To better understand the factors associated with Helicobacter pylori infection, it is important to quantify the prevalence of H. pylori and identify the clinical and demographic characteristics of individuals with the infection.

In this cross-sectional study 369 participants underwent a structured questionnaire, urease breath test, and endoscopy to determine their H. pylori status.

The frequency of H. pylori in the sample was 27.64%, and erosive antral gastritis, gastric ulcers, and duodenal ulcers were found to be significantly associated with infection. However, no differences were found in social status, family size, or shared utensil use between individuals with and without the infection.

These findings suggest that H. pylori is a significant risk factor for gastrointestinal conditions.

Helicobacter pylori γ-glutamyltransferase (gGT) is a virulence factor that promotes bacterial colonization and immune tolerance. Although some studies addressed potential functional mechanisms, the supportive role of gGT for in vivo colonization remains unclear. Additionally, it is unknown how different gGT expression levels may lead to compensatory mechanisms ensuring infection and persistence. Hence, it is crucial to unravel the in vivo function of gGT. We assessed acid survival under conditions mimicking the human gastric fluid and elevated the pH in the murine stomach prior to H. pylori infection to link gGT-mediated acid resistance to colonization. By comparing proteomes of gGT-proficient and -deficient isolates before and after infecting mice, we investigated proteomic adaptations of gGT-deficient bacteria during infection. Our data indicate that gGT is crucial to sustain urease activity in acidic environments, thereby supporting survival and successful colonization. Absence of gGT triggers expression of proteins involved in the nitrogen and iron metabolism and boosts the expression of adhesins and flagellar proteins during infection, resulting in increased motility and adhesion capacity. In summary, gGT-dependent mechanisms confer a growth advantage to the bacterium in the gastric environment, which renders gGT a valuable target for the development of new treatments against H. pylori infection.

Gastric or duodenal ulcers can lead to upper gastrointestinal (GI) bleeding. Infection with Helicobacter pylori (H. pylori) is one of the most common infections in the world and can cause both gastric ulcers and gastric cancer. The treatment aims to eradicate H. pylori and treatment with antibiotics has made it possible to cure gastric ulcers. The most common complication of untreated peptic ulcer disease is bleeding (hematemesis, melena, and anemia), while perforation occurs in a smaller proportion of patients. In some individuals, the infection causes mucosal changes with increasing age that lead to atrophy and intestinal metaplasia. It is believed that atrophy and especially intestinal metaplasia are a prerequisite for the most common form of gastric cancer, adenocarcinoma. There is presently a demand for an alternate treatment devoid of the current strategies drawbacks including recurrence, resistance and antibiotic abuse. The current workhighlights the possibility of bee product-based treatments for preventing and eliminating H. pylori infestation. Sci-finder, Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus were used for literature screening. Terms and keywords, i.e. "helicobacter pylori", "epidemiology", "chemotherapy", "honey", "propolis", "bee venom", "bioactive compounds", and "mechanism of action" were used in the search. Bee products are important alternatives that have been utilized for treating many ailments due to their diverse biochemical and biological characteristics. Various mechanisms, such as direct antibacterial, antioxidant, anti-inflammatory, and wound healing capacities, are proposed to explain the potential effect of bee products against H. pylori. The bee product's metabolites have a role in the adherence of H. pylori to stomach epithelial cells. The disruption of bacterial cell membranes and the inhibition of virulence factors are the two mechanisms behind the bee product's promising therapeutic applications against H. pylori.

Helicobacter pylori (H. pylori) infection is a highly prevalent causative agent of various gastric diseases. The search for natural alternatives to antibiotics that can effectively inhibit H. pylori has become a pressing concern. In the present study, the potential anti-H. pylori activity of organic acids in sea buckthorn was investigated. Sea buckthorn organic acid extracts (SOA) inhibited H. pylori growth at a minimal inhibitory concentration of 10 mg/mL. Oxalic, tartaric, L-malic, ascorbic, lactic, citric acid were detected in SOA with the concentration of 0.512, 14.446, 13.111, 2.699, 0.303, 1.822 mg/g, respectively. Notably, malic, oxalic and tartaric acid had pronounced anti-H. pylori properties by inhibiting biofilm formation, increasing outer membrane permeability, disrupting membrane integrity, decreasing urease activity and altering membrane protein conformation. The three organic acids could suppress H. pylori urease genes (ureA, ureB), virulence genes (VacA, CagA), replication genes (dnaE, dnaN, dnaQ), transcriptional genes (rpoA, rpoD, rpoN), motility genes (flhA, flaA, flgE), adhesion genes (alpA, alpB, hpaA, hpaZ) and outer membrane protein genes (BabA), and had an inhibitory capacity on VacA and CagA protein expressions. Furthermore, three organic acids may reduce the production of pro-inflammatory factors including interleukin-1β (IL-1β), IL-6, IL-8 and reactive oxygen species (ROS) in H. pylori-induced GES-1 human gastric mucosal epithelial cells, contributing to the amelioration of inflammation induced by H. pylori infection. It might provide a theoretical basis for subsequent animal and clinical trials, and potentially be applied as a promising value-added food ingredient candidate for protecting human against gastric diseases caused by H. pylori infection.

