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Seisenbekova A, Laryushina Y, Yukhnevich Y, Lavrinenko A, Shkreba A. Prevalence and risk factors of H. pylori infection among outpatient in Karaganda city (Kazakhstan). Future Sci OA 2025; 11:2461429. [PMID: 39927633 PMCID: PMC11812317 DOI: 10.1080/20565623.2025.2461429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/10/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND 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. METHOD In this cross-sectional study 369 participants underwent a structured questionnaire, urease breath test, and endoscopy to determine their H. pylori status. RESULTS 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. CONCLUSION These findings suggest that H. pylori is a significant risk factor for gastrointestinal conditions.
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Affiliation(s)
- Aizhan Seisenbekova
- Department of Internal Diseases, Karaganda Medical University, Karaganda, Kazakhstan
| | - Yelena Laryushina
- Department of Internal Diseases, Karaganda Medical University, Karaganda, Kazakhstan
| | | | | | - Alexey Shkreba
- University Clinic NC JSC “Karaganda Medical University”, Karaganda, Kazakhstan
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2
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Fuchs S, Fiedler MK, Heiduk N, Wanisch A, Mibus C, Singh D, Debowski AW, Marshall BJ, Vieth M, Josenhans C, Suerbaum S, Sieber SA, Gerhard M, Mejías-Luque R. Helicobacter pylori γ-glutamyltransferase is linked to proteomic adaptions important for colonization. Gut Microbes 2025; 17:2488048. [PMID: 40205659 PMCID: PMC11988274 DOI: 10.1080/19490976.2025.2488048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 03/18/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
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.
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Affiliation(s)
- Sonja Fuchs
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Michaela K. Fiedler
- Center for Functional Protein Assemblies (CPA), Chair of Organic Chemistry II, Department Biosciences, TUM School of Natural Sciences, Technical University of Munich (TUM), Garching, Germany
| | - Nicole Heiduk
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Andreas Wanisch
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Cora Mibus
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Dharmesh Singh
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Aleksandra W. Debowski
- Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia
- School of Molecular Sciences, The University of Western Australia, Crawley, Australia
| | - Barry J. Marshall
- Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Christine Josenhans
- Max von Pettenkofer Institute, Faculty of Medicine, Medical Microbiology and Hospital Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- DZIF - German Center for Infection Research, Partner Site Munich, Munich, Germany
| | - Sebastian Suerbaum
- Max von Pettenkofer Institute, Faculty of Medicine, Medical Microbiology and Hospital Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- DZIF - German Center for Infection Research, Partner Site Munich, Munich, Germany
| | - Stephan A. Sieber
- Center for Functional Protein Assemblies (CPA), Chair of Organic Chemistry II, Department Biosciences, TUM School of Natural Sciences, Technical University of Munich (TUM), Garching, Germany
| | - Markus Gerhard
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
| | - Raquel Mejías-Luque
- Institute for Medical Microbiology, Immunology and Hygiene, Department of Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany
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3
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Gao Q, Ma Y, Liu H, Wang S. A potential anti-Helicobacter pylori strategy: Exploring the antibacterial mechanism of organic acids in sea buckthorn (Hippophae rhamnoides L.). Microbiol Res 2025; 296:128133. [PMID: 40073720 DOI: 10.1016/j.micres.2025.128133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 02/11/2025] [Accepted: 03/01/2025] [Indexed: 03/14/2025]
Abstract
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.
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Affiliation(s)
- Qingchao Gao
- State Key Laboratory of Plateau Ecology and Agriculture, College of Agriculture and Animal Husbandry, Qinghai University, Xining 810016, China; College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.
| | - Yuwen Ma
- State Key Laboratory of Plateau Ecology and Agriculture, College of Agriculture and Animal Husbandry, Qinghai University, Xining 810016, China.
| | - Huicui Liu
- State Key Laboratory of Plateau Ecology and Agriculture, College of Agriculture and Animal Husbandry, Qinghai University, Xining 810016, China.
| | - Shulin Wang
- State Key Laboratory of Plateau Ecology and Agriculture, College of Agriculture and Animal Husbandry, Qinghai University, Xining 810016, China.
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4
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Sun W, Zhang C, Xu J, Zhao M, Li P. Natural small-molecule compounds targeting Helicobacter pylori virulence factors: A promising strategy for overcoming antibiotic resistance. Biochem Biophys Res Commun 2025; 768:151877. [PMID: 40334425 DOI: 10.1016/j.bbrc.2025.151877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/15/2025] [Accepted: 04/22/2025] [Indexed: 05/09/2025]
Abstract
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.
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Affiliation(s)
- Wenjing Sun
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China; State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China
| | - Congen Zhang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 100050 Beijing, China
| | - Junxuan Xu
- State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
| | - Mengran Zhao
- State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
| | - Peng Li
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China; State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
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5
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Oje A, Galati J, Peek RM. Current Understanding of Optimal Prevention of Helicobacter pylori-Induced Cancer. Gastroenterol Clin North Am 2025; 54:397-413. [PMID: 40348495 DOI: 10.1016/j.gtc.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
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.
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Affiliation(s)
- Adesola Oje
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Jonathan Galati
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
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6
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Syrjänen K, Rinne S, Koskela N, Michels B, Butt J, Grénman S, Waterboer T, Syrjänen S, Louvanto K. Helicobacter pylori multiplex serology and its dynamics within families during a 3-year prospective follow-up. Int J Infect Dis 2025; 155:107893. [PMID: 40120967 DOI: 10.1016/j.ijid.2025.107893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/19/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025] Open
Abstract
OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
| | | | | | | | - Julia Butt
- German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Seija Grénman
- Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland
| | - Tim Waterboer
- German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stina Syrjänen
- Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland
| | - Karolina Louvanto
- Tampere University, Tampere, Finland; University of Turku, Turku, Finland; Tampere University Hospital, Tampere, Finland.
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7
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Maubach G, Lim MCC, Naumann M. ALPK1-Dependent cIAP1 Degradation Regulates Helicobacter pylori-Induced Apoptosis. FASEB J 2025; 39:e70593. [PMID: 40357585 PMCID: PMC12070357 DOI: 10.1096/fj.202500764r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/02/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025]
Abstract
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.
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Affiliation(s)
- Gunter Maubach
- Medical FacultyOtto von Guericke University, Institute of Experimental Internal MedicineMagdeburgGermany
| | - Michelle C. C. Lim
- Medical FacultyOtto von Guericke University, Institute of Experimental Internal MedicineMagdeburgGermany
| | - Michael Naumann
- Medical FacultyOtto von Guericke University, Institute of Experimental Internal MedicineMagdeburgGermany
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8
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Almarmouri C, El-Gamal MI, Haider M, Hamad M, Qumar S, Sebastian M, Ghemrawi R, Muhammad JS, Burucoa C, Khoder G. Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora. Gut Pathog 2025; 17:37. [PMID: 40437630 PMCID: PMC12121022 DOI: 10.1186/s13099-025-00708-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 05/07/2025] [Indexed: 06/01/2025] Open
Abstract
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.
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Affiliation(s)
- Christina Almarmouri
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohammed I El-Gamal
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Mohamed Haider
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohamad Hamad
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Shamsul Qumar
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Merylin Sebastian
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Rose Ghemrawi
- College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
| | - Jibran Sualeh Muhammad
- Department of Biomedical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Christophe Burucoa
- Laboratoire de Bactériologie, U1070 INSERM, CHU de Poitiers, Université de Poitiers, 86000, Poitiers, France
| | - Ghalia Khoder
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
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9
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Wang Y, Jin RU, Xu J, Lin DC, Sun Z, Xu Y, Li QK, Zhang H. Harnessing technologies to unravel gastric cancer heterogeneity. Trends Cancer 2025:S2405-8033(25)00107-4. [PMID: 40425443 DOI: 10.1016/j.trecan.2025.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 04/14/2025] [Accepted: 04/21/2025] [Indexed: 05/29/2025]
Abstract
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.
