The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock.

Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model.

Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO-1, claudin 1, and occludin) and E-cadherin was markedly inhibited by PGR. The expression of P-glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68-positive rate, ß-defensins, and protein expression involved p38 MAPK/NF-κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial-derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans.

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays.

The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo-like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek's intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.

Comparing the permeability of human and porcine small intestinal mucus for particle transport studies.

The gastrointestinal mucus layer represents the last barrier between ingested food or orally administered pharmaceuticals and the mucosal epithelium. This complex gel structure plays an important role in the process of small intestinal absorption. It provides protection against hazardous particles such as bacteria but allows the passage of nutrients and drug molecules towards the intestinal epithelium. In scientific research, mucus from animal sources is usually used to simulate difficult-to-obtain human small intestinal mucus for investigating the intramucus transport of drug delivery systems or food nanoparticles. However, there is a lack of evidence the human mucus can be reliably substituted by animal counterparts for human-relevant transport models. In this report, a procedure for collecting human mucus has been described. More importantly, the permeability characteristics of human and porcine small intestinal mucus secretions to sub-micron sized particles have been compared under simulated intestinal conditions. Negatively charged, 500 nm latex beads were used in multiple-particle tracking experiments to examine the heterogeneity and penetrability of mucus from different sources. Diffusion of the probe particles in adult human ileal mucus and adult pig jejunal and ileal mucus revealed no significant differences in microstructural organisation or microviscosity between the three mucus types (P > 0.05). In contrast to this interspecies similarity, the intraspecies comparison of particle diffusivity in the mucus obtained from adult pigs vs. 2-week old piglets showed better penetrability of the piglet mucus. The mean Stokes-Einstein viscosity of the piglet jejunal mucus was approx. two times lower than the viscosity of the pig jejunal mucus (P < 0.05). All mucus structures were also visualised by scanning electron microscopy. This work validates the use of porcine small intestinal mucus collected from fully-grown pigs for studying colloidal transport of sub-micron sized particles in mucus under conditions mimicking the adult human small intestinal environment.

Short communication: Effect of delaying the first colostrum feeding on small intestinal histomorphology and serum insulin-like growth factor-1 concentrations in neonatal male Holstein calves.

The primary objective of this study was to determine the effect of delaying the first colostrum feeding on small intestinal histomorphology and serum insulin-like growth factor-1 (IGF-1) concentrations, and the secondary objective was to characterize the ultrastructure of the small intestine of neonatal calves at 51 h of life. Twenty-seven male Holstein calves were fed pooled, pasteurized colostrum (7.5% of birth body weight; 62 g of IgG/L) at 45 min (0H, n = 9), 6 h (6H, n = 9), or 12 h (12H, n = 9) after birth. At 12 h after their respective colostrum feeding, calves were fed milk replacer at 2.5% of birth body weight per meal and every 6 h thereafter. Blood samples were collected every 6 h using a jugular catheter and analyzed for serum IGF-1 concentrations using an automated solid-phase chemiluminescent immunoassay. At 51 h of life, calves were euthanized to facilitate collection of the duodenum, proximal and distal jejunum, and ileum. All segments of the small intestine were assessed for histomorphology, whereas scanning electron and transmission electron microscopy analyses were conducted only for the proximal jejunum and ileum. The results revealed that there was no overall effect of colostrum feeding time on serum IGF-1 concentrations; however, serum IGF-1 concentrations were influenced by time. Specifically, concentrations of serum IGF-1 at 48 h were 29% greater than concentrations at 0 h of life (312.8 ± 14.85 vs. 241.9 ± 14.06 ng/mL). Although there was no overall effect of colostrum feeding time on all histomorphological measures assessed, treatment × segment interactions were observed. Villi height was 1.4 times greater in the distal jejunum of 0H calves than in 6H and 12H calves, and 0H calves tended to have 1.2 times greater ileal villus height than 12H calves. In addition, 0H calves had 1.2 and 1.3 times greater ileal crypt depth than 6H and 12H calves, respectively, and 1.3 times greater surface area index than 12H calves in the distal jejunum. Qualitative ultrastructural evaluation of small intestinal enterocytes conducted irrespective of colostrum treatment revealed the presence of large vacuoles of electron-dense material, apical mitochondria, and apical canalicular systems in the jejunum and ileum. These results indicate that the calf intestine at 51 h of life contains unique enterocyte characteristics similar to fetal enterocytes and that delaying colostrum feeding may negatively influence intestinal growth and development.

Paternal weight of ducks may have an influence on offspring' small intestinal function and cecal microorganisms.

