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The large intestine epithelium plays an important role in water absorption and participates in fluid, acid-base and electrolyte balance, and the removal of waste products. The large intestine is rich in microorganism-presented enzyme activity. Apart from energy supply, the colon also participates in the synthesis of trophic factors and the modulation of the immune system and the systemic inflammatory response. The current study investigated the effects of dietary HMB administration to pregnant sows on the postnatal development of the colon in their offspring, at weaning. From the 70th to the 90th day of gestation, sows received either a basal diet (n = 12) or the basal diet supplemented with HMB (n = 12) at a dose of 0.2 g/kg of body weight/day. Maternal HMB treatment increased serum IgG and glucose concentrations and decreased serum urea concentration in the piglets. Basal histomorphometric analysis of offspring large intestines showed that prenatal HMB treatment led to a reduction in the thickness of the mucosa, submucosa and both types of myenterons, as well as reduced crypt thickness. The immunoreaction performed to mark T0 lymphocytes and total T lymphocytes in the colon wall showed that prenatal HMB treatment decreased the number of both types of lymphocytes. Greater expression for cadherin was found in the colon of piglets delivered by the HMB-treated sows. The expression of both tight junction proteins (occludin and claudin-3), as well as that of leptin, was stronger in the HMB-treated group. Vasoactive intestinal peptide (VIP) expression was stronger in the submucosal plexuses in the HMB maternal treated piglets, while no changes were observed in the myenteric plexuses. The results obtained indicate that the administration of HMB to pregnant sows significantly influenced the expression of leptin, VIP and some proteins of the intestinal barrier in their offspring, with less influence on large intestine basal morphology.

Objectives: The aim of this study was to determine the effects of whey proteins on methotrexate (MTX)-induced brain and small intestine damage. Materials and Methods: 30 Sprague Dawley rats (200-300 g) were divided into four groups: Control, control + whey, MTX, and MTX+whey. MTX was administered at 20 mg/kg (single dose) intraperitoneally to the MTX group rats, and 2 mg/kg of whey protein were administered by oral gavage for 10 days to the whey groups. Lipid peroxidation, glutathione, and nitric oxide (NO) levels, as well as glutathione-Stransferase and superoxide dismutase activities were measured in the brain and small intestine. SDS-polyacrylamide gel electrophoresis of the brain and intestine tissues were also carried out. Results: While MTX treatment caused oxidative damage in the brain and small intestine, whey protein administration ameliorated MTXinduced oxidative stress. MTX administration did not change the brain’s NO level, while an increase in intestinal NO level was detected. Conclusion: MTX induced oxidative stress in the brain and small intestine changed the protein metabolism in these tissues regardless of reduced food intake. Consecutive 10-day administration of whey proteins has shown its therapeutic effect on MTX-induced brain and small intestine oxidative damage

Small intestinal metastasis from lung cancer is a relatively rare occurrence, and often causes intestinal obstruction, gastrointestinal perforation, and/or gastrointestinal bleeding making it is an oncological emergency. Many patients have been reported to undergo emergency surgery owing to the rapid progression of the intestinal metastatic lesion; however, information regarding the changes that occur in such metastases over time remains lacking. Therefore, we analyzed 4 patients who had small intestinal metastases arising from lung cancer, who were treated during a 10-year period (January 2011 to December 2020), and whose tumor diameter changes were recorded. The average tumor volume growth rate was 1.48 (1.31-1.78) -fold, and the median observation period was 22 (4-39) days, showing a rapid increase. Histopathologically, in patients with a high degree of primary tumor atypia, rapid tumor growth caused by intratumoral hemorrhage may occur. This was considered to be one of the factors responsible for the rapid increase in tumor volume.

Organoid (hypermature) teratomas are highly specialized teratomas showing organ formation, most frequently from the digestive tract or bronchial wall. We present four cases of ovarian organoid teratomas, one with a distinguishable mandible with teeth, one with small intestine, one with large intestine containing a well differentiated neuroendocrine tumor and another with both large intestine and bronchial wall. These tumors have a distribution similar to conventional teratomas and usually behave benignly, although cases of malignancy have been reported.

Primary retroperitoneal neuroendocrine tumours (NETs) are extremely rare, and many a times, these are metastatic lesions with known or unknown primary location, most commonly arising from the stomach, duodenum, small intestine and rectum. NETs arising from the duodenum are more commonly seen in the first part of the duodenum followed by the second part. The incidence is increasing because of easy accessibility to endoscopies and cross-sectional imaging. In NETs, lymph node (LN) metastasis occurs commonly when the tumour size is more than 2 cm. In contrast, LN metastasis occurs even with subcentimetric lesions, especially the ampullary variant of NETs. A patient presented to us with mild abdominal pain and found to have retroduodenal mass. On evaluation found to be a metastatic LN deposit of NET with the primary arising from the first part and supra-ampullary part of duodenum.

Improved surgical resection and oncological treatment, or an earlier diagnosis may increase survival in small intestinal neuroendocrine tumours (SI-NETs), but only few studies have examined survival trends. We aimed to examine the trend in overall survival and associated factors in SI-NET patients. All patients with SI-NETs at a regional hospital from June 2005 to December 2021 (n = 242) were identified, and the cohort was divided in half, constituting a first period (until November 2012) and a second period (from November 2012). Disease and treatment characteristics, including European Neuroendocrine Tumour Society (ENETS) stage, surgery, oncological treatment and survival, were recorded. The majority (n = 205 (84.7%)) were treated surgically and surgery was considered curative in 137 (66.8%) patients. Median survival was longer in the second period (9.0 years 95% CI 6.4–11.7 in the first period vs. median not reached in the second period, p = 0.014), with 5-year survival rates of 63.5% and 83.5%, respectively. ENETS stage and oncological treatment did not differ between the periods, but factors associated with surgical quality, such as lymph node harvest and resection of multiple SI-NETs, were significantly higher in the second period. Age, ENETS stage, time period and tumour resection were independently associated with survival in a multivariate analysis.

