Search Results (230)

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

Graft-versus-host disease (GVHD) is one of the principal complications seen in the recipients of allogenic hematopoietic stem cell transplantation (allo-HSCT), and persists as a leading cause of post-transplant morbidity and mortality. Increasing evidence highlights the crucial influence of the gut microbiome (GM) on transplant outcomes. Microbial dysbiosis, characterized by reduced bacterial diversity and pathogenic overgrowth, is strongly associated with higher rates of complications and mortality. Patients with lower microbial diversity exhibit poorer overall survival (OS) and an increased incidence of acute GVHD (aGVHD). Conversely, restoration of beneficial commensal communities has been shown to enhance immune homeostasis, mitigate GVHD severity, and decrease infection risk. Emerging therapeutic strategies now focus on modulating the intestinal microbiome through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT). It has been demonstrated that bacterial metabolites, such as short-chain fatty acids (SCFAs) from the diet, especially a diet rich in fibers, reduce the occurrence/severity of GVHD by inducing regulatory T cells (Tregs), which release anti-inflammatory cytokines and regulate the host immune system. Hence, the implementation of dietary fibers (DFs) could increase beneficial commensals, Treg induction, and improve outcomes such as GVHD and OS in recipients of allo-HCT. Hereupon, this review addresses how a fiber-rich diet modulates GM composition, reinforces epithelial barrier integrity, and improves the efficacy of Treg-based immunotherapy by stabilizing their regulatory phenotype and increasing their functional persistence, ultimately leading to a reduction in GI complications associated with GVHD. Unlike prior reviews that primarily cover the microbiome–GVHD axis or Treg therapies in isolation, this review emphasizes fermentable dietary fibers as a mechanistically grounded, clinically actionable strategy to support Treg stability and persistence via microbiota-derived metabolites. We integrate mechanistic evidence with emerging clinical feasibility data and ongoing trials of prebiotic supplementation in allogeneic HSCT. Full article

Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the past decade to examine bidirectional relationships between dietary patterns and seven common GI disorders: celiac disease, irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Helicobacter pylori-associated gastritis, peptic ulcer disease, and lactose intolerance. Western dietary patterns, characterized by high intake of ultra-processed foods and saturated fats and low fiber consumption, are consistently associated with microbial dysbiosis, impaired barrier function, and enhanced inflammatory signaling. In contrast, Mediterranean and plant-forward dietary patterns show protective associations across multiple GI conditions. Mechanistically, diet influences GI pathophysiology largely through microbiome-derived metabolites, particularly short-chain fatty acids, which regulate epithelial homeostasis, immune tolerance, and inflammatory pathways. Condition-specific dietary strategies remain clinically important. Gluten exclusion is essential in celiac disease, low- fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) approaches provide evidence-based symptom control in IBS, and exclusive enteral nutrition or targeted exclusion diets support remission induction in Crohn’s disease. Selected probiotics and emerging postbiotics may provide adjunctive benefits in specific contexts. Despite growing evidence, dietary research remains limited by methodological heterogeneity and interindividual variability. Precision nutrition approaches integrating microbiome profiling and artificial intelligence represent a promising translational direction. Overall, dietary patterns—rather than isolated nutrients—form the foundation of GI dietary therapy. Full article

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its G_i protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive G_i signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis. Full article

