Search Results (819)

Endogenous candidiasis remains an underrecognized yet clinically relevant complication in non-neutropenic critically ill patients. This study examines Candida spp. infections in the intensive care unit (ICU) within a patient-safety and risk-management framework, focusing on the identification of patients at highest risk and the development of an early diagnostic and therapeutic strategy. The target population comprises long-stay ICU patients requiring prolonged mechanical ventilation who develop multiple organ dysfunction syndrome (MODS) associated with immunoparalysis, typically reflected by a Sequential Organ Failure Assessment (SOFA) score ≥ 5. In this population, Candida spp. colonization may evolve into multifocal candidiasis and subsequently invasive or disseminated disease. Notably, candidemia often represents a late manifestation and therefore lacks sensitivity as an early diagnostic marker. Drawing on a series of clinical investigations conducted from 1978 to the early 2000s, the authors developed a standardized diagnostic–therapeutic algorithm based on systematic surveillance cultures, identification of multifocal Candida spp. colonization, and early initiation of antifungal therapy. Implementation of this strategy, together with progressive individualization of antifungal treatment, was associated with a marked reduction in attributable mortality related to candidiasis in ICU patients. These findings support the concept of Candida spp. infection as a sentinel indicator of systemic immune dysfunction and physiological fragility in critical illness. Integrating risk-based surveillance with early targeted therapy may substantially improve outcomes and reinforce patient-safety strategies in the ICU. Full article

Oral administration is an ideal route for colon-targeted drug delivery; however, precise delivery to the colon remains a challenge. This work presents a magnetically actuated millirobot combined with a traditional pH-dependent strategy. It aims to combine the advantages of the two methods: under normal physiological conditions, it enables autonomous targeted drug delivery, effectively reducing manipulation costs; in abnormal physiological environments, precise targeted delivery can be achieved via external magnetic intervention. The millirobot uses a magnetic composite shell and a pH-dependent film to encapsulate drug carriers. The pH-dependent film ensures an appropriate delay in drug release under different simulated pH conditions. The magnetic composite shell exhibits satisfactory magnetic responsiveness and can perform stable tumbling motion on the surface of the ex vivo intestinal tract, demonstrating good controllability and motility. Furthermore, the millirobot can carry different types of drug carriers to achieve tunable drug-release rates, thereby improving its versatility. These experimental results demonstrate that this pH-dependent magnetically actuated millirobot is a promising platform for reducing manipulation costs and enhancing the reliability of colon-targeted drug delivery. Full article

There are currently no published methods for the controlled introduction of microplastic particles into the European rabbit (Oryctolagus cuniculus) as an animal model. The aim of this pilot study was to establish a novel rabbit-based experimental model for assessing the impact of microplastic particles by evaluating the physiological and biochemical responses to an eight-day oral administration of polystyrene latex (1 and 5 mg/kg/b.w./day), providing a foundation for future studies. This study was also aimed at evaluating the possibility of using Raman spectroscopy and Fourier-transform infrared spectroscopy to analyze the distribution of microplastics in rabbit samples. We observed a dose-dependent decrease in water and food consumption in the high-dose (5 mg/kg) study group. In addition, a decrease in alanine aminotransferase and total calcium levels, along with an increase in phosphorus levels, was detected. The rabbit’s stomach was the only organ where polystyrene microparticles were identified, with the colon, kidneys, ovaries, and uterus not showing any evidence of polystyrene presence. The selected doses of microplastics did not lead to pronounced toxic effects in rabbits and may be used on larger animal samples. Physiological and biochemical data obtained indicate predominantly negative metabolic shifts associated with the intake of microplastics, which warrants further study. Full article

