Search Results (5,393)

Mastitis limits yak dairy production and is associated with lipopolysaccharide (LPS)-mediated inflammation in yak mammary epithelial cells (YMECs). This study aimed to investigate the protective effect of caffeic acid (CA) against LPS-induced cellular injury and to elucidate the underlying mechanisms, with a particular focus on autophagy regulation via the NF-κB signaling pathway. LPS exposure strikingly reduced cellular viability and increased intracellular reactive oxygen species (ROS) levels, accompanied by activation of the NF-κB pathway. Furthermore, it increased the expression of pro-inflammatory cytokines (TNF-α, IL-8, and IL-1β). In addition, LPS enhanced endoplasmic reticulum (ER) stress and Ca²⁺ dysregulation, increased LC3-II/LC3-I ratio, and reduced synthesis of α-casein and β-casein. Pretreatment with CA resulted in the effective alleviation of these alterations by restoring cellular viability, suppressing inflammatory responses, and normalizing autophagy-related markers. Additionally, inhibition of Nrf2 reversed the partial reversal of the protective effects of CA, resulting in increased ROS accumulation and autophagy activation, but did not impact NF-κB suppression. These findings indicate that CA attenuates LPS-induced inflammatory injury in YMECs involved in both Nrf2-dependent and independent pathways. These findings provide a mechanistic analysis of yak mastitis pathogenesis and CA potential as a natural therapeutic for improving mammary health and milk quality in yak dairy systems. Full article

Bovine mastitis remains a major impediment to optimal dairy production. Somatic cell count (SCC) is commonly used as an indicator of mammary gland inflammation, while milk microbiota may also reflect mastitis-related changes. Here, we employed Oxford Nanopore full-length transcript sequencing to delineate the peripheral blood transcriptomic landscape of Xinjiang Brown cattle stratified by high (SCC ≥ 1,000,000 cells mL⁻¹) and low (SCC ≤ 200,000 cells mL⁻¹) SCCs, with the objective of identifying candidate genes underpinning mastitis resistance. We identified 226 differentially expressed genes and 441 differentially expressed transcripts. Genes in the high-SCC group were prominently enriched in immune response pathways and chemokine signalling cascades. Protein–protein interaction network analysis further delineated a core module of ten immune-related genes, including CCL4, IL1B and CXCL2. Integrative analysis with complementary second-generation sequencing data pinpointed CXCL2 as a high-priority candidate. Subsequent RT–qPCR and enzyme-linked immunosorbent assay (ELISA) validation revealed that CXCL2 expression was significantly elevated both in high-SCC individuals and in an LPS-induced bovine mammary epithelial cell inflammation model. Collectively, these findings establish CXCL2 as a putative molecular marker for mastitis resistance breeding and provide a foundational resource for deciphering the molecular mechanisms governing mammary health. Full article

The aqueous extract of Diaphragma Juglandis Fructus (AED), a by-product of Juglans regia L., represents a promising food-derived functional ingredient with potential benefits for intestinal health. This study evaluated the anti-colitis effects of AED and explored its underlying mechanisms using LPS-stimulated RAW264.7 macrophages and a DSS-induced colitis mouse model. In DSS-induced colitis in mice, AED at 10 μg/mL suppressed pro-inflammatory cytokine production and inhibited JAK1/STAT3 signaling. In DSS-induced colitis in mice, AED at 600 mg/kg for 7 days mitigated DSS-induced colonic injury, restored tight junction proteins, and improved epithelial barrier integrity. Integrated transcriptomic and metabolomic analyses identified AED-associated alterations in arginine-polyamine and taurine-hypotaurine metabolism, while network pharmacology and molecular docking suggested angiotensin-converting enzyme (ACE) and von Willebrand factor (VWF) as candidate functional targets for further investigation. Collectively, these findings indicate that AED exerts anti-colitis effects in association with coordinated changes in inflammatory signaling, metabolic pathways, and barrier-related markers, supporting its potential as a food-derived functional ingredient candidate for ulcerative colitis management. Full article

