Search Results (4,212)

Endothelial cells (ECs) play a critical role in physiological processes, including regulating blood fluidity, angiogenesis, and regulating the immune response. Integrins, which participate in sensing external stimuli and signal transduction, are crucial for the proper functioning of ECs. Like other cells, ECs undergo senescence, which is associated with their dysfunction and contributes to increased susceptibility to cardiovascular disease. However, the role of integrin-dependent pathways in endothelial senescence is poorly understood. Here, we identify integrin-linked kinase (ILK) as a crucial factor modulating endothelial function and senescence. Using two complementary models, replicative and stress-induced premature senescence, in endothelial cells of different origins, we show that the senescent endothelium shows phenotypic and functional dysfunction. Furthermore, we revealed that these modulations correlated with ILK downregulation. Functionally, ILK depletion in young ECs was sufficient to trigger a senescence-associated phenotype and manifested key features of endothelial dysfunction. In line with this, ILK restoration in senescent cells reduced selected senescence markers and improved endothelial function. Together, these findings show that ILK is not only correlated with endothelial ageing but also works as an active regulator of senescence-linked endothelial dysfunction. Thus, ILK, as a link between adhesion-dependent signalling and endothelial ageing, is a potential target for limiting age-associated vascular decline. Full article

To identify novel field control strategies against Pyrrhalta aenescens (Coleoptera: Chrysomelidae) and provide scientific support for its biocontrol in urban tree management, this study investigated the virulence of Beauveria bassiana against this pest under laboratory conditions, as well as its physiological and biochemical effects. Bioassays using the dipping method showed that B. bassiana was pathogenic to all developmental stages of P. aenescens, with the highest virulence observed against early-instar larvae (1st and 2nd instars). For these stages, corrected mortality and mycosis rate were positively correlated with conidial concentration, and the median lethal time (LT₅₀) was the shortest. In contrast, pupae and eggs exhibited the strongest resistance to fungal infection. In leaf-disk choice tests, larvae significantly preferred untreated leaves or those treated with low concentrations of B. bassiana, displaying a concentration-dependent repellent response to the fungus. Physiological measurements revealed that larval body length and weight gain were significantly inhibited following fungal exposure. Further analysis indicated that B. bassiana infection markedly reduced total hemocyte counts and triggered intense melanization and nodulation responses, particularly in younger larvae. Overall, these results suggest that B. bassiana has strong potential for the biological control of P. aenescens. Control measures targeting early-instar larvae are recommended for cost-effective management, providing a scientific basis for developing eco-friendly control technologies based on this entomopathogenic fungus. Full article

The gut–vagina axis has emerged as a growing area of interest in female health due to its potential role in mediating physiological processes via interactions between distinct microbiomes, including microbial migration, hormonal and immune regulation, and metabolite exchange. Recent advances in microbiome research suggest bidirectional communication between gut and vaginal communities, with potential effects on microbial composition, immune responses, hormonal balance, and metabolic activity in both sites. In this review, we outline the most promising features of the gut–vaginal relationship, emphasize the significance of their plausible bidirectional communication, and discuss how these interactions may affect local and systemic health. Full article

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous compounds capable of interfering with hormonal homeostasis and endocrine-regulated physiological processes. Their widespread occurrence in food, water, air, consumer products and industrial materials has raised increasing concern regarding their contribution to chronic disease burden. This review synthesizes current evidence on the exposure characteristics, molecular mechanisms, health effects, and prevention strategies related to major EDC classes, including bisphenol A and phthalates, dioxins and polychlorinated biphenyls, per- and polyfluoroalkyl substances, pesticides, and brominated flame retardants. Evidence indicates that EDCs may act through receptor-mediated signaling, altered hormone synthesis and metabolism, oxidative stress, mitochondrial dysfunction, immune modulation, and epigenetic mechanisms, with effects that may vary according to dose, timing, sex, age, and developmental susceptibility. Reported health outcomes include metabolic and cardiovascular disorders, reproductive dysfunction, hormone-dependent cancers, thyroid disruption, immune dysregulation, and adverse developmental effects. Although complete avoidance is unrealistic, exposure reduction and risk mitigation can be achieved through coordinated individual, clinical, environmental, and regulatory interventions. A life-course approach is essential to limit the health burden associated with endocrine disruption. Full article

