Human Gastritis Research Articles

USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.

Evidências de Helicobacter spp. em gatos domésticos na região central do Rio Grande do Sul - pré-estudo

ABSTRACT Non-Helicobacter pylori Helicobacters(NHPH) account for causing moderate and severe gastritis in humans. Moreover, they have already been documented in the oral cavity of feline animals. The current study aims to investigate Helicobacter spp. incidence in necropsied domestic cats from central Rio Grande do Sul. Stomach, liver, and bile samples derived from 30 cats’ cadavers were subjected to rapid urease test (RUT), histopathological analysis, PCR, and nucleotide sequencing to investigate the genetic material presence and to identify the main phylogenetic group. Based on RUT results, 64.2% and 53.5% of patients were positive for gastric body and pyloric antrum, respectively. Ten out of these 15 patients were male (70%) and the positive result observed for the pyloric antrum was associated with males. Mild histopathological changes were observed in most gastric and liver samples. Gastric samples subjected to PCR presented positive results in 60.7%, whereas liver samples accounted for positive results in 17.8% and bile samples, in 3.5% of cases. There was high nucleotide identity with NHPH species. This study has found evidence that NHPH can be found in the gastric and hepatic regions, as in the bile of domestic cats, besides emphasizing the zoonotic potential of this disease

Prevalence and associated risk factors of Helicobacter pylori infection in East Africa: a systematic review and meta-analysis.

Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer, lymphoma, and gastric cancer in humans. The prevalence and factors associated with H. pylori infection are varied across countries. Thus, a comprehensive review has not been done on prevalence and associated factors in East Africa. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence and identify factors associated with H. pylori infection in East Africa. Articles written in English language were retrieved from PubMed, Scopus, and Science Direct. Relevant articles were selected and screened using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Publication bias was assessed qualitatively and qualitatively using funnel plot symmetry and Egger's test, respectively. Heterogeneity was assessed using the I2 measure. Data were analyzed using Stata software, version 14, and the "metan" command. A total of 231 articles were retrieved from nineteen countries in East Africa. Of these, 70 articles were eligible for the review. The pooled prevalence of H. pylori in East Africa was 50.98% (95% CI: 45.05-56.90). The prevalence of H. pylori infection ranged from 7.7 to 94.5% in East African countries. The highest pooled prevalence was from Sudan (61.3%, 95% CI: 52.6-69.9), and the lowest prevalence was reported from Uganda (40.7%, 95% CI: 33-48.3). Persons with no formal education (OR: 2.03; 95% CI: 1.22-2.83), lack of hand washing habit after toilet (OR: 2.24; 95% CI: 1.45-3.02), having a history of dyspepsia (OR: 2.25; 95% CI: 1.31-3.18), living in rural areas (OR = 1.80; 95% CI: 0.38-3.23), and having unclean water source (OR = 1.5; 95% CI:0.45-3.45) were all associated with higher risk for H. pylori infection. More than half of the populations of East African countries were positive for H. pylori infection. Rural residence, source of water, and alcohol consumption were significantly associated with H. pylori infection. Therefore, healthcare workers could provide health education on the aforementioned risk factors, and the government and other stakeholders could improve the source of drinking water in East Africa.

Synthesis, Docking Studies and Evaluation of Chalcones as Anti-Helicobacter pylori and antitumoral Agents.

Helicobacter pylori colonizes the gastric epithelium of 50 % of world population and it is the main etiological agent of human chronic gastritis, peptic ulcer, and gastric cancer. In this study, we synthesized and characterized a series of 14 chalcones and evaluated their anti-H. pylori, NO inhibition (in vitro and in silico), and AGS cells cytotoxic effects. Compounds 3b and 3h showed MIC of 8 μg/mL. We observed structure-activity relationships, mainly related to the influence of methoxy substituent at C-2 (3b) and the nitro group at C-4 (3h) in chalcone scaffold. The fourteen chalcones inhibited the NO production in LPS-stimulated macrophages and showed potential for interaction on the active site of the iNOS enzyme. Finally, 3b and 3h showed the highest selectivity to the AGS cell lines. Thus, ours results suggest 3b and 3h as potential candidates for design of new and effective agents against H. pylori and related diseases.

