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Broiler chicks are typically hatched in a hatchery, exposing them to handling and transportation before being placed on the farm where (dry) feed and water is offered. This study compared different early life systems, including: (1) typical practice (control), (2) typical practice with wet feed offered upon placement, (3) access to water at the hatchery, (4) access to feed and water at the hatchery, (5) hatching on the farm. Birds were placed in groups of approximately 500 (day 0), with six replicates per treatment. Measures were taken between placement and slaughter (day 39) and included chick quality (navel and red hock scores), body weight, feed conversion ratio (FCR), mortality, gait and litter conditions scores, and behavioral and post-mortem assessments. There were no apparent treatment effects on gait score, play behaviour or novel object test measures, and no consistent effects on litter quality. Chick quality was only evaluated in Treatments 1 and 5 and was numerically worse in Treatment 5. Body weight at slaughter was lowest in Treatment 2, and did not differ between other treatments. Overall FCR was lowest (best) in Treatment 1, and did not differ between other treatments. There was higher overall mortality in Treatments 3 and 4 than in other treatments apart from Treatment 5. Treatment 4 appeared to promote feeding behaviour upon placement, and Treatment 5 birds rested the most, significantly more than in Treatment 2. Treatment 5 birds had the greatest bursa weights, and tibial dyschondroplasia appeared worse in Treatment 4. There were no consistent effects of early access to feed and water on gastrointestinal tract weight measures at slaughter. Compared to the control, there were few benefits in providing feed and/or water in the hatchery, or wet feed. Some benefits of in-house hatching were found, but negative effects were also apparent. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal tract (GIT) cancers are complex disorders affecting millions of people worldwide. The vascular endothelial growth factor (VEGF) helps in the development of different GIT cancers by promoting abnormal angiogenesis in cancer cells. The role of VEGF-2549I/D polymorphism in influencing GIT cancer susceptibility has been studied in different populations with inconclusive results. Therefore, the relationship between VEGF-2549I/D polymorphism with GIT susceptibility was studied by performing a meta-analysis study. Methods: Various online databases were used for identifying the articles. Based on study selection criteria, five studies on different GIT cancers including 1178 patients and 1520 controls were included in the meta-analysis. The accuracy of the study results was determined by performing a trial sequential analysis. Results: In this study, the VEGF-2549I/D polymorphism did not influence the GIT cancer susceptibility in the overall analysis as well as when stratified according to ethnicity (p > 0.05). Stratification of all the studies based on the different GIT cancers reported an increased susceptibility to gastric cancer under different genetic models including allele contrast (OR = 1.67, CI = 1.294–2.157, p = 0.00008), recessive (OR = 1.68, CI = 1.056–2.660, p = 0.029), dominant (OR = 2.49, CI = 1.617–3.823, p = 0.00003), over-dominant (OR = 1.52, CI = 1.055–2.177, p = 0.025), II vs DD (OR = 2.97, CI = 1.692–5.208, p = 0.00015) and ID vs DD model (OR = 2.35, CI = 1.501–3.669, p = 0.00018). Conclusion: There was no relationship between VEGF-2549I/D promoter polymorphism and GIT cancer susceptibility in the overall population and also in different ethnic groups. Stratification analysis revealed higher susceptibility towards gastric cancer development with VEGF-2549I/D polymorphism. [ABSTRACT FROM AUTHOR]

Background: Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood. Case presentation: We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis. Conclusions: In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Agonists targeting the receptors of incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, have been well established for the treatment of type 2 diabetes mellitus. There is increasing awareness that gastroenterologists and hepatologists should be treating obesity when patients present to their clinics. In addition, gastroenterologists and hepatologists should be aware of the effects of these classes of medications prescribed by other providers. Therefore, given the widespread use of incretin agonists for obesity treatment and weight loss, it is important to recognize their effects in the gastrointestinal tract, which could constitute significant benefits in weight loss and cardiometabolic benefits, but can be associated with adverse effects that constitute apotential barrier to their use, particularly at higher doses. Multiple studies reviewed inthis article document thediverse effects of these drugs onthe glucagon-likepeptide-1 receptors that are widely expressed in the human body, including the nervous system modulating appetite, the gastrointestinal tract modifying gastric emptying, and lipid metabolism regulation leading to reduction in fat deposition. The objective of this review is to summarize the mechanism of action of incretin receptor agonists, their effects in the gastrointestinal tract, and implications in clinical practice, particularly in the practice of gastroenterology, endoscopy, and surgery. [ABSTRACT FROM AUTHOR]

Background and Aim: There has been no report on a direct comparison between linked color imaging (LCI) and second‐generation narrow‐band imaging (2G‐NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G‐NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. Methods: This study was conducted as an open‐label, two‐arm‐parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20–85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G‐NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image‐enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image‐enhanced endoscopy. A WLI‐detected epithelial neoplasm was defined as a lesion that was detected in only WLI. Results: A total of 372 patients in the 2G‐NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G‐NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI‐detected epithelial neoplasms were in 11 patients in the 2G‐NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). Conclusions: Linked color imaging did not show superiority to 2G‐NBI for the detection of epithelial neoplasms. Also, the percentage of WLI‐detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI. [ABSTRACT FROM AUTHOR]

The increased demand and consumption of synthetic textiles have contributed to microplastic pollution in the form of microfibers. These particles are widely spread in the aquatic environment, leading to the exposure of marine biota, including edible species. The current study aimed to assess the extent of microfiber contamination in a commercially relevant fish species, Merluccius merluccius, which is considered a small-scale bioindicator for the monitoring of plastic ingestion in the Mediterranean coastal environment. The frequency of ingestion, abundance, and composition of textile microfibers isolated from the fish gut were characterized. Results showed the occurrence of microfibers in 75% of the samples, with a mean number of 10.6 microfibers/individual, of which 70% were classified as natural microfibers. The spectroscopic analyses confirmed both the visual identification of microfibers and the prevalence of cellulosic fibers. The obtained findings provided evidence of both natural/artificial and synthetic microfiber exposure in an important commercial fish species that, considering the consumption of small individuals without being eviscerated, may be a potential route of microfiber exposure in humans. Monitoring programs for fishery products from markets are needed to assess contamination levels and human health risks. In addition, measures to control microfiber pollution need to occur at multiple levels, from textile industries to international governments. [ABSTRACT FROM AUTHOR]

Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes. [ABSTRACT FROM AUTHOR]

A better understanding of how emulsifier type could differently influence the behavior of nanostructured lipid carriers (NLC) under the gastrointestinal digestion process, as well as at the cellular level, is of utmost importance for the NLC‐based formulations' optimization and risk assessment in the food field. In this study, NLC composed by fully hydrogenated soybean and high‐oleic sunflower oils were prepared using soy lecithin (NLC Lβ) or Tween 80 (NLC Tβ) as an emulsifier. β‐Carotene was entrapped within NLC developed as a promising strategy to overcome β‐carotene's low bioavailability and stability. The effect of emulsifier type on the digestibility of β‐carotene‐loaded NLC was evaluated using an in vitro dynamic digestion model mimicking peristalsis motion. The influence of β‐carotene‐loaded NLC on cell viability was assessed using Caco‐2 cells in vitro. NLC Tβ remained stable in the gastric compartment, presenting particle size (PS) similar to the initial NLC (PS: 245.68 and 218.18 nm, respectively), while NLC Lβ showed lower stability (PS > 1000 nm) in stomach and duodenum phases. NLC Tβ also provided high β‐carotene protection and delivery capacity (i.e., β‐carotene bioaccessibility increased 10‐fold). Based on the results of digestion studies, NLC Tβ has shown better physical stability during the passage through the in vitro dynamic gastrointestinal system than NLC Lβ. Moreover, the developed NLC did not compromise cell viability up to 25 µg/mL of β‐carotene. Thus, the NLC developed proved to be a biocompatible structure and able to incorporate and protect β‐carotene for further food applications. Practical Application: The findings of this study hold significant implications for industrial applications in terms of developing nanostructured lipid carriers from natural raw materials widely available and used to produce other lipid‐based products in the food industry, as an alternative to synthetic ones. In this respect, the β‐carotene‐loaded NLC developed in this study would find a great industrial application in the food industry, which is in constant search to develop functional foods capable of increasing the bioavailability of bioactive compounds. [ABSTRACT FROM AUTHOR]

Simple Summary: In humans and animals, the D-enantiomer of lactic acid (D-lactate) is normally produced from bacterial fermentation in the gastrointestinal tract. During gastroenteric diseases, D-lactate can be produced in large quantities and absorbed by the intestinal mucosa. The purpose of the present study was to measure the serum D-lactate concentrations in dogs with chronic inflammatory bowel disease (IBD). For this reason, the serum D-lactate concentrations were measured in 10 healthy dogs and 18 dogs with IBD using a commercially available colorimetric assay kit. Our results showed no significant difference (p > 0.05) in the serum concentrations of D-lactate between dogs with various degrees of IBD and healthy dogs. Further studies are needed to understand potential factors able to influence the serum D-lactate concentrations in dogs affected by IBD. The D-enantiomer of lactic acid (D-lactate) is normally produced from bacterial fermentation in the gastrointestinal tract in mammals. In humans, increased D-lactate concentrations are related to gastrointestinal disease, including short bowel syndrome and malabsorptive syndrome. Similarly, increased D-lactate concentrations have been described in calves affected by diarrhea, in cats with gastrointestinal diseases, and in dogs with parvoviral enteritis. The purpose of the present study was to measure the serum D-lactate concentrations in dogs with inflammatory bowel disease (IBD). We retrospectively reviewed data from the database of the VTH of Perugia University, and dogs affected by IBD with serum samples stored at −80 °C were considered eligible for inclusion. A total of 18 dogs with IBD and 10 healthy dogs were included in the study. The dogs with IBD were divided into three subcategories based on the severity of the disease. Serum D-lactate concentrations (μM) were determined using a commercially available colorimetric assay kit (D-Lactate Colorimetric Assay Kit; Catalog #K667-100, BioVision Inc., Milpitas, CA, USA). Our results showed no significant difference (p > 0.05) in the serum concentrations of D-lactate between dogs with various degrees of IBD and healthy dogs. However, the wide variability of the D-lactate concentrations in dogs with IBD and evidence of increased serum D-lactate concentrations in dogs with confirmed dysbiosis encourage further studies on this topic to understand potential factors influencing the serum D-lactate concentrations in dogs affected by IBD. [ABSTRACT FROM AUTHOR]

Simple Summary: This reassessment of the findings from our phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate–high-risk prostate cancer in the absence of androgen deprivation therapy due to patient refusal, with a median follow-up of 6.5 years. Our primary focus is on analyzing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade ≥ 2, both genitourinary and gastrointestinal. Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate–high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25–74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17–76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate–high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent. [ABSTRACT FROM AUTHOR]

Our epithelium represents a battle ground against a variety of insults including pathogens and danger signals. It encodes multiple sensors that detect and respond to such insults, playing an essential role in maintaining and defending tissue homeostasis. One key set of defense mechanisms is our inflammasomes which drive innate immune responses including, sensing and responding to pathogen attack, through the secretion of pro‐inflammatory cytokines and cell death. Identification of physiologically relevant triggers for inflammasomes has greatly influenced our ability to decipher the mechanisms behind inflammasome activation. Furthermore, identification of patient mutations within inflammasome components implicates their involvement in a range of epithelial diseases. This review will focus on exploring the roles of inflammasomes in epithelial immunity and cover: the diversity and differential expression of inflammasome sensors amongst our epithelial barriers, their ability to sense local infection and damage and the contribution of the inflammasomes to epithelial homeostasis and disease. [ABSTRACT FROM AUTHOR]

Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution. A series of in vitro dissolution experiments were gathered using the USP Apparatus I, III and IV in presence of biorelevant media, simulating both fasted and fed state conditions. A key outcome from the current study was to establish an in vitro-in vivo correlation (IVIVC) between (i) the dissolution profiles obtained from the USP I, III and IV methods and (ii) the fraction absorbed of drug as deconvoluted from the plasma concentration-time profile of the drug. When linking the fraction dissolved as measured in the USP IV model, a Level A IVIVC was established. Moreover, when using the different dissolution profiles as input for PBPK modeling, it was also observed that predictions for plasma C max and AUC were most accurate for USP IV compared to the other models (based on predicted versus observed ratios). Furthermore, the PBPK model has the utility to extract the predicted concentrations at the level of the colon which can be of utmost interest when working with specific in vitro assays. Graphical abstract was created with Biorender.com [Display omitted] • New IVIVC protocol evaluated the predictive capability of various USP apparatuses. • USP IV provided the best dissolution profiles for the HPMC formulation. • Biopredictive dissolution was input into PBPK to understand upadacitinib GI absorption. • USP IV data and PBPK model were used to predict drug levels in the colon. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non‐geriatric patients. Methods: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer‐specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5‐year survival (5YS). Log‐Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. Results: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7–69.5). Cancer‐specific death was 39.11% in 2000 & 3.33% in 2019. Non‐geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%–78.3%) and 53.3% (51.7%–54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%–51.4%) and 83.7% (82.7%–84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%–32.1%) and 62.8% (60.8%–64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42–2.70) (p < 0.0001). Conclusions: Cancer‐specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction. However, there is relatively little research on the composition and function of microorganisms in different GIT segments in dairy goats. Herein, 80 chyme samples were taken from ten GIT sites of eight Xinong Saanen dairy goats and then analyzed and identified the microbial composition via 16S rRNA V1-V9 amplicon sequencing. A total of 6669 different operational taxonomic units (OTUs) were clustered, and 187 OTUs were shared by ten GIT segments. We observed 264 species belonging to 23 different phyla scattered across ten GITs, with Firmicutes (52.42%) and Bacteroidetes (22.88%) predominating. The results revealed obvious location differences in the composition, diversity, and function of the GIT microbiota. In LEfSe analysis, unidentified_Lachnospiraceae and unidentified_Succinniclassicum were significantly enriched in the four chambers of stomach, with functions in carbohydrate fermentation to compose short-chain fatty acids. Aeriscardovia, Candidatus_Saccharimonas, and Romboutsia were significantly higher in the foregut, playing an important role in synthesizing enzymes, amino acids, and vitamins and immunomodulation. Akkermansia, Bacteroides, and Alistipes were significantly abundant in the hindgut to degrade polysaccharides and oligosaccharides, etc. From rumen to rectum, α-diversity decreased first and then increased, while β-diversity showed the opposite trend. Metabolism was the major function of the GIT microbiome predicted by PICRUSt2, but with variation in target substrates along the regions. In summary, GIT segments play a decisive role in the composition and functions of microorganisms. Key points: • The jejunum and ileum were harsh for microorganisms to colonize due to the presence of bile acids, enzymes, faster chyme circulation, etc., exhibiting the lowest α-diversity and the highest β-diversity. • Variability in microbial profiles between the three foregut segments was greater than four chambers of stomach and hindgut, with a higher abundance of Firmicutes dominating than others. • Dairy goats dominated a higher abundance of Kiritimatiellaeota than cows, which was reported to be associated with fatty acid synthesis. [ABSTRACT FROM AUTHOR]

Understanding how the gut communicates with the brain, via sensory nerves, is of significant interest to medical science. Enteroendocrine cells (EEC) that line the mucosa of the gastrointestinal tract release neurochemicals, including the largest quantity of 5-hydroxytryptamine (5-HT). How the release of substances, like 5-HT, from enterochromaffin (EC) cells activates vagal afferent nerve endings is unresolved. We performed anterograde labelling from nodose ganglia in vivo and identified vagal afferent axons and nerve endings in the mucosa of whole-mount full-length preparations of mouse colon. We then determined the spatial relationship between mucosal-projecting vagal afferent nerve endings and EC cells in situ using 3D imaging. The mean distances between vagal afferent nerve endings in the mucosa, or nearest varicosities along vagal afferent axon branches, and the nearest EC cell were 29.6 ± 19.2 μm (n = 107, N = 6) and 25.7 ± 15.2 μm (n = 119, N = 6), respectively. No vagal afferent endings made close contacts with EC cells. The distances between EC cells and vagal afferent endings are many hundreds of times greater than known distances between pre- and post-synaptic membranes (typically 10–20 nm) that underlie synaptic transmission in vertebrates. The absence of any close physical contacts between 5-HT-containing EC cells and vagal afferent nerve endings in the mucosa leads to the inescapable conclusion that the mechanism by which 5-HT release from ECs in the colonic mucosa occurs in a paracrine fashion, to activate vagal afferents. [ABSTRACT FROM AUTHOR]

Background: There is compelling evidence that microbe‐host interactions in the intestinal tract underlie many human disorders, including disorders of gut‐brain interactions (previously termed functional bowel disorders), such as irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been recognized for over a century in patients with predisposing conditions causing intestinal stasis, such as surgical alteration of the small bowel or chronic diseases, including scleroderma and is associated with diarrhea and signs of malabsorption. Over 20 years ago, it was hypothesized that increased numbers of small intestine bacteria might also account for symptoms in the absence of malabsorption in IBS and related disorders. This SIBO‐IBS hypothesis stimulated significant research and helped focus the profession's attention on the importance of microbe‐host interactions as a potential pathophysiological mechanism in IBS. Purpose: However, after two decades, this hypothesis remains unproven. Moreover, it has led to serious unintended consequences, namely the widespread use of unreliable and unvalidated breath tests as a diagnostic test for SIBO and a resultant injudicious use of antibiotics. In this review, we examine why the SIBO hypothesis remains unproven and, given the unintended consequences, discuss why it is time to reject this hypothesis and its reliance on breath testing. We also examine recent IBS studies of bacterial communities in the GI tract, their composition and functions, and their interactions with the host. While these studies provide important insights to guide future research, they highlight the need for further mechanistic studies of microbe‐host interactions in IBS patients before we can understand their possible role in diagnosis and treatment of patient with IBS and related disorders. [ABSTRACT FROM AUTHOR]

