Small Intestinal Mucosa Research Articles

Vibrio cholerae CsrA controls ToxR levels by increasing the stability and translation of toxR mRNA

ABSTRACT Intestinal colonization and virulence factor production in response to environmental cues is mediated through several regulatory factors in Vibrio cholerae , including the highly conserved RNA-binding global regulatory protein CsrA. We have shown previously that CsrA increases synthesis of the virulence-associated transcription factor ToxR in response to specific amino acids (NRES) and is required for the virulence of V. cholerae in the infant mouse model of cholera. In this study, we mapped the 5′ untranslated region (5′ UTR) of toxR and showed that CsrA can bind directly to an RNA sequence encompassing the 5′ UTR, indicating that the regulation of ToxR levels by CsrA is direct. Consistent with this observation, the 5′ UTR of toxR contains multiple putative CsrA binding sequences (GGA motifs), and mutating these motifs disrupted the CsrA-mediated increase in ToxR. Optimal binding of CsrA to a defined RNA oligonucleotide required the bridging of two GGA motifs within a single RNA strand. To determine the mechanism of regulation by CsrA, we assayed toxR transcript levels, stability, and efficiency of translation. Both the amount of toxR mRNA in NRES and the stability of the toxR transcript were increased by CsrA. Using an in vitro translation assay, we further showed that synthesis of ToxR was greatly enhanced in the presence of purified CsrA, suggesting a direct role for CsrA in the translation of toxR mRNA. We propose a model in which CsrA binding to the 5′ UTR of the toxR transcript promotes ribosomal access while precluding interactions with RNA-degrading enzymes. IMPORTANCE Vibrio cholerae is uniquely adapted to marine environments as well as the human intestinal tract. Global regulators, such as CsrA, which help translate environmental cues into an appropriate cellular response, are critical for switching between these distinct environments. Understanding the pathways involved in relaying environmental signals is essential for understanding both the environmental persistence and the intestinal pathogenesis of this devastating human pathogen. In this study, we demonstrate that CsrA directly regulates the synthesis of ToxR, a key virulence factor of V. cholerae . Under conditions favoring high levels of active CsrA in the cell, such as in the presence of particular amino acids, CsrA increases ToxR protein levels by binding to the toxR transcript and enhancing both its stability and translation. By responding to nutrient availability, CsrA is perfectly poised to activate the virulence gene regulatory cascade at the preferred site of colonization in the human host, the nutrient-rich small intestinal mucosa.

Adaptation of the small intestine mucosa after gastric bypass surgery with a single anastomosis

Objective. To compare the morphological and morphometric changes of the small intestine mucosa in its common and biliopancreatic loops at different times after gastric bypass surgery with a single anastomosis. Materials and methods. The study included 36 patients who received surgical treatment at the Department of Thoracoabdominal Surgery of the Shalimov National Research Center for Surgery and Transplantation of the National Academy of Medical Sciences of Ukraine for morbid obesity, which consisted of gastric bypass surgery with a single anastomosis in various variants (long–loop, distal, mini–gastric bypass) in the period from 2016 to 2022. Further outpatient follow–up included scheduled endoscopic examinations at 3, 12, and 24 months after surgery. Results. At 3 months after the operation, no morphological and morphometric changes were detected in the studied biopsies of the mucous membrane of the biliopancreatic and common loops of the small intestine. The first morphological and morphometric changes in the small intestinal mucosa were observed 12 months after surgery. There was a statistically significant (p < 0.05) difference in the length of intestinal villi in the common and biliopancreatic loops of the small intestine – (0.390 ± 0.199) and (0.377 ± 0.184) mm, respectively. These changes indicate hypertrophy of villi in the colon to increase the absorption area. The thickness of the basal layer was greater in the biliopancreatic loop than in the total loop and amounted to (0.196 ± 0.068) and (0.167 ± 0.043) mm, respectively (p > 0.05). There was no statistically significant difference between the number of crypts containing Paneth cells in the biliopancreatic and common loops, so the regulatory function of these cells was preserved in any variant of gastric bypass with a single anastomosis. Conclusions. Morphological and morphometric changes in the small intestinal mucosa after gastric bypass with a single anastomosis may be associated with various physiological conditions and have clinical significance for understanding the mechanisms of absorption and intestinal protection. Additional studies with a larger number of samples and the use of modern methods of morphological analysis are needed to deepen the understanding of these processes.