Heat stress (HS) is at the top of the challenges facing modern dairy production, with annual losses according to global projections, under high-emission scenarios, reaching US$14.7–40.0 billion by the end of the century. This review emphasizes three interconnected topics that account for most of the proportion of the productive and reproductive losses during HS. First, the physiological consequences of HS are reviewed, with emphasis on the pair-fed thermal neutral (PFTN) paradigm, which established that reduced dry matter intake (DMI) accounts for only 35–50% of the observed milk yield decline, with the remainder arising from tissue-level effects of hyperthermia on mammary function, metabolism, and reproductive performance. Second, HS-induced microbiome disruption is examined as an active pathophysiological amplifier, whereby rumen dysbiosis compromises intestinal barrier integrity and drives systemic endotoxaemia, chronically amplifying the immune suppression already imposed by the thermal insult. Third, we focus on the integration of multi-omics platforms as a management approach, since single-omics analyses capture only a fraction of the biological complexity underlying the HS response. As the available datasets expand in coverage and scale, their integration through AI-driven analytical frameworks has the potential to substantially advance beyond the current fragmented picture, progressively building toward a systems-level model of thermal stress. Evidence-based mitigation strategies spanning environmental cooling, targeted nutritional supplementation, and genomic selection are critically evaluated within this framework, with emphasis on equity of access to evidence-based solutions across global dairy production systems. Full article

Perinatal mental illness affects up to 20% of new mothers worldwide, yet despite a growing research interest over the past decade, the etiology is still not fully understood, and clinical treatment guidelines remain inconsistent across countries and services. In this review, recent findings on neurobiological processes and evolutionary mechanisms, as they occur during the menstrual cycle, pregnancy, birth, postpartum and breastfeeding, are discussed. The intention is to raise awareness of physiological changes in pregnancy that might be relevant to the differential diagnosis and clinical treatment of perinatal psychiatric disorders such as depression, anxiety, PTSD after childbirth, bipolar relapse, postpartum psychosis, obsessive-compulsive symptoms, substance-use disorders, and suicidality. Areas addressed include the activities of the immune system, thyroid gland, cortisol, sleep and individual sensitivity to ovarian hormone fluctuations. Evolutionary biological mechanisms intended to sustain pregnancy and to ensure the survival of the newborn are assumed to have potent effects on the maternal brain. These non-pathological adaptations could provide grounds for a better understanding of risk factors and the etiology of perinatal mental illness. Full article

The red sea urchin Loxechinus albus is a species of high commercial importance in Chilean aquaculture, whose performance is strongly influenced by environmental conditions such as temperature. The gut microbiota plays a central role in host physiology; however, its interaction with stress-induced molecular responses remains poorly understood. This study evaluated the effects of thermal stress on food consumption, gut microbial composition, oxidative status, and immune- and stress-related gene expressions in L. albus gut. Sea urchins were exposed to control (16 °C) and elevated temperature (22 °C) conditions for 7 and 14 days. Gut microbiota was characterized using 16S rRNA sequencing, while oxidative damage to DNA and proteins was quantified. Gene expression analyses targeted markers of apoptosis (casp3, casp10, bak1), cellular growth (mtor, raptor), stress response (hsp70), and immune regulation (nfκb, foxo). Thermal stress induced a marked reduction in microbial alpha diversity and promoted a shift toward opportunistic taxa. Heat-stressed individuals exhibited significantly increased oxidative DNA damage, whereas protein oxidation remained unchanged. Gene expression analyses revealed early upregulation of casp3, casp10, nfκb, foxo, and hsp70, suggesting activation of apoptotic, immune, and stress-response pathways. In contrast, bak1, mtor, and raptor showed limited or no significant modulation. These findings demonstrate that thermal stress disrupts host–microbiota homeostasis and induces oxidative and molecular responses in L. albus. This integrative response provides insight into mechanisms underlying physiological performance under thermal stress, with important implications for aquaculture sustainability. Full article