Microplastics (<5 mm in diameter) are ubiquitous in the oceanic environment, yet microplastic accumulation in marine mammals is vastly understudied. In recent years, efforts have been made to document microplastic profiles in odontocetes. The objective of the present study was to describe and quantify microplastics in the gastrointestinal (GI) tracts of deceased odontocetes that stranded in the southeastern United States. Our study included 24 bottlenose dolphins (Tursiops truncatus), two pygmy sperm whales (Kogia breviceps), one pantropical spotted dolphin (Stenella attenuata), one short‐snouted spinner dolphin (Stenella clymene), one Risso's dolphin (Grampus griseus), and one dwarf sperm whale (Kogia sima) obtained from stranding networks in Texas, Alabama, Florida, and Puerto Rico. Contents found in the GI tracts, namely, the stomach and portions of the intestinal tract, were subjected to a laboratory procedure to isolate microplastics. The physical characteristics of microparticles were analyzed with a stereomicroscope, and microplastics were classified by polymer type via Fourier‐transform infrared spectroscopy. There was an average of 47.6 ± 41.4 microparticles, ranging from 1 to 193 items per stomach. More specifically, there was an average of 5.6 ± 4.7 microplastics per stomach. The predominant morphologies, colors, and polymer types were fibers, white‐colored items, and polyester, respectively. This research contributes to the current knowledge of microplastic exposure in top marine mammal predators and sets the stage for further exploration into the associated risks of microplastics in odontocetes within the United States and worldwide. Environ Toxicol Chem 2024;43:1260–1273. © 2024 SETAC [ABSTRACT FROM AUTHOR]

The microbiota represents a crucial area of research in maintaining human health due to its potential for uncovering novel biomarkers, therapies, and molecular mechanisms relevant to population identification and experimental model characterization. Among these microorganisms, Enterococcus faecalis, a Gram-positive bacterium found in the gastrointestinal tract of humans and animals, holds particular significance. Strains of this bacterial species have sparked considerable debate in the literature due to their dual nature; they can either be utilized as probiotics in the food industry or demonstrate resistance to antibiotics, potentially leading to severe illness, disability, and death. Given the diverse characteristics of Enterococcus faecalis strains, this review aims to provide a comprehensive understanding of their impact on various systems within the host, including the immunological, cardiovascular, metabolic, and nervous systems. Furthermore, we summarize the bacterium-host interaction characteristics and molecular effects to highlight their targets, features, and overall impact on microbial communities and host health. [ABSTRACT FROM AUTHOR]

Information on the conditions under which drugs are transferred from the stomach through the upper small intestine after a high-calorie, high-fat meal is very limited. To simulate the drug presence after disintegration and arrival in the antral region, paracetamol solution and Sporanox® amorphous solid dispersion pellets at two dose levels were administered to the antrum of 8 healthy adults 30 min after administration of a high-calorie, high-fat meal on a crossover basis. The overall median buffer capacity of antral contents was estimated to be 18.0 and 24.0 mmol/ml/ΔpH when titrating with NaOH and HCl, respectively. The corresponding values for the contents of upper the small intestine were 14.0 and 16.8 mmol/ml/ΔpH, respectively. The drug transfer process from the antrum through the upper small intestine occurred with apparent first-order kinetics. The best estimate for the antral emptying half-life was 39min and 45min for paracetamol and itraconazole, respectively, the apparent volume of contents of the upper small intestine was more than double compared with previously reported values in the fasted state, the half-life of drug elimination from the upper small intestine was similar to recent estimates for highly permeable drugs in the fasted state, and the apparent volume of antral contents during the first couple of hours post drug administration was 303mL. Information collected in this study could increase the reliability of in silico and/or in vitro modelling approaches applied in clinical drug development. [Display omitted] [ABSTRACT FROM AUTHOR]

Grape pomace is the most important residual after wine making, and it is considered to be a very abundant source for the extraction of a wide range of polyphenols. These polyphenols exhibit a variety of bioactivities, such as antioxidant, anti-inflammatory, and anti-cancer. They are also beneficial in alleviating metabolic syndrome and regulating intestinal flora, etc. These health effects are most likely contributed by polyphenol metabolite, which are formed by the grape pomace phenolics after a complex metabolic process in vivo. Therefore, understanding the phenolic composition of grape pomace and its metabolism is the basis for an in-depth study of the biological activity of grape pomace polyphenols. In this paper, we first summarize the composition of phenolics in grape pomace, then review the recent studies on the metabolism of grape pomace phenolics, including changes in phenolics in the gastrointestinal tract, their pharmacokinetics in the systemic circulation, the tissue distribution of phenolic metabolites, and the beneficial effects of metabolites on intestinal health, and finally summarize the effects of human health status and dietary fiber on the metabolism of grape polyphenols. It is expected to provide help for the in-depth research on the metabolism and biological activity of grape pomace polyphenol extracts, and to provide theoretical support for the development and utilization of grape pomace. [ABSTRACT FROM AUTHOR]

The aims of the current study were to determine the frequencies of specific sleep disturbances in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBIs) and to assess relationships with psychological dysfunction. This was a retrospective evaluation of 226 consecutive patients diagnosed with an AP-DGBI. All had undergone a systematic evaluation of gastrointestinal symptoms, the Sleep Disturbance Scale for Children, and the Behavior Assessment System for Children. Disorders of initiation and maintenance of sleep (DIMS; 40%) and disorders of excessive daytime somnolence (DOES; 14%) were each present in more than 10% of the patients. Both DIMS and DOES scores were more likely to be elevated in patients with anxiety and/or depression scores in the at-risk or elevated-risk ranges. Sleep disorders are common in youth with AP-DGBIs and are associated with anxiety and depression, even in those patients with anxiety and depression in the at-risk range. [ABSTRACT FROM AUTHOR]

Background: The gastrointestinal (GI) tract represents one of the main targets of typical hemolytic uremic syndrome (HUS) in children. In this observational study, we tried to establish (1) the main features of GI complications during STEC-HUS and (2) the relationship between Escherichia coli serotypes and Shiga toxin (Stx) variants with hepatopancreatic involvement. Methods: A total of 79 STEC-HUS patients were admitted to our pediatric nephrology department between January 2012 and June 2021. Evidence of intestinal, hepatobiliary, and pancreatic involvements was reported for each patient, alongside demographic, clinical, and laboratory features. Frequency of gastrointestinal complications across groups of patients infected by specific E. coli serotypes and Stx gene variants was evaluated. Results: Six patients developed a bowel complication: two developed rectal prolapse, and four developed bowel perforation which resulted in death for three of them and in bowel stenosis in one patient. Acute pancreatitis was diagnosed in 13 patients. An isolated increase in pancreatic enzymes and/or liver transaminases was observed in 41 and 15 patients, respectively. Biliary sludge was detected in three, cholelithiasis in one. Forty-seven patients developed direct hyperbilirubinemia. Neither E. coli serotypes nor Shiga toxin variants correlated with hepatic or pancreatic involvement. Conclusions: During STEC-HUS, GI complications are common, ranging from self-limited elevation of laboratory markers to bowel perforation, a severe complication with a relevant impact on morbidity and mortality. Hepatopancreatic involvement is frequent, but usually short-lasting and self-limiting. [ABSTRACT FROM AUTHOR]