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Affiliation(s)
- Yuefan Wang
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
| | - Ramon U Jin
- Division of Oncology and Gastroenterology, Washington University School of Medicine, Saint Louis, MO 63110, USA
| | - Joanne Xu
- College of Engineering, The Ohio State University, Columbus, OH 43210, USA
| | - Ding Chiao Lin
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Zhenyu Sun
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Yuanwei Xu
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Qing K Li
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Hui Zhang
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
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10
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Yin ZY, Xu HM, Wang MY, Wang XL, Liu ZC, Jin Y, Zhang Y, Zhang JY, Zhou T, You WC, Pan KF, Li WQ. Integrating genetics and transcriptomics to decipher susceptibility genes for risk stratification of gastric cancer and effect modification of Helicobacter pylori treatment. EBioMedicine 2025; 116:105767. [PMID: 40424666 DOI: 10.1016/j.ebiom.2025.105767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 05/08/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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. FUNDING Funders are listed in the Acknowledgement.
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Affiliation(s)
- Zhou-Yi Yin
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Heng-Min Xu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Meng-Yuan Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xin-Ling Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Zong-Chao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yu Jin
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jing-Ying Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Wei-Cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Kai-Feng Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
| | - Wen-Qing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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11
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Propp JP, Castor DO, Spies MA. Real Way to Target Gram-Negative Pathogens: Discovery of a Novel Helicobacter pylori Antibiotic Class. J Med Chem 2025; 68:10128-10138. [PMID: 40163413 DOI: 10.1021/acs.jmedchem.5c00112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
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.
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Affiliation(s)
- Jonah Pascal Propp
- Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa College of Pharmacy, Iowa City, Iowa 52242, United States
| | - Damien Oz Castor
- Department of Biochemistry, Carver College of Medicine, The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa 52242-1109, United States
| | - M Ashley Spies
- Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa College of Pharmacy, Iowa City, Iowa 52242, United States
- Department of Biochemistry, Carver College of Medicine, The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa 52242-1109, United States
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12
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Gisbert JP. Helicobacter pylori and gastric disease. Med Clin (Barc) 2025; 165:106974. [PMID: 40409232 DOI: 10.1016/j.medcli.2025.106974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 01/22/2025] [Accepted: 01/23/2025] [Indexed: 05/25/2025]
Abstract
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.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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13
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Montanari E, Bernardo G, Le Noci V, Anselmi M, Pupa SM, Tagliabue E, Sommariva M, Sfondrini L. Biofilm formation by the host microbiota: a protective shield against immunity and its implication in cancer. Mol Cancer 2025; 24:148. [PMID: 40399923 PMCID: PMC12093748 DOI: 10.1186/s12943-025-02348-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Accepted: 05/05/2025] [Indexed: 05/23/2025] Open
Abstract
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.
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Affiliation(s)
- Elena Montanari
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Giancarla Bernardo
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Valentino Le Noci
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Martina Anselmi
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Serenella M Pupa
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Elda Tagliabue
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Michele Sommariva
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Lucia Sfondrini
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
- Department of Experimental Oncology, Microenvironment and Biomarkers of Solid Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
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14
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Kim JH, Kim JM, Park B, Lim SG, Shin SJ, Lee KM, Lee GH, Noh CK. The Potential Role of the Rapid Urease Test with the Sweeping Method in the Gray Zone of the Urea Breath Test after Helicobacter pylori Eradication. Gut Liver 2025; 19:355-363. [PMID: 40169396 PMCID: PMC12070212 DOI: 10.5009/gnl240470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/03/2025] [Accepted: 01/15/2025] [Indexed: 04/03/2025] Open
Abstract
Background/Aims 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. Methods 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. Results 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). Conclusions 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.
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Affiliation(s)
- Ji Hyun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Ji Min Kim
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Bumhee Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Sun Gyo Lim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Jae Shin
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Kee Myung Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Gil Ho Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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15
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Romyasamit C, Kaewdech A, Sripongpun P, Chamroonkul N, Samaeng M, Wongprot D, Saengsuwan P, Saki M, Sornsenee P. Development of a colorimetric loop-mediated isothermal amplification assay for Helicobacter pylori detection. Eur J Clin Microbiol Infect Dis 2025:10.1007/s10096-025-05153-1. [PMID: 40360926 DOI: 10.1007/s10096-025-05153-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 04/28/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE 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. METHODS 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). RESULTS 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). CONCLUSION 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.
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Affiliation(s)
- Chonticha Romyasamit
- Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand
- Center of Excellence in Innovation of Essential Oil and Bioactive Compounds, Walailak University, Nakhon Si Thammarat, 80160, Thailand
- Research Center in Tropical Pathobiology, Walailak University, Thasala District, Nakhon Si Thammarat, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Maseetoh Samaeng
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Dechawat Wongprot
- College of Graduate Studies, Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | - Phanvasri Saengsuwan
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Phoomjai Sornsenee
- Department of Family Medicine and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Rd., Hat Yai, Songkhla, 90110, Thailand.
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16
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El-Seedi HR, Refaey MS, Abd El-Wahed AA, Albadawy A, Karav S, El-Seedi SH, Cheng G, Salem MF, Liu L, Tang J, Abolibda TZ, Zou X, Guo Z, Khalifa SAM. Bee products in the fight against Helicobacter pylori and molecular interactions. Microb Pathog 2025; 205:107707. [PMID: 40378976 DOI: 10.1016/j.micpath.2025.107707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 04/23/2025] [Accepted: 05/13/2025] [Indexed: 05/19/2025]
Abstract
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.
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Affiliation(s)
- Hesham R El-Seedi
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Mohamed S Refaey
- Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia National University, Km Cairo-Alexandria Agricultural Road, Menoufia, Egypt.
| | - Aida A Abd El-Wahed
- Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, Giza 12627, Egypt.
| | - Aida Albadawy
- Translational Medicine Laboratory, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale, 17000, Turkey.
| | | | - Guiguang Cheng
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Mohamed F Salem
- Department of Environmental Biotechnology, Genetic Engineering and Biotechnology Research Institute, GEBRI, University of Sadat City, Sadat City, P.O. Box:79, Egypt.
| | - Lianliang Liu
- School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang, China.
| | - Jie Tang
- School of Food and Bioengineering, Xihua University, Chengdu, Si Chuan Province, China.
| | - Tariq Z Abolibda
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Xiaobo Zou
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Zhiming Guo
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Shaden A M Khalifa
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Neurology and Psychiatry Department, Capio Saint Göran's Hospital, Sankt Göransplan 1, 112 19, Stockholm, Sweden.
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17
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Xiao X, Wang Z, Zhang H, Li B, Hou Q, Wang J, Xiu W, Zhang R, Zhang G, Lan Y, Chen Y, Zhang M, Sun C, Gao Y, Li A, Zhu X, Gao C, He C, Lu F, Shuai P. Helicobacter pylori infection might be a protective factor against Parkinson's disease. Sci Rep 2025; 15:16689. [PMID: 40369112 PMCID: PMC12078797 DOI: 10.1038/s41598-025-01562-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 05/07/2025] [Indexed: 05/16/2025] Open
Abstract
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.
