Intestinal Mucosa Research Articles

The Importance of Intestinal Microbiota and Dysbiosis in the Context of the Development of Intestinal Lymphoma in Dogs and Cats.

Recent advancements have significantly enhanced our understanding of the crucial role animal microbiomes play in veterinary medicine. Their importance in the complex intestinal environment spans immune modulation, metabolic homeostasis, and the pathogenesis of chronic diseases. Dysbiosis, a microbial imbalance, can lead to a range of diseases affecting both individual organs and the entire organism. Microbial disruption triggers inflammatory responses in the intestinal mucosa and disturbs immune homeostasis, increasing susceptibility to toxins and their metabolites. These dynamics contribute to the development of intestinal lymphoma, necessitating rigorous investigation into the role of microbiota in tumorigenesis. The principles explored in this study extend beyond veterinary medicine to encompass broader human health concerns. There are remarkable parallels between the subtypes of lymphoproliferative disorders in animals and humans, particularly Hodgkin's lymphoma and non-Hodgkin's lymphoma. Understanding the etiology of a cancer of the lymphatic system formation is critical for developing both preventive strategies and therapeutic interventions, with the potential to significantly improve patient outcomes. The aim of this study is to discuss the optimal composition of the microbiome in dogs and cats and the potential alterations in the microbiota during the development of intestinal lesions, particularly intestinal lymphoma. Molecular and cellular analyses are also incorporated to detect inflammatory changes and carcinogenesis. A review of the literature on the connections between the gut microbiome and the development of lymphomas in dogs and cats is presented, along with potential diagnostic approaches for these cancers.

Morphological aspects of small intestinal mucosal injury and repair after electron irradiation.

Morphological evaluation of the small intestine mucosa and apoptosis activity (caspase-3) is necessary to assess the severity of damage to the small intestine. At the same time, proliferative index based on Ki-67 can be used to assess the regenerative potential of the small intestine. Fragments of small intestine of Wistar rats (n=60) of three groups: I) control (n=20); II) experimental group (n=20; local single electron irradiation at a dose of 2 Gy), III) experimental group (n=20; local single electron irradiation at a dose of 8 Gy) were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and caspase-3. In all samples of the experimental groups, a decrease in all morphometric indices was observed on day 1 with a tendency to recover on day 3. Small intestinal electron irradiation led to disturbances in the histoarchitecture of varying severity, and an increase in cell apoptosis was observed (increased expression of caspase-3 and decrease in Ki-67). In addition, modulation of the PI3K/AKT and MAPK/ERK signaling pathways was detected. The most pronounced destructive changes were observed in the group of 8 Gy single electron irradiation. Local irradiation of the small intestine with electrons at a dose of 2 and 8 Gy results in a decrease in the number of enterocytes, mainly stem cells of the intestinal crypts.

Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum.

Bile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate invivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were quantified by isometric force transduction. Ursodeoxycholic acid robustly increased contractile responses in a dose-dependent manner. Deoxycholic acid stimulated contractility at low doses but inhibited contractility at high doses. Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not alter contractility. The dose-dependent increase in contractility resulting from the application of ursodeoxycholic acid was recapitulated by INT-777, an agonist of the Takeda G protein-coupled receptor 5 (TGR5), and by cevimeline, a muscarinic acetylcholine receptor agonist. Agonists to the nuclear receptors farnesoid X receptor, glucocorticoid receptor, pregnane X receptor, vitamin D receptor, and to the plasma membrane epidermal growth factor receptor did not modify baseline contractile patterns. These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low-dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.

The Mucus-Binding Factor Mediates Lacticaseibacillus rhamnosus CRL1505 Adhesion but Not Immunomodulation in the Respiratory Tract.

Lacticaseibacillus rhamnosus CRL1505 possesses immunomodulatory activities in the gastrointestinal and respiratory tracts when administered orally. Its adhesion to the intestinal mucosa does not condition its beneficial effects. The intranasal administration of L. rhamnosus CRL1505 is more effective than the oral route at modulating immunity in the respiratory tract. Nonetheless, it has not yet been established whether the adherence of the CRL1505 strain to the respiratory mucosa is needed to provide the immune benefits to the host. In this study, we evaluated the role of adhesion to the respiratory mucosa of the mucus-binding factor (mbf) knock-out L. rhamnosus CRL1505 mutant (Δmbf CRL1505) in the context of a Toll-like receptor 3 (TLR3)-triggered innate immunity response. In vitro adhesion studies in porcine bronchial epitheliocytes (PBE cells) indicated that L. rhamnosus Δmbf CRL1505 adhered weakly compared to the wild-type strain. However, in vivo studies in mice demonstrated that the Δmbf CRL1505 also reduced lung damage and modulated cytokine production in the respiratory tract after the activation of TLR3 to a similar extent as the wild-type strain. In addition, the mutant and the wild-type strains modulated the production of cytokines and antiviral factors by alveolar macrophages in the same way. These results suggest that the Mbf protein is partially involved in the ability of L. rhamnosus CRL1505 to adhere to the respiratory epithelium, but the protein is not necessary for the CRL1505 strain to exert its immunomodulatory beneficial effects. These findings are a step forward in the understanding of molecular interactions that mediate the beneficial effects of nasally administered probiotics.

