Mucosal Damage Research Articles

A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy

Lysophosphatidic acid (LPA) is a bioactive phospholipid mediator that has been found to ameliorate nonsteroidal anti-inflammatory drug (NSAID)-induced gastric injury by acting on lysophosphatidic acid type 2 receptor (LPAR2). In this study, we investigated whether LPAR2 signaling was implicated in the development of NSAID-induced small intestinal injury (enteropathy), another major complication of NSAID use. Wild-type (WT) and Lpar2 deficient (Lpar2−/−) mice were treated with a single, large dose (20 or 30 mg/kg, i.g.) of indomethacin (IND). The mice were euthanized at 6 or 24 h after IND treatment. We showed that IND-induced mucosal enteropathy and neutrophil recruitment occurred much earlier (at 6 h after IND treatment) in Lpar2−/− mice compared to WT mice, but the tissue levels of inflammatory mediators (IL-1β, TNF-α, inducible COX-2, CAMP) remained at much lower levels. Administration of a selective LPAR2 agonist DBIBB (1, 10 mg/kg, i.g., twice at 24 h and 30 min before IND treatment) dose-dependently reduced mucosal injury and neutrophil activation in enteropathy, but it also enhanced IND-induced elevation of several proinflammatory chemokines and cytokines. By assessing caspase-3 activation, we found significantly increased intestinal apoptosis in IND-treated Lpar2−/− mice, but it was attenuated after DBIBB administration, especially in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Finally, we showed that IND treatment reduced the plasma activity and expression of autotaxin (ATX), the main LPA-producing enzyme, and also reduced the intestinal expression of Lpar2 mRNA, which preceded the development of mucosal damage. We conclude that LPAR2 has a dual role in NSAID enteropathy, as it contributes to the maintenance of mucosal integrity after NSAID exposure, but also orchestrates the inflammatory responses associated with ulceration. Our study suggests that IND-induced inhibition of the ATX-LPAR2 axis is an early event in the pathogenesis of enteropathy.

Descriptive Study of Malabsorption Syndrome at the Postgraduate Hospital in Khost, Afghanistan

Background: Malabsorption syndrome is a gastrointestinal condition hindering the efficient absorption of nutrients from food. Multiple factors contribute, primarily linked to mucosal damage within the small intestine, the primary site for nutrient absorption. (1)
 Research Goal: The Frequency and pattern of Malabsorption in khost provincial and specialized Hospital During year1400 hijri shamsi.
 Research rational: There is no medical information about the case in the civil and specialized hospital of khost, also the disease events constitute a large percentage of disease events if diagnosed and treat in time the complication rate will be reduced.
 Methodology: Our study is a descriptive case series conducted in the year 1400. Among the 2,311 patients admitted to Khost Hospital during that time, 80 individuals were diagnosed with Malabsorption Syndrome.
 Result: During the year 1400 ,2311 patients were hospitalized in khost hospital, among these, 30 patients were diagnosed as Malabsorption, most were younger than 20 and more than 60 years, most of them were female, the significant symptoms were chronic diarrhea, weight loss, dyspepsia and dehydration. most admitted patients were referred from center of khost city and major complications were weight loss, malnutrition, and anemia.
 Final result: the incidence of malabsorption contains 1.29% of all other diseases, the incidence is higher in patients who aged less than 20 and more than 60 years, the incidence is higher in female than male, the events are more in the central areas of the khost than the districts., the common symptoms are chronic diarrhea, weight loss, dyspepsia. The weight loss, malnutrition, and anemia were the major complications.

Interleukin-13 Mediates Non-Steroidal Anti-Inflammatory-Drug-Induced Small Intestinal Mucosal Injury with Ulceration.

Non-steroidal anti-inflammatory drugs (NSAIDs), which are antipyretics and analgesics, cause gastrointestinal disorders, such as inflammation and ulcers. To prescribe NSAIDs more safely, it is important to clarify the mechanism of NSAID-induced gastrointestinal mucosal injury. However, there is a paucity of studies on small intestinal mucosal damage by NSAIDs, and it is currently unknown whether inflammation and ulceration also occur in the small intestine, and whether mediators are involved in the mechanism of injury. Therefore, in this study, we created an animal model in which small intestinal mucosal injury was induced using NSAIDs (indomethacin; IDM). Focusing on the dynamics of immune regulatory factors related to the injury, we aimed to elucidate the pathophysiological mechanism involved. We analyzed the pathological changes in the small intestine, the expression of immunoregulatory factors (cytokines), and identified cytokine secretion and expression cells from isolated lamina propria mononuclear cells (LPMCs). Ulcers were formed in the small intestine by administering IDM. Although the mRNA expression levels of IL-1β, IL-6, and TNFα were decreased on day 7 after IDM administration, IL-13 mRNA levels increased from day 3 after IDM administration and remained high even on day 7. The IL-13 mRNA expression and the secretion of IL-13 were increased in small intestinal LPMCs isolated from the IDM-treated group. In addition, we confirmed that IL-13 was expressed in CD4-positive T cells. These results provided new evidence that IL-13 production from CD4-positive T cells in the lamina propria of the small intestine contributes to NSAID-induced mucosal injury.

