Search Results (87)

Mentha pulegium L. is reported to contain phytochemicals known to bind to estrogen receptors and modulate estrogenic effects. A hydroethanolic leaf extract of Mentha pulegium L. (MPE) was prepared, and its effects on uterine and ovarian tissues in immature rats were investigated, focusing on transcriptional endpoint-related estrogenic activity. Female Sprague Dawley rats were treated with varying doses of MPE alone or in combination with estradiol for seven days. Gene expression analysis was performed using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to evaluate the effect of MPE on estrogen-responsive biomarkers: Calbindin-D9k (CaBP-9k), Progesterone receptor (Pgr), Trefoil factor 1 (pS2), Intestinal calcium-binding protein integral (Icabp), Integral membrane-associated protein-1 (Itmap1) and Complement component 3 (CC3) genes. In ovarian tissues, MPE treatment decreased CaBP-9k and Icapb expression, with CC3 showing significant decreases in the 200 mg/kg group. Treatments with MPE and estradiol significantly reduced the expression of all estrogen-responsive genes compared to estradiol treatment. In uterine tissues, 1000 mg/kg MPE increased CaBP-9k and pS2 expression significantly but decreased Icapb, CC3, pS2, and Itmap across all treatment groups significantly. Combined estradiol treatment with MPE (500 and 1000) mg/kg showed significantly low CaBP-9k and CC3 expressions. Increased expression of Icapb, Itmap, and pS2 was observed when combined estradiol treatments with MPE (500 and 1000) mg/kg were compared to estradiol treatment. MPE influenced the expression of specific genes in the uterus and ovaries and thus may exhibit endocrine-modulatory activity by multiple mechanisms of action, highlighting its potential complexity in modulating estrogenic responses. Full article

The silver pomfret (Pampus argenteus) is a high-value marine food fish, but its aquaculture is limited by juvenile intestinal immaturity, characterized by impaired digestion, barrier dysfunction, and microbial dysbiosis. This study evaluated whether early-life dietary inulin could improve intestinal health and muscle nutritional composition. After an 8-week feeding trial, fish fed a 5 g/kg inulin-supplemented diet showed improved growth performance, as reflected by higher final body weight (+17.2%), WGR (+18.5%), and SGR (+6.4%) than the control group. These benefits were associated with enhanced intestinal morphology, increased α-amylase and lipase activities, upregulated expression of tight junction genes, and a remodeled gut microbiota. These gut-associated changes were accompanied by improved selected muscle compositional traits. Specifically, inulin supplementation enriched essential amino acids, including methionine and threonine, as well as flavor-related amino acids, such as glutamate, glycine, and serine. Meanwhile, the muscle lipid profile was also modified, as reflected by reduced levels of selected saturated fatty acids and increased levels of monounsaturated fatty acids, particularly oleic acid. Collectively, our findings suggest that early-life dietary supplementation with 5 g/kg inulin may support intestinal homeostasis-related indicators and improve selected muscle nutritional traits in farmed silver pomfret. Full article

Preterm birth is associated with a higher risk of neurodevelopmental adverse outcomes later in life. This increased risk is partly due to interrupted brain development during critical early periods. Early nutrition is a key factor that can influence both brain growth and the development of the gut microbiota, which plays an important role in overall health. Evidence shows that human milk, including fortified human milk, supports the growth of beneficial gut bacteria such as Bifidobacterium and Lactobacillus. These bacteria help protect the immature intestine, reduce inflammation, and support normal development. In contrast, formula feeding, frequent use of antibiotics, and perinatal stress, common conditions for preterm infants in neonatal intensive care units, can disturb the normal development of the gut microbiota. These factors may lead to dysbiosis, a state in which harmful bacteria become more dominant. Early changes in gut microbiota may affect brain development through the gut–brain axis. This communication system connects the gut and the brain through immune responses, metabolic products, and hormonal pathways. Disruption of this system during early life may have long-term effects on cognitive, motor, and behavioral development. Both clinical and experimental studies suggest that improving early nutrition may support better neurodevelopmental outcomes. Nutritional strategies such as optimizing protein and energy intake and using probiotics or prebiotics may help promote a healthier gut microbiota and support brain development. In conclusion, early nutrition in preterm infants plays a crucial role during a sensitive period of brain development. By supporting healthy gut microbiota formation, early nutritional interventions may help improve long-term neurodevelopmental outcomes in this vulnerable population. The aim of this narrative review is to explore the relationship between early nutrition, gut microbiota development, and later neurodevelopment in preterm neonates. Full article