Correction of iron deficiency and iron deficiency anemia in women of reproductive age: choice of a drug within framework of concept of patient blood management

The article presents a review of the literature and our own data on the problem of prevention, diagnosis and treatment of iron deficiency and iron deficiency anemia in patients of reproductive age with a burdened somatic status with the development of a chronic inflammatory process. In the concept of patient blood management (PBM), the diagnosis and treatment of anemia in patients with gynecological diseases requiring subsequent surgical treatment is given paramount importance, since anemia and iron deficiency are considered risk factors for worse treatment outcomes for patients. Women with gynecological pathology often have diseases that are accompanied by the development of a systemic inflammatory response, which leads to activation of hepcidin protein synthesis and the development of so-called anemia of inflammatory diseases. Data are presented indicating the effectiveness and safety of the sucrosomial iron drug (SiderAL® Forte) in obstetric and gynecological patients with increased levels of C-reactive protein in combination with iron deficiency and iron deficiency anemia. The increase in ferrokinetic parameters in patients receiving sucrosomial iron is due to the unique physicochemical and pharmacokinetic characteristics of sucrosome, which provides protection of sucrosomial iron from the effects of gastric juice, excluding contact with the mucous membrane of the gastrointestinal tract and its absorption through special M-cells of the small intestinal mucosa followed by the release of iron in liver cells. Sucrosomial iron is novel, convenient, effective, and well tolerated compared with traditional oral iron supplements.

Prostate-specific Membrane Antigen (PSMA): A Diagnostic and Therapeutic Target in Advanced Prostate Cancer

Prostate cancer is among the most prevalent malignant conditions globally, and both incidence and mortality are expected to increase markedly over the next two decades. Recently, the diagnostic and treatment landscape for managing this disease underwent remarkable advances that led to the incorporation of innovative approaches, such as prostate-specific membrane antigen (PSMA) theranostics. PSMA, which is also known as folate hydroxylase or glutamate carboxypeptidase, is a transmembrane protein 100- to 1000-fold overexpressed by prostate cancer cells compared to healthy cells found in the benign prostate gland, salivary glands, proximal renal tubules, small intestine mucosa, and hepatocytes, amongst others. Since its discovery over 30 years ago (see Figure 1 for this and other milestones), PSMA has caught the attention of the scientific community as a potential therapeutic target, and for the past two decades many efforts have been undertaken to identify and develop PSMA ligands and antibodies that could be exploited as prostate cancer therapeutics. This review aims to provide an overview of available PSMA ligands, their mechanisms of action, diagnostic and therapeutic applications, and future perspectives of PSMA-targeted therapeutic approaches within the field of radioligand therapy (RLT).

Viscosity Characteristics of Ideal Lubricants to Reduce Stress on Intestinal Mucosa During Balloon-Assisted Enteroscopy.

Balloon-assisted enteroscopy (BAE) is highly invasive and carries a higher risk of complications such as pain and perforation during enteroscope insertion. Applying lubricants to the small intestinal mucosa and reducing the dynamic friction coefficient (DFC) between the small intestinal mucosa and endoscopic shaft (ES) (or overtube (OT)) can minimize the invasiveness of BAE. However, the ideal viscosity characteristics of these lubricants remain unknown. In this study, a model is developed to measure the DFC using human small intestines from forensic autopsies and determine the ideal viscosity of low-friction lubricants that exhibit a minimal DFC, thus reducing the pressure on the intestinal lining during the procedure. The results reveal that the DFC is strongly correlated to the lubricant's viscosity rather than its chemical composition. Low-friction lubricants with viscosities within 0.20-0.32 and 0.35-0.58 Pa·s (at shear rates of 10 s-1) for the OT and ES, respectively, can significantly reduce the DFC, yielding optimal results. These findings highlight the role of viscosity in minimizing the friction between the equipment and small intestinal mucosa. The ideal low-friction lubricants satisfying the aforementioned viscosity ranges can minimize the invasiveness of BAE by decreasing the friction between the equipment and intestinal lining.

Vibrio cholerae CsrA controls ToxR levels by increasing the stability and translation of toxR mRNA.

