This study aims to examine the underlying mechanism of gastric mucosal atrophy induced by vacuolar cytotoxin A (VacA) produced by Helicobacter pylori.

A total of 942 endoscopic biopsy and endoscopic submucosal dissection samples of gastric mucosa infected with H. pylori were subjected to detailed histomorphological and immunohistochemical analysis.

H. pylori exhibited specific adherence to surface mucus cells, proliferating extensively while producing and secreting VacA. The atrophic process was initiated by the upward migration and compensatory proliferation of cells in the deeper regions of the gastric pit, isthmus, and mucous neck cells. VacA disrupted the normal physiological organization and polarity of the proliferative zone, altering the proliferation patterns and directional growth of stem cells. This disruption resulted in a disordered state of cell proliferation. Insufficient downward migration of cells within the proliferative zone led to atrophy of the lamina propria glands in the gastric mucosa. This process was accompanied by epithelial cell proliferation and transformation, along with interstitial infiltration of lymphocytes, a small number of plasma cells, and neutrophils. These histopathological changes ultimately contributed to the characteristic atrophic gastritis associated with H. pylori infection.

A comprehensive understanding of the histopathological features of VacA-induced gastric mucosal atrophy is essential for the prevention and management of H. pylori-related gastric carcinogenesis.

Helicobacter pylori (H.pylori) is considered to be the most important gastrointestinal pathogen causing gastritis, gastric ulcers and even gastric cancer. The treatment of these infections has failed due to the rapidly increasing antibiotic resistance to standard treatment regimens and the lack of an effective vaccine. This study investigates the production and therapeutic potential of Immunoglobulin Y (IgY) antibodies targeting key epitopes of the H. pylori UreB recombinant protein. Given the increasing challenge of antibiotic resistance in H. pylori treatment, this research underscores the necessity for alternative therapeutic strategies. A specific region of the UreB gene, containing critical immunogenic epitopes, was amplified using Polymerase Chain Reaction (PCR) and cloned into the pET32b vector. The recombinant plasmid was expressed in Escherichia coli BL21 (DE3), and the UreB protein was purified via Ni-NTA affinity chromatography, confirmed by SDS-PAGE and Western blot analysis. Hens were immunized with the recombinant UreB protein, resulting in the generation of specific IgY antibodies. The purified IgY-UreB antibodies exhibited a remarkable reduction in urease activity by 84.53 % at a concentration of 10 mg/mL, effectively neutralizing this critical virulence factor. Additionally, in vitro assays demonstrated that IgY-UreB antibodies significantly inhibited the growth of H. pylori at a concentration of 5 mg/mL. These findings highlight the potential of IgY as a viable alternative to traditional antibiotic therapies, particularly in the context of rising antibiotic resistance. This study paves the way for the development of innovative immunotherapeutic strategies that may improve treatment outcomes for H. pylori infections.

This article employed a bidirectional Mendelian randomization (MR) analysis to deduce the causal relationship between H. pylori infection (Seven H. pylori antibodies: CagA, Catalase, GroEL, IgG, OMP, UREA, and VacA) and allergic diseases. This study primarily employed the Inverse-Variance Weighted (IVW)method, supplemented by MR-Egger regression and the Weighted median (WM) method approach, to comprehensively assess the causal relationship between exposure and outcome. Sensitivity analysis, including Cochran's Q test, MR-Egger regression intercept, MR-PRESSO test, and leave-one-out analysis, verified the reliability of the results. In the forward MR analysis, the IVW analysis outcomes showed the causal relationship existed between the allergic urticaria (AU) and Catalase antibody, allergic asthma (AA) and allergic rhinitis (AR) with OMP antibody, and allergic conjunctivitis (AC) and VacA antibody; in the reverse MR analysis, the results of the IVW analysis revealed that CagA antibody was positively associated with AU. Sensitivity analysis indicated that the causal relationship was robust. Higher levels of Catalase antibody may potentially increase the risk of AU development; increased OMP antibody levels might be associated with a higher risk for AA, yet could potentially be a protective factor against AR; greater VacA antibody levels might possibly decrease the incidence of AC; individuals with AU might have a higher likelihood of exhibiting elevated CagA antibody levels. It is suggested that H. pylori infection could potentially influence the onset and progression of allergic diseases via the "gut-skin", "gut-lung", "gut-nose", and "gut-eye" axis; moreover, skin diseases may potentially impact the gut microbiota imbalance through the "skin-gut" axis.

Helicobacter pylori infection of the stomach is the main risk factor for gastric noncardia adenocarcinoma; however, less is known on how eradication of H pylori influences the risk of this tumor over time, particularly in Western populations. The aim of this study was to delineate how the risk of gastric noncardia adenocarcinoma develops over time after H pylori eradication treatment in a Western population compared with the background population.

