Search Results (207)

The application of essential oils and plant extracts as natural food preservatives has gained increasing interest; however, their potential impacts on gut health and host physiology remain unknown. This study evaluated the effects of synergistic combinations of peppermint essential oil (EO) + thyme EO and peppermint EO + feijoa peel extract on gut microbiota composition and colonic morphology in a rat model. Sprague–Dawley rats were orally given the synergistic combinations daily for 28 days, and their effects were assessed using 16S rRNA gene sequencing of the caecum microbiota and histological analysis of proximal colon tissues. Alpha diversity metrics showed no significant differences (p > 0.05) between treatment and control groups, and beta diversity indicated no treatment-related shift in the bacterial communities. Taxonomic profiling at the phylum, family, and genus levels showed comparable relative abundances of dominant microbial taxa across all treatments, with no evidence of dysbiosis. Histological examination of proximal colon tissues revealed no significant changes in crypt depth between treated and control groups, confirming the absence of adverse morphological effects on the intestinal epithelium. The results of this study indicate that synergistic combinations of peppermint EO, thyme EO, and feijoa peel extract do not adversely affect the gut microbiota composition and colonic morphology in rats, thereby supporting their application as preservatives in foods. Full article

Background and Rationale: Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) is a climbing medicinal plant with long-standing ethnopharmacological use, particularly in inflammatory and hepatic disorders and cancer-related conditions. There is a knowledge gap regarding how wild versus cultivated ecotypes differ in chemotype, bioactivity, and safety, and how this might support or refine traditional use. Study Objectives: This study aimed to compare wild and cultivated ecotypes of T. crispa from the Nile Delta (Egypt) in terms of quantitative and qualitative phytochemical profiles; selected in vitro biological activities (especially antioxidant and cytotoxic actions); genetic markers potentially associated with metabolic variation; and short-term oral safety in an animal model. Core Methodology: Standardized extraction of plant material from wild and cultivated ecotypes. Determination of total phenolics, total flavonoids, and major phytochemical classes (alkaloids, tannins, terpenoids). Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC₅₀ determination). Cytotoxicity against human cancer cell lines, with emphasis on HepG2 hepatoma cells and calculation of IC₅₀ values. Targeted genetic analysis to detect single-nucleotide polymorphisms (SNPs) in the gen1 locus that differentiate ecotypes. A 14-day oral toxicity study in rats, assessing liver and kidney function markers and performing histopathology of liver and kidney tissues. Principal Results: The wild ecotype showed a 43–65% increase in total flavonoid and polyphenol content compared with the cultivated ecotype, as well as substantially higher levels of key alkaloids, particularly berberine (around 12.5 ± 0.8 mg/g), along with elevated chlorogenic acid and borapetoside C. UHPLC-MS and NMR analyses confirmed the identity of the main bioactive constituents and defined a distinct chemical fingerprint for the wild chemotype. Bioassays demonstrated stronger antioxidant activity of the wild extract than the cultivated one and selective cytotoxicity of the wild extract against HepG2 cells (IC₅₀ ≈ 85 µg/mL), being clearly more potent than extracts from cultivated plants. Genetic profiling detected a C → T SNP within the gen1 region that differentiates the wild ecotype and may be linked to altered biosynthetic regulation. The 14-day oral toxicity study (up to 600 mg/kg) revealed no evidence of hepatic or renal toxicity, with biochemical markers remaining within physiological limits and normal liver and kidney histology. Conclusions and Future Perspectives: The wild Nile-Delta ecotype of T. crispa appears to be a stress-adapted chemotype characterized by enriched levels of multiple bioactive metabolites, superior in vitro bioactivity, and an encouraging preliminary safety margin. These findings support further evaluation of wild T. crispa as a candidate source for standardized botanical preparations targeting oxidative stress-related and hepatic pathologies, while emphasizing the need for: More comprehensive in vivo efficacy studies. Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species. Full article