Background/Objectives: Chronological age does not fully capture the heterogeneity of physiological aging among healthy individuals. Immune aging and redox imbalance are key hallmarks of biological aging, yet their interaction and relationship with circulating extracellular vesicles (EVs) remain incompletely understood. This study aimed to investigate whether endothelial- and platelet-derived EVs are associated with immune and oxidative aging processes in clinically healthy subjects. Methods: Circulating EVs were isolated and characterized by flow cytometry in a cohort of healthy volunteers spanning a wide age range. Endothelial-derived EVs (EeEVs) and platelet-derived EVs (PEVs) were quantified and analyzed in relation to chronological age, immune function parameters, redox biomarkers, ImmunolAge (an immune aging index), and OxyScore (a composite redox index). A normalized EV-Score was developed using an age- and sex-adjusted Z-score approach. Associations were assessed using correlation analyses, non-linear regression models, generalized additive models, and receiver operating characteristic (ROC) curves. Results: Both EeEVs and PEVs increased non-linearly with age, with a pronounced rise during midlife. EV concentrations were positively associated with molecular aging markers and inversely related to multiple immune function parameters. EVs were also linked to redox biomarkers, although oxidative status alone did not explain EV variability. EV-Score was strongly associated with immune aging and showed context-dependent relationships with oxidative status. Notably, high EV-Score values were observed primarily in individuals with accelerated immune aging, whereas subjects with high oxidative status but preserved immune aging exhibited low EV-Score values. ROC analyses demonstrated that the discriminative capacity of EV-Score for immune or oxidative aging depended on the combined immune–redox context. Conclusions: Circulating EVs may reflect the integrated state of immune and redox aging rather than chronological age alone. These findings suggest the potential utility of EVs as dynamic biomarkers of biological aging in healthy individuals and highlight the importance of considering immune and oxidative processes jointly to interpret EV-associated aging signatures. Full article

Background/Objectives: Immunonutrition uses dietary bioactive compounds to support immune function while preserving systemic physiological balance. Donkey milk, bovine colostrum, and royal jelly contain complementary antimicrobial, immunoglobulin-rich, and immunoregulatory components, but their combined effects remain insufficiently characterized. Methods: A 6-week controlled study was conducted in female rabbits assigned to four groups (n = 15/group): vaccinated only (G1), immunonutraceutical only (G2), vaccination plus immunonutraceutical (G3), and pre-conditioned immunonutraceutical followed by vaccination and continued supplementation (G4). Serum total immunoglobulins and lysozyme were measured longitudinally. Biochemical indices were monitored throughout the study, and hematological parameters were evaluated at the final time point. Mixed-effects models, generalized estimating equations, principal component analysis, and correlation-based systems analyses were applied. Results: Supplementation significantly modulated both humoral and innate immune responses. The strongest terminal immunoglobulin response was observed in G4 (26.00 ± 5.80 mg/mL), whereas sustained lysozyme elevation was most pronounced in supplemented groups, particularly G3 (3.13 ± 0.44 ng/mL). Within-subject analysis demonstrated significant innate–adaptive immune coherence (p = 0.000006). Biochemical analyses showed coordinated metabolic adaptation without evidence of organ toxicity, and hematological findings indicated preserved inflammatory and hematopoietic stability. Conclusions: Multi-component immunonutraceutical supplementation modulated humoral and innate immune dynamics in a timing-dependent manner while maintaining biochemical and hematological safety. These findings support the potential of combined donkey milk, bovine colostrum, and royal jelly as functional ingredients for coordinated immune support. Full article

