Search Results (4,591)

Chemotherapy-induced mucositis (CIM) is a dose-limiting toxicity of cancer therapy that is mainly associated with mitochondrial dysfunction in epithelial cells. We investigated whether GV1001, a mitochondrial protective peptide from human telomerase reverse transcriptase (hTERT), attenuates 5-fluorouracil (5-FU)-induced mucositis in a murine model. 5-FU induced notable mortality, leukopenia, and mucositis in the gastrointestinal (GI) tract, including tongue, esophagus and small intestine. It promoted epithelial–mesenchymal transition (EMT), nuclear factor kappa-B (NF-κB) activation, systemic and mucosal inflammation, DNA damage, impaired cell proliferation, and apoptosis throughout the GI tract. GV1001 blocked 5-FU–associated mortality, significantly attenuated leukopenia, and notably prevented mucositis. GV1001 also suppressed 5-FU-induced DNA damage, EMT, loss of proliferative capacity, apoptosis, and NF-κB activation in mucosal epithelium. In normal human keratinocytes, 5-FU inhibited the cell proliferation, disrupted mitochondrial function, as evidenced by reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production, impaired electron transport chain (ETC) complex integrity, decreased ATP synthesis, and cytochrome c release into the cytosol. GV1001 markedly mitigated these 5-FU-induced mitochondrial defects. Taken together, GV1001 mitigates CIM by most likely preserving mitochondrial integrity and function, supporting its potential as a strategy to prevent cancer chemotherapy-associated mucosal injury in patients. Full article

Salmonella enterica remains a major threat to animal and human health because of its broad host range, increasing antimicrobial resistance (AMR), and capacity to form biofilms. Biofilm formation enhances bacterial persistence in host tissues, farm environments, food-processing systems, and clinical reservoirs, while also contributing to their tolerance against antibiotics, disinfectants, and other stresses. However, biofilm capacity is not uniform across serovars and is influenced by host adaptation, niche specialization, and accessory genome content. This review synthesizes current knowledge on the relationship between biofilm formation, AMR, and serovar-specific adaptation in Salmonella. It examines biofilm-associated traits across various hosts (e.g., gastrointestinal tract and gallbladder, and environmental (e.g., food-production and clinical) niches, and discusses comparative evidence from genomic, transcriptomic, proteomic, and metabolomic studies. Particular attention is given to the emerging concept of comparative biofilmomics, which integrates phenotypic and multi-omics data across diverse serovars and host sources to identify conserved and niche-specific determinants of persistence. This framework may help define high-risk lineages that couple multidrug resistance (MDR) with enhanced biofilm-forming capacity. A better understanding of these linked traits will support the development of more targeted interventions for controlling persistent Salmonella in veterinary, food production, and public health settings. Full article

Background: Wireless capsule endoscopy is widely used for diagnosing gastrointestinal diseases, but manual interpretation of capsule videos is time-consuming and can vary between clinicians. Artificial intelligence has been increasingly studied to support capsule analysis and reduce clinical workload. This systematic literature review and meta-analysis summarizes current evidence on artificial intelligence methods applied to wireless capsule endoscopy, with a focus on diagnostic performance, validation strategies, and clinical readiness. Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and Google Scholar. Original journal articles were included based on predefined eligibility criteria. The reviewed studies addressed multiple artificial intelligence tasks, including detection, classification, segmentation, and localization of gastrointestinal abnormalities. Results: A total of 72 studies were included. Meta-analysis using random effects models showed high pooled diagnostic performance across clinical indications and gastrointestinal tract locations, with the strongest results reported for bleeding and vascular lesions and more variable performance for inflammatory bowel disease and mixed abnormality categories. The review also identified important clinical and technical barriers that may limit reliability and slow clinical adoption. These included limited external validation, small patient cohorts, retrospective study designs, and inconsistent reporting and evaluation practices. Conclusions: Artificial intelligence methods show strong potential to support wireless capsule endoscopy interpretation. Based on the findings, we propose practical recommendations to improve study design and validation. If these recommendations are applied, future studies may report more robust and reliable results, supporting better translation into clinical workflows. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder classically defined by cerebral amyloid-β (Aβ) plaque deposition and tau pathology. In recent years, AD has increasingly been recognized as a multisystem disorder rather than a purely brain-restricted condition, as mounting evidence indicates that Aβ metabolism is a dynamic, bidirectional process involving both central and peripheral compartments. Peripheral tissues, particularly platelets, liver, kidneys, and the gastrointestinal tract, contribute substantially to circulating Aβ levels and influence cerebral amyloid burden. Platelets are now considered the predominant source of peripheral Aβ, accounting for the majority of plasma Aβ under physiological and pathological conditions, while the liver and kidneys play critical roles in Aβ clearance through receptor-mediated uptake, enzymatic degradation and excretion. Disruption of these peripheral clearance pathways elevates circulating Aβ, increasing its transport into the brain via blood–brain barrier (BBB) mechanisms by enhanced RAGE-mediated influx and impaired LRP1-dependent efflux in AD. Peripheral Aβ entry into the central nervous system exacerbates neuroinflammation, mitochondrial dysfunction, and oxidative stress, thereby accelerating neuronal damage and disease progression. This review synthesizes updated evidence on peripheral sources of Aβ, differences between central and peripheral Aβ pools, mechanisms of Aβ transport across the BBB, pathological consequences of peripheral Aβ on the brain and emerging therapeutic strategies targeting peripheral Aβ metabolism, highlighting the importance of a systemic perspective in AD pathogenesis and treatment. Full article

