Search Results (3,016)

Styrene, a constituent of polystyrene food-contact materials, can migrate into hot beverages, but data on short-term consumer exposure and associated biological responses remain limited. In this single-arm longitudinal human biomonitoring pilot study, 40 healthy adults consumed tea or coffee daily in Styrofoam cups for approximately two weeks. Biomarkers were measured at baseline, day 6, and day 11, including urinary mandelic acid (MA) and phenylglyoxylic acid (PGA), salivary malondialdehyde (MDA), comet assay parameters in peripheral blood lymphocytes, and micronucleus (MN) frequency in buccal cells. Measured styrene migration into beverages ranged from 3.3 to 7.1 μg/L, below the World Health Organization guideline value. Urinary metabolites and salivary MDA showed substantial interindividual variability and no consistent temporal pattern. In contrast, generalized estimating equation models showed progressive increases in comet assay indicators over the exposure period. Tail intensity and tail moment increased over time, with stronger changes among participants consuming two cups daily. MN frequency did not change significantly. These findings suggest that repeated short-term consumption of hot beverages in polystyrene cups was associated with modest changes in selected early biomarkers of biological effect under consumer-use conditions. The results should be interpreted cautiously in light of the modest sample size, short follow-up, and absence of more specific mechanistic endpoints, but they support further study of repeated low-level exposure to food-contact materials. Full article

Circadian desynchronization is increasingly linked to metabolic, immune, neurocognitive, and oncological disease, but integrated clinical phenotyping across endocrine, microbiome, metabolic, and neuroimaging domains remains limited. We conducted a prospective, single-centre, observational study in 179 symptomatic patients referred for chronic multisystem features consistent with circadian dysregulation and 107 practically healthy controls. Circadian melatonin status was assessed using fractionated 24 h urinary 6-sulfatoxymelatonin (aMT6s) and standardized dim-light plasma sampling at daytime (14:00–16:00) and nocturnal (02:00–04:00) windows. Microbiome composition was assessed by 16S rRNA sequencing, urolithin A by targeted metabolomics, and putative glymphatic/perivascular clearance by MRI-derived DTI-ALPS index, perivascular space scoring, and white-matter-hyperintensity (WMH) volumetry. Patients showed markedly reduced nocturnal melatonin output and loss of day–night contrast (night aMT6s 10.2 vs. 40.6 ng/mL; urinary aMT6s day/night ratio 0.81 vs. 0.14; plasma nocturnal melatonin 12.7 vs. 54.4 pg/mL; all p < 0.0001), accompanied by altered cortisol day–night patterning. Patients also showed reduced microbiome diversity, depletion of Gordonibacter and Ellagibacter, lower plasma urolithin A, higher WMH volume and perivascular space scores, and a lower DTI-ALPS index. Age distributions broadly overlapped in the individual-level dataset, and key biomarkers were not significantly correlated with chronological age within the patient cohort; however, this finding is interpreted as an exploratory absence of detectable age gradient within the symptomatic cohort, not as proof of biological age-independence. Overall, the data support a coherent cross-sectional association among blunted nocturnal melatonin rhythmicity, dysbiosis/urolithin depletion, and MRI markers compatible with impaired perivascular clearance. The MGM axis framework should be regarded as hypothesis-generating; causal direction, melatonin receptor involvement, and AQP4-related mechanisms require longitudinal and mechanistic validation. Full article

Silver Pomfret is increasingly threatened by many diseases under intensive artificial culturing conditions, yet conserved host biomarkers across different infections remain poorly defined. In this study, we integrated transcriptomic datasets from independent infections with Cryptocaryon irritans, Nocardia seriolae, and Photobacterium damselae subsp. damselae to identify shared host-response genes. By combining differential expression analysis with weighted gene co-expression network analysis, we prioritized six candidate genes associated with cross-pathogen infection responses. Random Forest and support vector machine analysis further supported their classification potential across the three infection models. Phylogenetic and structural analyses provided additional evidence for the conserved annotation of these proteins. GSVA-based signature analysis supported the cross-pathogen discriminatory capacity of the six-gene panel and suggested context-dependent contributions of individual genes across infection models. Immune signature analysis indicated distinct host immune response patterns under different pathogenic challenges, and candidate genes showed positive associations with inferred T cell-related signatures. Upstream regulatory prediction identified CTCF and the miR-17/20/93 family as potential regulators of these genes. Quantitative real-time PCR of the kidney further highlighted canx, rnd3, and angptl4 as the most robust infection-responsive candidates, with consistent temporal expression patterns observed from 0 to 24 h post-infection. These findings suggest a potential cross-pathogen host-response pattern in Silver Pomfret and provide preliminary support for future exploration of molecular markers for disease monitoring in aquaculture. Full article

