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Alcohol abuse is a substantial cause of various health and societal issues, as well as a significant factor in global disease. Once alcohol is consumed in the gastrointestinal tract, it undergoes metabolism in the liver and lungs. In this investigation, the nonlinear deterministic and stochastic differential frameworks are analyzed numerically to predict the dynamic evolution of the virus in the drinker alcohol model. The framework for apprehending drinking patterns is categorized into three distinct groups: the susceptible population, risk drinkers, and moderate drinkers. The approximate solution for each population group is determined by exhaustively creating scenarios that vary the probability ratio of infection in susceptible individuals who do not consume alcohol, the increasing rate of alcohol consumption, the rate at which individuals transition from acute to chronic drinking categories, the rate at which new non-drinking consumers are attracted, the death rate of the population, the ratio affecting the rate of sociability in heavy drinkers, and the overall population rate. The Euler–Maruyama approach for the stochastic framework and the Adams method for the deterministic framework are utilized, respectively, to determine the solutions of the alcohol drinker model. This study compares deterministic and stochastic frameworks to underscore their distinct characteristics and efficiency, achieved through comprehensive simulations and in-depth analysis of the numerical outcomes. [ABSTRACT FROM AUTHOR]

Pectin is widely spread in nature and it develops an extremely complex structure in terms of monosaccharide composition, glycosidic linkage types, and non-glycosidic substituents. As a non-digestible polysaccharide, pectin exhibits resistance to human digestive enzymes, however, it is easily utilized by gut microbiota in the large intestine. Currently, pectin has been exploited as a novel functional component with numerous physiological benefits, and it shows a promising prospect in promoting human health. In this review, we introduce the regulatory effects of pectin on intestinal inflammation and metabolic syndromes. Subsequently, the digestive behavior of pectin in the upper gastrointestinal tract is summarized, and then it will be focused on pectin's fermentation characteristics in the large intestine. The fermentation selectivity of pectin by gut bacteria and the effects of pectin structure on intestinal microecology were discussed to highlight the interaction between pectin and bacterial community. Meanwhile, we also offer information on how gut bacteria orchestrate enzymes to degrade pectin. All of these findings provide insights into pectin digestion and advance the application of pectin in human health. [ABSTRACT FROM AUTHOR]

Nanoencapsulation has found numerous applications in the food and nutraceutical industries. Micro and nanoencapsulated forms of bioactives have proven benefits in terms of stability, release, and performance in the body. However, the encapsulated ingredient is often subjected to a wide range of processing conditions and this is followed by storage, consumption, and transit along the gastrointestinal tract. A strong understanding of the fate of nanoencapsulates in the biological system is mandatory as it provides valuable insights for ingredient selection, formulation, and application. In addition to their efficacy, there is also the need to assess the safety of ingested nanoencapsulates. Given the rising research and commercial focus of this subject, this review provides a strong focus on their interaction factors and mechanisms, highlighting their prospective biological fate. This review also covers various approaches to studying the fate of nanoencapsulates in the body. Also, with emphasis on the overall scope, the need for a new advanced integrated common methodology to evaluate the fate of nanoencapsulates post-administration is discussed. [ABSTRACT FROM AUTHOR]

Diet can be considered as one of the pivotal factors in regulating gastrointestinal health, and polyphenols widely distributed in human daily diet. The polyphenols and their metabolites playing a series of beneficial effects in human gastrointestinal tract that can regulate of the gut microbiota, increase intestinal barrier function, repair gastrointestinal mucosa, reduce oxidative stress, inhibit the secretion of inflammatory factors and regulating immune function, and their absorption and biotransformation mainly depend on the activity of intestinal microflora. However, little is known about the two-way interaction between polyphenols and intestinal microbiota. The objective of this review is to highlight the structure optimization and effect of flavonoids on intestinal flora, and discusses the mechanisms of dietary flavonoids regulating intestinal flora. The multiple effects of single molecule of flavonoids, and inter-dependence between the gut microbiota and polyphenol metabolites. Moreover, the protective effects of polyphenols on intestinal barrier function, and effects of interaction between plant polyphenols and macromolecules on gastrointestinal health. This review provided valuable insight that may be useful for better understanding the mechanism of the gastrointestinal health effects of polyphenols, and provide a scientific basis for their application as functional food. HIGHLIGHTS: Possible mechanism of flavonoids regulating intestinal flora. Flavonoids optimize the structure and composition of gut microbiota. Polyphenol improve intestinal barrier function. Interaction between polyphenols and macromolecules improves gastrointestinal health The two-way interaction between flavonoids and intestinal microflora to improve bioavailability [ABSTRACT FROM AUTHOR]

An 8‐year‐old, neutered female, Australian Silky Terrier presented to her primary veterinarian with non‐specific clinical signs of general unwellness, shaking, lethargy, inappetence and no defecation for 2–3 days. A rectal mass was found on physical examination. The rectal mass was surgically resected and histopathology was consistent with a mast cell tumour (MCT) with a mitotic count of 0 per 2.37mm2. The dog had follow‐up chemotherapy protocol comprising of vinblastine and prednisolone and was doing well with no evidence of tumour recurrence 30 weeks post surgical resection and is still alive and clinically normal at the time of writing, 9 months post initial diagnosis. Primary MCTs of the gastrointestinal tract have previously been reported to be associated with a poor prognosis. This is the first report of a canine rectal mast cell tumour with lower grade features of biological aggressiveness and a possibly more favourable prognosis compared with the current published literature. [ABSTRACT FROM AUTHOR]

Background: Radiation-mediated GI injury (RIGI) is observed in humans either due to accidental or intentional exposures. This can only be managed with supporting care and no approved countermeasures are available till now. Early detection and monitoring of RIGI is important for effective medical management and improve survival chances of exposed individuals. Objective: The present study aims to identify new signatures of RIGI using data mining approach followed by validation of selected hub genes in mice. Methods: Data mining study was performed using microarray datasets from Gene Expression Omnibus database. The differentially expressed genes were identified and further validated in total-body irradiated mice. Results: Based on KEGG pathway analysis, lipid metabolism was found as one of the predominant pathways altered in irradiated intestine. Extensive alteration in lipid profile and lipid modification was observed in this tissue. A protein–protein interaction network revealed top 08 hub genes related to lipid metabolism, namely Fabp1, Fabp2, Fabp6, Npc1l1, Ppar-α, Abcg8, Hnf-4α, and Insig1. qRT-PCR analysis revealed significant up-regulation of Fabp6 and Hnf-4α and down-regulation of Fabp1, Fabp2 and Insig1 transcripts in irradiated intestine. Radiation dose and time kinetics study revealed that the selected 05 genes were altered differentially in response to radiation in intestine. Conclusion: Finding suggests that lipid metabolism is one of the key targets of radiation and its mediators may act as biomarkers in detection and progression of RIGI. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing global health concern, as it has become the most prevalent chronic liver condition worldwide, currently estimated to affect up to 38% of the adult population. EVIDENCE ACQUISITION: MASLD is a complex disease impacting multiple systems, where systemic insulin resistance and related metabolic dysfunction play a pathogenic role in its development and progression of the disease. Despite its prevalence, MASLD is frequently under-recognized due to the lack of reliable non-invasive biomarkers for accurate diagnosis and staging, and effective treatments remain elusive. EVIDENCE SYNTHESIS: Growing evidence suggests that the gut microbiome significantly influences the occurrence and progression of MASLD due to gut dysbiosis. The Simulator of the Human Intestinal Microbial Ecosystem® (SHIME®) is a sophisticated gut models that mimics the entire gastrointestinal tract, incorporating stomach, small intestine, and different colon regions, each characterized by distinct physiology, anatomy, and microbial community. CONCLUSIONS: The SHIME® model emerges as a valuable tool for exploring therapeutic approaches based on gut microbiota management. This gastrointestinal simulator offers a unique platform for studying the complex interactions within the gut-liver axis. The ongoing development of this technology is expected to yield further insights into effective strategies for managing MASLD, improving patient outcomes through targeted microbiota interventions. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which involves not only the skeleton, but also the cardiopulmonary and gastrointestinal system, soft tissues, tendons, muscle, and joints, hearing, eyesight, dental health, and women's health in OI and potentially adds negative affect to health-related quality of life. We aim to guide clinicians as well as draw attention to obvious knowledge gaps and the need for further research in adult OI [ABSTRACT FROM AUTHOR]

