Search Results (16,379)

Colorectal cancer (CRC) demonstrates favorable clinical outcomes when diagnosed at an early stage; however, the prognosis declines substantially following recurrence or distant metastasis. Increasing evidence indicates that cancer stem cells (CSCs) are pivotal contributors to tumor recurrence, metastatic dissemination, and therapeutic resistance. The present study aimed to identify CSC-associated biomarkers through spatial transcriptomic profiling of normal colonic mucosa, primary CRC, and liver metastatic tissues, and to evaluate their functional relevance in CRC progression. Spatial transcriptomic analysis revealed that CCN2 was preferentially enriched within CSC clusters of primary CRC tissues, whereas APOC2 was predominantly upregulated in liver-metastatic CSCs. Functional validation of CCN2 was performed by establishing CCN2-knockout HCT116 cell lines using the CRISPR-Cas9 system. Loss of CCN2 expression markedly attenuated cell proliferation, migration, invasion, and oxaliplatin resistance compared with control cells. Furthermore, immunohistochemical analysis of tissue microarrays demonstrated a significant positive correlation between CCN2 expression and CSC markers SOX2 and Nestin. Collectively, these findings suggest that CCN2 functions as a central regulator of stemness and malignant potential in CRC and may represent a promising therapeutic target to prevent recurrence and metastasis. Additional mechanistic studies are warranted to further elucidate the molecular pathways of CCN2 and to validate the role of APOC2 in liver-metastatic CRC stem cells. Full article

Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut microbiome and metabolome respond to nutritional interventions in WF infants is scarce. This study explored gut microbiome and metabolome changes in Indonesian infants aged 6–12 months who overcame WF following a one-month intervention. Methods: Infants were assigned to either a Nutritional Advice (NA) group or a Nutritional Advice plus Oral Nutritional Supplements (NAONS) group. Stool samples were collected before and after the intervention for microbiome (16S rRNA sequencing) and metabolome (LC-MS) analysis. Results: Significant shifts in gut microbial composition (beta diversity) and species richness (Chao1 index) were observed in both groups, suggesting enhanced microbial diversity and gut resilience. Within-group analysis revealed increases in beneficial genera such as Faecalibacterium and Peptostreptococcus, and a reduction in pro-inflammatory Fusobacterium in the NA group. The NAONS group showed a notable decrease in Proteus, a potentially pathogenic genus. Between-group comparisons indicated higher abundances of Lactococcus and Leuconostoc in the NAONS group, likely reflecting the influence of milk protein-rich supplements on microbial colonization, favoring lactic acid bacteria over SCFA-producing taxa, leading to better gut health. Metabolome analysis revealed significant changes in the NA group, increases in metabolites like Threonine, Tryptophan, and Xylose pointed to improved energy metabolism and gut health, while a decrease in Oxalic Acid suggested better metabolic efficiency. In contrast, the NAONS group, while benefiting from rapid weight gain, displayed a distinct metabolic profile influenced by high milk protein intake. No significant correlations were found between microbiome and metabolome changes, highlighting the complexity of gut-host interactions, suggesting that the interventions led to independent shifts in the aforementioned profiles. Conclusions: Overall, the findings suggest that nutritional interventions may enhance gut health and support recovery from weight faltering, providing insights into strategies that may contribute to restoring healthy growth trajectories and preventing stunting by modulating gut health. Full article

