Search Results (521)

Background: Ochratoxin A (OTA) is a widespread mycotoxin with well-established nephrotoxic, immunotoxic, and carcinogenic properties. Despite decades of research, the structure, thematic evolution, and emerging directions of the scientific literature on OTA toxicity remain incompletely mapped. Methods: A bibliometric analysis was conducted using 883 publications indexed in the Web of Science Core Collection (1965–2025). Bibliometrix, VOSviewer, and BibExcel were integrated within a comparative cross-software workflow to assess publication trends, collaboration networks, thematic evolution, and thematic research directions in in vitro and in vivo OTA toxicity studies, while enabling cross-validation of the main bibliometric outputs. Results: After normalisation, authors, journals, author keywords, and Keywords Plus showed strong cross-software agreement, whereas country and institution outputs retained software dependent differences related mainly to country aggregation and affiliation parsing. Publication output increased substantially over the analysed period, particularly during the most recent decade, reflecting the growing visibility of OTA research in food safety and toxicology. The field is highly collaborative and multidisciplinary. Oxidative stress-related terms were prominent in the keyword and thematic analyses and co-occurred with terminology related to apoptosis, DNA damage, and mitochondrial dysfunction. Thematic evolution analyses showed a transition from early studies focused on nephrotoxicity and animal models toward more recent investigations addressing molecular pathways, cellular responses, and microbiota host interactions. Comparatively less prominent or emerging bibliometric themes included the gut immune axis, co-exposure to multiple mycotoxins, and the broader representation of animal-health and productivity-related research. Conclusions: The bibliometric and science mapping analyses indicate that the literature on OTA toxicity has evolved from predominantly organ, and animal model-related research, toward increasing attention to molecular, cellular, intestinal, and microbiota-related topics. These patterns describe changes in the conceptual structure of the literature rather than direct evidence of biological causality. Comparatively, less prominent themes, including human-relevant models, combined exposure scenarios, and microbiome-related research, may warrant further investigation. Full article

Gut microbiota research in inflammatory bowel disease (IBD) is transitioning from holistic community-level associations toward causal validation of individual bacteria and their metabolites. However, existing causal evidence is dispersed across diverse pathways and experimental models, lacking systematic integration and comparative assessment of evidence strength. Building on the concept of grading causal evidence in microbiome studies, we extend this approach into a five-tier progressive validation framework that covers the entire causal chain—from initial association discovery to the identification of specific effector metabolites. Using this framework, we systematically collate the single-bacterium–metabolite–host target axes that have been validated by high-level experimental methods. Focusing on four major pathways—AhR/tryptophan metabolism, bile acid/nuclear receptor signaling, short-chain fatty acid/vitamin/energy metabolism, and cell death-related pathogenic mechanisms—we integrate the molecular mechanisms through which specific bacteria and their causally linked metabolites regulate intestinal barrier integrity, immune responses, and inflammation resolution. We further discuss the modulatory influences of host genetics, diet, and medications on these axes, as well as therapeutic strategies such as live bacterial preparations, engineered probiotics, and postbiotics. Causal studies on individual bacteria and metabolites in IBD have progressed from isolated mechanistic discoveries towards systematic consolidation. It should be acknowledged, however, that most of the high-level evidence summarized in this review derives from animal models and preclinical studies, whereas robust human validation remains limited. In addition, protective mechanisms appear to considerably outnumber pathogenic ones, suggesting a marked imbalance in the current evidence base. To bridge the gap between mechanistic validation and clinical application, future research should focus on validating causal chains from animal models in well-designed human cohorts, exploring pathogenic mechanisms that drive disease onset, and clarifying interactions among different metabolites. By synthesizing available evidence, identifying key research gaps, and acknowledging translational limitations, this review aims to provide a foundational reference for researchers, while recognizing that further translational efforts are needed to move these preclinical findings toward clinical application. Full article