Postharvest rot caused by Neopestalotiopsis rosae severely threatens strawberry production globally. Here, a novel species of Streptomyces was isolated and identified through polyphasic taxonomy, for which we propose the name Streptomyces hanimojiang sp. nov. AMJ-169. Its volatile organic compounds (VOCs) inhibited N. rosae hyphal growth by 70 ± 3.81%, with (1S)-(-)-α-pinene identified as the key antifungal component (EC₅₀ = 0.018 mL·L⁻¹). Fumigation with 6× EC₅₀ α-pinene reduced fruit rot by 97.52% in a concentration-dependent manner. SEM observations showed that α-pinene caused severe hyphal damage and suppressed pathogen colonization on fruit surfaces. Transcriptomic analysis further indicated that α-pinene treatment was associated with redox regulation, glutathione metabolism, phenylpropanoid metabolism, and carbon-metabolism-related responses in strawberry fruit. These findings suggest that α-pinene controls postharvest anthracnose through direct antifungal activity on fungal hyphae together with host-associated physiological regulation, highlighting its potential as a sustainable postharvest biocontrol candidate. Full article

Opioid-induced constipation (OIC) represents a prevalent adverse effect of opioid analgesics, affecting 60–90% of patients and significantly compromising quality of life. This review delineates the multifactorial pathogenesis of OIC. Peripheral μ-opioid receptor (MOR) activation suppresses enteric neuronal excitability, inhibits intestinal motility and secretion, and impairs rectoanal function. Notably, the colon appears to exhibit a distinctive lack of tolerance to opioids. Enteric glial cell activation has been implicated in neuroinflammation, while interstitial cells of Cajal show impaired pacemaker function. Central mechanisms are increasingly recognized to involve the brain–gut axis. Furthermore, opioid-induced barrier disruption, microbiota dysbiosis, and LPS/TLR4-mediated inflammation are proposed to interact and may contribute to a self-reinforcing cycle. Animal models have been instrumental in dissecting these mechanisms. However, they present limitations in reproducibility, clinical phenotype fidelity, and translational validity, particularly regarding microbiome composition and neuroimmune responses. Future research should prioritize the development of standardized, physiologically relevant animal models incorporating multi-omics approaches, and validate mechanism-based therapeutic strategies, including peripherally acting MOR antagonists and microbiota-targeted interventions, for precision management of OIC. Full article

Lentils (Lens culinaris; family: Fabaceae) are increasingly recognized as functional legumes with potential benefits for gut health because they provide bioactive peptides, resistant starch, and polyphenol-rich fractions within a shared food matrix. However, most existing studies have focused on individual lentil-derived compounds, and their matrix-dependent complementary interactions during digestion and fermentation remain insufficiently resolved. This review synthesizes current evidence on lentil-derived peptides, resistant starch, and polyphenols, with particular emphasis on their matrix-dependent complementary relationships, digestion-dependent transformation, microbial co-metabolism, and implications for intestinal barrier function. During gastrointestinal digestion and colonic fermentation, lentil proteins, resistant starch, and phenolic compounds undergo sequential transformation, yielding bioactive peptides, fermentable substrates, short-chain fatty acids (SCFAs), and phenolic metabolites that may collectively influence microbial composition and metabolic activity. Emerging evidence suggests that these interconnected processes may support gut health through microbiota–host crosstalk by modulating tight junction-related markers, reducing intestinal permeability, and maintaining epithelial homeostasis. Mechanistically, these effects have been associated with SCFA-mediated G protein-coupled receptor (GPCR) signaling, suppression of TLR4–NF-κB/MAPK inflammatory cascades, and activation of Keap1–Nrf2 antioxidant defenses, thereby attenuating oxidative stress and pro-inflammatory responses. Current evidence is more consistent with matrix-dependent complementary or convergent actions than with demonstrated synergy. At present, phenolic-rich fractions provide clear pathway-level evidence, whereas fermentation-linked carbohydrate effects are more strongly supported by microbiota- and in vivo-associated outcomes, and protein- or peptide-related mechanisms remain comparatively underdefined. Nevertheless, the evidence base remains limited by the scarcity of integrated studies, well-controlled human intervention trials, and factorial experimental designs capable of distinguishing complementary, additive, and truly synergistic effects among lentil bioactives. This review therefore highlights the need to move from describing coexisting beneficial effects toward formally testing interaction effects within physiologically relevant lentil matrices. Full article