This ATLAS presents in appended form the complete monographic study on the subject. The idea is to bring the results out of the "heavier" didactic format required for the scientific presentation and at the same time to systematize all the information needed for the subsequent clinical research. The present excerpt from monographic work seeks to introduce the possibility that oncological diseases become chronic (like diabetes). The theoretical basis on which we refer is the fact that cancer cells feed only on carbohydrates. In turn, there is evidence that some nitrile glycosides have anti-cancer properties. The study is divided into four parts presented in the form of goals. Proceeding from the particular to the general, the fine molecular structure and all possible biochemical reactions of Amygdalin are examined. By itself, it is highly toxic to the physiologically active animal cell. Amygdalin has NO pronounced antitumor properties. In the first goal, he examines precisely the acceptable form for admission. It is concluded that the active anticancer molecular form is a stoichiometric mixture of the amide and carboxyl derivative of the nitrile glycoside. The second goal is to study the exact action of the anti-tumor product already introduced. After an extremely precise biochemical and mathematical analysis, a series of biochemical cycles of the exact passage of the product through the digestive system, penetration into the blood, approach to cancer cells and selective passage through their cell membrane have been deduced. The third goal is to define the chemical and pharmaceutical molecular forms. 54 methodological and/or pharmaceutical models with hundreds of variables for each are reviewed and analyzed here. The fourth goal (it is this purpose that is separately brought out in this edition) presents the interpretable prediction of anticancer susceptibility of glycosidic amides. The affinities of the pharmaceutical form to each known cancer cell line are reviewed. The results surpass many times all anti-cancer drugs and with significantly reduced toxicity. In an additional part, a generalized clinical control is presented. When conducting the treatment, it is also vitally important to not divert the therapy process to irreversible pathology. Result: The cancer can become chronic and become a practically curable disease., The theoretical basis is based on - https://doi.org/10.5281/zenodo.7295357 | Full calculations are posted here*: https://doi.org/10.5281/zenodo.7550371 | *- the information is constantly updated - choose the current version at the moment, {"references":["Cadow, J., Born, J., Manica, M., Oskooei, A., & Martínez, M. R. (2020). PaccMann: a web service for interpretable anticancer compound sensitivity prediction. Nucleic Acids Research, 48(W1), W502-8. doi:10.1093/nar/gkaa327","Christopher, A. (2017). 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Nucleic Acids Research, 41(D1), D955-61. doi:10.1093/nar/gks1111","Tsanov, V., Tsanov, H., Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product, Anti-Cancer Agents in Medicinal Chemistry 2020; 20(7), DOI: 10.2174/1871520620666200313163801","Tsanov, V., Tsanov, H., Theoretical Analysis of Anticancer Cellular Effects of Glycoside Amides, Anti-Cancer Agents in Medicinal Chemistry 2022; 22(6), DOI: 10.2174/1871520621666210903122831","Tsanov, V., Tsanov, H., Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell, Anti-Cancer Agents in Medicinal Chemistry 2021; 21(12), DOI: 10.2174/1871520620999201103201008","Tsanov, V.; Tsanov, H.,Theoretical study of anticancer activity of glycoside amides [ third supplemented edition ], pp. 857, ISBN: 978-619-91534-4-4, DOI: 10.5281/zenodo.7295357","Yordanova, D., Schultz, T., Kuseva, C., Tankova, K., Ivanova, H., Dermen, I., . . . Mekenyan, O. (2019). 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The pathogenesis of eosinophilic esophagitis involves immunoglobulin G4 (IgG4) deposition. However, the relationship between IgG4 and eosinophilic gastroenteritis (EGE) is unclear. To investigate gastrointestinal deposition of IgG4 in EGE. Biopsies of the esophagus, stomach, and small intestine were evaluated in patients with and without EGE. Immunohistochemical staining for IgG4 was performed, and the proportions of the stained areas were compared. Sera from patients with EGE were assayed for food-specific IgG4, including egg white, wheat, rice, soy, and cow milk. Seventeen patients were included in this study (EGE group, n = 10; control group, n = 7). Compared with the control group, the proportion of IgG4-stained area in the EGE group was approximately threefold higher (40.2% [32.3–49.5]) vs. 12.1% [4.0–21.9], p = 0.014) in the esophagus, fivefold higher in the stomach (17.3% [11.1–26.2] vs. 3.7% [1.5–5.2], p = 0.014), and sixfold higher in the small intestine (28.0% [15.0–33.2] vs. 4.5% [2.6–9.8], p = 0.019). There was no significant association between the proportion of IgG4-stained area and the number of infiltrating eosinophils. Serum egg white-specific IgG4 levels were correlated with the proportion of IgG4-stained areas in the small intestine (R = 0.7, p = 0.035). IgG4 accumulated within the gastrointestinal mucosa in EGE. The positive correlation between serum egg white-specific IgG4 levels and the proportion of IgG4-stained areas in the small intestine suggests a role for IgG4 in the disease pathophysiology.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Introduction Progression of carcinoid syndrome (CS) to carcinoid heart disease (CHD) is difficult to predict. This retrospective analysis evaluates the use of chromogranin A (CgA), a biomarker widely used in the diagnosis of neuroendocrine tumours (NET), in monitoring CS and disease progression. Patients and methods 108 patients with confirmed CS, selected from a group of 351 patients with neuroendocrine neoplasms of the small intestine (SI-NENs), including NETG1 well 40% and NETG2 60% moderately differentiated NET. CgA concentration was measured during initial diagnosis and clinical follow up in 84 patients, 27 of them subsequently developed CHD. The patient's overall survival (OS) was evaluated using the Kaplan-Meier method. Results Patients with CHD, were found to have significantly shorter OS than patients with CS but without CHD (67.22 vs. 73.03 months). Univariate and multivariate analyses revealed that initial high concentration of CgA and/or increased concentration of CgA is significantly associated with decreased median OS in patients with CS (p Conclusion CgA has potential as a clinically useful biomarker in reporting disease status and predicting outcome in patients with CS and with CHD.

Apart from its obvious agronomic interest in feeding billions of people worldwide, the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists. In this review, we give an overview on the fate of proteins that are not fully digested in the pig small intestine, and thus are transferred into the large intestine. In the large intestine, dietary and endogenous proteins are converted to peptides and amino acids (AA) by the action of bacterial proteases. AA, which cannot, except in the neonatal period, be absorbed to any significant level by the colonocytes, are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites. Of note, the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig’s diet. The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied. However, the available data, performed on colonic mucosa, isolated colonic crypts and colonocytes, indicate that some of them, like ammonia, butyrate, acetate, hydrogen sulfide (H2S), and p-cresol are active either directly or indirectly in energy metabolism in colonic epithelial cells. Further studies in that area will certainly gain from the utilization of the pig colonic organoid model, which allows for disposal of functional epithelial unities. Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.