L-citrulline is a non-protein amino acid with critical roles in perinatal and neonatal physiology through the intestinal–renal arginine–citrulline axis and nitric oxide (NO) production. During pregnancy, L-citrulline supports placental angiogenesis, vascular adaptation, and fetal growth through augmentation of arginine availability and endothelial NO production. In neonates, particularly preterm infants, developmental immaturity of citrulline and arginine synthesis contributes to hypoargininemia and may increase susceptibility to necrotizing enterocolitis, bronchopulmonary dysplasia with pulmonary hypertension, sepsis, and impaired intestinal function. Although L-citrulline has emerged as a promising modulator of NO bioavailability, prior reviews have largely focused on either adult cardiovascular disease or isolated neonatal applications, with limited integration of its mechanistic and translational relevance across the perinatal and neonatal continuum. Collectively, current evidence supports L-citrulline as a promising translational target in maternal–fetal and neonatal medicine because of its central role in vascular, inflammatory, and metabolic regulation. However, adequately powered clinical trials are needed to define optimal dosing, timing, patient selection, and long-term outcomes before routine clinical implementation can be recommended. This review provides a comprehensive evaluation of L-citrulline metabolism and its therapeutic potential from pregnancy through neonatal life, with emphasis on the intestinal–renal arginine–citrulline axis, endothelial function, and NO-mediated vascular regulation. We specifically examine the role of citrulline in key pathophysiologic mechanisms underlying maternal and neonatal disease, including endothelial dysfunction, impaired NO bioavailability, inflammation, oxidative stress, and abnormal placental vascular remodeling. Full article

We evaluated the effects of different levels of DON (LD 441 and HD 1223 μg DON/kg in diet) on the growth performance, immunity, reproductive hormones, and intestinal health of immature gilts. No significant differences were observed in average daily gain, average daily feed intake, or feed to gain ratio between the LD group and the HD group (p > 0.05). The red blood cell count and hematocrit were higher in the LD group compared with the HD group on d 21 (p < 0.05). The gamma-glutamyl transferase activity in the LD group on d 1, 21, 28, 35, and 42 was higher (p < 0.05) compared with the HD group. The aspartate aminotransferase, total antioxidant capacity, and lactic dehydrogenase levels on d 35 were higher in the LD group than those in the HD group (p < 0.05). On d 35, the levels of interleukin 1β, interleukin-4, interleukin-10, tumor necrosis factor-α, and interferon-γ in LD were higher than those in the HD group (p < 0.05). The levels of immunoglobulin A, immunoglobulin M, immunoglobulin G, and complement 4 on d 35 were higher in the LD group compared with those in the HD group (p < 0.05). The gonadotrophin-releasing hormone, luteotrophic hormone, follicle-stimulating hormone, or estradiol did not differ between LD and HD groups throughout the experiment (p > 0.05). For fecal microbiota, Streptococcus in the HD group was reduced compared with the LD group (p < 0.05). In summary, feeding diets contaminated with 1223 μg DON/kg exerted adverse effects on serum profiles of gilts but did not affect their growth performance or reproductive hormones in the present study. Full article