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta‐analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle‐Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta‐analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21–5.04]), gastric adenocarcinoma (2.03 [1.38–2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02–3.25]), and biliary tract adenocarcinoma (3.11 [2.46–3.93]) with high‐grade tumour budding. Additionally, high‐grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility. [ABSTRACT FROM AUTHOR]

Pythiosis is the disease caused by aquatic oomycetes of the genus Pythium. In dogs the typical course of the disease involves the gastrointestinal tract, characterized by transmural thickening of the stomach or intestines. However, infection by Pythium spp. has only rarely been recognized as a cause of esophagitis in dogs. Thus, the present reports a case of esophageal and gastric pythiosis in an eight-month-old female pit bull dog. The dog was attended at the hospital after two months presenting regurgitation and dyspnea. It was reported that the dog lived in an urban area and had no previous sanitary issues. At clinical examination it was noted that the dog presented crackling sounds at pulmonary auscultation. A support therapy accompanied by antibiotics has been employed; however, 22 days after hospitalization the clinical condition worsened, and the dog died. At necropsy, the wall of the distal segment of the esophagus and the cardia and part of the fundus of the stomach were expanded by a focal extensive irregular intramural annular mass. Additionally, there was a transmural esophageal fistula. At histology, the walls of the esophagus and stomach were extensively expanded by multifocal extensive areas of necrosis, associated with a pyogranulomatous infiltrate and abundant granulation tissue containing multiple negative images of hyphae that were highlighted by silver impregnation (Grocott). Furthermore, immunohistochemistry and PCR for P. insidiosum were both positive in samples of paraffin-embedded esophageal tissue. [ABSTRACT FROM AUTHOR]

Objective: This research aims to explore the nutritional and bioactive peptide properties of goat meat taken from various primal cuts, including the breast, shoulder, rib, loin, and leg, to produce these bioactive peptides during in vitro gastrointestinal (GI) digestion and absorption. Methods: The goat meat from various primal cuts was obtained from Boer goats with an average carcass weight of 30±2 kg. The meat was collected within 3 h after slaughter and was stored at -80°C until analysis. A comprehensive assessment encompassed various aspects, including the chemical composition, cooking properties, in vitro GI digestion, bioactive characteristics, and the bioavailability of the resulting peptides. Results: The findings indicate that the loin muscles contain the highest protein and essential amino acid composition. When the meats were cooked at 70°C for 30 min, they exhibited distinct protein compositions and quantities in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile, suggesting they served as different protein substrates during GI digestion. Subsequent in vitro simulated GI digestion revealed that the cooked shoulder and loin underwent the most significant hydrolysis during the intestinal phase, resulting in the strongest angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) inhibition. Following in vitro GI peptide absorption using a Caco-2 cell monolayer, the GI peptide derived from the cooked loin demonstrated greater bioavailability and a higher degree of ACE and DPP-IV inhibition than the shoulder peptide. Conclusion: This study highlights the potential of goat meat, particularly cooked loin, as a functional meat source for protein, essential amino acids, and bioactive peptides during GI digestion and absorption. These peptides promise to play a role in preventing and treating metabolic diseases due to their dual inhibitory effects on ACE and DPP-IV. [ABSTRACT FROM AUTHOR]

Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal antibody responses. Here, we report a strategy to effectively concentrate immunogens and adjuvants in gut-draining lymph nodes (LNs) to induce gut-associated mucosal immunity. We prepared nanoemulsions (NEs) based on biodegradable oils commonly used as vaccine adjuvants, which encapsulated a potent Toll-like receptor agonist and displayed antigen conjugated to their surface. Following intraperitoneal administration, these NEs accumulated in gut-draining mesenteric LNs, priming strong germinal center responses and promoting B cell class switching to immunoglobulin A (IgA). Optimized NEs elicited 10-to 1000-fold higher antigen-specific IgG and IgA titers in the serum and feces, respectively, compared to free antigen mixed with NE, and strong neutralizing antibody titers against severe acute respiratory syndrome coronavirus 2. Thus, robust gut humoral immunity can be elicited by exploiting the unique lymphatic collection pathways of the gut with a lymph-targeting vaccine formulation. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumours (GISTs) can develop throughout the entire gastrointestinal tract, but these tumours are usually found in the stomach and small intestine. In this case, a rare GIST arising from the anal canal was investigated using high-frequency endoanal ultrasound and external three-dimensional ultrasound with tomographic ultrasound imaging. The endoanal approach revealed the inner structure of the tumour. External ultrasound was used to determine the relationship between the lesion and surrounding tissues. In the limited reports of anal canal GISTs, no other lesions have been correctly diagnosed preoperatively or displayed in detail on imaging. The multilayer structure of the anal sphincter and these lesions can be clearly displayed by a variety of ultrasound imaging methods, which are nonradiative, low-cost and easily accessible. Modern ultrasound has the potential for broad application in anal canal tumour diagnosis and surveillance. [ABSTRACT FROM AUTHOR]

Background: Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood. Case presentation: We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis. Conclusions: In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Reliable in-vitro digestion models that are able to successfully replicate the conditions found in the human gastrointestinal tract are key to assess the fate and efficiency of new formulations aimed for oral consumption. However, current in-vitro models either lack the capability to replicate crucial dynamics of digestion or require large volumes of sample/reagents, which can be scarce when working with nanomaterials under development. Here, we propose a miniaturised digestion system, a digestion-chip, based on incubation chambers integrated on a polymethylmethacrylate device. The digestion-chip incorporates key dynamic features of human digestion, such as gradual acidification and gradual addition of enzymes and simulated fluids in the gastric phase, and controlled gastric emptying, while maintaining low complexity and using small volumes of sample and reagents. In addition, the new approach integrates real-time automated closed-loop control of two key parameters, pH and temperature, during the two main phases of digestion (gastric and intestinal) with an accuracy down to ± 0.1 °C and ± 0.2 pH points. The experimental results demonstrate that the digestion-chip successfully replicates the gold standard static digestion INFOGEST protocol and that the semi-dynamic digestion kinetics can be reliably fitted to a first kinetic order model. These devices can be easily adapted to dynamic features in an automated, sensorised, and inexpensive platform and will enable reliable, low-cost and efficient assessment of the bioaccessibility of new and expensive drugs, bioactive ingredients or nanoengineered materials aimed for oral consumption, thereby avoiding unnecessary animal testing. [ABSTRACT FROM AUTHOR]