Background/Objectives: Early progression (EP) occurs in a subset of patients with locally advanced pancreatic cancer (LAPC), limiting the clinical benefit of treatment, and it remains difficult to predict. Methods: We developed a multiparametric predictive model integrating baseline ¹⁸F-FDG PET/CT radiomic features with clinical and biological data. A total of 242 radiomic features were extracted from each imaging modality (CT and PET), including first-order, gray-level co-occurrence matrix (GLCM), and local binary pattern (LBP-TOP) features, and combined with PET-derived metrics and clinical variables. Model development included cross-validation procedures and rigorous feature selection, followed by the training of a two-level decision tree classifier. Results: The model achieved an accuracy of 80.7% and an area under the curve (AUC) of 0.83. Integrated analysis of CT and PET texture enabled the identification of patients at high risk of EP prior to treatment initiation. Conclusions: PET/CT-based radiomic biomarkers, combined with clinical data, can non-invasively capture tumor heterogeneity and improve risk stratification in LAPC, supporting more personalized therapeutic decision-making. Full article

Since the first approval of CTLA-4 blockade for melanoma, immune checkpoint inhibitors (ICIs) have expanded into a major class of cancer therapy, with more than 100 FDA-approved oncological indications across metastatic and earlier-stage disease settings, including use as monotherapy and in combination regimens. Preclinical research has largely focused on myocarditis and atherosclerosis, but a wider set of phenotypes, such as non-inflammatory left ventricular dysfunction (NILVD), arrhythmias, and vasculitis, can be observed, and they are rarely connected within a single mechanistic model. We aim to build a systems-oriented, mechanistic framework of the most widely studied biological processes; it will link the main checkpoint pathways to relevant cardiac and vascular cell types, molecular pathways, immune synapses, and candidate biomarkers. We searched PubMed, Scopus, and Web of Science using combinations of terms for immune checkpoint inhibition and cardiovascular-immune-related adverse events that provide mechanistic insight into cardiac-immune-related adverse reactions (irAEs). An AI-assisted semantic clustering approach was used only to organize the included literature. The integrated framework identifies PD-1/PD-L1 as the dominant mechanistic hub linking T-cell activation, endothelial recruitment, myocardial injury, and vascular inflammation. Across phenotypes, a shared immune core involving checkpoint pathways, cytokine signaling, and leukocyte trafficking coexists with phenotype-restricted mediators that may bias injury toward myocarditis, vascular inflammation, conduction-system disease, or NILVD. KEGG analyses support the enrichment of T-cell receptor signaling, Th17 differentiation, JAK-STAT signaling, cytokine–cytokine receptor interaction, and lipid and atherosclerosis pathways. Candidate biomarkers emerging from the reviewed literature include troponin, IL-6, CXCL9/CXCL10/CXCL13, S100A family proteins, ROCK2, HLA-linked susceptibility signals, and T-cell receptor clonality markers. The AI-assisted clustering broadly recapitulated the expert-defined thematic structure while identifying finer semantic neighborhoods within the literature. This framework provides a support map for further hypotheses about toxicity patterns with current and next-generation checkpoint strategies on the cardiac system, while AI-assisted clustering provides a complementary method for organizing the literature rather than an independent source of biological inference. Full article

