Search Results (918)

Background/Objectives: Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants resulting from the extensive production, use, and degradation of plastic materials. Human exposure occurs primarily through contaminated food and drinking water, with inhalation representing an additional important route. Growing concern has focused on the ability of these particles, particularly NPs, to cross biological barriers, enter the systemic circulation, and reach human tissues. The aim of this review was to summarize current evidence on dietary exposure to MPs and NPs, their gastrointestinal bioavailability and toxicokinetics, and their potential systemic health effects, with particular emphasis on organ-specific responses, underlying biological mechanisms, and the strength and limitations of the available evidence. Methods: A comprehensive narrative review of the scientific literature published between 2000 and 2026 was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles and review papers addressing dietary exposure, occurrence in food and drinking water, migration from food-contact materials, gastrointestinal absorption, translocation, biodistribution, bioaccumulation, elimination, molecular mechanisms, and potential organ-specific or systemic health effects were included. Publications without full-text availability, conference proceedings, editorials, commentaries, duplicate publications, and studies without relevance to human exposure or health were excluded. Results: Food, drinking water, beverages, and food-contact materials represent important sources of human exposure to MPs and NPs. Following ingestion, most larger particles are eliminated through the gastrointestinal tract, whereas smaller MPs and particularly NPs may cross biological barriers and potentially reach the systemic circulation and distant tissues. Experimental studies consistently identify interconnected biological responses involving oxidative stress, inflammation, mitochondrial dysfunction, barrier impairment, immune dysregulation, genotoxicity, apoptosis, and endocrine disruption. These mechanisms have been associated with alterations in the gastrointestinal, respiratory, cardiovascular, nervous, urinary, reproductive, endocrine, and skeletal systems and with biological processes relevant to carcinogenesis. However, most mechanistic evidence derives from in vitro and animal models, whereas human evidence remains limited and predominantly observational. Consequently, the extent to which these experimental findings translate into clinically significant effects in humans remains uncertain. Conclusions: Current evidence supports the biological plausibility of systemic effects associated with MNP exposure but is insufficient to establish causal relationships between chronic dietary exposure and specific human diseases. The detection of MNPs in human tissues and reported associations with pathological conditions should therefore be interpreted cautiously. Standardized analytical methods, improved characterization of realistic human exposure, and well-designed longitudinal epidemiological studies integrating quantitative exposure assessment with validated clinical outcomes are required to clarify dose–response relationships, long-term health effects, and the clinical significance of MNP exposure. Full article

Background: Eosinophilic esophagitis (EoE) is a chronic type 2 immune-mediated esophageal disease defined by esophageal dysfunction and eosinophil-predominant inflammation. Beyond classic gastrointestinal symptoms, patients may present with aerodigestive complaints such as chronic cough, hoarseness, recurrent croup, stridor, vocal fold abnormalities, and subglottic stenosis, creating diagnostic overlap with laryngopharyngeal reflux, vocal fold dysfunction, asthma, allergic rhinitis, and other airway disorders. Methods: This scoping review mapped evidence on the relationship between EoE and laryngeal manifestations. PubMed/MEDLINE was searched using terms related to EoE, laryngeal disease, reflux, vocal fold pathology, and subglottic stenosis. Human English-language case reports, case series, observational studies, clinical trials, and reviews were narratively charted by study design, population, diagnostic criteria, laryngeal findings, reflux evaluation, treatment, and outcomes. Results: Laryngeal involvement in EoE appears clinically relevant but remains incompletely characterized. Direct eosinophilic infiltration of laryngeal or hypopharyngeal tissue is rare, whereas indirect mechanisms—including shared type 2 inflammation, epithelial barrier dysfunction, eosinophil and mast-cell mediators, reflux or microaspiration, and comorbid atopic airway disease—may contribute to symptoms and lesions. Pediatric patients may be especially likely to show airway-predominant presentations, including recurrent croup, chronic cough, and subglottic stenosis. Evidence is limited by heterogeneous definitions, inconsistent laryngoscopy or biopsy, variable reflux testing, and small observational reports. Conclusions: EoE should be considered in persistent or recurrent laryngeal symptoms, particularly when refractory to reflux or airway-directed therapy or associated with atopy. Multidisciplinary evaluation may improve recognition and management. Future studies should use standardized laryngeal assessment, pediatric case–control designs, and biomarker approaches linking EoE activity with objective laryngeal findings. Full article