Uveal melanoma (UVM) is a rare cancer that represents the second most common melanoma (after the cutaneous) and the most common primary intraocular malignancy in adults. Despite recent advances in the understanding of UVM pathogenesis, its prognosis remains unchanged, with half of patients dying because of liver metastasis. Erythropoietin-producing human hepatocellular receptors (EPHs) constitute the largest known family of tyrosine receptors, and, along with their ligands, EFNs, regulate key physiological processes and are implicated in cancer pathogenesis. In this study, we used open-access web bioinformatics platforms to explore and analyze big datasets provided by The Cancer Genome Atlas (TCGA) UVM cohort of patients. We profiled the genomic alterations present in a subset of UVM patients, highlighting a likely pathogenic deep deletion of EPHA7. Survival analysis showed that overexpression levels of EPHA4, EPHA5, EPHA8, EPHB2, and EFNB2 are significantly associated with poor overall survival. Additionally, high expression levels of EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2 correlate with reduced progression-free interval and disease-free survival. Finally, we identified the EPHs (EPHA2, EPHA4, EPHA8, and EPHB4) and EFNs (EFNA1, EFNA3, EFNA4, and EFNB2) that are significantly overexpressed in the aggressive epithelioid histological subtype and revealed that the majority of EPHs/EFNs are overexpressed in metastatic disease. In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients. Full article

Ovarian interstitial tissue (IT) is a prominent but poorly characterised component of the koala ovary. This study analysed the morphology and immunohistochemical profile of IT in the koala ovary across different reproductive phases. Ovaries from ten sexually mature females were examined histologically and immunolabelled for aromatase, HSD3B2, HSD17B1, the follicle stimulating hormone receptor (FSHR), and the luteinizing hormone receptor (LHR). IT occurred as multifocal cortical aggregates composed of two distinct cell types. Large interstitial cells were polygonal with highly vacuolated and weakly eosinophilic cytoplasm and were morphologically consistent with a steroidogenic phenotype. Small interstitial cells were densely eosinophilic, non-vacuolated, and morphologically uniform across reproductive phases. Immunohistochemical analysis revealed that small interstitial cells exhibited the broadest expression of steroidogenic markers in the ovary, with coexpression of HSD3B2, HSD17B1, aromatase, FSHR, and LHR. In contrast, large interstitial cells exhibited comparatively limited enzyme and receptor expression. Staining intensity across all markers was strongest during the interoestrous phase, moderate in the proliferative phase, reduced in the luteal phase, and minimal or absent when the koalas were lactating, suggesting potential cyclical variation in IT function. Granulosa, theca and germinal epithelial cells showed variable expression of steroidogenic enzymes and gonadotropin receptors, indicating that ovarian steroidogenesis in the koala may be more heterogeneous than predicted by the classical two-cell, two-gonadotropin model. Together, these findings provide preliminary evidence for the steroidogenic capacity of ovarian IT in the koala, indicating that its activity varies across reproductive phases, and appear to suggest a unique cellular organisation compared to other mammals. As these results are based on morphology and immunohistochemistry alone, further functional studies are required to confirm the steroidogenic output and clarify the physiological significance of IT in this species. Full article

Cancer remains a leading cause of mortality worldwide. Patient-derived organoids (PDOs) are three-dimensional (3D) cultures that recapitulate tumor histology, genetics, and cellular heterogeneity, providing physiologically relevant preclinical models. Integrating PDOs with artificial intelligence (AI) and machine learning (ML) enables scalable analysis of high-dimensional datasets, including imaging, transcriptomics, proteomics, and pharmacological readouts. These approaches support prediction of drug sensitivity, biomarker discovery, and patient stratification. Recent advances—such as deep learning (DL), transfer learning, federated learning, and self-supervised learning—enhance phenotypic profiling, cross-institutional model training, and translational prediction. In this review, we summarize the current state of AI-driven PDO research, highlighting methodological approaches, preclinical and clinical applications, challenges, and emerging trends. We also propose strategies for standardization, validation, and multi-modal integration to accelerate patient-specific therapeutic strategies. Full article

