Rapid visual detection of Helicobacter pylori and vacA subtypes by Dual-Target RAA-LFD assay.

BACKGROUND: Helicobacter pylori (H. pylori) infects over 50% of the global population and is a significant risk factor for gastric cancer. The pathogenicity of H. pylori is primarily attributed to virulence factors such as vacA. Timely and accurate identification, along with genotyping of H. pylori virulence genes, are essential for effective clinical management and controlling its prevalence. METHODS: In this study, we developed a dual-target RAA-LFD assay for the rapid, visual detection of H. pylori genes (16s rRNA, ureA, vacA m1/m2), using recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD) methods. Both 16s rRNA and ureA were selected as identification genes to ensure reliable detection accuracy. RESULTS: A RAA-LFD assay was developed to achieve dual-target amplification at a stable 37 °C within 20 min, followed by visualization using the lateral flow dipstick (LFD). The whole process, from amplification to results, took less than 30 min. The 95 % limit of detection (LOD) for 16 s rRNA and ureA, vacA m1, vacA m2 were determined as 3.8 × 10-2 ng/µL, 5.8 × 10-2 ng/µL and 1.4 × 10-2 ng/µL, respectively. No cross-reaction was observed in the detection of common pathogens including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis, showing the assay's high specificity. In the evaluation of the clinical performance of the RAA-LFD assay. A total of 44 gastric juice samples were analyzed, immunofluorescence staining (IFS) and quantitative polymerase chain reaction (qPCR) were used as reference methods. The RAA-LFD results for the 16s rRNA and ureA genes showed complete agreement with qPCR findings, accurately identifying H. pylori infection as confirmed by IFS in 10 out of the 44 patients. Furthermore, the assay successfully genotyped vacA m1/m2 among the positive samples, showing complete agreement with qPCR results and achieving a kappa (κ) value of 1.00. CONCLUSION: The dual-target RAA-LFD assay developed in this study provides a rapid and reliable method for detecting and genotyping H. pylori within 30 min, minimizing dependency on sophisticated laboratory equipment and specialized personnel. Clinical validation confirms its efficacy as a promising tool for effectively control of its prevalence and aiding in the precise treatment of H. pylori-associated diseases.

Redefining the Gastric Microbes in Promoting Gastric Tumorigenesis: The Rise of the Non-H. pylori Microbiome.

Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non-H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies.

Effects and mechanisms of Helicobacter pylori on cancers development and immunotherapy.

Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors.

Long-term Outcomes and Prognostic Factors of Gastric MALT Lymphoma.

PURPOSE: This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. MATERIALS AND METHODS: Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. RESULTS: Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum. CONCLUSIONS: The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS.

[The prevalence of mutations underlying development of Helicobacter pylori resistance to antibiotics in Kazan].

BACKGROUND: One of the reasons for the decrease of Helicobacter pylori eradication effectiveness is its resistance to antibiotics. AIM: To examine the prevalence of H. pylori point mutations responsible for clarithromycin and levofloxacin resistance among the patients with upper gastrointestinal (GI) tract disorders in Kazan. MATERIALS AND METHODS: The study included 203 patients with symptoms of dyspepsia who underwent upper GI endoscopy at the University Hospital of Kazan Federal University (Kazan, Russia) in 2019-2021. DNA isolation from gastric antrum mucosal biopsies was performed using PureLink Genomic DNA Mini Kits (Thermo Fisher Scientific, USA). Polymerase chain reaction was performed using primers specific for the V-region of the 23S gene and the A subunit DNA gyrase encoding gyrA gene region. The sequencing of obtained DNA fragments was performed on 3730 DNA Analyzer. The sequences were searched for point mutations responsible for H. pylori resistance to clarithromycin (A2143G, A2142G and A2142C193 mutations) and levofloxacin (mutations of the gyrA gene). RESULTS: H. pylori was detected in 47.78% of biopsy specimens using polymerase chain reaction. The proportion of H. pylori strains with mutations leading to clarithromycin resistance was 17.53%. Amino acid substitutions in the gyrA gene were found in 12.37% of samples. In case of two H. pylori strains (2.06%), dual resistance to clarithromycin and levofloxacin was found. CONCLUSION: So high incidence of mutations underlying the development of H. pylori resistance to clarithromycin and levofloxacin was observed among examined patients in Kazan.

