Gastric Stress Research Articles

Troxerutin effect on gastric ulcers induced by ketorolac in rats: Relation with oxidative stress

Gastric ulcers are an essential side effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Free radicals are one of the important mechanisms contributing to the development of gastric ulcers caused by NSAIDs. This prompted us to choose troxerutin, which has antioxidant and anti-inflammatory effects, especially with a lack of studies investigating the preventive effect of troxerutin on gastric ulcers. Twenty-nine rats were divided into five groups: A Vehicle group, a Keto group (30 mg/kg of ketorolac), and two troxerutin groups (150 mg/kg or 200 mg/kg of troxerutin, respectively). A Miso group was used as a reference with (100 μg/kg of misoprostol). Troxerutin and misoprostol were administered orally 1 h before ketorolac. The ulcer index was determined considering the numbers and severity of ulcerations. Gastric tissue inflammation was evaluation microscopically. Both thiobarbituric acid reactive substance levels and catalase activity were measured as markers of oxidative stress in gastric tissue. Our data showed an improvement in ulcer indices with troxerutin and misoprostol compared with ketorolac, with improvement in gastric inflammation observed with misoprostol but not with troxerutin. These results were accompanied by a reduction in gastric oxidative stress induced by ketorolac with both troxerutin and misoprostol. This study highlights, for the first time, the antioxidant effect of troxerutin on gastric ulcers. This effect may contribute to the good prevention of ketorolac-induced gastric ulcers.

A Novel Bifidobacterium longum Subsp. longum T1 Strain from Cow's Milk: Homeostatic and Antibacterial Activity against ESBL-Producing Escherichia coli.

Background/Objectives: The global emergence of antibiotic-resistant zooanthroponotic Escherichia coli strains, producing extended-spectrum beta-lactamases (ESBL-E) and persisting in the intestines of farm animals, has now led to the development of a pandemic of extra-intestinal infectious diseases in humans. The search for innovative probiotic microorganisms that eliminate ESBL-E from the intestines of humans and animals is relevant. Previously, we received three isolates of bifidobacteria: from milk of a calved cow (BLLT1), feces of a newborn calf (BLLT2) and feces of a three-year-old child who received fresh milk from this calved cow (BLLT3). Our goal was to evaluate the genetic identity of BLLT1, BLLT2, BLLT3 isolates using genomic DNA fingerprinting (GDF), to study the tolerance, adhesion, homeostatic and antibacterial activity of BLLT1 against ESBL-E. Methods: We used a complex of microbiological, molecular biological, and immunological methods, including next generation sequencing (NGS). Results: GDF showed that DNA fragments of BLLT2 and BLLT3 isolates were identical in number and size to DNA fragments of BLLT1. These data show for the first time the possibility of natural horizontal transmission of BLLT1 through with the milk of a calved cow into the intestines of a calf and the intestines of a child. BLLT1 was resistant to gastric and intestinal stresses and exhibited high adhesive activity to calf, pig, chicken, and human enterocytes. This indicates the unique ability of BLLT1 to inhabit the intestines of animals and humans. We are the first to show that BLLT1 has antibacterial activity against ESBL-E strains that persist in humans and animals. BLLT1 produced 145 ± 8 mM of acetic acid, which reduced the pH of the nutrient medium from 6.8 to 5.2. This had an antibacterial effect on ESBL-E. The genome of BLLT1 contains ABC-type carbohydrate transporter gene clusters responsible for the synthesis of acetic acid with its antibacterial activity against ESBL-E. BLLT1 inhibited TLR4 mRNA expression induced by ESBL-E in HT-29 enterocytes, and protected the enterocyte monolayers used in this study as a bio-model of the intestinal barrier. BLLT1 increased intestinal alkaline phosphatase (IAP) as one of the main molecular factors providing intestinal homeostasis. Conclusions: BLLT1 shows promise for the creation of innovative functional nutritional products for humans and feed additives for farm animals that will reduce the spread of ESBL-E strains in the food chain.