Temporomandibular disorders (TMD) comprise a heterogeneous group of pain and dysfunction conditions involving the temporomandibular joint, masticatory muscles, and related structures. Although occlusal interference has long been discussed in relation to TMD, current evidence does not support an occlusion-centered etiological model for most patients. Within the contemporary biopsychosocial framework embodied by the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), occlusal interference is better regarded as one of several potential peripheral biomechanical inputs that may interact with individual pain susceptibility, parafunctional loading, inflammatory status, and psychosocial factors. This review synthesizes evidence on how peripheral biomechanical and inflammatory inputs may engage masticatory muscle–nerve signaling, trigeminal nociceptor activation, and neurogenic inflammation. We discuss altered masticatory muscle activity, proprioceptive and nociceptive afferent signaling, neuropeptide release, neurovascular and mast cell–nerve interactions, and glial activation within trigeminal pain pathways. Molecular mechanisms, including TRP channel and P2X3 receptor activation, voltage-gated ion channel dysregulation, MAPK, PI3K/Akt/mTOR, cAMP/PKA/CREB signaling, and epigenetic regulation, are reviewed as candidate pathways linking peripheral input to pain-related plasticity. These mechanisms are further considered in relation to hyperalgesia, mechanical allodynia, pain memory, emotional and cognitive modulation, and sex-related differences in pain processing. Finally, we evaluate translational implications, including mechanism-oriented animal models, exploratory biomarkers, human-derived experimental systems, and mechanism-informed interventions, while emphasizing their current limitations. Overall, this review proposes a cautious mechanistic framework in which peripheral inputs may contribute to TMD-related pain amplification in selected contexts, but clinical translation requires validated phenotyping, longitudinal evidence, and integration with conservative, reversible, and patient-centered standard-of-care management. Full article

This study investigated the effects of human–calf interactions on psychophysiological and emotional responses in humans. Thirty healthy adults (mean age: 25 ± 1.3 years) participated in four distinct 3 min activities with a Holstein calf: (1) watching a 2D video of a calf (video observation), (2) observing a calf directly (direct observation), (3) feeding a calf, and (4) grooming a calf. Electroencephalogram (EEG) measurements were recorded from the prefrontal, frontal, parietal, and occipital lobes during each activity. Participants’ emotional states were assessed using the Profile of Mood States (POMS) questionnaire before and after the sessions. Results showed that relative alpha power spectra, indicative of relaxation and resting states, significantly increased during both direct and video observation of the calf compared to feeding or grooming activities (p < 0.05). Relative beta power, associated with concentration and alertness without stress, was also elevated during the observation conditions relative to grooming (p = 0.044). Furthermore, POMS scores revealed a significant reduction in total mood disturbance after calf-related activities, particularly following observation (both video and direct) and grooming (p = 0.004). These findings suggest that brief interactions with calves may promote relaxation, enhance attention, reduce stress, and improve emotional well-being in healthy adults. The results provide preliminary evidence that may inform future research on the development of animal-assisted activity programs. Full article

Background/Objectives: Gabapentin is a first-line treatment for neuropathic pain, classically understood to reduce neuronal excitability through binding to the alpha-2-delta-1 (α2δ-1) subunit of voltage-gated calcium channels. However, this neuron-centric model does not fully explain its variable clinical efficacy across pain syndromes. In parallel, chronic pain is increasingly conceptualized as involving neuron–glia–immune interactions, in which microglial activation, astrocytic signaling, and inflammatory mediators may contribute to central sensitization. Methods: A structured narrative review was conducted using PubMed, Web of Science, and Google Scholar for articles available through December 2025. The search focused on gabapentin/gabapentinoids, chronic and neuropathic pain, α2δ-1 mechanisms, neuron–glia interactions, neuroinflammation, central and peripheral sensitization, nociplastic pain, cytokine/chemokine signaling, and neuroimmune modulation. Basic science studies, animal models, translational studies, clinical trials, reviews, meta-analyses, and guidelines were narratively synthesized. Results: Preclinical evidence indicates that gabapentin reduces neuronal hyperexcitability and may secondarily attenuate neuron-to-glia signaling, glial activation, and cytokine- and chemokine-related pathways. However, these neuroimmune effects remain predominantly preclinical, model-dependent, and incompletely validated in humans. Clinical evidence supports gabapentin for selected neuropathic pain conditions, but human studies rarely evaluate glial activation, cytokine signaling, or neuroimmune biomarkers. Conclusions: Gabapentin remains best understood as a neuronal α2δ-1 modulator. Although preclinical and translational evidence suggests biologically plausible secondary effects on neuroimmune signaling, these mechanisms have not been validated as biomarkers or prescribing targets in humans. The conceptual framework presented in this review supports mechanism-informed clinical reasoning and individualized pain management but should not be interpreted as a biomarker-guided prescribing algorithm. Clinically, gabapentin should be prescribed selectively for patients with neuropathic or sensitized pain features, using predefined functional goals, appropriate renal dose adjustment, careful safety monitoring, and discontinuation when meaningful benefit is not achieved. Full article