Early diagnosis of AMI is crucial for improving patient outcomes, yet current clinical tools often lack the requisite sensitivity and specificity for reliable early detection. As neutrophils are the first innate immune responders mobilized following infarction, we employed an integrated multi-omics and machine learning approach to identify neutrophil-driven molecular signatures with diagnostic potential. By analyzing multiple peripheral blood transcriptomic datasets, we conducted differential expression and immune infiltration analyses, followed by machine learning-based feature selection to pinpoint key genes linked to neutrophil activity. Integration of these findings with single-cell transcriptomic data further clarified the neutrophil-specific expression patterns of candidate genes during AMI progression. Using a joint diagnostic model, we identified MCEMP1, NFE2, and AQP9 as the most informative predictors, with MCEMP1 emerging as the primary contributor. Experimental validation in a murine model of myocardial infarction (MI) confirmed rapid upregulation of MCEMP1 after injury, closely mirroring the kinetics of neutrophil infiltration. Collectively, these findings delineate a neutrophil-associated molecular profile of early AMI and highlight MCEMP1 as a promising noninvasive biomarker and a potential therapeutic target for modulating neutrophil-driven myocardial injury. Full article

Oxidative stress is an important component of cancer biology and is characterized by an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. Excess ROS can cause molecular damage and genomic instability; at the same time, ROS signaling remains necessary for normal cellular function. Redox homeostasis is of particular importance in this balance. The aim of this structured narrative review was to summarize and critically discuss current evidence on how dietary antioxidants influence redox-sensitive pathways involved in cancer prevention, with particular attention to metabolic inflammation, mitochondrial quality control, and gut microbiota-related mechanisms. We performed a structured literature search of Scopus, Web of Science, and PubMed, focusing on articles published between 2021 and 2026. The evidence covered major redox-sensitive pathways, including Nrf2-Keap1-ARE signaling, AMPK-mTOR regulation, NF-κB-mediated inflammation, mitochondrial quality control (autophagy and mitophagy), and inflammasome activation. These pathways, which are involved in tumor initiation and progression, link oxidative stress to metabolic and inflammatory processes. Current evidence suggests that dietary antioxidants act primarily by supporting endogenous defense systems. This may help explain the “antioxidant paradox”, in which antioxidant-rich dietary patterns are associated with a lower risk of cancer. In some studies, high-dose supplementation with isolated antioxidants has produced inconsistent or sometimes adverse results. These effects depend on dose, chemical form, metabolic context, and baseline redox state. The gut microbiota is also an important mediator of antioxidant bioactivity; by converting dietary polyphenols into bioactive metabolites, it can influence systemic redox balance and metabolic signaling. This microbiota-dependent modulation may partially explain inter-individual variability in responses to dietary interventions. In conclusion, dietary antioxidants should be considered as modulators of redox-sensitive signaling networks, not merely as simple radical scavengers. Personalized modulation of redox homeostasis is a future strategy for cancer prevention, with a greater emphasis on whole-diet and biomarker-guided approaches. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) comprises biologically heterogeneous tumors, primarily lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), which differ in genomic landscape and clinical behavior. The tumor suppressor PTEN is a key negative regulator of the PI3K/AKT/mTOR pathway and is frequently inactivated in NSCLC through genetic and non-genetic mechanisms. Although reduced PTEN expression has been associated with poor outcomes in lung cancer, its prognostic relevance across these histological subtypes remains unclear. Methods: Here, we investigated the prognostic significance of PTEN in NSCLC subtypes using a multi-level approach combining protein, transcriptomic, and genomic analyses. PTEN protein expression was evaluated by immunohistochemistry in a tissue microarray from resected NSCLC patients, and findings were validated using publicly available datasets including TCGA-RPPA, GEO/EGA-based transcriptomic cohorts, and large genomic resources. In parallel, mutational landscapes and co-mutation patterns were analyzed in several independent datasets, and tumor immune microenvironment composition was inferred using CIBERSORT deconvolution analysis. Results: Low PTEN protein and mRNA levels, as well as PTEN mutations, were consistently associated with significantly worse overall survival (OS) in LUAD but not in LUSC. Multivariable Cox regression analysis confirmed PTEN as an independent prognostic factor in LUAD. Although PTEN mutations were more frequent in LUSC, they showed no prognostic value in this subtype. Co-mutation analyses revealed recurrent PTEN partnerships with TP53, EGFR, and APC in LUAD, with PTEN-TP53 co-alterations enriched in metastatic disease. Immune deconvolution demonstrated that PTEN-low LUAD tumors were characterized by an immunosuppressive microenvironment, including increased T regulatory cells and reduced inflammatory immune populations. Notably, increased M2-like macrophages were associated with shorter OS in PTEN-low LUADs, whereas a high number of total macrophages (CD68+ cells) emerged as an independent predictor of more favorable OS. Conclusions: Collectively, these results identify PTEN loss as a subtype-specific prognostic biomarker in LUAD and link its deficiency to immunosuppressive tumor microenvironment remodeling. Full article