The gut-liver axis: ways of maintaining the body’s homeostasis. Historical aspects and the current state of the problem. Literature review

There are close evolutionary anatomical and functional connections between the intestine and the liver. Whereas the peculiarities of functioning of these organs as components of the digestive system have long been the object of scientific research, their role in maintaining the body’s homeostasis has been studied relatively recently. This especially applies to the immune aspects of the interaction of these organs. The intestinal mucosa performs not only the function of a mechanical barrier, but also provides an immune response to pathogens while maintaining tolerance to one’s own flora, which together prevents the translocation of antigens into the internal environment of the body. In this aspect, the intestinal microbiocenosis is of particular interest, as it plays an important role in maintaining the integrity of the intestinal barrier and reducing bacterial translocation, forming and modulating the activity of the local immune system, and has a regulatory effect on the body’s metabolic processes. A decrease in the barrier function of the intestines leads to the contact of translocated antigens of bacterial origin and other xenobiotics with the structures of adaptive immunity, and through the portal blood flow with the lymphoid structures of the liver, triggers a cascade of inflammatory reactions, and as a result, to the development of pathological processes in the hepatobiliary zone and metabolic disorders. Understanding these processes contributes to the emergence of promising directions in the prevention and treatment of a wide range of pathological conditions, for example, violations of food tolerance, some allergic diseases. The review summarizes historical aspects and modern views on the role of the «intestine‑liver» axis in ensuring the metabolic and immune homeostasis of the body, as well as data on pathological conditions that develop when this axis is disturbed.

Critical study of Kala Shareera w.s.r. to Pittadhara Kala with its Modern Anatomy

In various classical texts of Ayurveda, Kala is described as an anatomical structure, which separates the Dhatu and Aashaya i.e., it provides boundary between Dhatu and Aashaya. Also called as Dhatwashayantaramaryada. As per Acharya Sushruta, the numbers of Kala are Seven. Acharya Sushruta said as the core of a piece of wood become exposed to view by cutting into it, so the Dhatus of the body may be seen by removing the successive layers. These Kala are extensively supplied with Snayus, bathed in mucus and encased in membranous covering. By sequential order, Pittadhara Kala is the sixth Kala mentioned by Acharya Sushruta. According to modern anatomy the mucus membrane presents many villi, the intestinal villi are finger like projection of mucous membrane. They give the surface of the intestinal mucosa a velvety appearance. Each villus is covered by a layer of absorptive columnar cells. This article lays emphasis on the types of Kala according to Ayurvedic perspective w.s.r. to Pittadhara Kala and its correlation with modern anatomy. This article describes the various aspects of Kala mainly Pittadhara Kala in all respects to types, structure etc. Since description of Kala and its types is present in both the sciences, so an attempt is made in this article to correlate and compare Kala with Membrane.

Intestinal perforation due to a ventriculoperitoneal shunting catheter

Introduction: The ventriculoperitoneal (VP) shunt allows the drainage of excess cerebrospinal fluid; among its gastrointestinal complications are intestinal volvulus, pseudocyst, and perforation, the last of which is rare but potentially serious, with a frequency between 0.1% and 0.7% and a mortality rate around 15%. We present the case of a male child who required VP shunt colocation and suffered GI tract perforation with transanal protrusion. Case report: A three-year-old male with a long clinical history of pilocytic astrocytoma in the posterior fossa that was partially resected in February 2022 and with VP shunt placement since March 2022. He was diagnosed with an intestinal perforation and anal externalization due to a VP shunt. He required surgery and management with combined antimicrobials. Discussion: Although the aetiology of GI tract perforation due to a VP shunt is not fully established, some risk factors have been described, including the use of abdominal trocars, rigid distal catheters, silicone allergies, and children's thin intestine walls. Treatment must be individualized, with some principles including external drainage of the proximal part until the CSF fluid reaches a biochemically near-normal state and becomes sterile on culture; secondly, the administration of intravenous antibiotics; and finally, the removal of the perforating section of the catheter. Conclusions: Bowel perforation due to a VP shunt is an extremely rare entity whose aetiology is not fully established, primarily affects children and may be mostly related to chronic-irritative gastrointestinal distress. Individualizing treatment is the cornerstone of the therapeutic approach that includes VP shunt replacement, antimicrobial therapy, and management of life-threatening complications.