The availability and quality of food resources can alter the intensity of competition and predation pressure within communities. Understanding species capacity to respond to global change‐driven shifts in resource distribution is therefore crucial for biodiversity conservation. Small mammal communities are often structured by competition for food resources, but understanding and monitoring these processes are currently hindered by lack of functional dietary trait information in these hard‐to‐sample systems. In this study, we collected a comprehensive suite of gastrointestinal (GI) measurements from 26 small mammal species (including some never reported), compared them with more traditional craniodental traits in predicting dietary guild, and used them in a novel way to understand how diet structures 22 small mammal communities across the Appalachian Mountains of eastern North America. As predicted, we found GI traits to be effective dietary trait proxies; they were equally or more accurate than craniodental proportions in predicting the dietary guild of individual species. Furthermore, at the community level, we found that both the mean and functional dispersion of GI length were positively correlated with latitude and measures of temperature seasonality. Our results indicate that small mammal communities in more seasonal environments are filtered to include species with longer GI tracts (on average) as well as those that can partition food resources more finely, as expected based on the lower productivity of these regions. Conversely, communities in less seasonal environments display functional redundancy from the addition of species with short to intermediate GI lengths. Proportions of the GI tract represent novel dietary traits that can illuminate community assembly processes across regional environmental gradients and in the face of changing timing and availability of resources. [ABSTRACT FROM AUTHOR]

Objective: To explore the application of small-sized magnetically controlled capsule gastroscopy (MCCG) in upper gastrointestinal diseases screening in asymptomatic individuals. Methods: A retrospective analysis of the clinical data of 2163 asymptomatic individuals who underwent small-sized MCCG at our center from September 2022 to December 2023. The detection of submucosal tumors, polyps and ulcers in the upper gastrointestinal tract, the tolerance and safety of the subjects were statistically analyzed. Results: Suspected submucosal tumors in the upper gastrointestinal tract were detected in 34 (1.57%) of 2136 subjects, with a higher incidence in females and no observed age difference. Polyps were detected in 328 subjects (15.16%), with a higher incidence in females and an increased detection rate with increasing age. Ulcers were detected in 27 subjects (1.25%), with a higher incidence in males and no observed age difference. There was no significant discomfort in all subjects, and no adverse event or capsule retention occurred. Conclusion: Small-sized MCCG can be used for focal lesion screening in the upper gastrointestinal tract and is comfortable and safe, making it a safe and efficient method for examining upper gastrointestinal diseases in the physical examination population. [ABSTRACT FROM AUTHOR]

The increasing demand for hydrocolloids with specific functionality has led researchers to seek new hydrocolloid sources. One of the methods to enhance the viability of probiotics under stressful conditions is microencapsulation, to deliver these bacteria to the body in sufficient numbers and utilize their health -promoting effects. The aim of this study is to investigate the feasibility of Lactobacillus acidophilus microencapsulation by ammonium gum (AMG) and its enrichment using nanoselenium, and determine its viability under stressful conditions. AMG was extracted from the mucilage of Dorema Ammoniacum plant using a solvent and then precipitated by alcohol. 1%, 5%, and 10% w/v solutions of AMG were prepared, and then nanoselenium particles synthesized at a concentration of 1.5% were added to the bacterial suspension with an average count of 6.85×1011 log CFU g -1 . The results showed that with an increase in the concentration of gum, the encapsulation efficiency significantly increased from 66% to 81%. The viability rate for 1%, 5%, and 10% concentrations of AMG under refrigeration conditions was 62.43%, 72.37%, and 81.83%, respectively. Under simulated gastric conditions at the pH levels used in this study, the counts of viable cells after 3 h of incubation for 5% and 10% concentrations of AMG remained higher than 7 log CFU g -1 . After 6 h of incubation in a 10 g L -1 solution, the free cells showed a decrease to 5.93 log CFU g -1, while for microencapsulated cells at concentrations of 1%, 5%, and 10%, it was only 3.93 log CFU g -1, 3.15 log CFU g -1, and 1.9 log CFU g -1, respectively. The results showed that AMG has very good encapsulation properties, which can be used in many food formulations for these purposes. [ABSTRACT FROM AUTHOR]

Nanocarriers, more commonly called nanoparticles (NPs), have found increasing use as delivery vehicles which increase the oral bioavailability of poorly water-soluble and peptide therapeutics. Therapeutic bioavailability is commonly assessed by measuring plasma concentrations that reflect the absorption kinetics. This bioavailability is a convolution of the gastrointestinal distribution of the NP vehicle, the release rate of the encapsulated therapeutic cargo, and the absorption-metabolism-distribution kinetics of the released therapeutic. The spatiotemporal distribution of the NP vehicle in the gastrointestinal tract is not well studied and is a buried parameter in PK studies used to measure the effectiveness of an NP formulation. This work is a study of the intestinal distribution and fate of orally dosed NPs in male CD-1 mice over 24 h. NPs have identical hydrophobic cores – composed of poly(styrene) homopolymer, a naphthalocyanine dye, and oleate-coated europium oxide colloids – with one of four different surface stabilizers: neutral poly(styrene)- block -poly(ethylene glycol) (PS-b-PEG), moderately negative hydroxypropyl methylcellulose acetate succinate (HPMCAS), highly negative poly(styrene)- block -poly(acrylic acid) (PS-b-PAA), and highly cationic adsorbed chitosan HCl on PS-b-PAA stabilized NPs. NP hydrodynamic diameters are all below 200 nm, with some variation attributable to the molecular properties of the stabilizing polymer. The encapsulated hydrophobic europium oxide colloids do not release soluble europium ions, enabling the use of highly sensitive inductively coupled plasma mass spectrometry (ICP-MS) to detect NP concentrations in digested biological tissues. Highly anionically-charged PAA and cationically-charged chitosan stabilized NPs showed statistically significant increased retention compared to the neutral PEG-stabilized NPs at p < 0.05 significance and (1-β) > 0.95 power. HPMCAS-stabilized NPs showed statistically insignificant greater retention than PEG-stabilized NPs, and all NP formulations showed clearance from the intestines within 24 h. Different surface charges preferentially reside in different segments of the intestines, where cationic chitosan-stabilized NPs showed increased retention in the small intestines (ileum) and anionic PAA-stabilized NPs in the large intestines (caecum and colon). Modifying the surface charge of a NP can be used to modulate mucoadhesion, total retention, and intestinal segment specific retention, which enables the rational design of delivery vehicles that maximize residence times in appropriate locations. [Display omitted] [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. This study evaluated the effects of short-term feed restriction in lactating dairy cows on regional permeability of the gastrointestinal tract (GIT), and the recovery of DMI, ruminal pH, and milk yield. In addition, sampling methods for a novel dual marker technique to characterize total GIT and post-ruminal permeability were validated. Six ruminally cannulated lactating Holstein cows were blocked by parity (3 primiparous, 3 multiparous; 189 DIM ± 25.2) and enrolled in a crossover design. Experimental periods included a 5-d baseline phase, 5-d challenge phase (CHAL), and 2 wk of recovery (REC1 and REC2). During CHAL, cows received either 100% ad libitum feed intake (AL) or 40% of ad libitum feed intake (FR). To assess total-tract and post-ruminal permeability, equimolar doses of Cr-EDTA and Co-EDTA were infused on d 3 of CHAL into the rumen and abomasum (0.369 mmol/kg BW). Following infusions, total urine and feces were collected every 8 h over 96 h, and blood samples were collected at h 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, and 64. The plasma area under the curve (AUC) for Cr and Co were calculated. By design, DMI for FR was reduced by 60% during CHAL and remained 19% lower than AL during REC1 but was not different from AL in REC2. Mean ruminal pH for FR was greatest during CHAL and least during REC1, with no differences detected between AL and FR in REC2. The duration that pH was <5.8 was least for FR during CHAL and greatest during REC1, which were different from AL and were no longer different between treatments in REC2. Milk yield was the least for FR during CHAL and REC1 and no longer different from AL in REC2. Feed restriction reduced milk fat, protein, and lactose yields by 26%, 31%, and 31%, respectively. Plasma Cr AUC was 34% greater and Co AUC tended to be 35% greater for FR than AL on d 3 of CHAL. Urinary Cr recovery after 48 h was not affected by treatment; however, urinary Co recovery was 36% greater for FR than AL. Positive correlations between plasma AUC and urinary recovery for Cr and Co were detected. It was determined that blood samples collected at h 2, 8, 20, 40, and 48 could predict the total plasma Cr and Co AUC within 1.9% and 6.2%, respectively. In summary, short-term FR in lactating dairy cows increases permeability of the total GIT and may increase permeability of the post-ruminal regions, with more than 60% of the permeability occurring post-ruminally. After FR, cows experienced low ruminal pH and a sustained reduction in milk yield. When using Cr- and Co-EDTA to evaluate regional GIT permeability, plasma AUC can be used as an alternative to urinary Cr and Co excretion. In addition, blood samples collected at h 2, 8, 20, 40, and 48 result in adequate prediction accuracy, at least when comparing GIT permeability for lactating dairy cows exposed to AL and FR. [ABSTRACT FROM AUTHOR]