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Affiliation(s)
- Xiao Xiao
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Zuo Wang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Huiwang Zhang
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- School of Public Health, Southwest Medical University, Luzhou, China
| | - Binghong Li
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Qinchuan Hou
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Nutrition Department, Third People's Hospital of Yibin City, Yibin, China
| | - Jinxia Wang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Wenbo Xiu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Rui Zhang
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- China Heart House, Suzhou, China
| | - Gao Zhang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yongli Lan
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yang Chen
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Mo Zhang
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chaonan Sun
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yanping Gao
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Core laboratory, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - An Li
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiong Zhu
- Department of Prenatal Diagnosis, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Caiping Gao
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chong He
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Fang Lu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
- Core laboratory, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
| | - Ping Shuai
- Health Management Center & Health Management Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
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18
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El Boury K, Boudarf H, Adoud I, Ouannass S, Abi O, Delsa H, Lahlou FA, Iskandar S, El Jemli M, Diawara I, Senhaji MA, Balouch L, Belrhiti Z, Kettani Halabi M. Clinical Effectiveness of Penicillin-Free Therapies in First-Line and Rescue Treatments for Helicobacter pylori: A Systematic Review. Antibiotics (Basel) 2025; 14:476. [PMID: 40426542 PMCID: PMC12108433 DOI: 10.3390/antibiotics14050476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 04/19/2025] [Accepted: 04/27/2025] [Indexed: 05/29/2025] Open
Abstract
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.
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Affiliation(s)
- Kenza El Boury
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
| | - Hind Boudarf
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
| | - Imane Adoud
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
| | - Soukaina Ouannass
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
| | - Oussama Abi
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
| | - Hanane Delsa
- Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (H.D.); (F.A.L.)
| | - Fatima Azzahra Lahlou
- Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (H.D.); (F.A.L.)
| | - Samy Iskandar
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
| | - Meryem El Jemli
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
| | - Idrissa Diawara
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
- Laboratory of Microbial Biotechnology and Infectiology Research, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco
| | - Mohamed Amine Senhaji
- Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada;
| | - Lhousaine Balouch
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
| | - Zakaria Belrhiti
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
- Mohammed VI International School of Public Health, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco
| | - Mohamed Kettani Halabi
- Research Laboratory in Drug Sciences, Mohammed VI Faculty of Pharmacy, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (K.E.B.); (H.B.); (I.A.); (S.O.); (O.A.); (S.I.); (M.E.J.); (L.B.)
- Research Unit, Mohammed VI Center for Research and Innovation, Rabat 10112, Morocco; (I.D.); (Z.B.)
- Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco; (H.D.); (F.A.L.)
- Laboratory of Microbial Biotechnology and Infectiology Research, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco
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19
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Vidović S, Borović S, Bašković M, Markić J, Pogorelić Z. Perforated peptic ulcers in children: a systematic review. BMC Pediatr 2025; 25:363. [PMID: 40335985 PMCID: PMC12057288 DOI: 10.1186/s12887-025-05725-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/29/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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%). CONCLUSIONS 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.
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Affiliation(s)
- Stipe Vidović
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, 31 000, Croatia
| | - Sara Borović
- School of Medicine, University of Split, Split, 21 000, Croatia
| | - Marko Bašković
- Department of Pediatric Surgery, Children's Hospital Zagreb, Zagreb, 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb, 10000, Croatia
| | - Joško Markić
- School of Medicine, University of Split, Split, 21 000, Croatia
- Department of Pediatrics, University Hospital of Split, Split, 21 000, Croatia
| | - Zenon Pogorelić
- School of Medicine, University of Split, Split, 21 000, Croatia.
- Department of Pediatric Surgery, University Hospital of Split, Spinčićeva ulica 1, Split, 21 000, Croatia.
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20
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Elshenawi Y, Hathroubi S, Hu S, Liu X, Ottemann KM. Genetic Basis of Gap Formation Between Migrating Helicobacter pylori Colonies in Soft Agar Assays. Microorganisms 2025; 13:1087. [PMID: 40431260 PMCID: PMC12114501 DOI: 10.3390/microorganisms13051087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 04/30/2025] [Accepted: 05/01/2025] [Indexed: 05/29/2025] Open
Abstract
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.
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Affiliation(s)
| | | | | | | | - Karen M. Ottemann
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA; (Y.E.); (S.H.); (X.L.)
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21
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Klungsaeng S, Hongsrichan N, Chaidee A, Intuyod K, Pinlaor P, Roytrakul S, Vaeteewoottacharn K, Charoenlappanit S, Dangtakot R, Mahaamnad N, Pinlaor S. Melatonin attenuates Helicobacter pylori-mediated cholangiocarcinoma-associated fibroblast activation via modulating integrin/FAK signaling pathway. Sci Rep 2025; 15:15780. [PMID: 40329017 PMCID: PMC12056007 DOI: 10.1038/s41598-025-99980-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 04/24/2025] [Indexed: 05/08/2025] Open
Abstract
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.
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Affiliation(s)
- Sirinapha Klungsaeng
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Nuttanan Hongsrichan
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Apisit Chaidee
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Kitti Intuyod
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Porntip Pinlaor
- Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Sittiruk Roytrakul
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Kulthida Vaeteewoottacharn
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Sawanya Charoenlappanit
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Rungtiwa Dangtakot
- Department of Medical Technology, Faculty of Allied Health Sciences, Nakhonratchasima College, Nakhon Ratchasima, 30000, Thailand
| | - Narumon Mahaamnad
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Somchai Pinlaor
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.
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22
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Poria R, Lutomia D, Kaushal A, Ramasamy SK, Gupta S. Polyaniline-graphene oxide (PANI/GO)-grafted paper-based nanosensor for the detection of Helicobacterpylori. Anal Biochem 2025; 704:115891. [PMID: 40334770 DOI: 10.1016/j.ab.2025.115891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 05/03/2025] [Accepted: 05/04/2025] [Indexed: 05/09/2025]
Abstract
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.
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Affiliation(s)
- Rachna Poria
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Desmond Lutomia
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Ankur Kaushal
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Selva Kumar Ramasamy
- Department of Chemistry, M.M Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Shagun Gupta
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India.
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23
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Zhang C, Shen W, Leng Z, Liu S, Pei P, Liu T, Hu L, Yang K. A novel radio-immunotherapy strategy: Gut microbiota metabolite combined with radioactive hydrogel for the treatment of low rectal cancer. Biomaterials 2025; 322:123386. [PMID: 40334526 DOI: 10.1016/j.biomaterials.2025.123386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/21/2025] [Accepted: 05/01/2025] [Indexed: 05/09/2025]
Abstract
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.
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Affiliation(s)
- Chonghai Zhang
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Wenhao Shen
- Department of Central Laboratory and Oncology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, 225290, Jiangsu, China
| | - Zhifang Leng
- WuXi Huishan Traditional Chinese Medicine Hospital , Wuxi, 214177, Jiangsu, China
| | - Shu Liu
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Pei Pei
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Teng Liu
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Lin Hu
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China.
| | - Kai Yang
- Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, 215123, Jiangsu, China; Institute of Clinical Pathology for Precision Diagnosis and Treatment, Soochow University, Suzhou, 215000, Jiangsu, China.
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24
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Abu-Qatouseh LF, Ahmad MIA, Amorim CG, Al-Adham ISI, Collier PJ, Montenegro MCBSM. Insights into the molecular antimicrobial properties of ferulic acid against Helicobacter pylori. J Appl Microbiol 2025; 136:lxaf112. [PMID: 40336146 DOI: 10.1093/jambio/lxaf112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 04/16/2025] [Accepted: 05/06/2025] [Indexed: 05/09/2025]
Abstract
AIM 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. METHODS AND RESULTS 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. CONCLUSIONS Results confirm the potent anti-Helicobacter pylori activity of ferulic acid affecting the expression of genes of its virulence factors, metabolism, and quorum sensing.