In male decapods, such as the Norway lobster Nephrops norvegicus, sexual maturity is not easily determined by macroscopic examination of gonads and few studies have been conducted on this topic. Sexual maturity is linked to changes in both external morphology and physiology. This study analyzed the maturity of N. norvegicus males in the Central-Western Mediterranean Sea (Sardinia), focusing on primary sexual characteristics (testes and vasa deferentia) and morphometric traits (appendix masculina and petasma). Since the testes showed no macroscopic changes in size during ontogeny, histological analysis was performed. It revealed that spermatogenesis occurred year-round in the Sardinian population, with the smallest mature individual at 18.3 mm carapace length (CL). All individuals above 23.5 mm CL had testes and vasa deferentia filled with spermatozoa and were considered physiologically mature. Morphometric maturity was observed between 27.7 and 36.2 mm CL, based on appendix masculina and petasma measurements. Despite a close association, secondary sexual characteristic development and physiological maturity were not synchronized, as seen in other crustaceans. This discrepancy likely reflects differences in male reproductive strategies, as males may produce spermatophores at smaller sizes (e.g., 23.5 mm CL), though there is no evidence that such males can successfully inseminate females in the wild. Full article

Food enrichment represents a novel feeding strategy for aquaculture. In the current study, juvenile Nibea albiflora (average weight 29.65 ± 0.13 g) were used and three feeding regimes (A—commercial diet; B—a diet comprising 90% commercial feed and 10% ice-fresh Palaemon gravieri; C—a diet consisting of 90% commercial diet, 5% ice-fresh Palaemon gravieri and 5% live Perinereis nuntia; named control group, Group 1, and Group 2) with comparable nutrient compositions: were designed to establish the food enrichment model and explore the effects of such feeding strategies on the fish. The cultivation period was 60 days, and the physiological, pathological, and RNA-seq analyses were performed to evaluate the effects. The results showed that the food enrichment feeding strategy significantly enhanced fish growth performance, immunity, and stress resistance without increasing the unit production cost (UPC). Furthermore, the tri-combined food feeding (C) was better than the two-combined food feeding (B). Liver transcriptomic analysis revealed that, in the comparison between the control group and Group 1, the up-regulated genes (alox15b, gng7, hif1a, ppara, and pla2g) and down-regulated genes (ins, gck, il4i1) influenced fish physiology and further improved growth. Similar to the comparison between the control group and Group 2, the major functional genes included ugt, nlrp3, mx1, col1a, gst (up-regulated), and map2k1, myc, mmp9, wnt7, socs3 (down-regulated) that participated in regulating the body growth, immunity, and stress resistance. The up-regulated genes (ins, mhc2, foxo3, ppara, and mx1) alongside the down-regulated genes (egfr, fos, cyc, myc, and mmp9) probably contributed to the enhanced efficacy of the tri-combined food feeding compared to the two-combined food feeding. In summary, this study demonstrates the beneficial effects of such a food enrichment model on the fish and provides empirical evidence supporting the implementation of the feeding strategies in the healthy culturing of the fish. Full article

Background/Objective: The effectiveness of blue-light phototherapy (PT) is mainly dependent on the total dose of light (time under PT and amount of skin exposed) received by infants. The primary aim of this study was the development of a novel, flexible, and stretchable device to provide continuous PT treatment, avoiding temporary interruptions that are often observed in practice, such as during breastfeeding, for example. This study evaluated the biocompatibility of a novel, low-cost blanket equipped with light-emitting diode (LED) lamps designed to maintain therapeutic efficacy while facilitating uninterrupted skin-to-skin contact. Methods: Fourteen New Zealand White rabbits, weighing approximately 2.9 kg and aged 4 months, were randomly assigned to an experimental group (TG, n = 7) or a control group (CG, n = 7). The TG received phototherapy directly on the skin (irradiance: 19.3 [13.0–22.0] µW/cm⁻²/nm⁻¹) during two 12 h sessions over consecutive days, while the CG remained under identical conditions with the device turned off. Biochemical, hematological, dermatological, and histological parameters, as well as rectal and skin temperatures, were assessed. Results: The results showed no differences in clinical appearance or histological analysis of skin tissue between the groups. Blood analysis indicated a reduction in absolute monocyte counts in the TG compared to the CG (p = 0.049), though levels remained within normal ranges. Skin temperature was consistently higher in the TG, except during the initial measurement. Rectal temperatures were similar on the first day but lower in the TG on the second day (mean 40.3 ± 0.21 °C vs. 40.7 ± 0.32 °C; p = 0.039). Conclusions: Temperature levels remained within physiological limits for both groups throughout the study. The device demonstrated biocompatibility and caused no adverse dermatological, hematological, or biochemical effects. Full article