Roux‐en‐Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic–pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed‐effect modeling approach. A parent–metabolite model with first‐order absorption, 2‐compartments for SV and 1‐compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL‐cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low‐intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post‐RYGB patients to maintain a comparable response to that of non‐operated subjects. Moderate‐intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non‐statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post‐RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non‐statin drugs to attain equivalent responses and mitigate potential adverse events. [ABSTRACT FROM AUTHOR]

Developing ice cream products as functional foods with less fat content and a high survival rate of probiotics aided by prebiotics is required to address the demands of health-conscious consumers. This study aimed to investigate the effects of fat content (2 and 10% fat as a low and full-fat, respectively) and different concentrations of prebiotics (galacto-oligosaccharide, GOS and fructo-oligosaccharide, FOS) on the survival rate of Bifidobacterium longum TISTR 2195 in yogurt ice cream (YIC) and in an in vitro gastrointestinal system. Fat content affected the fat particle size, melting rate, and solid-like characteristics of ice cream. The hardness and elasticity of YIC were enhanced more significantly by FOS, owing to its lower solubility and denser microstructure, manifesting more solid-like properties than those by YIC containing GOS. Moreover, type and prebiotic concentrations influenced B. longum TISTR 2195 survival in YIC. Moreover, B. longum TISTR 2195 content in YIC during storage for 180 d remained consistent at 106 CFU/g, which is considered beneficial to human health. The study findings could be useful for ice cream manufacturers to produce low- or full-fat YICs containing prebiotics and probiotics, as functional and healthy foods. [ABSTRACT FROM AUTHOR]

Ascorbic acid (vitamin C) is the most crucial antioxidant for the body. The biochemical capabilities of ascorbic acid are still being studied. It acts as a cofactor for many enzymes participating in various physiological functions. This review presents how ascorbic acid is a cofactor for multiple enzymes involved in numerous human activities. Ascorbic acid protects the immune system, reduces allergic reaction severity and assists the fight against infections and other disorders. Ascorbic acid is metabolized by several procedures in the gastrointestinal tract. Eukaryotes produce ascorbic acid via L-galactose (L-Gal) and GDP-D-mannose as part of its metabolic process. It is disseminated throughout the body cells after being readily absorbed by the digestive system. This review will uncover ascorbic acid's biological functions and metabolism in humans. [ABSTRACT FROM AUTHOR]

Background: Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum. Methods: Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry. Results: Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin‐15 (IL‐15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL‐15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL‐15 receptor was not increased either on Intraepithelial lymphocytes from CD patients. Conclusions: IL‐15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis. [ABSTRACT FROM AUTHOR]

• LGR5 is a GPCR-like receptor that enacts differently from GPCR, hence termed the "Orphan receptor." Primarily maintains cell-to-cell adhesion in healthy and cancer cells of the gastrointestinal tract. • Lgr5 is a potent gene to induce Wnt signalling and significantly modulates stem-cell renewal. However, Lgr5+ cancer stem cells also respond to GLI2A activator and increase mTOR signalling when activated by NOTCH signalling. • Lgr5+ cells flaunt their characteristic plasticity through ERK mechanosensory signalling. ERK/MAPK signalling prohibits apoptosis and is crucial for metastasis. Further, drug-resistant LGR5-cells are the result of EMT/MET transitions. • Prostate is a heterogeneous tissue with basal and luminal lineages that give rise to its stratified epithelium. These lineages give rise to both androgen-dependent and androgen-independent cells. Certain androgen-independent stem cells give rise to androgen-independent as well as androgen-sensitive cells. Amongst them, Lgr5+ cells were found to survive even after androgen substitution. • For prostate regeneration, LGR5+ cells must post castration and androgen substitution. However, their, resistance to castration gives rise to advanced Castration-Resistant Prostate Cancer- CRPC. • Lgr5+ cell ablation doesn't have an androgenic or neuro-sympathetic impact; instead, it amplifies tissue stiffness, heightening mechanosensory responses, and boosting prostate epithelial turnover. • Applying strong affinity between RSPO3 and LGR5, engineered liposomal drug delivery can effectfully target LGR5+ cells. Prostate cancer poses a significant risk to the well-being and way of life of countless men, with an increased likelihood of relapse recorded following modern treatment. This highlights the need for innovative approaches, specifically targeting LGR5. This systematic review aims to establish a connection between LGR5 and the various signaling pathways involved in the progression of prostate cancer. LGR5, a gene targeted by Wnt signaling, encodes a receptor protein that serves as a prognostic biomarker for stem cells and indicates the presence of cancer stem cells in colorectal and gastrointestinal cancers. The functions of LGR5 include processes such as cell proliferation, differentiation, and signaling pathways. Any modifications to the LGR5 gene, whether caused by mutations or mechanical stimuli, can lead to the development of treatment-resistant stem cell cancers. This review examines the molecular mechanisms associated with LGR5 and emphasizes methodologies aimed at targeting LGR5 to enhance understanding and promote the development of LGR5-specific therapies. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear. Methods: We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5–C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis. Results: We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6 ± 5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross‐sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy. Conclusions: Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv. [ABSTRACT FROM AUTHOR]

Background and Aims: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms. Methods: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych). Key Results: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2‐class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty‐two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%–97% for 2 clusters and 71–79% for 6 classes and 51%–63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non‐DGBI (range 97% with 2 clusters to 65% with 22 classes) groups. Conclusions & Inferences: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits. [ABSTRACT FROM AUTHOR]

This article has been co-authored by a patient living with hereditary transthyretin (ATTRv) amyloidosis and a neurologist. This rare, progressive disease is associated with impairment of multiple organ systems, including the nerves, heart, and the gastrointestinal tract, forcing patients to live with and adapt to a range of debilitating symptoms. Here, the patient and physician discuss how the symptoms of ATTRv amyloidosis profoundly impact day to day life, the difficulties with identifying the disease, and how this effects the diagnosis experience. In recent years, significant advancements have been made in the treatment and management of ATTRv amyloidosis. However, the authors highlight the urgency of increasing awareness of the disease among the wider medical community, as well as in patients who notice the symptoms, to ensure that earlier diagnosis and appropriate treatment are achieved. [ABSTRACT FROM AUTHOR]