Background: Lipid peroxidation is a primary driver of biological membrane damage and mediates the relationship between environmental exposure and adverse health outcomes. Malondialdehyde (MDA) is a widely recognized biomarker for quantifying oxidative stress intensity. Despite numerous studies on oxidative stress and metal exposure, nonlinear relationships between physiological characteristics, serum metal profiles and MDA levels in pubertal children remain insufficiently studied. Methods: The study included 105 conditionally healthy children aged 12–14 years from urban and rural regions of Tatarstan, Russia. Serum MDA concentrations were determined spectrophotometrically using the thiobarbituric acid assay, while Zn, Cu, Fe, Sr and Pb concentrations were measured by atomic absorption spectrometry. A multilayer perceptron neural network was applied to model nonlinear relationships between MDA levels, environmental exposure indicators and morphophysiological characteristics. Because the original relational dataset contained partially replicated participant-derived relational structures, primary validation was performed using independently reconstructed datasets without repeated observations. Additional repeated cross-validation and SHAP-based feature importance analysis were performed. Results: Urban-residing children demonstrated significantly higher serum MDA levels than rural counterparts, independent of sex, with girls consistently showing higher values. Reduction of predictor dimensionality improved model generalization behaviour. Validation using independently reconstructed datasets without repeated observations demonstrated reproducible exploratory predictive behaviour of the reduced neural network model, with independently reconstructed validation datasets yielding mean R² values of 0.901 ± 0.052 and 0.914 ± 0.046, respectively. SHAP analysis demonstrated that zinc, copper and iron consistently represented the dominant contributors to the nonlinear model, although substantial variability in the relative ranking of zinc and copper was observed between validation datasets. Conclusions: The proposed neural network model demonstrated the ability to capture reproducible nonlinear relationships between oxidative stress markers and environmental exposure parameters in a limited biomedical dataset. The model should primarily be interpreted as an exploratory explanatory tool rather than an individual clinical prediction instrument. Because of the limited dataset size, partially reconstructed relational structure and exploratory study design, the findings require cautious interpretation and further external validation. Full article

Background: The associations between mean corpuscular volume (MCV) and leukocyte-derived ratios and chronological aging remain poorly understood. We aimed to evaluate the association between MCV and leukocyte-derived ratios and chronological age in U.S. adults. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES, n = 9259) and the Health and Aging Brain Study–Health Disparities (HABS-HD, n = 770). Participants were aged ≥20 years, and individuals with hemoglobin levels outside 12–18 g/dL or C-reactive protein (CRP) > 1 mg/dL were excluded. Associations between age and MCV, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and platelet-to-white blood cell ratio (PWR) were examined using quartile comparisons and multivariable linear regression adjusted for sex, race/ethnicity, CRP, and red cell folate and hemoglobin. Results: In both cohorts, higher quartiles of MCV, NLR, and MLR were associated with older mean age. In adjusted marker-specific models, MCV, NLR, and MLR were each positively associated with chronological age. In composite models, MCV remained independently associated with older age in both NHANES (β = 0.646, 95% CI 0.567–0.725) and HABS–HD (β = 0.300, 95% CI 0.156–0.445). Conclusions: MCV and selected leukocyte-derived ratios are significantly associated with chronological age across two U.S. cohorts, with MCV showing the most consistent independent association. Full article

Bladder cancer worldwide has seen a sharp rise, making it a significant global health concern. Recurrence monitoring is the main concern in treating the disease, and drug resistance follows suit. Treatment options include first-line medications, adjuvant therapy with BCG (Bacillus Calmette–Guérin) instillations, and combination therapies targeting the PD-1/PD-L1 axis. It has varying 5-year relative survival rates depending on the stage at diagnosis. Despite initial treatment success, resistance often develops, leading to relapse. Resistant to standard treatment is often due to immune landscape changes that are controlled by the most aberrant genes in bladder cancer, which also have a hold in the immune environment of the bladder. Dysregulation of FGFR3 (Fibroblast Growth Factor Receptor 3) in bladder cancer contributes to cell proliferation and metastasis. Simultaneously, the alterations in EGFR (Epidermal Growth Factor Receptor) regulation are linked to cell migration and resistance to treatment. FGFR3 in non-muscle invasive bladder cancer and EGFR in muscle-invasive bladder cancer are central elements in triggering various signaling pathways that contribute to chemoresistance. Concentrating the roles of both genes within the bladder tumour, they present opportunities not only as therapeutic targets but also as potential points of resistance and monitoring for recurrence. Exploring FGFR3 and EGFR to enhance treatment efficacy when combined with ICIs and developing markers into reliable diagnostic tools for recurrence, ultimately aiming for improved patient well-being, is the key aspect we propose to target from this narrative. Full article