Gastrointestinal acute graft-versus-host disease (GI aGvHD) remains a leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Current diagnostic methods rely on invasive procedures with limited sensitivity. While circulating biomarkers have been proposed, little is known about the local transcriptomic landscape within inflamed GI tissue. We performed integrated profiling of mRNA and microRNA expression in colonoscopically resected GI biopsies from n = 8 HSCT patients, including n = 3 with histologically confirmed GI aGvHD and n = 5 without. Using NanoString nCounter technology, we quantified 770 immune-related mRNAs and 799 mature human microRNAs. Differential expression analysis, pathway enrichment, cell type deconvolution, and machine learning–based biomarker prioritisation were conducted to define disease-specific molecular signatures. GI aGvHD was marked by upregulation of inflammatory genes (e.g., IL1B, IL17RA, HLA-DRA) and immune-regulatory microRNAs (e.g., miR-155-3p, miR-223-3p), alongside downregulation of epithelial and anti-inflammatory markers (ST6GAL1, THBS1, miR-1915-3p, miR-145-5p). Enrichment analyses revealed activation of IL2/STAT5, JAK/STAT3, TCR signalling, and antigen presentation pathways. Machine learning identified LCN2, CXCL13, and miR-1269b as top-ranked biomarker candidates. Cell deconvolution showed increased M0 macrophage and decreased dendritic cell signatures in aGvHD tissue. This is the first study to integrate mRNA and microRNA profiling in GI tissue using NanoString technology to characterise the immune and epithelial transcriptomic landscape of aGvHD. Our findings reveal dysregulated immune pathways, altered myeloid cell populations, and novel biomarker candidates, offering tissue-specific insights into disease pathogenesis and potential diagnostic targets. Larger validation studies and functional assays are warranted to confirm clinical utility. Full article

Diseases of the gastrointestinal tract (GI) represent a major global health burden, leading to more than eight million deaths each year, largely driven by malignant conditions such as cancers and tumors. Early detection of such conditions can significantly improve survival rates. In this work, we present a compact two-port MIMO topology for high-speed telemetry and sensing. This system integrates two identical antennas, each operating at 915 MHz, positioned only 0.55 mm apart. It has just 11.9 mm³ (6.9 mm × 6.9 mm × 0.25 mm) volume, achieved through the use of meandered resonator and a high-dielectric laminate for miniaturization. Despite its small size, the design delivers a measured peak gain of −25.1 dBi at resonance. Low mutual coupling in the antenna-system is made possible by maintaining an optimized spacing and introducing a slot in the ground plane, resulting in isolation levels above 27.9 dB. The MIMO configuration was evaluated using standard performance metrics, and at an SNR of 20 dB, the system reached a better performance than single-element antenna. Beyond communication, this design also functions as a sensor, with its resonant frequency shifting in response to changes in the surrounding tissue’s permittivity: enabling real-time monitoring of internal physiological changes. Throughout the sensing process, the design maintains good gain and impedance matching, making it a strong candidate for biomedical implants. Full article

Background/Objectives: Oral health-related quality of life (OHRQoL) is a complex topic, encompassing the medical, functional and psychosocial aspects of well-being, especially in the context of systemic conditions that can trigger oral cavity impairment. While this subject has been extensively investigated in adults, evidence remains limited in pediatric populations, particularly in children with leukemia who are at high risk for oral complications related to the disease itself and its treatment. Moreover, children and parent perceptions of oral health are essential for guiding preventive and personalized therapeutic strategies, yet they are poorly explored in this clinical context. The objective of this study was to assess OHRQoL in children with leukemia and gingival inflammation, and compare it with that of children without this systemic condition. Methods: This observational, cross-sectional, case–control study was conducted on 99 subjects, divided into two groups: the study group n = 49 leukemia subjects and the control group n = 50 subjects without oncologic pathology. Clinical examination of all subjects was performed and oral health status was evaluated using Oral Health Index-Simplified (OHI-S) and Gingival Index (GI). Parents filled out a personalized exploratory questionnaire, adapted after established scales, designed to capture the child’s perceived impact of certain leukemia-related gingivo-periodontal alterations, including pain, ulcerations, gingival bleeding and xerostomia. Data were analyzed using descriptive statistics, Pearson’s Chi-square test and comparative graphical analyses (IBM SPSS Statistics 26). Results: Children with leukemia reported higher frequencies of xerostomia, ulcerations and gingival bleeding compared to children in the control group, with xerostomia showing a suggestive association to gingival inflammation. Oral hygiene status of children in the leukemia group was generally better among children receiving parental assistance during brushing or those practicing dental flossing. Comparative graphical analyses showed differences in symptom reporting and oral hygiene support between groups. Conclusions: The results suggest that xerostomia seemed to align with gingival inflammation in children with leukemia, while parental assistance and dental flossing seemed to be associated with better oral hygiene status. Our findings also support the need for developing standardized, disease-oriented scales of evaluating OHRQoL, as well as individualized oral care and continuous monitoring in order to improve oral health-related quality of life in this vulnerable pediatric population. Full article