Background: 2‐(2‐Nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC) treatment of alkaptonuria (AKU) leads to increased blood tyrosine levels, causing skin issues and potentially sight‐threatening corneal keratopathy. Adherence to dietary management of NTBC‐induced tyrosinemia, a low‐protein diet with or without protein substitutes, can be difficult for patients. This 28‐day interventional study evaluated a low tyrosine casein glycomacropeptide (cGMP) protein substitute (TYR sphere)®, a 20 g protein equivalent, cGMP‐based protein substitute, in terms of adherence, palatability, usability, comparison to amino acid (AA)–based protein substitutes, gastrointestinal tolerance and metabolic control in adults with NTBC‐induced tyrosinaemia. Methods: Four adults (mean 61.1 years, range 53.3–69.3 years) with AKU and NTBC‐induced tyrosinaemia were recruited from the United Kingdom National Alkaptonuria Centre (NAC). The cGMP protein substitute was prescribed based on individual nutritional requirements, replacing ≥1 AA‐based protein substitute. Participants recorded product‐related data in study diaries, using five‐point Likert scales and daily and weekly logs. To determine metabolic control, prestudy blood tyrosine levels were compared to weekly blood spot tests during the study. Results: Median cGMP protein substitute adherence was 98%. Most participants rated palatability and usability positively, and preferred cGMP protein substitute to AA‐based products. There were no notable gastrointestinal changes, and metabolic control was maintained. Conclusions: cGMP protein substitute is a palatable and well‐tolerated option in the dietary management of AKU patients with NTBC‐induced tyrosinaemia. Key points: Alkaptonuria (AKU) treated with 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC) induces tyrosinaemia that requires dietary management to prevent clinical consequences such as corneal keratopathy.A low tyrosine casein glycomacropeptide (cGMP)‐based protein substitute can be used to replace protein and other important nutrients where a protein restriction is indicated.The low tyrosine cGMP‐based protein substitute used in this study was well adhered to, with no notable effects on gastrointestinal tolerance and maintained metabolic control within acceptable parameters.Low tyrosine cGMP protein substitutes provide a viable, well‐tolerated alternative to traditional amino acid–based protein substitutes to help achieve treatment outcomes, of particular relevance should treatment begin earlier in life in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to improve the stability and utilization of sulforaphene (SFE) and to enhance the intestinal stability and pH‐sensitive release of SFE in the gastrointestinal tract. To achieve this objective, calcium chloride (CaCl2) was used as a crosslinking agent to fabricate novel SFE‐loaded gellan gum (GG)‐ε‐polylysine (ε‐PL) pH‐sensitive hydrogel microspheres by using the ionic crosslinking technique. RESULTS: The molecular docking results of GG, ε‐PL, and SFE were good and occurred in the natural state. The loading efficiency (LE) of all samples was above 70%. According to the structural characterization results, GG and ε‐PL successfully embedded SFE in a three‐dimensional network structure through electrostatic interaction. The swelling characteristics and in vitro release results revealed that the microspheres were pH‐sensitive, and SFE was mainly retained inside the hydrogel microsphere in the stomach, and subsequently released in the intestine. The result of cytotoxicity assay showed that the hydrogel microspheres were non‐toxic and had an inhibitory effect on human colon cancer Caco‐2 cells. CONCLUSION: Thus, the hydrogel microspheres could improve SFE stability and utilization and achieve the intestinal targeted delivery of SFE. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders. [ABSTRACT FROM AUTHOR]

Background and Objectives: Parkinson disease (PD), which is a neurodegenerative disorder, includes several gastrointestinal symptoms that are similar to those of Celiac disease (CD). However, the presence of celiac antibodies in PD patients has not yet been studied. Our aim in this study is to compare anti-transglutaminase (ATA) and antigliadin antibodies (AGA) as well as gastrointestinal symptoms and nutrition habits between patients with Parkinson's disease (PD) and healthy controls. Methods and Study Design: Serum AGA IgG and IgA and the ATA antibodies IgA and IgG were studied in 102 PD patients and 91 healthy controls. Gastrointestinal symptoms, specifically constipation, were investigated using the gastrointestinal system rating scale (GSRS) and the constipation rating scale (CRS). Dietary habits were also investigated and compared between the groups. Results: No significant differences were found between the two groups in terms of celiac antibodies. As expected, the hypokinetic GSRS and CRS scores were significantly higher in the PD group (p<0.001). Dietary habits, especially carbohydrate-rich diets, had a negative impact on gastrointestinal symptoms in the PD patients. Conclusions: Studies have suggested a connection between PD and CD, which infers a probable non-celiac gluten intolerance and the need to offer PD patients an elimination diet. However, the results of our study did not support any link between celiac antibodies and PD. Notwithstanding, the negative impact of a carbohydrate-rich diet in PD patients still leaves a question regarding gluten sensitivity in these patients. [ABSTRACT FROM AUTHOR]

Introduction: The administration of proton pump inhibitors (PPIs) is anticipated to elevate an individual's susceptibility to enteric infections as a result of altering the gut flora. The influence of PPIs on the clinical manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain. This study aims to investigate the impact of PPI usage on the clinical manifestation of COVID-19, namely its gastrointestinal symptoms. Methods: This is a cross-sectional cohort study involving COVID-19 patients. Patients were interviewed using a predesigned questionnaire that asked about their demographics, clinical manifestations of COVID-19 infection, and the extent and type of PPIs in use. PPI usage was confirmed by reviewing patients' electronic medical records. The primary outcome was to establish any association between the use of PPI and the symptoms and clinical presentation of COVID-19. Results: Out of a total of 254 participants, 69 (27.2%) were considered PPI users. Patients who were on PPI medications reported a significantly lower rate of myalgia (27.5% vs 51.9%; p=0.0006) and heartburn (5.7% vs 15.6%; p=0.03) but had a significantly higher rate of abdominal pain (27.5% vs 13.5%; p=0.001) and diarrhoea (28.9% vs 14.5%, p=0.02) when compared to those who were not using PPIs. Patients on PPIs were also shown to have significantly higher odds of developing diarrhoea (OR 2.0, 95% CI: 1.08 to 3.93, p=0.02) and abdominal pain (OR 2.0, 95% CI: 1.22 to 3.93, p=0.03), but a lower risk of developing myalgia (OR 0.5, 95% CI: 0.3 to 0.9, p=0.02) when compared to non-PPI users. Conclusion: This study shows that the use of PPIs could impact COVID-19 clinical presentation toward more gastrointestinal manifestations. Further studies investigating the link between other acid suppression medications and COVID-19 manifestations and severity should be carried out. [ABSTRACT FROM AUTHOR]

The mammalian gastrointestinal tract provides a habitat for multiple commensal and pathogenic organisms spanning all three domains of life. Both positive and negative interactions occur between gut inhabitants, with potential consequences for host health. Studies of parasite–microbiota associations in natural systems remain scarce, yet are important for understanding how parasite communities and commensal microbiota shape each other, and how these interactions influence host health. Here, we characterize associations between helminth and coccidial infections and gut microbiota profiles in a wild population of wood mice (Apodemus sylvaticus) over 3 years, using two complementary approaches. We first examined parasite–microbiota associations along the length of the gastrointestinal tract through destructive sampling. Then, in a larger non-invasive capture mark-recapture study, we assessed whether gut parasitic infections detected in feces predicted fecal microbiota diversity and composition. We found that while overall microbiota composition was not associated with infection by any common gut parasite species, microbiota richness was associated with gut parasitism in two ways: (i) infection by the trematode Corrigia vitta in the small intestine predicted higher microbiota diversity in the caecum; (ii) there was a negative relationship between gut parasite richness and fecal microbiota richness in the non-invasive study. As our results identified associations between gastrointestinal parasites and microbiota alpha diversity, a future experimental study in this tractable wild mammalian system would be valuable to definitively test the directionality of these interactions. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery (TDD) has significantly advanced medical practice in recent years due to its ability to prevent the degradation of substances in the gastrointestinal tract and avoid hepatic metabolism. Among different available approaches, microneedle arrays (MNAs) technology represents a fascinating delivery tool for enhancing TDD by penetrating the stratum corneum painless and minimally invasive for delivering antibacterial, antifungal, and antiviral medications. Polymeric MNAs are extensively utilized among many available materials due to their biodegradability, biocompatibility, and low toxicity. Therefore, this review provides a comprehensive discussion of polymeric MNAs, starting with understanding stratum corneum and developing MNA technology. Furthermore, the engineering concepts, fundamental considerations, challenges, and future perspectives of polymeric MNAs in clinical applications are properly outlined, offering a comprehensive and unique overview of polymeric MNAs and their potential for a broad spectrum of clinical applications. [ABSTRACT FROM AUTHOR]