Background/Objectives: The management of asymptomatic bacteriuria (ASB) and candiduria (ASC) in kidney transplant recipients during the early post-transplant period is controversial. This study aimed to evaluate whether treating, versus not treating, ASB and ASC episodes in the first two months after kidney transplantation influences clinical outcomes and the emergence of multidrug-resistant (MDR) infections. Methods: We conducted a single-center retrospective cohort study enrolling patients with ASB or ASC occurring in the first two months after kidney transplantation between January 2019 and July 2024. Patients were classified into treated and untreated groups. The primary endpoint was 30-day mortality. Secondary endpoints included mortality at 90, 180 and 360 days; incidence of sepsis or septic shock; bacteremia/candidemia, hospitalization, graft loss; decline in renal function, urinary tract infections (UTIs), recurrent UTI and rate of MDR colonization/infection. Results: We enrolled 59 kidney transplant recipients and observed 147 episodes of ASB/ASC. Of the 147 episodes, 95 were untreated and 52 were treated. No significant differences were observed between treated and untreated patients in 30-day (2.1% vs. 3.8%) or 90-day mortality (2.1% vs. 1.9%), nor in any of the secondary clinical outcomes. However, patients who received treatment tended to have a higher rate of MDR colonization/infection (63% vs. 46%). MDR pathogen isolation was significantly associated with increased risks of septic shock (OR 4.639, p = 0.04), bacteremia/candidemia (OR 3.734, p = 0.01), hospitalization (OR 2.183, p = 0.03) and renal function deterioration (OR 3.93, p = 0.03). Conclusions: Antimicrobial treatment of ASB and ASC in the early post-transplant period would seem not to confer clinical benefit and may be associated with the risk of MDR colonization/infection. Full article

The fungus Coleosporium zanthoxyli is the causal agent of leaf rust in Chinese prickly ash pepper (Zanthoxylum armatum ‘Hanyuan putaoqing’), seriously impacting its industrial development. However, little is currently known about the infection and pathogenesis of C. zanthoxyli on Z. armatum. In this study, the infection of Z. armatum by C. zanthoxyli was reported at histological and cytological levels by a fluorescence microscope and transmission electron microscopy (TEM) for the first time. Fluorescence microscopy with fluorophore Alexa 488 (WGA-FITC) stained samples revealed that the infection process comprised three distinct stages: penetration (0–1 days post inoculation, dpi), parasitic growth (3–5 dpi), and sporulation (≥7 dpi). The number of haustoria increased during the osmotic and parasitic periods and then decreased; the length of hyphae also increased rapidly and then decreased. TEM analysis during these stages demonstrated that as disease severity increased, chloroplasts and mitochondria enlarged significantly, accompanied by a marked accumulation of starch granules and osmiophilic granules. At later stages, the nuclei became irregular, the grana lamellae were blurred, and the lamellar structure was arranged disorderly, and leaf tissues were extensively colonized by fungal hyphae and haustoria, leading to cellular necrosis and distorted cell walls. Notably, the sporulation phase was characterized by dense rust spore clusters covering the leaf surface. These findings provide critical insights into the ultrastructural changes induced by C. zanthoxyli during infection, elucidating key mechanisms of rust-induced damage in Chinese prickly ash and identifying the parasitic phase as a critical window for control strategies. This study lays a foundation for further research on rust pathogenesis and the development of Chinese prickly ash targeted control strategies. Full article

Phenolic compounds are widely known for their beneficial effects on human health. However, it is essential to understand which low molecular weight metabolites are produced by the gut microbiota, when non-absorbed compounds reach the colon, and whether these metabolites are more biologically active than their precursors. In this context, this study aims to explore the gut microbiota metabolites of relevant phenolic compounds commonly found in the human diet. Therefore, ellagic acid, naringenin, and phloroglucinol were incubated with human feces for 48 h, and the ensuing metabolites were analyzed by ultra-high-performance liquid chromatography with diode array detector coupled to ion trap mass spectrometry (UHPLC-DAD-MSⁿ) and gas chromatography–mass spectrometry (GC-MS). Ellagic acid metabolism by the gut microbiota produced a diversity of urolithins, with 8-hydroxyurolithin being identified for the first time. Isomers of 4-hydroxybenzoic, 3,4-dihydroxybenozic, and p-coumaric acids were identified for the first time as naringenin metabolites, while phloroglucinic, 2-hydroxy-3-phenylpropanoic, 3-phenylpropanoic, and 2-phenylacetic acids are reported for the first time as phloroglucinol metabolites. These findings contribute to a more comprehensive understanding of the beneficial health effects of these metabolites through the evaluation of their biological activities in conjunction with their effects on the gut microbiota, thus providing the basis for the development of food supplements, novel probiotics or functional foods. Full article