Bovine mastitis remains a globally prevalent disease, with the limitations of antibiotic-based treatments—such as the rise in antimicrobial resistance and the presence of drug residues—highlighting the urgent need for alternative therapeutic approaches. Inflammation is intricately linked to various cytokines and immunomodulatory proteins, among which cyclophilin A (CypA) serves as a pivotal inflammatory mediator, significantly contributing to the initiation and amplification of inflammatory responses under such conditions. The acquisition of high-purity recombinant protein is a fundamental prerequisite for in vitro functional studies of bovine CypA. This study aimed to construct a eukaryotic expression vector for bovine CypA and verify its expression in CHO-K1 cells. Utilizing the bovine CypA gene sequence available in GenBank, the coding region was artificially synthesized and optimized for codon usage, subsequently being inserted into the pPB[Exp] backbone vector via BsrGI and BstEII double digestion. The resulting polycistronic expression vector contained a CAG promoter driving the CypA transcription, an EF1α promoter driving the EGFP reporter gene, a PGK promoter controlling the puromycin resistance gene, and a C-terminal His-tag. Restriction enzyme digestion and bidirectional Sanger sequencing confirmed that the inserted fragment sequence was completely consistent with the optimized design. Robust EGFP fluorescence was observed 24 h post-transfection and remained stable after puromycin selection. qPCR analysis showed that the Ct value of CypA in the experimental group was 16.20 ± 0.04, while no amplification signal was detected in the control group. Additionally, Western blot analysis identified a CypA-specific band at approximately 18 kDa, confirming the correct expression of the exogenous CypA protein in CHO-K1 cells. Collectively, these results demonstrate the successful construction and validation of a bovine CypA eukaryotic expression vector. The established CHO-K1 expression system exhibited stable and efficient expression, thereby providing a robust foundation for future research on the production and application of recombinant CypA protein. Full article

Background: Neurogenic bowel dysfunction (NBD) is a major chronic sequela of spinal cord injury (SCI) with substantial implications for rehabilitation and long-term management. However, population-level evidence describing how gastrointestinal (GI) diagnostic codes are used following SCI, particularly within administrative healthcare systems, remains limited. Methods: We conducted a nationwide retrospective cohort study using administrative claims data from the Korean National Health Insurance Service (NHIS). A total of 584,266 adults with trauma-related SCI encounters between 2009 and 2019 were identified. GI diagnostic codes—paralytic ileus (K56), irritable bowel syndrome (K58), and functional bowel disorders (K59)—were evaluated as administrative proxies for bowel dysfunction. Demographic characteristics, disability status, regional factors, and health behaviors were analyzed using multivariable logistic regression. Results: GI diagnostic codes were frequently recorded after SCI, most commonly irritable bowel syndrome (approximately 30%) and functional bowel disorders (approximately 37%), whereas paralytic ileus was uncommon. Greater disability severity, female sex, older age, and rural residence were consistently associated with higher odds of GI diagnostic coding. Physical activity showed robust inverse associations across all models. Inverse associations observed with smoking and alcohol consumption were interpreted as reflecting residual confounding or health-related selection, rather than biological protective effects. Conclusions: Patterns of GI diagnostic coding after SCI likely reflect the clinical burden and management needs of neurogenic bowel dysfunction within healthcare systems, rather than the development of new gastrointestinal diseases. These findings underscore the importance of individualized bowel management, incorporation of structured physical activity into rehabilitation programs, and equitable access to SCI rehabilitation services, particularly for individuals with greater disability or those living in rural areas. Full article