Exploring the Underlying Mechanisms of Preventive Treatment Related to Dietary Factors for Gastric Diseases.

Gastric diseases have emerged as one of the main chronic diseases in humans, leading to considerable health, social, and economic burdens. As a result, using food or "food and medicinal homologous substances" has become an effective strategy to prevent gastric diseases. Diet may play a crucial role in the prevention and mitigation of gastric diseases, particularly long-term and regular intake of specific dietary components that have a protective effect on the stomach. These key components, extracted from food, include polysaccharides, alkaloids, terpenoids, polyphenols, peptides, probiotics, etc. The related mechanisms involve regulating gastric acid secretion, protecting gastric mucosa, increasing the release of gastric defense factors, decreasing the level of inflammatory factors, inhibiting Helicobacter pylori infection, producing antioxidant effects or reducing oxidative damage, preventing gastric oxidative stress by inhibiting lipid peroxides, activating Nrf2 signaling pathway, and inhibiting NF-κB, TLR4, and NOS/NO signaling pathways.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study

Ethnopharmacological relevanceDioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. Aim of the studyThis study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. Materials and methodsThe active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. ResultsCYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1β. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. ConclusionThis study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

In vitro characterization of lactic acid bacteria from Indian fermented rice for probiotic applications

AimTo investigate probiotic attributes of lactic acid bacteria (LAB) isolated from under-explored Indian fermented rice for potential application in consumer health and functional product development. Methods and resultsThe isolates endured conditions resembling gastric stress, including pH (3), bile salt (4%), NaCl (6%), and phenol (0.6%). The selected isolates were identified as L. fermentum and L. plantarum strains by 16 S rRNA sequencing. In a simulated gastrointestinal tract (GIT), isolate SR1 outperformed other cultures in terms of viability. Auto-aggregation, and mucin adhesion abilities were tested for colonization potential. In which, compared to other isolates, MCR1 showed greater mucin adherence. SR1 and MCR1 showed higher percentages of auto-aggregation than GG. The auto-aggregation ranged from 9% to 88%., the levels significantly increase after 24 h incubation. The lower Salt aggregation Test (SAT) values indicated efficient hydrophobicity necessary for persistence in GIT and competitive inhibition to pathogens. All the isolates displayed considerably higher galactosidase activity than GG, isolate FCR2 expressed the highest, up to 613±0.92 Miller’s unit/ml activity. The probiotic candidates displayed broad spectrum antimicrobial activity against food-spoilage fungi and entero-pathogens. The study of safety aspects such as hemolytic, DNase activity, antibiotic susceptibility confirmed unavailability of any virulent factor. ConclusionThe isolates developed substantial galactosidase activity and significant broad-spectrum antibacterial activity. These characteristics make isolates an effective commercial option for β-galactosidase production in the food sector to create low-lactose or lactose-free products. Overall, the isolates' capacity for survival, colonization, and other useful traits may be of commercial relevance. Additionally, isolates can be researched for the production of antibacterial agents and in vivo studies for development of future functional food products. Moreover, these findings lay a robust groundwork for future exploration in probiotics, functional foods and nutraceuticals, while also shedding light on the mechanisms underlying the health benefits of the specified traditional food source. SignificanceThis investigation uncovered potential probiotic LAB of Indian fermented rice origin. By doing so, it expands our understanding of LAB diversity and presents promising candidates for applications in gut health improvement, functional food development, and exploration of natural antibacterial solutions.

Assessing Metschnikowia pulcherrima as a potential probiotic yeast for animal feed

Abstract In response to escalating antimicrobial resistance fuelled by their extensive use in livestock farming, this study explores alternative strategies in animal health management. We investigated the probiotic potential of Metschnikowia pulcherrima strains 4 × 3, DH5, ICS1 and QRI1 for their suitability in poultry environments. Our research demonstrated that previously discovered antimicrobial M. pulcherrima strains exhibit promising probiotic behaviours, including biofilm production, auto-aggregation, cell surface hydrophobicity, adhesion to Caco-2 cells, antioxidant capacity, and resilience to gastric stresses. Notable findings include DH5 exhibiting the highest biofilm formation, 4 × 3 and DH5 showing rapid auto-aggregation, 4 × 3 and ICS1 displaying high cell surface hydrophobicity, and all strains demonstrating considerable adherence to Caco-2 cells. 4 × 3 also exhibited exceptional bile tolerance, while ICS1 showed robust survival under simulated gastrointestinal conditions. These traits suggest M. pulcherrima’s capacity to colonise the poultry gastrointestinal tract, promote animal health, and support more sustainable livestock practices as a potential alternative to conventional antibiotics.

