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INTRODUCTION AND AIM Helicobacter pylori (H. pylori) is known to be capable of causing chronic inflammation of the gastric mucosa that slowly progresses through the premalignant stages, reaching localized gastric adenocarcinoma (GAC). Its outcome is closely related to the stage at which diagnosis is made. The aim of the present study was to determine cost-benefit by comparing esophagogastroduodenoscopy, serum pepsinogen detection, and no screening at all. MATERIAL AND METHODS Utilizing Markov chains and Monte Carlo simulation, the costs and effects of various detection modalities were simulated to analyze the cost-benefit of each strategy. For our population, we used the published data of patients with gastric cancer, applicable to the Mexican population. RESULTS The results were reported as incremental cost-effectiveness ratios. The best strategy was serum pepsinogen determination, followed by the strategy of endoscopic examination with continued monitoring every 3 years. CONCLUSIONS The performance of serum pepsinogen serology and directed endoscopic examination (and continued monitoring, if necessary) for GAC screening could be a cost-effective intervention in Mexico, despite the low-to-moderate general prevalence of the disease.

Background: Despite the fact that Helicobacter spp. has been detected in equine gastric mucosa, no evidence exists about this infection in Colombian horses affected by equine ulcerative gastric syndrome (EGUS), nor in dental tartar. Objective: To detect Helicobacter spp. DNA in equine gastric mucosa and dental tartar and determine the relationship between the presence of Helicobacter spp. and gastric lesions. Methods: Samples of glandular gastric mucosa and dental tartar were collected from 30 equine slaughterhouses. Macroscopic lesions of the stomachs were classified and the total DNA in all samples was extracted using a commercial extraction kit. A final-point PCR was performed using primers for amplification of a segment of 251 bp of the gene encoding the 16s rRNA region; the amplified fragments were subjected to a second PCR to determine the presence of H. pylori, the VacA gene was typified. The resulting amplicons were sequenced. Results: It was possible to amplify 16s rRNA in several samples but there was no amplification of VacA. Fragments of the sequences were compatible with H. heilmannii. The 23.3 and 10% of gastric and tartar samples were positive for 16s rRNA of Helicobacter spp., respectively. Conclusion: Although genetic material of Helicobacter spp. was found in some animals, there was no relationship with gastric lesions. It is possible that helicobacteriosis has no bearing in EGUS etiology.

Microgravity is an ecological factor that affects the environment of the body. In this study, quantitative isobaric labeling (tandem mass tag) method was used to study the changes in human gastric mucosal cells under simulated microgravity for the first time. Comparative proteomic analysis identified 394 (202 upregulated and 192 downregulated) and 542 (286 upregulated and 256 downregulated) proteins differentially regulated by simulated microgravity after 3 and 7 days, respectively. Then the identified proteins were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for further exploration. The results of the analysis showed that the ribosomes of gastric mucosal cells were significantly impacted after exposure to simulated microgravity for 3 days, and the cells appeared to be in a state of stress and inflammation. Exposure to simulated microgravity for 7 days significantly affected the mitochondria of the cells, oxidative stress became more evident, while inflammation and weakened connections were observed in the cells. The results of this study highlighted the temporal response trend of gastric mucosal cells to the stressor of microgravity at the two time points of 3 and 7 days. These findings will provide insights into the development of methods to protect the gastric mucosa during space flight.

The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications.

Eradication of Helicobacter pylori is the first-line treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphomas; however, lesions may persist in 20% of patients after initial treatment, thereby necessitating the use of an additional therapeutic approach. Other treatment options include radiation therapy, chemotherapy, endoscopic resection, rituximab therapy, or watchful waiting. We present a case of localized gastric MALT lymphoma that did not respond to H. pylori eradication therapy. The patient waited for 12 months but the tumor showed no signs of regression endoscopically. Histologic examination revealed residual MALT lymphoma. The tumor was then successfully treated using endoscopic submucosal dissection and the patient remained disease-free for 4 years. To our knowledge, this is the first case in which a gastric MALT lymphoma was treated with endoscopic submucosal dissection. In conclusion, endoscopic resection may be recommended as second-line therapy for properly selected patients with gastric MALT lymphoma as it is effective and minimally invasive.

MSI-78A (Pexiganan A) is one of the few antimicrobial peptides (AMPs) able to kill Helicobacter pylori, a pathogenic bacterium that colonizes the gastric mucosa of half of the world's population. Antibiotics fail in 20–40% of H. pylori-infected patients, reinforcing the need for alternative treatments. Herein, a bioengineered approach was developed. MSI-78A with a C-terminal cysteine was grafted onto chitosan microspheres (AMP-ChMic) by thiol-maleimide (Michael-addition) chemistry using a long heterobifunctional spacer (NHS-PEG113-MAL). Microspheres with ∼4 µm diameter (near H. pylori length) and stable at low pH were produced by spray drying using a chitosan solution with an incomplete genipin crosslinking. A 3 × 10−5 µg AMP/microsphere grafting was estimated/confirmed by UV/Vis and FTIR spectroscopies. AMP-ChMic were bactericidal against H. pylori J99 (highly pathogenic human strain) at lower concentrations than the free peptide (∼277 µg grafted MSI-78A-SH/mL vs 512 µg free MSI-78A-SH/mL), even after pre-incubation in simulated gastric conditions with pepsin. AMP-ChMic killed H. pylori by membrane destabilization and cytoplasm release in a ratio of ∼10 bacteria/microsphere. This can be attributed to H. pylori attraction to chitosan, facilitating the interaction of grafted AMP with bacterium membrane. Overall, it was demonstrated that the peptide-microsphere conjugation chemistry did not compromise the MSI-78A antimicrobial activity, instead it boosted its bactericidal performance against H. pylori. Statement of significance Half of the world's population is infected with Helicobacter pylori, a gastric bacterium that is responsible for 90% of non-cardia gastric cancers. Therefore, H. pylori eradication is now advocated in all infected individuals. However, available antibiotic therapies fail in up to 40% patients. Antimicrobial peptides (AMPs) are appealing alternatives to antibiotics, but their high susceptibility in vivo limits their clinical translation. AMP immobilization onto biomaterials surface will overcome this problem. Herein, we demonstrate that immobilization of MSI-78A (one of the few AMPs with activity against H. pylori) onto chitosan microspheres (AMP-ChMic) enhances its anti-H. pylori activity even at acidic pH (gastric settings). These results highlight the strong potential of AMP-ChMic as an antibiotic alternative for H. pylori eradication.

Introduction Currently, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can be induced to differentiate at the cellular level but not to form mature tissues or organs suitable for transplantation. ESCs/iPSCs form immature teratomas after injection into immunodeficient mice. In humans, immature teratomas often transform into fully differentiated mature teratomas after administration of anticancer agents. Methods We first investigated the ability of cisplatin to induce changes in mouse ESCs/iPSCs in vitro. Next, we designed experiments to analyze ESC/iPSC-derived immature teratoma tissue in vivo after treatment of cisplatin. Groups of six mice carrying ESC- or iPSC-derived teratomas were given either low or high dose intraperitoneal injection of cisplatin, while the control group received saline for 4 weeks. Results Treatment of ESC/iPSC cultures with cisplatin for 3 days caused a dose-related decrease in cell numbers without inducing any morphological changes to the cells. ESC/iPSC-derived teratomas showed lower growth rates with a significantly higher mature components ratio in a concentration dependent manner after cisplatin treatment (P, Highlights • Transformation of immature to mature teratoma after chemotherapy was verified. • Mice bearing ESC/iPSC-derived immature teratomas were used. • Mice were treated with intraperitoneal injection of cisplatin for 4 weeks. • Newly differentiated structures were found only in the tumors of treated mice. • Cisplatin can induce differentiation in ESC/iPSC-derived immature teratomas.