Population- and Gender-Based Investigation for Prevalence of Helicobacter pylori in Dhamar, Yemen.

Among 35 species of genus Helicobacter, H. pylori is the most common causative agent of human gastritis, peptic ulcer, and gastric cancer. The infection can spread through direct human-to-human contact, fecal-oral route, and contaminated water. The study was designed to investigate the rate of prevalence of H. pylori in the population of Dhamar, Yemen. In this one-year study, 460 including 250 male and 210 female stool specimens were collected between January to December 2020 in Dhamar Governorate, Yemen. Of the total 460, 215 rural (male: n = 120 and female: n = 95) and 245 urban (male: n = 130 and female: n = 115) specimens were investigated for identification of H. pylori by serological test using Helicobacter pylori stool antigen (HpSA) test. In addition, for comparing an improved recovery of H. pylori, conventional culture-based isolation was also carried out using three selective media. Modified Campy-blood Agar (MCA), Belo Horizonte Agar (BHA), and Egg yolk Emulsion (EYE) medium supplemented with antimicrobial agents including vancomycin (10 mg/L), cefsulodin (5 mg/L), trimethoprim (5 mg/L), and amphotericin B (5 mg/L) and isolates were phenotypically characterized. The HpSA test results revealed that of the total 460 specimens, 89 (19.3%) were positive for H. pylori with relatively low in male (n = 43; 17.2%) as compared to the female (n = 46; 21.9%) specimens. After 3-10 days of incubation, H. pylori was recovered at a variable rate on each selective (MCA: 16.5%; BHA: 15.0%; EYE: 13.0%) media. However, culture-based assay results showed less recovery (n = 81; 17.6%) with no significant difference among all selective media tested and between genders (male: n = 39; 15.6%; female: n = 42; 20.0%). The infection rate was comparatively higher in rural (n = 45; 20.9%) as compared to urban (n = 36; 14.7%) population. Overall, the study data showed the prevalence of infection in both genders of all age groups. The present study showed a relatively high rate of infection of H. pylori in the Dhamar population. The serological identification and culture-based methods are important for rapid detection, aid in treatment, and developing policies for the control and eradication of H. pylori infection and to prevent the disease in different age groups in Yemen.

In Silico Structural and Functional Annotation of Helicobacter Pylori (Strain Hpag1) Hypothetical Protein Hpag1_0137

Background and Aims: Helicobacter pylori (H. pylori) is a Gram-negative pathogenic bacterium that causes gastritis in humans. The exact molecular mechanism of most of the non-annotated hypothetical proteins involved in the virulence of H. pylori is yet to be identified. This paper aims to characterize the structure and function of the non-annotated hypothetical protein (HP) HPAG1_0137 from the H. pylori bacterium (strain HPAG1) in silico. Methods: We predicted several properties of HPAG1_0137, such as its physicochemical characteristics, secondary and tertiary structures, and functional annotation using different computational tools, followed by structural validation and quality assessment. We also performed virulence, protein crystallization, and active site predictions. Results: The study found that HPAG1_0137 has 242 amino acids and an acidic pI and is thermally stable, water-soluble, and distributed in the cytoplasm. Structurally, alpha-helices and random coils are this protein’s most prominent structural components. We found structural models to be highly native and of decent quality. Conclusions: This study will facilitate a better understanding of the HPAG1_0137 protein molecular mechanism of action. In addition, it will provide the basis for additional proteomic, genomic data, and structural and pharmacological research for functional and therapeutic potential identification.