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Affiliation(s)
- Luay F Abu-Qatouseh
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Mohammad I A Ahmad
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328 Amman, Jordan
- Pharmacological and Diagnostic Research Centre (PDRC), Al-Ahliyya Amman University, 19328 Amman, Jordan
| | - Célia G Amorim
- Department of Chemical Sciences, Faculty of Pharmacy, LAQV-REQUIMTE, University of Porto, Porto, 4169-007, Portugal
| | - Ibrahim S I Al-Adham
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Phillip J Collier
- Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Maria C B S M Montenegro
- Department of Chemical Sciences, Faculty of Pharmacy, LAQV-REQUIMTE, University of Porto, Porto, 4169-007, Portugal
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25
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Yang Y, Zhang C, Li H, He Q, Xie J, Liu H, Cui F, Lei Z, Qin X, Liu Y, Xu M, Huang S, Zhang X. A review of molecular interplay between inflammation and cancer: The role of lncRNAs in pathogenesis and therapeutic potential. Int J Biol Macromol 2025; 309:142824. [PMID: 40187457 DOI: 10.1016/j.ijbiomac.2025.142824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/31/2025] [Accepted: 04/02/2025] [Indexed: 04/07/2025]
Abstract
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.
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Affiliation(s)
- Yan Yang
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China; School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Chuxi Zhang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Huacui Li
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China; Tangshan Institute of Southwest Jiaotong University, Tangshan, China
| | - Qin He
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Jiang Xie
- Department of Pediatrics, The Third People's Hospital of Chengdu, Chengdu, China
| | - Hongmei Liu
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Fenfang Cui
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Ziqin Lei
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Xiaoyan Qin
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Ying Liu
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China
| | - Min Xu
- Department of Pharmacy, The Third People's Hospital of Chengdu, Chengdu, China.
| | - Shuai Huang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
| | - Xu Zhang
- Department of Pharmacy, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu University of TCM, Chengdu, China.
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26
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Khan M, Zhang B, Zhang H, Wu J, Gao P, Li J. Ureases in nature: Multifaceted roles and implications for plant and human health - A review. Int J Biol Macromol 2025; 306:141702. [PMID: 40043969 DOI: 10.1016/j.ijbiomac.2025.141702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/24/2025] [Accepted: 03/01/2025] [Indexed: 05/03/2025]
Abstract
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.
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Affiliation(s)
- Majid Khan
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China
| | - Bo Zhang
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China
| | - Han Zhang
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China
| | - Juhong Wu
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China
| | - Ping Gao
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China
| | - Jinyu Li
- College of Chemistry, Fuzhou University, 350116 Fuzhou, China; College of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology University, 132101 Jilin, China.
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27
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Fei X, Li N, Xu X, Zhu Y. Macrophage biology in the pathogenesis of Helicobacter pylori infection. Crit Rev Microbiol 2025; 51:399-416. [PMID: 39086061 DOI: 10.1080/1040841x.2024.2366944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 05/31/2024] [Accepted: 06/04/2024] [Indexed: 08/02/2024]
Abstract
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.
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Affiliation(s)
- Xiao Fei
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nianshuang Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Morris MT, Duncan BC, Piazuelo MB, Olfert IM, Xu X, Hussain S, Peek RM, Busada JT. Chronic Cigarette Smoke Exposure Masks Pathological Features of Helicobacter pylori Infection While Promoting Tumor Initiation. Cancer Prev Res (Phila) 2025; 18:271-281. [PMID: 39789851 PMCID: PMC12045739 DOI: 10.1158/1940-6207.capr-24-0378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 11/26/2024] [Accepted: 01/08/2025] [Indexed: 01/12/2025]
Abstract
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.
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Affiliation(s)
- Maeve T. Morris
- Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, 26505, USA
| | - Benjamin C. Duncan
- Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, 26505, USA
| | - M Blanca Piazuelo
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - I. Mark Olfert
- Division of Exercise Physiology West Virginia University West Virginia University, Morgantown, WV, 26505, USA
- Department of Physiology, Pharmacology and Toxicology, West Virginia University, Morgantown, WV, 26505, USA
| | - Xiaojiang Xu
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, United States
| | - Salik Hussain
- Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, 26505, USA
- Department of Physiology, Pharmacology and Toxicology, West Virginia University, Morgantown, WV, 26505, USA
| | - Richard M. Peek
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jonathan T. Busada
- Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, 26505, USA
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Neuner A, Schulz C. [Helicobacter pylori infection - modern approaches in diagnostics and therapy]. MMW Fortschr Med 2025; 167:54-60. [PMID: 40312646 DOI: 10.1007/s15006-025-4586-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2025]
Affiliation(s)
- Alexander Neuner
- LMU-Klinikum, Medizinische Klinik und Poliklinik II, Campus Großhadern, Marchioninistraße 15, 81377, München, Deutschland.
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II, Klinikum Großhadern der LMU München, Marchioninistr. 15, 81377, München, Deutschland
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Zhang L, Ruan X, Hang X, Heng D, Cai C, Zeng L, Zhang G, Zhou L, Bi H, Zhang L. Antagonist Targeting the Species-Specific Fatty Acid Dehydrogenase/Isomerase FabX for Anti-H. pylori Infection. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2414844. [PMID: 40089858 PMCID: PMC12079444 DOI: 10.1002/advs.202414844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 03/06/2025] [Indexed: 03/17/2025]
Abstract
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.
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Affiliation(s)
- Lin Zhang
- Department of Pharmacology and Chemical BiologySchool of MedicineShanghai Jiao Tong UniversityShanghai200025China
| | - Xiaoxue Ruan
- Department of Medicinal ChemistrySchool of PharmacyFudan UniversityShanghai201203China
| | - Xudong Hang
- Department of Pathogen Biology and Jiangsu Key Laboratory of Pathogen BiologyNanjing Medical UniversityNanjingJiangsu211166China
- NHC Key Laboratory of Tropical Disease ControlSchool of Tropical MedicineHainan Medical UniversityHaikouHainan571199China
| | - Ding Heng
- Department of Pathogen Biology and Jiangsu Key Laboratory of Pathogen BiologyNanjing Medical UniversityNanjingJiangsu211166China
- Department of GastroenterologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu210009China
| | - Chang Cai
- Department of Pharmacology and Chemical BiologySchool of MedicineShanghai Jiao Tong UniversityShanghai200025China
| | - Liping Zeng
- Department of Pathogen Biology and Jiangsu Key Laboratory of Pathogen BiologyNanjing Medical UniversityNanjingJiangsu211166China
| | - Guoxin Zhang
- Department of GastroenterologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu210009China
| | - Lu Zhou
- Department of Medicinal ChemistrySchool of PharmacyFudan UniversityShanghai201203China
- Quzhou Fudan InstituteQuzhou324002China
| | - Hongkai Bi
- Department of Pathogen Biology and Jiangsu Key Laboratory of Pathogen BiologyNanjing Medical UniversityNanjingJiangsu211166China
- NHC Key Laboratory of Tropical Disease ControlSchool of Tropical MedicineHainan Medical UniversityHaikouHainan571199China
| | - Liang Zhang
- Department of Pharmacology and Chemical BiologySchool of MedicineShanghai Jiao Tong UniversityShanghai200025China
- Department of Chemical BiologySchool of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
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31
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Bhutani MS, Faraoni EY, Mork ME, McAllister F. Gastric cancer prevention and screening during pancreatic cancer screening in high-risk individuals: an opportunity not to be missed. Gastrointest Endosc 2025; 101:1073-1076. [PMID: 39653170 DOI: 10.1016/j.gie.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 11/13/2024] [Accepted: 12/02/2024] [Indexed: 01/18/2025]
Affiliation(s)
- Manoop S Bhutani
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas.
| | - Erika Y Faraoni
- Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Maureen E Mork
- Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Florencia McAllister
- Department of Genetics, Clinical Cancer Genetics Program, Department of Gastrointestinal Medical Oncology, Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas.