Helicobacter pylori (H. pylori) infection is an important causal factor of gastritis, peptic ulcer, and gastric cancer. High infection rates and the increasing challenge of antibiotic resistance worldwide have prompted an urgent need to develop novel therapeutic options and antimicrobial agents. This review focuses on the potential of natural small-molecule compounds as novel anti-H. pylori agents-a promising approach that mitigates the risk of resistance development and maintains the microbiome's ecological balance. We detail how H. pylori virulence factors, including urease, CagA, VacA, and biofilm, contribute to pathogenicity and underline the reassuring fact that naturally derived compounds sourced from plants and microorganisms have shown remarkable efficacy in inhibiting these virulence factors. Some compounds also exhibit synergistic effects with conventional antibiotics, potentially overcoming challenges associated with resistant strains. Furthermore, we discuss recent advancements in identifying novel drug targets within the H. pylori virulence spectrum, offering insights into future directions for research and development in H. pylori therapy.

The intelligence and controllability of drug delivery systems (DDS) are crucial for enhancing therapeutic efficacy and minimizing side effects. Among these, DDS responsive switches play a pivotal role in precisely regulating the timing and spatial distribution of drug release in response to specific physiological environments within the body or external stimuli. Based on the origin of stimuli, they can be categorized into endogenous and exogenous stimuli. This paper reviews various types of stimulus-responsive switches, including dual-stimulus responsive switches, and elaborates on the drug release mechanisms of each intelligent switch. It summarizes the advantages and limitations of different stimulus-responsive systems, highlights the properties of commonly used temperature-sensitive materials, and discusses the applications of popular nano-engineered materials in pH and electromagnetic-responsive switches. Finally, the paper provides an outlook on the future of DDS, focusing on achieving more precise control, as well as ensuring clinical stability and reliability.

In a transcriptome-wide association study, we deciphered susceptibility genes that may predict gastric cancer (GC) risk and modify the effects of Helicobacter pylori (H. pylori) treatment.

Genetically predicted expression models of 4518 genes were developed based on the GTEx and applied to a nested case-control study (935 GCs and 1869 controls) of the Mass Intervention Trial in Linqu, Shandong Province (MITS), with genes associated with GC risk further validated in BioBank Japan (7921 GCs and 159,201 controls). Transcriptome risk scores (TRSs) integrating key genes were constructed, utilizing imputed transcriptomes from the Shandong Intervention Trial (SIT) and UK Biobank, and observed transcriptomes from the National Upper Gastrointestinal Cancer Early Detection (UGCED) program. We also examined whether TRS may modify the association of H. pylori infection and anti-H. pylori treatment with GC risk.

Integrating 11 independent GC-associated genes identified based on the MITS (FDR-q < 0.05) and BioBank Japan (P < 0.05), the TRS demonstrated a dose-dependent association with an elevated risk of incident GC in both the SIT (P-trend = 0.003) and UK Biobank (P-trend = 0.008), and exhibited an upward trend as gastric lesions progressed based on the UGCED program (P-trend = 5.01 × 10-4). In the SIT, the increased risk of GC associated with H. pylori infection (P-interaction = 0.03) and beneficial effect of successful H. pylori eradication (P-interaction = 0.05) were significant for individuals with high TRSs.

We identified a gene panel which may predict GC risk across populations of multiple ancestries, which offers important insights into GC risk stratification and presents a precision approach to primary prevention.

Funders are listed in the Acknowledgement.

Gastric cancer is the fifth most common cancer and the fifth most common cause of cancer-related death globally. The key to improving outcomes lies in effective prevention and early detection, which are critical for successful curative interventions. Helicobacter pylori is the strongest known risk factor for gastric cancer, and eradication of this pathogen is critical for reducing cancer risk. By synthesizing current evidence and exploring the advanced therapeutic approaches, this review provides a comprehensive overview of best practices for mitigating gastric cancer through targeted bacterial intervention.

Transmission routes of Helicobacter pylori (Hp) have been extensively studied, but many aspects remain unclear. This study explored the dynamics of multiplex Hp serology within regular families during a 36-month prospective follow-up.

Altogether, 329 families from the Finnish Family HPV study were subjected to sequential blood sampling and now tested also for six Hp proteins, HP0010, HP0073, HP0547, HP0875, HP0887, and HP1564, using multiplex serology assay.

Hp seropositivity, defined as being seropositive to at least three of the six Hp proteins, was more common among the fathers (20%) than mothers (10%). After maternal antibody decay, only a few children tested Hp-seropositive at later follow-up visits, indicating that acquisition of Hp infection is practically non-existent (0.4-2.0%) at an early age. No evidence was found to support the person-to-person transmission of Hp in this cohort because there was no correlation in Hp seropositivity or antibody levels between the spouses and/or their offspring, and individuals who were Hp-seropositive did not seem to increase the risk of other family members to co-test Hp-seropositive.

Our results perfectly agree with a recently published register-linkage study from Finland, where Hp and Hp-related co-morbidity are predicted to disappear among the native Finns during the 21st century.