We aimed to explore the correlation between P27 expression and Helicobacter pylori (H. pylori) infection in gastric cancer, so as to provide evidence for understanding the pathogenesis of gastric cancer caused by H. pylori infection. A total of 82 samples of gastric cancer tissues and 56 samples of tumor-adjacent normal tissues collected from the gastrectomy were enrolled in this study. Then, 14C-urease breathing test was carried out to evaluate the infection of H. pylori in gastric cancer tissues, the expression of P27 in the tissue samples was detected by the immunohistochemistry staining, and the correlation between the H. pylori infection and P27 expression in gastric cancer was analyzed. Of 82 gastric cancer patients, there were 53 patients with H. pylori infection (64.63%). Among the patients with highly or moderately differentiated gastric cancer, the expression of P27 was much higher than that of patients with poorly differentiated gastric cancer (p 0.01). Besides, comparison of the P27 expression between males and females, among different age groups, tumor sizes, TNM stages, tumor infiltration degrees, or lymph node metastasis, showed no significant differences (p 0.05). Analysis of the correlation revealed that P27 expression was negatively correlated with the infection of H. pylori (p 0.01). Multifactorial logistics regression analysis indicated that tumor differentiation was a risk factor of P27-positive expression in gastric cancer tissues (p 0.01). In addition, P27 expression in the gastric cancer tissues was lower than that in the tumor-adjacent normal tissues (p 0.01). In gastric cancer patients, expression of P27 is correlated with H. pylori infection which, via downregulating P27, can cause the cancerization of gastric mucosa, and P27, for its role in the development and progression of gastric cancer, is a potential auxiliary indicator for clinical diagnosis whether gastric cancer is complicated with H. pylori infection. So, P27 is a key indicator for diagnosis, treatment, and prognostic evaluation of disease in the advanced stage.

Objectives The Kyoto classification of gastritis was established for diagnosing Helicobacter pylori (H. pylori) infection via endoscopic findings. We investigated the role of the Kyoto classification of gastritis in the diagnosis of H. pylori infection and histological gastritis in Japanese individuals. Moreover, the histological findings of gastritis in H. pylori infection were examined based on age and sex differences. Methods We selected 561 patients aged 20-79 years who underwent gastroduodenal endoscopy at our hospital between 2010 and 2018. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic findings were based on the Kyoto classification of gastritis, and histological findings were based on the updated Sydney System. Results Endoscopic findings based on the Kyoto classification of gastritis (H. pylori positive, 303 patients; H. pylori negative, 258 patients, based on endoscopic findings) had 98.7% sensitivity and 98.4% specificity for histological gastritis. In addition, endoscopic findings in the three age groups (20-39, 40-59, and 60-79 years) had high sensitivity and specificity. Atrophy and intestinal metaplasia were found only in the H. pylori-positive group and progressed with age. Histological inflammation of pyloric mucosa in the younger age group of H. pylori-positive patients was significantly higher than that in the elderly group. Significant inflammation was observed in young women. Conclusions The Kyoto classification of gastritis can not only diagnose H. pylori infection but also detect histological gastritis. Histological gastritis has varying characteristics of inflammation, atrophy, and intestinal metaplasia, depending on age and sex.

PURPOSE: Gastric cancers are classified as diffuse-type (DTGC) or intestinal-type (ITGC). DTGCs have distinct clinical and histopathologic features, and carry a worse overall prognosis compared to ITGCs. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known precursors to ITGC. It is unknown if AG and IM increase risk for DTGC. METHODS: We performed a systematic review to identify studies reporting on the association of AG/IM and DTGC. We extracted the odds ratio (OR) of the association from studies, and performed pool analysis. Subgroup analysis was performed on studies reporting histologic severity (using operative link systems) to assess if histologic severity of AG/IM was associated with higher risk. RESULTS: We identified six case-control and eight cohort studies for inclusion. Both AG (pooled OR=1.9, 95% CI 1.5 to 2.4, p

The aim of the present study was to investigate the ability of fish collagen peptides (FCP) from the skin of great hammerhead shark (Sphyrna mokarran) to avert the occurrence of gastric ulcer in experimental rats. FCP treatment prevented the formation of ulcerative lesions on gastric tissues with 86% of inhibition. The histopathology analysis of gastric tissue revealed that the FCP intake prevented the occurrence of hemorrhage and erosion in gastric tissue with formation of mild edema and necrosis, as well as normalized the pH and volume of gastric juice. It also downregulated the expression of pro-inflammatory marker interferon-ɤ (IFN-ɤ) and upregulated the anti-inflammatory marker interleukin-4 (IL-4) in gastric tissue. FCP is capable to modulate the oxidative stress by enhancing the activity of antioxidant defense enzymes superoxide dismutase (SOD) and catalase and by lowering the levels of membrane lipid peroxidation.

Introduction. The aim of the study was to detect the dependence of the composition of the parietal microflora of the colon on the activity of Helicobacter pylori-associated chronic gastritis and the degree of Helicobacter pylori contamination of the gastric mucosa. Materials and methods. The study was carried out on 50 patients aged 24 to 72 years, who were diagnosed with HP-associated chronic gastritis in the phase of exacerbation based on the results of FEGDS and histological examination of biopsies of the mucous membrane of the antrum of the stomach in combination with a rapid urease test. A series of dilutions 10¹-10⁹ was prepared from a homogenized biopsy specimen of the mucous membrane of the sigmoid colon in 0.1 ml of isotonic sodium chloride solution, and 0.1 ml of a solution of the corresponding dilution was inoculated onto the surface of the nutrient medium. The study of mucosal microflora was carried out by means of bacteriological examination of biopsies of the mucous membrane of the sigmoid and cecum. The degree of H. pylori contamination of the gastric mucosa was assessed in the course of histological examination by a semi-quantitative method: low degree of contamination — up to 20 microbial bodies, average — 20-50 microbial bodies, strong — over 50 microbial bodies in the field of view. Results. The study demonstrated that the indicators of the average concentrations of bifidobacteria, lactobacilli and typical strains of E. coli progressively decreased with the transition to a higher degree of HP infection. This tendency was maximum in relation to bifidobacteria — 6.1-1.57-1.09 x 10⁸ CFU/g, with a difference between the maximum (I degree) and minimum (III degree) 5.59 times. A similar relationship, but much less pronounced, was observed for Lactobacterium spp. and E. coli. As the severity of HP infiltration of the gastric mucosa increases, there is a decrease in the concentration of the above microorganisms in the parietal mucin - the correlation coefficient is r = -0.74. Discussion. Since the mucous microflora is more stable and functionally significant than the cavity microflora, the data obtained allow us to consider Helicobacter pylori as an etiological factor of colonic dysbiosis. Conclusion. The probability of excessive growth of conditionally pathogenic fraction of intestinal parietal microflora has a direct dependence on the severity of Helicobacter pylori infestation, being maximum at degree III contamination. Content of bifidobacteria, lactobacilli and typical E. coli strains in the intestinal biotope of the large intestine is inversely related to the degree of histological activity of HP-associated gastritis.

We examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection inC57Bl/6zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = − 0.51, CI − 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p

Background The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death –ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. Methods A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors’ (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. Results The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. Conclusion Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Introduction: Sonneratia apetala Buch-Ham is a true mangrove inhabitant in Indian Sunderban and it is used in folk medicine for digestive disorders. Method: Hydro-methanolic (20:80) extract of Sonneratia apetala leaves (SA) was chemically standardized by HPTLC and evaluated for its antiradical and gastro-protective properties. Phenolics and flavonoids present in SA were determined and antiradical activities were assessed by in vitro methods like, DPPH (1,1-diphenyl-2-picrylhydrazyl), nitric oxides, superoxides, hydroxyl and ABTS (2,2/-azino-bis-3-ethyl benzthiazoline-6-sulphonic acid). Further, gastro-protective efficacy of SA was assessed in alcohol (50% v/v, 5 ml/kg) induced oxidative ulceration in rats. Results: Chemically standardized SA exhibited presence of polyphenolic compounds. It also showed strong antiradical properties. Oral administrations of SA (125 mg/kg and 250 mg/kg) significantly protected gastric mucosal membrane from ulcerative damage caused by alcohol, similar to Omeprazole (20 mg/kg) in rats. Moreover, SA treatment significantly reduced the elevation of lipid peroxides; while enhanced the concentration of glutathione and catalase in gastric mucosa in respect to ethanol induced untreated control rats. Conclusions The results obtained from this study suggest Sonneratia apetala leaf has antioxidant properties and has capabilities to protect gastric mucosal injury caused by alcohol ingestion.

Marta Szandruk-Bender,1 Anna Merwid-Ląd,1 Benita Wiatrak,1 Maciej Danielewski,1 Stanisław Dzimira,2 Danuta Szkudlarek,3 Łukasz Szczukowski,4 Piotr Świątek,4 Adam Szeląg1 1Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland; 2Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wrocław, Poland; 3Foundation of the Wroclaw Medical University, Wroclaw Medical University, Wrocław, Poland; 4Department of Chemistry of Drugs, Wroclaw Medical University, Wrocław, PolandCorrespondence: Marta Szandruk-BenderDepartment of Pharmacology, Wroclaw Medical University, Mikulicza-Radeckiego 2, Wrocław, 50-345, PolandTel +48717841438Fax +48717840094Email marta.szandruk@umed.wroc.plBackground and Purpose: Due to the risk of gastrointestinal damage and various tissue toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) use, investigating new anti-inflammatory agents with efficacy comparable to that of NSAIDs but reduced toxicity is still a major challenge and a clinical need. Based on our previous study, new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 6-butyl-3,5,7-trimethyl-1-[[4-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-5-thioxo-1,3,4-oxadiazol-2-yl]methoxy]pyrrolo[3,4-d]pyridazin-4-one and 6-butyl-1-[[4-[[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]methyl]-2-thioxo-1,3,4-oxadiazol-5-yl]methoxy]-3,5,7-trimethyl-pyrrolo[3,4-d]pyridazin-4-one (hereafter referred to as the compounds 10b and 13b, respectively) seem to be promising anti-inflammatory agents. This study aimed to elucidate the effects of these two new derivatives on the course of experimental rat inflammation, liver and kidney function, and gastric mucosa.Methods: The anti-inflammatory effect of compounds 10b and 13b was evaluated using the carrageenan-induced paw edema test in rats. The increase in paw volume (paw edema), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) levels, histological alterations, and inflammatory cell infiltration in paw tissue were determined. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, serum urea and creatinine levels, as well as changes in gastric mucosa, were measured as indicators of hepatic, renal, and gastric toxicity.Results: Pretreatment with both novel derivatives at 10 mg/kg and 20 mg/kg doses reduced paw edema, counteracted the increased PGE2 and TNF-α levels, reduced the influx of inflammatory cells, and decreased histopathological alterations in paw tissue. Compound 13b at a dose of 20 mg/kg was more effective than indomethacin in reversing the increased TNF-α levels and reducing the influx of inflammatory cells. Only compound 13b at all studied doses (5, 10, or 20 mg/kg) counteracted the increased MPO level in paw tissue. Both compounds neither caused alterations in ALT, AST, urea, creatinine parameters nor gastric mucosal lesions.Conclusion: New compounds exert an anti-inflammatory effect, presumably via inhibiting inflammatory mediators release and inflammatory cell infiltration. Moreover, both possess a more favorable benefit–risk profile than indomethacin, especially compound 13b.Keywords: carrageenan, anti-inflammatory agents, pyrrolo[3,4-d]pyridazinone, 1,3,4-oxadiazole, inflammatory mediators, toxicity

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease which is often associated with Helicobacter pylori (H. pylori) infection. First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. The presence of H. pylori resistance factors such as translocation t (11;18), peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall; or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy (RT). RT is an effective treatment in localized gastric MALT lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. After treatment, regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Aim. A study of the clinical and morphological traits and cytokine profile of gastritis in schoolchildren with familial history of gastric cancer.Materials and methods. A cross-sectional questionnaire survey was conducted in Siberian regions (Tuva, Even-kiya, Aginskiy Buryat National District, Krasnoyarsk). A total of 3,343 schoolchildren aged 7–17 were surveyed for gastrointestinal complaints and history of gastric cancer in their 1st–2nd degree kindred. Oesophagogastroduo-denoscopy (OGDS) with gastric mucosa biopsy were performed in 463 respondents with complaints. Gastritis was graded in the Sydney classification. Serum cytokine levels (IL-2, IL-4, IL-8, IL-18, IL-1β, IFN-α, TNM-α) were obtained in enzyme immunoassays (ELISA).Results. Schoolchildren with gastritis and familial history of gastric cancer revealed a higher 59.8% rate of dyspeptic complaints vs. 40.8% in negative history (p = 0.001), as well as complaints of weekly heartburn in 14.2 and 8.3% cas-es (p = 0.019), respectively. In positive history and negative H. pylori tests, the cell immune response regulator IL-18 37 was revealed elevated in histology. In histologically verified H. pylori, no cross-cohort differences were observed in serum IL-18 by positive familial history of gastric cancer.Conclusion. Gastritis in schoolchildren with familial predisposition to gastric cancer more often associates with GERD and dyspepsia usually presented in postprandial distress syndrome. The cytokine regulation properties of gastritis in schoolchildren with familial history of gastric cancer have been reported.

The inflammatory spectrum of gastric diseases includes different clinico-pathological entities, the etiology of which was recently established in the international Kyoto classification. A diagnosis of gastritis combines the information resulting form the gross examination (endoscopy) and histology (microscopy). It is important to consider the anatomical/functional heterogeneity of the gastric mucosa when obtaining representative mucosal biopsy samples. Gastritis includes self-limiting and non-self-limiting (long-standing) inflammatory diseases, and the latter are epidemiologically, biologically and clinically linked to the onset of gastric cancer (i.e. "inflammation-associated cancer"). Different biological models of inflammation-associated gastric oncogenesis have been proposed. Helicobacter pylori (H. pylori) gastritis is the most prevalent worldwide, and H. pylori is classified as a first-class carcinogen. On these bases, eradicating H. pylori is mandatory for the primary prevention of gastric cancer. Non-self-limiting gastritis may also be triggered by the immune-mediated destruction of gastric parietal cells, resulting in autoimmune gastritis. In both H. pylori-related and autoimmune gastritis, the non-self-limiting inflammation results in atrophy of the gastric mucosa, which is the main factor promoting gastric cancer. Long-term follow-up studies consistently demonstrate the prognostic impact of the histological staging of gastritis in gastric cancer secondary prevention strategies.