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He B, Hu Y, Wu Y, Wang C, Gao L, Gong C, Li Z, Gao N, Yang H, Xiao Y, Yang S. Helicobacter pylori CagA elevates FTO to induce gastric cancer progression via a "hit-and-run" paradigm. Cancer Commun (Lond) 2025; 45:608-631. [PMID: 39960839 PMCID: PMC12067399 DOI: 10.1002/cac2.70004] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 01/23/2025] [Accepted: 01/26/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Bing He
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Yiyang Hu
- Department of OncologyThe General Hospital of Western Theater CommandChengduSichuanP. R. China
| | - Yuyun Wu
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Chao Wang
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Limin Gao
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Chunli Gong
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Zhibin Li
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Nannan Gao
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Huan Yang
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Yufeng Xiao
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
| | - Shiming Yang
- Department of GastroenterologyXinqiao HospitalArmy Military Medical UniversityChongqingP. R. China
- Chongqing Institute for Brain and Intelligence, Guangyang Bay LaboratoryChongqingP. R. China
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Zhang X, Lin Z, Xu B, Ma C, Jiang B, Geng Y, Sheng Y, Dai Y, Xue Y, Ren Y. Unveiling gastric precancerous stages: metabolomic insights for early detection and intervention. BMC Gastroenterol 2025; 25:318. [PMID: 40301782 PMCID: PMC12042622 DOI: 10.1186/s12876-025-03898-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 04/15/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Xiaoyue Zhang
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Ziming Lin
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Boyan Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Chenyu Ma
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Bowen Jiang
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Yan Geng
- School of Life Science and Health Engineering, Jiangnan University, Wuxi, 214122, China
| | - Yingyue Sheng
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
| | - Yuanyuan Dai
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.
| | - Yilin Ren
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.
- Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
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Hu W, Chen ZM, Wang Y, Yang C, Wu ZY, You LJ, Zhai ZY, Huang ZY, Zhou P, Huang SL, Li XX, Yang GH, Bao CJ, Cui XB, Xia GL, Ou Yang MP, Zhang L, Wu WKK, Li LF, Tan LK, Zhang YX, Gong W. Single-cell RNA sequencing dissects the immunosuppressive signatures in Helicobacter pylori-infected human gastric ecosystem. Nat Commun 2025; 16:3903. [PMID: 40281037 PMCID: PMC12032416 DOI: 10.1038/s41467-025-59339-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 04/18/2025] [Indexed: 04/29/2025] Open
Abstract
Helicobacter pylori (H. pylori) manipulates the host immune system to establish a persistent colonization, posing a serious threat to human health, but the mechanisms remain poorly understood. Here we integrate single-cell RNA sequencing and TCR profiling for analyzing 187,192 cells from 11 H. pylori-negative and 12 H. pylori-positive individuals to describe the human gastric ecosystem reprogrammed by H. pylori infection, as manifested by impaired antigen presentation and phagocytosis function. We further delineate a monocyte-to-C1QC+ macrophage differentiation trajectory driven by H. pylori infection, while T cell responses exhibit broad functional impairment and hyporesponsiveness with restricted clonal expansion capacity. We also identify an HLA-DRs- and CTLA4-expressing T cell population residing in H. pylori-inhabited stomach that potentially contribute to immune evasion. Together, our findings provide single-cell resolution information into the immunosuppressive microenvironment shaped by H. pylori infection, offering critical insights for developing novel therapeutic approaches to eliminate this globally prevalent pathogen.
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Affiliation(s)
- Wei Hu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Ze Min Chen
- Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ying Wang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Chao Yang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Zi Ying Wu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Li Juan You
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Zhi Yong Zhai
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Zhao Yu Huang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Ping Zhou
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Si Lin Huang
- Department of Gastroenterology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, Guangdong, China
| | - Xia Xi Li
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Gen Hua Yang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Chong Ju Bao
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Xiao Bing Cui
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Gui Li Xia
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Mei Ping Ou Yang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Lin Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - William Ka Kei Wu
- Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Long Fei Li
- Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri-implantation, Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong, China
| | - Li Kai Tan
- Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yu Xuan Zhang
- Department of Pharmacology and Therapeutics, King's College London, London, UK
| | - Wei Gong
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
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Lu MC, Yang YC, Lee CJ, Chiu CW. Helicobacter pylori Detection Based on Synergistic Electromagnetic and Chemical Enhancement of Surface-Enhanced Raman Scattering in 3D Hotspot-Activated Gold Nanorods/Nano Mica Platelets/ZnO Quantum Dots. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2503562. [PMID: 40265978 DOI: 10.1002/advs.202503562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/06/2025] [Indexed: 04/24/2025]
Abstract
Gold nanorods (AuNRs) with a controllable aspect ratio are anchored on the surface of delaminated nano mica platelets (NMPs) in the presence of a cationic interfacial activator and protective agent enabling the positive charging of the AuNR and nanohybrid surfaces. The high anionic charge and specific surface area of NMPs stabilize AuNR growth and benefit the adsorption of anionic analytes. The nanohybrids (AuNRs/NMPs) exhibit a 3D hotspot effect due to self-assembly and feature regularly arranged AuNRs, thus enabling Raman signal enhancement and sensitive (limit of detection (LOD) = 10-9 m, Raman enhancement factor (EF) = 2.0 × 108) and reproducible (relative standard deviation (RSD) = 8.82%) adenine detection based on surface-enhanced Raman scattering (SERS). The further incorporation of ZnO quantum dots (QDs) affords nanohybrids (AuNRs/NMPs/ZnO QDs) that exhibit electromagnetic and chemical signal enhancement mechanisms and enable more sensitive and reproducible adenine detection (LOD = 10-10 m, EF = 1.6 × 109, RSD = 7.66%). AuNRs/NMPs/ZnO QDs are subsequently used for the selective and sensitive SERS-based detection of Helicobacter pylori (LOD = 90 CFU mL-1). Thus, this work paves the way for the noninvasive, nonfluorescent labeling, rapid, sensitive, selective, and reproducible detection of H. pylori.