Akkermansia muciniphila, a next-generation probiotic in the human intestinal mucus layer, exhibits significant health-promoting properties. However, traditional static culture systems fail to replicate the dynamic peristaltic environment of the gastrointestinal tract, limiting understanding of its metabolic characteristics. This study employed an improved gastrointestinal bioreactor simulating intestinal peristalsis to investigate A. muciniphila growth dynamics and metabolomic profiles under dynamic conditions. Dynamic cultivation significantly enhanced bacterial growth. Biomass reached 1.32 ± 0.03 g/L in bovine heart infusion (BHI) medium and 2.03 ± 0.05 g/L in BHI supplemented with 2.5 g/L porcine mucin. These values represent increases of 45.05% and 123.08% relative to static BHI cultures, respectively. Dynamic conditions markedly elevated short-chain fatty acid production (acetic, propionic, isobutyric, isovaleric acids). Untargeted metabolomics identified 1463 metabolites with 1294 showing significant differential expression. Dynamic cultivation substantially altered amino acid biosynthesis, fatty acid, purine, and pyrimidine metabolism. These findings advance the understanding of A. muciniphila physiology and provide insights into its metabolic characteristics under simulated intestinal conditions. Full article

Background/Objectives: The human gastrointestinal tract is a dynamic and interactive micro-ecosystem, with its distinct microbial population residing in the gut. The healthy condition of the gut is integrated into the normal functioning of all physiological activities. The gut microbiome is critical for the functioning of metabolism via several gut-axis connections with different systems in the human body; thus, it affects the status of health and general well-being. The fundamental physiology and homeostatic shifts are associated with specific diseases caused by a disrupted balance in the diversity of the gut microbiome, which could be due to a condition of dysbiosis in a host, instigated by several reasons. Some studies have been conducted on the selective isolation of probiotic species from dairy and other food sources to obtain effective probiotic strains, which have been studied and used by dietary intake strategies to restore gut microbial diversity, which is disturbed by some disease/s. Methods: Our search strategy included specific keywords—gut, microbiota, microbiome, disease, dysbiosis, probiotic bacteria and yeast—and was based on a timeframe of 15 years in the web-based electronic databases of PubMed, Scopus, and Web of Science. Among the few hundred results, a secondary screening was conducted to select references on probiotics studied for disease management with preclinical evidence and some reports on clinically validated outcomes; we excluded the search results for screening fermented foods for taxonomy studies of isolated probiotics. Results: The summarised information using two figures and two tables has been presented in this article from the review of 137 selected references: >75% have been published in the last 10 years. Conclusions: Further advances in modelling and analysis of the gut microbiota are required to understand their influence on the occurrence of certain diseases; this approach will allow us to establish research strategies for filling knowledge gaps, inconsistencies in clinical evidence, or limitations in translating probiotic effects from experimental models to humans. Full article