The role of inflammatory biomarkers in patients with ulcerative colitis and concomitant arterial hypertension, possibilities of treatment

Objective — to evaluate and compare inflammatory biomarkers (faecal calprotectin, serum zonulin) in patients with ulcerative colitis (UC) and concomitant arterial hypertension (AH) before and after use of the mesalazine medication (Pentasa, Ferring International Center, Switzerland). Materials and methods. The study involved 96 patients with UC aged 18 to 60 years. Patients underwent outpatient blood pressure measurement to assess the presence of arterial hypertension (AH). As a result, patients were allocated into two groups: group I consisted of patients with UC and concomitant AH (n=49; mean age 41.2±12.31 years, median age 38 years) and group II included patients with UC without concomitant AH (n=47; mean age 40.2±10.82 years, median age 41 years). All patients underwent physical examination. The diagnosis of UC was confirmed histologically with a preliminary colonoscopy. Endoscopic assessment of UC severity was performed according to the Mayo ulcerative colitis system. Clinically and endoscopically, patients were classified as having mild to moderate UC activity. The assessment of changes in inflammatory biomarkers (faecal calprotectin, serum zonulin levels) was performed in the groups both before treatment and after 6 weeks of mesalazine administration at a dose of 5.0 g/daily (4.0 g per os and 1.0 g per rectum). Faecal calprotectin levels were determined by enzyme‑linked immunosorbent assay (Bühlmann fCAL Elisa). Serum zonulin levels were determined by Elisa, IDK Zonulin Elisa (Immunodiagnostic AG, Germany). Statistical processing of the data was performed using licensed statistical packages «Statistica 10». Results. The average level of faecal calprotectin in group I was (367.05±148.23) mg/g, in group II - 319.57±146.65 mg/g. The difference of faecal calprotectin levels in groups I and II before and after treatment wasn’t significant (p=0.124 and р=0.263, respectively). The mean serum zonulin level in group I was 75.09±15.94 ng/ml, and in group II - 65.98±11.40 ng/ml. Serum zonulin levels after the treatment in group I were better than in group II, p=0.041. Serum zonulin is highly sensitive for assessing intestinal permeability in patients with UC and concomitant arterial hypertension. Conclusions. The use of the Pentasa medication by patients with UC proved to be effective owing to its active anti‑inflammatory effects on pathologically altered areas of the intestinal wall. Assessment of inflammation biomarkers, such as faecal calprotectin and serum zonulin, is safe, affordable, non‑invasive methods that can be used to monitor treatment of patients with UC and concomitant arterial hypertension. Pentasa can be used in patients both with isolated ulcerative colitis and in combination with hypertension

Interaction between inflammatory bowel disease, physical activity, and myokines: Assessment of serum irisin levels.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel’s appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

How the Microbiota May Affect Celiac Disease and What We Can Do.

Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD is a unique autoimmune condition, as it is the only one in which the environmental trigger is known: gluten, a storage protein present in wheat, barley, and rye. How and when the loss of tolerance of the intestinal mucosa to gluten occurs is still unknown. This event, through the activation of adaptive immune responses, enhances epithelial cell death, increases the permeability of the epithelial barrier, and induces secretion of pro-inflammatory cytokines, resulting in the transition from genetic predisposition to the actual onset of the disease. While the role of gastrointestinal infections as a possible trigger has been considered on the basis of a possible mechanism of antigen mimicry, a more likely alternative mechanism appears to involve a complex disruption of the gastrointestinal microbiota ecosystem triggered by infections, rather than the specific effect of a single pathogen on intestinal mucosal homeostasis. Several lines of evidence show the existence of intestinal dysbiosis that precedes the onset of CeD in genetically at-risk subjects, characterized by the loss of protective bacterial elements that both epigenetically and functionally can influence the response of the intestinal epithelium leading to the loss of gluten tolerance. We have conducted a literature review in order to summarize the current knowledge about the complex and in part still unraveled dysbiosis that precedes and accompanies CeD and present some exciting new data on how this dysbiosis might be prevented and/or counteracted. The literature search was conducted on PubMed.gov in the time frame 2010 to March 2024 utilizing the terms "celiac disease and microbiota", "celiac disease and microbiome", and "celiac disease and probiotics" and restricting the search to the following article types: Clinical Trials, Meta-Analysis, Review, and Systematic Review. A total of 364 papers were identified and reviewed. The main conclusions of this review can be outlined as follows: (1) quantitative and qualitative changes in gut microbiota have been clearly documented in CeD patients; (2) intestinal microbiota's extensive and variable interactions with enterocytes, viral and bacterial pathogens and even gluten combine to impact the inflammatory immune response to gluten and the loss of gluten tolerance, ultimately affecting the pathogenesis, progression, and clinical expression of CeD; (3) gluten-free diet fails to restore the eubiosis of the digestive tract in CeD patients, and also negatively affects microbial homeostasis; (4) new tools allowing targeted microbiota therapy, such as the use of probiotics (a good example being precision probiotics like the novel strain of B. vulgatus (20220303-A2) begin to show exciting potential applications.

MENIAR EXTRACT NANO CONCENTRATE AND MILK PROCESSING TRAINING TO BOOST KELOMPOK PERAH JAYA JOMBANG'S INCOME

Segunung is one of the six Dusun in Carangwulung, Wonosalam, Jombang, East Java where Sapi Perah Jaya and Wanita Tani Perah Jaya groups manage to breed 210 dairy cows. The milk produced is deposited to KUD Anjasmoro before being transferred to the milk processing industry and some is processed by Wanita Tani Perah Jaya into pasteurized milk. The problems faced by dairy farmers, especially after the Foot and Mouth Disease (FMD) outbreak, are the decreasing milk and feed production, and livestock health. The problem faced by Wanita Tani Perah Jaya is a lack of knowledge about dairy product verification and marketing. To solve this problem the researchers administer nano meniran extract containing bioactive compounds such as flavonoids and Saponin flavonoids, as an immunomodulator, stimulate and improve the immune system and the impaired immune function, while Saponins increase the diameter of the villi and the permeability of intestinal cell walls, thereby affecting the absorption of nutrients carried by feed. If the immunity increases and the absorption of feed nutrients is good, it will increase milk production in dairy cows. Through this community service activity, there will be increased empowerment of partners of the Sapi Perah Jaya Group with training in making concentrate with meniran nano extract as well as milk processing at the Wanita Tani Perah Jaya. The solution is to diversify milk in the form of yogurt. This activity was carried out using three methods: 1) Counseling on making beef concentrate with the addition of nano meniran extract, making yogurt and marketing dairy products, 2) Training on making the concentrate and making yogurt 3) Monitoring and evaluation that was carried out every month for 3 months after the counseling and training were carried out. The results obtained from this community service are the increased empowerment of partners and the increased skills of farmers in making concentrates and dairy products in the form of yogurt and marketing them. The successful application of technology through community service can increase the income and welfare of these two groups.

Bioengineered human colon organoids with in vivo-like cellular complexity and function

Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease invitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling invivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called "mini-colons." By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated invivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.

Clinical and diagnostic value of transrectal ultrasound in assessing the severity of ulcerative colitis