BACKGROUND: In animals, many factors affect the small intestinal function and cecal microorganisms, including body weight and genetic background. However, whether paternal weight impacts the small intestinal function and cecal microorganisms remains unknown to date. The current study used Nonghua sheldrake to estimate the effect of paternal weight on the intestine of the offspring by evaluating differences in small intestinal morphology, digestive enzyme activity, and cecal microorganisms between the offspring of male parents with high body weight (group H) and that of male parents with low body weight (group L). RESULTS: The results of the analysis of small intestinal morphology showed that the villus height of the jejunum of group H ducks was higher than that of group L ducks, and the difference was significant for ducks at 10 weeks of age. Moreover, the villus height/crypt depth of the duodenum in group H significantly exceeded that of group L at a duck age of 2 weeks. The amylase activity in the jejunum content of group H exceeded that of group L at 5 and 10 weeks of age. Furthermore, the proportion of the Firmicutes to Bacteroidetes was significantly higher in group H (duck age of 2 weeks). Among the genera with a relative abundance exceeding 1%, the relative abundances of genera Desulfovibrio, Megamonas, Alistipes, Faecalibacterium, and Streptococcus observed in group H were significantly different between group H and group L. CONCLUSIONS: For the first time, this study identifies the effect of paternal weight on offspring small intestinal function and cecal microorganisms. Consequently, this lays a foundation for further research on the relationship between male parents and offspring intestinal function.

A novel histidine-tryptophan-ketoglutarate formulation ameliorates intestinal injury in a cold storage and ex vivo warm oxygenated reperfusion model in rats.

AIM: The present study aims to evaluate protective effects of a novel histidine-tryptophan-ketoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. METHODS: Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4°C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs-Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. RESULTS: The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia-reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. CONCLUSION: HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.

Acute Colchicine Poisoning Causes Endotoxemia via the Destruction of Intestinal Barrier Function: The Curative Effect of Endotoxin Prevention in a Murine Model.

BACKGROUND: Colchicine binds to intracellular tubulin and prevents mitosis. Colchicine is also used as an anti-inflammatory drug. Meanwhile, excess administration of medication or accidental ingestion of colchicine-containing plants can cause acute colchicine poisoning, which initially results in gastrointestinal effects that may be followed by multiorgan dysfunction. However, the mechanism of colchicine poisoning remains unclear, and there are no standard therapeutic strategies. AIMS: We focused on intestinal barrier function and attempted to reveal the underlying mechanism of colchicine poisoning using an animal model. METHODS: Colchicine was orally administered to C57Bl/6 mice. Then, we performed histopathological analysis, serum endotoxin assays, and intestinal permeability testing. Additionally, the LPS-TLR4 signaling inhibitor TAK-242 was intraperitoneally injected after colchicine administration to analyze the therapeutic effect. RESULTS: We observed villus height reduction and increased numbers of apoptotic cells in the gastrointestinal epithelium of colchicine-treated mice. Both intestinal permeability and serum endotoxin levels were higher in colchicine-treated mice than in control mice. Although colchicine-poisoned mice died within 25 h, those that also received TAK-242 treatment survived for more than 48 h. CONCLUSION: Colchicine disrupted intestinal barrier function and caused endotoxin shock. Therapeutic inhibition of LPS-TLR4 signaling might be beneficial for treating acute colchicine poisoning.

Moderate Alcohol Consumption Uniquely Regulates Sodium-Dependent Glucose Co-Transport in Rat Intestinal Epithelial Cells In Vitro and In Vivo.

BACKGROUND: Chronic alcohol use often leads to malnutrition. However, how the intestinal absorption of nutrients such as glucose may be affected during moderate ethanol use has not been investigated. Glucose is absorbed via sodium (Na)-dependent glucose co-transport (SGLT1; SLC5A1) along the brush border membrane (BBM) of intestinal absorptive villus cells. OBJECTIVE: The aim of this study was to investigate how moderate alcohol consumption affects the absorption of glucose via SGLT1. METHODS: Intestinal epithelial cells (IEC-18; rat) were exposed to 8.64 mM ethanol over 1, 3, 6, and 12 h. Rats (16-wk-old, male, Sprague-Dawley) were administered 2 g/kg ethanol over 1, 3, and 6 h. Na-dependent 3H-O-methyl-d-glucose uptake was measured to assess SGLT1 activity. Na-K-ATPase activity was measured as a function of inorganic phosphate release. Protein expression was analyzed by Western blot analysis and immunohistochemical staining. RESULTS: Ethanol significantly decreased Na-dependent glucose absorption in enterocytes in vitro (ethanol treatment: 48.4% of controls at 1 h; P < 0.01) and in vivo (ethanol treatment: 60.0% of controls at 1 h; P < 0.01). Na-K-ATPase activity was significantly inhibited in vitro (ethanol treatment: 36.9% of controls at 1 h; P < 0.01) and in vivo (ethanol treatment: 42.1% of controls at 1 h; P < 0.01). Kinetic studies showed that the mechanism of inhibition of Na-glucose co-transport was secondary to a decrease in the affinity (1/Km) of the co-transporter for glucose both in vitro and in vivo. Western blots and immunohistochemistry further demonstrated unaltered amounts of SGLT1 after ethanol treatment. CONCLUSIONS: Moderate ethanol significantly decreases glucose absorption in IEC-18 cells and in villus cells of Sprague-Dawley rats. The inhibition of SGLT1 is secondary to an altered Na gradient at the cellular level and secondary to diminished affinity of the co-transporter for glucose at the protein level in the BBM. These observations may, at least in part, explain 1 possible mechanism of the onset of malnutrition associated with alcohol consumption.