This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota–sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient. Full article

Arbuscular mycorrhizal fungi (AMF) are widely applied as bioinoculants to enhance crop performance, yet their broader ecological effects on rhizosphere microbial assembly under field conditions remain insufficiently understood. Here, we evaluated the impact of a commercial AMF inoculant and its carrier material on lettuce performance and rhizosphere microbial communities in an open-field experiment. We hypothesized that both viable AMF propagules and formulation components contribute to shifts in rhizosphere processes. Active AMF inoculation significantly increased root colonization and fresh biomass at harvest, confirming successful establishment and enhanced plant performance under field conditions. Colonization levels in the heat-inactivated carrier treatment were comparable to the non-inoculated control, indicating that the carrier did not inhibit indigenous AMF activity or induce nutrient-mediated suppression of symbiosis. Plant physiological responses were stage-dependent, supporting the context-dependent nature of AMF effects in dynamic field environments. High-throughput sequencing revealed no significant treatment effects on bacterial or fungal alpha diversity. However, beta-diversity analyses demonstrated significant compositional restructuring of rhizosphere communities, particularly within the bacterial domain. A stable core microbiome persisted across treatments, yet relative abundances and community evenness were altered by both active inoculation and carrier application. These results suggest that AMF inoculation reorganizes microbial community structure predominantly via shifts in ecological niche occupation. Collectively, our results show that AMF inoculation functions not only as a symbiotic nutrient-acquisition strategy but also as a driver of rhizosphere microbial reorganization under field conditions. Integrating plant performance with microbiome dynamics provides a more comprehensive framework for understanding and optimizing microbial inoculants in sustainable agricultural systems. Full article

Ticks harbor complex microbial communities composed of symbionts, commensals, and tick-borne pathogens (TBPs). Together, these microorganisms form the tick holobiont. Within this system, the tick’s physiological architecture structures microbial communities by distributing microorganisms across distinct tissues. This compartmentalization creates spatially distinct ecological niches, which in turn shape how microbial communities assemble and interact. In this review, we integrate ecological theory with current knowledge of tick microbiome research to examine how pathogen–pathogen and pathogen–microbiome interactions emerge within these tissue-structured microbial communities. We first outline how baseline ecological filters, including tick species, developmental stage, tissue identity, vertical transmission, and environmental context, shape the microbiome configuration through community assembly processes. We then examined how TBPs, as high-impact colonizers, can further modify microbial networks by altering host-mediated selective pressures, influencing interaction topology, and reshaping community stability. Based on these observations, we propose a dual selective pressure framework in which (i) baseline ecological structuring processes and (ii) pathogen-associated selective pressures interact to determine the microbial network configuration and functional outcomes within the tick holobiont. These interacting forces may drive shifts in diversity, modularity, keystone taxa emergence, and network resilience, ultimately influencing vector competence. This review frames the microbial communities within the tick holobiont as spatially structured ecological systems shaped by multilevel selective pressures. This conceptual foundation provides a coherent framework for understanding microbial interactions in arthropod vectors and highlights avenues for mechanistic research and microbiome-based strategies to mitigate tick-borne diseases. Full article