Vibrio cholerae is uniquely adapted to life in marine environments as well as in the human intestinal tract. Global regulators such as CsrA, which help translate environmental cues into an appropriate cellular response, are critical for switching between these distinct environments. Understanding the pathways involved in relaying environmental signals is essential for understanding both the environmental persistence and the intestinal pathogenesis of this devastating human pathogen. In this study, we demonstrate that CsrA directly regulates synthesis of ToxR, a key virulence factor of V. cholerae . Under conditions favoring high levels of active CsrA in the cell, such as in the presence of particular amino acids, CsrA increases ToxR protein levels by binding to the toxR transcript and enhancing both its stability and translation. By responding to nutrient availability, CsrA is perfectly poised to activate the virulence gene regulatory cascade at the preferred site of colonization, the nutrient-rich small intestinal mucosa.

First Histopathological and Molecular Characterization of Giant Thorny-headed Worm, Macracanthorhynchus hirudinaceus (Pallas, 1781) (Acanthocephala: Oligacanthorhynchidae) in Wild Boars, Sus scrofa Linnaeus, 1758 from Eastern Türkiye.

Macracanthorhynchus hirudinaceus (Pallas, 1781) is a zoonotic acanthocephalan that parasitizes the small intestine of wild boars. It is a pathogenic that causes economic losses, and poses a public health threat due to increased emergence. The aims of this study is describes histopathologically the damage caused by M. hirudinaceus in the small intestine of wild boar Sus scrofa Linnaeus, 1758, and molecularly characterize this parasite (sequences, haplotypes, phylogeny) for the first time in Elazig city, Türkiye. A high prevalence of infection was obtained. Upon separating the worms, it was discovered that there were ulcers resembling craters in the center, of the small intestine mucosa, surrounded by edema. The intestine wall where the parasite attached was damaged, with the villi epithelium and lamina propria in the mucosa being destroyed. The genomic DNA was isolated from all M. hirudinaceus samples, and PCR amplified the 489bp gene fragments were sequenced and confirmed that all 21 sequences were M. hirudinaceus. The haplotype analysis of the sequences revealed the presence of a central star-shaped haplotype, in addition to four other haplotypes. After conducting sequence analysis, the genetic differences between the M. hirudinaceus sequences obtained in this study and those reported from Europe and Japan suggest that this parasite is endemic to Türkiye's local wild boar population. Also, four haplotypes were identified, distinguishing it from other haplotypes by 1-5 mutation steps. It is essential to consider the worm's sequences and the formation of haplotypes, since these intrinsic characteristics may impact in the epidemiology and pathology of the worm in the future.

Short-peptide-based enteral nutrition affects rats MDP translocation and protects against gut-lung injury via the PepT1-NOD2-beclin-1 pathway in vivo.

Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship. Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts. Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis.

Circulating MicroRNAs and Cytokines Associated with Celiac Disease.

The current research examines the molecular terrain of celiac disease (CD) through microRNA (miRNA) and cytokines as potential new diagnostic and therapeutic markers. Gluten-appropriate immune response is a key feature of an autoimmune clinical entity known as CD that leads to inflammation and degeneration of small intestine mucosa. However, the mechanisms responsible for this remain unclear. Quantitative reverse transcription polymerase chain reaction (RT-qPCR ) was carried out on serum samples obtained from patients with CD and control groups to unravel their pathogenesis. Assessing miR-155, miR-15b, interleukin (IL)-2, IL-7, IL-35and IL-37 levels in expression might be useful in diagnosing or treating the disorder. A significant dysregulation of these molecular players in patients with CD compared with healthy controls has been evidenced by results from this study. For instance, miR-155 was up-regulated, whereas miR-15b was significantly down-regulated in CD, illustrating their roles in immune responses and inflammation-mediated processes. Besides, there was an over-expression of IL-2 and an under-expression of IL-37 in patients with CD, indicating these biomolecules' role in immuno-dysregulation and inflammatory process underlying CD. In addition, a positive correlation between IL-2 and miRNA 155 expression levels was observed in patients with CD, suggesting that they could be involved together with other cytokines, showing the interplay between immune response pathways and inflammatory cascades during CD pathogenesis. These molecular signature discoveries might result in new and revolutionary diagnostic modalities and molecular-targeted therapies for CD pathogenesis. When used with the scientific understanding of miRNAs and cytokines associated with CD pathophysiology, it creates a basis for personalized medicine based on the individualized molecular profile of all patients. This will undoubtedly increase the efficacy of CD treatment strategies. In brief, more research on molecular pathways' workings should be done to harness their potential in CD diagnosis and treatment.