Background. Endoscopic and histological studies play a decisive role in the diagnosis of inflammatory bowel diseases, as they allow confirming the diagnosis, determining the degree of inflammatory activity, the extent of intestinal damage, and monitoring the course of disease and the effectiveness of therapy. Howe­ver, it is not possible to assess the state of all intestinal layers with colonoscopy. Modern non-invasive methods such as ultrasound, computed tomography, and magnetic resonance imaging cope best with this purpose. With their help, you can assess the state of the intestinal wall and obtain a cross-sectional image of the intestine, evaluate extraintestinal structures (lymph nodes, vessels, fatty tissue). It can be said that endoscopy and ultrasound search for the same type of information but look at different things. Deepening the knowledge about the role of ultrasound of the distal parts of the colon in ulcerative colitis (UC) will contribute to the improvement of diagnosis, development of methods for determining the activity of UC, control of therapy, which will allow optimizing the choice of adequate treatment measures. The goal of the work: to improve the diagnosis of ulcerative colitis based on the study of ultrasonographic parameters of the rectum. Materials and methods. Transrectal ultrasound was performed on an expert-class SonoScape S60 ultrasound scanner using a low-frequency convex probe of 3.5 MHz and a rectovaginal convex probe of 6 MHz. Transperineal and transrectal approaches were used. Results. Wall thickness and submucosal thickness differed significantly in moderate and severe UC. Analysis of transrectal ultrasound indicators depending on the endoscopic activity of the UC revealed no significant differences in the rectal wall thickness. But there was a tendency to increase in the thickness of the mucous layer and the coefficient of deformation with increasing endoscopic activity. Most patients had an increase in the degree of blood flow density, which depended on the disease severity. During the regression analysis, a relationship was found between the intestinal wall thickness (r = 0.44; p = 0.0121) and submucosal layer thickness (r = 0.86; p = 0.006) with the Mayo index. A correlation was revealed between the thickness of the colon wall and the frequency of bowel movements (r = 0.37; p = 0.018), leukocytosis (r = 0.38; p = 0.016) and erythrocyte sedimentation rate (r = 0.35; p = 0.027). The blood flow density in the intestinal wall positively correlated with the presence of edema (r = 0.32; р = 0.045), the severity of the vascular pattern (r = 0.42; р = 0.008), the presence of erosions (r = 0.4; р = 0.011) and bleeding of the mucous membrane (r = 0.50; p = 0.001). The coefficient of deformation positively correlated with the presence of flatulence (r = 0.35; р = 0.048). Conclusions. Endoscopic exa­mination in patients with UC should be supplemented with transrectal ultrasound. A correlation was found between the intestinal wall thickness and the thickness of the submucosal layer in patients with UC and the Mayo index. A tendency to increase in the thickness of the mucous layer and the coefficient of deformation with increasing endoscopic activity was determined. Relationships between endoscopic and ultrasound parameters can be used to assess disease activity.

Immunohistochemistry study of PHOX2B expression in Hirschsprung's disease allied disorders

ObjectiveThis study aimed to investigate the significance of PHOX2B expression in Hirschsprung's disease allied disorders (HAD). MethodsEight specimens of HAD were surgically resected and collected at Beijing Children's Hospital Affiliated to Capital Medical University Heilongjiang Hospital in recent years. Additionally, three specimens from patients with immature ganglion development in the intestinal wall and six control specimens from normal colons were also collected. PHOX2B, S-100, and CR antibodies were used for immunohistochemical staining to observe their expression at the mucosal, submucosal, and intrinsic muscular layer ganglia. ResultsIn the control group,the nuclei of the submucosal and myenteric ganglion cells showed strong or weak PHOX2B staining pattern,the mature ganglion cells showed weak PHOX2B staining,and the immature ganglion cells showed strong staining;S-100 only stained nerve fibers but not ganglion cells; CR stained nerve fibers in the mucosal layer and submucosal layer and also stained ganglion cells. These three antibodies showed different expression patterns in poorly developed enteric ganglia and immature enteric ganglion cells. ConclusionPHOX2B is only expressed in the nucleus of ganglion cells, has discriminatory significance in identifying mature and immature ganglion cells, and is an essential marker for diagnosing HAD.

Network Pharmacology and Bioinformatics Analysis identify potential therapeutic effects of Berberine on Colon Cancer complicated with Radiation Enteritis

Background: Patients with colon adenocarcinoma (COAD) who undergo radiation therapy develop radiation enteritis (RE). The predictive value of RE in COAD is yet to be established. Berberine, an active compound derived from the traditional Chinese medicinal plant, Coptis chinensis, has notable anti-inflammatory properties and offers protection to the intestinal mucosa. This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE (COAD&RE). Methods: Relevant genetic features of diverse COAD&RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model. The therapeutic targets of berberine were predicted using network pharmacology and molecular docking. In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking. Results: RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&RE. In addition, we identified five core therapeutic targets of berberine by network pharmacology and molecular docking: CCND1, MYC, AR, LEP, and CYP19A1. In vivo experiments showed that berberine increased short-term survival rate, body weight, and intestinal epithelial cell recovery in mice after radiation. In an in vitro study, berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation, and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects. Conclusions: This study predicted the potential therapeutic effects of berberine on COAD&RE and verified the relevant mechanisms, which may provide insights and suggestions for the clinical treatment of COAD&RE.

Gaps in our understanding of how vagal afferents to the small intestinal mucosa detect luminal stimuli.

Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection.