This population-based cohort study included all adults having received H pylori eradication treatment between 1995 and 2019 in any of the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by comparing the gastric noncardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country. Time trends in SIR were assessed using Poisson regression.

Among 659,592 participants having received H pylori eradication treatment, contributing 5,480,873 person-years at risk, 1311 developed gastric noncardia adenocarcinoma. During up to 24 years of follow-up, the SIR was initially higher than the background population (SIR, 2.27; 95% CI 2.10-2.44, 1-5 years after treatment), and then gradually decreased over time and approached the level of the background population from 11 years after treatment (SIR, 1.11; 95% CI 0.98-1.27, 11-24 years after treatment).

This study revealed a decreasing incidence of gastric noncardia adenocarcinoma after H pylori eradication treatment in 5 Western populations. The risk became virtually similar to the background population from 11 years after treatment.

This study aimed to assess the impact of Lactiplantibacillus plantarum Lp05 (Lp05) on the gastrointestinal microbiome and pathophysiological status of mice infected with Helicobacter pylori (H. pylori), exploring its potential as a probiotic treatment for H. pylori infections.

In vitro, the interaction between Lp05 and H. pylori was analyzed using laser confocal and scanning electron microscopy. In vivo, C57BL/6 mice infected with H. pylori were treated with Lp05 and divided into six groups: control, model, quadruple therapy, and three dosage levels of Lp05 (2×107, 2×108, 2×109 CFU/mouse/day). Over six weeks, the impact of Lp05 on the gastrointestinal microbiome and physiological markers was assessed. Measurements included digestive enzymes (α-amylase, pepsin, cellulase), inflammatory markers (interleukin-17A, interleukin-23, interleukin-10, interferon-β, interferon-γ, FoxP3, endothelin, IP-10, TGF-β1), oxidative stress markers (catalase, malondialdehyde, superoxide dismutase, myeloperoxidase), and tissue pathology (via modified Warthin-Starry silver and H&E staining). Microbial community structure in the stomach and intestines was evaluated through 16S rRNA gene sequencing.

In vitro studies showed Lp05 and H. pylori formed co-aggregates, with Lp05 potentially disrupting H. pylori cell structure, reducing its stomach colonization. In vivo, Lp05 significantly lowered gastric mucosal urease activity and serum H. pylori-IgG antibody levels in infected mice (p < 0.01). It also mitigated pathological changes in the stomach and duodenum, decreased inflammatory responses (ET, IL-17A, IL-23, TGF-beta1, and IP-10, p < 0.01 for all), and enhanced antioxidant enzyme activities (CAT and SOD, p < 0.01) while reducing MDA and MPO levels (p < 0.01), combating oxidative stress from H. pylori infection. Lp05 treatment significantly modified the intestinal and gastric microbiota, increasing beneficial bacteria like Lactobacillus and Ligilactobacillus, and decreasing harmful bacteria such as Olsenella, linked to pathological conditions.

Lp05 effectively modulates the gastrointestinal microbiome, reduces inflammation and oxidative stress, and suppresses H. pylori, promising for probiotic therapies with further research needed to refine its clinical use.

This study aimed to investigate the treatment effects of Bifidobacterium quadruple viable tablets combined with quadruple therapy on Helicobacter pylori (Hp)-infected peptic ulcer in children. A total of 124 children with Hp-infected peptic ulcers were allocated into 2 treatment groups: control group (quadruple therapy) and observation group (quadruple therapy plus Bifidobacterium quadruple viable tablets). After treatment, the 2 groups were compared in terms of ulcer healing, serum inflammatory cytokines, Hp elimination, gastrointestinal hormones, and intestinal flora. After treatment, the children in the observation group possessed lower serum interleukin-6, tumor necrosis factor α, procalcitonin, C-reactive protein, gastrin, and motilin levels, and higher ulcer healing rate, Hp clearance rate, somatostatin levels and bifidobacterium and lactobacillus versus those in the control group. Bifidobacterium quadruple viable tablets combined with quadruple therapy has good efficacy in Hp-associated peptic ulcer disease.

We investigated the clinical significance of serum Helicobacter pylori cytotoxin-associated gene A (CagA) antibody levels in 768 patients with unstable angina (UA).

Serum CagA levels were measured using ELISA. Demographic data, serum biomarkers, and SYNTAX scores were collected. Patients were followed up for 1 year for major adverse cardiac events (MACE).

CagA-positive UA patients had higher total cholesterol and hsCRP levels, and SYNTAX scores. CagA levels correlated positively with TC, hsCRP, and SYNTAX scores. Kaplan-Meier analysis showed shorter MACE-free survival in CagA-positive UA patients. CagA levels predicted MACE occurrence within 1 year, along with SYNTAX scores.

Serum H. pylori CagA antibody positivity is associated with worse prognosis in UA patients. CagA levels correlate with lipid metabolism and inflammatory markers.