Aim: To evaluate the prevalence of Helicobacter pylori (H. pylori) and related histopathological lesions in gastric mucosa samples in this single-center study. Methods: Esophagogastroduodenoscopy and endoscopic biopsy reports of 1605 elective cases were retrospectively evaluated. Histopathological examination was evaluated according to the Sydney classification. The data were analyzed according to the prevalence of H. pylori, age, gender, gastric atrophy and intestinal metaplasia rates, and the distribution of the study group in the population below 40 years old and over 40 years old. Results: 584 males (Mean age 51.5 ± 16.5 years) and 1021 females (mean age 49.6 ± 16 years), (p = 0.03), a total of 1605 cases were included in the study. The rate of atrophy, metaplasia and H. pylori positivity in total study population were 0.2%, 16%, 71%, respectively. The rate of atrophy in men and women were 1.2% and 0.8%, respectively (p = 0.006). The rate of metaplasia in men and women were 20.9% and 13.7%, respectively (p

The flavonoid myricetin is abundant in vegetables and has various bioactive properties, including anti-inflammatory and antioxidative activities. In the present study, we explored the effects of myricetin on alcohol-induced gastric ulcer in a rat model. To induce gastric ulcer, absolute ethanol (5 mL/kg body weight) was orally administrated to each rat. The positive control and myricetin-treated groups were given oral doses of omeprazole (20 mg/kg) or myricetin (12 mg/kg), respectively, 1 hour prior to the administration of absolute alcohol. We found that pretreatment with myricetin significantly decreased alcohol-induced gastric ulcer, hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Myricetin pretreatment reduced the level of malondialdehyde (MDA) and increased that of total glutathione (GSSG/GSH) and superoxide dismutase (SOD) in gastric tissues. In addition, it elevated the expression levels of cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) and decreased the phosphorylation of nuclear factor kappa B (NF-κB). Together, these results indicate that myricetin effectively inhibits ethanol-induced acute gastric injury by preventing oxidative damage, stimulating PGE2 production, and inhibiting NF-κB activation. We suggest that myricetin may be an alternative treatment for gastric injury caused by alcohol intake.

The numerous challenges and detrimental effects connected with the treatment of peptic ulcers in the world today calls for alternative attention. Ethnomedicinally, Dialium guineense pulp (DAGP) has numerous pharmacological activities. This study investigated the anti-ulcer activities of Dialium guineense pulp on gastric mucosa injury induced with aspirin in albino Wistar rats. DAGP extract was orally administered at doses of 250, 500 and 1000 mg/kg bw (mg per kg of the body weight) per day for 3 or 7 days followed by 400 mg/kg bw oral aspirin administration. Ulcer indices were determined, followed by a biochemical estimation of antioxidant enzymes using gastric mucosal tissue from the stomach. Student's t-test was used to compare significant differences among groups of animals at P ≤ 0.05. The results showed that Dialium guineense pulp caused a significant decrease (P ≤ 0.05) in the ulcer index in aspirin induced rats. This decrease in ulcer index is dose dependent and 1000 mg/kg bw per day caused the highest decrease in 7 days. The results showed a significant increase (P ≤ 0.05) in lipid peroxidation and a decrease (P ≤ 0.05) in antioxidant enzymes activities in the aspirin-induced ulcerated rats. Oral administration of DAGP increased antioxidant enzymes activities and decreased injury in the gastric mucosa in ulcer induced rats. Therefore, this study showed that DAGP exhibited anti-ulcer potential and that the gastrointestinal protection may be through the scavenging action of free radicals by its constituent antioxidants. Thus, Dialium guineense pulp has ameliorative medicinal potential for the curing of gastric disorders.

Helicobacter pylori is a Gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has reactivity against H. pylori antigens. Despite that IgA1 and IgA2 display structural and functional differences, their reactivity against H. pylori had not been previously determined. We attested titers and reactivity of human colostrum-IgA subclasses by ELISA, immunoblot, and flow cytometry. Colostrum samples from healthy mothers had higher titers of IgA; and IgA1 mostly recognized H. pylori antigens. Moreover, we found a correlation between IgA1 reactivity and their neutralizing effect determined by inhibition of cytoskeletal changes in AGS cells infected with H. pylori. In conclusion, colostrum-IgA reduces H. pylori infection of epithelial gastric cells, suggesting an important role in preventing the bacteria establishment during the first months of life. As a whole, these results suggest that IgA1 from human colostrum provides protection that may help in the development of the mucosal immune system of newborn children.

La strongiloidiasis es una infección causada por el parásito strongyloides stercolaris (SS), se asocia con una alta mortalidad en pacientes inmunosuprimidos debido a una diseminación larvaria y síndrome de hiperinfección. El compromiso de la mucosa gástrica es raro, pero cuando se presenta se caracteriza por sangrado digestivo y emesis persistente. Se presenta el caso de un paciente de 27 años con síntomas gastrointestinales, antecedente de infección por HTLV-1 y colitis ulcerativa, quien desarrolló síndrome de hiperinfección por SS. Se describe la presentación clínica, diagnóstico, tratamiento y complicaciones derivadas del cuadro infeccioso.

Вопросы, связанные с дисфункцией плотных контактов, на протяжении последних лет являются одними из самых актуальных и изучаемых в научном мире. Несмотря на значительные достижения, на сегодняшний день все еще остаются открытыми многие проблемы. В этом обзоре обсуждается молекулярная структура и регуляция плотных контактов слизистой оболочки желудка, роль бактерии Helicobacter pylori в развитии пищевой аллергии у детей, а также возможность медикаментозной регуляции парацеллюлярной проницаемости слизистой оболочки желудка. Для написания статьи осуществлялся поиск информации с использованием баз данных Scopus, Web of Science, MedLine, PubMed, Google Scholar.