Innovative swallowable capsule technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities to overcome challenges regarding oral delivery of biologics. Here, we report a swallowable capsule for intestinal drug delivery (SCIDD) with the potential of directly injecting biological therapeutics into the insensate small intestine wall. The design, optimization, and validation of the SCIDD's primary subsystems were performed both ex-vivo and in-vivo. The assembled capsule was further tested in vivo to validate the actuation sequence and showed a 70% (n = 17) success rate in an animal model. Additionally, a drug delivery study indicated systemic uptake of adalimumab via SCIDD compared with luminal delivery in the small intestine. The pilot study presented here establishes that the novel platform could be used to orally deliver systemic biologics.

Continuous and rapid renewal of the intestinal epithelium depends on intestinal stem cells (ISCs). A large repertoire of transcription factors mediates the correct maintenance and differentiation of ISCs along either absorptive or secretory lineages. In the present study, we addressed the role of TCF7L1, a negative regulator of WNT signalling, in embryonic and adult intestinal epithelium using conditional mouse mutants. We found that TCF7L1 prevents precocious differentiation of the embryonic intestinal epithelial progenitors towards enterocytes and ISCs. We show that Tcf7l1 deficiency leads to upregulation of the Notch effector Rbp-J, resulting in a subsequent loss of embryonic secretory progenitors. In the adult small intestine, TCF7L1 is required for the differentiation of secretory epithelial progenitors along the tuft cell lineage. Furthermore, we show that Tcf7l1 promotes the differentiation of enteroendocrine D- and L-cells in the anterior small intestine. We conclude that TCF7L1-mediated repression of both Notch and WNT pathways is essential for the correct differentiation of intestinal secretory progenitors.

The numerous components of the venoms of various animal species cause an extremely wide range of effects and symptoms in the recipient’s body. At the same time, the degree of severity of pathological changes is determined, in general, by the type of animal, the volume and method of toxin administration, as well as the characteristic features of the victim. Changes in the structural and functional parameters of the wall of the jejunum under the influence of viper venom are still poorly understood. Research aimed at identifying new components of snake toxins, determining the degree of their influence on the affected organism and using the obtained data for the production of antidotes, and thereby eliminating economic losses associated with snake bites, should be considered extremely relevant. The purpose of the study is to establish the manifestations of damage to the small intestine under the conditions of the action of the venom of the common European adder (Vipera berus berus). The experiment was conducted on 20 non-linear white male rats. During the study, rats were divided into two groups — control and experimental. Poisoning was modeled by intraperitoneal injection of common European adder venom at an ED50 dose of 1.576 μg/g to the rats of the research group. Histological preparations were examined under a SEO SСAN light microscope, images were processed using a Vision CCD Camera with an available image display system on a computer monitor. It was established that under the conditions of action of common European adder venom, the toxic substances of its venom cause destructive-degenerative changes in the relief and stromal-vascular components of the mucous membrane of the organ in the wall of the jejunum. Thus, increasing the permeability of the walls of vessels of the microcirculatory channel, thinning and complete destruction of the walls of hemocapillaries, together with the cytotoxic effect of the poison on erythrocytes, leads to the formation of multiple, small hemorrhages with hemolysis of erythrocytes., Численні компоненти отрут різноманітних видів тварин викликають в організмі реципієнтів надзвичайно широкий спектр ефектів та симптомів. При цьому ступінь вираженості патологічних змін визначається, загалом, видом тварин, об’ємом та способом введення токсину, а також характерними особливостями жертви. Зміни структурно-функціональних параметрів стінки порожньої кишки на тлі впливу отрути гадюки звичайної все ще є недостатньо вивченими. Вкрай актуальними слід вважати дослідження, які направлені на виявлення нових компонентів зміїних токсинів, визначення ступеня їх впливу на уражений організм та використання отриманих даних для виробництва антидотів, і тим самим, усунення економічних втрат, пов’язаних з укусами змій. Метою дослідження є встановлення проявів пошкодження тонкої кишки за умов дії отрути гадюки звичайної (Vipera berus berus). Експеримент проведено на 20 нелінійних білих щурах самцях. При дослідженні щурів розподіляли на дві групи — контрольну та дослідну. Отруєння моделювали введенням щурам дослідної групи внутрішньочеревно отрути гадюки звичайної в дозі ED50 1,576 мкг/г. Гістологічні препарати досліджували під світловим мікроскопом SEO SСAN, знімки опрацьовували за допомогою Vision CCD Camera з наявною системою виведення зображення на монітор комп’ютера. Було встановлено, що за умов дії отрути гадюки звичайної токсичні речовини її отрути викликають в стінці порожньої кишки деструктивно-дегенеративні зміни в рельєфі та стромально-судинному компонентах слизової оболонки органу. Таким чином, підвищення проникності стінок судин мікроциркуляторного русла, витончення і повна руйнація стінок гемокапілярів разом із цитотоксичною дією отрути на еритроцити призводить до утворення множинних, дрібних крововиливів з гемолізом еритроцитів.

Malic Enzyme 1 (ME1) supports lipogenesis, cholesterol synthesis, and cellular redox potential by catalyzing the decarboxylation of L-malate to pyruvate, and the concomitant reduction of NADP to NADPH. We examined the contribution of ME1 to the development of obesity by provision of an obesogenic diet to C57BL/6 wild type (WT) and MOD-1 (lack ME1 protein) female mice. Adiposity, serum hormone levels, and adipose, mammary gland, liver, and small intestine gene expression patterns were compared between experimental groups after 10 weeks on a diet. Relative to WT female mice, MOD-1 female mice exhibited lower body weights and less adiposity; decreased concentrations of insulin, leptin, and estrogen; higher concentrations of adiponectin and progesterone; smaller-sized mammary gland adipocytes; and reduced hepatosteatosis. MOD-1 mice had diminished expression of Lep gene in abdominal fat; Lep, Pparg, Klf9, and Acaca genes in mammary glands; Pparg and Cdkn1a genes in liver; and Tlr9 and Ffar3 genes in the small intestine. By contrast, liver expression of Cdkn2a and Lepr genes was augmented in MOD-1, relative to WT mice. Results document an integrative role for ME1 in development of female obesity, suggest novel linkages with specific pathways/genes, and further support the therapeutic targeting of ME1 for obesity, diabetes, and fatty liver disease.