Helicobacter pylori (H. pylori) infections may cause chronic gastritis, peptic ulcer disease, gastric cancers, and other conditions outside of the gastrointestinal tract. Hence, it is important to diagnose and treat it early. H. pylori is resistant to certain drugs in traditional eradication therapy, so alternative therapy protocols are needed, such as high-dose amoxicillin dual therapy (HDADT). This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases. In this study, the authors recruited 139 patients diagnosed with H. pylori, all treated with HDADT. Of these, 93 were treatment-naïve and 46 had received at least one alternative treatment in the past. Four weeks after the end of the treatment, the urea breath test was administered to estimate the eradication rate. The total eradication rate was 56% (78/139), 62% for the treatment-naïve arm and 43% for the previous treatment arm, thus indicating a lower success rate for the arm that had previously received a different treatment regimen. In conclusion, a therapeutic approach with first-line HDADT may potentially be a better treatment, but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.

Gastric and duodenal ulcers are increasingly becoming global health burdens. The side effects of conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and cytoprotective agents have necessitated the search for new medications. Plants are a rich source of active metabolites and herbal medicines have been used in the treatment of ulcers and cancers. In this study, we used in silico methods like molecular docking and MM-GBSA calculations to evaluate the effects of some anti-ulcer and anti-inflammatory phytochemicals on some key enzymes, cyclooxygenase (COX), and lipoxygenase (LOX), which are implicated in the protection and destruction of the gastric mucosa. The phytochemicals were retrieved from the literature and docked toward the binding sites of the three enzymes (COX-1, COX-2, and 5-LOX). Five compounds, rhamnetin, kaempferol, rutin, rosmarinic acid, and chlorogenic acid were observed to putatively bind to cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) but not to cyclooxygenase 1 (COX-1). The interaction mechanisms between these phytochemicals and the target proteins are discussed. The compounds' drug metabolism, pharmacokinetics, and toxicity have been evaluated to assess their suitability as potential next-generation anti-ulcer and anti-inflammatory drugs.

The online version contains supplementary material available at 10.1007/s40203-024-00269-2.

Correlative studies have linked human gut microbes to specific health conditions. Alistipes is one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role of Alistipes in IBD has not been studied and the underlying molecular mechanisms also remain unknown. In this study, colonization of Il10 -deficient mice with Alistipes timonensis DSM 27924 delays the development of colitis. Colonization with Alistipes does not significantly alter the gut microbiome composition during colitis development, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from Alistipes are also detected in the plasma of colonized mice, which carry metabolites with immunomodulatory potential into the host circulatory system. We further demonstrate that fractions of A. timonensis OMVs suppress LPS-induced Il6 , Il1b , and Tnfa expression in vitro in murine macrophages. We detect immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood of A. timonensis -colonized mice; and we identify other putative bioactive lipids in the A. timonensis OMVs. Thus, A. timonensis OMVs represent a potential mechanism for Alistipes -mediated delay of colitis progression in Il10 -deficient mice through the delivery of immunomodulatory lipids, including SoLs, and modulation of the host plasma lipidome.

Helicobacter pylori infection is a major issue worldwide, with widespread prevalence, combined with its link to gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Meanwhile, effectiveness of current treatment protocols is limited by increasing antibiotic resistance and patient compliance issues due to long regimens and side effects. Plukenetia volubilis, or sacha inchi, is a valuable source of bioactive molecules. However, studies on its antimicrobial activity, especially against H. pylori, are lacking.

In this study, the anti-H. pylori activity of P. volubilis leaves water extract was explored using in vitro and in silico approaches. High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESI- QTOF-MS-MS) analysis of the water extract from the leaves was used to characterise the chemical composition of the plant and allowed identification of some flavonoids, such as astragalin, and some phenolic compounds. Then, high-speed counter current chromatography (HSCCC) was used to fractionate the ethyl acetate partition obtained from the water extract from the leaves.

The presence of flavonoids derived from kaempferol was confirmed and astragalin was isolated for the first time in P. volubilis. The P. volubilis water infusion, ethyl acetate extract and the isolated astragalin exhibited anti-bacterial activity against H. pylori J99 and two clinical isolates (e.g., minimum inhibitory concentrations of 0.53, 0.51 and 0.49 μg/mL, respectively, for clarithromycin-resistant clinical isolate SSR366). Then, using molecular docking for potential protein targets for H. pylori, it was verified that astragalin could interact with these proteins by in silico analysis.

These findings highlight that P. volubilis and astragalin produce a bacteriostatic activity against H. pylori and may have potential to be used in treatment against H. pylori, after further research.

The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.

Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world's population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy.

Helicobacter pylori infection is associated with a decreased risk of esophageal adenocarcinoma, and the decreasing prevalence of such infection might contribute to the increasing incidence of this tumor. We examined the hypothesis that eradication treatment of H pylori increases the risk of esophageal adenocarcinoma.