Pasture-based fattening does not cause severe nonperforating lesions in veal calves of dairy breeds

Abomasal damage is a known health issue in intensive veal production and is associated with improper housing and feeding. Grass-based veal production could be an improvement, as access to pasture allows the expression of natural behaviors, such as species-specific foraging, and thus can contribute to calf welfare. However, data on the abomasal health of grazed calves have not yet been reported. As feed composition can affect the severity of mucosal damage, we compared the abomasa of calves that grazed on 2 swards with different plant composition. From 2018 to 2020, 111 calves of 2 dairy breeds, German Holstein and Jersey, were kept in whole-day strip grazing on these swards. Calves were sampled regularly for intestinal parasites and anthelmintic drug use was recorded. The animals were slaughtered at an age of 32 ± 2 wk (mean ± standard deviation) after individually varying grazing periods of 75 ± 22 d. After slaughter, dissection revealed that 104 of the 111 abomasa displayed low-grade nonperforating lesions, which were primarily located in the pyloric part. A more severe nonperforating lesion was registered in one calf only. In 46 abomasa, we observed diffuse inflammation. This inflammation was characterized by normal mucosal rugae but with slight discoloration that varied in the degree of redness and proliferation of the mucosa. Sward composition and breed did not affect the occurrence of abomasal lesions, but treatment with anthelmintics was negatively correlated with diffuse inflammation. Compared with the abomasa of calves fed under intensive conditions, the abomasa of calves kept on pasture in this study were not as severely altered, but completely unaffected abomasa were rarely observed either. This raises the question to what extent the observed changes in the abomasum were caused by husbandry and feeding conditions or whether they correspond to the normal condition of grazing animals.

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC]= 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Study of gastroesophageal reflux. Interpretation of functional tests in the obese patient

Overweight and obesity are a public health problem and in 1997 obesity was recognized as a global epidemic by the World Health Organization (WHO). Overweight and obesity affect almost 60% of adults and one in three children in Europe according to the most recent WHO report. Objectively, gastroesophageal reflux disease (GERD) is defined as the presence of characteristic esophageal mucosal damage assessed by endoscopy and/or the demonstra-tion of pathological acid exposure by reflux monitoring studies. The prevalence of GERD is increased in obese patientsIn overweight and obese patients, the clinical symptoms of GERD are especially present in the supine position and this correlates with more frequent episodes of nocturnal reflux in the 24-h pH monitoring, there is also an increase in the number of refluxes with content acid. In the population with symptoms, digestive endoscopy detects data of erosive esophagitis in 50% of patients, while 24-h pH-impedanciometry diagnoses 92% of patients with non-erosive reflux disease (NERD)The presence of persistent GERD in the mucosa affects esophageal motility and patients may develop ineffective esophageal motility-type disorders, so we will review the interpre-tation of the functional tests that determine motility, which is esophageal manometry, and those that determine reflux gastroesophageal, acid and non-acid, which is the pH measure-ment with or without 24-h impedanciometry.

Is the increased ozone dosage key factor for its anti-inflammatory effect in an experimental model of mesenteric ischemia?