Parturient paresis remains a major economic challenge in global ruminant production, causing acute periparturient hypocalcemia and predisposing high-yielding animals to a cluster of secondary pathologies. Traditional narratives often treat regulatory pathways in isolation, whereas this review synthesizes multi-organ endocrine networks to address the kinetic dyssynchrony between mammary calcium drain and homeostatic recruitment velocity. Beyond the classical parathyroid hormone–vitamin D axis, we integrate the mammary–gut–bone axis into a unified endocrine model, highlighting the critical role of the serotonin–parathyroid hormone-related protein rheostat for skeletal mineral mobilization and the fibroblast growth factor 23–Klotho axis in prepartum phosphorus-induced feedback suppression. We evaluate the molecular mechanisms underlying target-organ receptor resistance, driven by vitamin D receptor downregulation and epigenetic aging, which precipitate homeostatic feedback failure. Regarding clinical management, this synthesis contrasts reactive parenteral interventions with proactive nutritional priming strategies, such as negative dietary cation–anion difference acidification, zeolite-based gastrointestinal binders, and exogenous vitamin D or 5-hydroxytryptophan supplementation. Additionally, the role of microbiota-derived short-chain fatty acids in gut-bone communication and the potential of genomic selection to breed livestock with heritable metabolic resilience are explored. Ultimately, this comprehensive framework emphasizes a paradigm shift from emergency treatment to precision nutritional and genetic prophylaxis to mitigate PP across diverse ruminant species. Full article

Punica granatum L. (pomegranate) is one of the oldest medicinal plants known to humankind, valued across ancient civilisations for treating parasitic, microbial, and metabolic diseases. Its exceptionally rich phytochemical composition, dominated by punicalagins, ellagic acid, anthocyanins, flavonoids, piperidine alkaloids, and the unique conjugated fatty acid punicic acid, confers a remarkably broad spectrum of biological activities of direct relevance to contemporary veterinary medicine. While human-health applications have been extensively reviewed, a comprehensive synthesis of veterinary evidence across multiple species remains lacking. This review consolidates current preclinical and field knowledge on the pharmacological effects of pomegranate preparations in poultry, ruminants, swine, fish, companion animals, and laboratory models. In poultry—the most extensively studied taxon—dietary inclusion of pomegranate peel powder or extract consistently enhances growth performance, antioxidant status, and humoral immunity while exerting meaningful anticoccidial activity. The antiparasitic properties are compellingly supported by evidence against gastrointestinal nematodes of ruminants, tapeworms, schistosomes, and protozoa including Giardia, Cryptosporidium, and Leishmania spp., as well as monogenean fish parasites. Broad-spectrum antimicrobial activity extends to major veterinary pathogens such as Salmonella, Escherichia coli, Staphylococcus aureus (including MRSA), and Clostridium perfringens. Rodent models have validated antidiabetic, hepatoprotective, nephroprotective, and reproductive benefits, including improved post-thaw sperm quality and enhanced litter size. The safety profile is generally favourable at conventional doses, although high dietary inclusion elicits anti-nutritional effects from condensed tannins, and potential drug interactions via cytochrome P450 inhibition warrant clinical caution. Despite this substantial evidence, significant translational barriers persist, including extract heterogeneity, absence of pharmacokinetic data in target species, and scarcity of controlled clinical trials. By providing a species- and pathology-driven synthesis, this review identifies critical research priorities and highlights the immense potential of this ancient, accessible, and economically viable phytobiotic as a natural alternative to antibiotic growth promoters and synthetic antiparasitics in veterinary practice. Full article

Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for detecting minimal residual disease (MRD) and predicting recurrence after curative treatment, yet evidence in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cancer has largely been examined within individual tumor types. In this scoping review, we mapped this evidence across all three malignancies and clarified key methodological and clinical considerations. Following the PRISMA-ScR guidelines, we searched PubMed, Scopus, and the Cochrane Library (3 April 2026) for studies linking ctDNA to disease-free, recurrence-free, or overall survival after curative-intent treatment. Twenty-seven studies (1746 patients; 10 ESCC, 4 EAC, 8 gastric, and 5 mixed) were included. Across every tumor type, postoperative ctDNA MRD was the most informative timepoint, with independent multivariable hazard ratios for disease-free, recurrence-free, or event-free survival of 2.8 to 21.8, whereas preoperative ctDNA was seldom prognostic. Serial monitoring further improved performance and flagged recurrence 78 to 278 days before imaging. Tumor-informed assays showed higher sensitivity than tumor-agnostic ones (80% vs. 35%), though direct comparisons were limited; correction for clonal hematopoiesis was essential for tumor-agnostic assays, and blood-based assays performed poorly in diffuse-type and peritoneal disease. Postoperative ctDNA MRD is a consistent, independent prognostic biomarker across upper gastrointestinal cancers that adds prognostic information beyond conventional staging and pathological response, supporting prospective interventional trials of ctDNA-guided management. Full article

Parkinson’s disease (PD) is a multisystem disorder in which gastrointestinal dysfunction often precedes motor symptoms, yet the molecular links between peripheral stress and central neurodegeneration remain unclear. We investigated whether genes commonly dysregulated in PD and a classic model of intestinal inflammation (IBD) might reveal conserved stress-responsive molecules relevant to brain pathology. Shared gene signatures between PD and inflammatory bowel disease (IBD) were identified from peripheral blood transcriptomes using weighted gene co-expression network analysis (WGCNA). Hub genes were prioritized via protein–protein interaction (PPI) analysis and evaluated for expression consistency in independent brain tissue transcriptomic datasets. Single-cell RNA sequencing (scRNA-seq) of the PD substantia nigra was used to define the cellular context of the key hub gene, and CellChat analysis assessed intercellular communication changes. Immunofluorescence validation was performed in an MPTP-induced PD mouse model. We identified 79 shared genes and 6 hub genes, among which only HSP90AA1 showed consistent upregulation across independent PD transcriptomic validation datasets. Functional enrichment highlighted inflammation-related pathways. Because peripheral immune infiltration showed only minor changes, we further investigated the cellular context of HSP90AA1 within the PD brain. ScRNA-seq analysis of the PD substantia nigra demonstrated that HSP90AA1 was expressed across multiple cell populations. Integration with transcriptional regulatory analysis identified TP53 as a potential upstream regulator, and the strongest TP53–HSP90AA1 co-expression and cellular colocalization signals were observed in astrocytes, prompting further astrocyte-focused investigation. CellChat analysis revealed altered intercellular communication patterns in PD substantia nigra, including changes in synapse-associated ligand–receptor interaction signatures, particularly involving NCAM-related pathways. In the MPTP-induced PD mouse model, immunofluorescence identified astrocytic HSP90α upregulation, and increased nuclear p53 signal in astrocytes, accompanied by dopaminergic neuron loss. Conclusion: Astrocytic upregulation of HSP90AA1 is associated with altered synapse-related intercellular communication patterns in the PD substantia nigra, potentially involving a predicted TP53 associated regulatory component. These findings, validated in an MPTP mouse model, identify HSP90AA1 as a candidate stress-responsive hub linking peripheral inflammatory states with astrocyte-associated molecular alterations in PD, providing a framework for further experimental investigation. Full article