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Affiliation(s)
- Ming-Chang Lu
- Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan
| | - Yung-Chi Yang
- Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan
| | - Chia-Jung Lee
- Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan
| | - Chih-Wei Chiu
- Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan
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Chen D, Wang W, Chen X, Liang N, Li J, Ding W, Zhang H, Yang Z, Zhao H, Liu Z. Plant-derived extracts or compounds for Helicobacter-associated gastritis: a systematic review of their anti-Helicobacter activity and anti-inflammatory effect in animal experiments. Chin Med 2025; 20:53. [PMID: 40264171 PMCID: PMC12013188 DOI: 10.1186/s13020-025-01093-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 03/10/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Helicobacter infection, which is the leading cause of gastritis and stomach cancer, has become common worldwide. Almost all Helicobacter-infected patients have chronic active gastritis, also known as Helicobacter-associated gastritis (HAG). However, the eradication rate of Helicobacter is decreasing due to the poor efficacy of current medications, which causes infection to recur, inflammation to persist, and stomach cancer to develop. Natural components have robust antibacterial activity and anti-inflammatory capacity, as confirmed by many studies of alternative natural medicines. PURPOSE This article aimed to conduct a comprehensive search and meta-analysis to evaluate the efficacy of anti-Helicobacter and anti-inflammatory activities of plant-derived extracts or compounds that can treat HAG in animal experiments. We intended to provide detailed preclinical-research foundation including plant and compound information, as well as the mechanisms by which these plant-derived substances inhibit the progression of Helicobacter infection, gastritis and neoplasms for future study. METHODS The systematic review is aligned with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol was registered in PROSPERO (CRD42024527889). An extensive search was performed across multiple databases, including PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal database (VIP), the Wanfang database, and the China biomedical literature service system (SinoMed), up until November 2023. Meta-analysis on Review Manager software (RevMan 5.4) estimating anti-Helicobacter and anti-inflammatory activity was performed. We used the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool to evaluate the risk of bias of each study included. RESULTS Our study encompassed 61 researches, comprised 36 extracts and 37 compounds improving HAG by inhibiting Helicobacter infection, the inflammatory response, oxidative stress, and regulating apoptosis and proliferation. Sixteen families especially Asteraceae, Fabaceae and Rosaceae and nine classes including Terpenoids, Alkaloids, Phenols, and Flavonoids may be promising directions for valuable new drugs. The Meta-analyse demonstrated the plant-base substance treatments possess significant anti-Helicobacter and anti-inflammation activity comparing to control groups. The included plants and compounds confirmed that signaling pathways NF-κB, JAK2/STAT3, MAPK, TLR4/MyD88, PI3K/AKT, NLRP3/Caspase-1 and NRF2/HO-1 play a key role in the progression of HAG. CONCLUSION Plant-derived extracts or compounds actively improve HAG by modulating relevant mechanisms and signaling pathways, particularly through the anti-Helicobacter and inflammatory regulation ways. Further researches to apply these treatments in humans are needed, which will provide direction for the future development of therapeutic drugs to increase eradication rate and alleviate gastritis.
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Affiliation(s)
- Danni Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wenlai Wang
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China
| | - Xiangyun Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Ning Liang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jiawang Li
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wei Ding
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Hongrui Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Zhen Yang
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
| | - Hongxia Zhao
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China.
| | - Zhenhong Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China.
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China.
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Retnakumar RJ, Chettri P, Lamtha SC, Sivakumar KC, Dutta P, Sen P, Biswas S, Agarwal N, Nath AN, Devi TB, Thapa N, Tamang JP, Chattopadhyay S. Genome-wide accumulations of non-random adaptive point mutations drive westward evolution of Helicobacter pylori. BMC Microbiol 2025; 25:229. [PMID: 40263995 PMCID: PMC12013172 DOI: 10.1186/s12866-025-03944-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 04/01/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND For last seven decades we remained convinced that the natural point mutations occur randomly in the genome of an organism. However, our whole genome sequence analyses show that for the gastric pathogen Helicobacter pylori, which causes peptic ulcer and gastric cancer, accumulations of point mutations in the genome are non-random and they contribute to its unidirectional evolution. Based on the oncoprotein CagA, the pathogen can be classified into Eastern (East Asian countries like China and Japan; high incidence of gastric cancer) and Western (Europe, Africa, South-West Asian countries like India; low incidence of gastric cancer) types. RESULTS We have found a unique high-altitude Himalayan region, Sikkim (an Indian state bordering China, Nepal and Bhutan), where the evolving Eastern and Western H. pylori types co-exist and show the signs of genetic admixtures. Here, we present genomic evidence for more virulent Eastern-H. pylori getting converted to less virulent Western-H. pylori by accumulating non-random adaptive point mutations. CONCLUSION The lesser virulence of the westernized H. pylori is beneficial since this pathogen typically remains colonized in the stomach for decades before causing terminal diseases like gastric cancer. Moreover, the mutation-driven westward evolution of H. pylori is a global phenomenon, which occurred in the geographical regions where people from Eastern and Western ethnicities met and cohabited. The identified evolution of virulent Eastern H. pylori strains to lesser virulent Western variants by accumulation of point mutations also provides insight into the pathogenic potentials of different H. pylori strains.
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Affiliation(s)
- R J Retnakumar
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
- Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Prakash Chettri
- Biotech Hub, Department of Zoology, Nar Bahadur Bhandari Degree College, Tadong, Sikkim, India
| | | | - K C Sivakumar
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Priya Dutta
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Pahil Sen
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Sanjit Biswas
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
- Barry Marshall Research Centre for Helicobacter pylori, Asian Institute of Gastroenterology, Telangana, 500032, Hyderabad, India
| | - Nikita Agarwal
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Angitha N Nath
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - T Barani Devi
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Namrata Thapa
- Biotech Hub, Department of Zoology, Nar Bahadur Bhandari Degree College, Tadong, Sikkim, India.
| | | | - Santanu Chattopadhyay
- Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
- Barry Marshall Research Centre for Helicobacter pylori, Asian Institute of Gastroenterology, Telangana, 500032, Hyderabad, India.
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Xia K, Zhou Y, Wang W, Cai Y. Streptococcus anginosus: the potential role in the progression of gastric cancer. J Cancer Res Clin Oncol 2025; 151:143. [PMID: 40252119 PMCID: PMC12009222 DOI: 10.1007/s00432-025-06201-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Accepted: 04/11/2025] [Indexed: 04/21/2025]
Abstract
Gastric cancer (GC) is among the most common and aggressive malignancies worldwide, characterized by a poor prognosis. Research on its pathogenesis and progression continues to evolve. Streptococcus anginosus (S. anginosus, SA) is a Gram-positive coccus commonly found in the oral cavity and upper respiratory tract, serving as a commensal bacterium in the oral, gastrointestinal, and genitourinary tracts. It is frequently associated with abscess formation in various organs and tissues, as well as other purulent infections. In recent years, S. anginosus has gained increasing attention for its role in GC progression, potentially leading to chronic gastric inflammation and precancerous lesions, and ultimately promoting the development of GC. Emerging evidence indicates a strong association between S. anginosus and the malignant progression and unfavorable prognosis of GC. This review summarizes the role and underlying mechanisms of S. anginosus in GC and proposes that S. anginosus plays a pivotal role in its initiation and progression, underscoring its potential therapeutic significance.
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Affiliation(s)
- Kun Xia
- Department of General Surgery, People's Hospital of Ningxiang City, 209, North Road of 1st Ring, Ningxiang, Hunan, 410600, P. R. China
| | - Yaoxiang Zhou
- Department of General Surgery, People's Hospital of Ningxiang City, 209, North Road of 1st Ring, Ningxiang, Hunan, 410600, P. R. China
| | - Wei Wang
- Department of General Surgery, People's Hospital of Ningxiang City, 209, North Road of 1st Ring, Ningxiang, Hunan, 410600, P. R. China
| | - Yinzhong Cai
- Department of General Surgery, People's Hospital of Ningxiang City, 209, North Road of 1st Ring, Ningxiang, Hunan, 410600, P. R. China.