Chronic constipation: current options of pathogenetic therapy

Symptoms of constipation such as derangements of the motor, secretory and/or evacuation functions of the colon are recorded occasionally or for a long period in at least 20% of the population in economically developed countries. QoL is significantly impaired in patients with chronic constipation. The frequency, time of bowel movement and stool consistency is, in large part, determined by the motor function of the colon. The primary approach to the treatment algorithm for chronic constipation (CC) is modification of a lifestyle and a diet rich in dietary fiber. If dietary measures provide poor efficacy, laxatives are prescribed to the patients. According to the current guidelines, therapeutic approaches to the treatment of CC should include the sequential administration of laxatives that increase the volume of contents and stimulate the motor function of the colon. According to the Russian Gastroenterological Association guidelines for the diagnosis and treatment of chronic diseases in adult patients, it is reasonable to use stimulant laxatives as second-line drugs. Contact laxatives, which increase intestinal peristalsis due to stimulation of nerve endings in the intestinal mucosa, have been shown to be more effective in treating chronic constipation than placebo. Among the drugs in this group, Bisacodyl®, a diphenylmethane derivative, and Regulax® Picosulfate, a sodium picosulfate derivative, are the most studied ones. These substances are hydrolyzed into bis-(p-hydroxyphenyl)-pyridyl-2-methane in the intestine, which, on contact with the receptors in colonic mucosa, stimulates propulsive activity and increases intestinal secretions. Regulax® Picosulfate is effective and safe in patients with acute and chronic constipation of various origin.

In vitro evaluation of algae and their effect as dietary ingredient on growth, chemical composition and intestinal functionality in juvenile turbot (Scophthalmus maximus)

The objectives of this study were to evaluate the in vitro protein hydrolysis of five algae (Arthrospira sp., Chlorella sp., Tisochrysis sp., Microchloropsis sp. and Ulva rigida) by the digestive proteases of Scophthalmus maximus, and to assess the effect of feeding turbot juveniles on diets supplemented with these algae in a 60-day feeding trial. The in vitro results revealed that algal protein was hydrolysed by turbot digestive proteases. Besides, the quantification of total amino acids released during the in vitro hydrolysis evidenced noticeable amino acid bioavailability, mainly in the case of Arthrospira sp. with up to 42.7% of the amino acids released after 120 min of in vitro hydrolysis. However, the structural characteristics of cell wall of each species influenced the protein accessibility as evidenced by the lower values obtained in Microchloropsis sp. For the in vivo feeding trial, 255 specimens of turbot, with an average initial weight of 26.4 ± 7.6 g, were used, and were fed with diets including 5% and 10% of a blend of the same microalgae tested in vitro (M5 and M10) or U. rigida (U5 and U10), compared to a control feed without algal biomass (CT). At the end of the feeding trial, growth performance and nutrient utilization did not show differences among the experimental groups. In addition, the fish fed with the diets supplemented with algae showed lower lipid oxidation in the muscle, and an improvement in digestive functionality, as the activity of pancreatic and intestinal enzymes increased. The ultrastructural study of the intestinal mucosa revealed an increase in the length of the microvilli and the absorptive surface in fish fed with the algae-supplemented diets, as well as decreased thickness of the lamina propria and the number of goblet cells. These results confirmed that the supplementation of turbot juvenile diets with low percentage of microalgae or U. rigida is appropriate for improving digestive functionality, as well as reducing the oxidation of lipids in the muscle.

The toxic effects of tetracycline exposure on the physiological homeostasis of the gut-liver axis in grouper

Antibiotic residues, such as tetracycline (TET), in aquatic environments have become a global concern. The liver and gut are important for immunity and metabolism in aquatic organisms. In this study, juvenile groupers were subjected to 1 and 100 μg/L TET for 14 days, and the physiological changes of these fish were evaluated from the perspective of gut-liver axis. After TET exposure, the liver showed histopathology, lipid accumulation, and the elevated ALT activity. An oxidative stress response was induced in the liver and the metabolic pattern was disturbed, especially pyrimidine metabolism. Further, intestinal health was also affected, including the damaged intestinal mucosa, the decreased mRNA expression levels of tight junction proteins (ZO-1, Occludin, and Claudin-3), along with the increased gene expression levels of inflammation (IL-1β, IL-8, TNF-α) and apoptosis (Casp-3 and p53). The diversity of intestinal microbes increased and the community composition was altered, and several beneficial bacteria (Lactobacillus, Bacteroidales S24-7 group, and Romboutsia) and harmful (Aeromonas, Flavobacterium, and Nautella) exhibited notable correlations with hepatic physiological indicators and metabolites. These results suggested that TET exposure can adversely affect the physiological homeostasis of groupers through the gut-liver axis.