Search Results (472)

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

Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg⁻¹·day⁻¹ for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8⁺ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal. Full article

Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms. Full article

Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication. Full article

Evidence suggests that physical activity promotes bone health through mechanical loading and biochemical signaling between bone and muscle tissues. A class of signaling molecules known as exerkines is a key mediator of bone–muscle crosstalk. Although exercise regulates osteokines, the acute exerkine responses across different exercise modalities remain unclear. This randomized repeated-measures crossover study compared acute changes in serum sclerostin (SCL), dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteopontin (OPN), brain-derived neurotrophic factor (BDNF), irisin, and interleukin 6 (IL-6) following circuit training (CT) (cycle ergometer, push-up, step-ups, medicine ball twist, and front squats with kettlebell for three rounds) and traditional resistance (TR) exercise (3 sets 10 repetitions 50–60% 1 RM for leg press, seated cable row, barbell bench press, dumbbell deadlifts, and dumbbell seated shoulder press) in healthy young adults (n = 12). Participants performed two protocols separated by 2-week wash-out periods. Blood samples were analyzed before exercise training (pre), immediately post-exercise (IP), and 30 min post-exercise (30P) for all exerkines using ELISA. There was a significant interaction between protocol, timepoint, and sex (p = 0.038) for SCL levels. In males, SCL levels increased from Pre to IP under both training protocols (CT: 0.10 ± 0.02 ng/mL to 0.14 ± 0.02 ng/mL; TR: 0.20 ± 0.02 ng/mL to 0.21 ± 0.02 ng/mL). In both protocols, SCL levels decreased from IP to 30 P (CT: 0.14 ± 0.02 to 0.10 ± 0.01 ng/mL; TR: 0.22 ± 0.02 to 0.17 ± 0.02 ng/mL). In females, SCL levels increased from Pre to IP under both training protocols (CT: 0.03 ± 0.02 ng/mL to 0.06 ± 0.02 ng/mL; TR: 0.07 ± 0.02 ng/mL to 0.13 ± 0.02 ng/mL). There was a significant time effect for OPN and RANKL concentrations. Marginal means for the time point showed that OPN was significantly higher at the Pre time point. Post hoc analyses showed that OPN levels significantly decreased from 30P to Pre (18.84 ± 0.92 to 15.69 ± 1.32 pg/mL) (p = 0.01). RANKL showed a significant increase from Pre (0.38 ± 0.04 pg/mL) to 30P (0.57 ± 0.06 pg/mL) (p = 0.02); otherwise, there were no significant differences between protocols or sexes. Irisin significantly decreased from Pre (28,761.73 ± 238.52 pg/mL) to IP (2364.85 ± 243.79 pg/mL) in both protocols (p = 0.01). DKK-1, BDNF, and IL-6 levels were only different between protocols (p < 0.01). SCL and BDNF levels were expressed higher in the TR protocol, whereas DKK-1, IL-6, and Irisin levels were expressed higher in the CT protocol. Overall, the findings suggest that SCL, RANKL, OPN, and irisin responded to the exercise bout, while the other exerkines did not show meaningful changes over time. Full article

Zearalenone (ZEA) is a common contaminant in crops and animal feed. However, research on the effects of ZEA on animal mammary tissue is relatively limited. Sulforaphane (SFN) is a naturally active compound mainly derived from cruciferous vegetables (such as broccoli), with significant antioxidant and cytoprotective effects. The purpose of this study is the effect of SFN on ZEA-induced toxicity in bovine mammary epithelial cells (MAC-T). By treating MAC-T cells with different concentrations of ZEA and SFN for 24 h, the results showed that different concentrations of ZEA (10, 20, 40, 60, 80, or 100 μM) could inhibit MAC-T cell viability. Treatment with SFN at concentrations of 1, 2.5, and 5 μM had no significant effect on cell viability. The results of combined treatment with 10 μM ZEA and 1, 2.5, or 5 μM SFN showed that SFN could significantly reverse the decrease in cell viability caused by ZEA; reduce the increase in lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), and malondialdehyde (MDA) content induced by ZEA; and increase the levels of glutathione (GSH), superoxide dismutase (SOD), and mitochondrial membrane potential that were decreased by ZEA. SFN can significantly inhibit the upregulation of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) induced by ZEA exposure and markedly reverse the increase in cell apoptosis rate caused by ZEA. Compared with the control group, the expression of genes nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase 1 (GPX1) was significantly reduced in the ZEA group, while the addition of SFN effectively increased the expression levels of these genes. Corresponding protein detection results were consistent with the trends in gene expression. This study demonstrated that SFN alleviates ZEA-induced damage to MAC-T cells by activating the Nrf2 pathway, providing a theoretical basis for the subsequent application of SFN in dairy farming to prevent and control breast health risks related to mycotoxins. Full article