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC–MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6–108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Schwannomas are tumors that arise from Schwann cells that surround and support nerve cells. Most common sites for presentations are head, neck, and extremities. Schwannomas of gastrointestinal tract are rare, slowgrowing tumors, usually benign, arising from gastrointestinal tract's neural plexus. They are histologically distinguishable from conventional schwannomas that arise in soft tissue or the central nervous system. Preoperative diagnosis of gastrointestinal schwannoma is challenging, requiring immunohistological confirmation of the nature of the tumor. Here, we report a case of 57-year-old woman with an incidental finding of an asymptomatic submucosal jejunal schwannoma. Case Report: A 57-year-old woman with a medical history of hematological disorder underwent a contrast abdominal computed tomography as part of medical follow-up. The imaging revealed the presence of a jejunal mass. The patient underwent laparoscopic surgical resection of the lesion, followed by side-to-side jejuno-jejunal anastomosis with 4-cm clear surgical margins. The final pathologic study revealed the presence of jejunal schwannoma, as tested positive for S-100 protein. The patient was discharged home on the fourth postoperative day, having an uneventful recovery. Conclusions: Jejunal schwannoma are usually benign and asymptomatic, and they are often discovered incidentally during diagnostic tests for other conditions; therefore, it should be included in the differential diagnosis of gastrointestinal tumors. Surgical treatment appears to be necessary to achieve a definitive diagnosis through a biopsy of the tumor tissue. Benign jejunal schwannomas have a good prognosis. [ABSTRACT FROM AUTHOR]

Researchers who aim to globally analyze the gastrointestinal immune system via flow cytometry have many protocol options to choose from, with specifics generally tied to gut wall layers of interest. To get a clearer idea of the approach we should use on full-thickness colon samples from mice, we first undertook a systematic comparison of three tissue dissociation techniques: two based on enzymatic cocktails and the other one based on manual crushing. Using flow cytometry panels of general markers of lymphoid and myeloid cells, we found that the presence of cell-surface markers and relative cell population frequencies were more stable with the mechanical method. Both enzymatic approaches were associated with a marked decrease of several cell-surface markers. Using mechanical dissociation, we then developed two minimally overlapping panels, consisting of a total of 26 antibodies, for serial profiling of lymphoid and myeloid lineages from the mouse colon in greater detail. Here, we highlight how we accurately delineate these populations by manual gating, as well as the reproducibility of our panels on mouse spleen and whole blood. As a proof-of-principle of the usefulness of our general approach, we also report segment- and life stage-specific patterns of immune cell profiles in the colon. Overall, our data indicate that mechanical dissociation is more suitable and efficient than enzymatic methods for recovering immune cells from all colon layers at once. Additionally, our panels will provide researchers with a relatively simple tool for detailed immune cell profiling in the murine gastrointestinal tract, regardless of life stage or experimental conditions. [ABSTRACT FROM AUTHOR]

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy. [ABSTRACT FROM AUTHOR]

Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle cells, the immune system, and the microbiota. The disruption of this balance underpins the onset of gastrointestinal-related diseases. The scarcity of models replicating the intricate interplay between the ENS and the intestinal epithelium highlights the imperative for developing novel methods. We have pioneered a sophisticated tridimensional in vitro technique, coculturing small intestinal organoids with myenteric and submucosal neurons. Notably, we have made significant advances in (1) refining the isolation technique for culturing the myenteric plexus, (2) enhancing the isolation of the submucosal plexus—both yielding mixed cultures of enteric neurons and glial cells from both plexuses, and (3) subsequently co-culturing myenteric and submucosal neurons with small intestinal organoids. This co-culture system establishes neural innervations with intestinal organoids, allowing for the investigation of regulatory interactions in the context of gastrointestinal diseases. Furthermore, we have developed a method for microinjecting the luminal space of small intestinal organoids with fluorescently labeled compounds. This technique possesses broad applicability such as the assessment of intestinal permeability, transcytosis, and immunocytochemical and immunofluorescence applications. This microinjection method could be extended to alternative experimental setups, incorporating bacterial species, or applying treatments to study ENS-small intestinal epithelium interactions. Therefore, this technique serves as a valuable tool for evaluating the intricate interplay between neuronal and intestinal epithelial cells (IECs) and shows great potential for drug screening, gene editing, the development of novel therapies, the modeling of infectious diseases, and significant advances in regenerative medicine. The co-culture establishment process spans twelve days, making it a powerful asset for comprehensive research in this critical field. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) affects gastrointestinal (GI) motility, favoring gastroparesis, constipation, and fecal incontinence, which are more prevalent in women. The mechanisms are unknown. Given the G-protein-coupled estrogen receptor's (GPER) role in GI motility, we investigated sex-related diabetes-induced epigenetic changes in GPER. We assessed GPER mRNA and protein expression levels using qPCR and Western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4me3, H3Ac, and H3K27Ac) by ELISA kits. Targeted bisulfite and chromatin immunoprecipitation assays were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. GPER expression was downregulated in NOD, with sex-dependent variations. In the gastric smooth muscle, not in colonic smooth muscle, downregulation coincided with differences in methylation ratios between regions 1 and 2 of the GPER promoter of NOD. DNA methylation was higher in NOD male colonic smooth muscle than in NOD females. H3K4me3 and H3ac enrichment decreased in NOD gastric smooth muscle. H3K4me3 levels diminished in the colonic smooth muscle of NOD. H3K27ac levels were unaffected, but enrichment decreased in NOD male gastric smooth muscle; however, it increased in the NOD male colonic smooth muscle and decreased in the female NOD colonic smooth muscle. Male NOD colonic smooth muscle exhibited decreased H3K27ac levels, not female, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac at the GPER promoter, contrary to male NOD. Sex-specific epigenetic mechanisms contribute to T1D-mediated suppression of GPER expression in the GI tract. These insights advance our understanding of T1D complications and suggest promising avenues for targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