Microplastic pollution has attracted significant attention in recent years due to evidence that these particles can accumulate in organisms’ tissues and organs and induce adverse health effects, with oxidative stress being a key underlying mechanism of toxicity. The present study investigated the effects of polystyrene microplastics (0.1 μm in diameter) administered at a dose of 0.1 mg/day/animal for 4 weeks, followed by a 2-week recovery period without exposure, on oxidative stress markers in the liver, kidney, and spleen and on hematological and blood biochemical parameters in mice. The results showed a statistically significant increase in white blood cell counts, including lymphocytes, granulocytes, and monocytes, at week 5, indicating the development of an inflammatory response. During the last week of the recovery period (week 6), values returned to levels that approached baseline. Changes in lipid peroxidation demonstrated an induction of oxidative stress, accompanied by alterations in glutathione levels and antioxidant enzyme activities, with a tendency toward recovery after cessation of polystyrene microplastic exposure. In conclusion, these findings demonstrated that even short-term exposure to low doses of polystyrene microplastics could trigger oxidative stress and inflammatory responses, highlighting their potential health risks and the need for further investigation into their long-term biological effects. Full article

Background: Head trauma is a major public health concern. Computed tomography (CT) is frequently used to evaluate these patients but may expose them to unnecessary radiation exposure. Various biomarkers have been investigated to predict prognosis and reduce the need for unnecessary imaging. Red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) have been proposed as inflammatory markers; however, their diagnostic value in head trauma remains controversial. This study aimed to determine the value of complete blood count parameters in identifying intracranial injury in patients with mild head trauma. Methods: This prospective, single-center study enrolled 100 adults with mild head trauma. Demographic data, vital signs, neurological assessments, complete blood counts, CT results, and clinical outcomes were also recorded. Patients were categorized as intracranial injury positive (Group 1) or intracranial injury negative (Group 2). We statistically compared the laboratory and demographic data of the groups. Statistical significance was set at p < 0.05. Results: The study included 100 patients with mild head trauma who presented to the emergency department, of whom 11 were in Group 1. The median PLR and lymphocyte levels differed significantly between the groups (p < 0.05). Conclusions: The PLR may serve as a preliminary supportive marker to aid clinical assessment; however, its modest discriminatory performance suggests that it should not be used as a standalone diagnostic tool. Full article

Digestive tract structure is a key indicator of fish health and environmental adaptation, while seasonal dynamics of the gut microbiota reflect host responses to environmental changes. In this study, the digestive tract microstructure of Hypomesus nipponensis from Bosten Lake was characterized using H&E staining and scanning electron microscopy, followed by 16S rDNA gene V3-V4 region sequencing and analysis of the gut microbiota in spring, summer, and autumn. The results showed that the esophageal mucosa of H. nipponensis is a stratified columnar epithelium, with abundant gastric glands, and the circular muscle layer of the stomach caeca is significantly thickened (244.84 ± 49.01 μm). The pyloric caeca resemble the gut in structure; both are covered with dense microvilli on the luminal surface. Collectively, these features constitute the structural basis for its carnivorous diet. Microbiota analysis revealed that the diversity of gut microbiota fluctuated significantly with season: the Chao, Ace, and Sob indices in spring (144.63 ± 30.27) were significantly higher than in summer (82.13 ± 21.45) and autumn (83.25 ± 15.30) (p < 0.001), with no significant difference between summer and autumn (p > 0.05). The dominant marker genera of H. nipponensis in spring, summer, and autumn were Bacillus (31.60%), Clostridium (32.20%), and Sarcina (29.32%), respectively. This study describes the adaptive characteristics of the digestive tract structure and feeding habits of H. nipponensis and reveals the seasonal changes in its gut microbiota. Importantly, since the digestive tract structure data were collected only in summer, the direct relationship between the structure and seasonal microbial dynamics cannot be determined, and multi-season histological sampling is needed for further investigation. Nevertheless, these findings provide preliminary morphological and microbiological references for the ecological adaptation of this species in Bosten Lake and offer a scientific basis for water resource management in this area. Full article