Weifuchun capsules exhibit therapeutic effects in adjuvant treatment of severe pneumonia complicated with gastric stress ulcer by up-regulating the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 signaling pathway

Weifuchun capsules exhibit therapeutic effects in adjuvant treatment of severe pneumonia complicated with gastric stress ulcer by up-regulating the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 signaling pathway

Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/μm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

Evaluation of viability and survival of free and maltodextrin microencapsulated Bifidobacterium animalis subsp. animalis through spray-drying process

Bifidobacterium animalis subsp. animalis is a microorganism integrated into the human intestinal microbiota and performs a probiotic function through mechanisms that promote the absorption of nutrients, the modulation of the immune system, and the production of lactic acid, among other aspects. Microencapsulation using maltodextrin promotes the protection of microorganisms against physical and chemical factors, improving viability over time. Bifidobacterium animalis subsp. animalis was microencapsulated through spray-drying using maltodextrin. Survival under pH conditions, bile salts, and temperature were evaluated as well as its viability during storage conditions. The viability of the encapsulated agent stored at 25 °C remained high and constant during the first three weeks. The results for free and microencapsulated thermal tolerance showed an important difference among survival percentages of each tested temperature, and microencapsulation showed a protective effect against temperatures like or lower than 55 °C. Regarding pH 2.5 exposure for 3h, there is a survival of 5.38% for free microorganisms in contrast to 11.87% for encapsulated, whereas in a pH 3.5 for 3h, the encapsulated agent showed a survival of 23%. The results obtained from encapsulated cells stressed with a 1g/L concentration of bile salts showed a survival of 19%, while free cells presented a total loss of viability when subjected for 3h at the same concentration. Microencapsulated Bifidobacterium animalis subsp. animalis demonstrated potential for its use incorporated into foods, but it is necessary to improve viability conditions during storage and survival under gastric stress conditions.

Modern possibilities of prevention of gastrointestinal bleeding in patients with gastric and duodenal stress ulcers

The article discusses the prevention of gastrointestinal bleeding in critically ill patients who are hospitalized in intensive care units (ICU). The main factors contributing to the occurrence of GIB in such patients are considered. The leading place among them is occupied by a stay on artificial ventilation of the lungs for > 48 hours and blood coagulopathy. Patients at high risk of developing GIB need prophylactic administration of proton pump inhibitors, H2-blockers, sucralfate, which allows to prevent the occurrence of GIB and improve the prognosis of patients.

Ligilactobacillus salivarius 7247 Strain: Probiotic Properties and Anti-Salmonella Effect with Prebiotics.