Climate variability can modulate zoonotic disease risk by altering interactions among wildlife hosts, vectors, and human environments, yet long-term evidence linking large-scale climate oscillations to natural plague systems remains scarce. We investigated the influence of El Niño–Southern Oscillation (ENSO)-related climate variability on rodent host dynamics in a long-established plague focus in Jianchuan County, southwestern China. Using continuous monthly surveillance data from 1978 to 2025, we analyzed population dynamics of two ecologically distinct plague hosts—the wild rodent Apodemus chevrieri and the domestic rodent Rattus tanezumi—together with flea infection rates and local climate variables. Generalized additive models showed that ENSO, quantified by the Southern Oscillation Index (SOI), exerted significant delayed effects on both rodent populations, with El Niño conditions consistently associated with increased host abundance. Wavelet coherence analyses revealed synchronized ENSO–rodent oscillations at dominant 2–3-year periodicities, indicating persistent large-scale climate forcing. In contrast, responses to local environmental factors differed between species: surface temperature strongly constrained the wild rodent A. chevrieri, whereas the domestic R. tanezumi showed weaker thermal sensitivity, consistent with buffering by human-modified indoor habitats. Flea infection rates declined as rodent densities increased, suggesting a dilution effect within the host–vector system. By integrating long-term wildlife surveillance, climate indicators, and vector data, this study provides empirical evidence that ENSO-driven climate variability plays a central role in regulating plague source activity at the human–animal–environment interface. These findings highlight the value of climate-informed, ecology-based surveillance frameworks for anticipating periods of elevated plague risk and strengthening early warning systems in endemic regions. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Growing evidence implicates the gut microbiome in AD-related pathways through microbial metabolites, intestinal barrier function, and systemic immune signaling. This narrative review synthesizes current evidence on gut microbial alterations in AD, with particular attention to short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, intestinal permeability, gut–skin microbiome interactions, and microbiota-targeted interventions. Human studies have reported associations between AD and altered abundance of selected microbial taxa, metabolite profiles, and markers of intestinal barrier dysfunction, whereas animal and in vitro studies provide complementary mechanistic evidence. However, findings remain heterogeneous across age groups, disease phenotypes, geographic populations, analytical platforms, and treatment exposures, and causality is incompletely established. Probiotic and synbiotic interventions have shown strain-specific and context-dependent effects, while postbiotics, fecal microbiota transplantation, washed microbiota transplantation, and metabolite-directed approaches remain investigational. AI-assisted multi-omics methods may improve biological stratification and hypothesis generation, but current applications are limited by small sample sizes, cohort heterogeneity, overfitting, insufficient external validation, and limited clinical implementation. Current evidence therefore supports the gut microbiome as a mechanistically plausible contributor, potential biomarker, and therapeutic target in AD while underscoring the need for longitudinal, phenotype-aware, and externally validated studies before routine clinical translation. Full article

Toad poison (ChanSu), a traditional animal-derived medicine, has long been used in East Asian medical systems for the treatment of inflammatory conditions and tumor-related disorders. While bufadienolides have been extensively investigated as its major bioactive constituents, the contribution of peptide components to its antitumor effects remains largely unexplored. Here, we identified protein-derived candidate antiproliferative peptides from toad poison using an integrated proteomics and bioinformatics-guided strategy. Proteomic analysis identified 135 proteins, from which 2117 peptide sequences were generated via in silico digestion with trypsin and pepsin. Subsequent multi-step screening using PeptideRanker, AntiCP, iACP, and ACPred yielded twelve candidate peptides with predicted anticancer activity. Network pharmacology analysis suggested their potential involvement in cancer-related targets and pathways. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation was subsequently used as a complementary assessment of drug-like and safety-related properties, further prioritizing four peptides for experimental validation, while molecular docking supported their interactions with key lung cancer-associated targets. In vitro assays demonstrated that three of the four prioritized peptides (WEAWN, NSQWG, and ACGVIGICQ) exhibited initial antiproliferative activity against human lung cancer A549 cells, though these findings should be interpreted with caution given the absence of a positive control in the MTT assay. This study provides preliminary evidence suggesting that protein-derived peptide candidates from toad poison may possess antiproliferative potential, representing an early systematic exploration of its previously unexplored peptidome as a source of candidate antiproliferative peptides warranting further pharmacological investigation. The integrated strategy presented here offers an efficient approach for the discovery of bioactive peptides from animal-derived traditional medicines. Full article