Co-relationship between Helicobacter pylori infection and patient of phenotype RIPK3 and gastric carcinoma in AL-Diywaniah Province, Iraq

Objective: To diagnose H. pylori infection and assess the likelihood of developing gastric cancer. It is necessary to describe instances and phenotypes of necroptosis in gastric cells. Methodology: Fifty patients who had undergone gastrectomy from January 2020 to December 2022 were interviewed. A noninvasive investigation has been performed on each specimen to check for the presence of H. pylori by using stool, antibody test, urea breath test, and biopsy taken on endoscopy. Results: Increased population of RIPK3-positive cells was observed in both gastric glands and lamina propria in H. pylori infected human oxyntic gastritis and atrophic specimens. Phenotypic analysis revealed that many RIPK3-positive cells were H + K+ ATPase-positive parietal cells in the gastric glands and are predominantly CD3-positive T lymphocytes CD68-positive macrophages, and SMA-alpha-positive stromal cells. Positive tests for H. pylori were conducted on 50 individuals on chemotherapy who already had gastric cancer as a consequence of exposure to bacteria. The incidence of stomach cancer was 62% in males and 38% in females with age between 30-85 years. Conclusion: An increased population of RIPK3-positive cells was observed in several types of gastric cells. Future studies that define the effects and mechanisms developed of H. pylori disorders are needed.

Helicobacter Pylori Infection among Patients Attending the Gastroenterology Department in Tertiary Care Hospital, Kathmandu, Nepal.

Helicobacter pylori is one of the most pathogenic organisms that cause gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma in humans. The main aim of this study was to determine the H. pylori infection among patients undergoing upper GI endoscopy and to compare the efficacy of the diagnostic method of H. pylori infection including invasive tests (biopsy-based tests like the rapid urease test (RUT), direct smear, and culture) and the noninvasive test (HpSA). A total of 100 stool samples and 200 gastric biopsy specimens were collected (2 samples from each patient) from June to November 2019. Stool samples were processed for the detection of an H. pylori stool antigen (HpSA) by a kit method. One biopsy specimen was processed for the RUT, and another was transported to the laboratory in an Eppendorf tube containing normal saline for preparation of the smear and culture. Out of 100 participants, 26% were found to be H. pylori positive by the RUT, 11% by the direct smear, 6% by the culture, and 17% by the stool antigen test. The prevalence of H. pylori infection was found to be 14%, considering at least two of the three biopsy-based tests that gave positive results. H. pylori infection was found to be higher in the age group of 46-55 years. The overall prevalence of H. pylori infection was higher in gastric ulcer cases, followed by erosive pangastritis and gastroduodenitis. Tea drinking habits and the frequency of meal consumption more than twice a day were found to be significantly associated with H. pylori infection (P < 0.05). Hence, the RUT was found to be more efficient than the direct smear and the culture method for finding H. pylori in the biopsy sample. However, none of these methods can be considered to be the gold standard alone. Thus, the RUT combined with other tests is preferable for the detection of H. pylori.

S3692 What the Heil? H. heilmanni Causing Peptic Ulcer Disease and Severe GI Bleeding