Inflammatory bowel disease is a result of inappropriate continuous non-specific inflammation in the intestinal tract, which in turn is aggravated by defects in the activation of the mucosal immune system and in the barrier function of the intestinal epithelium. The most prominent manifestations of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). UC is characterized by a continuous pattern that commonly starts with lesions in rectum mucosa and is contained in the colon. On the other hand, CD affects the ileum and colon in a discontinuous pattern, and the lesions are often transmural. Conventional therapies often face limitations such as systemic side effects, poor drug stability, and low site-specificity. In recent years, nanoparticle (NP) systems have emerged as a promising strategy to overcome these challenges, offering improved targeting, controlled release, and enhanced therapeutic efficacy. Several studies have shown that the preferential accumulation of NPs in the inflamed colon is influenced by the pathophysiological changes associated with IBD, including alterations in transit time, pH value, enzymatic activity, microbial composition, and mucus integrity. These disease-specific characteristics provide unique opportunities to design smart and responsive NPs that enhance drug delivery and therapeutic efficacy while minimizing systemic exposure. This work presents an overview of novel technologies based on nanosystems, with the ability to specifically target the affected areas of the GI tract in inflammatory bowel disease. Full article

This study proposes a novel two-dimensional Empirical Mode Decomposition (2D EMD)-based deep learning framework to enhance model performance in multi-class image classification tasks and potential early detection of diseases in healthcare using medical imaging. To validate this approach, we apply it to gastrointestinal (GI) endoscopic image classification using the publicly available Kvasir dataset, which contains eight GI image classes with 1000 images each. The proposed 2D EMD-based design procedure decomposes images into a full set of intrinsic mode functions (IMFs) to enhance image features beneficial for AI model development. Integrating 2D EMD into a deep learning pipeline, we evaluate its impact on four popular models (ResNet152, VGG19bn, MobileNetV3L, and SwinTransformerV2S). The results demonstrate that subtracting IMFs from the original image consistently improves accuracy, F1-score, and AUC for all models. The study reveals a notable enhancement in model performance, with an approximately 9% increase in accuracy compared to counterparts without EMD integration for ResNet152. Similarly, there is an increase of around 18% for VGG19L, 3% for MobileNetV3L, and 8% for SwinTransformerV2. Additionally, explainable AI (XAI) techniques, such as Grad-CAM, illustrate that the model focuses on GI regions for predictions. This study highlights the efficacy of 2D EMD in enhancing deep learning model performance for GI image classification, with potential applications in other domains. Full article

Cannabinoid receptor (CB1), a G protein coupled receptor (GPCR), is a known pharmacological target in several diseases and modulates key physiological processes through Gi protein-mediated signaling. However, recent evidence suggests that CB1 can also activate other G proteins, including the stimulatory Gs protein, a phenomenon with unclear structural determinants. Here, we use a computational approach to elucidate the structural basis of the CB1-Gs interaction. Protein–protein docking and extensive molecular dynamics simulations yield a model for the CB1-Gs complex that agrees well with both existing experimental data and available GPCR-Gs structures, supporting its validity. This work provides new insights into the structural basis of CB1’s ability to couple with different G-proteins. The model provides a basis for future studies dissecting the functional consequences of CB1-Gs signaling and the development of improved therapeutics targeting the CB1 receptor and the wider endocannabinoid system. Full article