Helicobacter pylori infection poses a significant risk for disrupting the gastric epithelium by inducing inflammation and apoptosis. Here, we identify alpha kinase 1 (ALPK1) as essential in H. pylori-induced apoptosis. The absence of ALPK1 leads to the accumulation of cellular inhibitor of apoptosis 1 (cIAP1) upon H. pylori infection, which raises the threshold for the induction of apoptosis. Ablation of cIAP1 with a SMAC-mimetic restores the level of apoptosis induced by H. pylori in these cells. Our findings highlight the impact of ALPK1 on the stability of cIAP1, influencing H. pylori-induced apoptosis.

The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant challenges, such as increasing antibiotic resistance, high recurrence rates, and adverse effects such as gut microflora dysbiosis. These limitations have driven the exploration of alternative antibiotic-free therapies, including the use of plant-based compounds, probiotics, nanoparticles, phage therapy, antimicrobial peptides, and H. pylori vaccines. Among these, urease-targeted therapy has shown particular promise. Urease enables the survival and colonization of H. pylori by neutralizing stomach acidity. Targeting this urease without disrupting beneficial gut microflora offers a selective mechanism to impair H. pylori, due to the absence of this enzyme in most of the human gut microbiome. In this review, we highlight advancements and limitations in the field of antibiotic-free therapies, with a particular focus on anti-urease strategies. We explore the structural and functional characteristics of urease, its role in H. pylori pathogenesis, and its potential as a therapeutic target. For the first time, we provide a comprehensive analysis of natural, semisynthetic, and synthetic anti-urease compounds, emphasizing their mechanisms of action, efficacy, and safety profiles. Advances in silico, in vitro, and in vivo studies have identified several promising anti-urease compounds with high specificity and minimal toxicity. By focusing on urease inhibition as a targeted strategy, this review underscores its potential to overcome antibiotic resistance while minimizing gut dysbiosis and improving the outcomes of H. pylori infection treatment.

Gastric cancer arises from complex carcinogenic factor interactions, with limited treatment options due to the lack of targetable driver gene mutations and significant tumor heterogeneity. Recent studies have provided promising novel approaches to improve our understanding of gastric cancer heterogeneity through integrated characterization, combining genomics with emerging technologies. Delineating the molecular changes and targeting specific molecular subtypes will enhance the efficacy of gastric cancer treatment and improve clinical outcomes. This review provides a comprehensive overview of current technologies used in gastric cancer research, highlighting key discoveries and treatment strategies driven by these innovations. Finally, we discuss the emerging technology-guided directions and potential breakthroughs that could enhance the understanding of gastric cancer tumor heterogeneity, ultimately improving clinical outcomes.

In an era of escalating antibiotic resistance, there is a pressing need for innovative strategies to develop novel antibiotics. Gram-negative bacteria, characterized by their robust dual-membrane, are intrinsically resistant to a wide range of antibiotics and can readily develop new resistances. Members of this bacterial class comprise numerous pathogenic organisms, including the primary cause of gastric cancer, Helicobacter pylori. In this study, we used the Giga-sized collection of theoretical molecules inside Enamine's REAL Space to identify inhibitors for H. pylori glutamate racemase. These compounds displayed a diverse range of activity in preventing H. pylori growth, with our most potent hits capable of selective full growth inhibition for metronidazole and clarithromycin resistant H. pylori strains. Alongside the introduction of a novel antibiotic class for this carcinogenic pathogen, our unique implementation of REAL Space holds great promise for Gram-negative antibiotic development as a whole.

The infection caused by Helicobacter pylori is the most common on the planet, affecting half of the global population. It is usually transmitted during childhood and persists for life if untreated. It is the primary cause of chronic gastritis, peptic ulcer, and gastric cancer. In young dyspeptic patients without alarm symptoms, the test-and-treat strategy (detection of H. pylori through a non-invasive test and subsequent eradication) is the preferred approach. The causal role of the infection in the development of gastric adenocarcinoma provides an opportunity to implement preventive strategies. The infection can be diagnosed through invasive methods (requiring endoscopy, such as the rapid urease test or histology) and non-invasive methods (such as the breath test or stool antigen test). The treatment for H. pylori combines a proton pump inhibitor with several antibiotics or bismuth salts.

Human-resident microbes typically cluster into biofilms - structurally organized communities embedded within a matrix of self-produced extracellular polymeric substance (EPS) that serves as a protective shield. These biofilms enhance microbial survival and functional adaptability, favoring a symbiotic relationship with the host under physiological conditions. However, biofilms exhibit a dual role in modulating the immune response. If their ability to promote tolerance is key to safeguarding homeostasis, by contrast, their persistence can overcome the cutting-edge balance resulting in immune evasion, chronic inflammation and development of numerous diseases such as cancer. Recent evidence highlights the significance of cancer-associated microbiota in shaping the tumor microenvironment (TME). These microbial inhabitants often exhibit biofilm-like structures, which may protect them from host immune responses and therapeutic interventions. The presence of biofilm-forming microbiota within the TME may promote chronic inflammation, and release of bioactive molecules that interfere with immune surveillance mechanisms, thereby enabling cancer cells to evade immune destruction. This review delves into the complex interplay between biofilms and cancer, with particular focus on the tumor-associated microbiota and the implications of biofilm involvement in modulating the immune landscape of the TME. Addressing this intricate relationship holds promises for innovative therapeutic approaches aimed at reprogramming the microbiota-cancer axis for better clinical outcomes.

