In vitro anti-bactrical activity and its preliminary mechanism of action of the non-medicinal parts of Sanguisorba officinalis L. against Helicobacter pylori infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanguisorba officinalis L. (S. officinalis L.), known as Di Yu (DY) in Traditional Chinese Medicine (TCM), are used to treat burns, vomiting of blood, asthma, intestinal infections, and dermatitis. It has been reported that the root of DY has a significant inhibitory effect on Helicobacter pylori (H. pylori). However, there is currently little research on the composition analysis and anti-H. pylori infection properties of the non-medicinal parts of DY, such as its stems, leaves, and flowers. AIM OF STUDY: The commonly used eradication therapies for H. pylori infection are antibiotic-based therapies. With the increasing antibiotic resistance of H. pylori, it is urgent to find effective alternative therapies. To find alternative therapies and increase the utilization of DY, this study aims to investigate the phytochemistry profile, in vitro anti-H. pylori activity, and preliminary antibacterial mechanism of the non-medicinal parts of DY. MATERIALS AND METHODS: The non-medicinal parts of DY extracts were obtained by using hot water reflux method. The chemical composition of these extracts was analyzed using colorimetric method, high-performance liquid chromatography (HPLC), and ultra-high-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in vitro anti-H. pylori activity was investigated using broth microdilution method, checkerboard dilution method, time-kill curve, time-inhibition curve, scanning electron microscopy, and transmission electron microscopy. Transcriptional sequencing technology was used to study the effect of DY stems and flowers on the gene expression of H. pylori and explore possible antibacterial mechanisms. RESULTS: The non-medicinal parts of DY contain abundant phytochemicals, such as total phenols and total flavonoids, and possess strong inhibitory and bactericidal activity against both standard and clinical strains of H. pylori in vitro. The MIC was 80-1280 µg/mL and the MBC was 80-2560 µg/mL, and the strength of the antibacterial effects was dependent on the concentration of phytochemicals (total polyphenols, gallic acid and ellagic acid). In addition, the combination of non-medicinal parts of DY with antibiotics, such as amoxicillin, metronidazole, levofloxacin, and clarithromycin, did not result in any antagonistic effects. All of them could disrupt the morphology, internal microscopic and cell wall structures of H. pylori thereby acting as an inhibitor. The mechanism of action was found to be the disruption of H. pylori morphology, internal microstructure, and cell wall. Transcriptomic analysis showed that the non-medicinal parts of DY significantly regulated the gene expression of H. pylori, especially the metabolic pathway. CONCLUSIONS: This study analyzed the chemical composition of the non-medicinal parts of DY and confirmed its inhibitory and bactericidal activities against H. pylori, both standard and clinical strains. Additional, the mechanism of inhibition involves disrupting the structure of H. pylori cells, altering gene expression, and interfering with bacterial metabolic pathways. This study provides a reference for further resource utilization and the development of H. pylori drugs using the non-medicinal parts of DY.

Epiberberine inhibits Helicobacter pylori and reduces host apoptosis and inflammatory damage by down-regulating urease expression.

ETHNOPHARMACOLOGICAL RELEVANCE: With dramatically increasing antibiotic resistance in Helicobacter pylori (H. pylori), it is urgent to find alternative therapeutic agents. Rhizoma Coptidis is a traditional Chinese medicine for gastrointestinal diseases and shows excellent anti-H. pylori effect. Epiberberine (EPI), as one of the major alkaloids of Rhizoma Coptidis, has been reported to have urease-inhibiting activity, but its scavenging effect on H. pylori and the potential mechanism remain unclear. AIM OF THE STUDY: To investigate the inhibitory effect of EPI on H. pylori and explore its multi-action on Helicobacter pylori urease (HPU). MATERIALS AND METHODS: Using minimum inhibitory concentration (MIC) assay, minimum bactericidal concentration (MBC) assay, growth inhibition kinetics assay, bacterial resistance development, transmission electron microscope (TEM) assay, and animal experiments to investigate the inhibitory effect of EPI on H. pylori in vitro and in vivo. Using the Berthelot method, molecular docking and thermal displacement experiments to verify that EPI inhibits urease activity by interacting with HPU. Using transcriptome data, Real-Time PCR (RT-PCR) experiments to investigate the alterations in the expression of urease subunit ureB gene after EPI treatment. Using MTT cell viability assay, Hoechst 33342 staining method, JC-1 reagent detection method, western blot experiments, and Griess method to investigate the anti-apoptosis and anti-inflammation actions of EPI on gastric epithelial cells (GES-1) induced by HPU. RESULTS: In vitro experiments proved that EPI has significant anti-H. pylori activity without drug resistance, induces H. pylori fragmentation and apoptosis. In vivo experiments showed that EPI has a certain clearance effect of H. pylori, and can reduce gastric inflammation caused by H. pylori infection. Transcriptome data, RT-PCR experiments, and other experiments demonstrate that EPI has a triple effect: (1) inhibiting the expression of HPU subunits ureB, (2) directly inhibiting urease activity by interacting with HPU, and (3) inhibiting HPU-induced apoptosis and inflammation in GES-1. CONCLUSIONS: EPI is an excellent anti-H. pylori agent and reduces host apoptosis and inflammation by inhibiting the activity of urease and down-regulating the expression of ureB.