Introduction: Helicobacter pylori (H. pylori) has a well-known association with peptic ulcer disease (PUD) and gastritis. However, other helicobacter species cause similar diseases. We present a case of a patient with H. heilmanni infection causing PUD and significant gastrointestinal (GI) bleeding. Case Description/Methods: A 63-year-old man with CAD s/p stent on aspirin and recent root canal procedure who was taking ibuprofen for several weeks presented with a one day history of mixed melena and hematochezia. He had no prior history of PUD or GI bleeding. EGD revealed two Forrest class III gastric ulcers and three duodenal ulcers including a 7 mm Forrest class IIc ulcer. Gastric biopsies were taken. He required 3 units of packed red blood cells (PRBCs), and was discharged on pantoprazole BID with a Hgb of 8 g/dl and biopsy results pending. The following day, he presented with similar symptoms, requiring ICU admission for Hgb 5.4 g/dl and blood pressure 77/52 mm Hg. He required 5 units PRBCs without pressor support. Repeat EGD revealed a 12 mm Forest class IIb duodenal ulcer (image 1) which was injected with epinephrine, and a single hemoclip was placed with hemostatic control. Prior EGD biopsy results showed chronic gastritis and helicobacter-like species found to be Helicobacter heilmanni by genotyping, and negative for concurrent H. pylori. The patient was treated with triple therapy with pantoprazole, amoxicillin and clarithromycin. Repeat EGD 2 months after treatment confirmed eradication of H. heilmanni and healing of all ulcers. Discussion: H. heilmanni was first described as an organism causing gastritis in humans in 1987 under its former name Gastrospirillum hominis. H. heilmanni is found in less than 1% of patients undergoing EGD for upper GI symptoms compared to H. pylori which is found in as many as 60% of patients with similar symptoms. Complications of H. heilmanni infection in patients include: 82% developing gastritis, 16% PUD, 2% gastric cancer, and, in our patient’s case, severe GI bleeding. Concurrent infection with H. pylori and H. heilmanni infection is uncommon and identification of H. heilmanni via H. pylori via stool antigen or rapid urease testing has unclear efficacy. Our case highlights the need for H. heilmanni to be recognized as a potential cause of PUD and further testing might need to be considered when H. pylori testing is negative. Ultimately, definitive diagnosis is done via genetic PCR amplification, and treatment is possible using the same antibiotic regimen as H. pylori.Figure 1.: Duodenal ulcer with adherent clot (Forest class IIb).

Occurrences and phenotypes of RIPK3-positive gastric cells in Helicobacter pylori infected gastritis and atrophic lesions.

Research evidences suggest that diverse forms of programmed cell death (PCD) are involved in the helicobacter pylori (H. pylori)-induced gastric inflammation and disorders. To characterize occurrences and phenotypes of necroptosis in gastric cells in H. pylori infected gastritis and atrophic specimens. Occurrences and phenotypes of necroptosis in gastric cells were immunohistochemically characterized with receptor-interacting protein kinase 3 (RIPK3) antibody in both human H. pylori infected gastric gastritis, atrophic specimens, and transgenic mice. Increased populations of RIPK3-positive cells were observed in both gastric glands and lamina propria in H. pylori infected human oxyntic gastritis and atrophic specimens. Phenotypic analysis revealed that many RIPK3-positive cells were H+K+ ATPase-positive parietal cells in the gastric glands and were predominantly CD3-positive T lymphocytes, CD68-positive macrophages, and SMA-alpha-positive stromal cells in the lamina propria. Furthermore, we found an increased expression of RIPK3-positive gastric glandular cells along with the histological process of hyperplasia-atrophy-dysplasia progression in hypergastrinemic INS-GAS mice. An increased population of RIPK3-positive cells was observed in several types of gastric cells, future studies that define the effects and mechanisms of PCD implicated in the development of H. pylori induced gastric disorders are needed.

Mucosal Overexpression of Thymic Stromal Lymphopoietin and Proinflammatory Cytokines in Patients With Autoimmune Atrophic Gastritis.