Discovery of Cinnamic Acid Derivatives as Potent Anti-H. pylori Agents.

Antibiotics are currently used for the treatment of Helicobacter pylori (H. pylori), which is confirmed to be the major cause of gastric disorders. However, the long-term consumption of antibiotics has already caused antibiotic resistance and side effects in vivo. Therefore, there is an emerging need for searching for safe and effective anti-H. pylori agents. Inspired by the excellent bioactivities of cinnamic acid, a series of cinnamic acid derivatives (compounds 1-30) were synthesized and determined for H. pylori inhibition. The initial screening revealed that compound 23, a 2,4-dinitro cinnamic acid derivative containing 4-methoxyphenol, showed excellent H. pylori inhibition with an MIC value of 4 µM. Further studies indicated that compound 23 showed anti-bacterial activity and had a bactericidal effect on H. pylori due to the destruction of the bacterial structure. Molecular docking analysis revealed that the 2,4-dinitro groups in cinnamic acid moiety formed hydrogen bonding with amino acid residues in an active pocket of H. pylori protein. Interestingly, the ester moiety fitted into the hydrophobic pocket, attaining additional stability to compound 23. Above all, the present study reveals that compound 23 could be considered a promising anti-H. pylori agent to treat H. pylori causing gastritis.

Influence of oipA Phase Variation on Virulence Phenotypes Related to Type IV Secretion System in Helicobacter pylori.

BACKGROUND: oipA, an outer membrane protein of Helicobacter pylori, is linked to IL-8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of oipA phase variation in modulating the virulence traits of H. pylori, a bacterium strongly associated with the development of gastric cancer. MATERIAL AND METHODS: American clinical isolate AH868 strain for naturally occurring phase variations of the oipA gene, and G27 strain for in vitro-induced phase variations were used to elucidate oipA's impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL-8 induction. RESULTS: Using AH868 strain, natural oipA phase variation does not affect cell elongation and IL-8 induction. Interestingly, however, in vitro-induced oipA phase variations in G27 strain uncovered that 9.4% of oipA "Off" transformants exhibit reduced cell elongation while all maintaining consistent IL-8 induction levels. Additionally, complementation of oipA "Off to On" status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of oipA in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among oipA phase variation, cell elongation, and CagA phosphorylation, suggesting that oipA influences the functionality of the Type IV secretion system. Whole-genome sequencing of selected transformants reveals genetic variations in bab paralogue, cagY gene, and other genomic regions, underscoring the complex genetic interactions that shape H. pylori's virulence. CONCLUSIONS: Our research provides new insights into the subtle yet significant role of oipA phase variation in H. pylori pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of H. pylori on human health.

Study of the relationships among known virulence genes, coccoid transformation and cytotoxicity of Helicobacter pylori in different clinical diseases.

BACKGROUND: Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori. METHODS: The known important virulence genes of 35 H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) were infected with H. pylori strains in vitro to evaluate cytotoxicity of H. pylori. RESULTS: There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori. CONCLUSIONS: Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori. However, the correlation between the new virulence classification and pathogenic ability still needs to be further verified.

Fusobacterium nucleatum: Unraveling its potential role in gastric carcinogenesis.

Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.

A comparative study between current and past Helicobacter pylori infection in terms of microalbuminuria in patients with type 2 diabetes.

BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection and its potential relationship to various diseases is currently a focus of attention. The aim of this study is to investigate the association between current and past H. pylori infections and elevated levels of microalbuminuria in type 2 diabetic patients. METHODS: Two hundred patients with type 2 diabetes mellitus were tested for the presence of H. pylori infection. They were divided into three groups: 52 had a current H. pylori infection, 38 had a past H. pylori infection, and 110 had no H. pylori infection. All study participants underwent assessments of plasma glucose levels, glycated hemoglobin (HbA1c), albuminuria levels, inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as other relevant investigations. RESULTS: The prevalence of H. pylori infection (current and past) was detected in 90 out of 200 diabetic patients (45%). There was no statistically significant difference between the three groups in terms of age, diabetes duration, family history of DM, family history of hypertension, residence, or dyspeptic symptoms, indicating that current or past infection with H. pylori has no association with these variables. The current H. pylori infection group showed the highest levels of inflammatory markers, ESR and CRP, which were significantly different from those in the non-infected group (p = 0.013 and p < 0.001, respectively). The median (IQR) of albuminuria levels in the current H. pylori infection group, the past H. pylori infection group, and the non-infected group were 125 (4.8-290), 7.6 (2.4-271), and 5.1 (1.2-173), respectively. The current H. pylori infection group showed the highest albuminuria level, which was significantly different from that of the non-infected group (p = 0.001). CONCLUSION: There might be an association between microalbuminuria levels, general inflammatory markers (ESR and CRP), and current H. pylori infection in type 2 diabetic patients.