Cat cafés, where customers and resident cats share indoor spaces, create a distinctive yet understudied soundscape. This exploratory cross-sectional study examined cat cafés through three questions: acoustic conditions and customer perceptions using the ISO 12913 pleasant–eventful framework; associations between perceived sound sources, acoustic comfort, and mood; and links between perceptual ratings and typical activities. During weekday peak hours in July–August 2024, sound pressure levels were measured with NoiseCapture in three of four London cat cafés, while 50 customers completed questionnaires. SPLs generally ranged from 65–75 dB(A), exceeding the 45–50 dB(A) recommended for cafeterias; nevertheless, 88% of respondents described the soundscape as pleasant or very pleasant, mainly within the pleasant–uneventful region. Acoustic comfort was moderately positively associated with self-reported mood (r_s = 0.35, Holm-adjusted p = 0.01). Of six perceived source types, cat-generated sounds alone were positively associated with mood (r_s = 0.41, Holm-adjusted p = 0.02). Activity-related associations were non-significant after multiple-comparison correction, suggesting that larger samples may be needed. Attribute inter-correlations broadly reflected the established circumplex structure, preliminarily supporting the ISO framework in this setting. Overall, acoustic experience appears shaped not only by sound level but also by context, expectations, human–animal interaction, and possible biophilic associations. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Background/Objectives: The homeostatic imbalance between tumor metastasis-promoting genes and metastasis-suppressing genes determines the metastatic potential of lung adenocarcinoma (LUAD) cells. However, the post-transcriptional regulation mechanism mediated by RNA-binding proteins (RBPs) in maintaining the expression balance of tumor metastasis-related genes remains unclear. Methods: The expression of MCPIP3 and IGF2BP3 in human lung cancer tissues was analyzed using bioinformatics methods and validated using qRT-PCR, immunohistochemistry, and immunoblotting. In vitro cellular experiments and in vivo animal examinations were used to evaluate the effects of MCPIP3 and IGF2BP3 on metastasis. RNA sequencing, PCRarray, RNA pull-down and mass spectrometry, RNA-EMSA, RNA immunoprecipitation (RIP), mRNA stability, and luciferase assays were performed to elucidate the mechanism. Results: MCPIP3 is expressed at low levels, while IGF2BP3 is highly expressed in LUAD tissues. Lower MCPIP3 expression and higher IGF2BP3 expression in lung cancer tissues were significantly associated with poor prognosis in LUAD patients. MCPIP3 significantly inhibited the metastasis of lung cancer cells both in vitro and in vivo, whereas IGF2BP3 promoted metastasis. Mechanistically, MCPIP3 specifically bound to the stem–loop structure in the 3′UTR (untranslated region) of the METAP2 transcript and degraded its mRNA via its RNase domain. In contrast, by interacting with the common stem–loop structure, IGF2BP3 could stabilize METAP2 mRNA and promote its expression. Notably, inverse correlations were observed between the expression of MCPIP3 and IGF2BP3 and the expression of METAP2 in LUAD tissues. Conclusions: MCPIP3 and IGF2BP3 antagonistically control lung cancer cell metastasis by balancing the expression of metastasis-promoting genes through mediating mRNA stability, thereby providing potential targets for lung cancer treatment. Full article

As obesity, diabetes and other diet-related metabolic disorders continue to rise, non-nutritive artificial sweeteners (NASs) are widely used as sugar substitutes in free-sugar reduction and weight-management strategies, but their effects on the gut microbiota, host metabolism and related health outcomes remain debated. To clarify this evidence landscape, this review synthesizes current knowledge on the effects of major NAS on the gut microbiota and host metabolic and health-related outcome. A bibliometric analysis was conducted to characterize the development, knowledge structure and thematic evolution of this research area. For the eight NAS exposure categories included in this review (saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, neotame, neohesperidin dihydrochalcone and mixed NAS), we performed a compound-specific analysis integrating physicochemical characteristics, regulatory status, and research findings from in vitro, ex vivo, animal and human studies on gut microbiota alterations, host metabolic and health-related outcomes. These findings were further compared through four interpretive dimensions: exposure conditions, research model background, outcome assessment and interpretation of discordant results. Current research evidence does not support a class-wide conclusion that NAS are uniformly harmful or safe. To make research findings searchable, we developed the NAS-MAP knowledge graph, an interactive non-nutritive artificial sweetener–microbiota-associated phenotype knowledge graph. Overall, this review consolidates current knowledge, clarifies the sources of inconsistent findings, and provides a framework for more mechanistically informative studies, standardized evidence reporting, and more precise sweetener-, exposure- and population-specific dietary and public health guidance. Full article