Ischemia/reperfusion injury of the intestines is a severe surgical condition. This study aimed to reveal ozone therapy effects with relatively increased ozone dosage in a created ischemia/reperfusion injury model. In this study, 24 albino Wistar rats were examined in three groups. Rats in the control group (CG, n=8) underwent only a laparotomy. In the sham group (SG, n=8) and ozone group (OG, n=8), the superior mesenteric artery (SMA) of the rats was occluded for 1 h. After de-occluding the SMA, the abdomen was closed, physiological saline was infused intraperitoneally in the SG, and an increased ozone/oxygen mixture dose (from 0.7 mg/kg to 1 mg/kg) was infused intraperitoneally in the OG. Small intestine samples were obtained at the 24th h for histopathological examination of intestinal mucosal injury and evaluated according to the Chiu score. In addition, Malondialdehyde and Myeloperoxidase levels were evaluated for oxidant levels, whereas, Glutathione (GSH) enzyme activity was measured to evaluate the tissue antioxidant system. Histopathologically, the Chiu score was the lowest in the CG. It was lower in the OG compared to the SG showing the ameliorating effect of ozone on the intestinal mucosa. Chiu score in the OG was higher compared to that in the CG, but not statisti-cally significant. A significantly higher GSH level was observed in the OG compared to the SG, proving antioxidant activity. In this experimental model of ischemia/reperfusion in rats, treatment with an increased ozone level decreased the inflammatory process through antioxidant mechanisms and reduced intestinal mucosal damage. However, the effectiveness of ozone therapy depends on its dosages.

Green carbon dots derived from Atractylodes macrocephala: A potential nanodrug for treating alcoholic gastric ulcer.

Alcoholic gastric ulcer is a common acute gastric injury disease. The drugs currently used in clinical practice not only cannot fundamentally treat gastric injury, but also have serious side effects. There is an urgent demand for the discovery of a mild drug to treat alcoholic gastric ulcers. Herein, the green carbon dots derived from charred Atractylodes macrocephala (CAM-CDs) were acquired and have been proven to be safe and effective in alleviating alcoholic gastric ulcers at an inhibition rate up to 60%. CAM-CDs can markedly attenuate the gastric mucosa damage such as mucosal defect, bleeding and inflammatory cell infiltration by histopathological examination. Serum and tissue inflammatory cytokine measurements, as well as immunohistochemistry results, indicate that its mechanism of gastric mucosal protection may involve the reduction of IL-1β and TNF-α by regulating inflammatory signaling pathway of the NF-κB/NLRP3 axis, as well as elevation of IL-10 levels. CAM-CDs also can reduce oxidative stress markers (MDA), increase PGE2 and mucin secretion (MUC5AC), and it simultaneously exerts slight inhibition of hydrogen potassium ATPase and pepsin activity to protect gastric mucosa, as well as increases the microbial diversity and regulates species composition of gut microbiota in rats with gastric ulcer. Our work provides a new perspective on utilizing carbon-based nanomaterials in the development of new mild drugs.

Investigation of gastrointestinal injury-related biomarkers in dairy cattle with displaced abomasum.

Displaced abomasum (DA) is one of the most important metabolic disorders of dairy cattle. In DA, ischaemic damage may occur as a result of impaired perfusion due to abomasal displacement, which may result in gastrointestinal mucosal damage. Investigation of gastrointestinal tissue damage in cattle with right displacement of the abomasum (RDA) and left displacement of the abomasum (LDA) using intestinal-related biomarkers. Forty-eight DA (24 LDA, 24 RDA) and 15 healthy Holstein dairy cows were enrolled between March 2021 and July 2022. Serum biomarkers including gamma-enteric smooth muscle actin (ACTG-2), liver-fatty acid binding proteins (L-FABP), platelet activating factor (PAF), trefoil factor-3 (TFF-3), leptin, claudin-3 and interleukin-8 (IL-8) concentrations were measured from venous blood samples. L-FABP concentrations in the LDA group and TFF-3 concentrations in the RDA group were lower than in the control group. The leptin concentration of the RDA group was higher than that of the other groups. There was a negative correlation between lactate, leptin and IL-8 concentrations. There was a negative correlation between lactate and TFF-3, whereas leptin and lactate were positively correlated. Leptin was the more reliable biomarker for discriminating between RDA and LDA cases. Changes in serum L-FABP, TFF-3 and leptin concentrations in cattle with DA may reflect acute intestinal injury and the subsequent repair phase. However, these biomarkers had poor diagnostic performance in discriminating between healthy and cattle with DA, while leptin emerged as the most useful marker in differentiating LDA from RDA cases.

The effects of feeding sodium chloride pellets on the gastric mucosa, acid-base, and mineral status in exercising horses.