[STRUCTURAL FORM OF THE FOLLICLE-ASSOCIATED EPITHELIUM OF PEYERS' PATCHES OF THE ALBINO RATS' SMALL INTESTINE].

The paper was aimed at detailed specification of microscopic structure of the intestinal epithelium, associated with lymphoid nodules of the Peyer's patches of the albino rats' small intestine. 30 mature albino male rats weighted 200,0±20,0 g were involved into the study. Slices of the small intestine with Peyer's patches have been analyzed. Serial paraffin sections have been studied using the "Konus' light microscope. Morphometric characteristics of the tissue structures have been obtained using the Sigeta X 1 mm/100 Div.x0.01mm object-micrometer. The findings of the study of serial paraffin sections have discovered a hitherto unknown form of association of the intestinal epithelium with lymphoid nodules, which was called column-inline lymphoepithelial fractals. Between them, wide intercellular fissures were found; they separated both the limbic enterocytes, and columns of lymphocytic elements, located beneath them.

From 2-dimensional to 3-dimensional: Overcoming dilemmas in intestinal mucosal interpretation.

The purpose of this review is to provide a definitive account of small intestinal mucosal structure and interpretation. The coeliac lesion has been well known, but not well described to date and this review aims to identify the interpretative difficulties which have arisen over time with the histological assessment of coeliac disease. In early coeliac interpretation, there were significant inaccuracies, particularly surrounding intraepithelial lymphocyte counts and the degree of villous flattening which occurred in the tissue. Many of these interpretive pitfalls are still encountered today, increasing the potential for diagnostic errors. These difficulties are mostly due to the fact that stained 2-dimensional sections can never truly represent the 3-dimensional framework of the intestinal tissue under investigation. Therefore, this review offers a critical account occasioned by these 2-dimensional interpretative errors and which, in our opinion, should in general be jettisoned. As a result, we leave a framework regarding the true 3-dimensional knowledge of mucosal structure accrued over the 70-year period of study, and one which is available for future reference.

Use of a Novel, Reinforced, Low Immunogenic, Porcine Small Intestine Submucosa Patch to Repair a Supraspinatus Tendon Defect in a Rabbit Model.

BACKGROUND: Repairs of large to massive rotator cuff tears have a high failure rate. We investigated the efficacy of a novel, reinforced, low immunogenic, porcine small intestine submucosa (SIS) patch to repair a supraspinatus tendon defect in a rabbit model. We hypothesized that the histological and biomechanical results of SIS patch repair would be comparable with those of autologous fascia lata (FL) repair. METHODS: The study mainly comprised two parts. First, the characteristics of the SIS patch were evaluated, including its micromorphology, mechanical properties, and immunogenic properties. Second, a supraspinatus tendon defect model was created in 36 rabbits (72 shoulders). The bilateral shoulders were randomly chosen to undergo repair using either a SIS patch (SIS group) or autologous FL (FL group). At 4, 8, and 12 weeks, histological analysis was performed using four shoulders from each group, and biomechanical tests were performed using eight shoulders from each group. RESULTS: The SIS patch was a three-dimensional construct mainly composed of collagen fibers. The mean single and double suture retention loads of the SIS patch were 48.6 ± 5.8 N and 117.9 ± 2.7 N, respectively. The DNA content in the SIS patch was 53.9 ± 10.9 ng/mg dry weight. Both the histological score and ultimate load to failure increased in a time-dependent manner in both groups, with no significant differences between the SIS and FL groups at 12 weeks. CONCLUSION: Repair of a large supraspinatus tendon defect using a reinforced, low immunogenic, SIS patch achieves similar effects as autologous FL in a rabbit model. This novel patch might be useful to be employed as a structural tissue replacement in medical activities.