Effects of Helicobacter pylori and Helicobacter pylori eradication on the microbiota of tongue coating.

Eradicating Helicobacter pylori (H. pylori) can cause an imbalance in the microbiota. Dysbiosis of the gut microbiome may produce multiple diseases and bacterial infections. The objective of this study was to investigate the influence of Helicobacter pylori (H. pylori) infection and its eradication on the composition of the oral tongue coating microbiota. A cohort of 35 participants was recruited and categorized into two groups: the H. pylori negative group (N group) consisting of 12 individuals and the H. pylori positive group (23 individuals). Within the H. pylori positive group, subjects were further stratified into the H. pylori pre-eradicated group (HPQ group) and the H. pylori eradicated group (HPH group). H. pylori positive individuals were treated with a quadruple regimen containing bismuth, and tongue coating samples were collected both prior to and following treatment. Concurrently, tongue coating samples were collected from H. pylori negative individuals. High-throughput 16S rRNA sequencing technology was employed to assess the microbial composition of the tongue coating in the N group, HPQ group, and HPH group. Pertinent clinical data were documented.Microbial diversity was found to significantly differ among the N group, HPQ group, and HPH group, as evidenced by variations in Chao1 index, Shannon index, and Partial Least Squares Discriminant Analysis (PLS-DA). The dominant bacterial phyla identified across all groups included Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, Actinobacteria, and Saccharibacteria. At the phylum level, Firmicutes exhibited higher relative abundance in the HPQ group in comparison to both the N group and HPH group. Conversely, Bacteroidetes displayed greater prevalence in the N group and HPH group. Linear Discriminant Analysis Effect Size (LEfSe) analysis indicated a higher abundance of Romboutsia, Rothia, and Turiciactor in the HPQ group. Our study revealed significant disparities in microbial diversity and richness among the three groups. Furthermore, our findings suggest a potential association between the presence of Streptococcus, Rothia and H. pylori positive individuals.

Salivary glands - a new site of Helicobacter pylori occurrence.

OBJECTIVE: The role of Helicobacter pylori (Hp) in the pathological processes of the gastric mucosa is well understood. Decreasing trend in successful eradication of HP from the stomach was observed in last years. This lack of succes is mainly caused by increasing ATB resistance. Nevertheless other possible causes of this phenomenon are being explored. Thus, many studies have focused on the search for extragastric reservoirs as potential sources of persistence or reinfection after successful Hp eradication. The pathological potential of Hp at these localities has also been studied. METHODS: Our study aimed to determine the presence of Hp inside the salivary glands ductal system through its detection from sialolites. Subsequently, we tried to prove the possible ability of Hp to penetrate the salivary gland parenchyma by detecting Hp from the tissue of salivary tumors. Concrements and salivary tumor tissue samples were collected using sialendoscopy or standard surgery, and Hp detection and genotyping were performed through PCR. RESULTS: Hp was detected in 68.3% of the sialopathy samples. VacA S1AM1 was the most common genotype. CagA-positive genotype represented only 34% of the total number of positive samples. CONCLUSION: Our findings of Hp positivity in concrements provide compelling evidence of Hp presence in the ductal system of salivary glands. Confirmation of Hp presence in tumor tissue suggests its potential ability to infiltrate the gland's parenchyma. Further research is needed to confirm Hp's ability to cause local infection, as well as the possible causal association between Hp presence in the studied region, sialolithiasis, and salivary gland tumors.

Negative feedback loop in the activation of non-homologous end joining DNA repair pathway in Helicobacter pylori infected patients with gastritis.