Diabetic cardiomyopathy (DC) is a serious health issue. MicroRNA-155b expression dysregulation might be involved in the fibrotic cycle in DC. L-Arginine (l-arg) is reported to have a preferable impact on the cardiovascular system. We aimed to understand the pathogenesis of DC and to detect the potential protective effect of l-arg through modulation of apoptosis, inflammation, fibrosis, and miR-155b expression. This study comprised four groups of forty adult male rats (10 rats in each group): diabetics, l-arg diabetics, l-arg, and controls. Blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body weight, and cardiac hypertrophy index (HW/BW ratio) were assessed. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) was done. Expressions of toll-like receptor-4 (TLR4), pro-inflammatory interleukin 1 beta (IL-1β), interleukin 6 (IL-6), anti-inflammatory interleukins (IL-4, IL-13), apoptotic markers (bcl-2, bax) and microRNA-155b were measured by real-time PCR. Myocardial light, electron microscopic and morphometric studies were performed. Results showed a significant decrease in cardiac hypertrophy (HW/BW = 0.0030 ± 0.0002 mg/g), echocardiographic parameters (LVEF = 54.12 ± 1.628% and LVFS = 20.40 ± 0.541%), hemodynamic parameters (HR = 411.0 ± 9.684 bpm, SBP/DBP = 84 ± 4.998/60 ± 3.062 mmHg) and downregulation of the expression of IL-4, IL-13, IL- 1β, IL-6 and TLR4 in the l-arg diabetic group compared to diabetic rats. Additionally, restoration of normal appearance of most cardiac myofibrils, intact blood vessels, decreased cardiac fibrosis and upregulation of bax expression were observed. Expression of microRNA-155b increased by 0.007 for each gram increase in blood glucose (>1.45, it showed 100% specificity and 96.7% sensitivity). In conclusion, microRNA-155b upregulation is associated with enhancement of the transcription of inflammatory cytokines and apoptotic genes. L-arginine may be a useful protective strategy for DC through modulation of apoptosis, inflammation, and fibrosis, in addition to regulating the expression of miR-155b. Full article

Celastrol (CSL), a natural triterpenoid extracted from Tripterygium wilfordii, demonstrates a wide range of biological activities. In this study, we explored whether CSL alleviates kidney damage in spontaneously hypertensive rats (SHRs) through the modulation of the Nrf2/Ho-1 pathway, a crucial target in renal injury models. A total of 40 male SHRs, aged 6–8 weeks, were randomly allocated to four groups: the control group (CON, serving as the healthy control), the spontaneously hypertensive rat group (SHR), the SHR group treated with low-dose CSL (L-CSL + SHR, 0.5 mg/kg/d), and the SHR group treated with high-dose CSL (H-CSL + SHR, 1 mg/kg/d). All drugs were formulated using physiological saline as the solvent and administered via intraperitoneal injection. The control group received an equivalent volume of physiological saline via intraperitoneal injection, and all groups underwent continuous daily administration for 6 weeks. The results indicated that, in comparison with the control group, the serum levels of angiotensin, angiotensin-converting enzyme, and aldosterone in the SHR group were relatively high, and CSL treatment further downregulated these indices. Simultaneously, CSL downregulated pro-inflammatory factors (tumor necrosis factor-α and interleukin-1β) and upregulated interleukin-6. Regarding renal function-related indicators, CSL reduced malondialdehyde levels and enhanced the activities of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase. Moreover, CSL inhibited the overexpression of Keap1. Significantly, the mRNA levels of Nrf2, Nqo1, and Ho-1 in the CSL-treated groups were notably higher than those in the SHR group. These findings suggest that CSL mitigates renal pathological damage in SHR by activating the Nrf2/Ho-1 pathway, offering a potential therapeutic approach for hypertension-induced renal injury. Full article