Although the urea breath test (UBT) is widely used as a representative monitoring test after Helicobacter pylori eradication, false-negative results can occur because of the gray zone related to its cutoff value. This study aimed to compare the diagnostic performances of the rapid urease test (RUT), the RUT with sweeping method, and the UBT, and to investigate the role of the sweeping method in the gray zone of UBT values.

We retrospectively reviewed 216 patients who received standard first-line H. pylori eradication treatments (n=216). All participants underwent to testing using the sweeping method and UBT on the same day. The sensitivity, specificity, and accuracy were analyzed to compare the two methods.

The sensitivity (0.537 vs 0.806, p=0.002) and accuracy (0.843 vs 0.870, p=0.026) of the UBT were inferior to those of the sweeping method. A total of 31 individuals tested positive for H. pylori according to the UBT, whereas 54 individuals tested positive according to the sweeping method. In the group for which the gold standard definition indicated H. pylori positivity but UBT results were negative (n=31), all individuals had a UBT value under 2.5‰. In the multivariate logistic regression model, a UBT value of 1.4‰ to 2.5‰ increased the risk of false-negative results by 6.5 times (odds ratio, 6.5; 95% confidence interval, 2.077 to 20.288; p=0.001).

After H. pylori eradication, false-negative results can occur for individuals undergoing the UBT, primarily for values below the UBT cutoff. The RUT with the sweeping method can potentially help detect H. pylori in the gray zone of the UBT, improving diagnostic accuracy.

Helicobacter pylori is an important pathogen responsible for various gastrointestinal disorders, including peptic ulcers and gastric cancer. Rapid and accurate detection of H. pylori infection is crucial for its early diagnosis and treatment. This study aimed to develop and evaluate the efficacy of a colorimetric loop-mediated isothermal amplification (C-LAMP) assay for the detection of H. pylori in tissue biopsy samples.

In total, 302 gastric biopsy samples were collected, and the performance of the C-LAMP assay was compared with that of conventional diagnostic methods, including culture, PCR, and rapid urease test (CLO test).

The detection limit of the C-LAMP assay was 1 CFU/mL with a rapid reaction time of 15 min at 61 °C, highlighting its efficiency for rapid diagnosis. Compared to culture, the assay demonstrated a sensitivity of 80% and specificity of 98%, whereas compared to PCR, sensitivity was 60% and specificity was 100%. ROC analysis revealed superior diagnostic accuracy of the C-LAMP assay (AUC = 0.80 using PCR as reference; AUC = 0.89 using culture as reference) relative to the CLO test (AUC = 0.63 vs. PCR; AUC = 0.65 vs. culture), culture (AUC = 0.60 vs. PCR), and PCR (AUC = 0.78 vs. culture).

These results suggest that the C-LAMP assay is a highly sensitive, specific, and cost-effective tool for rapid detection of H. pylori, offering significant advantages over conventional diagnostic methods, particularly in resource-limited settings, and the C-LAMP assay is a promising alternative for early and reliable H. pylori detection in both clinical and field settings.

The gastrointestinal tract is not only an important component of the digestive system but also a crucial part of the body's immune system. Numerous studies have reported that gastrointestinal immunity plays a critical role in many extraintestinal diseases, including neurodegenerative disorders. However, the relationship between gastric mucosal immunity and neurodegenerative diseases, such as Parkinson's disease(PD), remains underexplored. The rate of H. pylori infection was assessed using the 13 C-Urea Breath Test (13 C-UBT) in a case-control study involving 315 PD patients and a control group of 22,383 outpatients. Multivariate regression and propensity score matching (PSM) analyses were employed to adjust for confounding factors. A lower H. pylori infection rate was found in PD cases compared to outpatient controls (DOB ≥ 8, 22.5% versus 27.5%, p = 0.049; DOB ≥ 4, 28.6% versus 33.9%, p = 0.046). After adjusting for confounding factors, the H. pylori infection rate remained lower in PD cases compared to controls. The study revealed an inverse correlation between H. pylori infection and PD, suggesting that H. pylori infection could potentially act as a protective factor against the development of PD.