As two representative environmental contaminants, the individual toxic effects of microplastics and triclosan have been extensively studied; however, systematic evidence regarding their combined toxicity in mammals and the underlying mechanisms remains lacking. In this study, mice were orally exposed to triclosan (TCS) or/and polystyrene microplastics (PS), and their toxicity to intestine and liver was evaluated through histopathological examination, biochemical assays, and 16S rRNA sequencing. Results demonstrated that co-exposure to TCS and PS elicited markedly aggravated toxicological effects compared to individual exposures. Histopathological evaluation revealed exacerbated tissue damage, with histological scores substantially higher in co-exposed mice (colon: 7.27; liver: 5.0) than in PS-alone (colon: 6.07; liver: 3.0) or TCS-alone (colon: 3.0; liver: 0.7) groups. Quantitative Integrated Biomarker Response (IBR) analysis confirmed this potential additive or synergistic interaction: co-exposure not only dramatically elevated colonic oxidative stress (R_IB = 12.30 vs. 5.88 in PS and 0.23 in TCS groups) but also exacerbated inflammatory responses (R_IB = 11.69 vs. 3.52 in PS and 0 in TCS). Hepatic assessment demonstrated the most severe compromise in liver function and oxidative homeostasis following co-exposure (R_IB = 16.48), markedly exceeding the effects of individual PS (4.75) or TCS (0.43) exposure. In-depth exploration found that co-exposure to TCS and PS significantly disrupted gut microbiota homeostasis, characterized by enrichment of opportunistic pathogens and depletion of short-chain fatty acid-producing bacteria; these alterations were not only correlated with intestinal barrier impairment but also exacerbated gut–liver axis dysregulation. Together, the findings not only highlight the synergistic toxicity of triclosan and polystyrene microplastics in mice but also identify the gut–liver axis as a mediator of this effect, thereby providing novel evidence for health risk assessment and underscoring a potential concern for human health under co-exposure. Full article

Papaya (Carica papaya L.) processing generates by-products that can serve as sustainable sources of bioactive compounds. This study aimed to extract and characterize the bioactive compounds from the peel and seeds of different papaya varieties and evaluate their antioxidant and antimicrobial potential, as well as their behavior under simulated digestion. The results indicated that Maradol seeds possessed the highest total phenolic content and antioxidant values, demonstrating superior compositional and functional profiles, and that seed extracts overall had greater antibacterial efficacy than peel extracts, with Hawaiian seed extracts exhibiting the greatest overall inhibition. Furthermore, under simulated gastrointestinal conditions, the combined extracts from peel and seeds effectively preserved phenolics through the gastric and intestinal phases and notably enhanced the generation of acetate and propionate during colonic fermentation. These findings robustly substantiate the functional valorization of papaya by-products and suggest that selecting extracts based on their specific bioactive profiles can significantly enhance their applications as natural, functional ingredients in the food industry. Full article

Epichloë is a genus of endophytic fungi that forms systemic, vertically transmitted, and asymptomatic mutualistic associations with grasses in the subfamily Pooideae. These symbioses are non-pathogenic and are of considerable importance in agronomic and livestock systems due to their roles in enhancing host fitness under biotic and abiotic stress. Several studies have reported associations between Epichloë endophytes and species of the genus Bromus, a taxonomically complex group characterized by varying ploidy levels and frequent hybridization. Among its sections, Bromopsis includes the highest number of species naturally colonized by Epichloë fungi, while sections Bromus and Ceratochloa show lower infection rates. In South America, endophytes such as E. pampeana, E. tembladerae, E. typhina, and morphotypes of Neotyphodium spp. have been documented in species including B. auleticus, B. brachyanthera, and B. setifolius, where they appear to contribute to stress resilience. Although most findings originate from Argentina, significant knowledge gaps remain regarding the diversity and distribution of these endophytes in native Bromus species across the continent. This review synthesizes the current understanding of Epichloë–Bromus interactions, emphasizing their ecological and agronomic relevance, particularly in South America. Key factors influencing the establishment of these symbioses are examined, and future research directions are proposed to advance the study of these associations. Full article