Background/Objectives:Helicobacter pylori infection is traditionally associated with gastrointestinal diseases; however, increasing evidence suggests that it may have systemic effects involving inflammatory, metabolic, and hematological pathways. Despite this, integrated evaluations of these domains remain limited, particularly in Middle Eastern populations. This study aimed to assess the impact of H. pylori infection on inflammatory, metabolic, and hematological parameters among adults. Methods: A case–control study was conducted including 100 participants (50 H. pylori-positive patients and 50 healthy controls) recruited from Qassim Health Cluster, Saudi Arabia. Demographic and clinical data were collected, and blood samples were analyzed for random blood sugar (RBS), glycated hemoglobin (HbA1c), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, ferritin, and white blood cell count (WBC). Statistical analyses included group comparisons, Spearman correlation, logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: The infected group showed significantly higher levels of RBS and HbA1c, indicating impaired glycemic control. Inflammatory markers (CRP and ESR) were also significantly elevated compared to controls (p < 0.001). Hemoglobin and ferritin levels were significantly lower in the infected group (p < 0.001), suggesting disturbed iron metabolism. Correlation analysis revealed positive associations between inflammatory markers and glycemic indices, and negative associations with hemoglobin and ferritin. Multivariable logistic regression identified CRP (adjusted OR = 1.33, 95% CI: 1.04–1.71) and ESR (adjusted OR = 1.09, 95% CI: 1.02–1.16) as independent predictors of H. pylori infection after adjustment for smoking status and fast-food consumption. The combined model demonstrated acceptable discriminatory performance with an AUC of 0.82 (95% CI: 0.74–0.90). Conclusions:Helicobacter pylori infection was associated with significant inflammatory, metabolic, and hematological alterations, supporting its potential role as a systemic condition beyond the gastrointestinal tract. These associations remained significant after adjustment for major lifestyle-related confounders, including smoking status and fast-food consumption. Although the combined inflammatory model demonstrated acceptable discriminatory performance, it should currently be considered mainly for research or preliminary screening purposes and not as a replacement for established diagnostic methods for active H. pylori infection. Further large-scale longitudinal and interventional studies are warranted to clarify causality and evaluate the impact of eradication therapy on systemic outcomes. Full article

Background and Objectives: C-reactive protein (CRP), a marker of systemic inflammation, is frequently elevated in individuals with excessive adiposity. However, the relationship between specific body fat parameters and CRP levels across sexes and age groups remains unclear. This study aimed to investigate the association between CRP levels and body fat parameters using data from the 2022 Korea National Health and Nutrition Examination Survey. Methods: A total of 3369 participants (representing 32,635,626 Korean adults) were included. Demographic, lifestyle, and clinical data were collected, and body composition parameters were measured using bioelectrical impedance analysis. The primary exposure variables included fat mass index (FMI; total body fat mass/height²) and trunk fat mass. The primary outcome was log-transformed high-sensitivity CRP (ln[hsCRP]). Pearson correlation and sex-stratified multivariate linear regression analyses were performed. Results: The mean age of participants was 49.6 years, and 53.3% were male. ln[hsCRP] was positively associated with body mass index, waist circumference, total body fat mass, FMI, appendicular fat mass, and trunk fat mass in both sexes (all p < 0.001). FMI showed a stronger association with ln[hsCRP] in females (r = 0.373) than in males (r = 0.232). In multivariable analyses, FMI remained independently associated with ln[hsCRP] in both males (β = 0.10) and females (β = 0.14), with a stronger effect observed in females. Trunk fat mass was also independently associated with ln[hsCRP] (β = 0.06 in males; β = 0.10 in females). Age-stratified analyses demonstrated that these associations were more pronounced in younger adults (19–40 years old) than in those aged 41–70 years. Conclusions: In Korean adults, total and truncal fat masses were independently associated with systemic inflammation, and this association was stronger among females and younger adults. Full article

Steatotic liver disease (SLD) is characterised by profound metabolic reprogramming, yet no single biomarker reliably distinguishes disease entities, stages or sex-specific risk profiles. By integrating serum metabolomic signatures as a liquid biopsy with tumour-associated CSC marker profiles in a sex-stratified analytical framework, we aimed to identify biologically meaningful differences and improve strategies for early, presymptomatic detection of SLD progression and HCC. The present study focuses on a targeted panel of 12 strongly dysregulated serum metabolites as candidate biomarkers of disease progression, quantified by NMR-based metabolomics and ELISA and complemented by CSC marker staining. We combined these NMR-based metabolomic ‘liquid biopsy’ data with circulating tumour-associated biomarkers, MELD-based risk assessment and tissue-level CSC marker expression across MetALD, MASLD, immune-mediated and cancerogenic liver disease, HCC and healthy controls. Female MetALD patients showed the second highest mortality after HCC, with lower survival than male cancer patients, despite MELD 3.0 assigning ~50% higher scores in women. MetALD mortality clustered with GP73, CD44, metabolomics and AA/3HB ratio, indicating a distinct, high-risk female phenotype. Integrating liquid-based metabolomic profiling, AA/3HB redox assessment, CSC markers and MELD 3.0 into sex-sensitive diagnostic pathways may improve early detection and risk stratification of alcohol-associated SLD, especially in women. Full article