The myocardium possesses one of the highest vascular densities in the body. The outermost wall layer of large and medium-sized vessels, the adventitia, forms a critical interface between the vasculature and the myocardium and serves as a reservoir for stem and progenitor cells capable of differentiating into all vascular wall lineages as well as innate immune cells, including macrophages. Current cardiac organoid models intrinsically develop networks of endothelial cords and small capillary-like structures that resemble cardiac microvessels. However, these microvessels mostly lack an adventitial compartment in vivo. Here, we present a potential alternative assembloid strategy that combines vascular segments from mouse and human origin with either cardiomyocytes or cardiac spheroids derived from human induced pluripotent stem cells, thereby incorporating large diameter vessels and the vascular adventitia into a cardiac tissue model. Within the assembloids, the myocardial component remained contractile and connected to the vascular adventitia, which displayed cellular sprouting toward the hiPSC-derived cardiac tissue. Immunostaining for vascular and immune markers revealed that the adventitia gave rise to endothelial sprouts and macrophage-like cells which integrated into the myocardial tissue. In summary, we present proof of concept for complex assembloids composed of vessel segments and human iPSC-derived cardiomyocytes which contain and maintain an in vivo-like adventitial compartment. We suggest this model may serve as a platform for investigating myocardial–stromal interactions, cardiac tissue repair, and functional remodeling under both physiological and pathological conditions. Furthermore, the incorporation of large-lumen vessel segments may enable future experimental perfusion, rendering the model particularly suitable for drug testing via intravascular delivery. Full article

Dietary emulsifiers, common in processed and ultra-processed foods, improve food texture and shelf life but may affect gut health by interacting with the microbiota and intestinal barrier. While emulsifiers have long been considered safe, growing evidence links their presence in ultra-processed foods to chronic disease risk. This review aims to evaluate the current understanding of the factors and mechanisms underlying individual differences in intestinal mucosal susceptibility to dietary emulsifiers. A search of PubMed and Embase through February 2026 identified eight relevant studies. Overall, the available evidence indicates a heterogeneous and highly individualized host response to dietary emulsifiers. These differences appear to be strongly influenced by the gut microbiota and its functional properties, while animal studies further suggest that host factors such as sex-related differences in microbial composition may also contribute to variability in response. Importantly, not all emulsifiers have the same effects, underscoring compound-specific impacts on gut physiology. The findings demonstrate that sensitivity to dietary emulsifiers varies substantially between individuals, challenging the long-standing assumption that these additives are universally safe. Given the multifactorial nature of this susceptibility, particularly the role of the gut microbiota, future research should adopt an integrative approach that combines microbial profiling with host genetics, immune responses, and early-life exposures. Such efforts will be essential to identify at-risk individuals and to inform more personalized dietary recommendations aimed at preserving intestinal health and reducing disease risk. Importantly, there is a clear need for larger, well-powered studies that can validate and expand upon these initial observations. Full article

Anaerobutyricum is a Gram-positive, obligately anaerobic genus within the family Lachnospiraceae that is widely distributed in the gut microbiota of humans and animals. This genus has attracted increasing attention because of its ability to produce short-chain fatty acids, particularly butyrate, a key microbial metabolite involved in intestinal homeostasis, immune regulation, and host energy metabolism. The genus currently comprises only two validly described species, Anaerobutyricum hallii and Anaerobutyricum soehngenii. Despite this limited taxonomic representation, accumulating evidence has linked variation in Anaerobutyricum abundance to host health and disease. In humans, alterations in Anaerobutyricum abundance have been linked to metabolic, inflammatory, and neurodegenerative disorders. In livestock, especially pigs, limited evidence suggests that this genus may also be associated with growth-related traits, intestinal health, and reproductive performance. In this review, we summarize current knowledge of the taxonomy, physiological characteristics, genomic features, metabolic potential, and major factors influencing the abundance of Anaerobutyricum. We further discuss its reported associations with human health and its possible relevance to animal production, with particular attention to pigs at different developmental stages. Overall, Anaerobutyricum appears to be a promising functional genus; however, most available evidence remains association based rather than causal, livestock studies are still sparse, host interaction mechanisms remain poorly understood, and its utility as a probiotic candidate, biomarker, or microbiome-based intervention target requires further strain-level, mechanistic, and in vivo validation. Full article

