months (IQR: 10–72), and the median age at diagnosis was 3.7 years (IQR: 1.5–7.6). Crohn’s disease was diagnosed in 53.2% (n = 25), ulcerative colitis in 38.3% (n = 18), and unclassified IBD in 8.5% (n = 4). Monogenic IBD was identified in 36.2% (n = 17) of patients, including nine with Familial Mediterranean Fever and others with glycogen storage disease type 1b (n = 2), XIAP deficiency, chronic granulomatous disease, DOCK8 deficiency, IL10 receptor alpha defect, LRBA deficiency, and NFKB2 deficiency (n = 1 each). A novel SLC29A3 gene variant (c.480_481delTGinsCA, p.V161I) (transcript ID: ENST00000479577.2) was identified in 76.6% (n = 36) of patients. Conclusions: This study underscores the importance of genetic variants in early-onset IBD, particularly MEFV and the novel NFKB2. The frequent detection of the SLC29A3 variant may suggest its potential involvement in the pathogenesis of the disease. Full article

Background/Objectives: This study piloted a 24-week bodybuilding program combining resistance training (RT) with a dietary bulk-and-cut protocol in middle-aged adult males. Methods: Seven untrained males (33 ± 3.0 years; BMI = 35.0 ± 4.6 kg/m²; body fat = 36 ± 5%) completed a 24-week intervention combining RT with a dietary protocol consisting of 12-week cycles of caloric bulking (0–12 weeks) and cutting (12–24 weeks). The participant retention rate was 64%, while compliance with training was 96.7%, and adherence to dietary cycles was over 93%. To assess the preliminary efficacy of the intervention, venous blood samples and measurements of body composition (BodPod), muscle strength, and VO₂max (cycle ergometer) were collected at baseline (week 0) and following the bulking (week 12) and cutting (week 24) cycles. Circulating lipids (triglycerides, total, low-density, and high-density cholesterol), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured in serum. Results: The training led to significant increases in muscle strength, especially in the deadlift (+46%, p < 0.001) and squat (+65%, p < 0.001). Improvements in body composition were characterized by an increase in fat-free mass and a decrease in body fat percentage over the 24-week intervention (+3% and −6%, respectively, p < 0.05). Lipids, CRP, IL-6, and IL-10 did not change significantly, but there was a notable reduction in TNF-α (time effect p = 0.05, _pη² = 0.39), with 15% lower concentrations at week 24 compared to baseline, indicating reduced inflammation. Conclusions: Overall, the pilot intervention achieved high compliance and adherence rates, leading to improvements in body composition and lower resting TNF-α concentrations in a group of middle-aged males with obesity. Full article

There are approximately 130 reported medicinal effects attributed to mushrooms. We investigated the anti-inflammatory effects of hot-water extracts of 66 wild and cultivated fungi species (both edible and poisonous) by analyzing the inhibition of platelet aggregation and interleukin-8 (IL-8) gene expression induced by sodium arachidonate (A-Na), platelet-aggregating factor (PAF), and adenosine diphosphate (ADP). All species exhibited inhibitory effects: 38.3–98.1%, 37.3–96.8%, and 41.0–96.6% species inhibited platelet aggregation induced by A-Na, PAF, and ADP, respectively, while 17.0–97.0% inhibited IL-8 expression. Gyromitra esculenta showed the highest inhibition rate in all assays. High inhibition (≥80%) of A-Na-, PAF-, and ADP-induced platelet aggregation was observed in 29 (43.9%), 29 (43.9%) and 31 (47.0%) species, respectively. Half (33) of the species exhibited high inhibition of IL-8 expression. Four (6.1%), five (7.6%), and seven (10.6%) species exhibited inhibition rates of <50% for A-Na-, PAF-, and ADP-induced platelet aggregation, while nine (13.6%) exhibited low inhibition of IL-8 expression. The majority (87.5–100%) of poisonous species exhibited high inhibition. Our findings suggest that anti-inflammatory effects are universal among fungi, with poisonous species showing particular potential as raw materials for drug discovery. It can be inferred that many fungi contain universal or pleiotropic compounds with anti-inflammatory activities. Full article

Background: Pediatric sepsis remains the main cause of morbidity and mortality among children. Interleukin (IL)-6 is usually produced after infection, and elevated IL-6 levels may cause multisystemic damage. This study aimed to evaluate the effect of tocilizumab, an IL-6 receptor antibody, on children with septic shock. Methods: We conducted a retrospective cohort study of children diagnosed with septic shock and admitted to the pediatric intensive care unit (PICU) between 2018 and 2024. Tocilizumab was administered within 24 h to patients with high IL-6 levels who developed refractory septic shock. Outcomes, including 28-day mortality, morbidity, length of PICU stay, and shock duration, were analyzed between septic children with different etiologies and differed treatments. Results: Fifty-four children with refractory septic shock were included. Patients treated with tocilizumab (n = 21) showed improved outcomes compared to those without tocilizumab (n = 33), including shorter PICU stays and lower mortality rates (14.2% vs. 54.5%, p = 0.03). Subgroup analysis revealed that in the non-hematologic group, tocilizumab-treated patients had a 0% mortality rate compared to 50% in untreated patients (p = 0.006). In the hematologic group, tocilizumab-treated patients exhibited a 27.2% mortality rate compared to 61.5% in untreated patients (p = 0.09). Trends in IL-6 levels (D1 to D7) were significantly higher in non-survivors compared to survivors and in patients with hematological malignancies compared to those without. No adverse events, including secondary infections or long-term liver impairment, were observed. Conclusions: Tocilizumab appears to mitigate systemic inflammation and improve outcomes in children with refractory septic shock and elevated IL-6 levels. Further prospective studies are warranted to confirm these findings and establish treatment guidelines. Full article

Intestinal inflammation significantly compromises broiler health and adversely affects growth performance. Epigallocatechin gallate (EGCG) was found to maintain the gut health of animals. However, the role and mechanism of EGCG in preventing lipopolysaccharide (LPS)-induced intestinal inflammation in chicks have not yet been fully elucidated. In the 35-day study, 140 one-day-old Wenchang chickens were randomly assigned to four treatments: CON (basal diet), LPS (basal diet + 1 mg/kg body weight (BW) LPS), L-EGCG (basal diet + 40 mg/kg BW EGCG + 1 mg/kg BW LPS), and H-EGCG (basal diet + 60 mg/kg BW EGCG + 1 mg/kg BW LPS). On days 31, 33, and 35 of age, broilers in the LPS, L-EGCG, and H-EGCG treatments received intraperitoneal injections of LPS. The LPS reduced jejunal villus height, villus height/crypt depth ratio, Claudin1 mRNA, catalase (CAT) activity, and interleukin-10 (IL-10) levels compared to CON while elevating diamine oxidase (DAO), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α). EGCG improved growth performance in LPS-challenged broilers, elevating jejunal villus height and Claudin1/ZO-1 mRNA with reduced serum DAO. It enhanced antioxidant capacity via increased serum total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), CAT, glutathione peroxidase (GSH-Px) activities, and a decreased malondialdehyde (MDA) concentration. Concurrently, EGCG lowered IL-1β/TNF-α and raised IL-10 in serum/jejunum. Crucially, EGCG suppressed jejunal TLR4/MyD88/NF-κB mRNA and protein expression under LPS. These findings demonstrate EGCG’s protective role against LPS-induced intestinal inflammation in Wenchang chickens through TLR4/MyD88/NF-κB pathway inhibition. Full article