This population-based multinational cohort, entitled "Nordic Helicobacter Pylori Eradication Project (NordHePEP)," included all adults (≥18 years) receiving H pylori eradication treatment from 1995-2018 in any of the 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) with follow-up throughout 2019. Data came from national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) by dividing the cancer incidence in the exposed cohort by that of the entire Nordic background populations of the corresponding age, sex, calendar period, and country. Analyses were stratified by factors associated with esophageal adenocarcinoma (ie, education, comorbidity, gastroesophageal reflux, and certain medications).

Among 661,987 participants who contributed 5,495,552 person-years after eradication treatment (median follow-up, 7.8 years; range, 1-24 years), 550 cases of esophageal adenocarcinoma developed. The overall SIR of esophageal adenocarcinoma was not increased (SIR = 0.89; 95% CI, 0.82-0.97). The SIR did not increase over time after eradication treatment, but rather decreased and was 0.73 (95% CI, 0.61-0.86) at 11-24 years after treatment. There were no major differences in the stratified analyses. The overall SIR of esophageal squamous cell carcinoma, calculated for comparison, showed no association (SIR = 0.99; 95% CI, 0.89-1.11).

This absence on an increased risk of esophageal adenocarcinoma after eradication treatment of H pylori suggests eradication is safe from a cancer perspective.

There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies.

The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting.

The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations.

The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12).

These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

The eradication regimen for Helicobacter pylori (H. pylori) infection can induce gut dysbiosis. In this open-label, prospective, and randomized clinical trial, we aimed to assess the effects of fucoidan supplementation on the eradication rate and gut microbial homeostasis in the context of quadruple therapy, as well as to investigate the combined effects of fucoidan and synbiotics supplementations.

Eighty patients with H. pylori infection were enrolled and randomly assigned to one of four treatment groups: the QT (a 2-week quadruple therapy alone), QF (quadruple therapy plus a 6-week fucoidan supplementation), QS (quadruple therapy plus a 6-week synbiotics supplementation), and QFS (quadruple therapy with a 6-week fucoidan and synbiotics supplementation), with 20 patients in each group. The QT regimen included rabeprazole, minocycline, amoxicillin, and bismuth potassium citrate. The synbiotics supplementation contained three strains of Bifidobacterium, three strains of Lactobacillus, along with three types of dietary fiber. All of the patients underwent 13C-urea breath test (13C-UBT) at baseline and at the end of the 6th week after the initiation of the interventions. Fresh fecal samples were collected at baseline and at the end of the 6th week for gut microbiota analysis via 16S rRNA gene sequencing.

The eradication rates among the four groups showed no significant difference. In the QT group, a significant reduction in α-diversity of gut microbiota diversity and a substantial shift in microbial composition were observed, particularly an increase in Escherichia-Shigella and a decrease in the abundance of genera from the Lachnospiraceae and Ruminococcaceae families. The Simpson index was significantly higher in the QF group than in the QT group. Neither the QS nor QFS groups exhibited significant changes in α-diversity or β-diversity. The QFS group was the only one that did not show a significant increase in the relative abundance of Escherichia-Shigella, and the relative abundance of Klebsiella significantly decreased in this group.

The current study provided supporting evidence for the positive role of fucoidan and synbiotics supplementation in the gut microbiota. The combined use of fucoidan and synbioticss might be a promising adjuvant regimen to mitigate gut dysbiosis during H. pylori eradication therapy.

To investigate the role of equine herpesvirus-2 (EHV-2) and equine herpesvirus-5 (EHV-5) in equine glandular gastric disease (EGGD) by visualizing and quantifying these gamma herpesviruses in EGGD-affected and normal glandular gastric mucosa of horses. A secondary objective was to describe the histopathological abnormalities in the equine gastric glandular mucosa in horses with EGGD.

29 horses (n = 21 postmortem and 8 gastroscopy) categorized as normal (11), EGGD (12), or both EGGD and equine squamous gastric disease (6).

Glandular gastric mucosal samples were collected from horses by gastroscopy or postmortem. Histopathology and in situ hybridization targeting EHV-2 and EHV-5 were performed on grossly normal and abnormal glandular gastric mucosa. The number of in situ hybridization-positive cells per millimeter squared of tissue was calculated. Evaluators were blinded to groups.

Glandular gastric tissues from horses without EGGD had higher viral loads in the mucosa than normal or abnormal tissues from EGGD horses. There was no difference in viral loads for EHV-2 or EHV-5 between grossly or endoscopically normal to abnormal gastric tissues within horses with EGGD. Lymphocytic plasmacytic gastritis was the most common histopathological abnormality, with only 3 horses having mucosal disruption (glandular ulcer or erosion).

Equine gamma herpesviruses are unlikely to play a role in the pathophysiology of EGGD. EGGD is frequently inflammatory with occasional mucosal disruption (ulcer or erosion).

