Search Results (2,553)

Plants of the genus Salacia (Celastraceae) have long been used in traditional medical systems of South and Southeast Asia for the management of diabetes and related metabolic disorders. Modern phytochemical and pharmacological studies have confirmed the antidiabetic potential of several Salacia species, leading to the identification of a distinctive group of sulfur-containing sugars as their principal bioactive constituents. Salacinol, neosalacinol, kotalanol, neokotalanol, and related analogues represent a novel class of thiosugar sulfonium compounds that act as potent and selective α-glucosidase inhibitors, providing a clear mechanistic basis for their glucose-lowering effects. Simpler thiosugars, such as 5-thiomannose, further contribute to the overall metabolic activity of Salacia extracts and may serve as biosynthetic or functional precursors. Beyond Salacia, sulfur-containing natural products are widespread in nature and perform diverse biological roles. In particular, the genus Allium is well known for producing organosulfur compounds, including thioethers and polysulfides, which exhibit antidiabetic, hypolipidemic, antioxidant, and cardioprotective activities. In a different context, sulfur-containing hopanes have been identified in sediments and petroleum as products of early diagenetic sulfurization of bacterial hopanoids. Although these compounds have been studied primarily as geochemical biomarkers, recent QSAR/PASS analyses suggest that sulfur hopanes may also possess biologically relevant activities, particularly related to metabolic and cardiovascular regulation. Recent PASS-based QSAR evaluations of Salacia-derived thiosugars and sulfur hopanes predict significant antidiabetic activity, including potential type 2 diabetes-related pharmacological effects, supported by predicted α-glucosidase inhibitory, hypoglycemic, hepatic, and gastrointestinal activities. Collectively, these findings highlight sulfur-containing natural products from both plant and sedimentary sources as chemically diverse yet functionally convergent scaffolds with promising potential for the development of functional foods and therapeutic agents targeting metabolic disorders. Full article

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria. Full article

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by heterogeneous behavioral symptoms and systemic comorbidities, including immune and gastrointestinal dysfunctions. Emerging studies suggest that glycosylation—a fundamental post-translational modification regulating cellular communication and immune responses—may play a role in ASD pathophysiology, yet its contribution remains underexplored. Methods: In this study, we developed an integrative transcriptomic and network analysis framework to investigate glycosylation-related gene expression changes and their functional associations in ASD. Using publicly available datasets from bulk and single-cell RNA sequencing of brain and blood tissues, we focused on four prior-knowledge gene subsets: glycogenes, extracellular matrix glycoproteins, immune response genes, and autism risk genes. Results: Differential expression and pathway enrichment analyses revealed consistent dysregulation of glycosylation pathways, including mucin-type O-glycan biosynthesis, glycosaminoglycan metabolism, GPI-anchor formation, and sialylation, across ASD tissues. These transcriptional changes were functionally linked to altered immune signaling (e.g., IL-17, Toll-like receptor, and complement pathways) and synaptic development pathways, forming a distinct glyco-immune axis. Network analysis identified key glycogenes such as GALNT10, NEU1, LMAN2L, and CHST1 as central molecular nodes, interacting with immune and neuronal regulators. Linkage disequilibrium analysis further revealed ASD-associated SNPs influencing the expression of these glycogenes in both blood and brain tissues. Conclusions: Together, these findings support a model in which disrupted glycosylation contributes to ASD pathophysiology by mediating immune dysregulation and altered neuronal connectivity. This study offers a systems-level framework to understand the molecular complexity of ASD and highlights glycogenes as potential biomarkers and targets for future therapeutic exploration. Full article

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and an established therapeutic target in diseases such as cancer and ocular disorders. However, long-term use of most current anti-VEGF agents is often limited by their associated side effects, including hypertension, bleeding, and gastrointestinal complications. These limitations have stimulated interest in naturally occurring VEGF inhibitors derived from dietary sources, which may offer safer alternatives due to their favorable safety profiles. In this study, we investigated shared structural features of potent VEGFR2 inhibitors, focusing on naturally derived polyphenols. Polyphenols representing multiple structural subclasses were evaluated for their ability to inhibit VEGFR2 kinase activity using an in vitro kinase assay, to suppress VEGF-induced phosphorylation of VEGFR2 and downstream MAPK signaling in endothelial cells by Western blot, and to reduce VEGF-stimulated endothelial cell proliferation. Across all assays, flavonoids with strong VEGFR2 inhibitory activity displayed consistent structural characteristics, including the number and specific positioning of hydroxyl groups on the A- and B-rings, as well as specific structural elements of the C-ring. Our findings provide a strong foundation for further structure–activity relationship (SAR) studies and facilitate identification of key molecular determinants required for VEGFR2 inhibition. Elucidation of these structural patterns may contribute to the development of more effective and safer angiogenesis inhibitors with reduced adverse effects. Full article