Morphometric features of the duodenal wall in piglets during different periods of postnatal and neonatal ontogenesis under the influence of the ‘Globigen Jump Start’ feed additive

The morphological parameters of the small intestinal mucosa, such as villi size and crypts, play a key role in the formation of the intestinal tube’s absorption surface. The number of goblet and enterochromaffin cells indicates the epithelium’s functional condition in terms of mucus secretion and production of catecholamines and hormones (serotonin, dopamine). That is why it is important to study and determine certain morphometric parameters of the duodenal wall in piglets during different periods of neonatal and postnatal development, especially during stress situations, namely weaning and transition to protein feeding. The article presents the resulting effect studies of ‘Globigen Jump Start’ feed additive on the histo-morphological parameters of the piglets’ duodenal mucosa on day 7, 14 and 28 of life. A positive effect on mitigating weaning stress was manifested by a decrease in the quantitative and linear indicators of histoarchitectonics of intestinal wall’s individual morphological components. A significant increase in goblet cells, especially in the experimental group, had a positive impact on the mucopolysaccharide synthesis. The piglets’ gastrointestinal tract physiology involves a complex interaction between the central nervous system, metasympathetic nervous system, APUD system, and endocrine system. Due to these systems, the information is transmitted according to the direct and reverse communication mechanisms in the regulation of the gastrointestinal tract function. An increase in the number of enterochromaffin cells and their nuclei diameter in the experimental group of piglets indicated an increased synthesis of catecholamines and hormones. It has an extremely positive effect on the immune and physiological status of piglets, thus emphasizing the crucial role of serotonin in neuronal metabolism and the formation of stress resistance. The increase in the thickness of the duodenal wall muscle layer, in our opinion, occured due to the active peristalsis, which was enhanced by the action of some catecholamines, which were synthesized in a slightly larger amount under the influence of nutrients making up the ‘Globigen Jump Start’ feed additive.

Effects of Chinese Gallotannins on Antioxidant Function, Intestinal Health, and Gut Flora in Broilers Challenged with Escherichia coli Lipopolysaccharide.

This experiment was conducted to study the protective effects of dietary Chinese gallotannins (CGT) supplementation against Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury in broilers. Four hundred and fifty healthy Arbor Acres broilers (one-day-old) were randomly divided into three groups: (1) basal diet (CON group), (2) basal diet with LPS challenge (LPS group), and (3) basal diet supplemented with 300 mg/kg CGT as well as LPS challenge (LPS+CGT group). The experiment lasted for 21 days. Intraperitoneal LPS injections were administered to broilers in the LPS group and the LPS+CGT group on days 17, 19, and 21 of the trial, whereas the CON group received an intraperitoneal injection of 0.9% physiological saline. Blood and intestinal mucosa samples were collected 3 h after the LPS challenge. The results showed that LPS administration induced intestinal inflammation and apoptosis and damaged small intestinal morphology and structure in broilers. However, dietary supplementation with CGT alleviated the deleterious effects on intestinal morphology and barrier integrity caused by the LPS challenge, while also reducing intestinal apoptosis and inflammation, enhancing intestinal antioxidant capacity, and increasing cecal microbial alpha diversity in the LPS-challenged broilers. Therefore, our findings demonstrated that a 300 mg/kg CGT addition could improve intestinal morphology and gut barrier structure, as well as maintaining bacterial homeostasis, in broilers exposed to LPS. This might partially be attributed to the reduced cell apoptosis, decreased inflammatory response, and enhanced antioxidant capacity in the small intestinal mucosa.

Intestinal lymphangiectasia: Understanding the bigger picture

Intestinal lymphangiectasia (IL) is characterized by the dilation of intestinal lymphatic vessels, which can rupture and cause loss of lymph into the intestine. Due to the high content of proteins, lipoproteins, and lymphocytes in the intestinal lymph, loss of lymph might result in hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and lymphocytopenia. In addition, there may be a depletion of minerals, lipids, and fat-soluble vitamins. IL can be primary due to inherent malfunctioning of the lymphatic system, or secondly, a result of various factors that may hinder lymphatic drainage either directly or indirectly. This condition has emerged as a subject of significant clinical interest. Given that the intestinal lymphatic system plays an important role in the body’s fluid homeostasis, adaptive immunity, nutrient and drug absorption, intestinal transport, and systemic metabolism, its dysfunction may have wider implications. Although primary IL is rare, with varied clinical features, complications, treatment response, and outcomes, secondary IL is more common than previously believed. The definitive diagnosis of IL requires endoscopic demonstration of whitish villi (which frequently resemble snowflakes) and histological confirmation of dilated lacteals in the small intestinal mucosa. Treatment of IL is challenging and involves dietary modifications, managing underlying medical conditions, and using medications such as sirolimus and octreotide. Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition. This article provides a comprehensive exploration of the clinical implications associated with IL. In addition, it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.