The responsiveness of the stress axis is fundamental for maintaining health and sustaining productive performance; however, the effect of modulating this stress axis with bovine appeasing substance and its effects on biochemical, immunological, oxidative parameters and uterine involution have not been determined, which are the objectives of this experiment. To elucidate these questions, Holstein cows, from the prepartum to lactation period in a cross-ventilation system, received an application of a bovine appeasing substance (treated group) and a 0.9% saline solution (control group) at the time of calving, and blood samples were collected on calving day and on days 3, 7, 14 and 21 postpartum for analysis. Modulation of the stress axis by bovine appeasing substance increased magnesium levels on days 7 and 14 postpartum, with a reduction in fructosamine levels on days 3, 7, 14, and 21 postpartum. A reduction in ferritin levels, an acute-phase protein, and a reduction in interleukin 1 beta and interleukin 6 were also observed, demonstrating an anti-inflammatory effect in cows of the treated group. Creatine kinase activity decreased on day 21 postpartum in cows treated with bovine appeasing substances. An increase in cholinesterase activity on day 7 and a marked decrease on day 21 postpartum in treated cows were observed compared to the control. This was accompanied by a reduction in beta-hydroxybutyrate levels on day 7 and a reduction in reactive oxygen species levels on day 14 in animals of the treated group, indicating modulation of ketogenesis and reduced oxidation through an anti-inflammatory effect. Mean uterine thickness was also affected by the bovine appeasing substance, with a lower mean thickness on day 21 postpartum in treated cows. Modulation of the stress axis by the bovine appeasing substance reduces inflammation, improving energy dynamics and reducing oxidation, thus facilitating tissue repair associated with postpartum uterine involution in dairy cows. Full article

This study estimates the association between respiratory outcomes among employees of a secondary aluminum plant and airborne pollutants. Additionally, it looks into the relationship between pulmonary dysfunction in workers and X-Ray repair cross-complementing one (XRCC1) gene polymorphisms. 110 exposed workers and 58 non-exposed workers were enrolled in the study. Measurements were conducted on sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and particulate particles. Pulmonary function was tested. Eosinophil cationic protein (ECP), C-reactive protein (CRP), matrix metalloproteinase-1 (MMP-1), interleukin 6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), XRCC1 protein, and genotyping of XRCC1 gene polymorphisms were examined. The annual average concentrations of particulate matter (PM_2.5, PM₁₀), total suspended particulates (TSP), SO₂, and NO₂ were lower than the permissible limit. The areas around ovens, evaporators, and cold rolling mills exhibited the highest amounts. The majority of employees in these departments had impaired lung function. Prolonged exposure was associated with a significant decrease in forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) among the exposed group (p = 0.001 & 0.04, respectively). Serum XRCC1 levels were significantly higher among exposed workers (p = 0.02). Inflammatory biomarkers showed no statistically significant differences between groups. Aluminum workers are at risk of developing respiratory disorders. The level of serum XRCC1 may serve as a potential biomarker for detecting susceptible workers. Full article

Background/Objectives: Heart failure (HF) has been associated with adverse outcomes in coronavirus disease 2019 (COVID-19), but it remains unclear whether HF independently predicts sepsis and mortality once inflammatory and cardiac biomarkers are considered. Methods: This single-center retrospective cohort analysis included 127 adult patients hospitalized with laboratory-confirmed COVID-19 at a tertiary infectious diseases hospital between March 2020 and December 2024. Pre-existing HF was defined based on cardiology records and chronic HF therapy. Baseline assessments included clinical characteristics, echocardiography, and biomarkers (NT-proBNP, high-sensitivity troponin, C-reactive protein [CRP], interleukin 6 [IL-6], procalcitonin, and D-dimer) measured within 24 h of admission. Primary outcomes were sepsis and all-cause mortality (in-hospital or 30-day). Independent associations with sepsis and mortality were examined using multivariable logistic regression incorporating demographic factors, major comorbidities, baseline disease severity, and inflammatory and cardiac biomarkers. Results: Of 127 patients (mean age 70.1 ± 14.8 years, 63.8% male), 30 (23.6%) had pre-existing HF. Patients with preexisting heart failure exhibited significantly reduced left ventricular ejection fraction and higher admission levels of NT-proBNP and high-sensitivity troponin, accompanied by a substantially increased burden of in-hospital cardiovascular complications (53.3% vs. 14.4%, p < 0.001). However, sepsis (6.7% vs. 7.2%, p = 1.000) and total mortality (20.0% vs. 17.5%, p = 0.971) did not differ significantly between HF and non-HF groups. In multivariable analyses, HF was not independently associated with sepsis (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.05–12.34, p = 0.855) or mortality (aOR 0.63, 95% CI 0.16–2.46, p = 0.506). By contrast, higher CRP (aOR 1.01 per 1 mg/L, 95% CI 1.00–1.01, p = 0.007), IL-6 (aOR 1.01 per 1 pg/mL, 95% CI 1.00–1.01, p = 0.025), and high-sensitivity troponin (aOR >999, 95% CI 138–>999, p = 0.001) were independently associated with mortality. Conclusions: In hospitalized COVID-19 patients, pre-existing HF identifies a subgroup with heightened cardiac biomarker activation and a substantially higher burden of cardiovascular complications but does not associate with sepsis or short-term mortality in this cohort after adjustment for inflammatory and cardiac biomarkers. Mortality risk appears to be driven primarily by systemic inflammation and acute myocardial injury, as reflected by CRP, IL-6, and high-sensitivity troponin. These findings support a biomarker-driven approach to risk stratification in COVID-19, in which dynamic inflammatory and cardiac injury profiles provide more prognostic information than HF status alone, while still warranting intensified cardiovascular surveillance in patients with HF. Full article