Obesity in women of reproductive age is a major issue. It is associated with reduced fertility and an increased risk of obstetric and perinatal complications. Bariatric surgery is the most effective treatment for severe obesity, leading to substantial weight reduction, improvement of metabolic disorders, and enhanced fertility. Consequently, an increasing number of women are becoming pregnant after undergoing bariatric surgery. The aim of this paper is to review current recommendations and research data regarding the care of women after bariatric surgery in the periconceptional and perinatal periods, as well as throughout pregnancy, delivery, and the postpartum period. Research suggests that pregnancy after bariatric surgery is associated with a lower risk of gestational diabetes, hypertension, preeclampsia, and fetal macrosomia compared with pregnancies in women with similar baseline BMI (body mass index) who have not undergone surgical treatment. At the same time, an increased risk is observed for low birth weight, maternal micro- and macronutrient deficiencies, and complications characteristic of bariatric procedures, such as dumping syndrome or intra-abdominal hernias. Most scientific societies recommend postponing pregnancy planning for 12–18 months after surgery and using effective contraception, preferably methods that do not require gastrointestinal absorption. Regular monitoring of laboratory parameters, individually tailored supplementation, and interdisciplinary care are essential for the safe management of pregnancy after bariatric surgery. In particular, care should include achieving a stable body weight before conception, monitoring of nutritional status, verifying proper weight gain during pregnancy, and considering alternative methods for gestational diabetes screening (e.g., glycaemic monitoring instead of oral glucose tolerance testing) due to the risk of dumping syndrome. Appropriate preparation for pregnancy and proper management throughout its course allow for reducing the risk of perinatal complications. Bariatric surgery itself is not a contraindication to vaginal delivery. Full article

Autoimmune hepatitis (AIH) has long been regarded as an organ-specific disorder. However, increasing evidence supports its systemic nature, with extrahepatic manifestations representing key aspects of clinical management. These manifestations can affect musculoskeletal, gastrointestinal, haematologic, and other systems. They also reflect the complex interplay between systemic inflammation, concomitant autoimmune diseases, and drug-related toxicity. A careful evaluation is therefore essential to distinguish between these scenarios, especially for symptoms like fatigue and cytopenias. This narrative review provides a comprehensive, symptom-based overview of extrahepatic clinical and laboratory findings in AIH. By integrating current evidence with practical diagnostic considerations, it aims to offer clinicians a patient-centred and clinically relevant framework for navigating the multifaceted systemic landscape of AIH. Full article

Background: The prevalence of neurodegenerative diseases like Alzheimer’s and mental disorders like depression or anxiety appears higher in patients with gastrointestinal tract diseases like inflammatory bowel disease (IBD). Conversely, depressed patients have higher rates of gastrointestinal disorders. These observations suggest bidirectional communication between the brain and the gastrointestinal tract, the so-called “gut–brain axis”. Moreover, an altered microbiota, called “dysbiosis”, has been reported in these diseases, highlighting the network between gut microbes and their host. The emergence of the microbiota as a key regulator of the gut–brain dialog has led to the establishment of the concept of the “microbiota–gut–brain axis”. Objectives: In this narrative review, we outline the main interaction channels between the gastrointestinal tract and the brain. Then, we summarize current knowledge of two major diets (i.e., Western and Mediterranean diets) and the principal dietary components that modulate the microbiota–gut–brain axis to discuss the mechanisms putatively involved in intestinal, psychiatric, and neurological disorders. Conclusions: Diet is a major factor influencing the gut microbiota, and consequently, also putatively systemic mechanisms through the microbiota–gut–brain axis. Indeed, the composition of the diet is crucial for health and disease. Despite the main role of diet, the physiological, cellular, or molecular mechanisms involved in the complex communication between the microbiome, gut, and brain are still poorly understood. Full article