Background: Coptis deltoidea C.Y. Cheng et Hsiao (CD), commonly used in the treatment of heat-toxin congestion and excessiveness. However, CD needs to be processed with wine for alleviating the bitter and cold of CD, meanwhile, reducing the gastrointestinal damage. The research assessed the discrepant effects of CD on gastrointestinal system before and after processing with wine, and explore the potential mechanisms. Methods: The ingredients in CD and CD processed with wine (PCD) were performed on Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS). The mice were treated with CD and PCD once a day for 6 weeks (0.65 and 2.6 g/kg, i.g.). The pathological changes of gastrointestinal tract were evaluated, and the serum inflammatory factors and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) RelA (p65) protein of tissues were determined. The short chain fatty acids (SCFAs) of feces were analyzed by UPLC-MS, the gut microbiota (GM) changes were performed on 16 S rRNA sequencing. Results: Ingredients analysis declared that the alkaloids, flavonoids, phenylpropanoid compounds were the main metabolites in CD and PCD. CD reduced body weight and food intake, and the effect of CD on fecal water content increased first and then decreased with the prolongation of administration time, while its effect on intestinal transport time was exactly the opposite, reduced the SCFAs contents of feces. CD caused different degree of damage to the gastrointestinal tract, and the effect on the small intestine and colon was more obvious, which increased the expression of NF-κB p65 and elevated the inflammatory factors levels. PCD were weaker than that of CD. In addition, CD and PCD can change the composition of GM, and reduced the levels of Lactobacillus , Allobaculum , Ruminococcus , and norank_f_S24-7 , increased the levels of Akkermansia , Dorea , Bacteroides , and Blautia at the genus level. However, PCD induced a milder effect of GM dysregulation than that of CD. Conclusion: CD can cause damage to the gastrointestinal tract, which may be related to the GM disorders, SCFAs changes-mediated by GM, abnormal NF-κB p65 expression and increased inflammatory factors levels, interestingly, PCD had a lower effect than CD, which may be related to the differences in the types and contents of ingredients in CD after processing. And this study provided data support for the mechanism of processing with wine to alleviate "bitter-cold injury the stomach" of CD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Wuda Granule (WDG) on recovery of gastrointestinal function after laparoscopic bowel resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care. Methods: A total of 108 patients aged 18 years or older undergoing laparoscopic bowel resection with a surgical duration of 2 to 4.5 h were randomly assigned (1:1) to receive either WDG or placebo (10 g/bag) twice a day from postoperative days 1–3, combining with ERAS-based perioperative care. The primary outcome was time to first defecation. Secondary outcomes were time to first flatus, time to first tolerance of liquid or semi-liquid food, gastrointestinal-related symptoms and length of stay. Subgroup analysis of the primary outcome according to sex, age, tumor site, surgical time, histories of underlying disease or history of abdominal surgery was undertaken. Adverse events were observed and recorded. Results: A total of 107 patients [53 in the WDG group and 54 in the placebo group; 61.7 ± 12.1 years; 50 males (46.7%)] were included in the intention-to-treat analysis. The patients in the WDG group had a significantly shorter time to first defecation and flatus [between-group difference −11.01 h (95% CI −20.75 to −1.28 h), P=0.012 for defecation; −5.41 h (−11.10 to 0.27 h), P=0.040 for flatus] than the placebo group. Moreover, the extent of improvement in postoperative gastrointestinal-related symptoms in the WDG group was significantly better than that in the placebo group (P<0.05). Subgroup analyses revealed that the benefits of WDG were significantly superior in patients who were male, or under 60 years old, or surgical time less than 3 h, or having no history of basic disease or no history of abdominal surgery. There were no serious adverse events. Conclusion: The addition of WDG to an ERAS postoperative care may be a viable strategy to enhance gastrointestinal function recovery after laparoscopic bowel resection surgery. (Registry No. ChiCTR2100046242) [ABSTRACT FROM AUTHOR]

Background: Cytisine is an alkaloid that is molecularly similar to nicotine and it is commonly used to treat smoking cessation. While it is considered a reasonably safe treatment option, cytisine intoxication in humans exhibits several adverse effects. These involve the gastrointestinal system (nausea, vomiting, diarrhea), the central nervous system (drowsiness, fatigue, delirium), and the motor system (muscle twitching and fasciculation, difficulties in walking). Case presentation: We present a unique case report in which a Caucasian patient (an Italian 64-year-old woman) who was undergoing smoking cessation treatment with cytisine, and due to her misunderstanding of the therapeutic indications provided, took twice the recommended dose every day for 8 days, leading to an intake of 54 mg/dl of cytisine for 3 consecutive days. Notwithstanding the high dosage, the patient did not report any adverse reactions. Conclusion: This confirms the safety of the drug, even at high doses, in patients aiming to quit smoking. [ABSTRACT FROM AUTHOR]

New design techniques are required to improve the stability of vitamin C (VC), which is essential for human health but is sensitive to environmental factors, in the stomach and its release in the body. The purpose of this study is to develop and characterise a fibre interlaced liposome (FIL) as a vehicle for better delivery of VC, with fruit fibres providing surface protection against degradation, which was confirmed by various studies. The optimised formulation was evaluated for its structural and surface morphological properties through zeta potential, FTIR, XRD, SEM, TEM, and DSC analyses. In vitro release studies were also conducted, and FIL-VC displayed a sustained release of VC (19.31%) compared to the control (67.54%) during the period of 8 h. FIL-VC demonstrates better release in simulated intestinal fluids (95.34%) than in gastric fluids (21.15%), indicating better stability and absorption in the gastrointestinal tract. In a randomized, double-blind, active-controlled, two-way crossover clinical study, FIL-VC showed 5.77-fold higher relative oral bioavailability in comparison with the unformulated VC. The AUC0−t for VC in FIL-VC (23.80 μg mL−1) was found to be significantly higher compared to unformulated VC (4.13 μg mL−1) after the oral administration of a single dose. These data show that FIL formulation resulted in a sustained release of VC with increased bioavailability, which could be beneficial for extended-release applications. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases constitute a group of persistent and irreversible conditions marked by gradual degeneration and impairment of the central and/or peripheral nervous systems. Elevated oxidative stress, impaired sleep, aging, altered immune and disturbed mitochondrial functions, etc., are recognized as shared pathophysiological occurrences linked to various neuro-disorders. Melatonin, as a chronobiotic molecule, plays a role in stabilizing body cycles and acts as a synchronizer. It is synthesized by various organs and tissues, including the pineal gland, skin, gastrointestinal tract, lymphocytes, and others, in response to darkness. Due to its widely recognized antioxidant and anti-inflammatory properties, along with its neuroprotective effects, melatonin can offer significant benefits in the treatment of neurological disorders. Melatonin and its analogues bind to the MT1 and MT2 melatonin receptors and are used to treat a variety of CNS illnesses, including insomnia, epilepsy, Alzheimer’s disease etc. In current review article, an attempt has been made to explore the potential of melatonin in various neurological conditions and authors aim to explain the mechanism of melatonin implicated in all of the aforementioned illnesses. [ABSTRACT FROM AUTHOR]