Background: In phenylketonuria (PKU), the lifelong phenylalanine (Phe)-restricted diet may contribute to altered feeding behaviours and disordered eating. The true prevalence of disordered eating and eating disorders remains uncertain, partly because validated PKU-specific assessment tools are lacking. This systematic review aimed to identify, appraise, and synthesise the evidence on disordered eating and eating disorders in PKU. Methods: Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane) were searched from inception to 24 February 2026. English-language studies reporting disordered eating or eating disorders in early-diagnosed individuals with PKU managed with a Phe-restricted diet, with or without drug therapy, were included. Studies of late- or never-treated patients, pregnancy, lactation, reviews, and preclinical studies were excluded. Two independent reviewers conducted study selection and data extraction. Outcomes included the prevalence of eating disorders, disordered eating behaviours and attitudes, associated factors, and the influence of drug treatment. Findings were synthesised qualitatively, and risk of bias was assessed using the NIH Study Quality Assessment Tools. Results: Twenty-four studies (2928 individuals with PKU) met the inclusion criteria. Most were observational or survey-based. Eating disorders were reported more frequently in PKU (3–13%) than in the general population (n = 4 studies). Common disordered eating features included food neophobia (n = 5 studies), limited food variety (n = 9), food aversion or refusal (n = 5), poor appetite (n = 5), prolonged mealtimes (n = 3), negative parent–child mealtime interactions (n = 6), and specific taste preferences (n = 5). Delayed feeding skill development (n = 6 studies), reduced social eating (n = 6), gastrointestinal symptoms (n = 8), and psychological or neurodevelopmental difficulties (n = 7) were also associated with disordered eating. Early feeding difficulties frequently persisted into adulthood, and longstanding eating behaviours did not consistently improve with pharmaceutical treatment (n = 6 studies). Most studies were rated as fair quality (19/24), with common limitations including small sample sizes, lack of sample-size justification, non-validated assessment tools, and absence of randomised controlled trials. Conclusions: Current evidence suggests that people with PKU experience a greater burden of eating-related difficulties than the general population, although robust estimates of eating disorder prevalence remain lacking. Existing screening tools may misclassify treatment-related dietary behaviours as pathological or fail to identify PKU-specific eating concerns. Development of PKU-specific screening tools could support routine clinical discussions about eating behaviours and the psychosocial impact of dietary treatment, facilitating earlier identification of individuals requiring specialist eating disorder assessment. (Prospero registration: CRD42024539600). Full article

Histamine plays an essential role in gastrointestinal physiology and immune control, while its balance in the intestinal environment is largely maintained through degradation by diamine oxidase (DAO), a copper-dependent enzyme mainly produced by differentiated enterocytes. Impaired DAO activity reduces the intestinal barrier to luminal histamine, leading to increased local and systemic exposure and contributing to altered motility, permeability, visceral sensitivity, and immune activation. Accumulating research suggests that disturbances in diamine oxidase regulation contribute to the development of various gastrointestinal diseases, including histamine intolerance, inflammatory and functional bowel disorders, intestinal ischemia, and liver pathology. This review summarizes current knowledge on the biochemistry, localization, and regulation of DAO, as well as histamine signalling via H1–H4 receptors in the gastrointestinal tract. We highlight the interaction between epithelial injury, immune activation, dysbiosis, and histamine accumulation, and discuss the divergent interpretation of mucosal versus circulating DAO activity. Finally, we critically assess the diagnostic limitations of serum DAO and explore emerging therapeutic strategies targeting impaired histamine degradation. Although DAO represents a promising adjunctive biomarker and therapeutic target, its clinical utility requires standardized measurement methods and integrative diagnostic approaches. Full article

Artificial intelligence (AI) has emerged as a promising tool for inferring molecular biomarkers directly from digitized histopathologic slides. However, the current evidence in gastrointestinal and hepatobiliary cancers remains fragmented across tumor types and biomarker categories. Relevant studies were systematically identified and screened according to the PRISMA 2020 statement. PubMed, Embase, Web of Science Core Collection, Scopus, and IEEE Xplore were searched from 1 January 2015 to the date of search. Eligible studies involved gastrointestinal or hepatobiliary malignancies, used histopathology images, applied AI-based methods, and reported molecular biomarker prediction or inference. A total of 110 studies were included. Most studies focused on colorectal, gastric, liver, and pancreatic cancers, with microsatellite instability, mutation status, molecular subtypes, and tumor mutational burden being the most commonly investigated targets. Model architectures evolved from conventional convolutional neural networks to multiple-instance learning and transformer-based methods. While many studies reported promising predictive performance, direct comparison across studies remained challenging because of substantial heterogeneity in datasets, model architectures, and validation strategies. AI-based molecular biomarker identification from pathologic slides shows substantial promise in gastrointestinal and hepatobiliary cancers, but current evidence is constrained by heterogeneity and limited validation. Standardized, multicenter studies are needed before routine clinical implementation. Full article