This study aimed to investigate the activation of error-prone DNA repair pathway in response to Helicobacter pylori infection. Relative changes in the expression levels of genes involved in the non-homologous end-joining pathway (NHEJ) in H. pylori-infected (Cases) and non-infected patients (Controls) with chronic gastritis were measured. A significant increase in the relative expression level of TP53, and significant decrease in the relative transcription of lncRNA LINP1 and XRCC5 were detected in the case group. The transcription of Lig4 and XRCC6 was increased in the case group, which was not statistically significant. The Spearman's Correlation Coefficient analysis showed a significant positive-correlation between the transcriptional levels of LINP1 and XRCC4/XRCC5/Lig4, and between XRCC5 and TP53/Lig4 both in the case and control groups. Moreover, a significant positive correlation between LinP1 and XRCC6 in the case, and a significant positive correlation between XRCC4 and Lig4, and a negative correlation between TP53 and LinP1/XRCC4/XRCC5 in the control group was detected. Although a relative difference was detected in transcriptional levels of the NHEJ gene mediators, downregulation of LinP1 in H. pylori-infected patients proposed the activation of a negative feedback loop, which may interfere with the NHEJ activity at the early stages of gastritis.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

OBJECTIVE: To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. METHODS: A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. RESULTS: In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). CONCLUSION: The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

Helicobacter pylori PldA modulates TNFR1-mediated p38 signaling pathways to regulate macrophage responses for its survival.

Helicobacter pylori, a dominant member of the gastric microbiota was associated with various gastrointestinal diseases and presents a significant challenge due to increasing antibiotic resistance. This study identifies H. pylori's phospholipase A (PldA) as a critical factor in modulating host macrophage responses, facilitating H. pylori 's evasion of the immune system and persistence. PldA alters membrane lipids through reversible acylation and deacylation, affecting their structure and function. We found that PldA incorporates lysophosphatidylethanolamine into macrophage membranes, disrupting their bilayer structure and impairing TNFR1-mediated p38-MK2 signaling. This disruption results in reduced macrophage autophagy and elevated RIP1-dependent apoptosis, thereby enhancing H. pylori survival, a mechanism also observed in multidrug-resistant strains. Pharmacological inhibition of PldA significantly decreases H. pylori viability and increases macrophage survival. In vivo studies corroborate PldA's essential role in H. pylori persistence and immune cell recruitment. Our findings position PldA as a pivotal element in H. pylori pathogenesis through TNFR1-mediated membrane modulation, offering a promising therapeutic target to counteract bacterial resistance.

Systematic optimization of UCNPs-LFA for Helicobacter pylori nucleic acid detection at point-of-care.

Helicobacter pylori (Hp) prevail globally as the primary cause of gastritis, gastric ulcer, and potential gastric cancer, highlighting the need for rapid and precise point-of-care (POC) detection of Hp nucleic acid. Upconversion nanoparticle-based lateral flow assay (UCNPs-LFA) exhibit great potential in POC detection, due to their high optical stability and absence of background fluorescence. However, insufficient sensitivity for nucleic acid detection remains a key challenge. This study systematically optimizes UCNPs-LFA by focusing on target capture, signal transduction, signal separation, and signal analysis, to enhance its detection capabilities for Hp nucleic acid. The optimized UCNPs-LFA platform features a significantly decreased detection limit, a broadened detection range, and high reliability. Results demonstrate that the limit of detection (LOD) is 25 fM, a 105-fold improvement over the initial platform. This systematic optimization strategy is versatile and can be applied to optimize other nanoparticle-based LFAs.

Prevalence of metronidazole resistance and Helicobacter pylori infection in Moroccan children: a cross-sectional study.

Introduction: the prevalence of Helicobacter pylori (H. pylori) infection in children is very high in Morocco. Eradication rates of H. pylori infection decrease due to the emergence of resistance to antibiotics. Data on the antimicrobial susceptibility of H. pylori in Moroccan children are not available. This study aims to assess the prevalence of H. pylori infection and the metronidazole resistance rate of H. pylori in Moroccan pediatric patients, and their association with epidemiologic factors. Methods: a cross-sectional study was conducted on 132 pediatric patients who had an indication for upper gastrointestinal endoscopy and attended pediatric hospital Abderrahim Harouchi of the University Hospital Ibn Rochd, Casablanca, Morocco. Detection of H. pylori infection and the susceptibility to metronidazole was performed by classic PCR. Statistical analysis was performed using R Studio software. Results: the overall prevalence of H. pylori infection was 80.3%. vomiting was significantly associated with H. pylori infection (p-value=0.01). Regarding the resistance rate of metronidazole, we found that the prevalence of H. pylori resistance to metronidazole was high (70.8%) and it significantly increased, especially in pediatric patients living in urban areas (p-value=0.01). Conclusion: the prevalence of H. pylori infection and resistance rate of metronidazole were very high in Moroccan children. Therefore, triple therapy with metronidazole must be preceded by a study of the bacterium's susceptibility to the prescribed antibiotics, in particular to metronidazole.