Background. Helicobacter pylori infection is an important factor in chronic gastritis and duodenal ulcer in children. Over the past decade, different virulence of H.pylori strains has been determined, which depends on its toxicity genes. The purpose was to study the clinical manifestations, endoscopic and histological changes of the gastric mucosa in children with chronic gastritis, induced by H.pylori, with its different toxicity. Materials and methods. One hundred thirty-six children with chronic H.pylori-induced gastritis aged 7–17 years (main group) and 30 healthy children of the same age (control group) were examined clinically and instrumentally. Patients were divided into 2 groups: group IA consisted of 72 children with chronic gastritis, induced by H.pylori CagA “+”, and group IB included 64 children with chronic gastritis, induced by H.pylori CagA “–”, according to the results of determining the total IgG antibodies to CagA antigen in the blood serum or evaluating CagA in gastric mucosal biopsy specimens using polymerase chain reaction. Clinical manifestations, endoscopic and histological changes of the gastric mucosa were analyzed. Statistical processing was performed using the statistical software package Statgra­phics 16.0. Results. In children with chronic gastritis, induced by H.pylori CagA “+” (group IА), the clinical manifestations of pain, abdominal and dyspeptic syndromes were not significantly different from those in patients with chronic gastritis, induced by H.pylori CagA “–” (group IB). There were no significant endoscopic changes in the form of erythematous gastropathy and antral nodularity in children with chronic gastritis, induced by both H.pylori CagA “+” and CagA “–”. Histological changes in groups IA and IB were different: children with chronic gastritis, induced by H.pylori CagA “+”, had inflammatory activity degree II and I and degree II, I, III of gastric contamination by H.pylori, while children with chronic gastritis, induced by H.pylori CagA “–”, had degree I, II activity of the gastric mucosal inflammation and stages II and I of H.pylori contamination. In children with H.pylori-induced chronic gastritis, it is advi­sable to diagnose toxicity of CagA “+” and CagA “–” in order to evaluate H.pylori CagA “–” child’s status. Conclusions. Clinical manifestations of H.pylori-induced chronic gastritis in children are epigastric pain, symptoms of dyspepsia, and chronic intoxication syndrome. Endoscopic manifestations are erythematous gastopathy and/or antral nodularity. In children with chronic gastritis, induced by H.pylori CagA “+” and CagA “–”, there was no significant difference in clinical and endoscopic manifestations. Histological change in gastric mucosa in chronic gastritis, induced by H.pylori, at the stage of exacerbation is diffuse lymphocytic-plasmocytic infiltration of the lamina propria of gastric mucosa with epithelial damage. In the chronic gastritis, induced with H.pylori CagA “+”, II and III degrees of H.pylori contamination predominate, in combination with degrees I and II of inflammation activity. In chronic gastritis, induced by H.pylori CagA “–”, stages II and I of H.pylori contamination predominate. In children with H.pylori-induced chronic gastritis, it is advisable to diagnose its CagA “+”toxicity in order to evaluate H.pylori CagA “–” child’s status., Актуальность. Инфекция Helicobacter pylori является важным фактором хронического гастрита (ХГ) и дуо­денальной язвы у детей. За последнее десятилетие установлена разная вирулентность штаммов H.pylori, которая зависит от его генов токсигенности. Цель: изучить клинические проявления, эндоскопические и гистологические изменения слизистой оболочки желудка (СОЖ) у детей с хроническим гастритом, индуцированным H.pylori, с разной его токсигенностью. Материалы и методы. Проведено клинико-инструментальное обследование 136 детей с хроническим гастритом, индуцированным H.pylori, в возрасте 7–17 лет (основная группа) и 30 здоровых детей этого же возраста (контрольная группа). Пациенты были разделены на 2 группы: IА группу составили 72 ребенка с хроническим гастритом, индуцированным H.pylori CagA «+»; IБ группу — 64 ребенка с хроническим гастритом, индуцированным H.pylori CagA «–», по результатам определения суммарных антител IgG к антигену CagA сыворотки крови и/или определения антигена CagA в биоптатах СОЖ методом полимеразной цепной реакции. Изучали и анализировали клинические проявления, эндоскопические и гистологические изменения слизистой оболочки желудка. Статистическая обработка проводилась с помощью пакета статистических программ Statgrafics 16.0. Результаты. У детей с ХГ, индуцированным H.pylori CagA «+» (IА группа), клинические проявления болевого абдоминального и диспептического синдромов существенно не отличаются от таковых у детей с ХГ, индуцированным H.pylori CagA «–» (ІБ группа). Не выявлены существенные эндоскопические изменения в виде эритематозной гастропатии и антральной нодулярности как у детей с ХГ, индуцированным H.pylori CagA «+», так и у детей с ХГ, индуцированным H.pylori CagA «–». Гистологические изменения в ІА и ІБ группах были разные: детям с ХГ, индуцированным H.pylori CagA «+», свойственны II и I степень активности воспаления и ІІ, І, ІІІ степени обсемененности Н.pylori слизистой оболочки желудка, а детям с ХГ, индуцированным H.pylori CagA «–», свойственны I, II степень активности воспаления слизистой оболочки желудка и II и I степень обсемененности Н.pylori. Выводы. Клиническими проявлениями ХГ, индуцированного H.pylori, у детей в стадии обострения является эпигастральная боль, симптомы диспепсии и хронического интоксикационного синдрома. Эндоскопическими проявлениями являются эритематозная гастропатия и/или антральная нодулярнисть. У детей с ХГ, индуцированным H.pylori СagA «+», и у детей с ХГ, индуцированным H.pylori СagA «–», по клиническим и эндоскопическим проявлениям существенного различия не выявлено. Гистологическим изменением СОШ при ХГ, индуцированном H.pylori, в стадии обострения является диффузная лимфоцитарно-плазмоцитарная инфильтрация собственной пластинки СОЖ с нарушением эпителия. При ХГ, индуцированным H.pylori СagA «+», преобладает II и III степень обсеменения H.pylori в сочетании с I и II степенью активности воспаления СОЖ. При ХГ, индуцированном H.pylori СagA «–», преобладает II и I степень обсеменения H.pylori СОЖ. У детей с ХГ, индуцированным H.pylori, целесообразно диагностировать его токсигенность CagA «+» для оценки H.pylori CagA-статуса ребенка., Актуальність. Інфекція Helicobacter pylori є важливим чинником хронічного гастриту (ХГ) та дуоденальної виразки у дітей. За останнє десятиріччя встановлено різну вірулентність штамів H.pylori, яка залежить від його генів токсигенності. Мета: вивчити клінічні прояви, ендоскопічні та гістологічні зміни слизової оболонки шлунка (СОШ) у дітей з хронічним гастритом, індукованим H.pylori, з різною його токсигенністю. Матеріали та методи. Проведено клініко-інструментальне обстеження 136 дітей з хронічним гастритом, індукованим H.pylori, віком 7–17 років (основна група) та 30 здорових дітей цього ж віку (контрольна група). Пацієнти були розподілені на 2 групи: ІА групу становили 72 дитини з хронічним гастритом, індукованим H.pylori CagA «+»; ІБ групу — 64 дитини з хронічним гастритом, індукованим H.pylori CagA «–», за результатами визначення сумарних антитіл IgG до антигену CagA сироватки крові та/або визначення антигену CagA в біоптатах СОШ методом полімеразної ланцюгової реакції. Вивчали та аналізували клінічні прояви, ендоскопічні та гістологічні зміни слизової оболонки шлунка. Статистична обробка проводилась за допомогою пакета статистичних програм Statgrafics 16.0. Результати. У дітей з ХГ, індукованим H.pylori CagA «+» (ІА група), клінічні прояви больового абдомінального та диспептичного синдромів суттєво не відрізняються від таких у дітей з ХГ, індукованим H.pylori CagA «–» (ІБ група). Не виявлено суттєвих ендоскопічних змін у вигляді еритематозної гастропатії та антральної нодулярності як у дітей з ХГ, індукованим H.pylori CagA «+», так і у дітей з ХГ, індукованим H.pylori CagA «–». Гістологічні зміни в ІА та ІБ групах були різні: дітям з ХГ, індукованим H.pylori CagA «+», властивий ІІ та І ступінь активності запалення і ІІ, І, ІІІ ступені обсіменіння Н.pylori слизової оболонки шлунка, а дітям з ХГ, індукованим H.pylori CagA «–», властивий І та ІІ ступінь активності запалення слизової оболонки шлунка і ІІ та І ступінь обсіменіння Н.pylori. Висновки. Клінічними проявами ХГ, індукованого H.pylori, у дітей в стадії загострення є епігастральний біль, симптоми диспепсії та хронічного інтоксикаційного синдрому. Ендоскопічними проявами є еритематозна гастропатія та/або антральна нодулярність. У дітей з ХГ, індукованим H.pylori СagA «+», та у дітей з ХГ, індукованим H.pylori СagA «–», за клінічними та ендоскопічними проявами суттєвої різниці не виявлено. Гістологічною зміною СОШ при ХГ, індукованому H.pylori, в стадії загострення є дифузна лімфоцитарно-плазмоцитарна інфільтрація власної пластинки СОШ з порушенням епітелію. При ХГ, індукованому з H.pylori СagA «+», переважає II та III ступень обсіменіння H.pylori в поєднанні з I та II ступенем активності запалення СОШ. При ХГ, індукованому H.pylori СagA «–», переважає II та I ступінь обсіменіння H.pylori СОШ. У дітей з ХГ, індукованим H.pylori, доцільно діагностувати його токсигеннісь CagA «+» для оцінки H.pylori CagA-статусу дитини.