The Ligilactobacillus salivarius 7247 (LS7247) strain, originally isolated from a healthy woman's intestines and reproductive system, has been studied for its probiotic potential, particularly against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) as well as its potential use in synbiotics. LS7247 showed high tolerance to gastric and intestinal stress and effectively adhered to human and animal enterocyte monolayers, essential for realizing its probiotic properties. LS7247 showed high anti-Salmonella activity. Additionally, the cell-free culture supernatant (CFS) of LS7247 exhibited anti-Salmonella activity, with a partial reduction upon neutralization with NaOH (p < 0.05), suggesting the presence of anti-Salmonella factors such as lactic acid (LA) and bacteriocins. LS7247 produced a high concentration of LA, reaching 124.0 ± 2.5 mM after 48 h of cultivation. Unique gene clusters in the genome of LS7247 contribute to the production of Enterolysin A and metalloendopeptidase. Notably, LS7247 carries a plasmid with a gene cluster identical to human intestinal strain L. salivarius UCC118, responsible for class IIb bacteriocin synthesis, and a gene cluster identical to porcine strain L. salivarius P1ACE3, responsible for nisin S synthesis. Co-cultivation of LS7247 with SE and ST pathogens reduced their viability by 1.0-1.5 log, attributed to cell wall damage and ATP leakage caused by the CFS. For the first time, the CFS of LS7247 has been shown to inhibit adhesion of SE and ST to human and animal enterocytes (p < 0.01). The combination of Actigen prebiotic and the CFS of LS7247 demonstrated a significant combined effect in inhibiting the adhesion of SE and ST to human and animal enterocytes (p < 0.001). These findings highlight the potential of using the LS7247 as a preventive strategy and employing probiotics and synbiotics to combat the prevalence of salmonellosis in animals and humans caused by multidrug resistant (MDR) strains of SE and ST pathogens.

A Rational Approach to Predicting Immediate Release Formulation Behavior in Multiple Gastric Motility Patterns: A Combination of a Biorelevant Apparatus, Design of Experiments, and Machine Learning.

Gastric mechanical stress often impacts drug dissolution from solid oral dosage forms, but in vitro experiments cannot recreate the substantial variability of gastric motility in a reasonable time. This study, for the first time, combines a novel dissolution apparatus with the design of experiments (DoE) and machine learning (ML) to overcome this obstacle. The workflow involves the testing of soft gelatin capsules in a set of fasted-state biorelevant dissolution experiments created with DoE. The dissolution results are used by an ML algorithm to build the classification model of the capsule's opening in response to intragastric stress (IS) within the physiological space of timing and magnitude. Next, a random forest algorithm is used to model the further drug dissolution. The predictive power of the two ML models is verified with independent dissolution tests, and they outperform a polynomial-based DoE model. Moreover, the developed tool reasonably simulates over 50 dissolution profiles under varying IS conditions. Hence, we prove that our method can be utilized for the simulation of dissolution profiles related to the multiplicity of individual gastric motility patterns. In perspective, the developed workflow can improve virtual bioequivalence trials and the patient-centric development of immediate-release oral dosage forms.

Evaluation of Gastroprotective Effect of Betalain-Rich Ethanol Extract from Opuntia stricta var. Dillenii Employing an In Vivo Rat Model

The goal of this study is to investigate the antiulcer effects of betalain-rich extract (BRE). Gastric ulcer was induced by the administration of ethanol by gastric gavage route. This study showed that the supplementation of the BRE from pulp and peel at 800 mg/kg to rats with ethanol-induced gastric-ulcer significantly reduced the volume of gastric secretion (VGS) by 35% ( p = 0.001 ) and 34% ( p = 0.0009 ), the ulcer index (UI) by 41% ( p = 0.001 ) and 68% ( p = 0.0008 ), and the curative radio (CR) by 41% and 68%, respectively, as compared to untreated ethanol-induced gastric ulcer. In addition, the administration of pulp and peel BRE to rats at dose 800 mg/kg significantly attenuates the variation in pH of gastric juice ( p = 0.008 and p = 0.001 ) and its total acidity (TA) ( p = 0.001 and p = 0.001 ). The antiulcer effect of BRE was confirmed by macroscopic and histological evaluation. Furthermore, pulp and peel BRE attenuated gastric ulcer-induced stress oxidants in rats’ stomachs showed by a significant decrease in the lipid peroxidation rate ( p = 0.007 and p = 0.001 ) and LDH activity ( p = 0.01 and p = 0.008 ) and a potential increase in the superoxide dismutase (SOD) ( p = 0.01 and p = 0.008 ), glutathione peroxidase (GPX) ( p = 0.006 and p = 0.001 ), and catalase (CAT) ( p = 0.001 and p = 0.0009 ). Conclusion. Therefore, this study shows for the first time that BRE, a natural colorant from O. stricta, is efficient in the amelioration of ulcer and stomach inflammation.