Background and Aims: Amoxicillin is one of the most effective antibiotics for treating Helicobacter pylori infections and is widely used in first-line treatment regimens. However, patients with penicillin allergies cannot receive penicillin-based therapies, which significantly limits effective eradication options. This allergy often compels clinicians to choose alternative regimens that may be less effective, thereby increasing the risk of treatment failure. Consequently, therapeutic options for these patients are more restricted, and clinicians must carefully select the most appropriate regimen, taking into account both efficacy and the potential for antimicrobial resistance. This review aims to systematically evaluate the efficacy of penicillin-free treatment regimens for the eradication of H. pylori in patients with penicillin allergies. Specifically, it seeks to identify, analyze, and synthesize current clinical evidence to determine the most effective alternative therapies, thereby supporting evidence-based clinical decision-making. Methods: A literature search was conducted using the PubMed and Scopus databases. We began by reviewing the titles and abstracts of all identified studies to determine eligibility. Next, we assessed the full text of potentially eligible articles according to inclusion and exclusion criteria to establish the eligibility of each study. Results: This review included 26 studies comprising 2713 participants, evaluating penicillin-free therapies for H. pylori eradication in penicillin-allergic patients. Key findings demonstrated high eradication rates with bismuth-based quadruple therapies (88-97%), doxycycline-based regimens (86%), and quinolone-based therapies (75-100%), with Sitafloxacin exceeding 90% efficacy. Minocycline-based regimens also showed promising outcomes, with eradication rates between 80% and 85%. Although the PPI-clarithromycin-metronidazole combination was moderately effective, it was less favored as a first-line option. Overall, bismuth-based and quinolone-based therapies emerged as the most effective alternatives. Conclusions: In patients allergic to penicillin, bismuth quadruple therapy has demonstrated an excellent rate of eradication. Quinolone-based regimens are emerging as a promising alternative in first-line treatment or in cases of treatment failure. Vonoprazan-based therapy is an effective regimen. Combined with clarithromycin and metronidazole, vonoprazan enhances eradication rates and demonstrates effectiveness, including in clarithromycin-resistant strains.

Perforated peptic ulcers (PPU) represent a significant complication of peptic ulcers, associated with high mortality. As no systematic review of the literature on PPU in children currently exists, this study aims to summarize findings from studies focusing on its risk factors, etiology, treatment modalities, and outcomes.

A systematic review was conducted following the PRISMA guidelines. A literature search was performed on 24 November 2024, using four electronic databases: Web of Science, Scopus, PubMed, and ScienceDirect. The inclusion criteria were studies published in English, focusing on perforated peptic ulcers in paediatric patients. The exclusion criteria were: studies published in languages other than English; publication formats such as conference abstracts, personal communications, and single case reports; studies focusing on non-perforated peptic ulcers; studies involving participants > 18 years; and studies reporting ulcer perforations outside the stomach or duodenum.

Out of 1963 records identified, 12 studies met the inclusion criteria and were included in the review. A total of 239 children with perforated peptic ulcers were analyzed, with a median age of 11 years (range 3.2-16.5 years). The results indicate that ulcer perforations were more prevalent in males (74.8%). Furthermore, duodenal perforations (73%) were more common than gastric perforations (27%). The most commonly reported symptoms were abdominal pain (n = 175, 73.2%), vomiting (n = 82, 34.3%), peritoneal signs (n = 79, 33%), and fever (n = 38, 15.9%). Subdiaphragmatic free air was detected in 141 patients (58.9%). Of the total number of patients, 207 (86.6%) were treated surgically, while 32 (13.4%) received conservative treatment. Regarding the surgical approach, most patients underwent open surgery (n = 143, 69%) compared to laparoscopic repair (n = 64, 31%). Among the surgical procedures, 114 involved simple sutures, with or without an omental patch. Postoperative complications were reported in 30 children (14.5%). Reoperation was required in 4 patients (1.9%), and mortality was recorded in 9 patients (3.8%).

PPU was more prevalent in males and predominantly located in the duodenum. Ulcer suturing, with or without an omental patch, was the most commonly utilized treatment modality, demonstrating a relatively low complication rate. Further studies are needed to provide more comprehensive and unbiased evidence on PPU in children.

Helicobacter pylori is a motile bacterial pathogen that causes severe gastric diseases. H. pylori motility and chemotaxis are key colonization factors. Motility and chemotaxis are studied in many microbes, including H. pylori, using soft agar assays. In these assays, bacteria are inoculated into low-percentage agar and expand in a motility- and chemotaxis-dependent manner. H. pylori similarly expands in soft agar, but, if a plate was inoculated at multiple points, the expanded H. pylori colonies did not merge and left gaps. The basis of these gaps was unknown. We report here that gap formation was not affected by media components such as nutrient and agar concentrations, nor did it require chemotaxis, but it did rely on quorum sensing. To broaden our understanding of this H. pylori property, an H. pylori Tn7 transposon library was screened for mutants that lost gap formation. Fourteen mutants were identified, with transposon sites mapped to genes encoding outer membrane proteins, cysteine-rich proteins, phosphatidyl glycerophosphate synthase, an endorestriction nuclease, and several hypothetical proteins. Our results suggest that H. pylori may use specific proteins to avoid contact with other H. pylori, a behavior that may relate to previous observations that different H. pylori strains do not mix populations in stomach glands.