Electrolyte supplementation may be a risk factor for gastric mucosal lesions, but relevant evidence is limited in horses. Investigate the effects of PO sodium chloride (NaCl) supplementation on the gastric mucosa of exercising horses. We hypothesized that NaCl supplementation would neither cause nor exacerbate existing gastric mucosal damage. Fifteen 3-year-old healthy Warmblood stallions from a stud farm. Placebo-controlled study with a crossover design. Horses were fed either a NaCl pellet at a dosage adequate to replace the electrolyte losses in 10 L sweat or a placebo for 19 days with a washout period of 14 days between treatments. The gastric mucosa was evaluated by gastroscopy before and after treatment. Blood samples were collected for evaluation of acid-base status, packed cell volume (PCV), and total protein, creatinine and blood urea nitrogen concentrations. Urine was collected, and urine specific gravity, electrolyte, creatinine, and urea concentrations were measured. The initial prevalence of gastric mucosal lesions was 85%. Sodium chloride pellets did not adversely affect the gastric mucosa and treatment did not significantly alter the hematologic and serum biochemical variables. Urine creatinine concentrations significantly decreased and urinary sodium concentrations significantly increased after supplementation with NaCl pellets. Water intake did not significantly differ between treatments. Daily NaCl pellet supplementation is a palatable and safe way to replace electrolyte losses from sweating in exercising horses and has no negative effects on the gastric mucosa.

Mucosal damage and γ-H2AX formation in the rat urinary bladder induced by aromatic amines with structures similar to o-toluidine and o-anisidine.

Although aromatic amines are widely used as raw materials for dyes, some, such as o-toluidine and o-anisidine, have shown concerning results regarding carcinogenicity in the urinary bladder. We have recently developed a short-term detection method for bladder carcinogens using immunohistochemistry for γ-H2AX, a DNA damage marker. Here, using this method, we evaluated aromatic amines with structures similar to o-toluidine and o-anisidine for bladder mucosal damage and potential carcinogenicity. In total, 17 aromatic amines were orally administered to male F344 rats for 28days, and histopathological examination and γ-H2AX immunostaining of the urinary bladder were performed. Histopathological analysis revealed that seven aromatic amines, including 4-chloro-o-toluidine (4-CT), o-aminoazotoluene, 2-aminobenzyl alcohol (ABA), o-acetotoluidine (o-AT), 3,3'-dimethoxybenzidine, 4-aminoazobenzene (AAB), and 4,4'-methylenedianiline (MDA), induced various bladder lesions, such as hemorrhage, necrosis, and urothelial hyperplasia. The morphological characteristics of mucosal damage induced by these substances were divided into two major types: those resembling o-toluidine and those resembling o-anisidine. Six of these aromatic amines, excluding MDA, also caused significant increases in γ-H2AX formation in the bladder urothelium. Interestingly, 4-CT did not cause mucosal damage or γ-H2AX formation at the lower dose applied in previous carcinogenicity studies. These results showed for the first time that o-AT and ABA, metabolites of o-toluidine, as well as AAB caused damage to the bladder mucosa and suggested that they may be bladder carcinogens. In addition, 4-CT, which was thought to be a noncarcinogen, was found to exhibit bladder toxicity upon exposure to high doses, indicating that this compound may contribute to bladder carcinogenesis.

Unveiling the potential mechanisms of Amomi fructus against gastric ulcers via integrating network pharmacology and in vivo experiments

Ethnopharmacological relevanceAs a well-known traditional Chinese medicine, Amomi fructus (A. fructus) (Sharen) has been used therapeutically to treat gastrointestinal illnesses, including gastric ulcer (GU). The mechanism underlying this impact is still not fully known, though. Aim of the studyTo investigate the hidden mechanism by which A. fructus influences the pathogenesis of GU, we employed network pharmacology approaches and in vivo validated studies. Materials and methodsMultiple public databases were used to compile information on bioactive compounds, potential targets of A. fructus, and associated genes of GU. Then, the STRING database's protein-protein interaction (PPI) data of the drug-disease overlapping gene targets was obtained, and the core targets for A. fructus against GU were discovered. Additionally, molecular docking was done to examine the binding capabilities of the active substances and core targets. Then, the pathways of A. fructus that target GU were examined using the Annotation, Visualization and Integrated Discovery (DAVID)'s Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway studies. In a mouse model of acute stomach mucosal damage brought on by absolute ethanol, the findings of network pharmacology were finally validated. ResultsIn total, 610 targets derived from the 196 bioactive compounds in A. fructus, were discovered, and along with 115 A. fructus target genes for therapy of GU. Then, ten core targets associated with apoptosis and inflammation were determined based on node degree, and ALB, AKT1, TNF, EGFR, MAPK3, CASP3, MMP9, STAT3, SRC, and HRAS were identified as promising therapeutic targets of A. fructus against GU. The results of molecular docking also revealed that 65 active compounds had strong binding activity with the core targets, with volatile chemicals being the most significant active ingredients. So, for following in vivo tests, A. fructus volatile oils (AVO) were used. The KEGG analysis showed that the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway may be crucial for the therapeutic mechanism of GU. In experiments that were validated in vivo, AVO considerably decreased the ulcer area and enhanced the histological appearance of the gastric tissues. In addition, compared to the model group, up-regulated the expression of IGF-1, p-PI3K, and p-AKT and down-regulated the protein levels of TNF-α and Caspase 3 in the stomach tissues. ConclusionAccording to preliminary findings from this work, A. fructus may influence inflammatory response and apoptosis via regulating the PI3K/AKT signaling pathway and associated gene targets. Importantly, our research might offer a theoretical foundation for future research into the intricate anti-GU mechanism of A. fructus.