Can We StoP Worrying about Long-term PPIs and Gastric Cancer Risk?

Proton pump inhibitors (PPI) are a cornerstone of management for many digestive diseases. While chronic PPI use induces physiologic changes including gastric acid suppression and hypergastrinemia, existing data are conflicting on whether this impacts the risk of gastric cancer among PPI users. Sassano and colleagues utilized pooled case-control data from five studies in the Stomach cancer Pooling (StoP) Project to investigate the association between PPI use and histologically confirmed gastric cancer. Short-term PPI use (6 months) was associated with increased risk of gastric cancer, but no association was found between long-term PPI use (3 years or more) and gastric cancer. Although the authors relied on patient-reported PPI use data, and data related to Helicobacter pylori infection and eradication rates were missing, no histologic gastric cancer subtypes in this international case-control study were associated with any PPI use. Currently reported findings provide patients and clinicians with reassuring observations that long-term PPI use does not significantly increase gastric cancer risk. The relationship identified among short-term PPI users may reflect reverse causality. Our understanding will be furthered by additional assessment of potential confounders, including comorbid conditions, PPI metabolism, and social determinants of health. See related article by Sassano et al., p. 1174.

Helicobacter pylori intragastric colonization and migration: Endoscopic manifestations and potential mechanisms.

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection.

Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Developing Operational Definitions Related to Helicobacter pylori Eradication Therapy.

BACKGROUND: The lack of well-established operational definitions is a major limitation of Helicobacter pylori eradication studies that use secondary databases. We aimed to develop and validate operational definitions related to H. pylori eradication therapy. METHODS: Operational definitions were developed by analyzing a nationwide H. pylori eradication registry and validated using real-world data from hospital medical records. The primary endpoint was the sensitivity of the operational definitions in identifying individuals who received H. pylori eradication therapy. The secondary endpoint was the sensitivity and specificity of the operational definition in identifying successful H. pylori eradication therapy. RESULTS: H. pylori eradication therapy was defined as a prescription for one of the following combinations: 1) proton pump inhibitor (PPI) + amoxicillin + clarithromycin, 2) PPI + amoxicillin + metronidazole, 3) PPI + metronidazole + tetracycline, 4) PPI + amoxicillin + levofloxacin, 5) PPI + amoxicillin + moxifloxacin, or 6) PPI + amoxicillin + rifabutin. In the validation set, the sensitivity of the operational definition for identifying individuals who received H. pylori eradication therapy was 99.7% and 99.8% for the first- and second-line therapies, respectively. Operational definition to determine success or failure of the H. pylori eradication therapy was developed based on a confirmatory test and the prescription of rescue therapy. The sensitivity and specificity of the operational definition for predicting successful eradication were 97.6% and 91.4%, respectively, in first-line therapy and 98.6% and 54.8%, respectively, in second-line therapy. CONCLUSION: We developed and validated operational definitions related to H. pylori eradication therapy. These definitions will help researchers perform various H. pylori eradication-related studies using secondary databases.

Investigation of the prevalence and risk factors of Helicobacter pylori infection and the value of different gastric cancer screening methods in a low-risk region of gastric cancer in China.

BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.

Identification and characterization of shark VNARs targeting the Helicobacter pylori adhesin HpaA.