The interaction of Helicobacter pylori with cancer-associated fibroblasts (CAFs) to promote cholangiocarcinoma (CCA) genesis is unclear. We aimed to demonstrate the effect and mechanism of H. pylori on function of CAFs in vitro as well as the role of melatonin as an anti-fibrotic agent capable of modulating CAFs. CAF cells were generated by co-culture of human fibroblasts (OUMS cell line) with O. viverrini-associated CCA cells (KKU-100 cell line). In the presence of H. pylori lysate, these CAF cells exhibited increased proliferation and migration. The interaction of CAFs and H. pylori lysate also promoted KKU-100 cell migration. Proteomic analysis revealed that the fibrosis-associated integrin signaling pathway was enriched in CAFs stimulated by H. pylori lysate. Expression of focal adhesion kinase (FAK), a molecule that plays a pivotal role in cell proliferation and migration and known to be a downstream target of integrin, was upregulated in CAFs exposed to H. pylori lysate. Interestingly, melatonin treatment significantly attenuated both proliferation and migration of CAFs by reducing FAK phosphorylation and its downstream PI3K and β-catenin. These results suggest that H. pylori promotes proliferation and migration of CAFs cells and possibly fibrosis via the integrin/FAK signaling pathway, which could be attenuated by melatonin treatment.

A polyaniline-graphene oxide (PANI-GO) nanocomposite-grafted DNA biosensor for detecting Helicobacter pylori-specific toxins, oncoprotein cytotoxin-associated gene A (CagA), has been reported. The nanocomposite was fabricated on Screen printed paper electrode (SPPE) and modified with a 5'NH2-labelled single-stranded DNA (ssDNA) probe specific to the CagA gene via an EDC/NHS cross-linker. Under optimized electrochemical experimental conditions, CV and DPV were used to analyse the performance of the developed biosensor. A linear dynamic range for H. pylori ssDNA was established between 0.00001 ng/μl and 0.1 ng/μl, with correlation coefficients of R2 = 0.9813 for the CV and R2 = 0.9343 for the DPV. The sensitivities of the developed sensor in the CV studies were 50.261 μA μL/ng∙mm2 and 66.5 μA μL/ng∙mm2 in the DPV studies. CV demonstrated an LOD of 0.0026 ng/μL, whereas the LOD of the DPV studies was 0.001 ng/μL. The developed sensor was validated using different concentrations of H. pylori ssDNA spiked in human stool samples. The results highlight the potential of the developed biosensor to detect and quantify H. pylori genomic DNA in a sensitive and reliable manner to aid in clinical diagnostics and pathogen detection applications.

Colorectal cancer (CRC), especially low rectal cancer, often requires surgical resection of the anus, which severely affects the quality of life of patients. This study aims to develop a novel treatment method that can effectively control tumor growth while preserving anal function. We design a radioactive hydrogel (177Lu-RH) based on the cross-linking of metal ions and sodium alginate, which can be directly injected into the tumor to achieve local radiotherapy. In mouse experiments, we observe significant differences in the therapeutic efficacy of 177Lu-RH among treated mice. Through 16S rDNA microbial diversity and targeted metabolomics studies, it has been revealed that the intestinal microbiota, particularly the Rikenella bacteria, and their metabolite propionate, are positively correlated with a favorable treatment response. We subsequently select the genus Rikenella, which exhibit a significantly higher abundance in the near-complete response (nCR) compared to the partial response (PR) group, for further mechanistic investigation. We discover that propionate, a metabolite produced by Rikenella, plays a crucial role in promoting tumor cell apoptosis and may augment the efficacy of tumor immunotherapy. Therefore, we improve the radioactive hydrogel by adding sodium propionate (SP) to form 177Lu-RH@SP. In vivo experiments show that 177Lu-RH@SP combined with anti-programmed death ligand 1 (αPD-L1) not only inhibits tumor growth but also promotes DC maturation and reverses T cell exhaustion, thereby enhancing the efficacy of tumor immunotherapy. Our work provides a new approach for the treatment of low rectal tumors, with the potential to improve the prognosis and quality of life for patients.

Natural compounds have gained attention as potential alternatives or adjuvants to antibiotics against several pathogens. Ferulic acid, a natural plant product, has demonstrated promising antimicrobial properties against a wide range of microorganisms. This paper aims to characterize the molecular mechanism underlying the potential inhibitory effects of ferulic acid on Helicobacter pylori.

The impact of ferulic acid on the growth and expression of genes associated with urease enzyme, flagellar and motility, acid stability, toxin production, and quorum sensing in H. pylori using quantitative real-time polymerase chain reaction (qPCR) was investigated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ferulic acid were 167.7 ± 58.9 µg mL-1 and 250 µg mL-1, respectively. Exposure of H. pylori to 0.1% ferulic acid revealed strong induction of the regulatory genes hup and rpoN transcription factors and fliA flagellar regulatory factor and the cytotoxin genes cagA and vacA.

Results confirm the potent anti-Helicobacter pylori activity of ferulic acid affecting the expression of genes of its virulence factors, metabolism, and quorum sensing.