Gastric cancer (GC) is a common malignancy of the digestive system. According to global 2018 cancer data, GC has the fifth-highest incidence and the third-highest fatality rate among malignant tumors. More than 60% of GC are linked to infection with Helicobacter pylori (H. pylori), a gram-negative, active, microaerophilic, and helical bacterium. This parasite induces GC by producing toxic factors, such as cytotoxin-related gene A, vacuolar cytotoxin A, and outer membrane proteins. Ferroptosis, or iron-dependent programmed cell death, has been linked to GC, although there has been little research on the link between H. pylori infection-related GC and ferroptosis.

To identify coregulated differentially expressed genes among ferroptosis-related genes (FRGs) in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.

Gene expression profiles of GC patients and those with H. pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The FRGs were acquired from the FerrDb database. A ferroptosis-related gene prognostic index (FRGPI) was created using least absolute shrinkage and selection operator-Cox regression. The predictive ability of the FRGPI was validated in the GEO cohort. Finally, we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.

Four hub genes were identified (NOX4, MTCH1, GABARAPL2, and SLC2A3) and shown to accurately predict GC and H. pylori-associated GC. The FRGPI based on the hub genes could independently predict GC patient survival; GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group. The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression. Moreover, the gene expression levels of common immune checkpoint proteins dramatically increased in the high-risk subgroup of the FRGPI cohort. The hub genes were also confirmed to be highly overexpressed in GC cell lines and tissues and were found to be primarily localized at the cell membrane. The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.

In this study, we developed a predictive model based on four FRGs that can accurately predict the prognosis of GC patients and the efficacy of immunotherapy in this population.

Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics.

Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates.

In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021.

Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

Helicobacter pylori (H. pylori) infection is a prevalent global health issue, associated with several gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. The landscape of H. pylori treatment has evolved over the years, with increasing challenges due to antibiotic resistance and treatment failure. Traditional diagnostic methods, such as the urea breath test, stool antigen test, and endoscopy with biopsy, are commonly used in clinical practice. However, the emergence of antibiotic-resistant strains has led to a decline in treatment efficacy, necessitating a re-evaluation of common diagnostic tools. This narrative review aims to explore the possible changes in the diagnostic approach of H. pylori infection in the era of treatment failure. Molecular techniques, including polymerase chain reaction and whole genome sequencing, which have high sensitivity and specificity, allow the detection of genes associated with antibiotic resistance. On the other hand, culture isolation and a phenotypic antibiogram could be used in the diagnostic routine, although H. pylori is a fastidious bacterium. However, new molecular approaches are promising tools for detecting the pathogen and its resistance genes. In this regard, more real-life studies are needed to reveal new diagnostic tools suitable for identifying multidrug-resistant H. pylori strains and for outlining proper treatment.

Helicobacter pylori infection is acquired in childhood via the oral cavity, although its relationship with the characteristics of the oral microbiome has not been elucidated. In this study, we performed comprehensive analysis of the oral microbiome in children and adults with or without H. pylori in the oral cavity.

Bacterial DNA was extracted from 41 adult and 21 child saliva specimens, and H. pylori was detected using PCR. 16S rRNA gene amplification was performed for next-generation sequencing. Bioinformatic analyses were conducted using Quantitative Insights into Microbial Ecology 2 (QIIME 2).

Faith's phylogenetic diversity analysis showed a significant difference between H. pylori-negative adult and child specimens in terms of α-diversity (p < 0.05), while no significant difference was observed between H. pylori-positive adult and child specimens. There was also a significant difference in β-diversity between H. pylori-positive and negative child specimens (p < 0.05). Taxonomic analysis at the genus level revealed that Porphyromonas was the only bacterium that was significantly more abundant in both H. pylori-positive adults and children than in corresponding negative specimens (p < 0.01 and p < 0.05, respectively).

These results suggest unique oral microbiome characteristics in children with H. pylori infection in the oral cavity.

Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC.

To explore the effects of H. pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC (PLGC).

Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected.

Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group.

H. pylori can activate the Wnt/β-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway, thereby decreasing the progression of PLGC.