The immune mechanisms underlying human autoimmune atrophic gastritis (AAG) are poorly understood. We sought to assess immune mucosal alterations in patients with AAG. In 2017-2021, we collected gastric corpus biopsies from 24 patients with AAG (median age 62 years, interquartile range 56-67, 14 women), 26 age-matched and sex-matched healthy controls (HCs), and 14 patients with Helicobacter pylori infection (HP). We investigated the lamina propria mononuclear cell (LPMC) populations and the mucosal expression of thymic stromal lymphopoietin (TSLP) and nicotinamide phosphoribosyltransferase (NAMPT). Ex vivo cytokine production by organ culture biopsies, under different stimuli (short TSLP and zinc-l-carnosine), and the gastric vascular barrier through plasmalemma vesicle-associated protein-1 (PV1) were also assessed. In the subset of CD19+ LPMC, CD38+ cells (plasma cells) were significantly higher in AAG compared with HC. Ex vivo production of tumor necrosis factor (TNF)-α, interleukin (IL)-15, and transforming growth factor β1 was significantly higher in AAG compared with HC. At immunofluorescence, both IL-7R and TSLP were more expressed in AAG compared with HC and HP, and short TSLP transcripts were significantly increased in AAG compared with HC. In the supernatants of AAG corpus mucosa, short TSLP significantly reduced TNF-α, while zinc-l-carnosine significantly reduced interferon-γ, TNF-α, IL-21, IL-6, and IL-15. NAMPT transcripts were significantly increased in AAG compared with HC. PV1 was almost absent in AAG, mildly expressed in HC, and overexpressed in HP. Plasma cells, proinflammatory cytokines, and altered gastric vascular barrier may play a major role in AAG. TSLP and NAMPT may represent potential therapeutic targets, while zinc-l-carnosine may dampen mucosal inflammation.

Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice.

Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells.

BACKGROUNDGastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities. However, the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear.AIMTo assess whether tumor necrosis factor-α (TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells.METHODSThe normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the anti-inflammatory effects of quercetin. The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line. Cell migration was measured using Transwell assay. The expression of proto-oncogene tyrosine-protein kinase Src (c-Src), phospho (p)-c-Src, extracellular-signal-regulated kinase 2 (ERK2), p-ERK1/2, c-Fos, p-c-Fos, nuclear factor kappa B (NF-κB/p65), and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity. p65 expression was detected by immunofluorescence. MMP-9 mRNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction (qRT–PCR) and gelatin zymography, respectively.RESULTSqRT-PCR and gelatin zymography showed that TNF-α induced MMP-9 mRNA and protein expression in a dose- and time-dependent manner. These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-α antagonist (TNFR inhibitor) in a dose- and time-dependent manner. Quercetin and TNF-α antagonists decreased the TNF-α-induced phosphorylation of c-Src, ERK1/2, c-Fos, and p65 in a dose- and time-dependent manner. Quercetin, TNF-α antagonist, PP1, U0126, and tanshinone IIA (TSIIA) reduced TNF-α-induced c-Fos phosphorylation and AP-1–Luciferase (Luc) activity in a dose- and time-dependent manner. Pretreatment with quercetin, TNF-α antagonist, PP1, U0126, or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65–Luc activity in a dose- and time-dependent manner. TNF-α significantly increased GES-1 cell migration, and these results were reduced by pretreatment with quercetin or a TNF-α antagonist.CONCLUSIONQuercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src–ERK1/2 and c-Fos or NF-κB pathways.

Phlegmonous gastritis in 2 yearling horses.

Phlegmonous gastritis was diagnosed in 2 yearling fillies that were presented with a 1-wk history of fever, lethargy, and hypoproteinemia, associated with a previous diagnosis of equine proliferative enteropathy based on clinical signs and PCR assay detection of Lawsonia intracellularis in fecal samples. Abdominal ultrasound revealed enlargement of the stomach and expansion of its submucosal layer with hypoechoic fluid, as well as thickened hypomotile small intestinal segments. Given the poor prognosis and poor response to treatment, both horses were euthanized, one on the day of presentation and the other after 3 wk of intensive medical management including a combination of antimicrobials, analgesics, and intravenous colloids. At autopsy, acute mural gastritis characterized by severe submucosal edema with suppurative inflammation (i.e., phlegmonous gastritis) and necroulcerative enteritis compatible with the necrotizing form of equine proliferative enteropathy were identified in both horses. The gastric inflammation was associated with thrombosis and mixed bacterial populations, including Clostridium perfringens, that were confined to the submucosa without evidence of mucosal involvement; toxin genes compatible with C. perfringens type C were identified in one case. Human phlegmonous gastritis is an uncommon, often-fatal pyogenic infection that is often associated with mucosal injury, bacteremia, or immunocompromise. Our finding of this unusual gastric lesion in 2 horses with similar signalment, clinical disease, and spectrum of postmortem lesions suggests a similar etiopathogenesis that possibly involves local, regional, or distant hematogenous origin, and should be considered a potential complication of gastrointestinal mucosal compromise in horses.