Background/Objectives: Constipation is a common gastrointestinal problem in older adults and is associated with reduced quality of life, functional decline, frailty, and an increased risk of delirium and cognitive impairment. Its pathogenesis is multifactorial, involving age-related changes in gastrointestinal motility, neural regulation, comorbidities, and polypharmacy. However, this condition has traditionally been regarded as a localized gastrointestinal disorder, which may not fully reflect its systemic clinical significance in older populations. While prior narrative reviews have described multifactorial contributors to constipation, none have formally applied a geriatric syndrome framework to integrate these dimensions. This review proposes a three-criterion operational definition—multifactorial pathogenesis, association with functional decline and frailty, and contribution to adverse systemic outcomes—to characterize constipation in older adults as a “systemic geriatric syndrome,” and evaluates available evidence against each criterion. Methods: A narrative literature search was conducted using PubMed to identify relevant studies published between 1 January 2023, and 31 December 2025. MeSH terms included “Constipation” [Major Topic] and “Aged” [MeSH Terms]. Eligible articles included English-language original studies, systematic reviews, and clinical or epidemiological studies involving individuals aged ≥65 years. Results: Diagnosis in older adults is often complicated by secondary causes, including medications and neurological disorders, as well as atypical symptom presentations in individuals with cognitive impairment. Key pathophysiological mechanisms include reductions in interstitial cells of Cajal, impaired smooth muscle contractility, dysfunction of the enteric and autonomic nervous systems, and gut microbiota dysbiosis, which may promote chronic low-grade inflammation. Major contributing factors include physical inactivity, sarcopenia, dehydration, inappropriate defecation posture, and polypharmacy, particularly opioids and anticholinergic agents. Importantly, these factors interact through the brain–gut–microbiota axis, contributing not only to gastrointestinal dysfunction but also to systemic outcomes such as frailty, cognitive decline, and increased healthcare burden, thereby supporting a multidimensional disease framework. Conclusions: The available evidence collectively supports the plausibility of framing constipation in older adults as a systemic geriatric syndrome, though formal validation of this classification requires further longitudinal and mechanistic research. Comprehensive and individualized management strategies, extending beyond simple laxative use, are essential to reduce complications and preserve functional health in aging populations. Further studies are required to validate this framework. Full article

Postoperative complications in gastrointestinal (GI) cancer patients remain a significant challenge for physicians. It leads to increased morbidity, prolonged hospital stays, and higher healthcare costs. Enteral immunonutrition (EIN) has emerged as a promising add-on treatment to modulate immune response following surgery. In fact, it reduces inflammation and promotes patients’ recovery. Indeed, the literature data on its real clinical impact for the patients are inconsistent and, yet, poorly investigated. Thus, the aim of this review was to narratively assess the current evidence for the use of EIN in postoperative GI cancer patients, evaluating the effect on clinical and immunological outcomes of patients. Therefore, a literature search was conducted using the following keywords and associations: enteral immunonutrition, gastrointestinal cancer, immune response, inflammation, and postoperative complication. GI cancers, mainly esophageal and gastric cancer, represent a significant global health burden, characterized by high incidence and mortality rates. The complex interplay between tumor progression, systemic inflammation, and host nutritional status profoundly impacts patient outcomes. Traditional cancer treatments are effective and often lead to severe side effects. The latter includes malnutrition and immunosuppression and can significantly affect patients’ recovery. In recent times, the concept of immunonutrition has emerged as a promising add-on therapy able to consensually modulate immune response and improve nutritional status. Several studies and meta-analyses suggest that EIN can reduce postoperative infections (e.g., wound infections and sepsis incidence), shorten hospital stays, and improve overall outcomes in GI cancer surgery patients vs. standard enteral feeding. EIN is a promising add-on approach for the management of postoperative GI cancer patients. It can significantly reduce postoperative complications and enhance their recovery. However, the result seems consistent for gastric but not yet esophageal cancer patients. EIN shows high tolerance and a high safety profile. Full article