As modern competitive sports continue to evolve, athletes are under increasing pressure to optimize both performance and recovery. Sports supplements have therefore become widely used among athletes because of their purported benefits in enhancing athletic performance, delaying fatigue, and accelerating physiological recovery. However, misuse, excessive intake, and other inappropriate patterns of supplement use remain common in some athletes and may impair performance, compromise health, and increase the risk of anti-doping rule violations. Although existing research has largely focused on the ergogenic benefits of sports supplements, their potential health risks in athletes remain insufficiently characterized. This review summarizes the potential adverse effects of sports supplements on the endocrine, cardiovascular, and gastrointestinal systems, with an emphasis on the underlying pathological mechanisms, thereby providing a theoretical basis for the evidence-based selection and responsible use of sports supplements in athletic populations. Full article

The clinical translation of nucleic acids is severely hindered by multiple delivery barriers, such as enzymatic degradation, poor cellular uptake, endosomal entrapment, and rapid systemic clearance. Despite the remarkable therapeutic potential of these agents, conventional delivery systems often fail to address these challenges. Lipid nanoparticles (LNPs) have emerged as a versatile platform to overcome these obstacles, offering tunable physicochemical properties, high encapsulation efficiency, and pH-responsive endosomal escape. This review summarizes recent advances in LNP-based respiratory and gastrointestinal mucosal delivery of nucleic acids, with emphasis on formulation strategies for overcoming mucus and epithelial barriers. To overcome mucosal barriers, LNP studies have shown that keeping particle size below the local mucus mesh size (~100 nm), tuning surface charge toward near-neutrality via pH-responsive ionizable lipids, and maintaining a neutral, deformable, moderately PEGylated surface during the mucin transport stage can increase transmucosal diffusivity several-fold over conventional cationic LNPs. We further discuss current limitations and propose future directions, emphasizing the need for the integration of the pathological and physiological characteristics of specific mucosa with artificial intelligence (AI) platforms to develop intelligent and personalized delivery platforms with “spatiotemporal adaptive” capabilities. Full article

Ewing sarcoma is a highly malignant tumor whose histological appearance often overlaps with that of other undifferentiated round-cell and ovoid-cell tumors, making accurate diagnosis challenging. Selecting the most appropriate immunohistochemical and molecular tests is critical, particularly when only limited core biopsy material is available and tissue preservation for additional molecular or biomarker testing is required. Artificial intelligence (AI)-based histopathological image analysis is emerging as a promising diagnostic tool in oncology. This study evaluated the potential of AI-based histopathological analysis to assist pathologists in the morphologic classification of Ewing sarcoma and selected histological mimics using tissue microarrays (TMAs), rather than to identify or predict molecular alterations. We analyzed 1926 digitized histological cores, from 729 patients, assembled into 45 tissue microarrays. The dataset comprised 517 Ewing sarcomas (ESs), 367 rhabdomyosarcomas (RMSs), 187 chondrosarcomas (CHSs), 138 gastrointestinal stromal tumors (GISTs), and 124 synovial sarcomas (SSs). A weakly supervised multiple-instance learning (MIL) framework with transformer-based aggregation was developed using only core-level diagnostic labels. The model achieved classification accuracies of 97.1% for Ewing sarcoma, 80.0% for rhabdomyosarcoma, 85.7% for gastrointestinal stromal tumors, 80.0% for chondrosarcoma, and 76.0% for synovial sarcoma. The overall classification accuracy was 91.6%, with no misclassifications between Ewing sarcoma and rhabdomyosarcoma. These findings highlight the model’s robustness in distinguishing tumor entities that present a well-recognized diagnostic challenge in routine pathology. The AI algorithm demonstrated strong potential as a diagnostic adjunct for assisting pathologists in the morphologic classification of Ewing sarcoma and selected tumor entities based on histopathological features. Although these tumor entities are characterized by specific molecular alterations, the model was not designed to identify or predict molecular alterations directly. Instead, it supports clinical decision-making by recognizing morphologic patterns associated with diagnostically defined tumor entities. The integration of AI-based histopathological analysis with immunohistochemistry and contemporary molecular diagnostic techniques has the potential to improve diagnostic accuracy, optimize the use of ancillary testing, enhance our understanding of genotype–phenotype relationships, and ultimately support more effective patient management. Full article