The lipidome is a key determinant of structural and functional characteristics of tissues, contributing to optimal gut function and efficiency of nutrient use in the gastrointestinal tract (GIT). Our objective was to study lipidomic profiles in different sections of the GIT in lactating dairy cows and to link them with biological functions. We studied the lipid species in ruminal papillae and epithelium from duodenum, jejunum, and ileum harvested after slaughter from five lactating Holstein cows. Extracted lipids were identified by LC/MS/MS and analyzed via Lipidsearch, Metaboanalyst 5.0, and lipid ontology (LION). Of 1259 lipid species identified across the GIT, 387, 565, 193, and 86 were neutral lipids, phospholipids, sphingolipids, and derivatized lipids, respectively. Among the 1223 lipid species common to the GIT, a PLS-DA analysis revealed similar profiles for jejunum and ileum and discriminated them from rumen and duodenum. The content of 12 out of 28 lipid classes differed (p < 0.05) among GIT sections. The average fatty acid chain length in lipid species spanned from 9 to 37 carbons, and the average degree of unsaturation ranged from 0 to 6. The term ‘membrane component’ from LION analysis differed markedly between the rumen and the small intestine. Future studies will help better understand what factors (function or cellular component) in a given section of the GIT are related to the different lipid species. This is the first description of the lipidome profiles across sections of the GIT in lactating dairy cows. The unique lipidome profiles uncovered distinct structural and functional properties across the bovine GIT, which may impact the efficiency of nutrient use.

Background The effects of fermented food consumption on the small intestine microbiome and its role on host homeostasis are largely uncharacterised as our knowledge on intestinal microbiota relies mainly on faecal samples analysis. We investigated changes in small intestinal microbial composition and functionality, short chain fatty acid (SCFA) profiles, and on gastro-intestinal (GI) permeability in ileostomy subjects upon the consumption of fermented milk products. Results We report the results from a randomised, cross-over, explorative study where 16 ileostomy subjects underwent 3, 2-week intervention periods. In each period, they consumed either milk fermented by Lacticaseibacillus rhamnosus CNCM I-3690, or milk fermented by Streptococcus thermophilus CNCM I-1630 and Lactobacillus delbrueckii subsp. bulgaricus CNCM I-1519, or a chemically acidified milk (placebo) daily. We performed metataxonomic, metatranscriptomic analysis, and SCFA profiling of ileostomy effluents as well as a sugar permeability test to investigate the microbiome impact of these interventions and their potential effect on mucosal barrier function. Consumption of the intervention products impacted the overall small intestinal microbiome composition and functionality, mainly due to the introduction of the product-derived bacteria that reach in several samples 50% of the total microbial community. The interventions did not affect the SCFA levels in ileostoma effluent, or gastro-intestinal permeability and the effects on the endogenous microbial community were negligible. The impact on microbiome composition was highly personalised, and we identified the poorly characterised bacterial family, Peptostreptococcaceae, to be positively associated with a low abundance of the ingested bacteria. Activity profiling of the microbiota revealed that carbon- versus amino acid-derived energy metabolism of the endogenous microbiome could be responsible for the individual-specific intervention effects on the small intestine microbiome composition and function, reflected also on urine microbial metabolites generated through proteolytic fermentation. Conclusions The ingested bacteria are the main drivers of the intervention effect on the small intestinal microbiota composition. Their transient abundance level is highly personalised and influenced by the energy metabolism of the ecosystem that is reflected by its microbial composition (http://www.clinicaltrials.gov, ID NCT NCT02920294).

Background: This study aimed to characterize and evaluate the main markers of T lymphocytes, B lymphocytes, immunoglobulin (Ig) A and IgG plasmocytes, macrophages, and dendritic cells of the intestinal mucosa of newborn yaks. Materials and methods: Ten newborn yaks (2–4 weeks old) were choosed. Immunohistochemistry and real-time quantitative polymerase chain reaction were used to analyze the immune cell distribution and specific markers at the mRNA expression level in the duodenum, jejunum, and ileum. Results: The results showed in the epithelium, CD3-positive T lymphocyte levels were higher than other immune cell levels (P

Weaning stress may cause reduced energy intake for maintenance of mucosal structure. Gln, Glu, and Asp are major energy sources for the small intestine. This study investigated whether Gln, Glu, and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: Control (Basal diet + 1.59% L-Ala); T1 (Basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); T2 (Low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). Jejunum and ileum were obtained on d 5 or 21 post-weaning. T1 enhanced growth performance. T1 and T2 treatments improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth. Day-post-weaning affected the efficacy of T2, but not T1, on energy metabolism. At normal energy supplementation, Gln, Glu, and Asp restored small intestinal energy homeostasis via replenishing the Krebs’ cycle and down-regulating the AMPK (adenosine monophosphate activated protein kinase) pathway. As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning, the AMPK, glycolysis, beta-oxidation, and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes. These data indicated that Gln, Glu, and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed. Low energy feeding may increase the susceptibility of piglets to stress, which may decrease the efficacy of Gln, Glu, and Asp on the restoration of energy balance. These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.

Objective: An experiment was conducted to evaluate the effect of different levels of crude protein (CP) and two rearing systems (cage and floor), on blood parameters and digestive and reproductive organ development of brown laying hens.Methods: A total of 400 Hisex Brown laying hens between 30 and 45 weeks of age were distributed in a completely randomized design and a 2×4 factorial arrangement, with main effects including two rearing systems (cage and floor) and levels of CP (140, 150, 160, and 180 g/kg), in a total of eight treatments and five replicates of 10 birds each with initial body weight of 1,877 g (laying hen in cage) and 1,866 g (laying hens in floor). The parameters evaluated were plasma total protein, albumin, uric acid, total cholesterol, relative weights of oviduct, abdominal fat, liver, gizzard, crest and dewlap, length of small intestine and oviduct.Results: The blood parameters were similar in birds reared in cage and floor systems. The birds reared on the floor showed greater small intestine and oviduct weight (%) and lower liver and pancreas weight (%). A significant interaction was observed between factors for the relative gizzard, crest and dewlap weight, serum protein, uric acid, and total cholesterol (p