Background/Objectives: Recently, a randomized clinical trial evaluated whether a six-month probiotic administration could reduce symptom severity in preschool children with Autism Spectrum Disorders (ASD), with (GI) or without (NGI) gastrointestinal symptoms. Significant positive changes were observed only in NGI children. A second explorative study on children prior to intervention identified a fecal metabolome fingerprint associated with ASD severity. Building on these findings, the present study aimed to assess whether metabolomics could monitor changes in ASD severity following probiotic administration using a subset of samples from the same trial. Second, this study aimed to identify fecal metabolites to be monitored in children to predict whether their autism severity may decrease after probiotic or placebo treatment. Methods: Evaluations of the fecal metabolome and microbiota could be completed on 57 children before and after a double-blind administration of a probiotic mixture or a placebo. Results: In NGI children the probiotic was found to influence the concentration of the amino acids aspartate, leucine, tryptophan, and valine, together with nicotinate and the short chain fatty acids acetate, butyrate, isobutyrate, and propionate. Lactobacilli and Sutterella showed significant changes in response to probiotic administration (p < 0.05). Acetate, 4-hydroxyphenyl, galactose, proline, and tyramine were identified as key fecal metabolites for prediction purposes. Conclusions: The present exploratory analysis, despite the small sample size, suggests that fecal metabolomics may provide a useful approach for monitoring and potentially for predicting changes in ASD severity following probiotics administration. Full article

Background/Objectives: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier integrity, innate immune regulation, metabolic activity, and mast cell effector mechanisms in CU. Methods: Forty CU patients and 40 healthy controls were evaluated. Clinical parameters included disease severity, disease subtype, antihistamine response, IgE levels, anti-TPO status, gastrointestinal symptoms, and angioedema. Serum levels of histamine, intestinal fatty acid-binding protein (IFABP), soluble CD14 (sCD14), diamine oxidase (DAO), D-lactic acid, endotoxin, zonulin, calprotectin, and related ratios were measured. Disease activity and control were assessed using the UAS7 and UCT scores. Results: CU patients exhibited significantly higher DAO (p = 0.003) and lactic acid (p = 0.004) levels compared to controls, whereas other markers showed no significant differences. In anti-TPO-positive patients, sCD14 levels were reduced (p = 0.024), while histamine/sCD14 (p = 0.005), lactic acid/sCD14 (p = 0.014), IFABP/sCD14 (p = 0.008), and zonulin/sCD14 (p = 0.027) were significantly elevated, suggesting relative amplification of metabolic and barrier-related signals under impaired innate immune regulation. Severe anti-TPO-positive patients exhibited lower sCD14 (p = 0.022) and NLR (p = 0.013) but higher UAS7 (p = 0.032), histamine (p = 0.011), calprotectin (p = 0.041), and CD14-normalized ratios, including histamine (p = 0.003), IFABP (p = 0.028), lactic acid (p = 0.019), zonulin (p = 0.029), and calprotectin (p = 0.011) compared with severe anti-TPO-negative patients, indicating a mast cell-dominant and metabolically active inflammatory phenotype. The lactic acid/DAO ratio was significantly lower in controlled versus uncontrolled CU (p = 0.013) and showed discriminatory potential for disease control. Patients with angioedema had higher CRP (p = 0.038) and UAS7 scores (p < 0.001). Conclusions: CU exhibits marked immunometabolic heterogeneity. Elevated DAO and lactic acid indicate increased histamine turnover and metabolic activation, whereas altered sCD14-normalized biomarker profiles reveal immune dysregulation in anti-TPO-positive patients. Severe CU with features suggestive of thyroid autoimmunity manifests as a mast cell-dominant, metabolically active phenotype with relative suppression of innate immune modulators, contrasting with alternative pathways in other CU phenotypes. The lactic acid/DAO ratio may serve as a candidate biomarker of disease control. These results underscore the importance of phenotype-tailored therapeutic strategies in CU. Full article

The preweaning period is a critical phase for dairy calves, during which gastrointestinal disorders, particularly diarrhea, remain a major cause of morbidity and antimicrobial use. Astaxanthin, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, has shown potential to support intestinal health in several animal species, but information in preweaning dairy calves is limited. The objective of this study was to evaluate the effects of astaxanthin supplementation administered through milk replacer on growth performance, clinical health, metabolic profile, and fecal microbiota in preweaning Holstein calves. Twenty-four female Holstein calves (body weight, mean ± SD: 49.51 ± 12.14 kg) were randomly assigned to a control group (CTR; n = 12) or an astaxanthin-supplemented group (TRT; n = 12). Treated calves received 40 mg/d of astaxanthin from week 0 to 4 and 80 mg/d from week 4 to 8. Body weight, feed intake, rectal temperature, and fecal consistency score, fecal color score and clinical scores were recorded throughout the trial. Blood samples were collected in weeks 0 and 8 for metabolic profiling, and fecal samples were collected in weeks 0, 4, and 8 to assess fecal consistency and bacterial populations. Astaxanthin supplementation did not affect body weight, average daily gain, or overall feed intake. However, treated calves exhibited a lower frequency of abnormal fecal consistency scores, indicating reduced diarrhea incidence compared with control calves. Fecal microbiological analysis revealed lower coliform counts in astaxanthin-supplemented calves in weeks 4 and 8, whereas total bacterial counts were greater in week 8. Most blood metabolites were primarily influenced by age-related physiological changes; however, circulating calcium concentrations were greater in treated calves. These results suggest that astaxanthin may represent a promising nutritional strategy to support gastrointestinal health during early life, although larger studies are needed to confirm these findings. Full article