Recent epidemiological research suggests a possible negative correlation between Helicobacter pylori infection and inflammatory bowel disease (IBD). However, conflicting studies have provided unclear evidence regarding these causal relationships. Therefore, recommending specific prevention and treatment strategies for H. pylori infection and IBD is challenging. We used various antibodies (anti-H. pylori IgG, VacA, and GroEl) related to H. pylori infection as indicators. We acquired relevant genetic variants from public databases within the Genome-wide Association Studies (GWAS) dataset using IBDs tool variables from 2 different GWAS datasets. We thoroughly examined the data and screened for IVs that fulfilled these criteria. Subsequently, Bidirectional Mendelian randomization (MR) was conducted to predict the potential causality between the 2. To ensure the accuracy and robustness of our results, we conducted a series of sensitivity analyses. Based on our comprehensive MR analysis, no potential causal relationship was observed between H. pylori infection and IBD. Across various methodologies, including IVW, MR-Egger, and weighted median, our findings showed P values > .05. The only exception was observed in the reverse MR analysis using the MR-Egger method, which yielded a P value of < .05. However, because the IVW method is considered the most statistically significant method for MR, and its P value was > .05, we do not believe that a potential causal relationship exists between them. Our sensitivity analysis did not suggest significant horizontal pleiotropism. Although heterogeneity was detected in the analysis of IBD (IIBDGC source) versus H. pylori GroEL antibody levels (MR-Egger, Qp = 0.038; IVW, Qp = 0.043), the results remained reliable because we selected IVW as a random-effects model in our MR analysis method. Based on our MR research, no direct correlation was observed between H. pylori infection and IBD risk. This implies that eradicating H. pylori may not provide substantial benefits in preventing or treating regional IBD, and vice versa. Nevertheless, the use of H. pylori serological index substitution has limitations, and further research using histological diagnosis and additional MR studies is required to comprehensively assess the link between H. pylori infection and IBD.

Gastric cancer (GC) is a prevalent malignant tumor within the digestive system, with over 40% of new cases and deaths related to GC globally occurring in China. Despite advancements in treatment modalities, such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents, the prognosis for GC remains poor. New targeted therapies and immunotherapies are currently under investigation, but no significant breakthroughs have been achieved. Studies have indicated that GC is a heterogeneous disease, encompassing multiple subtypes with distinct biological characteristics and roles. Consequently, personalized treatment based on clinical features, pathologic typing, and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer (PLGC). Current research has categorized GC into four subtypes: Epstein-Barr virus-positive, microsatellite instability, genome stability, and chromosome instability (CIN). Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas. Among these, ultrasensitive chromosomal aneuploidy detection (UCAD) can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology, in conjunction with bioinformatics analysis, to achieve qualitative and quantitative detection of chromosomal stability. This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Background: A shorter treatment duration potentially offers the advantage of reducing adverse events (AEs) and enhancing patient compliance for Helicobacter pylori eradication. However, the difference in eradication rates between short-duration vonoprazan-based regimens and fourteen-day proton pump inhibitor (PPI)-based therapy remained unknown. Objective: This meta-analysis aimed to compare the efficacy and safety of ten-day vonoprazan-based regimens with fourteen-day conventional PPI-based therapy for H. pylori eradication. Methods: We performed a comprehensive literature search up to November 28, 2023, using PubMed. A random-effects model was applied to conduct a meta-analysis to determine the pooled Odds Ratio (OR) with 95% confidence intervals (CIs). Results: This meta-analysis included four randomized controlled clinical trials with 1560 patients. The H. pylori eradication rate of ten-day vonoprazan-based regimens was comparable to that of fourteen-day PPI-based therapy (88.7% vs 82.9%, OR 1.53, 95% CI [0.85-2.75], p = .16) in ITT analysis. The incidence of AEs in ten-day vonoprazan-based therapy was also similar to the control group (11.2% vs 17.6%, OR 0.66, 95% CI [0.33-1.31], p = .24). Conclusion: Current evidence suggests that the ten-day vonoprazan-based regimen is as effective as fourteen-day PPI-based therapy in eradicating H. pylori, with comparable AEs. However, additional research is required for confirmation.

Helicobacter pylori infection is the predominant risk factor for the development of gastric cancer. Risk is enhanced by specific H. pylori virulence factors, diet, and the inflammatory response. Chronic activation of T helper (Th) 1 and Th17 pathways contributes to prolonged inflammation; yet, higher expression of IL-17 receptor (IL-17RA) is a favorable prognostic marker for survival after gastric cancer diagnosis. The protective impact of IL-17RA signaling is not understood. To investigate if IL-17RA signaling protects during H. pylori-induced carcinogenesis, the transgenic InsGAStg/tg mouse, which is prone to H. pylori-induced gastric cancer, was utilized. InsGAStg/tg mice and InsGAStg/tgIl17ra-/- mice were infected with a cag type 4 secretion system (T4SS) positive H. pylori strain for up to 6 months. Six weeks post-infection, IL-17RA deficiency led to increased bacterial burden, increased gastritis, and development of lymphoid follicles. Increased inflammation was associated with heightened cellular proliferation and earlier loss of parietal and chief cells in InsGAStg/tgIl17ra-/- mice. Gastric cancers developed more frequently by 3- and 6-months post-infection in H. pylori-infected InsGAStg/tgIl17ra-/- mice compared to InsGAStg/tg mice. Chronic inflammation was exacerbated with IL-17RA deficiency, characterized by elevated Th1/Th17 cytokines, increased B cell infiltration, and enhanced IgA production, despite reduced expression of the polymeric immunoglobulin receptor. Further, paragastric lymph nodes of InsGAStg/tgIl17ra-/- mice were enlarged relative to controls and displayed altered gene expression profiles. Increased inflammation was accompanied by a significant increase in Cybb expression, which encodes NADPH oxidase 2, suggesting that increased oxidative damage may occur in the absence of IL-17RA. Further, there is increased phosphorylation of histone 2AX in IL-17RA deficient mice, indicating that the DNA damage response is highly activated. These data suggest that IL-17RA signaling activates a protective pathway to prevent excessive inflammation which otherwise can lead to increased oxidative stress, DNA damage, and drive gastric carcinogenesis after H. pylori infection.