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a major cause of cancer death. Zinc finger proteins (ZNFs) have been implicated in LUAD progression, functioning either as oncogenes or tumor suppressors. Therefore, an in-depth investigation of ZNFs may contribute to the development of novel diagnostic and therapeutic strategies for LUAD. Methods: Transcriptomic and clinical data were obtained from the TCGA and GEO databases. Prognosis-related ZNF genes were identified using univariate Cox, LASSO, and multivariate Cox regression analyses. An eight-gene ZNF-based prognostic signature was constructed and validated in two independent external cohorts (GSE50081 and GSE26939). A nomogram integrating independent prognostic factors was developed. Immune infiltration, somatic mutation profiles, and drug sensitivity were systematically analyzed. We further focused on FGD3, a key gene from the signature, examining its expression in LUAD cells and tissues, including lorlatinib-resistant models. Results: The prognostic signature comprising TRIM6, TRIM29, CTCFL, FGD3, GATA4, CASZ1, TRAF2, and ZNF322 effectively stratified patients into distinct risk groups with significantly different overall survival (p < 0.05). The risk score, together with T and N stage, served as independent prognostic predictors (n = 500, p < 0.05). High-risk patients exhibited an immune-desert phenotype, increased tumor mutational burden, and distinct drug sensitivity patterns. Notably, FGD3 expression was downregulated in LUAD tissues (n = 14, p < 0.0001) and lorlatinib-resistant cells, and its restoration suppressed resistant cell proliferation and partially reversed drug resistance. Conclusions: This study establishes a promising ZNF-based prognostic model for LUAD, providing a potential tool for risk stratification and individualized therapeutic decision-making. The identification of FGD3 as a potential mediator of drug resistance highlights its promise as a candidate biomarker and therapeutic target in LUAD. Full article

The gut–heart axis plays a role in cardiac injury due to the disruption of barriers, endotoxemia, and inflammatory signaling; yet, it is not clear whether sodium butyrate (SB) is capable of alleviating isoprenaline-induced myocardial injury through coordinated intestinal, microbial, and metabolic restoration. This study used male Sprague-Dawley rats, which were grouped into control, control + SB, isoprenaline (ISO)-induced myocardial injury, and ISO + SB groups. We evaluated cardiac biomarkers of injury, oxidative stress, histopathologic, intestinal barrier (16S rRNA sequencing), and serum metabolomics (LC-MS). SB treatment decreased serum cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase; relieved oxidative stress; and lowered myocardial necrosis and fibrosis. It re-established colonic architecture, upregulated the expression of ZO-1 (zonula occludens-1) and claudin-1, and reduced endotoxin in the bloodstream. SB also prevented the production of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β; cardiac TLR4; IκBα degradation; and NF-κB p 65 phosphorylation. In addition, SB altered the gut microbiota in favor of beneficial commensals, including Ligilactobacillus and Bifidobacterium, and reduced Desulfovibrio. It normalized key circulating metabolites and enriched cardiometabolic pathways, and the patterns of correlation suggested the coordinated remodeling of the microbiome–metabolome. These findings reveal that SB prevents myocardial injury caused by ISO through strengthening gut barrier protection, alleviating endotoxemia, inhibiting TLR4/NF-κB, and remodeling the microbiome–metabolome axis, indicating its potential for use as a gut-targeted cardioprotective intervention. Full article