Application of a novel PhysioCell apparatus for biopredictive dissolution tests of oral immediate release formulations – A case study workflow for in vitro-in vivo predictions

Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tablets: the originator (Brintellix) and generic product candidates (VORTIO). The dissolved drug was monitored in the gastric (StressCell) and intestinal (Collection Vessel) compartments that contained biorelevant media. Simulated intermittent gastric stress at 15 min and “housekeeping wave” at 30 min increased the dissolution of Brintellix formulations only. A mechanistic model that best described the observations involved the first-order tablet disintegration with a stress-induced enhancement for Brintellix, dissolution of solid particles in the StressCell, and drug transfer to the Collection Vessel. Then, a semi-mechanistic pharmacokinetic model with dissolution parameters as inputs simulated vortioxetine plasma concentrations in healthy volunteers after single and multiple dosing of Brintellix. Despite different dissolution characteristics, VORTIO provided similar concentration profiles to the originator. In conclusion, PhysioCell dissolution tests, combined with semi-mechanistic IVIVP, can be successfully used to develop IR dosage forms exhibiting gastric stress-related effects.

Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility.

Perinatal high-fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction, in vivo recordings of gastric tone, motility and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN-DMV inputs and dysregulates vagal brain-gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF -DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress. KEY POINTS: Maternal high-fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring. The present study demonstrates that perinatal high-fat diet exposure downregulates hypothalamic-vagal oxytocin (OXT) inputs but upregulates hypothalamic-vagal corticotropin releasing factor (CRF) inputs. Both in vitro and in vivo studies demonstrated that, following perinatal high-fat diet, CRF receptors were tonically active at NTS-DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT. The current study suggests that perinatal high-fat diet exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress.

Characterization of the heteropolysaccharides produced by Liquorilactobacillus sicerae CUPV261 and Secundilactobacillus collinoides CUPV237 isolated from cider

Some lactic acid bacteria (LAB) strains isolated from alcoholic beverages are able to produce exopolysaccharides (EPS). The present work focuses on the physico-chemical characterization of the heteropolysaccharides (HePS) produced by Liquorilactobacillus sicerae CUPV261T (formerly known as Lactobacillus sicerae) and Secundilactobacillus collinoides CUPV237 (formerly known as Lactobacillus collinoides) strains isolated from cider. Genome sequencing and assembly enabled the identification of at least four putative HePS gene clusters in each strain, which correlated with the ability of both strains to secrete EPS. The crude EPS preparation from CUPV261T contained glucose, galactose and rhamnose, and that of CUPV237 was composed of glucose, galactose and N-acetylglucosamine. Both EPS were mixtures of HePS of different composition, with two major soluble components of average molecular weights (Mw) in the range of 106 and 104 g.mol−1. These HePS were resistant to gastric stress conditions in an in vitro model, and they significantly reduced zebrafish larvae mortality in an in vivo model of inflammatory bowel disease.

17β-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic Female Mice.

Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed predominantly in women. It is characterized by abnormal gastric emptying (GE) without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It plays a critical role in gastrointestinal (GI) motility and stomach emptying. Here, we wanted to demonstrate the protective effects of supplemental 17β-estradiol (E2) on NO-mediated gastric function. We showed E2 supplementation to alleviate oxidative and inflammatory stress in streptozotocin (STZ)-induced diabetic female mice. Our findings suggest that daily administration of E2 at therapeutic doses is beneficial for metabolic homeostasis. This restoration occurs via regulating and modulating the expression/function of glycogen synthase kinase-3β (GSK-3β), nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), Phase II enzymes, MAPK- and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)-mediated inflammatory cytokines (IL-1β, IL-6, TNFα, IGF-1), and gastric apoptotic regulators. We also showed E2 supplementation to elevate GCH-1 protein levels in female diabetic mice. Since GCH-1 facilitates the production of tetrahydrobiopterin (BH4, cofactor for nNOS), an increase in GCH-1 protein levels in diabetic mice may improve their GE and nitrergic function. Our findings provide new insights into the impact of estrogen on gastric oxidative stress and intracellular inflammatory cascades in the context of Gp.