Many studies have shown that antibiotic resistance genes (ARGs) can be facilitated by a variety of antibacterial substances. Cyanobacteria are photosynthetic bacteria that are widely distributed in the ocean. Some extracellular substances produced by marine cyanobacteria have been found to possess antibacterial activity. However, the impact of these extracellular substances on ARGs is unclear. Therefore, we established groups of seawater microcosms that contained different concentrations (1000, 100, 10, 1, 0.1, 0.01, and 0 μg mL-1) of cyanobacterial extracellular substances (CES), and tracked the changes of 17 types of ARGs, the integron gene (intI1), as well as the bacterial community at different time points. The results showed that CES could enrich most ARGs (15/17) in the initial stage, particularly at low concentrations (10 and 100 μg mL-1). The correlation analysis showed a positive correlation between several ARGs and intI1. It is suggested that the abundance of intI1 increased with CES may contribute to the changes of these ARGs, and co-resistance of CES may be the underlying reason for the similar variation pattern of some ARGs. Moreover, the results of qPCR and high-throughput sequencing of 16S rRNA showed that CES had an inhibitory impact on the growth of bacterial communities. High concentrations of CES were found to alter the structure of bacterial communities. Co-occurrence networks showed that bacteria elevated in the high concentration group of CES and might serve as the potential hosts for a variety of ARGs. In general, marine cyanobacteria could play an important role in the global dissemination of ARGs and antibiotic-resistant bacteria (ARBs).

Forsythiae Fructus is a traditional Chinese medicine frequently in clinics. It is extensive in the treatment of various inflammation-related diseases and is renowned as 'the holy medicine of sores'. Phillygenin (C21H24O6, PHI) is a component of lignan that has been extracted from Forsythiae Fructus and exhibits notable biological activity. Modern pharmacological studies have confirmed that PHI demonstrates significant activities in the treatment of various diseases, including inflammatory diseases, liver diseases, cancer, bacterial infection and virus infection. Therefore, this review comprehensively summarizes the pharmacological effects of PHI up to June 2023 by searching PubMed, Web of Science, Science Direct, CNKI, and SciFinder databases. According to the data, PHI shows remarkable anti-inflammatory, antioxidant, hepatoprotective, antitumour, antibacterial, antiviral, immunoregulatory, analgesic, antihypertensive and vasodilatory activities. More importantly, NF-κB, MAPK, PI3K/AKT, P2X7R/NLRP3, Nrf2-ARE, JAK/STAT, Ca2+-calcineurin-TFEB, TGF-β/Smads, Notch1 and AMPK/ERK/NF-κB signaling pathways are considered as important molecular targets for PHI to exert these pharmacological activities. Studies of its toxicity and pharmacokinetic properties have shown that PHI has very low toxicity, incomplete absorption in vivo and low oral bioavailability. In addition, the physico-chemical properties, new formulations, derivatives and existing challenges and prospects of PHI are also reviewed and discussed in this paper, aiming to provide direction and rationale for the further development and clinical application of PHI.

Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field.

Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis.

36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co-occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota.

The United States has been the most productive and influential country on H. pylori research, and H. pylori-related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention.

Helicobacter pylori is one of the most widespread infections, and it is reaching alarming resistance levels worldwide. The recommended first-line empirical treatment differs according to the local rate of clarithromycin resistance. Macrolide resistance is mainly associated with three point mutations in the 23S rRNA gene. The aim of this study was to describe the antibiotic susceptibility of H. pylori in our healthcare area and the main mechanisms involved in clarithromycin resistance. Gastric biopsies (n = 641) were collected and cultured in a one-year prospective study. Antibiotic susceptibility testing was performed by gradient diffusion. A multiplex real-time PCR test (AllplexTMH.pylori & ClariR Assay, Seegene) was used to detect the most frequent mutations associated with clarithromycin resistance. Overall, 141 isolates were available for antibiotic susceptibility testing. The highest resistance rates were detected in metronidazole and levofloxacin. The rate of clarithromycin resistance was 12.1%, and the associated mutations were A2143G and A2142G. More than half of the clarithromycin-resistant isolates presented high MIC values (>256 mg/L). Tetracycline resistance was not detected, suggesting that therapies that contain tetracycline could be a suitable option. The low clarithromycin resistance rate coupled with the high rates of metronidazole resistance may support the recovery of the classical triple therapy in our healthcare area.