Helicobacter pylori (H. pylori) is recognized as a pathogen associated with several gastrointestinal diseases. The current treatments exhibit numerous drawbacks, including antibiotic resistance. H. pylori can adhere to and colonize the gastric mucosa through H. pylori adhesin A (HpaA), and antibodies against HpaA may be an effective therapeutic approach. The variable domain of immunoglobulin new antigen receptor (VNAR) is a novel type of single-domain antibody with a small size, good stability, and easy manufacturability. This study isolated VNARs against HpaA from an immune shark VNAR phage display library. The VNARs can bind both recombinant and native HpaA proteins. The VNARs, 2A2 and 3D6, showed high binding affinities to HpaA with different epitopes. Furthermore, homodimeric bivalent VNARs, biNb-2A2 and biNb-3D6, were constructed to enhance the binding affinity. The biNb-2A2 and biNb-3D6 had excellent stability at gastrointestinal pH conditions. Finally, a sandwich ELISA assay was developed to quantify the HpaA protein using BiNb-2A2 as the capture antibody and BiNb-3D6 as the detection antibody. This study provides a potential foundation for novel alternative approaches to treatment or diagnostics applications of H. pylori infection.

Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms.

Objectives: Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains' application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases. Methods: The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar. Results: The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study. Conclusion: This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

Helicobacter pylori infection altered gastric microbiota in patients with chronic gastritis.

Objective: The present study aims to investigate the effect of Helicobacter pylori (Hp) infection on gastric mucosal microbiota in patients with chronic gastritis. Methods: Here recruited a population of 193 patients with both chronic gastritis and positive rapid urease, including 124 patients with chronic atrophic gastritis (CAG) and 69 patients with chronic non-atrophic gastritis (nCAG). Immunoblotting was used to detect four serum Hp antibodies (UreA, UreB, VacA and CagA) to determine the types of virulent Hp-I and avirulent Hp-II infections. Gastric microbiota was profiled by 16S rRNA gene V3-V4 region, and R software was used to present the relationship between the microbial characteristics and the type of Hp infection. Results: In the stomach of patients with Hp-positive gastritis, the dominant gastric bacterial genera included Ralstonia (23.94%), Helicobacter (20.28%), Pseudonocardia (9.99%), Mesorhizobium (9.21%), Bradyrhizobium (5.05%), and Labrys (4.75%). The proportion of Hp-I infection was significantly higher in CAG patients (91.1%) than in nCAG patients (71.0%) (P < 0.001). The gastric microbiota richness index (observed OTUs, Chao) was significantly lower in CAG patients than in nCAG patients (P <0.05). Compared with avirulent Hp-II infection, virulent Hp-I infection significantly decreased the Shannon index in CAG patients (P <0.05). In nCAG patients, Hp-I infected patients had lower abundances of several dominant gastric bacteria (Aliidiomarina, Reyranella, Halomonas, Pseudomonas, Acidovorax) than Hp-II infected patients. Meanwhile, in CAG patients, Hp-I infected patients occupied lower abundances of several dominant oral bacteria (Neisseria, Staphylococcus and Haemophilus) than Hp-II infected patients. In addition, bile reflux significantly promoted the colonization of dominant oral microbiota (Veillonella, Prevotella 7 and Rothia) in the stomach of CAG patients. There was no significant symbiotic relationship between Helicobacter bacteria and non-Helicobacter bacteria in the stomach of nCAG patients, while Helicobacter bacteria distinctly linked with the non-Helicobacter bacteria (Pseudolabrys, Ralstonia, Bradyrhizobium, Mesorhizobium and Variovorax) in CAG patients. Conclusions: Virulent Hp infection alters the gastric microbiota, reduces microbial diversity, and enhances the symbiotic relationship between the Helicobacter bacteria and non-Helicobacter bacteria in patients with chronic gastritis. The data provides new evidence for treating Hp infection by improving the gastric microbiota.

Association between Helicobacter pylori infection and triglyceride levels: a nested cross-sectional study.

Background: Currently, the available evidence regarding the relationship between the lipid profile and Helicobacter pylori (H. pylori) infection is limited and conflicting. There is also a dearth of studies that have explored the possibility of sex-specific differences in the association between H. pylori infection and triglyceride levels. Methods: We conducted a cross-sectional study involving 1,146 participants utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 conducted in the United States. A logistic regression model was employed to evaluate the association between H. pylori seropositivity and triglyceride levels. Subgroup analyses stratified by sex were conducted to explore sex-specific differences in this association. Results: Serum triglyceride levels were significantly higher in H. pylori-seropositive participants than in H. pylori-seronegative participants. In the logistic regression analysis, there was a positive correlation between H. pylori seropositivity and triglyceride levels (OR=1.231; 95% CI, 1.016-1.491; P=0.033). In the subgroup analysis, the adjusted association between serum triglycerides and H. pylori seropositivity was significant in females (OR=1.732; 95% CI, 1.113-2.696; P=0.015) but not in males (OR=1.091; 95% CI, 0.698-1.705; P=0.704). Conclusion: The association between high triglyceride levels and H. pylori infection is specific to the female population.

Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation.

Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Significance: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

Antibiotic-Resistant Strains of Helicobacter pylori in 50 Antibiotic Treatment-Naive Children in Northeast Poland Diagnosed by Gastric or Duodenal Biopsy Between February 2019 and May 2022.

BACKGROUND In recent years, an increasing prevalence of Helicobacter pylori resistance to antibiotics has been observed. The aim of this study was to assess antibiotic resistance of Helicobacter pylori in previously untreated children from northeast Poland. MATERIAL AND METHODS Inclusion criteria comprised suspicion of Helicobacter pylori infection based on the presence of Helicobacter pylori antigen in the stool and/or characteristic macroscopic lesions seen on esophagogastroduodenoscopy. Samples of the gastric and/or duodenal mucosa were collected from 82 children with a median age of 13 years (range 3-17) during esophagogastroduodenoscopy between February 2019 and May 2022. The material was cultured, and positive Helicobacter pylori strains were tested for drug resistance to amoxicillin, metronidazole, and clarithromycin using the quantitative antibiotic concentration gradient stripe method E-test. RESULTS Based on biopsy culture, Helicobacter pylori infection was confirmed in 50 (61%) children. Helicobacter pylori resistance was most common to clarithromycin (n=19; 38%), followed by metronidazole (n=15; 30%), and the least frequent to amoxicillin (n=13; 26%). The resistance to 1 antibiotic was found in 14 children (28%). Double-drug resistance was noted in 3 children (6%) and triple drug resistance in 9 children (18%). In the whole group, 24 children (48%) were susceptible to all 3 antibiotics. CONCLUSIONS In this study, conducted for the first time in treatment-naïve children in northeast Poland, we found a high proportion of Helicobacter pylori strains resistant to at least 1 antibiotic. Our results may help in the appropriate choice of antibiotics for treatment of Helicobacter pylori in our region.

Association between helicobacter pylori infection and primary open-angle glaucoma: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma. METHODS: Eligible studies reporting an association between H. pylori infection and Glaucoma were identified through an extensive search of the Excerpta Medica (EMBASE), Web of Science, Scopus, and PubMed databases and an assessment of the reference list of the top articles until October 2022. Analysis was performed with random effects model using Stata 16. RESULT: Twenty-four studies were included in the systematic review. This study involved 1602 glaucoma patients and 2800 control individuals. The combined RRs of cohort studies and overall combined ORs of case-control studies showed a significant correlation between H. pylori infection and Glaucoma. Subgroup analysis showed that glaucoma patients had a higher risk of having H. pylori infection if they were residents of Europe countries (Cohort: RR: 1.69; 95% CI: 1.3-2.19) and (Case-Control: RR: 3.71; 95% CI: 2.07-6.64), if they had POAG type (Cohort: RR: 1.76; 95% CI: 1.37-2.27) and (Case-Control: RR: 3.71; 95% CI: 2.934.70), if their diagnostic method of HP was histology (Cohort: RR: 1.95; 95% CI: 1.26-3.01) and (Case-Control: RR: 4.06; 95% CI: 2.28-7.22), and if they were over 60 years old (Cohort: RR: 1.63; 95% CI: 1.33-2.00) and (Case-Control: RR: 2.95; 95% CI: 2.27-3.83). DISCUSSION: The results of this meta-analysis suggest a statistically significant association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.

Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation.

BACKGROUND: Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study. AIM: To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections. METHODS: H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified. RESULTS: Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes. CONCLUSION: Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Activation of the DNA damage response pathway in the infected gastric tissue with Helicobacter pylori: a case-control study.