Background/Objectives: Healthy longevity depends on not only lifespan but also the maintenance of physiological, metabolic, physical, and cognitive functions throughout aging. Identifying early determinants of health is crucial for preventing age-related decline. This narrative review aims to synthesize current evidence on how diet and specific nutrients relate to these early risk factors and indicators of healthy longevity. Methods: A review was performed to identify the links between dietary factors, energy balance, and gut microbiota composition and normal body weight; blood cholesterol, pressure, and glucose; healthy sleep; an active lifestyle; and normal physical function and cognitive performance. Particular attention was given to Mediterranean and other plant-based dietary models as sources of key nutrients. Evidence from observational studies, randomized controlled trials, and meta-analyses was considered. Results: Across all markers, dietary quality and nutrient adequacy emerged as consistent determinants of health outcomes. Key nutrients were associated with favorable cardiometabolic, cognitive, and musculoskeletal functions, such as omega-3 fatty acids, fiber, vitamins D and B, minerals like magnesium and potassium, and polyphenols. Common nutrition gaps included insufficient intake of fiber, unsaturated fats, and micronutrients, which was often linked to a shift toward less plant-based diets. Gut microbiota diversity may mediate several of these associations, influencing metabolism, inflammation, sleep quality, and cognitive performance, although inter-individual variability and causal pathways remain incompletely understood. Conclusions: An integrated dietary approach emphasizing the consumption of whole and plant-rich foods, with moderate amounts of animal foods, supports multiple early markers, risk factors, and indicators of healthy longevity. The modulation of the gut microbiota through plant-based diets and fermented foods represents a promising strategy for maintaining health across aging trajectories. Full article

Background: The contribution of oral inflammatory conditions to systemic disease burden remains underexplored within multimorbidity frameworks. Emerging evidence suggests that periodontal inflammation may play a role in the clustering of chronic diseases, yet few studies have evaluated this at a population level using robust datasets. The aims of this study were to investigate whether periodontal diseases are associated with Multiple long-term conditions (MLTCs) burden and severity in two population-based cohorts and to examine whether systemic inflammatory biomarkers mediate these associations. Materials and Methods: We analyzed two population-based cohorts: the UK Biobank (UKB; n = 500,612) and the US National Health and Nutrition Examination Survey (NHANES; n = 10,714). MLTCs were defined as the coexistence of ≥2 chronic diseases. Associations between periodontal diseases and MLTCs were assessed using multivariable logistic and multinomial logistic regression. Causal mediation analyses examined the contribution of systemic inflammatory markers. Results: Approximately half of all participants had MLTCs. The prevalence of periodontal diseases was 17.8% in UKB (self-reported symptoms), and 42.3% in NHANES (clinically assessed). Periodontal diseases were independently associated with greater odds of MLTCs in both UKB (OR 1.12; 95% CI 1.10–1.14) and NHANES (OR 1.22; 95% CI 1.09–1.37). Associations were stronger among adults aged ≤ 60 years. A consistent dose-response relationship was observed between periodontal status and the number and severity of chronic conditions, as well as inflammatory-related MLTCs. Mediation analyses suggested partial effects through white blood cell count, neutrophils, and C-reactive protein. Conclusions: Periodontal inflammation is independently associated with greater multimorbidity burden, particularly in younger adults. Systemic inflammation may offer a plausible biological link, and these findings position oral health as an underrecognized and modifiable target in multimorbidity prevention and management frameworks, warranting prospective investigation. Full article

Exposure to air pollution is linked to adverse health outcomes. To better reflect real-world conditions, we employed a mobile exposure system enabling direct field exposure of the human airway epithelial model MucilAir™ to ambient air in a traffic-burdened locality. This study represents a follow-up to our previous work, in which a 5-day exposure period under extreme traffic-related pollution conditions resulted in premature cell loss. Under different meteorological conditions characterized by increased precipitation and lower particle number concentrations, MucilAir™ cultures were exposed to traffic-polluted air for 2 days. The exposure resulted in a mild but significant increase in cytotoxicity markers, including lactate dehydrogenase release and elevated levels of 15-F_2t-isoprostane, indicating induction of the cellular stress response rather than severe cytotoxicity. A transcriptomic analysis revealed extensive gene expression changes; the enrichment of the pathways related to polycyclic aromatic hydrocarbon detoxification and amino acid biosynthesis suggests adaptive metabolic responses to oxidative and genotoxic stress. In parallel, the pathways associated with epithelial proliferation and repair, extracellular matrix organization, focal adhesion, and immune signaling were suppressed, indicating potential disruption of the epithelial homeostasis. Overall, these findings demonstrate that 2 days of exposure to real-world traffic-polluted air elicits adaptive stress responses in airway epithelial cells while simultaneously impairing the processes essential for epithelial integrity, potentially leading to airway dysfunction. Full article