Muskmelon (Cucumis melo) is a widely cultivated and economically important fruit crop that is severely affected by Fusarium wilt caused by Fusarium oxysporum f. sp. melonis (race 1.2) (Fom). Conventional management practices have shown limited effectiveness and pose environmental and health risks; therefore, sustainable and eco-friendly alternatives are required to manage this disease. In the present study, 23 endophytic fungal isolates belonging to eight genera were isolated from Ecballium elaterium and screened to determine antifungal potential against Fom using an in vitro antagonistic assay. Two endophytic isolates (Fusarium sp. EeR4 and Fusarium clavum EeR24) exhibited an inhibitory effect against Fom on quarter-strength PDA plates. In growth chamber experiments, F. clavum EeR24-colonized melon seedlings and significantly protected plants from wilting compared to non-colonized pathogen-challenged seedlings. Under greenhouse conditions, F. clavum EeR24 significantly improved morphological and physiological traits, including plant height, weight, number of leaves, membrane stability, photosynthesis, stomatal conductance, and transpiration, in Cucumis melo. Endophytic colonization improved catalase (56%), guaiacol peroxide (47%), and superoxide dismutase activity (25%), and increased flavonoid and phenolic content by 11–59% compared to non-colonized Fom-challenged plants. Lipid peroxidation significantly decreased by 37% and proline accumulation increased by 70% in colonized plants compared to non-colonized plants. Histochemical analysis also indicated that endophytic colonization considerably reduced the levels of H₂O₂, O₂⁻, malondialdehyde, and cell mortality in Fom-challenged plants. In addition, the culture filtrate and organic residues of F. clavum EeR24 inhibited the mycelial growth of Fom by 52–58%, respectively. Furthermore, a study on spatial colonization of the endophyte and the pathogen using GFP and RFP tagging indicated that both the endophyte and the pathogen simultaneously colonized the root tissues of C. melo; however, the endophyte significantly reduced the pathogenicity of Fom. These results suggest that endophytic F. clavum EeR24 may be developed as an effective biocontrol agent for the management of Fusarium wilt in melon plants under field conditions. Full article

Bile acids, the primary constituents of mammalian bile, are synthesized in the liver from cholesterol and secreted into the intestine to perform essential physiological functions. Primary bile acid synthesis is the principal pathway for cholesterol catabolism and whole-body cholesterol homeostasis, occurring predominantly via the classical and alternative pathways. To elucidate the effects of altitude on serum bile acid profiles and synthesis pathways in SD rats, this study utilized UPLC-MS/MS to analyze serum bile acid composition in animals housed at high and low altitudes. Additionally, qRT-PCR and Western blotting assessed mRNA transcription and protein expression of key genes involved in primary bile acid synthesis in the liver and intestinal tissues (ileum, duodenum, and colon). Results showed that serum levels of total and primary bile acids significantly decreased with increasing altitude. Furthermore, hepatic mRNA and protein expression of Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1 were significantly downregulated. Fxr mRNA expression in the liver, ileum, duodenum, and colon was significantly decreased with increasing altitude. Meanwhile, the protein expression of both FGF15 and SHP showed a downward trend, with a significant decrease for FGF15 and a non-significant decrease for SHP. These findings suggest that primary bile acid synthesis in SD rats is dominated by the classical pathway. As altitude increases, bile acid synthesis in SD rats is significantly inhibited, indicating that high-altitude hypobaric hypoxia is the primary inhibitory factor. This study provides critical data for elucidating the adaptive mechanisms of bile acid metabolism in mammals exposed to high-altitude hypoxia, thereby establishing a theoretical foundation for investigating the regulation of host lipid metabolism influenced by such conditions. Full article