Sheep Milk Symbiotic Ice Cream: Effect of Inulin and Apple Fiber on the Survival of Five Probiotic Bacterial Strains during Simulated In Vitro Digestion Conditions.

We conducted a study to determine the survival of bacterial cells under in vitro digestion. For this purpose, ice cream mixes were prepared: control, with 4% inulin, 2.5% inulin and 1.5% apple fiber and 4% apple fiber. Each inoculum (pH = 4.60 ± 0.05), containing 9 log cfu g-1 bacteria, at 5% (w/w) was added to the ice cream mixes (Lacticaseibacilluscasei 431, Lactobacillus acidophilus LA-5, Lacticaseibacillus paracasei L-26, Lacticaseibacillusrhamnosus, Bifidobacterium animalis ssp. lactis BB-12) and fermentation was carried out to pH 4.60 ± 0.05. The in vitro digestion method simulated the stages of digestion that occur in the mouth, stomach and small intestine under optimal controlled conditions (pH value, time and temperature). At each stage of digestion, the survival rate of probiotic bacteria was determined using the plate-deep method. As expected, in the oral stage, there was no significant reduction in the viability of the probiotic bacteria in any ice cream group compared to their content before digestion. In the stomach stage, Bifidobacterium animalis ssp. lactis BB-12 strain had the highest viable counts (8.48 log cfu g-1) among the control samples. Furthermore, a 4% addition of inulin to ice cream with Bifidobacterium BB-12 increased gastric juice tolerance and limited strain reduction by only 16.7% compared to the number of bacterial cells before digestion. Regarding ice cream samples with Bifidobacterium BB-12, replacing part of the inulin with apple fiber resulted in increased survival at the stomach stage and a low reduction in the bacterial population of only 15.6% compared to samples before digestion. At the stomach stage, the positive effect of the addition of inulin and apple fiber was also demonstrated for ice cream samples with Lacticaseibacilluscasei 431 (9.47 log cfu g-1), Lactobacillus acidophilus LA-5 (8.06 log cfu g-1) and Lacticaseibacillus paracasei L-26 (5.79 log cfu g-1). This study showed the highest sensitivity to simulated gastric stress for ice cream samples with Lacticaseibacillusrhamnosus (4.54 log cfu g-1). Our study confirmed that the 4% addition of inulin to ice cream increases the survival rate of L. casei and Bifidobacterium BB-12 in simulated intestinal juice with bile by 0.87 and 2.26 log cfu g-1, respectively. The highest viable count in the small intestine stage was observed in ice cream with L. acidophilus. The addition of inulin increased the survival of L. rhamnosus by 10.8% and Bifidobacterium BB-12 by about 22% under conditions of simulated in vitro digestion compared to their control samples. The survival rates of L. casei and L. paracasei were also highly affected by the 4% addition of apple fiber, where the increase under gastrointestinal passage conditions was determined to range from 7.86-11.26% compared to their control counterparts. In comparison, the lowest survival rate was found in the control ice cream with L. rhamnosus (47.40%). In our study at the intestinal stage, only five ice cream groups: a sample with 4% inulin and L. acidophilus, a control sample with Bifidobacterium BB12, a sample with 2.5% inulin and 1.5% apple fiber with Bifidobacterium BB12, a control sample with L. rhamnosus, a sample with 4% fiber and L. rhamnosus reported bacterial cell counts below 6 log cfu g-1 but higher than 5 log cfu g-1. However, in the remaining ice cream groups, viable counts of bacterial cells ranged from 6.11 to 8.88 log cfu g-1, ensuring a therapeutic effect. Studies have clearly indicated that sheep milk ice cream could provide a suitable matrix for the delivery of probiotics and prebiotics and contribute to intestinal homeostasis. The obtained results have an applicative character and may play an essential role in developing new functional sheep milk ice cream.