Background Zinc homeostasis is essential for human health and is regulated by several zinc transporters including ZIP and ZnT. ZIP4 is expressed in the small intestine and is important for zinc absorption from the diet. We investigated in the present study the effects of Panax ginseng (P. ginseng) extract on modulating Zip4 expression and cellular zinc levels in mouse Hepa cells. Methods Hepa cells were transfected with a luciferase reporter plasmid that contains metal-responsive elements, incubated with P. ginseng extract, and luciferase activity was measured. Using 65ZnCl2, zinc uptake in P. ginseng-treated cells was measured. The expression of Zip4 mRNA and protein in Hepa cells was also investigated. Finally, using a luciferase reporter assay system, the effects of several ginsenosides were monitored. Results The luciferase activity in cells incubated with P. ginseng extract was significantly higher than that of control cells cultured in normal medium. Hepa cells treated with P. ginseng extract exhibited higher zinc uptake. P. ginseng extract induced Zip4 mRNA expression, which resulted in an enhancement of Zip4 protein expression. Furthermore, some ginsenosides, such as ginsenoside Rc and Re, enhanced luciferase activity driven by intracellular zinc levels. Conclusion P. ginseng extract induced Zip4 expression at the mRNA and protein level and resulted in higher zinc uptake in Hepa cells. Some ginsenosides facilitated zinc influx. On the basis of these results, we suggest a novel effect of P. ginseng on Zip4-mediated zinc influx, which may provide a new strategy for preventing zinc deficiency.

This study was to characterise the undigested nutrients present along the gastrointestinal tract of birds offered common wheat- or maize-based diets, with the goal of optimising utilisation of enzymes to enhance digestive efficiency. Wheat- and maize-based diets were offered to 240 mixed-sex broilers (10 birds/pen; n = 12) from 1 to 35 d post–hatch. Digestibility of dry matter, starch, crude protein and non-starch polysaccharides (NSP) were measured in the crop, gizzard, duodenum, jejunum, ileum, caeca and excreta at d 12 and 35 post–hatch. Analysis of nutrient levels in the excreta presented that more than 30% of nutrients provided in the feed was wasted, irrespective of wheat or maize diet type. On average, 92 g/kg crude protein, 92 g/kg insoluble NSP and 14 g/kg oligosaccharides were not utilised by birds at d 12 post–hatch. The quantity of water-insoluble NSP in the small intestine at d 12 was lower in birds offered the wheat-based diet compared to those fed the maize-based diet (P

Background and Aim: Antibiotic, improves the growth performance of laying hens when used as a feed additive; however, it has been banned in Europe. Furthermore, secondary metabolites used as a substitute for antibiotics are compounds produced by plants. Therefore, this aims to determine the effect of dates water extract (DWE) on the performance of laying hens. This study used dates containing secondary metabolites as a feed additive and substitute for antibiotics. Materials and Methods: A completely randomized design was used, dividing 400 Lohmann brown day old chick into five groups (each group has five replications and each replication consisted of 16 laying hens). Furthermore, there were two control groups such as mineral water control group and antibiotic growth promoters (basal feed+50 mg/kg of bacitracin), and three DWE groups such as 5% DWE (50 mg/mL), 10% DWE (100 mg/mL), and 20% DWE (200 mg/mL). Dates extract treatment was administered through drinking water for 54 days, whereby three laying hens from each replication were taken randomly and decapitated on the neck. Afterwards, a necropsy was performed for histological preparations of the small intestine, ovary, and lymphoid organs. The structure and morphology of the small intestine, and ovaries were observed through histological preparations, while lymphoid organs were observed through histological preparation and morphometry, and body morphometry, body weight, feed intake and weight gain were observed by measurements and weighing. Results: Small intestine morphology, ovarian follicle, and growth performance of the DWE2 group increased significantly compared to the control group, but the lymphoid organs index was influenced by DWE1. Conclusion: The administration of 10% dates extract (100 mg/mL) in drinking water improves the morphology of the small intestine, ovarian follicles, lymphoid organs, and growth performance.

Peripheral monocyte-derived CX3C chemokine receptor 1 positive (CX3CR1(+)) cells play important roles in tissue homeostasis and gut repopulation. Increasing evidence also supports their role in immune repopulation of the brain parenchyma in response to systemic inflammation. Adoptive bone marrow transfer from CX3CR1 fluorescence reporter mice and high-resolution confocal microscopy was used to assess the time course of CX3CR1(+) cell repopulation of steady-state and dextran sodium sulfate (DSS)-inflamed small intestine/colon and the brain over 4 weeks after irradiation. CX3CR1(+) cell colonization and morphologic polarization into fully ramified cells occurred more rapidly in the small intestine than in the colon. For both organs, the crypt/mucosa was more densely populated than the serosa/muscularis layer, indicating preferential temporal and spatial occupancy. Repopulation of the brain was delayed compared with that of gut tissue, consistent with the immune privilege of this organ. However, DSS-induced colon injury accelerated the repopulation. Expression analyses confirmed increased chemokine levels and macrophage colonization within the small intestine/colon and the brain by DSS-induced injury. Early increases of transmembrane protein 119 and ionized calcium binding adaptor molecule 1 expression within the brain after colon injury suggest immune-priming effect of brain resident microglia in response to systemic inflammation. These findings identify temporal differences in immune repopulation of the gut and brain in response to inflammation and show that gut inflammation can impact immune responses within the brain.

Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life. Male and female mice were tested several weeks later using novel object recognition (recognition memory) and 5-choice serial reaction time task (executive function). Gene expression of proinflammatory, white matter and synapse-associated molecules was assessed in the prefrontal cortex and small intestine both acutely after chemotherapy and chronically after cognitive testing. Early life cancer-chemotherapy exposure resulted in recognition memory and executive function deficits in adult male mice. Prefrontal cortex expression of the chemokine Ccl2 was increased acutely, while small intestine expression of the proinflammatory cytokine tumor necrosis factor-alpha was elevated both acutely (both sexes) and chronically (males only). Inflammation in the small intestine was correlated with prefrontal cortical proinflammatory and synaptic gene expression changes, as well as to executive function deficits. Collectively, these data indicate that the current protocol results in a robust mouse model in which to study cognitive deficits in leukemia survivors, and suggest that small intestine inflammation may represent a novel contributor to adverse CNS consequences of early life chemotherapy.