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations. Full article

Adenosine nucleotides are vital bioactive molecules with potential applications in functional foods and clinical nutrition; however, their poor membrane permeability limits their bioavailability. The utilization of plant proteins is often hindered by their poor solubility and digestibility. To address these challenges, we developed a strategy involving the formation of complexes between the walnut protein (WP) and four adenosine nucleotides. Spectroscopy, mass spectrometry, cell model, molecular docking, and other experimental techniques were conducted in this study; these methods demonstrated that such a complexation significantly enhanced the solubility of the WP to 3~4 mg/mL, while also enhancing its digestive stability in the gastrointestinal tract by 2~3-fold. Most notably, while all adenosines interacted with the protein matrix, cAMP exhibited a superior absorption efficiency, around 100-fold compared with its linear counterparts. Mass spectrometry and molecular docking were combined to reveal a new absorption mechanism for cAMP with the WP hydrolysate. These findings suggest that the complexation of WP and adenosine nucleotides offers a platform to overcome plant protein limitations and achieve efficient intracellular adenosine delivery, thereby establishing a foundation for its use in the development of functional foods. 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

Ten substituted quinobenzothiazinium salts were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All the compounds inhibited AChE in the IC₅₀ range of 0.03–0.658 µM, with 5,8,10-trimethyl-12H-quinolino[3,4-b][1,4]benzothiazin-5-ium chloride (3d) being the most potent inhibitor, with an IC₅₀ value significantly better than that of the clinically used rivastigmine and galantamine and comparable to that of tacrine and donepezil. The IC₅₀ values for BChE inhibition ranged from 0.34 to 4.25 µM; 5,9-dimethyl-12H-quinolino[3,4-b][1,4]benzothiazin-5-ium chloride (3b) exhibited the strongest BChE inhibitory activity and in general, all the investigated compounds were more potent inhibitors than rivastigmine and galantamine. Based on the calculated selectivity index values, they are rather preferential inhibitors of AChE. Cytotoxicity tests performed on normal human dermal fibroblasts (HFF-1) did not demonstrate any significant cytotoxicity under the tested conditions. The distance-oriented structure distribution for the studied molecules was related with the activity data using principal component analysis and hierarchical clustering analysis. (SAR)-based evaluation is reported to predict activity cliffs using a similarity–activity landscape index for the AChE inhibitory response values. Moreover, direct protein-mediated in silico methods were utilized to identify factors that may be relevant for quantitative (Q)SAR modeling. In practice, target-oriented molecular docking was used to organize the spatial distribution of the ligand property space for the anti-AChE system. In general, this series of alkylated quinobenzothiazinium salts with potent inhibitory activity against cholinesterases fulfills Lipinski’s rule of five based on in silico predictions and is also expected to have high absorption in the human gastrointestinal tract. All active derivatives are also expected to penetrate the blood–brain barrier, making them promising compounds for further research and possible use in Alzheimer’s disease therapy. Full article

Trained immunity is a concept that is currently in development and refers to the long-term functional reprogramming of innate immune cells in response to microbial or inflammatory stimuli. This process serves a dual purpose in the gastrointestinal tract, contributing to chronic inflammatory conditions like inflammatory bowel disease and maintaining host defense. The production of pro-inflammatory mediators is augmented by epigenetic and metabolic changes that are induced by the persistent activation of innate immune cells, which is triggered by microbial components and damage-associated signals. Although this increased responsiveness may initially be protective, sustained activation leads to tissue damage, epithelial barrier dysfunction, and chronic inflammation. These mechanisms are significant contributors to colorectal carcinogenesis, particularly in colitis-associated cancer. Through the activation of oncogenic signaling pathways, the establishment of a pro-tumorigenic microenvironment, and an increase in oxidative stress, trained immunity also influences tumor development. Additionally, the systemic reprogramming of hematopoietic progenitor cells has the potential to exacerbate inflammation and facilitate the progression of tumors. The identification of epigenetic and metabolic biomarkers associated with trained immunity can lead to novel diagnostic opportunities. Targeting metabolic and epigenetic pathways, as well as regulating the intestinal microbiota, is a promising therapeutic approach that could enhance the effectiveness of treatments for colorectal cancer while minimizing adverse effects on the immune system. Nevertheless, it is necessary to maintain a delicate equilibrium to suppress pathological inflammation without compromising protective immune responses. In general, trained immunity may represent a potentially relevant mechanistic link between chronic inflammation and colorectal cancer; however, its role remains context-dependent and not yet fully defined. Full article