Gold Nanoparticles Cure Bacterial Infection with Benefit to Intestinal Microflora.

Antibiotics that are most used to cure bacterial infections in the clinic result in the imbalance of intestinal microflora, destroy the intestinal barrier, and induce bacterial resistance. There is an urgent need for antibacterial agent therapy for bacterial infections that does not destroy intestinal microflora. Herein, we applied 4,6-diamino-2-pyrimidinethiol (DAPT)-coated Au nanoparticles (D-Au NPs) for therapy of bacterial infection induced by Escherichia coli ( E. coli) in the gut. We cultured D-Au NPs and E. coli in an anaerobic atmosphere to evaluate their bactericidal effect. We studied the microflora, distribution of Au, and biomarkers in mice after a 28-day oral administration to analyze the effect of Au NPs on mice. D-Au NPs cured bacterial infections more effectively than levofloxacin without harming intestinal microflora. D-Au NPs showed great potential as alternatives to oral antibiotics.

Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine.

CD4 T cells differentiate into RORγt/IL-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats†.

A decellularized uterine scaffold (DUS) prepared from rats permits recellularization and regeneration of uterine tissues when placed onto a partially excised uterus and supports pregnancy in a fashion comparable to the intact uterus. The underlying extracellular matrix (ECM) together with an acellular, perfusable vascular architecture preserved in DUS is thought to be responsible for appropriate regeneration of the uterus. To investigate this concept, we examined the effect of the orientation of the DUS-preserving ECM and the vascular architecture on uterine regeneration through placement of a DUS onto a partially defective uterine area in the reversed orientation such that the luminal face of the DUS was outside and the serosal face was inside. We characterized the tissue structure and function of the regenerated uterus, comparing the outcome to that when the DUS was placed in the correct orientation. Histological analysis revealed that aberrant structures including ectopic location of glands and an abnormal lining of smooth muscle layers were observed significantly more frequently in the reversed group than in the correct group (70% vs. 30%, P < 0.05). Despite the changes in tissue topology, the uteri regenerated with an incorrectly oriented DUS could achieve pregnancy in a way similar to uteri regenerated with a correctly oriented DUS. These results suggest that DUS-driven ECM orientation determines the regenerated uterus structure. Using DUS in the correct orientation is preferable when clinically applied. The disoriented DUS may deteriorate the tissue topology leading to structural disease of the uterus even though the fertility potential is not immediately affected.

Prophylactic Potential of Synbiotic (Lactobacillus casei and Inulin) in Malnourished Murine Giardiasis: an Immunological and Ultrastructural Study.

Giardiasis is a re-emerging infectious disease with outbreaks reported globally specially in children and malnourished individuals leading to malabsorption, growth retardation, and severe diarrhea. Thus, in the present study, prophylactic administration of synbiotic as the functional food was used to assess its antigiardial potential in malnourished murine giardiasis. Interestingly, prior administration of synbiotic (Lactobacillus casei + inulin) even to malnourished-Giardia-infected mice led to increased body mass, small intestine mass, lactobacilli counts, and reduced severity of giardiasis as evident by decreased cyst and trophozoite counts. Synbiotic therapy further boosted the innate and acquired immune response resulting into increase in nitric oxide, antigiardial secretory IgA and IgG antibody levels along with IL-6 and IL-10 cytokines, and decreased levels of inflammatory TNF-α cytokine in both serum and intestinal fluid in malnourished-synbiotic-Giardia-infected mice compared with malnourished-Giardia-infected mice. More specifically, histopathological and scanning electron microscopy analysis of the small intestine also confirmed the modulatory potentials of synbiotic in malnourished-synbiotic-Giardia mice which had less cellular and mucosal damage compared with severely damaged, mummified, and blunted villi in malnourished-Giardia-infected mice. Taken together, this is the first experimental study to report that prior supplementation of synbiotic restored the gut morphology and improved the immune status of the malnourished-Giardia-infected mice, and could be considered as the prophylactic adjunct therapy for malnourished individuals.

Influences of Short-Term Fasting and Carbohydrate Supplementation on Gut Immunity and Mucosal Morphology in Mice.