In recent years, particular attention has been paid to the serotonin 4 receptor, which is well expressed in the brain, but also peripherally in various organs. The cerebral distribution of this receptor is well conserved across species, with high densities in the basal ganglia, where they are expressed by GABAergic neurons. The 5-HT4 receptor is also present in the cerebral cortex, hippocampus, and amygdala, where they are carried by glutamatergic or cholinergic neurons. Outside the central nervous system, the 5-HT4 receptor is notably expressed in the gastrointestinal tract. The wide distribution of the 5-HT4 receptor undoubtedly contributes to its involvement in a plethora of functions. In addition, the modulation of this receptor influences the release of serotonin, but also the release of other neurotransmitters such as acetylcholine and dopamine. This is a considerable asset, as the modulation of the 5-HT4 receptor can therefore play a direct or indirect beneficial role in various disorders. One of the main advantages of this receptor is that it mediates a much faster antidepressant and anxiolytic action than classical selective serotonin reuptake inhibitors. Another major benefit of the 5-HT4 receptor is that its activation enhances cognitive performance, probably via the release of acetylcholine. The expression of the 5-HT4 receptor is also altered in various eating disorders, and its activation by the 5-HT4 agonist negatively regulates food intake. Additionally, although the cerebral expression of this receptor is modified in certain movement-related disorders, it is still yet to be determined whether this receptor plays a key role in their pathophysiology. Finally, there is no longer any need to demonstrate the value of 5-HT4 receptor agonists in the pharmacological management of gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

The purpose of this review is to focus on the diagnostic endoscopic ultrasound of the gastrointestinal tract. In the last decades, EUS has gained a central role in the staging of epithelial and sub-epithelial lesions of the gastrointestinal tract. With the evolution of imaging, the position of EUS in the diagnostic work-up and the staging flow-chart has continuously changed with two extreme positions: some gastroenterologists think that EUS is absolutely indispensable, and some think it is utterly useless. The truth is, as always, somewhere in between the two extremes. Analyzing the most up-to-date and strong evidence, we will try to give EUS the correct position in our daily practice. [ABSTRACT FROM AUTHOR]

Speciation analysis plays a key role in understanding the biological activity and toxicity of an element. So far, classical speciation analysis focused only on the dissolved fraction of an elemental species, whereas nanoparticle forms of analytes are being widely found in consumer and industrial products. A significant contributor to human exposure to nanoparticles is through food into which nanoparticles can be incorporated from endogenous sources or they may be formed naturally in the living organisms. Nanoparticles often undergo changes in the food matrices and upon consumption, in the gastrointestinal tract, which present a significant challenge to their characterisation. Therefore, a combination of both classical and nanoparticle speciation analytical techniques is needed for the characterisation of both dissolved and particulate forms of the chemical species. This article presents and discusses the current trends in analysis of nanoparticle behaviour in the gastrointestinal tract and formation and characterisation of biogenic nanoparticles. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients. [ABSTRACT FROM AUTHOR]

Streptococcus intermedius is an inhabitant of the oral cavity and gastrointestinal tract, known to cause deep-seated abscesses. Thereby, we present a previously healthy adolescent with esophageal perforation (EP) and secondary mediastinal and brain abscesses due to Streptococcus intermedius. EP is a potentially life-threatening condition that requires a prompt diagnosis. [ABSTRACT FROM AUTHOR]

The microbiome is a complex ecosystem comprising microbes, their genomes, and the surrounding environment. The microbiomeplays a critical role inearlyhumandevelopment, including maturation of the host immune system and gastrointestinal tract. Multiple factors, including diet, antibiotic use, and other environmental exposures, influence the establishment of the microbiome during infancy. Numerous studies have identified associations between the microbiome and neonatal diseases, including necrotizing enterocolitis, sepsis, and malnutrition. Furthermore, there is compelling evidence that perturbation of the microbiome in early life can have lasting developmental effects that increase an individual’s risk for immune and metabolic diseases in later life. Supplementation of the microbiome with probiotics reduces the riskofnecrotizingenterocolitisandsepsis inat-risk infants. This review focuses on the structure and function of the infant microbiome, the environmental and clinical factors that influence its assembly, and its impact on infant healthanddevelopment. [ABSTRACT FROM AUTHOR]

The great majority of patients admitted to the intensive care unit (ICU) for critical gastrointestinal bleeding (GIB) will have a predictable etiology. Once the site is localized to the upper versus the lower gastrointestinal tract, the number of typically encountered etiological possibilities is quite limited. On rare occasions, the cause of GIB requiring ICU care is not one of the standard considerations, potentially leading to diagnostic and therapeutic delays. Within a short time period, three patients were admitted to our institution's medical ICU each with a different unexpected cause of GIB. All three cases generated a variety of instructive images, which are used in the present series to illustrate these conditions and the role of radiology in their evaluation and management. [ABSTRACT FROM AUTHOR]