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Talebi G, Nabavi-Rad A, Sadeghloo Z, Doulberis M, Zali MR, Yadegar A. Inhibitory effects of Lactobacillus reuteri strain I300 against Helicobacter pylori adhesion, invasion, and inflammatory response in gastric epithelial cells in vitro. Folia Microbiol (Praha) 2025:10.1007/s12223-025-01263-7. [PMID: 40244552 DOI: 10.1007/s12223-025-01263-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 04/09/2025] [Indexed: 04/18/2025]
Abstract
The increasing rate of Helicobacter pylori (H. pylori) antibiotic resistance has attenuated the effectiveness of conventional antibiotic-based treatment regimens. This study was aimed at investigating the in vitro inhibitory effects of Lactobacillus reuteri (L. reuteri) strain I300 against H. pylori. The inhibitory effects of live L. reuteri I300 and its different formulations I300L, I300G, and I300T were examined on H. pylori adhesion and invasion to AGS cells. Auto-aggregation and co-aggregation assays and also scanning electron microscopy were performed, evaluating L. reuteri capacity to auto-aggregate and co-aggregate with H. pylori. RT-qPCR and ELISA were used to investigate the expression, and production level of inflammation-related cytokines TNF-α, IL-8, and IL-10. E-cadherin expression level was also measured, determining L. reuteri potential effect on AGS cells integrity. L. reuteri presented a time-dependent capacity to auto-aggregate and co-aggregate with H. pylori. Live L. reuteri and its formulations significantly reduced H. pylori adhesion and invasion of AGS cells. H. pylori treatment with L. reuteri reduced proinflammatory cytokines TNF-α and IL-8 production while increasing anti-inflammatory cytokine IL-10 production. L. reuteri promoted the epithelial cell-cell contact by upregulating E-cadherin expression. This study indicated L. reuteri I300 as a potential probiotic strain with co-aggregation capacity and inhibitory effects against H. pylori adhesion, invasion, and inflammation.
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Affiliation(s)
- Ghazaleh Talebi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Sadeghloo
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Michael Doulberis
- Gastroklinik, Private Gastroenterological Practice, Horgen, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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40
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Wan Z, Chung CH, Lau CML, Chung JT, Chau Y, Fan Z, Zhang S, Yao S. Metal-Organic Frameworks-Based Microrockets for Controlled and Sustained Drug Release. NANO LETTERS 2025; 25:5989-5996. [PMID: 40094425 PMCID: PMC12007105 DOI: 10.1021/acs.nanolett.4c04628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 03/13/2025] [Accepted: 03/13/2025] [Indexed: 03/19/2025]
Abstract
Gastritis, linked to chronic stress and poor diets, poses significant risks, including ulcers and gastric cancers. Current treatments involving frequent dosing of multiple drugs face challenges with patient nonadherence and antibiotic resistance. To overcome these issues, metal-organic framework (MOF)-based microrockets utilizing a zinc-powered engine were engineered with pH-sensitive coatings for targeted gastritis treatment. These microrockets can self-propel into the gastric mucus via bubble propulsion and slowly release pharmaceutical ingredients from MOF components. A poly(3,4-ethylenedioxythiophene) shell and pH-sensitive enteric coating is designed for protection of MOFs in acid while allowing sustained drug release at the mucosa's neutral pH. In vivo studies demonstrate these microrockets sustain a prolonged drug retention for 48 h. This biocompatible design represents a promising strategy for active and controlled drug delivery with sustained release in acidic environments, presenting the potential for diverse biomedical applications.
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Affiliation(s)
- Zixi Wan
- Department
of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
- Department
of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Casper H.Y. Chung
- Department
of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Chi Ming Laurence Lau
- Department
of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Jin Teng Chung
- Department
of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Ying Chau
- Department
of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Zhiyong Fan
- Department
of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
- Department
of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Shuaizhong Zhang
- Department
of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
| | - Shuhuai Yao
- Department
of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
- Department
of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, SAR, China
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41
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Wei Y, Zhou L, Zhao X, Qiu H, Hu D, Shi Z. Helicobacter pylori outer membrane vesicles mediate central tolerance in C57BL/6J mice offspring T cells via maternal-fetal transmission. Front Immunol 2025; 16:1522842. [PMID: 40303395 PMCID: PMC12037491 DOI: 10.3389/fimmu.2025.1522842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 03/26/2025] [Indexed: 05/02/2025] Open
Abstract
Outer membrane vesicles (OMVs) released by Helicobacter pylori (H.pylori) can enter the blood circulation of the host and cause extra-gastric lesions such as atherosclerosis and hyperemesis gravidarum. This study aimed to investigate the effect of OMVs released by H.pylori on the development of thymic T cells in offspring mice and its underlying mechanisms. Through experimental observations, we found that H.pylori OMVs were able to cross the placental barrier, leading to a decrease in the number of CD3+ and CD4+ T cells in the peripheral blood of the offspring mice and a decrease in the response of T cells to H.pylori stimulation. After stimulation with OMVs in T cell positive selection experiments, the expression levels of CHMP5, IKK-β, and NF-κB are up-regulated, and the release of cytokines IL-7, IL-2, IL-4, and IFN-γ is simultaneously increased, whereas in T cell negative selection experiments, the expression of JNK is up-regulated, and the expression of CHMP5 and Bcl-2 is down-regulated in E15-16 fetal thymus organ culture. These results indicate that transmission of H pylori OMVs from mother to fetus might be related to the development of central tolerance in offspring T cells. The underlying mechanism may involve an interaction between the OMVs-stimulated pathway and the TCR pathway, although further research is needed to confirm this hypothesis. The study highlights the importance of preventing H.pylori infection during pregnancy and suggests that the effect of centrally tolerated antigens needs to be considered in vaccine design to maximize prevention.
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Affiliation(s)
- Yusen Wei
- Graduate School, Hebei Medical University, Shijiazhuang, China
- Department of Oncology, Hebei General Hospital, Shijiazhuang, China
| | - Lu Zhou
- Graduate School, Hebei Medical University, Shijiazhuang, China
| | - Xiaofei Zhao
- Department of Pharmacy, Hebei General Hospital, Shijiazhuang, China
| | - Huiqing Qiu
- Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Dailun Hu
- Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, China
| | - Zhongli Shi
- Graduate School, Hebei Medical University, Shijiazhuang, China
- Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, The First Hospital of Hebei Medical University, Shijiazhuang, China
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Yamada H, Abe S, Charvat H, Ando T, Maeda M, Murakami K, Oka S, Maekita T, Sugimoto M, Furuta T, Kaise M, Yamamichi N, Takamaru H, Sasaki A, Oda I, Nanjo S, Suzuki N, Sugiyama T, Kodama M, Mizukami K, Ito M, Kotachi T, Shimazu T, Yamamoto S, Ushijima T. Precision risk stratification of primary gastric cancer after eradication of H. pylori by a DNA methylation marker: a multicentre prospective study. Gut 2025:gutjnl-2025-335039. [PMID: 40240063 DOI: 10.1136/gutjnl-2025-335039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 03/14/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Precision cancer risk stratification for gastric cancer is urgently needed for the growing number of healthy people after Helicobacter pylori eradication. The epimutation burden in non-malignant tissues has been associated with cancer risk in multiple cross-sectional studies. OBJECTIVE To confirm the clinical usefulness of a DNA methylation marker for epimutation burden, and to identify a cut-off methylation level for a super-high-risk population. DESIGN Healthy people after H. pylori eradication with open-type atrophy were prospectively recruited. DNA methylation levels of a marker gene, RIMS1, were measured in biopsy specimens from gastric antrum and body. The primary endpoint was the incidence rate of gastric cancer in quartiles of the methylation levels. RESULTS 1624 participants had at least one endoscopic follow-up with a median follow-up of 4.05 years, and a primary gastric cancer developed in 27 participants. The highest quartile of RIMS1 methylation levels had a higher incidence rate (972.8 per 100 000 person-years) than the lowest quartile (127.1). Cox regression analysis revealed a univariate HR of 7.7 (95% CI 1.8-33.7) and an age- and sex-adjusted HR of 5.7 (95% CI 1.3-25.5). As a secondary objective, a cut-off methylation level of 25.7% (95% CI 1.7-7.7) was obtained to identify a population with a super-high risk based on the number needed to screen of 1000. CONCLUSION A DNA methylation marker can risk-stratify healthy people after H. pylori eradication even though all of them have clinically high risk. Individuals with super-high risk will need more frequent gastric cancer screening than currently recommended. TRIAL REGISTRATION NUMBER UMIN-CTR000016894.