Pyroptosis, a gasdermin-mediated and highly immunogenic form of regulated cell death, has surfaced as a critical determinant in the progression and therapeutic landscape of gastrointestinal (GI) cancers. Unlike non-inflammatory apoptotic pathways, pyroptosis involves the assembly of inflammasome complexes and the subsequent activation of caspases, leading to the cleavage of gasdermin proteins and the formation of transmembrane pores. It contributes to tumor suppression via immunogenic cell death and activation of antitumor immunity but may also promote tumor progression through chronic inflammation and remodeling of the tumor microenvironment. In this comprehensive review, we delineated the molecular architecture of pyroptotic signaling within the GI tract, highlighting the “double-edged sword” nature of this process. We further evaluated its role in the pathogenesis of GI cancers and in emerging translational strategies, including the pharmacological modulation of gasdermins and microbiome-based interventions, aiming to integrate pyroptosis induction into current immunotherapeutic frameworks. 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: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). This study aims to report the experience in the surgical treatment of GIST patients, evaluate the prognostic factors and discuss some controversial issues regarding the significance of microscopically margin-negative resection in GIST patients and the importance of tumor rupture during intraoperative surgical manipulation. Methods: Fifty-four GIST patients with primary disease without metastasis were admitted and treated during the past 15 years. Patients initially presenting with metastatic lesions and those who underwent adjuvant systemic therapy prior to surgical treatment were excluded from the study. Results: The median patient follow-up was 84 weeks. The 5-year overall survival was 34.34% and disease-free survival (DFS) was 35.37%. The median DFS was 244 weeks. In multivariate analysis, survival was affected by a high mitotic rate, resection margin status and the tumor rupture occurrence. Tumor size and tumor location did not show an impact. Conclusions: Surgical resection remains the mainstay of GIST treatment. Mitotic rate, resection margin status, and the occurrence of tumor rupture were predicators for DFS in patients presenting with primary disease. Recurrence of disease after resection was predominantly intra-abdominal and involved the original tumor size and the liver. Full article

Early post-hatch feeding strategies supplementing nutrients, particularly functional amino acids, have been proposed to enhance gastrointestinal tract (GIT) maturation and health in broilers in the post-antibiotic era. However, reported effects on performance and gut morphology remain inconsistent. Hence, this meta-analysis synthesized and clarified the efficacy pattern of supplemental FAA (Arg, Gln, Gly) evidence on growth performance, gut morphology, and lymphoid organ development. From a search spanning 2015 to September 2025, data were extracted from 23 eligible studies among 582 reports identified and pooled from five online databases. Standardized mean differences (SMDs) were calculated using Hedges’ g estimator with 95% confidence intervals, and heterogeneity was explored using subgroup and meta-regression procedures. Internal validity and reliability of included studies and publication bias were also assessed. The random-effects meta-analyses revealed that the FAA increased BWG (SMD = 1.01; p = 0.0006) and reduced feed conversion ratio (SMD = −0.45; p < 0.0001). Likewise, they enhanced intestinal architecture in both the jejunum and ileum. This was characterized by increased villus height (p < 0.05), reduced crypt depth (p < 0.05), and an elevated villus-to-crypt ratio (p < 0.0001), with the ileum exhibiting the greatest morphological response. In contrast, supplementation had no significant effect on spleen weight (SMD = 0.24; p = 0.2483) or bursa weight (SMD = 0.31; p = 0.1575). These effects, however, can be influenced by dosage used, dietary crude protein level, and broiler strain. In addition to enhancing the small intestine morphology early on, longer supplementation increased feed efficiency. Specifically, L-arginine and glycine efficaciously stimulated BWG, while L-glutamine and L-arginine enhanced morphology. Overall, early dietary supplementation with arginine, glutamine, or glycine is an effective post-antibiotic nutritional strategy to alleviate early post-hatch physiological stress and support broiler growth and intestinal development. However, to optimize nutrient utilization and sustain growth performance comparable to that achieved with standard CP diets, these FAAs in practical broiler nutrition should be strategically integrated into low-CP formulations. Full article