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disorder with marked clinical heterogeneity, frequently leading to delayed diagnosis. We describe a 71-year-old woman with lifelong episodic inflammatory symptoms beginning in infancy, including recurrent fevers, lymphadenopathy, and gastrointestinal and mucocutaneous manifestations, later evolving into intermittent arthralgia, myalgia, and fatigue. A unifying diagnosis was established when genetic testing identified two missense pathogenic MVK variants consistent with compound heterozygous MKD, supported by elevated serum IgD levels and a characteristic clinical phenotype. This case illustrates the essential role of molecular genetic testing in resolving prolonged diagnostic odyssey, in guiding surveillance for complications such as AA amyloidosis, and enabling targeted therapeutic strategies. Full article

Background: Astragalus membranaceus Fisch. ex Bunge has long been used in East Asian medicine for gastrointestinal disorders and immune modulation. Astragaloside IV (AS-IV), a major bioactive saponin from its roots, exhibits potent anti-inflammatory and antioxidant activities, yet its protective effects against inflammatory bowel disease (IBD)-associated multi-organ damage via the gut–liver–brain axis remain unclear. Methods: Experimental colitis was induced in C57BL/6N mice by administering 5% dextran sulfate sodium (DSS) in drinking water for seven days. AS-IV (100 mg/kg/day) was orally administered during DSS exposure. Disease severity was evaluated using body weight, colon length, disease activity index, and histopathology. Inflammatory cytokines and oxidative stress markers were measured using ELISA, and NF-κB and MAPK signaling were analyzed through Western blotting and immunohistochemistry in colonic, hepatic, and brain tissues. Results: AS-IV significantly alleviated DSS-induced weight loss, disease activity, and colon shortening, while improving intestinal histopathological damage. AS-IV also reduced systemic pro-inflammatory cytokine levels and oxidative stress. Mechanistically, AS-IV was associated with a reduced expression of phosphorylated NF-κB and MAPK proteins, including p-NF-κB, p-IκBα, p-ERK, p-JNK, and p-p38, across the colon, liver, and brain. Conclusions: AS-IV attenuates DSS-induced multi-organ inflammation via gut–liver–brain axis modulation through NF-κB and MAPK pathway inhibition in experimental colitis models. Full article

Irritable bowel syndrome (IBS) and mental health disorders represent common and significant health concerns in pediatric populations. Objectives: This study aimed to evaluate psychological and social risk factors associated with IBS in children and to identify correlations with their gastrointestinal symptoms. Materials and Methods: Children aged 4 to 18 years diagnosed with IBS according to Rome IV criteria were eligible for inclusion. Both patients and parents completed a comprehensive questionnaire detailing gastrointestinal symptom characteristics. Additionally, all children underwent psychological assessment. Results: The study included 24 children with IBS, with a mean age of 12.7 ± 3.4 years. Anxiety was present in 54.2% of cases, and depression in 12.5%. Comparing children with IBS and anxiety to those without these, no statistically significant differences emerged regarding the duration and frequency of abdominal pain; however, abdominal pain intensity was significantly higher in children without anxiety (p = 0.04). The duration of IBS symptoms did not significantly differ in children with or without anxiety (p = 0.21). Impaired emotional self-regulation was identified in 54.2% of participants, and 41.6% exhibited vegetative symptoms in response to stress. Furthermore, 70.8% of parents and/or children reported experiencing a negative family event. Conclusions: The findings suggest that psychological characteristics and adverse family events are important risk factors associated with pediatric IBS. These factors should be systematically considered as integral components of clinical assessment and management. Full article