Functional Properties of the Water Extract from Eriocheir sinensis (Chinese mitten crab) Via Evaluation of Protective Effects on Reflux Esophagitis Model

Objectives In the study, we investigated the effects of an Eriocheir sinensis water extract on a reflux esophagitis-induced rat model. Background The crab has been used as a traditional medicine and food source in many countries worldwide for a long time, and the crab contains various useful substances such as chitin, protein, calcium carbonate, etc. Materials and Methods All rats were fasted for 24 h and then orally pretreated with saline, Eriocheir sinensis (100 mg/kg), or ranitidine (40 mg/kg). Reflux esophagitis was induced by pylorus and forestomach ligation. Morphological changes in the mucosal damage in the esophagus were analyzed by the ImageJ program. Also, the expression of the inflammatory proteins and cytokine in the esophagus was measured by western blot assay to demonstrate the protective effects of Eriocheir sinensis in reflux esophagitis model. Histological analysis of esophagus was performed by hematoxylin & eosin (H&E) staining. Results In the reflux esophagitis induction group, the esophageal tissue damage caused by the induction of reflux was 60% of the whole. Eriocheir sinensis administration significantly ameliorated esophageal mucosal damage by 40%, also determined by histological evaluation of reflux esophagitis in rats. Eriocheir sinensis was also found to downregulate the expression levels of proteins such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and tight junction protein (claudin-5) compared to the reflux esophagitis induction group. In addition, Eriocheir sinensis markedly attenuated the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the phosphorylation of the inhibitor of NF-κB (IκBα). Conclusion These results indicated that Eriocheir sinensis suppressed the development of esophagitis and modulated inflammation by regulating NF-κB activation. Based on these findings, we concluded that Eriocheir sinensis can protect the esophageal mucosa from reflux esophagitis.

Discovery of Bacteroides uniformis F18-22 as a Safe and Novel Probiotic Bacterium for the Treatment of Ulcerative Colitis from the Healthy Human Colon.

Previous studies have demonstrated that the intestinal abundance of Bacteroides uniformis is significantly higher in healthy controls than that in patients with ulcerative colitis (UC). However, what effect B. uniformis has on the development of UC has not been characterized. Here, we show for the first time that B. uniformis F18-22, an alginate-fermenting bacterium isolated from the healthy human colon, protects against dextran-sulfate-sodium (DSS)-induced UC in mice. Specifically, oral intake of B. uniformis F18-22 alleviated colon contraction, improved intestinal bleeding and attenuated mucosal damage in diseased mice. Additionally, B. uniformis F18-22 improved gut dysbiosis in UC mice by increasing the abundance of anti-inflammatory acetate-producing bacterium Eubacterium siraeum and decreasing the amount of pro-inflammatory pathogenetic bacteria Escherichia-Shigella spp. Moreover, B. uniformis F18-22 was well-tolerated in mice and showed no oral toxicity after repeated daily administration for 28 consecutive days. Taken together, our study illustrates that B. uniformis F18-22 is a safe and novel probiotic bacterium for the treatment of UC from the healthy human colon.

Design and Evaluations of a Nanostructured Lipid Carrier Loaded with Dopamine Hydrochloride for Intranasal Bypass Drug Delivery in Parkinson's disease