Background: Gastrointestinal (GI) involvement is the most frequent visceral complication of systemic sclerosis (SSc), affecting up to 90% of patients, yet it remains poorly understood compared to pulmonary or cutaneous manifestations. The aim of this review is to integrate current knowledge on the cellular mechanisms underlying GI disease in SSc and to identify research priorities. Methods: A narrative literature review was conducted through a systematic PubMed search up to September 2025, complemented by manual reference screening. Results: Histopathological and functional evidence consistently demonstrates that neuromuscular alterations, including degeneration of enteric neurons, loss of interstitial cells of Cajal, and smooth muscle atrophy, can precede fibrosis, challenging the traditional “fibrosis-first” paradigm. Fibroblast and myofibroblast activation are present in gastric and colonic samples, sustained by profibrotic mediators such as TGF-β, CTGF, and endothelin-1, although the cellular origins of these stromal cells remain uncertain. Additional pathogenic contributions include autonomic dysfunction, barrier dysfunction with dysbiosis, impaired vascular reserve of vessels perfusing the gut, and functional autoantibodies targeting interneural and neuromuscular function and communication. Compared with skin and lung, the GI tract displays less fibrosis and fewer inflammatory infiltrates, but immune-derived mediators and autoantibodies suggest distinct immunopathogenic pathways are activated. Conclusions: Collectively, these findings depict GI involvement in SSc as a multi-compartmental process integrating neural, epithelial, endothelial, stromal, and immune alterations. Addressing the lack of validated biomarkers, mechanistic models, and biomarker-stratified trials will be essential to move beyond symptomatic care and toward precision medicine approaches for SSc-related GI disease. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) frequently experience upper gastrointestinal (GI) symptoms such as epigastric discomfort, nausea, vomiting, and early satiety. These symptoms can contribute to malabsorption and intermittent dehydration, ultimately accelerating the decline of residual renal function. However, they are often attributed to electrolyte imbalances or fluid overload, and the possibility of underlying gastroparesis is frequently overlooked by both patients and caregivers. This study aimed to provide new insights into the relationship between CKD and gastroparesis through a dual, population-based retrospective analysis that incorporated both inpatient and outpatient data. Methods: From the National Inpatient Sample (NIS) database, 3,579,372 patients diagnosed with gastroparesis, with or without CKD, were identified. From the TriNetX database, 6,263,251 patients presenting to ambulatory clinics with a chief complaint of nausea and vomiting were included. In both datasets, gastroparesis was defined using ICD-10-CM codes. Results: In the inpatient cohort, the prevalence of gastroparesis increased in proportion to CKD severity, with the highest likelihood observed in advanced stages compared to patients without CKD. An increased risk of gastroparesis was also observed in the outpatient CKD cohort from an independent TriNetX database, while the severity-dependent phenotype was not consistent. However, after rigorous propensity score matching, advanced CKD remained significantly associated with higher odds of gastroparesis, with the greatest risk observed in patients with end-stage renal disease (ESRD). Conclusions: These findings, validated across two large and independent datasets representing both inpatient and outpatient populations, demonstrate a consistent association between CKD severity and gastroparesis. They highlight the importance of routine screening and early management of gastroparesis in patients with advanced CKD to improve outcomes and reduce disease burden for CKD patients with sign of early satiety or dyspepsia. Full article

Introduction: Robotic-assisted surgery offers technological advantages such as three-dimensional visualization and improved dexterity, yet its clinical adoption in gastrointestinal (GI) malignancies is supported by evidence of varying quality, consisting mainly of retrospective studies. This review provides a structured summary of the current evidence for robotic surgery in pancreatic, gastric, liver, and colorectal cancers. Methods: A comprehensive literature review was conducted to assess and summarize the perioperative, long-term, and oncological outcomes of robotic-assisted surgery compared to laparoscopic and open approaches for the aforementioned GI malignancies. Results: The application of the robotic platform is most advanced in colorectal surgery. High-quality evidence for rectal cancer demonstrates improved quality of mesorectal specimens, better preservation of urinary and sexual function, and lower local recurrence rates. Across all reviewed GI malignancies, robotic surgery consistently shows advantages in lower conversion-to-open rates, reduced intraoperative blood loss, and shorter hospital stays, though it is associated with longer operative times and higher costs. The evidence for pancreatic and liver surgery is less mature due to the complexity of these procedures. Data for gastric surgery suggests improved lymph node retrieval and, in one long-term study, better disease-free survival. Conclusions: The highest-quality evidence supports the robotic approach for rectal cancer, showing clear functional and oncological benefits. While several perioperative advantages are consistently reported across all GI sites, robust data demonstrating superior long-term survival are still limited for most procedures. Full article