(1) Background: Metabolic disorders, including hypertension, hyperlipidemia, and hyperglycemia (HHH), rank at the top of the disease burden in China. However, population-level assessment of pharmacological treatment remains limited by the lack of scalable metrics for monitoring medication use and outcomes. (2) Methods: We pioneered the use of standardized combined “HHH” medication usage—encompassing antihypertensive, antidiabetic, and lipid-lowering agents—as an integrated proxy for evaluating interventions for cardiovascular diseases and diabetes. Leveraging wastewater-based epidemiology (WBE), we quantified HHH medication loads (mg/d/1000 persons) across 30 prefectures covering all regions in China, and mapped the associated geographical disparities using independent t-tests. Associations with environmental, socioeconomic, demographic, social service, and health-related behavioral and lifestyle factors were further examined via correlation analysis. (3) Results: Our findings confirmed a pronounced north–south gradient in HHH medication uses (the mean standardized loads in the north were approximately twice as high as those in the south, p < 0.05). Furthermore, aging, sex ratio, nicotine consumption, obesity rate, the comprehensive Air Quality Index (AQI), precipitation and the Urban Wellness and Healthcare Index were identified as the top seven influencing factors (|r| values ranging from 0.37 to 0.71, all p < 0.05). (4) Conclusions: As a comprehensive national-scale analysis of multi-drug use for HHH via WBE, this study provides valuable insights into national multi-disease pharmacological treatment, offering evidence-based support for refining clinical prescribing guidelines and rationalizing the allocation of healthcare resources. Full article

Background: Breast cancer is the most prevalent malignant disease among women. Here, we investigate whether there is an association between disease recurrence in breast cancer patients and the quantitative methylation pattern of seven genes of different DNA repair pathways. Methods: Clinical and pathological data from 30 patients treated for sporadic breast cancer were selected according to the following inclusion criteria: follow-up of 5 years, adjuvant chemotherapy and recurrence. Histopathology was verified, and genomic DNA was accessed by tumor cryosectioning. We also determined the methylation levels of seven DNA repair genes (BRCA1, BRCA2, XRCC1, PARP1, ERCC4, MGMT, and XPC). Results: Patients without recurrence demonstrated a higher index of positive progesterone receptor status compared to patients with recurrence (p = 0.025). All other clinical characteristics of the patients did not differ between the groups. BRCA1 and BRCA2 genes showed methylation, and there was a higher level of BRCA1 gene methylation in patients without recurrence. BRCA1 methylation was not associated with the clinical characteristics of patients. All other genes analyzed showed no difference in methylation between patients with and without recurrence. Conclusions: We showed that sporadic breast cancer patients with a lower incidence of recurrence demonstrate a higher level of BRCA1 gene methylation after 5 years of follow-up, suggesting its role as a predictive biomarker. Full article