The inflammatory microenvironment (IME) has been demonstrated to facilitate the initiation and progression of tumors throughout the inflammatory process. Simultaneously, cancer can initiate or intensify the inflammatory response, thereby promoting tumor progression. This review examines the dual role of long non-coding RNAs (lncRNAs) in the interplay between inflammation and cancer. LncRNA modulate inflammation-induced cancer by influencing the activation of signaling pathways (NF-κB, Wnt/β-catenin, mTOR, etc), microRNA (miRNA) sponging, protein interactions, interactions with immune cells, and encoding short peptides. In contrast, lncRNAs also impact cancer-induced inflammatory processes by regulating cytokine expression, mediating tumor-derived extracellular vesicles (EVs), modulating intracellular reactive oxygen species (ROS) levels, and facilitating metabolic reprogramming. Furthermore, the therapeutic potential of lncRNA and the challenges of clinical translation were explicitly discussed as well. Overall, this review aims to provide a comprehensive and systematic resource for future researchers investigating the impact of lncRNAs on inflammation and cancer.

Urease, a multifunctional enzyme that catalyzes the hydrolysis of urea into ammonia, plays a pivotal role in nitrogen metabolism across diverse organisms. While essential for survival, its unregulated activity is implicated in numerous pathologies, including peptic ulcers, nephropathy, and gastric cancer, as well as agricultural challenges such as soil ammonium depletion and reduced nitrogen-use efficiency. Beyond its canonical enzymatic function, urease engages in protein-protein interactions with bioactive counterparts like jaburetox, canatoxin, and soyuretox plant-derived proteins with insecticidal, antifungal, and membranolytic properties. Exploring the relationship between ureases and these proteins, along with their mechanistic synergies, presents novel opportunities to develop targeted inhibitors for urease-related diseases while unlocking broader therapeutic and biotechnological applications. This review delves into the dual roles of ureases in plants and humans, bridging the gap between their ureolytic and non-ureolytic activities. We highlight recent advances in the design of urease inhibitors, which have emerged as critical tools for managing pathologies such as Helicobacter pylori-induced ulcers and urease-mediated kidney stone formation. These inhibitors also hold transformative potential in agriculture, where they mitigate nitrogen loss by stabilizing urea fertilizers, thereby enhancing crop yields and reducing environmental pollution. Furthermore, their utility extends to industrial biotechnology, including biofilm disruption and wastewater treatment, where urease inhibition prevents microbially induced corrosion and ammonia toxicity. The collected information is anticipated to offer insightful guidance and effective strategies for developing novel potent and safe urease inhibitors in the future.

Infection with H. pylori induces chronic gastric inflammation, progressing to peptic ulcer and stomach adenocarcinoma. Macrophages function as innate immune cells and play a vital role in host immune defense against bacterial infection. However, the distinctive mechanism by which H. pylori evades phagocytosis allows it to colonize the stomach and further aggravate gastric preneoplastic pathology. H. pylori exacerbates gastric inflammation by promoting oxidative stress, resisting macrophage phagocytosis, and inducing M1 macrophage polarization. M2 macrophages facilitate the proliferation, invasion, and migration of gastric cancer cells. Various molecular mechanisms governing macrophage function in the pathogenesis of H. pylori infection have been identified. In this review, we summarize recent findings of macrophage interactions with H. pylori infection, with an emphasis on the regulatory mechanisms that determine the clinical outcome of bacterial infection.

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium Helicobacter pylori is the most prominent gastric cancer risk factor, but only 1% to 3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, and H. pylori-infected smokers are at a 2- to 11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke (CS) on H. pylori pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with H. pylori and began smoking within 1 week of infection. The mice were exposed to CS 5 days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared with filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly blunted H. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of H. pylori infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated H. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of H. pylori infection but enhance the accumulation of mutations and accelerate gastric cancer initiation. Prevention Relevance: These findings suggest that cigarette smoking suppresses pathophysiological hallmarks of H. pylori infection while accelerating gastric carcinogenesis. Therefore, smokers should receive screening for H. pylori infection to reduce gastric cancer risk. See related Spotlight, p. 257.

Introduction Dyspepsia is a frequent complaint in patients with end-stage renal disease (ESRD). Helicobacter pylori (H. pylori) is a well-established etiological factor for dyspepsia in the general population; however, its role in ESRD patients remains to be determined. Therefore, this study aimed to determine the frequency of H. pylori infection among ESRD patients presenting with dyspeptic symptoms. Methodology A cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation from January 2023 to June 2024. A total of 200 adult ESRD patients undergoing maintenance hemodialysis and experiencing dyspepsia for at least three months were included. The patients with history of H. pylori infection or prior history of H. pylori eradication, those with history of usage of proton pump inhibitors or antibiotics or H2-receptor blockers within the past month, patients with gastric or duodenal ulcers, gastrointestinal malignancies or other systemic diseases causing dyspepsia and pregnant or breastfeeding females were excluded from the study. Upper gastrointestinal endoscopy and gastric biopsies were performed for histological confirmation of H. pylori. Data were analyzed using SPSS (IBM SPSS Statistics for Windows, IBM Corp., Version 27, Armonk, NY). Results Out of 200 patients, 80 (40%) were positive for H. pylori. Significant associations were observed between H. pylori infection and diabetes (p = 0.036), hypertension (p = 0.043), NSAID usage (p = 0.024), postprandial fullness (p ≤ 0.001), and epigastric pain (p = 0.041). Inversely, longer hemodialysis duration was associated with a lower prevalence of H. pylori (p = 0.012). Patients with H. pylori had lower hemoglobin and BMI levels and higher total leukocyte counts. Conclusion Our study showed that H. pylori is a common cause of dyspepsia in the ESRD population. Screening and eradication strategies may improve symptom control and enhance quality of life in this population. Multi-centered studies with larger sample sizes are not only required to validate our results but also to assess therapeutic outcomes.