Human milk is widely recognised as the optimal source of nutrition for newborns and infants, providing not only an ideal macronutrient composition but also a range of bioactive components that exert important non-nutritional functions, and as such it represents the first functional food consumed in early life. Among these bioactive components, the human milk oligosaccharides (HMOs)—a structurally diverse family of glycans present in human milk at concentrations 100- to 1000-fold higher than in the milk of other mammalian species—have emerged as multifunctional contributors to the establishment of the intestinal microbiome, immune development, anti-infective defence, and epithelial barrier integrity during a developmental window characterised by immune immaturity. The aim of the present narrative review is to synthesise current evidence on the anti-infective properties of HMOs in infancy and to integrate, within a single framework, five interconnected mechanisms through which HMOs protect the infant against infection: glycan-mimicry-based competitive inhibition of pathogen adhesion, direct antimicrobial and antibiofilm activity, selective prebiotic shaping of the gut microbiome, modulation of innate and adaptive immune responses, and reinforcement of mucosal barrier integrity in the gut and lungs. Breastfeeding constitutes a natural strategy for anti-infective protection in early childhood, while infant formulas supplemented with biotechnologically produced HMOs that are structurally identical to those in human milk provide measurable benefits for non-breastfed infants. Full article

During the early growth stage, lambs are highly susceptible to pathogenic microbial invasion due to an underdeveloped intestinal structure, unstable microbial colonization, and immature mucosal immune function, leading to diarrhea, growth retardation, and elevated mortality factors that severely constrain the production efficiency and economic viability of the sheep industry. This study aimed to compare the regulatory effects of compound yeast culture (CYC) and yeast polysaccharides (YPs) on intestinal barrier function in Mongolian male lambs and clarify their underlying molecular mechanisms. Eighteen lambs were randomly assigned to three groups (n = 6/group): control group (basal diet), CYC group (40 g/kg), and YP group (3 g/kg). After a 30-day feeding trial, intestinal histomorphology, tight junction proteins, immune signaling pathways, and gut microbiota were analyzed. The results showed that both additives improved intestinal villus morphology, and CYC markedly increased the villus height/crypt depth ratio (p < 0.05). At the mechanical barrier level, CYC upregulated the protein expression of occludin, claudin-1, and ZO-1, whereas YPs increased occludin and ZO-1 expression (p < 0.05). Immunologically, CYC inhibited intestinal inflammation via the TLR4/TRAF6/MyD88/NF-κB pathway, increasing interleukin-10 (IL-10) and secretory immunoglobulin A (sIgA) while decreasing pro-inflammatory cytokines. YPs exerted similar anti-inflammatory effects through the TLR2/MyD88 pathway. Microbial analysis indicated that both additives increased the relative abundance of beneficial bacteria including Eubacterium, Bacillus, and Succinivibrio, while reducing the potential pathogen Mogibacterium. Spearman correlation analysis revealed that Mogibacterium was positively correlated with TNF-α and negatively correlated with occludin expression. In conclusion, CYC and YPs effectively enhance intestinal mechanical, immune, and biological barriers via different TLR-mediated pathways and microbial modulation. Both natural additives have great application potential for improving lamb health, reducing antibiotic dependence, and promoting sustainable green animal husbandry. Full article

Weanling piglets, with immature immune system and physiological functions, often experience post-weaning diarrhea. This study investigated the effects of combined supplementation of live yeast and yeast postbiotics on the growth performance, antioxidant capacity and intestinal health of weaned piglets. A total of 224 weaned piglets (22 days old) were randomly assigned to four groups: a basal diet (CON) or the same diet supplemented with 1600 ppm zinc oxide (ZnO), high-dose live yeast and yeast postbiotics (LYYP-H), or low-dose live yeast and yeast postbiotics (LYYP-L). The trial lasted 28 days, with diets divided into 2 phases. The results showed that dietary combined supplementation with live yeast and yeast postbiotics did not significantly affect the average daily gain (ADG), average daily feed intake (ADFI), or the diarrhea rate (p > 0.05). However, dietary combined supplementation with live yeast and yeast postbiotics significantly enhanced fecal consistency in piglets (p < 0.05). Moreover, dietary combined supplementation with live yeast and yeast postbiotics significantly improved representative antioxidant indices, notably superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and strengthened immune capabilities; additionally, a marked improvement in intestinal morphology was observed (p < 0.05). In conclusion, the combination of live yeast and yeast postbiotics can improve antioxidant capacity and intestinal health and show the potential to replace high doses of ZnO during the first two weeks post-weaning. Full article