With an upsurge of biodegradable metal implants, the research and application of Mg alloys in the gastrointestinal environment of the digestive tract have been of great interest. Digestive enzymes, mainly pepsin in the stomach and pancreatin in the small intestine, are widespread in the gastrointestinal tract, but their effect on the degradation of Mg alloys has not been well understood. In this study, we investigated the impacts of pepsin and pancreatin on the degradation of Mg-2Zn alloy wires. The results showed that the pepsin and pancreatin had completely different even the opposite effects on the degradation of Mg, although they both affected the degradation product layer. The degradation rate of Mg wire declined with the addition of pepsin in simulated gastric fluid (SGF) but rose with the addition of pancreatin in simulated intestinal fluid (SIF). The opposite trends in degradation rate also resulted in completely different degradation morphologies in wires surface, where the pitting corrosion in SGF was inhibited because of the physical barrier effect of pepsin adsorption. In contrast, the adsorption of pancreatin affected the integrity of magnesium hydrogen phosphate film, causing a relatively uneven degraded surface. These results may help us to understand the role of different digestive enzymes in the degradation of magnesium and facilitate the development and clinical application of magnesium alloy implanted devices for the digestive tract., Graphical abstract Image 1, Highlights • The pepsin in SGF and pancreatin in SIF have opposite effects on the degradation rate of Mg. • Both enzymes can adsorb on the surface of Mg wire and affect the formation of the degradation layer. • The physical barrier effect of pepsin adsorption retarded the pitting corrosion and corrosion rate in SGF. • Adsorbed pancreatin affected the integrity of the products layer in SIF, resulting in an accelerated corrosion rate.

Background/Aims: Extracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs.Methods: LpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance.Results: The isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner.Conclusions: EVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.

Background and purpose Inhibitors of DNA-dependent protein kinase (DNA-PK) are effective radiation sensitisers in preclinical tumours, but little is known about risks of normal tissue radiosensitisation. Here, we evaluate radiosensitisation of head and neck squamous cell carcinoma (HNSCC) cells by DNA-PK inhibitor AZD7648 under oxia and anoxia in vitro, and tumour (SCCVII), oral mucosa and small intestine in mice. Materials and methods Radiosensitisation of human (UT-SCC-54C) and murine (SCCVII) HNSCC cells by AZD7648 under oxia and anoxia was evaluated by clonogenic assay. Radiosensitisation of SCCVII tumours in C3H mice by oral AZD7648 (75 mg/kg) was determined by ex vivo clonogenic assay 3.5 days post-irradiation, with evaluation of normal tissue surrogate endpoints using 5-ethynyl-2’-deoxyuridine to facilitate detection of regenerating crypts in the ileum and repopulating S-phase cells in the ileum and oral mucosa of the same animals. Results AZD7648 potently radiosensitised both cell lines, with similar sensitiser enhancement ratios for 10% survival (SER10) under oxia and anoxia. AZD7648 diffused rapidly through multicellular layers, suggesting rapid equilibration between plasma and hypoxic zones in tumours. SCCVII tumours were radiosensitised by AZD7648 (SER10 2.5). AZD7648 also enhanced radiation-induced body weight loss and suppressed regenerating intestinal crypts and repopulating S-phase cells in the ileum and tongue epithelium with SER values similar to SCCVII tumours. Conclusion AZD7648 is a potent radiation sensitiser of both oxic and anoxic tumour cells, but also markedly radiosensitises stem cells in the small intestine and oral mucosa.

Background and AimsSingle-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 humans.Methods12,590 single epithelial cells from three independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and capacity for response to extrinsic signals along the gut axis across different humans.ResultCells were assigned to 25 epithelial lineage clusters. Human intestinal stem cells (ISCs) are not specifically marked by many murine ISC markers. Lysozyme expression is not unique to human Paneth cells (PCs), and PCs lack expression of expected niche-factors. BEST4+ cells express NPY and show maturational differences between SI and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell-junction, and nutrient absorption genes show unappreciated regional expression differences across lineages. Differential expression of receptors and drug targets across lineages reveals biological variation and potential for variegated responses.ConclusionsOur study identifies novel lineage marker genes; covers regional differences; shows important differences between mouse and human gut epithelium; and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomical regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.

We evaluated the environment in TIM-1 luminal compartments using paracetamol and danazol solutions and suspensions and the fed state configuration. Data were compared with recently published data in healthy adults. TIM-1 experiments were performed with a 3-fold downscale. Volumes of secretions in gastric and duodenal compartments adequately reflected the luminal data in adults up to 3 h post drug dosing. pH values in duodenal and jejunal compartments adequately reflected average pH values in adults. In gastric compartment pH values where initially higher than average values in adults and reached baseline levels earlier than in adults. The environment in the TIM-1 gastric compartment and jejunal compartment adequately reflected the average total paracetamol and danazol amounts per volume of contents in the adult stomach and upper small intestine, respectively. Total bile acids concentrations in the micellar phase of contents in duodenal and jejunal compartments overestimated micellar concentrations in the upper small intestine of adults. Adjustments in gastric emptying/acid secretion rates and bile acids identities in the duodenal and jejunal compartments, and application of dynamic bile acids secretion rates are expected to further improve the relevance of luminal conditions in TIM-1 compartments with those in adults.

Background & Aims: Intestinal stem cells (ISCs) are sensitive to dietary alterations and nutrient availability. Neurotensin (NT), a gut peptide localized predominantly to the small bowel and released by fat ingestion, stimulates the growth of intestinal mucosa under basal conditions and during periods of nutrient deprivation, suggesting a possible role for NT on ISC function. Methods: Leucine-rich repeat-containing G-protein coupled receptor 5-Enhanced Green Fluorescent Protein (Lgr5-EGFP) NT wild type (Nt+/+) and Lgr5-EGFP NT knockout (Nt-/-) mice were fed ad libitum or fasted for 48 hours. Small intestine tissue and crypts were examined by gene expression analyses, fluorescence-activated cell sorting, Western blot, immunohistochemistry, and crypt-derived organoid culture. Drosophila expressing NT in midgut enteroendocrine cells were fed a standard diet or low-energy diet and esg-green fluorescent protein+ ISCs were quantified via immunofluorescence. Results: Loss of NT impaired crypt cell proliferation and ISC function in a manner dependent on nutrient status. Under nutrient-rich conditions, NT stimulated extracellular signal-regulated kinases 1 and 2 signaling and the expression of genes that promote cell-cycle progression, leading to crypt cell proliferation. Under conditions of nutrient depletion, NT stimulated WNT/β-catenin signaling and promoted an ISC gene signature, leading to enhanced ISC function. NT was required for the induction of WNT/β-catenin signaling and ISC-specific gene expression during nutrient depletion, and loss of NT reduced crypt cell proliferation and impaired ISC function and Lgr5 expression in the intestine during fasting. Conversely, the expression of NT in midgut enteroendocrine cells of Drosophila prevented loss of ISCs during nutrient depletion. Conclusions: Collectively, our findings establish an evolutionarily conserved role for NT in ISC maintenance during nutritional stress. GSE182828

Background The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain’s susceptibility is not known. Objective We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. Methods We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. Results In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Conclusions Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.

