Search Results (664)

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT. Full article

Background/Objectives: Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and causes various gastrointestinal diseases. Although antibiotic therapy is the most effective method for its eradication, the increasing prevalence of antibiotic resistance has made treatment increasingly challenging in recent years. In this study, the antimicrobial activity, synergistic effects with antibiotics, and mechanisms of action of Bicarinalin, an antimicrobial peptide (AMP) derived from the venom of Tetramorium bicarinatum, were investigated against H. pylori. Methods: To determine the antibacterial activity of Bicarinalin, a well diffusion assay was performed, yielding an inhibition zone of 18.3 mm at a concentration of 32 µg/mL for ATCC strain. MIC₉₉ values were determined by microdilution tests as 4.8 μg/mL for the reference strain. The enhancement of the antimicrobial potential of levofloxacin and clarithromycin when administered together with Bicarinalin has been demonstrated using the well diffusion method. Results: Inhibition zones increased from 14.2 mm to 20 mm for levofloxacin and from 7.3 mm to 16 mm for clarithromycin. This study is the first to identify DNA and protein leakage caused by Bicarinalin in H. pylori. Intracellular protein and DNA leakage were measured, with protein and DNA levels released into the extracellular environment determined as 33.25% and 55.10%, respectively, following Bicarinalin treatment. Furthermore, to investigate its effect on membrane damage, scanning electron microscopy (SEM) was performed, revealing disrupted cell membrane structures, penetration between cells, and severe deterioration of morphological integrity. Conclusions: This study has demonstrated for the first time that, when administered concomitantly, Bicarinalin enhances the antimicrobial activities of levofloxacin and clarithromycin. This highlights its potential as an adjunctive treatment for H. pylori alongside existing drugs. Full article

Sea turtles, particularly the opportunistic feeder species loggerhead turtles (Caretta caretta), are increasingly reported as a source of disturbance to mussel farming operations, especially in the Adriatic Sea. Despite the evident damage caused by these interactions, comprehensive national data on the phenomenon are still lacking. This study aimed to address this gap through a survey conducted among Italian mussel farmers, combined with the analysis of gastrointestinal contents from stranded sea turtles along the Adriatic and Tyrrhenian coasts, focusing on the ingestion of Mediterranean mussels (Mytilus galloprovincialis). Survey results revealed frequent turtle sightings in the northern Adriatic (Veneto and Emilia-Romagna) during summer months (June to August), while southern regions (Molise and Puglia) reported more sightings in autumn (September to October), likely influenced by seasonal water temperatures. The Mediterranean mussel was identified as the most commonly ingested mollusk in the Adriatic, with a notable increase in presence from 2018 to 2021. Although mussels are not a targeted prey, they appear to be a consistent dietary component due to adaptive feeding behavior. These interactions are increasingly and consistently reported, leading to significant management challenges for mussel farms. Based on these findings, a broader national and international assessment is recommended to evaluate the overall impact of sea turtles on shellfish aquaculture in the Mediterranean. Full article

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target. Full article

Aging is the result of the accumulation of a great variety of molecular and cellular damage over time. During aging, the brain undergoes changes and diseases such as depression, dementia, anxiety, Alzheimer’s, delirium, behavioral disorders and aggression, and prolonged mourning, among others, appear. The gut–brain axis suggests that the gut and the brain have a bidirectional communication, so it is important to maintain proper intestinal health to strengthen the neurological changes of this age group. The intestinal microbiota is a dynamic and highly complex ecosystem of microorganisms residing in the gastrointestinal tract. The bidirectional and dynamic communication between the homeostatic systems, such as the endocrine and immune systems, as well as the nervous system, allow us to face problems associated with several diseases. Probiotics are defined as non-pathogenic live microorganisms that provide beneficial effects to the organism and participate in the prevention and treatment of diseases, which is the reason why it is important to promote interventions that keep intestinal microbiota in eubiosis (microbiota balance). The concentration and balance of the intestinal microbiota depend on several conditions, such as diet, antibiotic consumption, and lifestyle, to mentioned a few. However, interventions with probiotics have shown improvements in both cognitive function and processes that promote neurodegeneration. It is such that the research has been directed on designing strategies that improve not only oral bioavailability but also intestinal adhesion and retention, to clarify the frequency and dosage that should be consumed. Full article

Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses demonstrated that ORL significantly attenuated TBI-induced neurological damage. Microglial depletion experiments revealed that ORL’s neuroprotective effects were largely mediated through microglial modulation. In vitro and in vivo studies showed that ORL suppressed microglial activation, phagocytosis, and migration. Single-cell RNA sequencing identified upregulation of lipoprotein lipase (LPL) in a TBI-induced microglial subpopulation. Molecular docking predicted ORL-LPL binding, suggesting direct enzymatic inhibition. Transcriptomic and metabolomic analyses further revealed ORL’s modulation of microglial metabolic pathways and inflammatory responses. Our findings position ORL as a promising repurposed therapeutic for TBI through its novel mechanism of targeting microglial LPL-mediated neuroinflammation. Full article