Microplastics (MPs) are emerging environmental contaminants increasingly detected in foods, beverages, and food-contact materials, making dietary intake a relevant route of human exposure. In sports nutrition, this issue may be particularly important because athletes often have high food and fluid consumption, frequent use of packaged sports nutrition products, dietary supplements, bottled beverages, and sport-specific hydration strategies. This narrative review, supported by a structured literature search, examines dietary MP exposure and its potential relevance to gastrointestinal function, gut microbiota, oxidative stress, inflammation, mitochondrial activity, endocrine regulation, metabolism, recovery, adaptation, and performance-related outcomes in athletes. Current evidence suggests that MPs and nanoplastics may interact with biological systems through mechanisms involving intestinal barrier disruption, microbiota alterations, inflammatory activation, oxidative damage, mitochondrial perturbation, endocrine-disrupting chemicals, and metabolic dysregulation. However, most available data derive from in vitro studies, animal models, food contamination analyses, exposure-estimation studies, and indirect human biomonitoring evidence. Direct studies in athletic populations are currently lacking. Therefore, the possible implications of MP exposure on recovery, adaptation, and exercise performance should be interpreted as biologically plausible but unproven. From a practical perspective, evidence-informed strategies may include reducing avoidable plastic-related exposure while maintaining adequate hydration, energy availability, nutrient timing, supplement quality, and dietary patterns that support antioxidant defenses, inflammatory balance, gut health, and physiological resilience. Future research should prioritize standardized exposure assessment, validated biomarkers, human biomonitoring, and sport-specific studies evaluating MP exposure in relation to physiological and performance-related outcomes. Full article

Background/Objectives: Chronic orofacial pain represents a heterogeneous group of disorders affecting the trigeminal system and remains difficult to treat due to its complex pathophysiology, which involves glial cells in the development and maintenance of persistent pain states. This systematic review aimed to synthesize evidence from animal studies investigating the pathophysiological role of glial cells in chronic orofacial pain. Methods: After registering on PROSPERO, a systematic search of the literature, based on PRISMA guidelines, was conducted to identify experimental animal studies evaluating glial involvement in orofacial pain models. After screening and eligibility assessment, 10 studies met the inclusion criteria. Data regarding experimental models, glial populations investigated, and pain-related behavioral outcomes were extracted and qualitatively synthesized. Results: Activation of satellite glial cells, microglia, and astrocytes was consistently associated with increased neuroinflammatory signaling and enhanced neuronal excitability within trigeminal pathways, demonstrating that both peripheral and central nervous tissues were involved. Several studies reported that pharmacological modulation of glial activity may reduce pain-related behaviors. Conclusions: Glial cells are key modulators of chronic orofacial pain through neuroimmune interactions that contribute to peripheral and central sensitization. Although these findings highlight promising therapeutic targets, further translational research is required to clarify their relevance for human pain conditions. Full article

Malocclusion arises from complex interactions among genetic, environmental, and developmental factors. While genetic contributions are well established, epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and RNA chemical modifications, have emerged as plausible regulators of craniofacial growth and dentoalveolar remodeling. This structured narrative review critically evaluates current evidence on the role of epigenetic regulation in the development of malocclusion and in orthodontic tooth movement. Most available data derive from in vitro studies, animal models, and investigations of related craniofacial processes rather than from direct analyses of defined malocclusion phenotypes in humans. Consequently, the evidence base is largely indirect and heterogeneous. To address this limitation, we applied a qualitative appraisal framework that considered study design, methodological rigor, and the directness of the evidence. Experimental findings indicate that epigenetic mechanisms are dynamically regulated by mechanical forces and may influence osteogenesis, chondrogenesis, periodontal remodeling, and individual variability in orthodontic response. However, robust causal studies directly linking specific epigenetic modifications to malocclusion phenotypes remain lacking. Although biological plausibility is strong, a substantial gap persists between mechanistic insights and clinical translation. At present, the clinical utility of epigenetic markers in orthodontic diagnosis, treatment strategy, or prognosis remains limited. Future research should prioritize well-designed longitudinal human studies integrating epigenetic profiling with clearly defined malocclusion phenotypes to establish causal relationships and enable clinically relevant applications. Full article