1. Six pelleted diets with different ratios of whole oats to dehulled oats, ground either finely (2 mm) or coarsely (6 mm), resulting in 0.05% (LOH), 6.5% (MOH) and 11.4% (HOH) OH inclusion, were fed to broilers to study gizzard functionality and its influence on passage of large oat hull (OH) particles. The hypothesis was that coarse OH would be selectively retained in gizzard for grinding, but higher levels would increasingly result in passage of unground OH.2. In experiment 1, gizzard and small intestinal contents were sampled from 78 birds at 28–29 d of age. Neutral detergent fibre (NDF) of gizzard contents was over three times higher than that of diets, indicating selective retention. An interaction effect of OH and screen size was seen for large particles (>1.6 mm) in the upper ileum, which was higher for MOH and HOH than LOH and only for coarse diets. This indicated that passage of unground coarse large particles from the gizzard increased when it exceeded a maximum retention level.3. In experiment 2, pre-weighed amount of HOH 2 mm and HOH 6 mm diets were fed to 80 birds for 2 h and were sampled on d 30 at 0, 2, 4, 8 and16 h to study OH degradation and flow. Contents were sampled from the crop, gizzard, small intestine, colon/cloaca and excreta. Unrecovered NDF in gastrointestinal tract plus excreta increased with more time and coarseness. An interaction effect between time and screen size was found for large particles in excreta, which was higher for 6 mm diets than 2 mm diets at 16 h.4. The presence of large OH particles in excreta challenged the previous assumption that particles are ground in the gizzard to a certain critical size before passing down further down the digestive tract. Some OH seemed to escape grinding in gizzard and this was higher for coarser particles. [ABSTRACT FROM AUTHOR]

Gemella morbillorum is a gram-positive coccus that is part of the normal microbiota of the human oral cavity and gastrointestinal tract. It is an opportunistic pathogen that can cause invasive infections, including septic arthritis. Septic arthritis caused by Gemella morbillorum is relatively rare, but when it occurs, it can lead to severe joint damage and other complications if not promptly diagnosed and treated. Here, we report a case of recurrent septic arthritis caused by Gemella morbillorum. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic gastroenteritis is a rare disease characterized by eosinophilic infiltration into one or more layers of the gastrointestinal tract. It commonly affects children more than adults. The clinical features depend on the site of gut involvement, but the most common symptoms include abdominal pain and diarrhea. The most common cause reported in the literature is hypersensitivity, as many patients have a history of seasonal allergies, atopy, asthma, food allergies, and so on. However, drugs can be a rare triggering factor. In the literature review, we found multiple case reports of eosinophilic gastroenteritis; however, only one other case of carbimazole-induced eosinophilic gastritis has been reported. Case presentation: We report herein the case of a 36-year-old female from the Philippines who developed eosinophilic gastroenteritis localized to the esophagus and ileum 12 months following treatment with carbimazole for hyperthyroidism. In our facility, she was extensively investigated for malignancy, autoimmune pathologies and infectious etiologies. As the symptoms coincided with carbimazole exposure and other causes were ruled out, we labeled her as carbimazole-induced eosinophilic gastroenteritis. On subsequent follow-up after discharge, her symptoms and eosinophilia resolved when carbimazole was discontinued, suggesting a causative role. This is the first case of eosinophilic gastroenteritis secondary to carbimazole encountered in our region. Conclusion: Diagnosis of eosinophilic gastroenteritis requires three criteria, namely (1) presence of gastrointestinal symptoms, (2) histologic evidence of eosinophilic infiltration in one or more areas of the gastrointestinal tract, and (3) exclusion of other causes of tissue eosinophilia. Our patient fulfilled all the criteria; additionally, she had a positive history of atopic tendencies and drug exposure. The diagnosis of hyperthyroidism was established a year ago and in another facility, so we were not sure of the underlying etiology of hyperthyroidism. Upon subsequent follow-up, her thyroid function remained stable. The case highlights the need for a collaborative multidisciplinary approach toward managing rare conditions. [ABSTRACT FROM AUTHOR]

There are over 1000 varieties of steroids that have been reported in nature, including the endogenous sex steroid hormones (i.e., progesterone, testosterone, and 17β‐estradiol) and corticosteroids which are mainly synthesized by gonads and adrenals, respectively. In addition, an extra‐glandular steroidogenesis has been also reported in the brain and in the gastrointestinal tract (GIT). The reason why intestinal steroidogenesis and consequently gut steroids draw our attention is for the communication and interaction with the gut microbiota, which functions like a virtual endocrine organ, and it is also involved in the steroid production. Moreover, both GIT and gut microbiota communicate through neural, endocrine, and humoral ways with the brain, in the so‐called gut‐microbiota‐brain axis. On this basis, in this review, we will discuss several aspects such as (1) intestinal steroidogenesis and its possible regulation, (2) the potential role of gut steroids in physiopathological conditions, and (3) the role of microbiome in steroidogenesis and steroid metabolism. Overall, this review highlights new points of view considering steroid molecules as potential therapeutic approach for gastrointestinal disorders and brain comorbidities. [ABSTRACT FROM AUTHOR]

The application of micro/nanomotors (MNMs) in the gastrointestinal tract has become a Frontier in the treatment of gastrointestinal diseases. These miniature robots can enter the gastrointestinal tract through oral administration, achieving precise drug delivery and therapy. They can traverse mucosal layers and tissue barriers, directly targeting tumors or other lesion sites, thereby enhancing the bioavailability and therapeutic effects of drugs. Through the application of nanotechnology, these MNMs are able to accomplish targeted medication release, regulating drug release in response to either external stimuli or the local biological milieu. This results in reduced side effects and increased therapeutic efficacy. This review summarizes the primary classifications and power sources of current MNMs, as well as their applications in the gastrointestinal tract, providing inspiration and direction for the treatment of gastrointestinal diseases with MNMs. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion Renourishment and weight restoration are critical first steps in anorexia nervosa (AN) treatment. The ability of the gastrointestinal tract to harvest and utilize energy from food is essential for successful weight restoration, but the functional capacity of the intestine after prolonged caloric restriction remains unknown. In an exploratory study, we quantified the stool energy content of individuals with AN before and after renourishment.We used archived stool samples from a multisite cohort (NCT03119272) of 103 individuals with AN at admission and discharge from inpatient renourishment and 122 sex‐matched non‐eating disorder controls (non‐ED). To determine whether bomb calorimetry may have utility in AN, we measured stool calorie loss as the number of kilocalories per gram of stool. Analyses included ANOVA, paired/unpaired t‐tests, and Spearman rank correlations for associations between stool energy and clinical variables.Following 25.10 ± 19.73 days of renourishment, patients gained an average of 5.67 ± 4.27 kg. Raw stool energy at discharge (AN‐DIS: 5.72 ± 0.86 kcal/g) was significantly higher than admission (AN‐AD: 5.41 ± 0.86 kcal/g; p < 0.01). Weight and BMI at admission and discharge were negatively correlated with raw stool energy at discharge.Energy content in stool increases after inpatient refeeding, likely due to increased calorie consumption. Findings should be interpreted cautiously due to methodological limitations in this post hoc study design. Future studies should use a priori, gold‐standard protocols to investigate stool calorie loss in AN, as prolonged restriction in AN may disrupt the gut and impede energy harvest.Trial Registration: clinicaltrials.gov: NCT03119272 [ABSTRACT FROM AUTHOR]

The D-enantiomers of L-amino acids are non-proteinogenic but widely present in foods. This is due to spontaneous racemization or processing, such as heating or alkali treatment, leading to substantial dietary exposure. Additional exposure to D-amino acids (D-AAs) comes from the human microbiota; D-AAs are present in bacterial surface proteoglycans, essential for bacterial competition and growth. Humans and other mammals have a complex set of genes for D-AA transport and degradation, and capacity to synthesize several D-AAs. Free D-AAs are present at low levels in human tissues and body fluids, yet they are apparently of considerable physiological and pathological importance. Amino acid transport regulates their presence and favors specific D-AAs, e.g. D-serine, D-aspartate, D-cysteine, and D-glutamate, over many others. Some of these D-AAs interact with the ubiquitous glutamate-gated Ca2+ channels, affecting signaling functions in most organs, especially the intestine, kidney, and brain. Consequently, the exposures, synthesis, local and systemic transport of D-AAs could be much more biologically important in humans than previously assumed, likely playing a role in gut-organ signaling and in many degenerative diseases. [ABSTRACT FROM AUTHOR]