This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1β], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.

BACKGROUND: The Prex2 protein is a member of the Rac family proteins that belongs to small G proteins with a critical role in cell migration, cell proliferation, and apoptosis through its effects on PI3K cell signaling pathway and phosphatase activity of PTEN protein. The effect of PREX2 gene expression has been shown in some cancer cells. A survey of PREX2 gene expression in gastric antral epithelial cells of gastric cancer patients with Helicobacter pylori various genotypes infection can conduct to better understanding H. pylori infection’s carcinogenesis. METHODS: In a case-control study, PREX2 gene expression was evaluated in gastric antral biopsy samples on four groups of patients referred to Sanandaj hospitals, including gastritis with (n=23) and without (n=27) H. pylori infection and gastric cancer with (n=21) and without (n=32) H. pylori infection. Each gastric biopsy sample’s total RNA was extracted and cDNA synthesized by using Kits (Takara Company). The PREX2 gene expression was measured using the relative quantitative real-time RT-PCR method and ΔΔCt formula. RESULTS: The PREX2 gene expression increased in gastric antral biopsy samples of gastritis and gastric cancer patients with H. pylori infection (case groups) than patients without H. pylori infection (control groups) 2.38 and 2.27 times, respectively. The patients with H. pylori vacA s1m1 and sabB genotypes infection showed a significant increase of PREX2 gene expression in gastric cancer antral epithelial cells. CONCLUSION: H. pylori vacA s1m1 and sabB genotypes have the positive correlations with PREX2 gene expression in gastric antral epithelial cells of gastritis and gastric cancer patients. RESUMO CONTEXTO: A proteína Prex2 é membro das proteínas da família Rac que pertencem a pequenas proteínas G com um papel crítico na migração celular, na proliferação celular e na apoptose através de seus efeitos na via de sinalização celular PI3K e atividade fosfatase da proteína PTEN. O efeito da expressão genética PREX2 tem sido mostrada em algumas células cancerosas. Um levantamento da expressão genética PREX2 em células epiteliais antrais gástricas de pacientes infectados com vários genótipos de Helicobacter pylori pode conduzir a um melhor entendimento da carcinogênese da infecção por H. pylori. MÉTODOS: Em estudo de caso-controle, a expressão genética PREX2 foi avaliada em amostras de biópsia antral gástrica em quatro grupos de pacientes encaminhados aos hospitais de Sanandaj, incluindo gastrite com (n=23) e sem (n=27) infecção por H. pylori e de câncer gástrico com (n=21) e sem (n=32) infecção por H. pylori. O RNA total de cada amostra de biópsia gástrica foi extraído e cDNA sintetizado por meio de kits (Takara Company). A expressão genética PREX2 foi medida utilizando-se o método RT-PCR em tempo real quantitativo relativo e a fórmula ΔΔCt. RESULTADOS: A expressão genética PREX2 aumentou em amostras de biópsia antral gástrica de pacientes com gastrite e câncer gástrico com infecção por H. pylori (grupos de casos) em relação aos sem infecção por H. pylori (grupos de controle) 2,38 e 2,27 vezes, respectivamente. Os pacientes com infecção por genótipos H. pylori vacA s1m1 e sabB apresentaram um aumento significativo da expressão genética PREX2 em células epiteliais antrais de câncer gástrico. CONCLUSÃO: Os genótipos H. pylori vacA s1m1 e sabB têm correlações positivas com a expressão genética PREX2 em células epiteliais antrais gástricas de pacientes com câncer gástrico e gastrites.

Peripheral lymphoid organs respond immediately to a decrease in the body's defence responses, and their localisation and morphological specificity account for their active involvement in immunogenesis (especially in animals). This fact accentuates the morpho-functional estimation of the lymphoid tissue condition with the purpose of timely diagnostics of starting deviations and preventing the development of decompensated changes. Thus, the analysis of histological changes of the latter in natural and experimental prototypes of babesiosis is relevant. The aim of the research is to define the role of histological changes of lymphoid masses in the stomach and small intestine in the formation of the clinical and pathogenetic profile of babesiosis. We studied the structural changes of lymphoid masses of the stomach and small intestine in animals with babesiosis postmortem by histological methods. Fixation was traditionally carried out in 12% aqueous formalin solution, dehydration in alcohol (30º to absolute), and pouring (paraffin/ celloidin). Staining was conducted with eosin and haematoxylin, Van Gizon, Brasche. Analysis was performed using an Olympus BX-41 microscope, Japan (x 100; x 200; x 1350). Verification was carried out by cytological, ultramicroscopic, molecular genetic methods (polymerase chain reaction) and in a biological experiment on animals. Analysis of specimens of the lamina propria in the gastric mucosa of the animals in the experimental group and clinical observation group established that the latter contained diffuse accumulations of the lymphoid tissue. Their dispersal involved different parts of the organ, including quite large areas. Haematoxylin and eosin staining gave a clear histological pattern with a marked contrast of fragments, which contributed to diagnostic resources. Lymphoid follicles were observed occasionally, their marginal, mantle zones were blurred. The germinative centres were not detected and did not show any lucency. Neutrophilic granulocytes, monocytes and plasma cells predominated among the cellular leucocyte populations. Examination of the lymphoid apparatus of the small intestine showed predominantly diffuse nodular hyperplasia, which was widespread. A focal version of the nosological prototype was observed in individual specimens occasionally, presented as single cells (most often in the terminal parts of the organ). Histological changes of lymphoid masses of the stomach and small intestine in animals with babesiosis consisted in the development of expressive diffuse nodular hyperplasia with disorganization of the structure of lymphoid follicles, destruction of zonality of the latter, making it impossible to detect germinative centres.