Conventional cancer treatments have limited efficacy for aggressive subtypes such as triple-negative breast cancer (TNBC), which points to the importance of new therapeutic strategies. Functionalized nanoparticles in conjunction with photodynamic therapy (PDT) represent a promising alternative. Additionally, 3D cell culture emerges as a more effective model, as it better replicates the structural and functional characteristics of the tumor microenvironment. In this study, 3D microtumors of TNBC were cultivated and treated with PDT using gold nanoparticles functionalized with Chlorin e6 (AuNPs@Ce6). Cell viability was assessed using the MTT colorimetric assay, combined with histological analysis using hematoxylin-eosin staining. The MTT assay and histological evaluation of the 3D spheroids demonstrated that PDT with AuNPs@Ce6 effectively reduced cell viability and induced necrotic morphological changes, while maintaining biocompatibility with the non-irradiated control group. These findings reinforce the potential of this approach for further investigation in TNBC models and underscore the value of 3D cultures as physiologically relevant and ethical alternatives to animal testing. Full article

Background and Objectives: Sexual dysfunction (SD) is common in cancer but remains poorly characterized among patients receiving immune checkpoint inhibitors (ICIs). This study aimed to determine the prevalence and predictors of SD in ICI-treated patients using validated instruments. Materials and Methods: In this cross-sectional study, adults with histologically confirmed malignancies who received ≥ 3 cycles of ICIs and reported sexual activity were included. Sexual function was evaluated with the Arizona Sexual Experience Scale (ASEX) and the Golombok–Rust Inventory of Sexual Satisfaction (GRISS). Univariate and multivariate logistic regression analyses identified demographic and clinical predictors of SD. Results: Among 208 patients (median age 59 years; 35.1% female), SD prevalence was 66.3% by ASEX and 59.1% by GRISS. ASEX revealed impairment across five domains—sexual drive, psychological and physiological arousal, orgasm, and satisfaction—while GRISS indicated dysfunction mainly in impotence/orgasmic disorder, avoidance, and satisfaction subscales. In multivariate analysis, age ≥ 60 years (OR: 3.14, 95% CI 1.51–6.53, p = 0.002), female sex (OR: 3.19, 95% CI 1.31–7.74, p = 0.010), Eastern Cooperative Oncology Group (ECOG) performance status ≥ 1 (OR: 2.82, 95% CI 1.39–5.71, p = 0.004), ≥2 metastatic sites (OR: 3.08, 95% CI 1.53–6.19, p = 0.002), and later treatment lines (OR: 2.43, 95% CI 1.20–4.94, p = 0.013) independently predicted ASEX-defined SD. GRISS-based analysis revealed comparable outcomes, identifying ECOG ≥1 and higher metastatic burden as the most prominent predictors of SD, consistent with ASEX findings. Conclusions: SD affected nearly two-thirds of patients receiving ICIs. Female sex, later treatment lines, poor ECOG performance status, and higher metastatic burden were key determinants, emphasizing the importance of routine sexual health evaluation in cancer care. Full article