Proteus mirabilis, a member of the family Enterobacteriaceae, is widely distributed in the environment and commonly colonizes the gastrointestinal tract of animals. Although traditionally regarded as an opportunistic zoonotic pathogen, increasing evidence suggests that it may also contribute to bovine diseases. However, information regarding the antimicrobial resistance, virulence determinants, and genomic characteristics of bovine-associated P. mirabilis in China remains limited. In this study, a P. mirabilis strain, designated A3, was isolated from one of 19 diarrheic adult beef cattle sampled in Anhui Province, China, and comprehensively characterized through phenotypic, genomic, and pathogenicity analyses. Strain A3 exhibited typical swarming motility and a multidrug-resistant phenotype. PCR screening identified the resistance genes aac(6′)-Ib and qnrA, together with seven virulence genes (pmfA, atfA, ureC, mrpA, ucaA, zapA, and atfC) involved in adhesion and colonization. Whole-genome sequencing generated a 3,965,086 bp draft genome with a GC content of 38.37% and identified 85 resistance-associated genes and 147 virulence-associated genes, including multidrug efflux pumps and virulence factors related to adhesion, motility, iron acquisition, secretion systems, and host interaction. Comparative genomic analysis demonstrated high genomic similarity to other bovine-derived P. mirabilis isolates, with average nucleotide identity (ANI) values ranging from 99.06% to 99.32%, while pangenome analysis identified 5680 orthologous gene clusters, including 2959 core genes, indicating an open pangenome structure. Multiple insertion sequences, prophages, and genomic islands were identified, highlighting substantial genomic plasticity and adaptive potential. In a mouse infection model, strain A3 exhibited clear dose-dependent pathogenicity. All eight mice challenged with 2.22 × 10⁹ CFU/mL died within 12 h post-infection and developed severe pathological lesions in multiple organs, whereas only one of eight mice in the low-dose group died during the same period. Collectively, these findings indicate that bovine-derived P. mirabilis A3 combines multidrug resistance, genomic plasticity, and opportunistic pathogenic potential. This study expands current knowledge of bovine-associated P. mirabilis and provides a genomic and experimental basis for surveillance, risk assessment, and prevention strategies in cattle production systems. Full article

Background: The Braak hypothesis proposes that α-synuclein (α-syn) pathology may originate in the gastrointestinal tract and propagate to the central nervous system along the gut–brain axis; however, the precise propagation routes and the factors influencing this process remain controversial. Methods: A gut-originating Parkinson’s disease model was established by injecting α-syn preformed fibrils (PFF) into the duodenal muscularis of C57BL/6J and A53T transgenic mice. Phosphorylated α-synuclein (p-α-syn) pathology, motor behavior, and gut microbiota were assessed, with truncal vagotomy included to evaluate its association with gut-to-brain propagation. Results: In C57BL/6J mice, at 4 months post-injection, p-α-syn deposition was observed in both the duodenal muscular layer and the striatum, accompanied by gut microbiota alterations and motor behavioral deficits. Truncal vagotomy was associated with reduced p-α-syn levels in the brain and alterations in the gut microbiota. In A53T transgenic mice, p-α-syn pathology and neurodegenerative changes were also observed following α-syn PFF injection, though the lack of a genetically matched wild-type control precludes definitive attribution of these phenotypes solely to the A53T transgene. Conclusions: These results align with the Braak hypothesis, showing that gut-derived p-α-syn pathology and associated functional impairments are intimately linked to vagal pathways during their propagation to the brain. Additionally, this gut-origin PD mouse model may serve as a useful tool for future mechanistic investigations. Full article