Background & Aims Intestinal ischemia-reperfusion injury is a serious and life-threatening condition. A better understanding of molecular mechanisms related to intestinal ischemia-reperfusion injury in human beings is imperative to find therapeutic targets and improve patient outcome. Methods First, the in vivo dynamic modulation of mucosal gene expression of the ischemia-reperfusion–injured human small intestine was studied. Based on functional enrichment analysis of the changing transcriptome, one of the predominantly regulated pathways was selected for further investigation in an in vitro human intestinal organoid model. Results Ischemia-reperfusion massively changed the transcriptional landscape of the human small intestine. Functional enrichment analysis based on gene ontology and pathways pointed to the response to unfolded protein as a predominantly regulated process. In addition, regulatory network analysis identified hypoxia-inducing factor 1A as one of the key mediators of ischemia-reperfusion–induced changes, including the unfolded protein response (UPR). Differential expression of genes involved in the UPR was confirmed using quantitative polymerase chain reaction analysis. Electron microscopy showed signs of endoplasmic reticulum stress. Collectively, these findings point to a critical role for unfolded protein stress in intestinal ischemia-reperfusion injury in human beings. In a human intestinal organoid model exposed to hypoxia-reoxygenation, attenuation of UPR activation with integrated stress response inhibitor strongly reduced pro-apoptotic activating transcription factor 4 (ATF4)-CCAAT/enhancer-binding protein homologous protein (CHOP) signaling. Conclusions Transcriptome analysis showed a crucial role for unfolded protein stress in the response to ischemia-reperfusion in human small intestine. UPR inhibition during hypoxia-reoxygenation in an intestinal organoid model suggests that downstream protein kinase R-like ER kinase (PERK) signaling may be a promising target to reduce intestinal ischemia-reperfusion injury. Microarray data are available in GEO (https://www.ncbi.nlm.nih.gov/gds, accession number GSE37013)., Graphical abstract

Background Fetus in fetu is a rare congenital anomaly. Its incidence is 1/500,000 births. So, pediatric surgeons may encounter this pathology only once or twice during their professional careers. Case presentation We present a rare case of a fetus extracted from the small intestinal mesentery of a healthy neonate who was explored after delivery. The extracted fetal mass included a fully differentiated skull and limbs with a celomic cavity. The fetal mass was supplied by a main feeding vessel branching from the superior mesenteric artery. Conclusion Fetus in fetu, despite being a rare variant, must be kept in mind when dealing with a neonatal abdominal mass showing bony parts on radiography.

Background: A particularly pressing problem is determining consumer-safe doses of potentially health- and life-threatening substances, such as acrylamide. The aim of the study was to determine how acrylamide affects the pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive intramural neurons in the small intestine of sexually immature gilts. Methods: The study was conducted on 15 sexually immature Danish gilts receiving for 28 days empty gelatin capsules or acrylamide in low (0.5 µg/kg of body weight (b.w.)/day) and high (5 µg/kg b.w./day) doses. After euthanasia, intestinal sections were stained using the double immunofluorescence staining procedure. Results: Studies have shown that oral administration of acrylamide in both doses induced a response of intramural neurons expressed as an increase in the population of PACAP-immunoreactive neurons in the small intestine. In the duodenum, only in the myenteric plexus (MP) was an increase in the number of PACAP-immunoreactive (IR) neurons observed in both experimental groups, while in the outer submucous plexus (OSP) and inner submucous plexus (ISP), an increase was noted only in the high-dose group. In the jejunum, both doses of acrylamide led to an increase in the population of PACAP-IR neurons in each enteric plexus (MP, OSP, ISP), while in the ileum, only supplementation with the higher dose of acrylamide increased the number of PACAP-IR enteric neurons in the MP, OSP, and ISP. Conclusions: The obtained results suggest the participation of PACAP in acrylamide-induced plasticity of enteric neurons, which may be an important line of defence from the harmful action of acrylamide on the small intestines.

There are no studies reporting the effects of Salmonella enterica subsp. enterica serovar Infantis (S. Infantis) on intestinal architecture and immunoglobulin serum levels in chickens. Here, we measured these parameters and hypothesized whether probiotic administration could modulate the observed outcomes. Two-hundred 1-day-old COBB 500 male chicks were allocated into four groups: (I) the control, (II) the group treated with L. fermentum, (III) the group exposed to S. Infantis, and (IV) the group inoculated with both bacteria. At 11 days post infection, blood was gathered from animals which were then euthanized, and samples from the small intestine were collected. Intestinal conditions, as well as IgA and IgM serum levels, were assessed. S. Infantis reduced villus-height-to-crypt-depth (VH:CD) ratios in duodenal, jejunal, and ileal sections compared to control conditions, although no differences were found regarding the number of goblet cells, muc-2 expression, and immunoglobulin concentration. L. fermentum improved intestinal measurements compared to the control; this effect was also evidenced in birds infected with S. Infantis. IgM serum levels augmented in response to the probiotic in infected animals. Certainly, the application of L. fermentum elicited positive outcomes in S. Infantis-challenged chickens and thus must be considered for developing novel treatments designed to reduce unwanted infections.

This book is a long-term study and analysis presented in a more scientifically popular form. The matter is presented in a freer way in order to explain the matter. The present monographic work seeks to introduce the possibility that oncological diseases become chronic (like diabetes). The theoretical basis on which we refer is the fact that cancer cells feed only on carbohydrates. In turn, there is evidence that some nitrile glycosides have anti-cancer properties. The study is divided into four parts presented in the form of goals. Proceeding from the particular to the general, the fine molecular structure and all possible biochemical reactions of Amygdalin are examined. By itself, it is highly toxic to the physiologically active animal cell. Amygdalin has NO pronounced antitumor properties. In the first goal, he examines precisely the acceptable form for admission. It is concluded that the active anticancer molecular form is a stoichiometric mixture of the amide and carboxyl derivative of the nitrile glycoside. The second goal is to study the exact action of the anti-tumor product already introduced. After an extremely precise biochemical and mathematical analysis, a series of biochemical cycles of the exact passage of the product through the digestive system, penetration into the blood, approach to cancer cells and selective passage through their cell membrane have been deduced. The third goal is to define the chemical and pharmaceutical molecular forms. 54 methodological and/or pharmaceutical models with hundreds of variables for each are reviewed and analyzed here. The fourth goal presents the interpretable prediction of anticancer susceptibility of glycosidic amides. The affinities of the pharmaceutical form to each known cancer cell line are reviewed. 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Biomarkers profiling of human blood serum. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal illness in children and travelers in low- and middle-income countries. When volunteers are infected with ETEC strains, as part of experimental infection studies, some do not develop diarrhea. To improve our understanding of how these volunteers are protected, we investigated the association between stool ETEC DNA concentration, as determined by quantitative PCR, and the development and severity of disease in 21 volunteers who had been experimentally infected with ETEC strain TW10722. We found a strong association between maximum stool ETEC DNA concentration and the development of diarrhea: all of the 11 volunteers who did not develop diarrhea had