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles.

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

Investigation of the enzymes required for the biosynthesis of an unusual formylated sugar in the emerging human pathogen Helicobacter canadensis.

It is now well established that the Gram-negative bacterium, Helicobacter pylori, causes gastritis in humans. In recent years, it has become apparent that the so-called non-pylori Helicobacters, normally infecting pigs, cats, and dogs, may also be involved in human pathology via zoonotic transmission. Indeed, more than 30 species of non-pylori Helicobacters have been identified thus far. One such organism is Helicobacter canadensis, an emerging pathogen whose genome sequence was published in 2009. Given our long-standing interest in the biosynthesis of N-formylated sugars found in the O-antigens of some Gram-negative bacteria, we were curious as to whether H. canadensis produces such unusual carbohydrates. Here, we demonstrate using both biochemical and structural techniques that the proteins encoded by the HCAN_0198, HCAN_0204, and HCAN_0200 genes in H. canadensis, correspond to a 3,4-ketoisomerase, a pyridoxal 5'-phosphate aminotransferase, and an N-formyltransferase, respectively. For this investigation, five high-resolution X-ray structures were determined and the kinetic parameters for the isomerase and the N-formyltransferase were measured. Based on these data, we suggest that the unusual sugar, 3-formamido-3,6-dideoxy-d-glucose, will most likely be found in the O-antigen of H. canadensis. Whether N-formylated sugars found in the O-antigen contribute to virulence is presently unclear, but it is intriguing that they have been observed in such pathogens as Francisella tularensis, Mycobacterium tuberculosis, and Brucella melitensis.

Clinical Outcomes after Oat Beta-Glucans Dietary Treatment in Gastritis Patients.

The prevalence of gastritis in humans is constantly growing and a prediction of an increase in this health problem is observed in many countries. For this reason, effective dietary therapies are sought that can alleviate the course of this disease. The objective of this study was to determine the effect of chemically pure oat beta-glucan preparations with different molar masses, low or high, used for 30 days in patients with histologically diagnosed chronic gastritis. The study enrolled 48 people of both genders of different ages recruited from 129 patients with a gastritis diagnosis. Before and after the therapy, hematological, biochemical, immunological and redox balance parameters were determined in the blood and the number of lactic acid bacteria and SCFA concentrations in the feces. Our results demonstrated a beneficial effect of oat beta-glucans with high molar mass in chronic gastritis in humans, resulting in reduced mucosal damage and healthy changes in SCFA fecal concentration and peripheral blood serum glutathione metabolism and antioxidant defense parameters. This fraction of a highly purified oat beta-glucan is safe for humans. Its action is effective after 30 days of use, which sheds new light on the nutritional treatment of chronic gastritis.

Therapeutic Potential of Poncirin Against Numerous Human Health Complications: Medicinal Uses and Therapeutic Benefit of an Active Principle of Citrus Species.