Helicobacter pylori is a bacterium that causes infections in the gastrointestinal tract. This type of bacterium is very common and contagious at the same time. H. pylori enters the mouth and continues its course along the gastrointestinal tract. H. pylori infection induces an inflammatory response that leads to the activity of neutrophils, lymphocytes, plasma cells, and macrophages. In addition to the bacterial role in gastric mucosa, the host's inflammatory response may also play a role in disease outcome. In inflammation, the risk of carcinogenesis increases due to DNA damage increased proliferation and the creation of an environment rich in cytokines and growth factors. Genetic methods and diagnosis of H. pylori genes are used to identify healthy and healthy gastric cancer patients infected with H. pylori. In relation to the genes associated with H. pylori pathogenesis, the presence of genes such as cagA, hopQI, hopQII and so on is used, and PCR of a part of these genes amplified fragments of different lengths. One of the less-studied cases is the association of two or more pathogenic genes simultaneously with H. pylori. In this research, the frequency of disease and healthy individuals who are infected with H. pylori and have two genotypes cagA and hopQI at the same time, was examined. In order to diagnose H. pylori-infected individuals in healthy and gastric cancer patients, after PCR of glmM gene, PCR product electrophoresis on agarose gel was used. For this purpose, gastric tissue biopsy was used in patients and saliva was used in healthy individuals. For this purpose, 100 gastric biopsy samples were collected from patients with gastric cancer and 100 saliva samples from healthy individuals. According to the data, there is a significant relationship between the simultaneous presence of two genes cagA and hopQI and gastric cancer. In patients, 45.3% showed both genotypes, while in healthy individuals only 10.5% have this genotype and other healthy but infected with H. pylori (90.8%) do not have this genotype. To be. No report was observed on the simultaneous study of cagA and hopQI genes. No report was observed regarding the simultaneous study of cagA and hopQI genes.

This study investigated the histomorphological, ultrastructural and morphometrical postnatal developmental changes in the rabbit fundic region, especially during changing of the feeding intake. Seventy-two New Zealand rabbits (V-Line breed) at the ages of 1, 7, 15, 23, 30 and 60 days were obtained for light and electron microscopy and morphometric studies of the fundic region. The newborn rabbit's fundic wall was thin and organized into mucosa, submucosa, musclosa and serosa, with a significant increase in thickness with ageing. The fundic glands were few at the first week of life, then increased in length and diameter compared to the preceding age with prominent zonation at 23 days. The gastric pits appeared wide and deep at the first week of life then became typically narrow and shallow at the third week. The mucous cells were the main cell types lining the fundic glands in the first week of life. These cells showed remoulding with a marked increase in Periodic Acid-Schiff reactivity with age. Parietal cells were differentiated earlier (on the first day of life) than the chief cells and distributed at the neck and basal zones. Chief cells differentiated at 15 days old at the base of the glands, followed by an increase in the number and activity. Few active enteroendocrine cells were first seen at 15 days old and then widely distributed throughout the glands. Conclusion: Pronounced histomorphological changes in the fundic mucosal layer, especially the surface and glandular epithelium, correlate with the postnatal rabbit-feeding intake changes.

Background Gastric mucosal hypertrophy, also known as Menetrier's disease (MD), is more common in men over 50 years of age, and the cause is unknown. The symptoms of the disease are atypical, mostly accompanied by hypoproteinemia and edema, and sometimes accompanied by symptoms such as epigastric pain, weight loss, and diarrhea. Most experts believe that the site of the disease is mainly located in the fundus of the stomach and the body of the stomach. We found that the site of the disease in this patient involved the antrum of the stomach. Case summary We introduced the case of a 24-year-old woman who had repeated vomiting for 5 d and was admitted to our hospital. After various examinations such as computed tomography and pathology in our hospital, the final diagnosis of the presented case is MD. The salient feature is that the mucosal folds in the fundus and body of the stomach are huge and present in the shape of gyrus. The greater curvature is more prominent, and there are multiple erosions or ulcers on the folds. The patient did not undergo gastric surgery and did not undergo re-examination. She is drinking Chinese medicine for treatment, and her vomiting and abdominal pain symptoms have improved. This disease is relatively rare in clinical practice, and it is easy to be misdiagnosed as gastric cancer, chronic gastritis and gastric lymphoma, etc. Conclusion MD can occur in the antrum, it is necessary to raise awareness of the disease and reduce misdiagnosis.

Vonoprazan-associated gastric mucosal redness is rare, and its endoscopic and pathological features remain poorly described. We report 4 cases of vonoprazan-associated gastric mucosal redness, that is, 2 cases each in non-Helicobacter pylori-infected and -eradicated stomach. In all cases, esophagogastroduodenoscopy demonstrated spotty and linear redness newly appearing in the greater curvature of the gastric body after initiation of vonoprazan but disappearing after its discontinuation. A tissue biopsy taken from the gastric mucosa with redness revealed various pathological findings and included inflammatory cell infiltration, parietal cell protrusions, oxyntic gland dilatations, congestion, focal hemorrhage with congestion beneath the basement membrane, and vacuolar degeneration of parietal cells. To our knowledge, this is the second report describing the endoscopic and pathological features of vonoprazan-associated gastric mucosal redness.

Introduction: Gastric cancer is one of the most common causes of cancer-related deaths worldwide. Many epidemiological studies have shown several risk factors associated with the development of gastric cancer, including gastritis. The most common cause of gastritis is H. pylori infection. In the H.pylori-infected mucosa, there was a significant increase in VEGF levels. Several SNPs are thought to be involved in the etiology of malignancy, one of which is the VEGF-2578C>A polymorphism. Methods: A cross sectional study was conducted in Medan with 59 H. Pylori gastritis patients. Endoscopic examination was performed to assess the gastric mucosa. H.pylori status was determined by examination of Urea breath Test (UBT) and Campylobacter Like Organism (CLO) test followed by histopathological studies evaluating the presence of changes to pre-malignant lesions such as chronic atrophic gastritis, intestinal metaplasia, intestinal dysplasia. Genotype analysis was carried out using Polymerase Chain Reaction (RT-PCR). Data analysis was carried out by univariate and bivariate Result: Of the 59 patients with H. pylori gastritis, 35.8% of patients showed premalignant lesions. The majority of premalignant lesions had a CC genotype (37.9%, n = 11), but there was no significant relationship between the VEGF-2578 C>A polymorphism and the incidence of gastric premalignant lesions. Conclusion: Based on this study, the VEGF -2578C>A polymorphism was not associated with gastric premalignant lesions in H. pylori gastritis patients.. Keywords: Polymorphism VEGF, VEGF -2578C>A, Premalignant lesions, H. Pylori.

Mucosal damage in people with gastritis causes the production of VEGF. VEGF is a neoangiogenesis function to repair damaged tissue. Excess production can cause cancer risk. VEGF genotype polymorphisms are thought to affect the production of serum VEGF levels. The aim of this study was to determine the relationship between VEGF - 2578 C> A polymorphism and serum VEGF levels in H. pylori gastritis. Method: cross-sectional study was conducted at H. Adam Malik General Hospital and Network Hospital with 100 samples. Endoscopic examination was performed to assess the gastric mucosa and a tissue biopsy was performed. The urea breath test (UBT) test and the Campylobacter like organism (CLO) test to determine H. pylori infection. VEGF - 2578 C> A was checked by Polymerase Chain Reaction (PCR). The data will be analyzed by univariate and bivariate. Result: One hundred people with gastritis, of which 59 people were infected with H. pylori. In this study, H. pylori infection did not have a significant relationship with VEGF levels. VEGF - 2578 C> A polymorphisms also had no relationship to serum VEGF levels. Conclusion: There is no correlation between VEGF - 2578 C> A polymorphism with VEGF serum levels (p> 0.05). Keywords: VEGF polymorphisms, VEGF - 2578 CA, H. pylori, Gastritis.