Colorectal cancer (CRC) persists as a significant public health burden due to its high morbidity and mortality rates worldwide, yet the molecular events that govern its initiation and progression remain incompletely understood. We recently conducted microRNA (miRNA) profiling and identified multiple dysregulated miRNAs in CRC compared to adjacent normal tissue. Among those, miR-138-5p emerged as a potential tumor suppressor due to its marked downregulation in CRC tissue; however, the stage-specific expression of this miRNA during CRC progression and underlying molecular mechanisms remains to be unraveled. In this study, we performed differential expression profiling of healthy colon, adenomatous polyp (AP), and CRC tissues based on public datasets, revealing significant downregulation of miR-138-5p in CRC compared to controls, but not during the AP stage, suggesting a role in later stages of malignant progression. Forced expression of miR-138-5p in HCT116 and HT-29 CRC models suppressed clonogenic survival, proliferation, and migration while inducing cell death. Additionally, miR-138-5p significantly inhibited tumor formation under three-dimensional culture settings, reinforcing its tumor-suppressive function in a physiologically relevant context. Transcriptomic profiling of miR-138-5p-overexpressing CRC models revealed widespread changes in the pathways related to zinc ion binding, cilium morphogenesis, smoothened signaling, and nuclear transport. Integrated computational and experimental analyses identified 41 potential gene targets, among which TCF3, UBE2C, EIF4EBP1, LYPLA1, and CD44 were validated as potential miR-138-5p-regulated genes. Collectively, these findings establish miR-138-5p as a stage-specific tumor suppressor in CRC, acting through coordinated regulation of oncogenic networks across multiple pathways. Downregulation of miR-138-5p appears to be a late oncogenic event, conferring proliferative, survival, and invasive advantages to tumor cells. Restoration of miR-138-5p or therapeutic targeting of its downstream effectors may represent promising avenues for CRC therapeutic intervention. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic–pituitary–adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan–kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors. Full article

Recently, an oral–gut communication axis has been proposed. Herein, we review clinical studies reporting differences in oral microbial communities in inflammatory bowel diseases (IBDs), with a focus on Crohn’s Disease (CD), as well as evidence from experimental models. While available studies support evidence for the direct transmission of oral-derived bacteria to gut, further work is needed to clarify whether such transmission results in stable colonization of intestinal niches and the establishment of a persistent host–microbe state that influences host physiology. To date, evidence from clinical and murine studies suggests three routes of the oral–gut axis, which in turn directly or indirectly exacerbate intestinal inflammation and contribute to IBD pathogenesis: (i) direct invasion of pathobionts through swallowing, (ii) migration of the oral pathogen activated pro-inflammatory immune cells, (iii) systemic inflammation triggered by oral pathogens such as Porphyromonas gingivalis. Although the role of oral microbiome in systemic diseases is becoming more apparent, sophisticated clinical and experimental studies are needed to elucidate the direct and indirect oral–gut communication mechanisms, including the contribution of oral microbial metabolites. Future directions may include evaluating the diagnostic and therapeutic potential of the oral microbiome and metabolome. Full article

Menopause is a pivotal stage in women’s life that brings with it multiple physiological changes that significantly increase the risk of cardiometabolic diseases. (Poly)phenols are plant secondary metabolites that present several mechanisms of action that could improve human health, including the regulation of gene expression, the control of lipid metabolism, the maintenance of glucose homeostasis, a reduction in blood pressure, prebiotic effects, and antioxidant and anti-inflammatory activities. This narrative review summarizes current evidence on the main cardiometabolic risk factors associated with menopause (i.e., obesity, dyslipidemia, high blood pressure, and insulin resistance) and examines the potential of dietary strategies focused on (poly)phenol intake to mitigate these alterations. Current evidence suggests that dietary intervention based on (poly)phenol intake could be a great strategy to mitigate cardiometabolic alterations during menopause. Moreover, this review underscores the crucial need to develop personalized nutrition strategies to optimize the effectiveness of (poly)phenol-rich diets for postmenopausal women’s health, thereby alleviating the cardiometabolic risk associated with this pivotal stage of women’s lives. In addition, this work emphasizes that future research should comprehensively address the key factors involved in the main mechanisms of action of (poly)phenols in promoting health, including (poly)phenol bioavailability, the role of the gut microbiota in the colonic metabolization of these bioactive compounds, and the regulation of gene expression via nutrigenomic effects related to cardiometabolic diseases. This integrative approach will be essential for establishing evidence-based dietary recommendations for (poly)phenol intake during menopause. Full article