Copper (Cu) contamination in aquatic environments induces oxidative stress and structural damage to crustaceans. This study investigated the protective effects and associated mechanisms of exogenous melatonin (MT) against Cu-induced toxicity in Procambarus clarkii using integrated physiological, histopathological, proteomic, and molecular analyses. MT supplementation enhanced antioxidant defense by elevating SOD, CAT, and T-AOC activities, while reducing MDA accumulation, with peak effects observed at 24 h. MT also restored endogenous melatonin levels and regulated phosphatase activity, thereby maintaining immune and metabolic homeostasis. Histopathology showed reduced hepatopancreatic damage, characterized by reduced epithelial vacuolization and preserved basement membrane integrity. Proteomics suggested that MT modulates a multilayered network associated with detoxification, redox balance, and cellular homeostasis. Pathway enrichment showed that Cu exposure dysregulated proteins involved in mitochondrial biogenesis, ABC transporters, membrane trafficking, and apoptosis. MT administration partially counteracted these alterations and was associated with the regulation of glutathione metabolism, as well as reduced enrichment of lysosome- and apoptosis-related pathways. Quantitative RT-PCR results were consistent with the proteomic data. Overall, MT partially alleviated Cu-induced toxicity and was associated with enhanced antioxidant defense, improved cellular homeostasis, and metabolic regulation. Our study provides new molecular insights and suggests its potential application for mitigating metal toxicity in aquaculture. Full article

The cribriform plate (CP) functions as a dynamic neuroimmune interface through which olfactory nerve bundles exit the brain within a specialized perineural microenvironment (cpPME). While traditionally viewed as a passive structural barrier, emerging evidence positions the CP as a central hub for cerebrospinal fluid (CSF) drainage, glymphatic–lymphatic clearance, and antigen presentation. This review provides a comprehensive understanding of recent advances in cpPME research, highlighting the adaptive remodeling of the immune landscape in response to neuroinflammation and aging. We critically evaluate the translational gap between rodent models and human physiology, discussing the implications for neurodegenerative diagnostics, neuroinflammatory conditions, infectious diseases and “nose-to-brain” therapeutic delivery. By integrating anatomical, physiological, and immunological perspectives, we offer a comprehensive framework for understanding the CP’s role in CNS homeostasis and its potential as a transformative diagnostic and therapeutic target. Full article

With the growing interest in the microbiome, short-chain fatty acids (SCFAs) have emerged as key metabolites due to their critical roles in host physiology, including immune regulation, energy homeostasis, and inflammatory control. As a result, the accurate quantification of SCFAs in various biological samples has become increasingly important. However, reliable and standardized methods for measuring SCFAs across different sample types remain underdeveloped, highlighting the need for methodological refinement. To address this need, we optimized two analytical methods, headspace GC-MS and GC-MS/MS, for SCFA quantification. These techniques were applied to a range of biological matrices, including pure microbial cultures, low-abundance animal liver, animal feces, and standardized simulated human fecal samples. The headspace GC-MS approach enables direct analysis with minimal sample preparation, thereby enhancing throughput and ease of use. In contrast, the GC-MS/MS method, involving methanol extraction, alkaline treatment, and derivatization with MTBSTFA, offers superior sensitivity and precision, making it particularly suitable for small-volume and low-abundance samples. Together, these optimized protocols provide robust, sensitive platforms for profiling SCFAs across diverse biological matrices, facilitating a deeper understanding of microbiome–host interactions and supporting future translational applications. Full article