INTRODUCTION: Gastritis is among the most common human diseases worldwide. Although the involvement of Helicobacter pylori infection as a class I human carcinogen for gastric cancer progression is accepted, it is not well known how gastritis progression to atrophy and stomach cancer occurs. In this case-control study, the potential link of H. pylori infection with alteration in the transcription of genes involved in DNA Damage Response pathways was investigated among the patients with gastritis. METHODOLOGY: To measure the difference in the relative mRNA expression level of ATM, CHEK2, TP53, DCLRE1C, POLM, and XRCC4 genes between H. pylori-infected and non-infected patients, gastric biopsies of 30 H. pylori infected patients with moderate chronic gastritis and 30 non-infected patients with mild chronic gastritis were analyzed. RESULTS: Up-regulation of genes linked to non-homologous end joining (NHEJ) pathway (DCLRE1C, POLM, and XRCC) was shown in 40% (8.44 fold ± 13.91), 63.33% (15.72 fold ± 33.08) and 50% (9.99 fold ± 21.55), respectively, and also to DDR pathway (ATM, CHEK2, and TP53) in 33% (2.42 fold ± 3.17), 40% (2.86 fold ± 3.61) and 50% (5.00 fold ± 6.52), respectively. No correlation was detected between alteration in the transcription level of the studied genes and age or gender. CONCLUSIONS: Our results provide new data that may support the potential involvement of H. pylori infection in the activation of genes involved in DNA damage response, mainly through a non-homologous end-joining DNA repair system that might be linked to mutagenesis in the pre-cancerous gastric tissue.

Biosynthesis, structure and biological function of cholesterol glucoside in Helicobacter pylori: A review.

Helicobacter pylori (H pylori) is a common pathogen, and about 50% of the world population have been infected with it, so the infection of H pylori has been an urgent public health problem worldwide. H pylori has evolved a variety of strategies to help itself colonize, adapt to the environment and proliferate. Cholesterol glucoside (CG), a characteristic substance in H pylori, is related to the membrane stability, morphology, inflammation induction and immune evasion of H pylori. Therefore, CG may be a new target to weaken the infection effect of H pylori. The biosynthesis process, structure and biological function of CG specific to H pylori, as well as anti-CG drugs are discussed and analyzed in this review, in order to explore whether the inhibition of CG synthesis can be an effective strategy to eradicate H pylori.

Inflammation and Digestive Cancer.

Chronic inflammation is linked to carcinogenesis, particularly in the digestive organs, i.e., the stomach, colon, and liver. The mechanism of this effect has, however, only partly been focused on. In this review, we focus on different forms of chronic hepatitis, chronic inflammatory bowel disease, and chronic gastritis, conditions predisposing individuals to the development of malignancy. Chronic inflammation may cause malignancy because (1) the cause of the chronic inflammation is itself genotoxic, (2) substances released from the inflammatory cells may be genotoxic, (3) the cell death induced by the inflammation induces a compensatory increase in proliferation with an inherent risk of mutation, (4) changes in cell composition due to inflammation may modify function, resulting in hormonal disturbances affecting cellular proliferation. The present review focuses on chronic gastritis (Helicobacter pylori or autoimmune type) since all four mechanisms may be relevant to this condition. Genotoxicity due to the hepatitis B virus is an important factor in hepatocellular cancer and viral infection can similarly be central in the etiology and malignancy of inflammatory bowel diseases. Helicobacter pylori (H. pylori) is the dominating cause of chronic gastritis and has not been shown to be genotoxic, so its carcinogenic effect is most probably due to the induction of atrophic oxyntic gastritis leading to hypergastrinemia.

Dimethylaminododecyl Methacrylate-Incorporated Dental Materials Could Be the First Line of Defense against Helicobacter pylori.

Oral cavity is an essential reservoir for H. pylori. We aimed to investigate the antibacterial effects of dimethylaminododecyl methacrylate (DMADDM) against H. pylori. Modified giomers were prepared by introducing 0%, 1.25% and 2.5% DMADDM monomers. Broth microdilution assay, spot assay, Alamer Blue assay, PMA-qPCR, crystal violet staining, scanning electron microscopy observation and live/dead bacterial staining were performed to evaluate the antibacterial and antibiofilm effects of DMADDM and modified giomers in vitro. Urease assay, qPCR, hematoxylin-eosin staining and ELISA were performed to evaluate the inflammation levels and colonization of H. pylori in vivo. In vitro experiments indicated that the minimum inhibitory concentration and minimum bactericidal concentration of DMADDM were 6.25 µg/mL and 25 µg/mL, respectively. It inhibited H. pylori in a dose- and time-dependent manner, and significantly reduced the expression of cagA, vacA, flaA and ureB. DMADDM-modified giomers inhibited the formation of H. pylori biofilm and reduced live cells within it. In vivo experiments confirmed that the pretreatment with DMADDM-modified dental resin effectively reduced the gastric colonization of oral-derived H. pylori, suppressed systemic and local gastric inflammation. DMADDM monomers and DMADDM-modified giomers possessed excellent antibacterial and antibiofilm effects on H. pylori. Pretreatment with DMADDM-modified giomers significantly inhibited the gastric infection by H. pylori.