Objective: Our previous genotyping studies suggest that some anatomical locations act as reservoirs of genotypes that may cause further candidemia, since we found identical genotypes in gastrointestinal tract or catheter tip isolates and blood cultures, in contrast, we did not find blood culture genotypes in vagina samples. We observed that some genotypes can be found in blood cultures more frequently than others, some of them being called widespread genotypes because have been found in unrelated patients admitted to different hospitals. The presence of widespread genotypes may be more frequently found because of their predisposition to cause candidemia. It is unclear whether genotypes colonizing other anatomical sites different from the gastrointestinal tract can also be detected in this way; we studied C. albicans , C. parapsilosis , and C. tropicalis colonizing genotypes to assess what proportion could be found in blood cultures and the proportion of widespread genotypes. Methods: The isolates (n= 640 Candida isolates from 323 patients) studied herein were obtained from samples processed at the Clinical Microbiology and Infectious Diseases Department of the Gregorio Marañón Hospital (Madrid, Spain) from July 1, 2016, to June 30, 2019. C. albicans (n=486), C. parapsilosis (n=94), and C. tropicalis (n=60) isolates were genotyped using species-specific microsatellite markers and sourced from blood (n=120) and colonized anatomical sites (n=520; catheter [n=50], lower respiratory tract [n=227], skin/mucosa [n=132], and urinary tract [n=111]). Isolates with identical genotypes were those presenting the same alleles for all markers or with only differences at one locus of a given marker. Identical genotypes were further classified as a match (identical genotype found in different groups of samples from a given patient) or as a cluster (identical genotype found in ≥2 patients). Finally, singletons were genotypes detected once. The genotypes found were then compared with our in-house database containing 587 blood genotypes from patients admitted to the Gregorio Marañón Hospital (2007-2023) to assess the proportion of genotypes found in colonized samples that were also found in blood cultures. Moreover, since some of our in-house database genotypes had been tagged as widespread genotypes, we compared the proportions of widespread genotypes as well as the proportions of matches, clusters, and patients involved in clusters found among exclusively colonizing genotypes, exclusively blood culture genotypes, and both colonizing and blood culture genotypes using a standard binomial method. Results: Intra-patient analysis was conducted exclusively on those patients (n=225; 69.7%) who had ≥2 isolates from a given species; the proportion of patients with matches was lower in exclusively colonized patients than in patients with candidemia and colonizing genotypes (87.3% vs. 94.1%; p = 0.126). Inter-patient analysis was conducted considering all patients (n=323) and isolates from groups 1, 2, and 3 (n=640). Overall, we detected 341 genotypes, of which 320 were singletons and 21 were clusters (6.16%). Clusters involving blood cultures and colonizing isolates sourced from catheter tips (14.6%), skin and mucosa (7.5%), urine (7.4%), and lower respiratory tract (4.6%). Cluster-involved patients had not been admitted to the same ward at the same time. Of the 290 colonizing genotypes, 91 (31.1%) were also found in blood cultures, the highest proportion being C. parapsilosis (p < 0.05); proportions of identical genotypes found in blood cultures and catheter tips were higher than those found in blood cultures and other colonized samples (79.2% vs. 26.7%; p < 0.001). Widespread genotype ratios were significantly higher among genotypes found in both blood and colonized samples than among genotypes found exclusively in either blood culture or other colonizing genotypes (31.9% vs. 7.1% vs. 3.7%, respectively; p < 0.001). Conclusion: We observed that 94% of patients with candidemia were colonized by a genotype causing the infection; likewise, a total of 31% of colonizing genotypes were detectable in blood cultures. Finally, identical genotypes found in both colonized samples and blood cultures had a higher probability of being widespread. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the FDA's Adverse Event Reporting System (FAERS) data to investigate the correlation between oral bisphosphonates (BPs) and oesophageal adverse events (AEs). Methods: We systematically extracted data on adverse reactions to oral alendronate, risedronate, and ibandronate from the FAERS database, covering the period from the 2004 Q1 to the 2023 Q4. The role_code of AEs mainly includes primary suspect (PS), secondary suspect (SS), concomitant (C), and interaction (I). This study targeted reports with a role_code of "PS." According to the FDA deduplication rule, the latest FDA_DT is selected when the CASEID is the same, and the higher PRIMARYID is selected when the CASEID and FDA_DT are the same. Our analysis leveraged four statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS), to assess the relationship between oral bisphosphonates and oesophageal AEs. The Kaplan-Meier method was utilized to evaluate the cumulative incidence of oesophageal toxicity, while the log-rank test examined the temporal onset profiles of these toxicities. Additionally, the Pearson chi-squared test was employed to identify any significant differences in mortality and hospitalization rates associated with the oesophageal AEs caused by these medications. Results: The FAERS database had 41,590 AE reports for oral BPs, with 3,497 (8.41%) related to oesophageal AEs. Our findings indicate that oral BPs are disproportionately associated with an increased incidence of gastrointestinal system AEs at the system organ class (SOC) level. The adverse events identified at the preferred terms (PTs) level encompassed conditions such as gastroesophageal reflux disease, oesophagitis, and oesophageal pain. A significant divergence in the cumulative incidence of oesophageal AEs was observed among patients treated with the three different oral bisphosphonates, as confirmed by the log-rank test (p < 0.0001). Hospitalization rates varied significantly among patients receiving different BPs (p < 0.05), but no significant difference in mortality rates was found. Conclusion: The study establishes a significant link between oral BPs and oesophageal toxicity, highlighting the need for further research into the mechanisms of BP-induced oesophageal toxicity and potential preventive measures. [ABSTRACT FROM AUTHOR]

Background: For several decades, the European wildcat (Felis silvestris) has gradually been returning to the forests of Germany, mainly in the central and southwestern regions. To increase the knowledge about this threatened species, the endoparasite status of dead found specimens from Germany was surveyed. Methods: A total of 118 wildcats were examined for endoparasites in peritoneal organs and skeletal muscles. Owing to decomposition or incomplete carcasses, 104 gastrointestinal tracts (stomachs and intestines), 101 livers with gallbladders, 99 urinary bladders, as well as kidneys of 95 and skeletal muscles of 112 specimens were available for examination. All detected parasites were identified morphologically to genus or species level, followed by molecular examinations of one to ten specimens of each parasite species. Results: Overall endoparasite prevalence in peritoneal organs was 99.0% (103/104). Among the 99.0% (103/104) infected gastrointestinal tracts, the most frequent species were Toxocara cati (95.2% [99/104]), Hydatigera kamiyai (84.6% [88/104]), Mesocestoides litteratus (69.2% [72/104]), Strongyloides spp. (58.7% [61/104]), Cylicospirura petrowi (37.5% [39/104]), Ancylostoma tubaeforme (31.7% [33/104]), Capillaria putorii (24.0% [25/104]), and Echinococcus multilocularis (18.3% [19/104]). In 77.8% (77/99) of the urinary bladders, Capillaria plica and/or Capillaria feliscati were detected. Moreover, the liver fluke Metorchis bilis occurred in 2.0% (2/101) of the livers, and roundworm larvae (presumably Toxocara spp.) were detected in 33.0% (37/112) of the muscle samples. Conclusions: These results show a broad spectrum of endoparasite species infecting European wildcats in Germany. It might be assumed that some of the endoparasites could pose a risk to domestic cats (Felis catus) and humans through spillover events, or may be transmitted from domestic cats to the free-ranging population, posing a potential risk to wildcats. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CD) is an autoimmune disorder characterized by gluten intolerance, primarily affecting the gastrointestinal system but potentially influencing cardiovascular health. Emerging evidence suggests an association between CD and myocardial infarction (MI), though studies have produced inconsistent results. This study aimed to systematically review and conduct a meta-analysis of existing literature to quantify the risk of MI in individuals diagnosed with CD. Methods: A comprehensive literature search was performed across PubMed, Embase, and Web of Science up to August 2024. Studies were included if they investigated the association between CD and MI in adult populations and provided relevant effect estimates. Data from eligible studies were extracted, and a random-effects meta-analysis was conducted to calculate pooled hazard ratios (HRs) and odds ratios (ORs), along with an assessment of heterogeneity. Statistical analysis has been performed by R software (V 4.4). Results: A total of 8 studies were included in the systematic review. Pooled HR analysis showed no significant association between CD and MI (HR = 1.143, 95% CI: 0.619–2.109), and pooled OR analysis also revealed non-significant results (OR = 0.879, 95% CI: 0.481–1.606). High heterogeneity was observed (I2 = 86% for HR, 99% for OR). Conclusion: This meta-analysis found no significant association between CD and MI. However, substantial heterogeneity across studies indicates variability in results, highlighting the need for further research with larger, more homogeneous cohorts to better understand cardiovascular risks in CD patients. Future studies should explore subgroups and the impact of gluten-free diet adherence. [ABSTRACT FROM AUTHOR]