The article aimed to review the current literature analysing the complexity of an exercise-induced acute phase response in athletic horses undergoing intense training and endurance competitions. Since the endurance discipline demands physical fitness, exceptional health and excellent adaptation to an increasing workload, diagnostic methods of assessing the factors mentioned above are highly required. Athletic horses in endurance training undergo numerous metabolic but also immune adaptations, including changes in pro-inflammatory and anti-inflammatory cytokine levels. The inflammatory reaction resembles typical inflammation only to some extent; therefore, the term exercise-induced acute phase response (APR) has been introduced. Among many biomarkers, acute phase proteins (APPs), like serum amyloid A (SAA) and different types of cytokines, especially interleukin 1 (IL-1), interleukin 6 (IL-6), and tumour necrosis factor α (TNF-α), appear to play a key role. These markers may be modulated by many factors; however, proper training seems to result in the occurrence of an “anti-inflammatory state”, which is beneficial for the horse’s health and highly required in high-performance equine athletes. Further understanding of the inflammatory reaction associated with extreme physical effort is crucial for ensuring the long-term career and welfare of endurance horses. Full article

Neuroinflammation is a critical pathological process implicated in several neurological disorders. It arises from complex interactions among immune cells and the excessive release of pro-inflammatory mediators, ultimately leading to neuronal damage. Ergothioneine (EGT), a naturally occurring antioxidant, has attracted attention for its potential anti-inflammatory role in neuroinflammation, although it remains poorly understood. We employed a comprehensive strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to explore how EGT influences neuroinflammatory pathways. Computational analyses indicated that EGT might regulate several inflammation-related signaling cascades by targeting key molecules such as Tumor Necrosis Factor (TNF), AKT Serine/Threonine Kinase 1 (AKT1), Caspase 3 (CASP3), and Interleukin 6 (IL-6). Docking and dynamics simulations confirmed strong and stable binding between EGT and these targets. Experiments using lipopolysaccharide-stimulated BV2 microglia cells demonstrated that EGT significantly reduced pro-inflammatory cytokine production, primarily through modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. By integrating multi-omics approaches with cellular validation, this study sheds light on the molecular mechanisms underlying EGT’s anti-inflammatory effect and supports its potential application as a functional food ingredient for managing neuroinflammation. Full article

Cannabis seed (CS), also known as hemp seed, is a nutrient-dense plant-derived food material rich in polyunsaturated fatty acids and bioactive components with reported anti-inflammatory properties. However, potential nutritional effects of CS on acute pancreatitis (AP), an inflammation-driven disease with limited dietary management strategies, have not yet been investigated. In this study, we examined the effects of dietary CS extract in a cerulein-induced AP mouse model. CS extract (5, 10, or 50 mg/kg) or vehicle (dimethyl sulfoxide) was orally administered 1 h prior to cerulein injection, and mice were euthanized 6 h after the final challenge. Oral supplementation with CS significantly attenuated AP severity, indicated by reducing pancreatic weight-to-body weight ratio, serum amylase and lipase activities, histopathological pancreatic injury, and pancreatic myeloperoxidase activity. CS administration alleviated AP-associated acute lung injury; markedly suppressing pancreatic mRNA expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. High-performance liquid chromatography analysis identified α-linolenic acid, an omega-3 polyunsaturated fatty acid, as a major nutritional component of CS extract. Collectively, these findings suggest that CS supplementation may contribute to nutritional modulation of inflammatory responses and systemic organ injury in experimental AP, supporting its potential as a functional food ingredient in inflammation-associated pancreatic disorders. Full article

The severity of cardiovascular disease is linked to C-reactive protein, interleukin 6, and C-type natriuretic peptide levels, stressing the need for a sensitive sensor that can detect these biomarkers at ultralow levels in real time. Whole blood samples from confirmed cardiovascular patients were analyzed for C-type natriuretic peptide, C-reactive protein, and interleukin 6 using three stochastic sensors. These sensors were designed using carbon paste matrices decorated with Ag nanoparticles (AgNPs), on which different phthalocyanines were physically immobilized. The sensors exhibited exceptionally low detection limits (1 × 10⁻²¹ g mL⁻¹) and broad linear concentration ranges (1 × 10⁻²¹ to 1 × 10⁻⁶ g mL⁻¹). The analysis conducted using the Student t-test indicated that there is no statistically significant difference between the results obtained from the three stochastic sensors used in the screening tests of whole blood, with ELISA at a confidence level of 99%. Full article