To explore the induction of low temperature the Tiger Puffer (Takifugu rubripes) In this study, the influence of temperature on the pituitary gland during masculinization was investigated through chronic hypothermia stress experiments. Metabolomics was used to analyze the metabolic regulatory network of the pituitary gland under hypothermia stress. ELISA technology was employed to determine the activity content of oxidative stress-related enzymes in the pituitary gland. Further, TUNEL fluorescence labeling and qPCR were used to detect the apoptosis level of pituitary cells. Finally, to assess the impact of low-temperature stress on muscle tissue, HE staining and qPCR techniques were employed. The results showed that after 45 days of low-temperature stress, the differential metabolites of the pituitary gland were mainly enriched in the amino acid metabolic signaling pathway, and the contents of amino acids such as GSH and its synthetic precursors in the pituitary tissue changed significantly. The contents of oxidative stress indicators such as ROS and MDA all showed a trend of first increasing and then decreasing. The qPCR results of TUNEL fluorescence labeling and apoptosis-related genes were consistent, indicating that the apoptotic level of pituitary cells first increased and then decreased with the stress process. Histological analysis revealed that low temperature led to muscle cell atrophy and increased interstitial space in muscle tissue. The expression changes in genes related to muscle development further confirmed that low temperature significantly inhibited muscle growth and development. Therefore, this study speculates that after being subjected to chronic low-temperature stress, the pituitary gland of the red-finned Oriental pufferfish can alleviate the oxidative stress response of the body by strengthening the amino acid metabolic pathway, and the fish body has shown a physiological trend of gradually adapting to low-temperature stress, but the growth and development of muscles are still significantly inhibited. The results of this study can provide theoretical support for understanding the physiological adaptation mechanism of the red-finned Oriental pufferfish to low-temperature stress and lay a foundation for subsequent in-depth exploration of the pituitary response mechanism to low temperatures. Full article

Carbon quantum dots (CQDs) are photoluminescent nanomaterials (<10 nm) with excellent hydrophilicity, biocompatibility, and low cytotoxicity, making them attractive for biological applications. However, their use in aquaculture nutrition has remained largely unexplored. This study investigated the effects of dietary CQDs on zebrafish (Danio rerio), a model organism with approximately 70% genetic homology with humans. CQDs were synthesized hydrothermally from unripe Citrus limon and characterized by UV–visible (UV-Vis) spectroscopy, UV–vis transillumination, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), Fourier-transform infrared spectroscopy (FT-IR), and photoluminescence (PL) spectroscopy. Zebrafish were fed diets containing varying CQD concentrations, and growth performance, condition factor (K), hematological parameters, enzymatic activity, and tissue morphology were assessed. Feeds supplemented with 2 mL CQDs produced significant improvements in growth and biochemical indicators without adverse effects. Hematological and enzymatic profiles remained within normal ranges, and histological examination revealed no morphological abnormalities, indicating the absence of toxicity. These findings suggest that citrus-derived CQDs can enhance zebrafish growth and maintain physiological health, thereby supporting their potential as safe functional feed additives in aquaculture. This approach may open new opportunities for the application of CQDs in sustainable fish farming and the broader food industry. Full article

Introduction: Maternal thrombophilia is associated with numerous obstetric complications, often occurring without overt clinical manifestations during pregnancy. Histological evaluation of the placenta can provide valuable insights into the etiology of these complications. Objective: To compare the placental histopathological profile in pregnancies with thrombophilia versus physiological pregnancies and to develop a synthetic score capable of retrospectively indicating thrombophilic risk. Materials and Methods: A retrospective observational study was conducted on two groups (n = 80 thrombophilia, n = 31 control). Macroscopic and histopathological placental parameters were analyzed. A histological score (range 0–5 points) was constructed based on the presence of villous stasis, stromal fibrosis, infarction, acute atherosis, and intervillous thrombosis. Results: The mean histological score was significantly higher in the thrombophilia group (2.20 ± 1.4) compared to the control group (1.18 ± 1.1; p = 0.0011). A score ≥ 3 was present in 39.1% of thrombophilic cases versus 13.6% in controls. Regression analysis showed that only placental diameter was significantly correlated with the histological score (p = 0.0379). Conclusions: The proposed histological score may serve as a simple and effective tool for the indirect identification of potential thrombophilic risk in complicated pregnancies. Its validation in future studies could support its implementation in routine obstetric and histopathological practice. Full article