The aim of this study was to quantitatively analyse lactobionic acid obtained from bioreactor cultures using whey as a liquid medium with bacteria of the Pseudomonas taetrolens species. The most important culture parameters affecting the production of the acid are indicated and evaluated. The highest lactobionic acid yield was 37.42 g/L, selecting the appropriate strain (Pseudomonas taetrolens 4′) and environmental conditions (2% lactose concentration in the bioreactor). The amount of lactose and lactobionic acid was determined by high-performance liquid chromatography. Microorganism analysis was also carried out using a flow cytometer with imaging to study the metabolic activity of microorganisms during lactobionic acid production. In addition, during the study, Bifidobacteria were microencapsulated with lactobionic acid and their survival was evaluated in an in vitro model of the gastrointestinal tract, checking the prebiotic properties of the acid. The highest number of viable cells in the microcapsules after digestion was obtained using the Bifidobacterium bifidum strain DSM 20082. The antagonistic activity of lactobionic acid was also analysed. [ABSTRACT FROM AUTHOR]

Simple Summary: Gut microbiota significantly influences dogs' well-being, and several researchers have made strides in characterizing canine gut microbiota composition. Recent research has revealed that the canine gut microbiota is highly impacted by the type of diet. Prebiotics (non-digestible oligosaccharides able to promote the growth of beneficial bacteria) and probiotics (live microorganisms that confer a health benefit by enhancing microbial diversity) can modulate the gut microbiota and promote gastrointestinal health. A growing interest has recently been in combining prebiotics and probiotics (synbiotics) to achieve synergistic effects. The present study aimed to investigate the effects of supplementation with a prebiotic (Microbiotal) and a probiotic (L. reuteri) using the fecal microbiota of a healthy canine donor. The investigators used a novel in vitro fermentation platform (SCIME™), which closely mimics the canine gastrointestinal tract, allowing long-term experiments. This study demonstrates the promising modulatory effects of prebiotics and probiotics, especially when combined. The gut microbiota plays a crucial role in dogs' health, influencing immune function, digestion, and protection against pathogens. This study evaluates the effects of three canine dietary supplements—Microbiotal (prebiotic), Lactobacillus reuteri (probiotic), and a combination of both—on the gut microbiota composition of a healthy canine donor using an in vitro colonic fermentation model. The SCIME™ platform, adapted to simulate the canine gastrointestinal tract, was used to monitor microbial shifts in the luminal and mucosal environments of the proximal and distal colon over a 2-week treatment period. The microbial communities were analyzed using 16S rRNA sequencing to assess changes at various taxonomic levels. Alpha- and beta-diversity indices were calculated, while LEfSe and treeclimbR were employed to identify taxa-driving microbial shifts. Results indicated that all treatments led to significant modulations in key microbial groups, with enrichment of Limosilactobacillus, Bifidobacterium, Prevotella, and Faecalibacterium. These changes suggest improved saccharolytic fermentation and butyrate production, particularly when prebiotics and probiotics were co-administered. This study highlights the promising benefits of combined prebiotic and probiotic supplementation in promoting gut health and microbial diversity, providing a basis for future studies targeting the metabolic activity of the gut microbiota using the same supplements and technology. [ABSTRACT FROM AUTHOR]

Simple Summary: Intestinal health is crucial for safeguarding overall well-being. 1-Deoxynojirimycin (DNJ) from mulberry leaves can reduce oxidative stress and inflammatory responses, ensuring intestinal health. This study evaluated the effects of DNJ extract of mulberry leaves (DNJ-E) as an antioxidant on intestine function in broilers under oxidative stress. The addition of DNJ-E led to improvements in the morphology and ultrastructure of the intestine, as evidenced by increased villus height, an enhanced villus-to-crypt ratio, and strengthened tight junctions. Treatment with 40 mg/kg DNJ-E resulted in elevated levels of SOD and CAT in the jejunum, along with an upregulation of MUC mRNA expression. These findings suggest that DNJ-E plays a significant role in enhancing intestinal barrier function by increasing the activity of antioxidant enzymes, thereby contributing to the protection of intestinal health in broilers. The poultry industry struggles with oxidative stress affecting gut health and productivity. This study examined using 1-Deoxynojirimycin (DNJ) extracts from mulberry leaves as an antioxidant in broilers feed to combat this issue. We divided 240 broilers, aged 16 days, into six groups, including a control and groups exposed to oxidative stress through H2O2 injections, with different supplement levels of DNJ-E (40, 80, 120, and 160 mg/kg of the basal diet) lasting until the broilers reached 42 days old. We evaluated intestinal morphology, ultrastructure, oxidative stress markers, the tight junction, and inflammatory cytokines. Adding 40 mg/kg DNJ-E improved villus height, the villus-to-crypt ratio, and cellular ultrastructure, and increased SOD levels in the jejunum and ileum, as well as CAT levels in the duodenum and jejunum (p < 0.05), compared to the H2O2 group. The addition of DNJ had differential effects on oxidative stress, the intestinal barrier, and immune-related genes. Importantly, the dosages of 40 mg/kg and 80 mg/kg resulted in an upregulation of MUC2 mRNA expression (p < 0.05). These findings suggest that DNJ-E holds potential as a beneficial feed additive for enhancing broiler health, particularly at supplementation levels below 80 mg/kg, as higher concentrations may negatively influence intestinal health. Future investigations should aim to elucidate the underlying mechanisms through which DNJ-E operates within the avian gastrointestinal system. [ABSTRACT FROM AUTHOR]

A total of 16 organic sunscreens and over 160 products of their degradation in biotic and abiotic conditions were investigated in the context of their safety during pregnancy. Drug-likeness and the ability of the studied compounds to be absorbed from the gastrointestinal tract and cross the human placenta were predicted in silico using the SwissADME software (for drug-likeness and oral absorption) and multiple linear regression and "ARKA" models (for placenta permeability expressed as fetus-to-mother blood concentration in the state of equilibrium), with the latter outperforming the MLR models. It was established that most of the studied compounds can be absorbed from the gastrointestinal tract. The drug-likeness of the studied compounds (expressed as a binary descriptor, Lipinski) is closely related to their ability to cross the placenta (most likely by a passive diffusion mechanism). The organic sunscreens and their degradation products are likely to cross the placenta, except for very bulky and highly lipophilic 1,3,5-triazine derivatives; an avobenzone degradation product, 1,2-bis(4-tert-butylphenyl)ethane-1,2-dione; diethylamino hydroxybenzoyl hexyl benzoate; and dimerization products of sunscreens from the 4-methoxycinnamate group. [ABSTRACT FROM AUTHOR]

Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance. [ABSTRACT FROM AUTHOR]