Background/Objectives: Evidence-based nutritional recommendations for obesity management require understanding of sex-specific and age-specific body composition patterns and their associations with metabolic biomarkers, habitual dietary intake and chronic low-grade inflammation. This study aimed to characterize body composition phenotypes in a large clinical cohort of adults with obesity, to evaluate associated metabolic and inflammatory biomarker patterns, to contextualise these patterns against habitual nutrient intake assessed in a dietary subcohort, and to derive age- and sex-specific nutritional recommendations based on the identified patterns. Methods: We performed a cross-sectional analysis of 29,544 adults with obesity (BMI ≥ 30; 21,374 women, 8170 men; age 30–69) who underwent multi-frequency bioelectrical impedance analysis (BIA; InBody 770). Biochemical assessments (fasting glucose, lipid profile, uric acid, HbA1c, insulin) were available for 2019 hospitalized patients from the same population. Habitual dietary intake was quantitatively assessed in a dietary subcohort of 423 patients using the validated Russian software-based questionnaire “Scientific Nutrition Analysis Tool”. Inflammatory biomarkers (high-sensitivity CRP, IL-6) and adipokines (leptin, adiponectin) together with serum 25(OH)D were measured in an inflammation/adipokine subcohort of 116 patients. A body composition phenotype with low relative muscle mass and high visceral fat (VFA ≥ 100 cm²) was defined using FNIH criteria (ALM/BMI < 0.789 men, <0.512 women). Benjamini–Hochberg FDR correction (q < 0.05) was applied for multiple comparisons. Results: The body composition phenotype prevalence increased progressively with age: men 24.6% (30–39) to 42.0% (60–69); women 10.3% (30–39) to 31.8% (60–69). Skeletal muscle mass (SMM) was positively associated with uric acid (r = +0.347, p < 0.001, FDR q < 0.05) and inversely associated with HDL-cholesterol (r = −0.321, p < 0.001, FDR q < 0.05)—both associations with direct nutritional implications. BMI was associated with fasting insulin (r = +0.233, p < 0.001, FDR q < 0.05). Women showed significant age-related metabolic differences between the 30–39 and 60–69 age groups: fasting glucose +12.9%, triglycerides +34.8%, uric acid +15.0% (all p < 0.001); in men, significant differences were observed for fasting glucose (+7.0%) and HbA1c (+5.2%) (both p < 0.001), while lipid parameters did not reach significance. In the dietary subcohort, habitual saturated-fat intake exceeded recommended values in 70–72% of patients of both sexes, dietary fibre intake was below recommended levels in 73–85%, and habitual calcium intake decreased significantly with age in women (1022 → 746 mg/day, p = 0.028). Serum CRP was elevated (median 5.59 mg/L, n = 59). In a separate extended laboratory subcohort, serum oestradiol declined markedly with age in women (55.0 → 16.8 pmol/L between 30–39 and 50–59 years, p < 0.001), consistent with the menopausal transition; serum testosterone in men remained stable across age groups; and 25(OH)D insufficiency (<30 ng/mL) was prevalent in 49.7–55.8% of patients. Conclusions: The identified sex-specific and age-specific body composition patterns provide a rationale, supported by observed dietary and inflammatory patterns, for targeted nutritional intervention: increased dietary protein, omega-3 fatty acids supplementation, low-glycemic-index dietary patterns, and purine restriction with hyperuricemia. Routine BIA-based nutritional screening combined with quantitative dietary assessment should begin at age 30, with preventive monitoring at age 40 and intensification of control at age 50, to guide personalized dietary planning in obesity. Full article

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; BMI < 25 = 64) from the Michigan Mother–Infant Pair cohort were profiled to assess how BMI influences urinary exposomes and related biological responses. A validated approach measured 96 chemicals and biomarkers of oxidative stress and glucocorticoids. Women in both groups reported similar lifestyles and consumer product use. Women with high BMI had lower urinary concentrations of several chemicals than women with low BMI. Phytoestrogens, polycyclic aromatic hydrocarbons, and insect repellants showed a higher magnitude of positive associations with other markers of exposure, oxidative and glucocorticoid stress in the high-BMI group, while UV filters, flame retardants, and phthalates showed a higher magnitude of positive associations with oxidative stress markers in the low-BMI group. The patterns of associations of exposure markers with stress markers and pregnancy outcomes (gestational age and birthweight) differed by maternal BMI. This highlights the importance of incorporating maternal BMI into the evaluation of exposure burden and its effects, as a factor that may actively shape biological responses. Full article

Wearable sensors enable continuous recording of electrocardiographic, photoplethysmographic, and inertial signals and have accelerated the development of digital biomarkers in cardiovascular medicine. Transthyretin amyloidosis (ATTR) is a progressive multisystem disease characterized by arrhythmia, conduction disturbances, hemodynamic impairment, autonomic dysfunction, and gait abnormalities, making it theoretically suitable for multimodal wearable monitoring. This review summarizes current knowledge on wearable applications in amyloidosis with ATTR serving as an illustrative case, evaluates the plausibility of extrapolating signal-based biomarkers from related cardiovascular and neurological cohorts, and outlines methodological and implementation challenges. ATTR-specific data remain limited to small observational studies, mainly on long-term rhythm monitoring and supervised functional assessment. More comprehensive findings support the extraction of metrics such as atrial fibrillation burden, activity patterns, gait variability, and heart rate variability. However, ATTR-related structural remodeling and high arrhythmia burden may distort conventional digital biomarkers, necessitating disease-specific preprocessing and prospective validation. Wearable monitoring in ATTR is technically feasible and biologically plausible but remains investigational. Before routine integration into care pathways can be recommended, standardized, phenotype-stratified studies are needed that link wearable-derived characteristics to assessed clinical outcomes. Full article