Necrotizing enterocolitis (NEC) and sepsis/late-onset sepsis (LOS) are significant contributors to preterm infant morbidity and mortality, with prematurity and low birth weight representing major risk factors for these interconnected conditions. Although the pathogenesis of NEC and LOS is not fully understood, there is a clear association with an immature intestinal mucosal barrier, which may enable bacterial invasion and translocation, resulting in an inflammatory cascade. Increasing recognition of the gut microbiome as a marker for health and disease has driven interest in probiotics, particularly Bifidobacterium spp. and Lactobacillus spp., as potential adjunctive agents for the prevention and management of NEC and LOS in preterm infants, which is the area of focus of this review. The focus of this paper was to analyze clinical studies using different probiotic strains, and compare single-strain versus multi-strain probiotic formulations. Several studies support that probiotic supplementation in preterm infants has the potential to decrease NEC incidence and, to a lesser extent, sepsis/LOS. Nonetheless, inconsistent results due to strain differences and clinical heterogeneity limit the widespread adoption of this mode of therapy, as do safety concerns in this vulnerable population. Further high-quality standardized studies are necessary to establish consistent guidelines for probiotic use in preterm infants. Full article

The intestinal barrier undergoes profound changes with age, impacting local immunity and systemic health, yet the mechanisms coordinating immune and microbial dynamics across the lifespan remain incompletely understood. Toll-like receptor 4 (TLR4) serves as a key mediator of host–microbiota interactions. This study investigated age-related changes in barrier function and the role of TLR4 using C57BL/6J and TLR4 knockout (TLR4^−/−) mice across key developmental stages: pups (postnatal day 9), adults (2–4 months), middle-aged (7–9 months), and old (16–19 months). Through a multi-layered approach integrating histology, microbiome profiling, short-chain fatty acid (SCFA) analysis, cytokine quantification, ex vivo functional assays, and transcriptomics, we identified a multi-phase process of intestinal remodeling. Pup-P9 mice exhibited immature colonic structure, a simple microbiota dominated by Firmicutes and Proteobacteria, and undetectable acetic acid level. Adults reached peak diversity and SCFA concentrations, marked by a rise in Bacteroidota and the emergence of Akkermansia. In middle and old age, pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) increased, Bacteroidota declined while Firmicutes, Actinobacteria, and Turicibacter expanded, and aged colons showed blunted ex vivo responses to IL-1β. This age-associated functional decline phenotype was absent in TLR4^−/− mice, supporting the involvement of TLR4 signaling. Transcriptomics further revealed biphasic PI3K/Akt activation in both pups-P9 and old mice. Together, these findings suggest a systemic rewiring of host metabolic and immune signaling pathways in response to an aging microbiota, highlighting this dynamic, lifespan-wide microbiota–host signaling axis as a potential intervention target. Full article