Celiac disease (CD) is an autoimmune disorder that affects genetically susceptible individuals, characterized by specific serological and histological features, and is triggered by the consumption of gluten. The current diagnosis is based on the demonstration of intestinal damage in small bowel biopsies, as well as the serological presence of CD-specific antibodies (usually IgA) against tissue transglutaminase (tTG), deamidated gliadin peptides (DGP), and endomysium (EMA). The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), in the 2020 updated guidelines, states that the diagnosis of CD in children and adolescents can be established without a biopsy if they have IgA tTG2 >10 ULN confirmed by positive IgA endomysial antibodies on two separate blood tests. Challenges, though, arise in serological and clinical diagnosis: in several cases false-positive results are observed. False-negative serological tests may also occur in children < 2 years of age, in patients adhering to a gluten-free diet, in individuals on immunosuppressive therapy, in cases of selective IgA deficiency, and finally due to potential laboratory errors. CD has a wide range of clinical manifestations, either gastrointestinal or extraintestinal. However, CD may be clinically silent and diagnosed through screening. Delayed diagnosis and treatment can lead to serious complications. Therefore, understanding and awareness of these challenges is imperative. Hence, the aim of this review is to highlight the diagnostic challenges of celiac disease in children and adolescents and stress the importance of prompt recognition in order to ensure appropriate management and prevention of complications. Full article

Neuropeptides and their corresponding receptors have been observed to play a significant role in modulating immune cell functions and epithelial barrier functions. In teleost, Neuropeptide Y (NPY) is identified to be involved in the immune regulation of intestinal tissues during bacterial infections. However, the mechanism of NPY on infected gastrointestinal tissue remains unclear, as does whether other members of the NPY family, like ligand PYYb and some receptors Y7 and Y8b, also contribute to this immunoregulatory process. Herein, the responses of PYYb and receptors Y7 and Y8b were explored after pathogen challenging, as well as the effect of NPY on the gastrointestinal tissues of Nile tilapia (Oreochromis niloticus). Using a NPY and S. agalactiae co-injection model, we measured the expression of pyyb, y7, and y8b and the inflammatory and oxidative stress responses in gastrointestinal tissues. S. agalactiae infection significantly upregulated pyyb expression, while co-treatment with NPY further amplified its expression. Infection caused an imbalance between y7 and y8b and was alleviated by NPY. Moreover, NPY contributed to immune protection. NPY co-treatment reduced inflammatory cytokine expression in the gastrointestinal tissues and alleviated tissue damage inflicted by S. agalactiae. Additionally, NPY mitigated immune and oxidative stress by enhancing lysozyme, AKP and ACP activities, normalizing glucose and albumin levels, and reducing lipid peroxidation (MDA). These findings demonstrated that PYYb and receptors Y7 and Y8b were involved in the immune response caused by S. agalactiae. NPY not only enhanced their reactions but also reduced inflammation and oxidative stress induced by the pathogen, indicating its potential as a therapeutic intervention for S. agalactiae infections in fish. Full article

Environmental pollution with microplastics (MPs) and nanoplastics (NPs) continues to increase. These pollutants have been found in the environment (water, soil, and air) as well as in human tissues and biological fluids. Oral, inhalation, and dermal pathways play key roles in human exposure to plastic particles. The primary sources of exposure are foods, beverages, air, and dust. Polymers can penetrate the skin primarily via endocytosis, exocytosis, passages through cell-to-cell junctions, and interaction with the extracellular matrix. However, the health effects of dermal exposure remain poorly understood. Microplastics and NPs have been detected in the gastrointestinal, respiratory, circulatory, urinary, reproductive, and nervous systems, causing detrimental effects in each. Such effects include oxidative stress, inflammation, cellular damage, and protein aggregation. Furthermore, their presence has been linked to cardiovascular and neurodegenerative diseases. However, standardized protocols for analyzing NPs and MPs in human organs and tissues have not yet been established or legally regulated. Further research is needed to fully determine exposure thresholds, but legislative and lifestyle changes can already be implemented. Full article