Aim- The goal of this study is to optimization and evaluation of dopamine-loaded NLC (NLC-DOPA) for achieve dopamine concentrations into brain for treatment of Parkinson's disease which causes progressive neuronal death. Method- NLC-DOPA prepared by homogenization method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer- 188) as major excipients, optimized by central composite design using design expert-13 software. The optimized formulations were characterized by particle size, zeta potential, entrapment efficiency, SEM, TEM, FTIR, DSC, XRD, stability study and in-vitro drug release. The histopathology of rat brain tissues and goat nasal tissues were performed. The ex-vivo (permeability and nasal ciliotoxicity study) and in vivo pharmacodynamics study were also accomplished to determine its efficacy and potency of NLC. Result- The NLC-DOPA formulations were optimized in particle size and (EE)% with range from 85.53 ± 0.703 to 106.11 ± 0.822 nm and 82.17 ± 0.794 to 95.45 ± 0.891%, respectively. The optimized formulation F11 showing best goodness-fitted model kinetic, followed by Korsmeyer-Peppas equation and zero order kinetic. The SEM and TEM confirmed the spherical and smooth morphology of formulation. FTIR and DSC spectra were given compatibility of compound and XRD diffractograms confirmed the amorphous nature. An ex-vivo study was showed the high permeability coefficient (6.67*10−4 cm/min, which is twice, compare to pure drug) and there was no damage in nasal mucosa, confirmed by the ciliotoxicity study. In-vivo study was shown significant effects of optimized NLC-DOPA on locomotor activity, force-swimming test and neurochemical assessment using rotenone induced Parkinson’s model on Albino wistar rats. Conclusion- NLC-DOPA was prepared and optimized successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson’s disease.

Coptidis Rhizoma processed with Evodia Rutaecarpa improves the effect on ulcerative colitis by increasing intestinal energy metabolites alpha-ketoglutarate and Lactobacillus reuteri

BackgroundEvodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated. PurposeCoptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology. Study DesignA preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays. MethodsMice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and β-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice. ResultsECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/β-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity. ConclusionECR processing improves the therapeutic effects of UC via the α-KG–L. reuteri–epithelial regeneration axis.

Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

Diagnostika heterotopické žaludeční sliznice horního jícnu a její vliv na sliznici hrtanu

Introduction: Heterotopic gastric mucosa of the proximal esophagus (IP – inlet patch) is an islet of gastric mucosa close to the upper esophageal sfincter. Its cells may be able to produce acids and digestive enzymes. Methodology: Prospective study from 2020–2021 follows patients of groups A and B who underwent gastroduodenal endoscopic procedure or direct esophagoscopy in general anesthesia. In group C, patients with confirmed inlet patch underwent ENT videoendoscopic procedure to asses any laryngeal mucosa damage. Results: The prevalence of IP in our group was determined to be 4.87%. We diagnosed 40 IPs out of 821 examinations performed. Group C does not show any signs of laryngeal mucosal damage in patients with inlet patch. Conclusion: The prevalence of IP in the Nový Jičín region was 4.87%. In our study group, we didn’t find any significant laryngeal mucosal damage in patients with IP. t is necessary to think about IP in patients with laryngopharyngeal reflux without the effect of conservative therapy as a possible cause of difficulties. In the treatment of extraoesophageal reflux, which is difficult to influence with conservative therapy, it is advisable to supplement the gastrofibroscopic examination with a focus on the evidence of IP and its biopsy. Keywords: heterotopic gastric mucosa – inlet patch – GERD – extraesophageal reflux – rigid esophagoscopy

A multi-omics study to investigate the progression of the Correa pathway in gastric mucosa in the context of cirrhosis

BackgroundPatients with liver cirrhosis (LC) are prone to gastric mucosa damage. We investigated the alterations of gastric mucosa in LC patients and their possible mechanisms through multi-omics.ResultsWe observed significant gastric mucosa microbial dysbiosis in LC subjects. Gastric mucosal microbiomes of LC patients contained a higher relative abundance of Streptococcus, Neisseria, Prevotella, Veillonella, and Porphyromonas, as well as a decreased abundance in Helicobacter and Achromobacter, than control subjects. The LC patients had higher levels of bile acids (BAs) and long-chain acylcarnitines (long-chain ACs) in serum. The gastric mucosal microbiomes were associated with serum levels of BAs and long-chain ACs. Transcriptome analyses of gastric mucosa revealed an upregulation of endothelial cell specific molecule 1, serpin family E member 1, mucin 2, caudal type homeobox 2, retinol binding protein 2, and defensin alpha 5 in LC group. Besides, the bile secretion signaling pathway was significantly upregulated in the LC group.ConclusionsThe alterations in the gastric mucosal microbiome and transcriptome of LC patients were identified. The impaired energy metabolism in gastric mucosal cells and bile acids might aggravate the inflammation of gastric mucosa and even exacerbate the Correa’s cascade process. The gastric mucosal cells might reduce bile acid toxicity by bile acid efflux and detoxification.Trial registration: ChiCTR2100051070.

COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.