Helicobacter pylori (H. pylori) is a group-1 definite pathogenic carcinogen that infects approximately half of the global population, yet no species-specific chemotherapy has yet been developed. It is previously discovered that H. pylori encodes an atypical dehydrogenase/isomerase FabX in the Type-II fatty acid biosynthesis pathway to produce unsaturated fatty acids (UFA) as well as superoxide (ROS). Here, it is demonstrated that FabX is essential for H. pylori growth and gastric colonization by retaining UFA synthesis and producing ROS, respectively, and is a species-specific anti-H. pylori drug target. The first small molecule inhibitor FBX-1991 against FabX, which inhibits the enzymatic activity with an IC50 value of 0.158 × 10-6 m in vitro, is developed. FBX-1991 binds inside the catalytic tunnel of FabX, disrupts the conformation of the key catalytic loop, and prevents the insertion of the acyl substrate for catalysis. Further in vivo studies suggest that FBX-1991 inhibits the H. pylori growth by partially inhibiting UFA synthesis and ROS excretion through targeting FabX. This study identifies a species-specific anti-H. pylori drug target, FabX, and discovers the first highly potent and selective FabX inhibitor against H. pylori infection, which provides the molecular basis for developing species-specific anti-H. pylori chemotherapy.

Helicobacter pylori (H. pylori) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of H. pylori-host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential role of fat mass and obesity-associated protein (FTO) in mediating Cytotoxin-associated gene A (CagA)-induced GC progression.

The effects of H. pylori infection on N6-methyladenosine (m6A) modification were evaluated in both human samples and GC cell lines. The function of FTO in the progression of GC was elucidated through in vitro and in vivo studies. A series of techniques, including methylated RNA immunoprecipitation sequencing, RNA sequencing, RNA binding protein immunoprecipitation, and chromatin immunoprecipitation assays, were utilized to investigate the mechanism by which FTO mediates the capacity of cagA-positive H. pylori to promote GC progression. Furthermore, the therapeutic potential of the FTO inhibitor meclofenamic acid (MA) in impeding GC progression was evaluated across GC cells, animal models, and human GC organoids.

Infection with cagA-positive H. pylori upregulated the expression of FTO, which was essential for CagA-mediated GC metastasis and significantly associated with a poor prognosis in GC patients. Mechanistically, CagA delivered by H. pylori enhanced FTO transcription via Jun proto-oncogene. Elevated FTO induced demethylation of m6A and inhibited the degradation of heparin-binding EGF-like growth factor (HBEGF), thereby facilitating the epithelial-mesenchymal transition (EMT) process in GC cells. Interestingly, eradication of H. pylori did not fully reverse the increases in FTO and HBEGF levels induced by cagA-positive H. pylori. However, treatment with a combination of antibiotics and MA substantially inhibited cagA-positive H. pylori-induced EMT and prevented GC metastasis.

Our study revealed that FTO mediates the "hit-and-run" mechanism of CagA-induced GC progression, which suggests that the therapeutic targeting of FTO could offer a promising approach to the prevention of CagA-induced cancer progression.

Gastric precancerous lesions (GPL) represent a heterogeneous, multi-stage process that involves transition from a benign to a malignant state. To optimize prevention and intervention strategies, accurate methods must clearly distinguish between precancerous stages and predict progression risks at early stages.

The metabolomic profiles of 188 GPL tissues and matched normal tissues were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry. Both multivariate and univariate statistical analyses were used to identify metabolomic features differentiating normal, atrophic, and intestinal metaplasia states in the stomach, followed by preliminary functional validation.

From experiments conducted on two cohorts, we established a reliable clinical gastric tissue metabolomic map, which clearly distinguished between normal, atrophic, and intestinalized gastric tissues. We then identified metabolic biomarkers that differentiated various GPL stages. Furthermore, key metabolites were validated in in vitro studies. Relative acyl group and glycerophospholipid abundance was higher in normal gastric tissue when compared to GPL, whereas organic acids were more prevalent in precancerous tissues than in normal tissues. A combination of glycerophosphocholine, tiglylcarnitine, malate, sphingosine, and γ-glutamylglutamic acid may serve as powerful biomarkers to distinguish normal tissue from GPL.

We used ultra-high-performance liquid chromatography with tandem mass spectrometry to effectively characterize metabolomic profiles in clinical gastric tissue samples. Key metabolites were identified and validated using targeted metabolomics. This study identified the metabolomic profiles of gastric tissues with atrophy and intestinal metaplasia of the gastric mucosa, uncovering and preliminarily validating key metabolites that may be used to assess high-risk populations and diagnose GPL, potentially advancing targeted gastric cancer prevention and treatment efforts.