Aims BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder hereditary hemorrhagic telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms downstream of BMP9 to better characterize its role in vascular homeostasis in different organs. Methods and results For this, we performed an RNA-seq analysis on LSEC from adult WT and Bmp9 -KO mice and identified over 2000 differentially expressed genes. Gene ontology analysis showed that Bmp9 deletion led to a decrease in BMP and Notch signalling, but also LSEC capillary identity while increasing their cell cycle. The gene ontology term 'glomerulus development' was also negatively enriched in Bmp9 -KO mice vs. WT supporting a role for BMP9 in kidney vascularization. Through different imaging approaches (electron microscopy, immunostainings), we found that loss of Bmp9 led to vascular enlargement of the glomeruli capillaries associated with alteration of podocytes. Importantly, we also showed for the first time that the loss of Bmp9 led to spontaneous arteriovenous malformations (AVMs) in the liver, gastrointestinal tract, and uterus. Conclusion Altogether, these results demonstrate that BMP9 plays an important role in vascular quiescence both locally in the liver by regulating endothelial capillary differentiation markers and cell cycle but also at distance in many organs via its presence in the circulation. It also reveals that loss of Bmp9 is sufficient to induce spontaneous AVMs, supporting a key role for BMP9 in the pathogenesis of HHT. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resveratrol (Res) is promising food functional factor with favorable antioxidant and anti‐inflammatory properties, although its poor water solubility and low bioavailability limit extensive application. Therefore, in combination with another promising polysaccharide (Mesona chinensis polysaccharides, MCP), Res‐loaded food nanocarriers (ResNPs) were developed to increase its water solubility, bioactivity and targeting properties. ResNPs were then applied to alleviate dextran sulfate sodium (DSS)‐induced ulcerative colitis. RESULTS: Resveratrol can be well encapsulated in MCP‐based nanoparticles in an amorphous state, improving its water solubility. ResNPs showed pH‐response controlled release behavior in the gastrointestinal tract and increased the enrichment of Res in the colon. In vivo experiments of ResNPs against DSS‐induced ulcerative colitis (UC) revealed that ResNPs significantly improved UC symptoms, modulated intestinal inflammation and down‐regulated oxidative stress levels compared to free Res. ResNPs also play an positive role with respect to inhibiting the mitogen‐activated protein kinase pathway and promoting the expression of tight junction proteins. In addition, ResNPs improved the species composition and relative abundance of intestinal flora in UC mice, which effectively regulated the balance of intestinal flora and promoted the production of short‐chain fatty acids. CONCLUSION: These results suggest that MCP‐based nanoparticles can effectively improve the solubility of resveratrol and enhance its in vivo bioactivity. Moreover, the present study also provides a new strategy for the prevention and treatment of UC with food polyphenol. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma that affects the brain, skin, and bone marrow. We describe the case of a 75-year-old man who was admitted to the hospital after 4 h of stomach aches. A thorough physical examination indicated stomach discomfort and skin discoloration. Laboratory tests revealed thrombocytopenia and elevated lactate dehydrogenase levels. A computed tomography scan of the abdomen revealed that the small intestine wall was thickened, edematous, and necrotic. The necrotic small bowel was surgically removed, revealing many little round, homogenous, and unusual cells in the mesenteric vein. In-situ hybridization revealed that these cells were positive for PAX5, CD20, CD79a, CD10, and BCL2, as well as Epstein-Barr virus-encoded small RNA. After 1 week of hospitalization without treatment, the patient was diagnosed with IVLBCL and died of multiple organ dysfunction syndrome. IVLBCL is a rare illness that affects the small intestine and possibly the gastrointestinal system. It has an insidious start, a fast development, and a dismal prognosis. Knowing its clinicopathologic traits helps in understanding the illness, making an early diagnosis, and preventing rapid worsening. [ABSTRACT FROM AUTHOR]

Micro- and nanoplastics (MNPs) have become ubiquitous contaminants of water and foods, resulting in high levels of human ingestion exposure. MNPs have been found in human blood and multiple tissues, suggesting that they are readily absorbed by the gastrointestinal tract (GIT) and widely distributed. Growing toxicological evidence suggests that ingested MNPs may pose a serious health threat. The potential genotoxicity of MNPs, however, remains largely unknown. In this study, genotoxicity of primary and environmentally relevant secondary MNPs was assessed in a triculture small intestinal epithelium (SIE) model using the CometChip assay. Aqueous suspensions of 25 and 1000 nm carboxylated polystyrene spheres (PS25C and PS1KC), and incinerated polyethylene (PEI PM0.1) were subjected to simulated GIT digestion to create physiologically relevant exposures (digestas), which were applied to the SIE model at final MNP concentrations of 1, 5, and 20 μg/mL for 24 or 48 h. PS25C and PS1KC induced DNA damage in a time- and concentration-dependent manner. To our knowledge, this is one of the first assessment of MNP genotoxicity in an integrated in vitro ingestion platform including simulated GIT digestion and a triculture SIE model. These findings suggest that ingestion of high concentrations of carboxylated PS MNPs could have serious genotoxic consequences in the SIE. [ABSTRACT FROM AUTHOR]

The enteric nervous system (ENS) comprises millions of neurons and glia embedded in the wall of the gastrointestinal tract. It not only controls important functions of the gut but also interacts with the immune system, gut microbiota, and the gut–brain axis, thereby playing a key role in the health and disease of the whole organism. Any disturbance of this intricate system is mirrored in an alteration of electrical functionality, making electrophysiological methods important tools for investigating ENS-related disorders. Microelectrode arrays (MEAs) provide an appropriate noninvasive approach to recording signals from multiple neurons or whole networks simultaneously. However, studying isolated cells of the ENS can be challenging, considering the limited time that these cells can be kept vital in vitro. Therefore, we developed an alternative approach cultivating cells on glass samples with spacers (fabricated by photolithography methods). The spacers allow the cells to grow upside down in a spatially confined environment while enabling acute consecutive recordings of multiple ENS cultures on the same MEA. Upside-down culture also shows beneficial effects on the growth and behavior of enteric neural cultures. The number of dead cells was significantly decreased, and neural networks showed a higher resemblance to the myenteric plexus ex vivo while producing more stable signals than cultures grown in the conventional way. Overall, our results indicate that the upside-down approach not only allows to investigate the impact of neurological diseases in vitro but could also offer insights into the growth and development of the ENS under conditions much closer to the in vivo environment. NEW & NOTEWORTHY: In this study, we devised a novel approach for culturing and electrophysiological recording of the enteric nervous system using custom-made glass substrates with spacers. This allows to turn cultures of isolated myenteric plexus upside down, enhancing the use of the microelectrode array technique by allowing recording of multiple cultures consecutively using only one chip. In addition, upside-down culture led to significant improvements in the culture conditions, resulting in a more in vivo-like growth. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract is complex and consists of multiple organs with unique functions. Rare gene variants can cause congenital malformations of the human GI tract, although the molecular basis of these has been poorly studied. We identified a patient with compound-heterozygous variants in RFX6 presenting with duodenal malrotation and atresia, implicating RFX6 in development of the proximal intestine. To identify how mutations in RFX6 impact intestinal patterning and function, we derived induced pluripotent stem cells from this patient to generate human intestinal organoids (HIOs). We identified that the duodenal HIOs and human tissues had mixed regional identity, with gastric and ileal features. CRISPR-mediated correction of RFX6 restored duodenal identity. We then used gain- and loss-of-function and transcriptomic approaches in HIOs and Xenopus embryos to identify that PDX1 is a downstream transcriptional target of RFX6 required for duodenal development. However, RFX6 had additional PDX1-independent transcriptional targets involving multiple components of signaling pathways that are required for establishing early regional identity in the GI tract. In summary, we have identified RFX6 as a key regulator in intestinal patterning that acts by regulating transcriptional and signaling pathways. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors. [ABSTRACT FROM AUTHOR]