Catalase catalyzed tannic acid-Fe3+ network coating: A theranostic strategy for intestinal barrier restoration

Epithelial barrier impairment of intestinal inflammation leads to the leakage of bacteria, antigens and consequent persistent immune imbalance. Restoring the barrier function holds promise for management of intestinal inflammation, while the theragnostic strategies are limited. In this study, we developed a novel coating by catalase (CAT)-catalyzed polymerization of tannic acid (TA) and combined chelation network with Fe3+. TA-Fe3+ coating was self-polymerized in situ along the small intestinal mucosa, demonstrating persistent adhesion properties and protective function. In enteritis models, sequential administration of TA-Fe3+ complex solution effectively restored the barrier function and alleviated the intestinal inflammation. Overexpressed CAT in inflammatory lesion is more favorable for the in situ targeting growth of TA-Fe3+ coating onto the defective barrier. Based on the high longitudinal relaxivity of Fe3+, the pathologically catalyzed coating facilitated the visualization of intestinal barrier impairment through MRI. In conclusion, the novel TA-Fe3+ delivery coating proposed an alternative approach to promote theranostic intervention for intestinal diseases.

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.

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.

Clinical characteristics and literature review of ectopic gastric mucosa in the small intestine

The study aims to summarize the clinical characteristics of patients with ectopic gastric mucosa in the small intestine, comparing clinical presentation differences between domestic and foreign patients through literature review. The clinical characteristics of cases diagnosed with ectopic gastric mucosa in the small intestine at Peking Union Medical College Hospital from January 2000 to January 2024 were retrospectively analyzed. By searching databanks, such as PubMed, EMBASE, the Cochrane Library, Wanfang, VIP, CNKI, and etc (the inclusion period was from the establishment of the database to January 1, 2024). The literature review was conducted on ectopic gastric mucosa in the small intestine. A total of 10 cases were included, all male, age [M (Q1, Q3)] was 27 (13-69) years old. Gastrointestinal bleeding was the first manifestation in most cases, with severe cases leading to hemorrhagic shock. Abdominal CT indicated local intestinal wall thickening and luminal narrowing in 3 cases. Four cases lesions were located at the beginning of the jejunum and 6 lesions were located in the end segment of ileum. All cases underwent local lesion resection, with postoperative pathology confirming ectopic gastric mucosa. Symptoms disappeared postoperatively, with a follow-up period of 0.5-3.0 years. Literature review indicates that the main clinical manifestation of gastric mucosa ectopia in the small intestine in China is gastrointestinal bleeding, while foreign patients are often complicated with intestinal duplication and intussusception, with abdominal pain and vomiting as the primary and main symptoms. The occurrence rate of intestinal obstruction in female patients, both domestically and abroad, is higher than that in male patients. The occurrence rate of ileal lesions with intestinal obstruction and small intestinal duplication is higher than that of duodenal lesions in both domestic and foreign patients. Local small intestine resection is an effective treatment method with generally good prognosis. Ectopic small intestinal mucosa is relatively rare, with symptoms of gastrointestinal bleeding and intestinal obstruction being common presentations, which can serve as one of the differential diagnoses for unexplained gastrointestinal bleeding.

Substrate specificity of exopeptidases in small intestinal mucosa determines the structure of food-derived collagen peptides in rat lumen and blood

Gly-Pro-Hyp-Gly is the most common motif in collagen. Ingestion of collagen hydrolysate (CH) has been reported to significantly increase Pro-Hyp and Hyp-Gly in human peripheral blood. However, the elevation of Gly-Pro content remains negligible. This study seeks to elucidate the underlying reasons behind the bioavailability of CH-derived peptides using in vivo and in vitro digestion. After oral administration of CH (800 mg/kg body weight) to rats, Pro-Hyp significantly increased in the lumen, small intestinal tissue, and blood from the abdominal vein, while only negligible amounts of Gly-Pro were detected. In vitro digestion of CH by digestive exopeptidases, including aminopeptidase N, leucine aminopeptidase, and carboxypeptidase A predominantly generated Gly-Pro. Interestingly, the digestion of CH with crude extract of small intestinal mucosa predominantly generated Pro-Hyp and negligible amounts of Gly-Pro. Furthermore, synthetic Gly-Pro was rapidly degraded by crude extract of the intestinal mucosa, while Pro-Hyp showed higher resistance. These facts indicate prolidase activity in the mucosa plays a crucial role in determining collagen-derived peptides in the body.