BACKGROUND: Preoperative carbohydrate (CHO) supplementation has been recommended in enhanced recovery after surgery protocols. However, the effects of CHO supplementation on gut and systemic immunity are not well understood. METHODS: Mice (n = 60) were randomized to 1 of the following 5 groups: control (ad lib feeding), 12-hour fasting without CHO administration (fasting), and 12 hours of fasting with CHO administration at 2, 4, and 8 hours before sacrifice. Then, lymphocytes were isolated from gut-associated lymphoid tissue, that is, Peyer's patches, the intraepithelial space, and the lamina propria of the small intestine. These lymphocyte numbers and phenotypes were evaluated. IgA levels in respiratory and small-intestinal washings were determined by ELISA. Morphology, proliferation, and apoptosis of the intestinal epithelium were also evaluated histologically. RESULTS: Although there were no significant differences in IgA levels among the 5 groups, fasting decreased intraepithelial and lamina propria, but not Peyer's patches lymphocyte numbers. CHO at 2 hours prevented lymphocyte loss in intraepithelial, whereas CHO at 4 hours reversed lamina propria lymphocytes numbers. Percentages of lymphocyte phenotypes were similar in each site among the 5 groups. Fasting caused villous atrophy; however, CHO at 2 hours restored villous structure along with maintenance of epithelial cell proliferation rate. CONCLUSIONS: Only 12 hours of fasting causes marked gut-associated lymphoid tissue cell loss along with gut atrophy. However, CHO at 2 hours preserves gut immunity and morphology not completely but moderately.

Investigation of the effects of naringin on intestinal ischemia reperfusion model at the ultrastructural and biochemical level.

We aimed to evaluate the ultrastructural effect of reversing cellular damage, occurring in rats due to ischemia-reperfusion (I/R) in the intestine, with naringin implementation through biochemical parameters. Rats were divided the sham/control, I/R and the naringin groups (n = 7). For I/R group, 120 min of ischemia and 120 min of reperfusion was applied to the superior mesenteric artery. In the naringin group, after 120 min, 50 mg/kg naringin was implemented, and then 120 min of reperfusion was applied. Morphological evaluation was performed via Chiu score and electron microscopy. The antioxidant parameters were examined. Chiu score in I/R (p < 0.01) and naringin (p < 0.05) groups were higher than the sham/control group. In ultrastructural level some irregularity were observed in I/R group. Although it decreased in the naringin group, the damage was observed to continue. Malondialdehyde (MDA) amount and Superoxide dismutase activity (SOD) in I/R group were higher in comparison to the sham/control group (p < 0.01), while glutathione peroxidase activity (Gpx) was found to be lower (p < 0.01). SOD (p < 0.05) and MDA (p < 0.01) were decreased by naringin group. Gpx was decreased in I/R group compared to sham/control group (p < 0.01) and elevated due to naringin administration (p < 0.05). Catalase activity was observed to decrease in the naringin group compared to control and I/R groups (p < 0.01). It was determined that naringin provided limited healing at the ultrastructural level but also effected recovery within antioxidant parameters.

Microscopic features of small bowel mucosa of patients with Crohn's disease.

BACKGROUND: Double-balloon enteroscopy enables performing numerous small bowel biopsies for pathologic analysis. However, most histopathological characteristics of Crohn's disease are non-specific characteristics. We aimed to explore the small bowel mucosal histopathologic characters of Crohn's disease and identify some disease-specific changes. METHODS: We included 253 patients without tumors and grouped them into Crohn's disease, suspected Crohn's disease, and non-Crohn's disease groups. These patients underwent double-balloon endoscopy examination and small bowel biopsy at Renji Hospital, Shanghai. All histopathological sections were reviewed, and > 20 histopathological parameters were assessed. Immunohistochemistry was conducted when necessary. RESULTS: There were different forms of granulomatous lymphangitis on the small bowel mucosa in Crohn's disease. They showed as various macrophages or epithelioid cells in the lumina of lymphatics or in the center of the villi with or without evident obstruction. These features were only observed in Crohn's disease patients. Furthermore, they were correlated with granuloma and lymphangiectasia. Additionally, 15 other features showed significant differences among the three groups, and Crohn's disease patients showed an average of almost seven histopathological characteristics. CONCLUSIONS: We described the detailed morphologies of granulomatous lymphangitis on the small bowel mucosa and recommend it as a useful histopathological feature for the diagnosis of Crohn's disease. In terms of specificity and sensitivity, it was superior to non-caseating epithelioid granuloma.

An intracellular diamine oxidase triggered hyperpolarized 129Xe magnetic resonance biosensor.

Here, a novel method was developed for suppressing 129Xe signals in cucurbit[6]uril (CB6) until the trigger is activated by a specific enzyme. Due to its noncovalent interactions with amino-groups and CB6, putrescine dihydrochloride (Put) was chosen for blocking interactions between 129Xe and CB6. Upon adding diamine oxidase (DAO), Put was released from CB6 and a 129Xe@CB6 Hyper-CEST signal emerged. This proposed 129Xe biosensor was then tested in small intestinal villus epithelial cells.