Clear aligners have gained popularity in orthodontics due to their aesthetics, comfort, and removability; however, their prolonged intraoral wear and frequent removal–reinsertion cycles create favorable conditions for microbial colonization. This in vitro study evaluated the efficacy of seven commercially available mouthwash formulations in inhibiting biofilms of Streptococcus mutans, Streptococcus oralis, and Candida albicans formed on four different clear aligner materials. Standardized aligner fragments were incubated for 24 h with microbial suspensions to allow biofilm formation, treated for 1 min with one of the mouthwashes, and then assessed for residual viability through spectrophotometric optical density measurements after a further 24 h incubation. Biofilm inhibition varied according to both mouthwash composition and aligner material. The chlorhexidine-based rinse (MW-D) consistently showed the highest inhibition across microorganisms, while the fluoride–cetylpyridinium chloride rinse (MW-B) performed strongly for S. oralis and C. albicans. An essential oil-based formulation with xylitol (MW-G) showed notable antifungal activity against C. albicans. Monolayer polyurethane aligners generally achieved higher inhibition rates than multilayer or copolyester-based materials. These findings indicate that antimicrobial efficacy on aligners depends on both mouthwash type and material, supporting a tailored approach to biofilm management in clear aligner therapy to reduce the risk of caries, periodontal disease, and candidiasis. Full article

Sessile serrated lesions (SSLs) are well-known precursors of colorectal cancer in the general population, but their role in inflammatory bowel disease (IBD) is less clear. This narrative review summarizes what is known about the prevalence, molecular features, endoscopic detection, malignant potential, and management of SSLs in patients with IBD, highlighting where evidence supports action nowadays and where prospective studies are urgently needed. IBD-associated colorectal cancer has long been considered a consequence of the inflammation–dysplasia–carcinoma sequence, distinct from the conventional adenoma–carcinoma pathway. Increasing evidence, however, suggests that the serrated pathway, typically characterized by SSLs and traditional serrated adenomas (TSAs), may also contribute to IBD-related oncogenesis. This review synthesizes histopathological, molecular, endoscopic, and clinical data on SSLs in patients with IBD, with contextual reference to TSAs, sessile serrated lesions with dysplasia, and serrated epithelial change only when relevant to their interpretation or risk stratification. SSLs are now more frequently identified in IBD surveillance, especially in ulcerative colitis and the proximal colon, although prevalence estimates remain heterogeneous due to evolving definitions and significant interobserver variability. Molecular studies indicate that IBD-associated serrated lesions often harbor BRAF mutations but display a lower CpG island methylator phenotype than their sporadic counterparts, suggesting an inflammation-modified biology. While most hyperplastic polyps and non-dysplastic SSLs appear to pose limited neoplastic risk, dysplastic serrated lesions carry a markedly higher likelihood of synchronous or metachronous advanced neoplasia. Advances in high-definition endoscopy and chromoendoscopy improve the detection of these subtle, mucus-capped, flat lesions, while endoscopic resection is nowadays feasible in expert hands. Future priorities should include prospective multicenter cohorts integrating molecular profiling to refine surveillance strategies. Full article