Background: Schistosomiasis affects more than 250 million people, and praziquantel remains the only drug available for treatment; however, its activity is restricted to adult worms. Previously, our group evaluated six thiazole derivatives (PBT1–PBT6) in vitro against adult Schistosoma mansoni, identifying PBT2, PBT5, and PBT6 as the most active compounds. The present study aimed to evaluate the in vitro activity of PBT2, PBT5, and PBT6 against schistosomula and juvenile worms, as well as their in vivo efficacy against adult S. mansoni. Methods: Mechanically transformed schistosomula and juvenile worms recovered from mice (21 days post-infection) were incubated with the compounds (12.5–200 μM). Cytotoxicity was assessed using murine splenocytes and peritoneal macrophages exposed to the same concentration range. For in vivo evaluation, infected mice were orally treated with compounds (50, 100, or 200 mg/kg) for five consecutive days. Results: All compounds induced 100% mortality in schistosomula and juvenile worms within 3 h of exposure at 100 and 200 μM. Parasite cell viability was markedly reduced (>90%) at concentrations between 50 and 200 μM. The LC₅₀ values ranged from 15.3 to 30.9 μM for schistosomula and from 27.8 to 34.9 μM for juvenile worms, with low cytotoxicity observed in mammalian cells (CC₅₀ ≥ 193.9 μM). In vivo treatment resulted in significant reductions in fecal egg counts (~80% at 200 mg/kg), total worm burden (~60%), and egg loads in liver and intestinal tissues, in addition to an increased proportion of dead eggs in the intestine. Conclusions: The evaluated thiazole derivatives demonstrated potent in vitro activity against immature stages of S. mansoni and significant in vivo efficacy against adult parasites, accompanied by favorable changes in key parasitological parameters. These findings reinforce the potential of thiazole-based compounds as promising multistage schistosomicidal candidates. Full article

Vitamin K prophylaxis represents a paradigmatic example of how molecular mechanisms directly translate into effective neonatal preventive care. In newborns, physiological immaturity of vitamin K metabolism, including limited placental transfer, low hepatic reserves, immature intestinal absorption, and dependence on vitamin K-dependent γ-carboxylation pathways, creates a unique vulnerability to vitamin K deficiency bleeding (VKDB). This narrative review integrates molecular and biochemical mechanisms with neonatal physiology and clinical evidence to examine the effectiveness of current prophylactic strategies. At the molecular and pharmacokinetic level, intramuscular (IM) administration ensures sustained bioavailability and reliable activation of vitamin K-dependent proteins, whereas oral regimens are more sensitive to formulation, dosing schedules, and absorption efficiency. Consistently, clinical and surveillance data demonstrate near-complete protection against both classic and late VKDB following IM prophylaxis, while oral approaches show greater variability, particularly in real-world settings. Importantly, increasing parental refusal of IM vitamin K undermines an intervention with well-established molecular efficacy, contributing to preventable severe bleeding events. By linking mechanistic foundations to clinical outcomes and implementation challenges, this review provides a translational framework for clinicians, researchers, and policymakers aiming to optimize neonatal vitamin K prophylaxis in contemporary practice. Full article

Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease of preterm infants, increasingly viewed as a cytokine-driven disorder of the immature intestine. We aimed to characterize local peritoneal concentrations of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in a standardized neonatal rat NEC model and relate them to histopathological injury. Seventy-four SPRD/Mol/Lodz rat pups were allocated to a control group (CTRL; n = 12) or subjected to a hypoxia-hypothermia-formula-feeding NEC protocol (NEC; n = 62). After 72 h, small-intestinal samples were scored using a four-tier NEC scale (0–3), and peritoneal fluid cytokine levels were measured by ELISA. All CTRL animals exhibited normal histology (grade 0), whereas NEC pups showed a wide spectrum of lesions, with 66.6% classified as grade 2–3 and a significantly higher mean NEC score in NEC than CTRL (p < 0.001). Peritoneal IL-1β and TNF-α concentrations were markedly elevated in NEC versus CTRL animals (both p < 0.001), while IL-6 levels showed no statistically significant between-group difference. These findings indicate that experimental NEC in this model is accompanied by a pronounced local pro-inflammatory response dominated by IL-1β and TNF-α, whereas IL-6 may follow distinct temporal or compartment-specific kinetics. Peritoneal cytokine profiling may help refine mechanistic understanding and guide future biomarker and immunomodulatory strategies in NEC. Full article