Background/Objectives: Despite significant advancements in cancer treatment outcomes, side effects, such as gastrointestinal mucositis (GIM), continue to impair patients’ quality of life. The recent literature suggests L-citrulline as a novel treatment for GIM. However, no in vitro model to study the potential for L-citrulline as a treatment for GIM is currently available, and the effect of L-citrulline on the gut microbiota remains unclear. This study aims to propose a suitable in vitro model to study the effect of L-citrulline on the gut microbiota and to determine whether it can mitigate GIM. Methods: The CaCo-2 and T84 cell lines were cultured using cell impedance assays and treated with different doses of methotrexate and melphalan to select an appropriate model for L-citrulline research. The selected model was further used to investigate the impact of L-citrulline on gut microbiota cultured using microbial culture assays containing YCFAG. Results: Neither CaCo-2 nor T84 cells treated with methotrexate were suitable models for our study due to varying responses to treatment. T84 cells treated with 100 μg/mL melphalan demonstrated a consistent response, making them a suitable model for in vitro research on treatments for GIM. The use of L-citrulline demonstrated potential protective effects, as melphalan-treated enterocytes showed less cellular damage in its presence and slightly reduced enteroaggregative E. coli growth. Conclusions: L-Citrulline supplementation reduced epithelial cell injury due to melphalan, suggesting therapeutic potential. Further testing is required to determine its efficacy in vivo and clarify the mechanisms underlying this potential benefit. Full article

Background: Inflammatory bowel disease (IBDs) are chronic, immune-mediated disorders of the gastrointestinal tract, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), and primarily affecting individuals with genetic susceptibility. IBDs are characterized by dysregulated mucosal immune responses to intestinal microbiota, leading to sustained inflammation and tissue damage. These conditions not only pose a significant burden on healthcare systems but are also frequently associated with distinct comorbidities. Rationale: Given the immunological nature of both IBDs and type 2 diabetes (T2D)—each involving a complex interplay between genetic predisposition and environmental triggers—an increasing number of studies have suggested a pathophysiological link between the two. Both diseases involve chronic low-grade inflammation and alterations in immune signaling pathways, such as cytokine dysregulation, T-cell imbalance, and aberrant innate immune activation. Methods: To investigate this association more robustly, we conducted a cohort study involving 49 consecutive patients diagnosed with both IBD and T2D. Results: Our findings revealed a strong correlation between the two conditions, with UC emerging as the predominant IBD subtype linked to T2D. Notably, the highest prevalence was observed in patients aged 65–74 years, suggesting age-related immune modulation may play a role. In a matched case-control analysis (48 cases vs. 96 controls), 70.8% of the IBD–T2D cases were diagnosed with UC, 25.0% with CD, and 4.2% with indeterminate colitis. Similarly, in the cohort study, UC accounted for 73.81% of cases, CD for 21.43%, and non-determined colitis for 4.76%. Conclusions: These data support the hypothesis that UC, more so than CD, exhibits a stronger immunological and clinical association with T2D. Interestingly, CD was absent in the 55–64 age group, potentially indicating age-specific immunological trajectories or differential environmental exposures. The observed patterns reinforce the concept that immune dysregulation is a shared underpinning of both IBD and T2D, and that UC may serve as an immunological bridge linking gastrointestinal and metabolic inflammation. Full article

Curcumin is a natural bioactive compound of plant origin, characterised by a wide variety of properties that make it useful in numerous industries. Furthermore, due to its health-promoting properties, such as anti-inflammatory, antioxidant, and antimicrobial effects, it has found applications in medicine and animal husbandry. Unfortunately, curcumin has low bioavailability; its hydrophobic nature means it is poorly absorbed through the gastrointestinal tract, and it is rapidly metabolised in the liver. In recent years, research has been conducted into adding nanoencapsulated active ingredients, such as curcumin, to animal feed. This research aims to improve the bioavailability and stability of these ingredients, extend their shelf life, and enhance their absorption. These effects are expected to improve overall animal health, increase production efficiency, and enhance the quality of animal products. However, a significant challenge remains: the irreversible aggregation and chemical instability of bioactive substances due to the hydrolysis of their polymeric encapsulants, which can lead to toxic effects. This study utilised peripheral whole blood from five Blanc de Termonde rabbits. In vitro cell exposure was conducted using three distinct concentrations of nanoencapsulated curcumin (C1–C3: 10, 5.0, and 2.5 µg/mL) and a control. Cytotoxicity was determined by assessing viability using trypan blue exclusion, the comet assay, and the micronucleus assay. The results indicated that all tested concentrations of nanocurcumin significantly decreased the viability of blood cells to approximately 1–9%. In contrast, the encapsulation matrices themselves were not toxic (results were statistically significant). In the comet assay, the nanocurcumin formulations were toxic at all concentrations, and the results were statistically significant. Following exposure, the micronucleus assay revealed cell damage and a high percentage of apoptotic cells (up to 30% for Cur1 at 10 ug/mL). A significant number of binucleated cells with two micronuclei (BNCs + 2MN) were also observed, again for Cur1. In view of the considerable variation in the results from the individual tests, it is advisable to repeat the research using different matrix forms and concentrations of curcumin. Full article