S710 Hyperthyroid State Is Associated with Reduced Mortality in Patients Admitted for Nonvariceal Upper Gastrointestinal Bleeding

Introduction: Through an uncertain mechanism, previous animal models proved that thyroid hormones act on mucosal lesions and reduce the formation of gastric stress ulcers. In this study, authors aim to investigate the influence of hyperthyroid state on outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB). Up to our knowledge, such association have never been studied in literature before. Methods: This is a retrospective cohort examining data from the National Inpatient Sample (NIS) Database of the years 2016 to 2019. Using ICD-10 codes, authors identified hyperthyroid and non-hyperthyroid patients who were principally hospitalized for NVUGIB. Univariate and Multivariate logistic regression analysis was performed to determine the risk of mortality and in-hospital complications. Baseline patients and facilities characteristics were incorporated into the analysis. Data was considered statistically significant with p-value < 0.05. Results: A total of 1,638,754 patients were identified with a principal diagnosis of non-variceal UGIB, among those 7,205 (0.43%) had a history of hyperthyroidism. Study groups baseline comorbidities are illustrated in Figure. After running a multivariate logistic analysis for inpatient mortality, patients with non-variceal UGIB and hyperthyroidism had a 38% reduction in risk of mortality (OR 0.62, 95% CI 0.40 – 0.97, P= 0.039) compared to non-hyperthyroid subjects. In term of secondary outcomes, both groups had no difference in risk of sepsis (OR 0.74, 95% CI 0.50 – 1.09, P= 0.135), hypovolemic shock (OR 1.03, 95% CI 0.74 – 1.43, p=0.853), acute kidney injury (OR 1.06, 95% CI 0.92 – 1.21, p=0.394), acute respiratory failure (OR 0.73, 95% CI 0.54 – 1.00, p=0.050), acute coronary syndrome (OR 1.27, 95% CI 0.95 – 1.71, p=0.097) and In-hospital cardiac arrest (OR 0.62, 95% CI 0.17 – 2.17, p=0.457). Length of stay (aMD 0.33 days, 95% CI -0.09– 0.77, p=0.124) and charges of care (aMD 6146$, 95% CI -852.3– 13145, p=0.085) were not affected by hyperthyroid state as well. Conclusion: Interestingly, our analysis concludes that hyperthyroid state can influence the mortality of patient with non-variceal UGIB. This beneficial effect is likely related to the modulatory effect of thyroid hormones on the responsiveness of the gastrointestinal mucosa to stress. Further studies are needed to investigate and confirm the clinical impact of thyroid state on the outcomes of patients with gastrointestinal bleeding.Figure 1.: Baseline comorbidities of NVUGIB patients stratified by past history of Hyperthyroidism.

6′-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway

As a common disease of the digestive system, chronic gastritis is inflammation of the gastric mucosa caused by various factors. Helicobacter pylori (H. pylori) is one of the main causes of chronic gastritis, which can lead to gastric mucosal damage and gland atrophy, thereby promoting gastrocarcinogenesis. Oxidative stress and the inflammatory response are important mechanisms of H. pylori-induced gastritis. 6′-O-Galloylpaeoniflorin (GPF) is a substance isolated from peony root with antioxidant and anti-inflammatory activities. However, its role and mechanism in the pathogenesis of H. pylori-induced chronic gastritis remain unclear. This study explored the effects of GPF on H. pylori-induced gastric mucosal oxidative stress and inflammation using flow cytometry, western blotting, real-time quantitative PCR, and immunohistochemistry. We found that H. pylori infection increased oxidative stress and expression of inflammatory cytokines in vitro and in vivo and that these outcomes were inhibited by GPF. Furthermore, GPF activated nuclear factor erythroid-related factor-2 (Nrf2) and its downstream target genes in H. pylori-infected GES-1 cells and mice. The anti-inflammatory and antioxidant effects of GPF on H. pylori-infected cells were attenuated by an Nrf2 inhibitor. Taken together, these data suggest that GPF reduces H. pylori-induced gastric mucosa injury by activating Nrf2 signaling and that GPF is a potential candidate for the treatment of H. pylori-associated gastritis.