The gastric proton pump (H+,K+-ATPase) responsible for the H+ secretion of gastric acid is an essential therapeutic target for acid-related diseases. H+,K+-ATPase belongs to a P2-type ATPase family. Here, we examined the effects of a newly synthesized dihydropyrazole derivative KYY-008 on the H+,K+-ATPase. KYY-008 concentration-dependently inhibited the enzyme activity of the ATPase in the membrane fractions prepared from isolated hog gastric mucosa and from human kidney HEK293 cells in which gastric H+,K+-ATPase is exogenously expressed. The IC50 values in these samples were 3.4 μM and 3.7 μM, respectively. In addition, KYY-008 significantly inhibited the H+,K+-ATPase-derived H+ uptake into the tightly sealed vesicles prepared from the hog gastric mucosa. In contrast, KYY-008 has no effect on the activities of other P2-type ATPases such as Na+,K+-ATPase and Ca2+-ATPase. KYY-008 did not change the ionic currents of voltage-dependent Ca2+ channels, that were potential targets for some dihydropyrazole derivatives. Together, we discovered a new dihydropyrazole derivative which acts as a selective inhibitor of gastric H+,K+-ATPase.

Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.

HIV preferentially infects α4 s7 + CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4 s7 + CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α4 s7 + CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α4 s7 + CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α4 s7 in HIV infection.

Objective To understand the protective effect of NF-κB signaling pathway inhibitor pyrrolidinedithiocarbamate (PDTC) on mice with chronic atrophic gastritis (CAG). Methods Helicobacter pylori (H. pylori) infection combined with high-salt diet was used to construct the CAG mouse model, and 100 or 200 mg/kg/day PDTC was intragastrically treated for 8 weeks. Then, hematoxylin and eosin (HE) and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to observe the pathology of gastric mucosa, while immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immuno sorbent assay (ELISA) and western blotting were determined to detect the expression of related molecules. Results The nuclear content of NF-κB p65 in the gastric mucosa of the CAG mice was increased accompanying by the structural disorder of the gastric mucosal epithelium, inflammatory cell infiltration, intestinal metaplasia, and increased MUC2 expression, but the symptoms were alleviated after PDTC treatment. In addition, the expressions of TNF-α, IL-1β, IL-6 and COX2 in the gastric mucosa and serum of CAG mice were higher than those control mice, which were reduced in CAG mice treated with either 100 or 200 mg/kg PDTC. Furthermore, 100 mg/kg and 200 mg/kg PDTC treatments reduced the serum PGE2 in CAG mice with the decreased PCNA and Ki-67 expression in gastric mucosa. The therapeutic effect of 200 mg/kg PDTC was significantly better than that of 100 mg/kg PDTC. Conclusion PDTC inhibited inflammation and the excessive proliferation of gastric mucosal epithelial cells, thereby exerting a potential therapeutic effect on CAG.

Flow cytometry is widely used for lymphocyte immunophenotyping in clinical settings. However, few studies have applied it for analyzing lymphocytes of the gastric mucosa. This review offers an overview of methodologies for isolating lymphocytes from the human stomach. Previously reported articles were reviewed, focusing on procedures for isolating human gastric mucosal lymphocytes. Helicobacter pylori-associated peptic diseases and gastric cancer are two major subjects of research in this field. Enzymatic dissociation, mechanical dissociation, or a combination of the two have been used to isolate lymphocytes from the stomach. Intra-epithelial and lamina propria lymphocytes were separately isolated in several studies. We also summarize the history and present trends in analyzing lymphocytes in patients with gastric disease.

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.

Background Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. Methods The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18. Results In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. Conclusion These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.

The article presents the results of study of the degree of contamination of the gastric mucosa with Helicobacter pylori infection and its relationship with duodenogastric reflux. There was revealed a direct correlation between the bile acids level in the gastric acid, and the presence of Helicobacter pylori, that in combination with duodenogastric reflux negatively affect the state of the gastric mucosa.

Gastric cancer is a malignancy with high incidence and mortality worldwide. In gastric cancer, epithelial-mesenchymal transition (EMT) and metastasis further increase the mortality rate. Trefoil factor 1 (TFF1) has been reported as a protective factor in the gastric mucosa. In this study, TFF1 inhibited the migration and invasive capability of gastric cancer cells. Elevated TFF1 levels induced the expression of E-cadherin, the epithelial marker, and reduced the expression of N-cadherin, vimentin, Snail, Twist, Zinc finger E-box binding homeobox (ZEB) 1 and ZEB2, well-known repressors of E-cadherin expression. In addition, the expression of matrix metalloproteinase (MMP)-2, MMP-7 and MMP-9, which are major markers of cancer metastasis, was suppressed by TFF1. Upregulation of TFF1 inhibited TGF-β, a major signaling for EMT induction, and the phosphorylation of Smad2/3 activated by TGF-β in AGS cells. In conclusion, TFF1 inhibits EMT through suppression of TGF-β signaling in AGS cells, which might be used in therapeutic strategies for reducing metastatic potential and invasiveness of these cells.

Background and aim The biological characterization of microbial environment in early gastric cancer (EGC), other than Helicobacter pylori, is limited. This study aimed to explore the microbial microenvironment in chronic gastritis (CG), fundic gland polyps (FGPs), low-grade intraepithelial neoplasia (LGIN) and EGC. Methods 16S-rRNA gene sequencing and bioinformatic analysis were performed on 63 individuals with 252 mucosal biopsies or endoscopic submucosal dissection margin samples from endoscopy. Results The microbiota in gastric LGIN functions analogously to EGC in terms of functional prediction. Neoplastic lesions showed a significant difference to CG or FGPs in beta diversity of the microbiota. Bacteria genera including Paracoccus, Blautia, Barnesiella, Lactobacillus, Thauera, Collinsella were significantly enriched in gastric neoplastic mucosa (LGIN and EGC) compared to non-neoplastic tissues (CG and FGPs). Whilst Pseudomonas and Kingella were depleted in neoplastic tissues. FGPs showed a distinctive microbial network system that negatively interacted with Helicobacter. Conclusions In terms of the mucosal microbial microenvironment, gastric LGIN and EGC showed no significant difference as early neoplastic lesions. We observed a coordinated microbial microenvironment that correlated negatively with Helicobacter.

Necroptosis is a novel manner of programmed cell death and important for tissue development, homeostasis, damage, and repair. Activation of receptor-interacting protein kinase 3 (RIPK3), a key member of receptor-interacting protein family in contributing significantly to necroptosis, in tissues is a hallmark of cells dying by necroptosis. However, there are few studies that examine the expression of RIPK3 in the glandular cells of stomachs under physiological condition. We have therefore conducted this study to immunohistochemically characterize the key element of necroptosis, RIPK3, in the mouse and human stomach. Results showed that RIPK3 positive cells could be observed in the surface mucosal cells, granular cells, and lamina propria cells in both mouse and human stomach tissues. Ratios of PCNA/RIPK3 positive cells in the glandular cells were ~ 2.1 in mouse and ~ 4.15 in human sections respectively. Morphological and double immunofluorescence analysis confirmed that these RIPK3 positive cells were mucous, parietal and lamina propria cells. Our results indicate that the expression of RIPK3 in different cell types might contribute to cell turnover of gastric mucosa in the mouse and human stomach under physiological condition.