Background and Clinical significance: Cowden syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in the PTEN tumor suppressor gene. It is characterized by multiple hamartomas and an increased lifetime risk of malignancies affecting the breast, thyroid, endometrium, and gastrointestinal (GI) tract. Pediatric presentations may include macrocephaly, scrotal tongue, and intellectual disability. Gastrointestinal involvement is frequent, with juvenile-like hamartomatous polyps occurring in at least half of patients and distributed throughout the GI tract, posing a risk for malignant transformation. Early diagnosis and surveillance are crucial for improving patient outcomes. Case Presentation: We report a case of a 10-year-old Caucasian female with Cowden syndrome, with a history of a malignant germ cell tumor of the ovary consisting of a yolk sac tumor and low-grade immature teratoma diagnosed at age six, and thyroidectomy at age nine. The patient has mild intellectual disability. Routine radiological surveillance revealed a right colon intraluminal mass, prompting referral for pediatric gastroenterology evaluation. Endoscopy identified multiple polyps throughout the colon, stomach, and small intestine. Polypectomy of larger lesions was performed, and histopathology confirmed juvenile-like hamartomatous polyps without dysplasia or malignancy. This case highlights the necessity of comprehensive gastrointestinal evaluation in pediatric Cowden syndrome patients. Endoscopic surveillance is essential for early detection and management of polyps. Conclusions: Given the multisystem involvement and elevated cancer risk associated with PTEN mutations, a multidisciplinary approach that includes genetic counseling, dermatologic evaluation, and ongoing oncologic monitoring is recommended. Increased awareness of gastrointestinal manifestations enables timely intervention and may reduce morbidity and mortality in this high-risk population. Full article

Weaned piglets have a fragile gastrointestinal tract and immature digestive function. Supplementation of Bacillus can enhance intestinal barrier function and improve nutrient digestion and absorption efficiency. It is an important nutritional regulation method to alleviate weaning stress, reduce the incidence of diarrhea and promote growth performance. This experiment was conducted to investigate the effects of Bacillus subtilis, Bacillus pumilus and their combination on growth performance, diarrhea incidence, nutrient apparent digestibility, intestinal morphology and barrier function of weaned piglets. A total of 128 weaned piglets weighing 6.68 kg (±0.35 kg) were selected, divided into 4 treatment groups, and fed with a basal diet (CTR), a Bacillus subtilis (BS1), a Bacillus pumilus (BS2) and a Bacillus subtilis + Bacillus pumilus (BS1 + BS2) for 42 days. Each group had 8 replicates with 4 piglets per replicate. One piglet was selected from each replicate and euthanized to collect intestinal samples. The results showed that compared with the CTR group, the BS1 + BS2 group significantly increased the average daily gain (ADG) of weaned piglets on days 0–14 (p < 0.05), and the BS2 group significantly increased the ADG on days 0–42 (p < 0.05). Compared with the CTR group, the BS1 + BS2 group significantly reduced the full-time diarrhea rate (p < 0.05), and weaned piglets of the BS2 group significantly reduced the incidence of diarrhea on days 0–14, 15–28, and 0–42 of the study, in comparison to the control (p < 0.05). Compared with the CTR group, the piglets in the BS1 + BS2 group significantly decreased the serum tumor necrosis factor-α (TNF-α) content on day 21 (p < 0.05), and the BS1, BS2, and BS1 + BS2 groups significantly decreased the serum TNF-α content on day 42 (p < 0.05). Compared with the CTR group, the BS1 + BS2 group significantly reduced the expression of Interleukin-8 (IL-8) mRNA in the ileum (p < 0.05). The BS1, BS2, and BS1 + BS2 groups significantly reduced the expression of TNF-α mRNA in the ileum, IL-8 mRNA in the jejunum, and TNF-α mRNA in the jejunum (p < 0.05). In addition, compared with the CTR group, the BS2 and BS1 + BS2 groups significantly increased Claudin-1 mRNA expression in the jejunum (p < 0.05). Compared with the CTR group, the BS1 and BS2 groups significantly increased Occludin mRNA expression in the jejunum (p < 0.05). In summary, dietary supplementation with Bacillus-based probiotics can significantly improve growth performance in weaned piglets, reduce diarrhea incidence, alleviate inflammation, and enhance intestinal barrier function. Full article