Влияние внутрижелудочного введения гидрокарбоната натрия или соляной кислоты на кишечную эндотоксемию у крыс при миелоабляции циклофосфамидом

Toxic effects of the myeloablative cyclophosphamide (CP) doses include damage to the gastrointestinal tract. This is manifested by gastrointestinal stasis, cytostatic drug-induced damage to the small intestinal mucosa, and acute gut-derived endotoxemia. The study was aimed to identify causal relationships between gastrointestinal stasis, enterocytopenia, and acute gut-derived endotoxemia in the rat model of the CP myeloablative conditioning. We assessed the effects of the intragastrically administered 0.48 М sodium bicarbonate (NaHCO3) solution or the 0.1 М hydrochloric acid (HCl) solution on the indicators of gastrointestinal stasis, enterocytopenia, portal blood levels of endotoxin, ammonia, urea, and urinary indican excretion. The stomach overfilled with chyme, decreased alkaline phosphatase and cholinesterase activity in the small intestinal tissues, 4.4-fold increased endotoxin levels, 4.6-fold increased urea levels, twofold increased portal blood plasma creatinine levels, and twofold increased urinary indican excretion were observed three days after intravenous administration of CP in a dose of 390 mg/kg. Intragastric administration of NaHCO3 or HCl partially prevented gastric stasis, but not acute gut-derived endotoxemia. Administration of NaHCO3, not HCl, prevented enterocytopenia in the duodenum. Acute gut-derived endotoxemia resulted mainly from the more intense release of the cecal microflora waste products into blood. Testing the use of sodium bicarbonate intragastric administration combined with the enteral detoxification and/or options for suppression of colonic microflora vegetation for prevention of the myeloablative cytostatic therapy complications is promising.

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1β and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1β and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1β and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Identification of Circular Patterns in Capsule Endoscopy Bubble Frames.

A significant number of frames captured by the wireless capsule endoscopy are involved with varying amounts of bubbles. Whereas different studies have considered bubbles as nonuseful agents due to the fact that they reduce the visualization quality of the small intestine mucosa, this research aims to develop a practical way of assessing the rheological capability of the circular bubbles as a suggestion for future clinical diagnostic purposes. From the Kvasir-capsule endoscopy dataset, frames with varying levels of bubble engagements were chosen in two categories based on bubble size. Border reflections are present on the edges of round-shaped bubbles in their boundaries, and in the frequency domain, high-frequency bands correspond to these edges in the spatial domain. The first step is about high-pass filtering of border reflections using wavelet transform (WT) and Differential of Gaussian, and the second step is related to applying the Fast Circlet Transform (FCT) and the Hough transform as circle detection tools on extracted borders and evaluating the distribution and abundance of all bubbles with the variety of radii. Border's extraction using WT as a preprocessing approach makes it easier for circle detection tool for better concentration on high-frequency circular patterns. Consequently, applying FCT with predefined parameters can specify the variety and range of radius and the abundance for all bubbles in an image. The overall discrimination factor (ODF) of 15.01, and 7.1 showing distinct bubble distributions in the gastrointestinal (GI) tract. The discrimination in ODF from datasets 1-2 suggests a relationship between the rheological properties of bubbles and their coverage area plus their abundance, highlighting the WT and FCT performance in determining bubbles' distributions for diagnostic objectives. The implementation of an object-oriented attitude in gastrointestinal analysis makes it intelligible for gastroenterologists to approximate the constituent features of intra-intestinal fluids. this can't be evaluated until the bubbles are considered as non-useful agents. The obtained results from the datasets proved that the difference between the calculated ODF can be used as an indicator for the quality estimation of intraintestinal fluids' rheological features like viscosity, which helps gastroenterologists evaluate the quality of patient digestion.