The expansion of genomes is a major evolutionary force, yet its role in facilitating adaptation to extreme environments remains enigmatic. Here, we investigate alpine Parnassius butterflies, a rare genus characterized by exceptionally large genomes, to unravel the interplay between genome architecture and high-altitude colonization. We present a new, 1.46 Gb draft genome assembly for Parnassius epaphus and perform a comparative analysis across six species. Our findings reveal a massive 3- to 5-fold genome expansion driven predominantly by Long Interspersed Nuclear Elements (LINEs). Counterintuitively, we discover that larger genomes possess a proportionally smaller fraction of young, active transposable elements (TEs), challenging the prevailing paradigm that recent TE proliferation is the primary driver of genome size. Instead, our temporal analysis demonstrates that this expansion is a legacy of two ancient TE waves (~8 and ~14 Mya), which remarkably coincide with major uplift phases of the Tibetan Plateau. We propose a model where the selective retention of these ancient TEs, mechanistically linked to major geological upheavals, provided the crucial genomic plasticity for colonizing Earth’s most extreme terrestrial habitats. This study re-frames TEs not merely as genomic parasites but as pivotal architects of adaptive genome evolution in response to profound environmental change. Full article

Implant-associated infections remain a major clinical challenge, often leading to implant failure, revision surgery, and increased healthcare burden. Systemic antibiotic administration is limited by poor local bioavailability and systemic side effects, highlighting the need for localized drug-delivery systems that can simultaneously support tissue integration and prevent bacterial colonization. This study aimed to develop and characterize a novel generation of chitosan membranes loaded with hydroxyapatite–clindamycin phosphate (CS/HA-CLY) for localized infection prevention at implantation sites. The composite membranes’ physicochemical characteristics were analyzed using ATR FT-IR, XPS, SEM, XRD, and contact angle measurements. Furthermore, the in vitro biomineralization potential was assessed employing the Taguchi method, while the in vitro release of clindamycin phosphate was examined through UV-Vis spectrophotometry. The CS/HA-CLY membranes exhibited improved wettability, drug release behavior, and biomineralization ability compared to neat CS. These results suggest that the developed composite membranes could successfully combine antibacterial efficacy and biocompatibility, supporting their potential as multifunctional biomaterials for preventing implant-related infections while promoting tissue integration. These findings provide a promising basis for further biological assays and in vitro evaluation. Full article

The growing demand for sustainable alternatives to animal and synthetic leathers has accelerated interest in mycelium-based materials as an eco-friendly solution for the fashion industry. This study explores the potential of mushroom mycelium to create leather-like materials that align with circular fashion principles. Five species of edible and medicinal mushrooms were cultivated on sawdust substrates and evaluated for their growth performance, physical properties, and suitability as leather substitutes. Growth analysis revealed distinct species-specific behaviors: Cubamyces flavidus and Lentinus squarrosulus exhibited rapid colonization, achieving full substrate coverage within five days and forming dense mycelial networks at 14 days. In contrast, despite growing more slowly, Sanghuangporus vaninii and Ganoderma gibbosum formed thicker, more compact mats that might be suitable for strong leather-like materials. Visual and structural assessments showed diverse textures, colors, and hyphal architectures resembling natural leather. Physical characterization revealed shrinkage ranging from 13.17% to 24.09%, higher than for cow tanned leather (>5%) and PU microfiber (0.1–1.2%), suggesting a need for stabilization treatments. Apparent densities ranged from 0.13 g/cm³ to 0.30 g/cm³, lower than those of cow leather (0.49 g/cm³) and PU leather (0.38 g/cm³), highlighting species-specific hyphal structures that influence flexibility, porosity, and strength. SEM imaging confirmed the presence of interwoven hyphal mats resembling the fibrous architecture of natural leather, with S. vaninii showing the most uniform and continuous structure. Water absorption was significantly higher in mycelium sheets, consistent with their microporous nature, though S. vaninii showed the lowest uptake, reflecting possible natural water absorption. Thermogravimetric analysis revealed three-stage degradation profiles, with S. vaninii and G. gibbosum retaining >35% mass at 400 °C, indicating strong thermal stability for processing techniques such as hot pressing and finishing. Overall, the results demonstrate mycelium-based leathers as a biodegradable, low-impact alternative that can replicate the visual and functional characteristics of traditional leather, with opportunities for further improvement in substrate optimization, eco-tanning, surface coating, and scalable production toward a sustainable fashion future. Full article