Silent information regulator type 1 (SIRT1), a NAD⁺-dependent deacetylase, is a central regulator of cancer cell adaptation to oxidative stress and senescence. By deacetylating redox-sensitive transcription factors, such as p53, FOXOs, PGC-1α, and NF-κB, SIRT1 suppresses apoptosis, delays senescence, enhances mitochondrial function, and attenuates pro-inflammatory senescence-associated secretory phenotypes. These mechanisms collectively promote tumor progression and contribute to resistance to therapy. Reactive oxygen species (ROS), long regarded as damaging byproducts, are now recognized as critical modulators of cancer biology. Although moderate ROS levels drive oncogenic signaling, excessive ROS accumulation triggers DNA damage, oxidative stress, and senescence. To survive these hostile conditions, cancer cells reinforce antioxidant defenses and exploit the NAD⁺–SIRT1 axis to maintain redox balance and evade senescence. The objective of this review was to provide an integrated framework linking SIRT1-mediated deacetylation to redox regulation and senescence control in cancer. We synthesized mechanistic insights into SIRT1 interactions with its substrates, highlighted cancer type-specific functions in ovarian, breast, liver, lung, and gastrointestinal malignancies, and critically evaluated the dual role of SIRT1 as both a longevity factor and an oncogenic driver. Finally, we explored the therapeutic implications of the pharmacological inhibition of SIRT1 as a strategy to restore senescence, increase ROS vulnerability, and overcome therapy resistance. This synthesis underscores the potential of the SIRT1–redox–senescence axis as a promising target in precision oncology. Full article

Background: The population affected by gastrointestinal atresias and neurodevelopmental outcomes has not been well studied. Current evidence suggests that damage to the central nervous system is important in congenital gastrointestinal malformations. This study aims to understand the effects of gastrointestinal atresias on neurodevelopmental outcomes in our patient group. Methods: This cross-sectional, population-based study examined patients with congenital gastrointestinal atresias who were admitted to the neonatal intensive care unit and underwent gastrointestinal surgery. The Bayley III scale was administered to 32 patients aged 7–42 months. Results: Thirty-two patients with gastrointestinal atresia were included in the study. Eighteen (56.2%) of the patients were male. The median gestational age was 37 weeks (range 25–39 weeks) and the median birthweight was 2700 g (range 700–3800 g). A Bayley III evaluation was performed at a median age of 13.7 months (range 7–41 months). The cognitive, motor, and language composite scores were 90, 86, and 89, respectively. The motor score was lower than the cognitive and language scores. No statistical difference was found between low scores, gender and stoma presence in all three neurodevelopmental categories (p < 0.05). Conclusion: Patients with congenital gastrointestinal malformations are reported in the literature to have lower motor and language development scores. In our study, lower cognitive and language scores were observed in only one patient, whereas motor delay was more prevalent in the study population. The close neurodevelopmental follow-up of infants with gastrointestinal atresies may improve the quality of life. Full article

Background: Helicobacter pylori (H. pylori) is a major pathogen associated with a variety of gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. As a natural bioactive product, propolis exhibits multifaceted and multi-mechanistic effects. Due to its immunomodulatory, anti-inflammatory, and antioxidant properties, propolis has emerged as a promising therapeutic alternative, offering an innovative approach to managing H. pylori infections and providing new insights into addressing antibiotic resistance. Methods: This comprehensive review, synthesizing data from PubMed, ScienceDirect, and SciFinder, examines the mechanisms by which propolis combats H. pylori. Results: Propolis has demonstrated significant antibacterial efficacy against H. pylori in both in vitro and in vivo models. Its multitargeted mechanisms of action include direct inhibition of bacterial growth, interference with the expression of virulence factors, suppression of virulence-associated enzymes and toxin activity, immunomodulation, and anti-inflammatory effects. These combined actions alleviate gastric mucosal inflammation and damage, reduce bacterial colonization, and promote mucosal healing through antioxidant and repair-promoting effects. Furthermore, propolis disrupts oral biofilms, restores the balance of the oral microbiome, and exerts bactericidal effects in the oral cavity. Synergistic interactions between propolis and conventional medications or other natural agents highlight its potential as an adjunctive therapy. Conclusions: Propolis demonstrates dual functionality by inhibiting the release of inflammatory mediators and suppressing H. pylori growth, highlighting its potential as an adjuvant therapeutic agent. However, clinical translation requires standardized quality control and higher-level clinical evidence. Future research should focus on validating its clinical efficacy and determining optimal dosing regimens, and exploring its role in reducing H. pylori recurrence. Full article