Ammonia is a key factor in the water, impacting the physiological functions of aquatic organisms. To explore the effect of ammonia stress on mature eggs, female A. baerii at the end of the fourth stage of ovarian development were subjected to varying ammonia concentrations (0 mg/L (control, C), 10 mg/L (low concentration, T1), and 50 mg/L (high concentration, T2)) for 96 h. After 96 h of stress, histological analysis revealed that the follicular membranes of group T1 remained intact and clear compared to group C, although the vacuole fusion had begun. In contrast, the T2 group exhibited ruptured follicular membranes and adhered yolk granules compared to the C group, indicating structural damage. Transcriptome analysis generated 97.89 Gb of clean data, with each sample yielding over 6.09 Gb. A total of 5576, 3719, and 9446 differentially expressed genes (DEG_S) were screened from T1 vs. C, T2 vs. C, and T2 vs. T1 comparisons, respectively. Gene Ontology analysis (GO) functional enrichment analysis showed that DEG_S were significantly enriched in multicellular organism processes (T1 vs. C), cell surface receptor signaling pathways (T2 vs. C), and immune system processes (T2 vs. T1) during biological processes. It indicates that ammonia exposure may enrich cellular components in the extracellular space, potentially disrupting the function of the extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated significant impacts on amino acid metabolism, particularly glutamate and arginine pathways, as well as key pathways involved in steroid biosynthesis and antioxidation. Weighted gene co-expression network analysis (WGCNA) revealed that a total of 26,369 DEGs were divided into 29 distinct modules, displaying obvious associations with their traits. In the T2 vs. C group, antioxidation-related genes such as GST and GCLM were significantly downregulated, and the expressions of key enzymes for steroid synthesis, such as CYP11A1, CYP17, and CYP19A1 were suppressed, indicating that high ammonia nitrogen concentrations impair oocyte function by inducing oxidative stress and disrupting hormone synthesis. This study provides a comprehensive repertoire of candidate genes associated with ammonia stress in the mature egg of A. baerii, which will be useful for development of sturgeon breeding and reproduction. Full article

Background/Objectives: Acute spinal cord injury (ASCI) often leads to pulmonary complications, yet reliable, non-invasive assessment tools are limited. This study aimed to evaluate the utility of lung ultrasound (LUS) in assessing lung injury following ASCI in a rat model. Methods: Fifty-four female Sprague Dawley rats were randomized into sham (n = 27) or ASCI (n = 27) groups. LUS was performed at 12 h, 48 h, and 1 week post-injury, with lung injury quantified using a modified B-line score (BLS). Pulmonary function was assessed non-invasively, and histopathological evaluation and wet-to-dry (W/D) weight ratios were conducted post-mortem. Correlations between BLS and functional and pathological parameters were analyzed. Results: Histological analysis revealed progressive pulmonary hemorrhage, edema, and inflammatory infiltration peaking at 48 h post-injury, with residual hemorrhage and fibroplasia at 1 week. LUS findings evolved from narrow-based B-lines at 12 h to confluent B-lines with pleural abnormalities by 1 week. ASCI rats showed significant reductions in respiratory frequency, peak inspiratory and expiratory flow, and EF₅₀ at all time points (p < 0.05). Tidal volume and minute volume decreased initially, with partial recovery at 1 week. BLS negatively correlated with all pulmonary function parameters and positively with the histological score and W/D ratio (p < 0.001). Conclusions: LUS reliably detects and tracks lung injury after ASCI, correlating well with physiological and pathological indicators. These findings support its potential as a non-invasive monitoring tool. Future refinement of ultrasound scoring may improve clinical applicability in ASCI-related pulmonary assessment. Full article