Background/Objectives: The aim of this study was to reveal the influence of the natural nanoparticles (Nnps) isolated from Gegen–Qinlian Decoction (GQD), i.e., GQD-Nnps, on the intestinal absorption and pharmacokinetic properties of several representative active GQD constituents. Methods: The morphology of GQD-Nnps was examined using scanning electron microscopy (SEM). Protein and polysaccharide contents were measured using the bicinchoninic acid (BCA) assay and phenol–sulfuric acid method, respectively. Major GQD constituents were quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Formation mechanisms were explored using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and high-resolution mass spectrometry (HRMS). Pharmacokinetic studies were conducted in mice with dextran sulfate sodium (DSS)-induced UC. Results: GQD-Nnps were spherical, with a size of 110.9 ± 8.1 nm and a zeta potential of −13.7 ± 1.5 mV. GQD-Nnps were primarily composed of proteins and polysaccharides. FTIR analysis revealed significant hydrogen bonding interactions between the small molecular and macromolecular constituents of GQD. HRMS analyses indicated complex formation among small molecules, particularly berberine, baicalin, and glycyrrhizic acid. DLS demonstrated good stability of GQD-Nnps in artificial gastric and intestinal fluids. Pharmacokinetic studies showed that, except for puerarin, blood and liver exposure levels of several constituents in the GQD-Nnps group were significantly higher than those in the GQD extract group, suggesting enhanced colonic absorption and hepatic distribution. Conclusions: GQD-Nnps create an oral drug delivery system through complex interactions, significantly enhancing the colonic absorption and hepatic distribution of several active GQD constituents. Full article

This study characterized leaf extracts of Cymbopogon flexuosus (Ryukyu Lemongrass Corporation, Okinawa, Japan) and evaluated the bioaccessibility and bioactivities of phenolic compounds following a simulated in vitro gastrointestinal model of digestion (in vitro GID) of plant material. Undigested (controls, AqC, EtC) and digested aqueous (AqD) and ethanolic (EtD) extracts were analyzed. Control extracts contained higher total phenolics and flavonoids than digested ones, with EtC showing the highest values. UHPLC-QToF-MS (ultra-high-performance liquid chromatography system coupled to a quadrupole time-of-flight mass spectrometer) identified 32 compounds, including phenolic acids, flavone aglycones, C-glycosides, and derivatives. Hydroxybenzoic acids, coumaric acid, caffeic esters, flavones, tricin derivatives, vitexin, and isoorientin exhibited reduced recovery, while coumaric acid hexoside, ferulic acid hexoside, and isoschaftoside/schaftoside exceeded 100% recovery, suggesting release from the matrix. Some compounds were absent from AqD, and many were found in the pellet, indicating potential colonic metabolism. Antioxidant activity (DPPH, reducing power, β-carotene/linoleic acid) was stronger in controls but always weaker than BHT/ascorbic acid. Extracts mildly inhibited α-amylase but more strongly inhibited α-glucosidase as shown with applied enzyme inhibition assays, especially EtD (76.93% at a concentration of 10 mg/mL), which showed stronger activity than controls but remained below acarbose (87.74% at 1 mg/mL). All extracts promoted HaCaT keratinocyte growth and reduced HCT-116 colon cancer cell viability at 250 µg/mL, with the strongest effects in AqC and AqD. Overall, GID decreased antioxidant activity but enhanced antidiabetic potential, confirming the safety and selective anticancer effects of C. flexuosus extracts. Full article