Systematic Review and Meta-Analysis: Bismuth Enhances the Efficacy for Eradication of Helicobacter pylori.

BACKGROUND: In the eradication of Helicobacter pylori, the efficacy of bismuth remains inconclusive. We aimed to compare the efficacy of bismuth on various H. pylori eradication regimens. METHODS: Randomized controlled trials were collected to compare the efficacy of bismuth to nonbismuth regimens in H. pylori eradication. We pooled information to study eradication, adverse events, and drug compliance. In addition, subgroup analyses for eradication efficacy were performed according to high or low clarithromycin-resistance area, bismuth drug form, and amount of bismuth element. RESULTS: Records for a total of 2506 patients in 15 trials from 13 randomized controlled studies were included. The eradication of H. pylori was superior when bismuth compared to nonbismuth regimen (odds ratio [OR] = 1.63, 95% confidence interval [CI], 1.33-2.00 in intention-to-treat [ITT]; OR = 2.05, 95% CI, 1.58-2.68 in per-protocol [PP] analyses), without significant difference in drug compliance or adverse events. Bismuth regimens in the high clarithromycin resistance area tend to enhance the eradication rate (OR = 1.66, 95% CI, 1.34-2.05 in ITT; OR = 2.22, 95% CI, 1.67-2.95 in PP analyses). Bismuth potassium citrate and bismuth subcitrate were more effective drug forms in regard to eradication rate. Bismuth at a dosage of < 500 mg/day was significantly higher for the eradication rate. CONCLUSIONS: Bismuth to the H. pylori eradication regimens achieve a higher eradication rate, especially in the high clarithromycin resistance area. It could be an eradication option achieving sufficient resistance rates without increasing antibiotic resistance, side effects, or poor compliance.

Effects and mechanisms of Helicobacter pylori infection on the occurrence of extra-gastric tumors.

Helicobacter pylori (H. pylori) colonizes the human stomach and many studies have discussed the mechanisms of H. pylori infection leading to gastric diseases, including gastric cancer. Additionally, increasing data have shown that the infection of H. pylori may contribute to the development of extra-gastric diseases and tumors. Inflammation, systemic immune responses, microbiome disorders, and hypergastrinemia caused by H. pylori infection are associated with many extra-gastric malignancies. This review highlights recent discoveries; discusses the relationship between H. pylori and various extra-gastric tumors, such as colorectal cancer, lung cancer, cholangiocarcinoma, and gallbladder carcinoma; and explores the mechanisms of extra-gastric carcinogenesis by H. pylori. Overall, these findings refine our understanding of the pathogenic processes of H. pylori, provide guidance for the clinical treatment and management of H. pylori-related extra-gastric tumors, and help improve prognosis.

Identification of interaction partners of outer inflammatory protein A: Computational and experimental insights into how Helicobacter pylori infects host cells.

Outer membrane proteins (OMPs) play a key role in facilitating the survival of Helicobacter pylori within the gastric tissue by mediating adherence. Among these proteins, Outer inflammatory protein A (OipA) is a critical factor in H. pylori colonization of the host gastric epithelial cell surface. While the role of OipA in H. pylori attachment and its association with clinical outcomes have been established, the structural mechanisms underlying OipA's action in adherence to gastric epithelial cells remain limited. Our study employed experimental and computational approaches to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we conducted a proteomic analysis using a pull-down assay with recombinant OipA and gastric epithelial cell membrane proteins to identify the OipA interactome. This analysis revealed 704 unique proteins that interacted with OipA. We subsequently analyzed 16 of these OipA partners using molecular modeling tools. Among these 16 partners, we highlight three human proteins, namely Hepatocyte growth factor (HGF), Mesenchymal epithelial transition factor receptor (Met), and Adhesion G Protein-Coupled Receptor B1 (AGRB1) that could play a role in H. pylori adherence to the gastric epithelial cell surface with OipA. Collectively, these findings reveal novel host interactions mediated by OipA, suggesting their potential as therapeutic targets for combating H. pylori infection.