Merkel cell carcinoma is a rare primary neuroendocrine malignant neoplasm of the skin, which recurs in about 40 % of cases. The main factors are Merkel cell polyomavirus (MCPyV) and mutations caused by ultraviolet radiation [Paulson, 2018]. In this study, we report a case of Merkel cell carcinoma with metastasis to the small intestine. In a 52-year-old woman, a subcutaneous formation of a nodule up to 2.0 cm in diameter was detected during the examination. This neoplasm was removed and sent for histological analysis. Dot-like expression of CK pan, CK 20, chromogranin A, and Synaptophysin was observed in tumor cells, and Ki-67 in 40 % of tumor cells. There is no reaction in tumor cells to CD 45, CK 7, TTF 1, and S100. The morphological picture corresponded to Merkel cell carcinoma. A year later, the patient underwent surgery for intestinal obstruction. The pathohistological changes and immunophenotype of the small bowel tumor were consistent with Merkel cell carcinoma metastasis. Міністерство освіти інауки України, грантовий договір №РН 1740-2023

Metabolites profiling of urine samples. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically.

The article describes the experience of surgical treatment of 50 patients with isolated injuries of small and large intestine. The diagnostic algorithms were studied. The diagnostic program included a medical history, clinical and objective data, the results of ultrasonic, X-ray methods and videolaparoscopy. Depending on the nature of the damage, the indications for surgical treatment of patients with this pathology are specified. The developed diagnostic program and selection of the optimal option of surgery allowed the reduction of the number of adverse outcomes among patients with injuries of the small and large intestine.

Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospecific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus aggregation. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitizes mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium. We illustrate the jejunal mucus layer as a microbial habitat, and link the regiospecific mucus dependency of the microbiota to distinctive properties of the jejunal niche. Together, our data demonstrate a symbiotic mucus-microbiota relationship that normally prevents jejunal pathogen colonization, but is highly sensitive to disruption by exposure to a WSD.

Effects of whole foods on the microbial production of tryptophan-derived aryl hydrocarbon receptor (AhR) ligands in the intestine were investigated in a pig model. Ileal digesta and faeces of pigs after feeding of eighteen different foods were analyzed. Indole, indole-3-propionic acid, indole-3-acetic acid, indole-3-lactic acid, kynurenine, tryptamine, and indole-3-aldehyde were identified in ileal digesta, which were also identified in faeces but at higher concentrations except indole-3-lactic acid, together with skatole, oxindole, serotonin, and indoleacrylic acid. The panel of tryptophan catabolites in ileal digesta and faeces varied across different foods. Eggs induced the highest overall concentration of catabolites in ileal digesta dominated by indole. Amaranth induced the highest overall concentration of catabolites in faeces dominated by skatole. Using a reporter cell line, we observed many faecal samples but not ileal samples retained AhR activity. Collectively, these findings contribute to food selection targeting AhR ligands production from dietary tryptophan in the intestine.

Metabolites profiling of blood samples. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically.

Growing evidence suggests the importance of the small intestinal bacteria in the diet-host-microbiota dialogue in various facets of health and disease. Yet, this body site is still poorly explored and its ecology and mechanisms of interaction with the host are just starting to be unraveled. In this review, we describe the current knowledge on the small intestinal ecology, its composition and diversity, and how the intestinal bacteria in homeostatic conditions participate in nutrient digestion and absorption. We illustrate the importance of a controlled bacterial density and of the preservation of absorptive surface for the host's nutritional status. In particular, we discuss these aspects of the small intestinal environment in the framework of two disease conditions, namely small intestinal bacterial overgrowth (SIBO) and short bowel syndrome (SBS). We also detail in vivo, ex vivo and in vitro models developed to simulate the small intestinal environment, some applied for (diet-)host-bacteria interaction studies. Lastly, we highlight recent technological, medical and scientific advances applicable to investigate this complex and yet understudied body environment to broaden our knowledge in support of further progress in the medical practice, and to proceed towards the integration of the (small)intestinal bacteria in personalized therapeutic approaches.

Currently, research in theoretical and clinical immunology has made significant progress. Due to the considerable development of these scientific directions and their realization in practical medicine the interest in studying structural and functional features of different organs and systems in general is understandable. Numerous publications that have appeared in recent years reflect various aspects of morpho-physiology of central and peripheral organs of immune system. A significant part of scientific achievements is in demand in practice and has been realized in investigations of immunomorphology and ultrastructure of lymphoid organs in norm, experiment and pathology. The achieved success provides a better understanding of individual characteristics of immune system in norm, pathology, primary and secondary immunodeficiency, so common nowadays. The scientific data obtained in recent years contribute to a better understanding of the cellular basis of immunity, the mechanisms of immunological recognition and the nature of intercellular interactions in the formation of the immune response.

The human gut microbiota continues to demonstrate its importance in human health and disease, largely owing to the countless number of studies investigating the fecal microbiota. Underrepresented in these studies, however, is the role played by microbial communities found in the small intestine, which, given the essential function of the small intestine in nutrient absorption, host metabolism, and immunity, is likely highly relevant. This review provides an overview of the methods used to study the microbiota composition and dynamics along different sections of the small intestine. Furthermore, it explores the role of the microbiota in facilitating the small intestine in its physiological functions and discusses how disruption of the microbial equilibrium can influence disease development. The evidence suggests that the small intestinal microbiota is an important regulator of human health and its characterization has the potential to greatly advance gut microbiome research and the development of novel disease diagnostics and therapeutics.