The antibiotic resistance of Helicobacter pylori (H. pylori) is a common cause of treatment failure. Previous studies showed that H. pylori resistance may be related to some characteristics of patients. This study intended to investigate the resistance of H. pylori to five commonly used antibiotics and risk factors in Yangzhou, China.

We recruited the subjects who joined the endoscopic screening program organized by the Affiliated Hospital of Yangzhou University between April 2018 and September 2019 and endoscopists would take biopsy samples from the antrum and the corpus of the stomach. The antrum biopsy specimens were used to culture H. pylori. Next, we extracted DNA from H. pylori strains and performed the specific DNA amplification. Finally, we use gene chip technology to test the susceptibility to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline. Multivariate logistic analyses were also performed to determine the risk factors for antibiotic resistance of H. pylori.

A total of 461 H. pylori strains were finally collected. The resistance rate of H. pylori to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was 41.0%, 44.9%, 38.8%, 6.3% and 1.1%, respectively. In addition, 16 multi-resistance patterns were detected, and strains resistant to all five antibiotics were not found. Multivariate analysis showed that past medical history and clinical outcomes were significantly associated with the resistance to clarithromycin. Drinking, gastrointestinal symptoms and a family history of gastric cancer were significantly associated with the resistance of H. pylori to levofloxacin. Especially gastrointestinal symptoms were significantly associated with the resistance of H. pylori to any antibiotic.

The resistance rates of H. pylori to clarithromycin, levofloxacin and metronidazole were very high in Yangzhou, China, various factors were related to bacterial resistance, and grasping these influencing factors can guide treatment.

Helicobacter pylori (H. pylori) is a common pathogen that infects more than half of the world's population. Its infection can not only lead to a variety of gastrointestinal diseases, such as chronic gastritis and gastric cancer (GC) but also be associated with many extra-gastrointestinal diseases. Exosomes, as a new intercellular information transmission medium, can carry biological signal molecules such as microRNAs (miRNAs) to regulate a variety of cellular physiological activities and are involved in multiple cancer processes. In this article, we provide a systematic review on the role of exosomal miRNAs in H. pylori-associated GC.

Cell surface molecules play important roles in cell signal transduction pathways during microbial infection.

In this study, the expression and the functions of CD59 was investigated in H. pylori infected gastric cancer (GC).

The differential expression of CD59 and the influence of H. pylori on the expression of CD59 were analyzed via bioinformatics through Gene Set Enrichment in GC. In addition, the expression of CD59 in GES-1, AGS cells and GC tissues infected with H. pylori was confirmed by Western blot. Bioinformatics results and H. pylori infection experiments showed CD59 decreased obviously in H. pylori infected GC cells and tissues. The expression of CD59 was linked to the survival rate of GC patients, and influenced various immune cells in the immune microenvironment of GC. CD59 interacts with other genes to form a network in H. pylori infected GC. Certainly, CD59 decreased significantly in H. pylori infected GC tissues, GES-1 and AGS cells in vitro.

H. pylori infection could influence the expression of CD59 in GC indicating that CD59 may be a promising treatment target.

In patients with atrophic gastritis involving gastric body mucosa the pH value of gastric juice is distinctly increased, so that pH assessment would allow predict this precancerous lesion. We tested whether EndoFaster® - a device allowing real-time pH measure and H. pylori diagnosis - may optimize the need of taking gastric biopsies.

In this prospective, multicentre study, the accuracy of EndoFaster® for ruling out gastric atrophy involving corporal mucosa was assessed. Real-time pH and ammonium determination was performed by aspirating 3-6 ml gastric juice during endoscopy. Histology performed on 5 standard gastric biopsies was used as gold standard.

A total of 1008 consecutive patients were observed in 12 centres. At histology, gastric body mucosa atrophy/metaplasia was detected in 65 (6.4%) cases, and a pH value >4.5 in the gastric juice was observed in 150 patients. The values of EndoFaster® performance in predicting the presence of atrophic gastritis were as follow: 51% sensitivity, 84% specificity, 18% PPV, 96% NPV, and 82% accuracy. The NPV value was not distinctly affected by neither ongoing proton pump inhibitor therapy nor H. pylori infection. By considering also data of ammonium concentrations, the values of EndoFaster® in detecting extensive atrophy on gastric mucosa were 74% sensitivity, 84% specificity, 24% PPV, 98% NPV, and 83% accuracy.

The very high NPV of EndoFaster® might allow to safely rule out presence of atrophic gastritis, reducing the need of taking gastric biopsies in unselected patients managed in clinical practice.