Medicinal plants have been used in the indigenous system of medicine for the treatment of numerous human health complications. Medicinal plants were used for the separation and isolation of pure phytochemical and some of the best examples are tubocurarine, aspirin, morphine, digoxin, atropine, quinine and reserpine. Phytoconstituents are pure, plant-derived, natural chemicals found to be present in medicinal plants and examples are flavonoids, alkaloids and phenolic compounds, etc. In modern medicine, there has been a global growth of herbal medicines due to their nutrition, physical effectiveness and pharmacological activities. Plants have been used in the traditional medicines and modern drug discoveries program. In order to investigate the biological potential of poncirin in modern medicine, here, different scientific data have been analyzed in the present investigation through various literature sources. Detailed pharmacological activities of poncirin were also investigated in the present investigation to reveal the medicinal properties of poncirin in medicine and other allied health sectors. Analytical techniques used for the isolation of poncirin from various medicinal plants have been also presented in this study. Poncirin is a flavanone glycoside found to be present in the Poncirus trifoliata and Citrus reticulate having a bitter taste. The biological importance of poncirin for their anti-inflammatory activity through inhibition of PGE2 and IL-6 production has been investigated in the scientific field. The biological importance of poncirin against bacterial, viral infections, gastric disease and human gastric cancer has been investigated in medicine. Pharmacological data analysis revealed the biological application of poncirin against bone loss, inflammation, colitis, human gastric cancer, gastritis, liver injury and Alzheimer's disease. From the analysis of the presented scientific information of poncirin, it was found that poncirin has significant biological activities and health benefits in the modern health sectors for the treatment of human health complications and could be used as a drug in the future.

Gentiopicroside ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling

Background: Excessive ethanol consumption results in gastric mucosa damage, which could further develop into chronic gastritis, peptic ulcer, and gastric cancer in humans. Gentiopicroside (GPS), a major active component of Gentianae Macrophyllae radix, was reported to play a critical role in anti-inflammation. In the study, we aimed to investigate the functional role and underlying mechanism of GPS in ethanol-induced gastritis. Methods: A model of gastritis was created by ethanol in C57BL/6 mice. Enzyme-linked immunosorbent assay was used to determine the concentration of TNF-α, IL-1β, IL-8, and IL-10. Results: We found that GPS treatment significantly ameliorated ethanol-induced gastritis in mice, with lower production of pro-inflammatory cytokine TNF-α, IL-1β, and IL-8 and higher levels of anti-inflammatory cytokine IL-10. The anti-inflammatory effect of GPS was further confirmed in vitro in ethanol-treated human gastric mucosal GES cells. Mechanistically, we demonstrated that GPS regulated matrix metallopeptidase expression and pERK1/2 signaling. Knockdown of matrix metallopeptidase 10 (MMP-10) greatly improved cell survival and suppressed inflammatory response in ethanol-treated GES cells. Moreover, inhibition of pERK1/2 signaling using U0126 decreased the expression of MMP-10 in ethanol-induced gastritis. U0126 treatment also suppressed the expression of TNF-α, IL-1β, and IL-8, and enhanced IL-10 expression in mice gastric mucosa. Conclusions: Taken together, our findings suggest that GPS ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling, which might provide a promising therapeutic drug for ethanol-induced gastritis.

RIPK1 Distinctly Regulates Yersinia-Induced Inflammatory Cell Death, PANoptosis.

Bacterial pathogens from the genus Yersinia cause fatal sepsis and gastritis in humans. Innate immune signaling and inflammatory cell death (pyroptosis, apoptosis, and necroptosis [PANoptosis]) serve as a first line of antimicrobial host defense. The receptor-interacting protein kinase 1 (RIPK1) is essential for Yersinia-induced pyroptosis and apoptosis and an effective host response. However, it is not clear whether RIPK1 assembles a multifaceted cell death complex capable of regulating caspase-dependent pyroptosis and apoptosis or whether there is cross-talk with necroptosis under these conditions. In this study, we report that Yersinia activates PANoptosis, as evidenced by the concerted activation of proteins involved in PANoptosis. Genetic deletion of RIPK1 abrogated the Yersinia-induced activation of the inflammasome/pyroptosis and apoptosis but enhanced necroptosis. We also found that Yersinia induced assembly of a RIPK1 PANoptosome complex capable of regulating all three branches of PANoptosis. Overall, our results demonstrate a role for the RIPK1 PANoptosome in Yersinia-induced inflammatory cell death and host defense.