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Affiliation(s)
- Harumi Yamada
- Department of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan
- Department of Gastrointestinal Surgery, Kyoto University, Kyoto, Japan
- Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Seiichiro Abe
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hadrien Charvat
- Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan
- Division of International Health Policy Research, Institute for Cancer Control, National Cancer Center, Tokyo, Japan
| | - Takayuki Ando
- Third Department of Internal Medicine, University of Toyama, Toyama, Japan
| | - Masahiro Maeda
- Department of Gastrointestinal Surgery, Kyoto University, Kyoto, Japan
- Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Shiro Oka
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Takao Maekita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan
- Division of Genome-Wide Infectious Microbiology, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Oita, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Mitsuru Kaise
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
| | - Nobutake Yamamichi
- Department of Gastroenterology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan
| | | | - Akiko Sasaki
- Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kanagawa, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Sohachi Nanjo
- Third Department of Internal Medicine, University of Toyama, Toyama, Japan
| | - Nobuhiro Suzuki
- Department of Internal Medicine, Joetsu General Hospital, Niigata, Japan
| | - Toshiro Sugiyama
- Third Department of Internal Medicine, University of Toyama, Toyama, Japan
- Health Sciences University of Hokkaido, Hokkaido, Japan (Present adrress)
| | - Masaaki Kodama
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Advanced Medical Sciences, Faculty of Medicine, Oita University, Oita, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Masanori Ito
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Takahiro Kotachi
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Research Center for Cancer Prevention andScreening, National Cancer Center, Tokyo, Japan
| | | | - Toshikazu Ushijima
- Department of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan
- Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan
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Qiu J, Liu D, Wu C, Chen H, Xie J, Chen S, Wang Y, Zhou F, Fang J, Lai Q, Zhao R, Xie Y. Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and Helicobacter pylori infection. Sci Rep 2025; 15:12560. [PMID: 40221572 PMCID: PMC11993665 DOI: 10.1038/s41598-025-96851-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Evidence on the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and Helicobacter pylori (H. pylori) infection remains limited. This study investigates this correlation based on the U.S. population. This cross-sectional research included data on 834 U.S. participants from the National Health and Nutrition Examination Survey 1999-2000. The association between the NHHR and H. pylori infection was examined using logistic regression models, restricted cubic spline (RCS) curve and subgroup analyses. Individuals with H. pylori infection exhibited significantly higher NHHR value. A significant positive association between NHHR and H. pylori infection was observed across all three models, even after adjusting for potential confounders, with a stronger association noted in males, individuals under 60 years of age, and non-Hispanic White participants. These findings suggest NHHR may act as a non-invasive biomarker for detecting H. pylori infection in U.S. populations.
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Affiliation(s)
- Jiayu Qiu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Dingwei Liu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Chengyun Wu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Hao Chen
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jinliang Xie
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Sihai Chen
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Youhua Wang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Feng Zhou
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jiasheng Fang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Qirui Lai
- Huan Kui College of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Rulin Zhao
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
- Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
| | - Yong Xie
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
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Said KB, Alshammari KF, Moussa S, Ahmed RME, Aljadani AH, Albalawi NB, Al-Hujaili L, Alharbi R, Alotaibi AA, Alshammary FM, Alfouzan FR, Albayih ZA, Alkharisi BI, Alsdairi GN, Alshubrami SH. Clinical Pathologic Profiles of Helicobacter pylori Reveal Age-Specific Peaking with Concomitant Chronic Gastric Inflammation, Robust Immunity, and Tissue Alterations Implying Potential Predisposition to Malignancy in Ha'il, Saudi Arabia. J Clin Med 2025; 14:2643. [PMID: 40283473 PMCID: PMC12028268 DOI: 10.3390/jcm14082643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/06/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives:Helicobacter pylori (H. pylori) is a significant global health issue causing chronic gastritis, peptic ulcers, and gastric malignancies. Unfortunately, many, particularly in the Middle East, continue to exhibit alarming rates of prevalence. This study aimed to elucidate local epidemiological patterns of H. pylori and examine its histopathological impact on the gastric mucosa. Methods: This retrospective-cross-sectional study included 805 symptomatic adults (329 males, 476 females) who underwent endoscopic evaluation at King Salman Hospital, Ha'il, Saudi Arabia. Biopsies from the antrum and body were processed using routine formalin fixation and paraffin embedding. Staining with hematoxylin-eosin (H&E) and Giemsa permitted assessment of chronic gastritis and detection of H. pylori. Data were evaluated by IBM SPSS (version 23, IBM Corp., Armonk, NY) for associations among infection, histopathology, and patient characteristics. Results: A total of 727 (90.3%) were H. pylori-positive with marginally higher rates in females (91.2%) than males (89.0%). Infection spanned all age groups, reaching 100% in males aged 60-80 years. Overall chronic GI complications were identified in 726 (99.9%), with chronic gastritis being the most profound histopathologically (19.3%). Lymphoid aggregates in 93.0% biopsies reflected a pronounced immune response. Advanced lesions, including metaplasia (0.8%), atrophy (0.3%), and lymphoma (0.1%), were uncommon, though indicative of potential malignant progression. Despite both sexes exhibiting universal symptoms of gastritis, dyspepsia, and heartburn, there were no statistically significant gender-based differences (p > 0.05); specifically, post-H. pylori signs such as vomiting, nausea, weight loss, bleeding or hematemesis occurred equally in all. Histopathology consistently revealed chronic active gastritis with glandular distortion, lymphoplasmacytic infiltration, and occasional mucosal erosions. Giemsa staining further confirmed abundant spiral shapes underscoring a high bacterial load. Conclusion: These findings highlight the age-specific persistently elevating rates of H. pylori significantly associated with chronic gastric inflammatory complications. Although advanced gastric lesions remain rare, reflecting regional epidemiology, early screening, and sleeve treatment efforts, the potential for malignant transformation makes it imperative for continued vigorous eradication, therapy, and vigilant follow-up to avert severe disease outcomes.
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Affiliation(s)
- Kamaleldin B. Said
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Khalid F. Alshammari
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Safia Moussa
- Department of Clinical Microbiology, King Salman Specialist Hospital Ha’il 55462, Saudi Arabia; (S.M.)
| | - Ruba M. Elsaid Ahmed
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Ahmed H. Aljadani
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Najd B. Albalawi
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Layan Al-Hujaili
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Ruaa Alharbi
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Arwa A. Alotaibi
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Fahad M. Alshammary
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Fayez R. Alfouzan
- Department of Clinical Microbiology, King Salman Specialist Hospital Ha’il 55462, Saudi Arabia; (S.M.)
| | - Zaid A. Albayih
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Bader I. Alkharisi
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
| | - Ghadah N. Alsdairi
- Family Medicine Resident, Ha’il Health Cluster, Ha’il 55462, Saudi Arabia
| | - Shumukh H. Alshubrami
- Department of Pathology, College of Medicine, University of Ha’il, Ha’il 55462, Saudi Arabia
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Grabarek M, Tabor W, Krzyżek P, Grabowiecka A, Berlicki Ł, Mucha A. Halogenated N-Benzylbenzisoselenazolones Efficiently Inhibit Helicobacter pylori Ureolysis In Vitro. ACS Med Chem Lett 2025; 16:675-680. [PMID: 40236561 PMCID: PMC11995230 DOI: 10.1021/acsmedchemlett.5c00057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/21/2025] [Accepted: 03/25/2025] [Indexed: 04/17/2025] Open
Abstract
Inspired by the recognized activity of Ebselen against urease, we optimized the structure of 1,2-benzisoselenazol-3(2H)-one to provide potent inhibitors of ureolysis in Helicobacter pylori cells. To achieve this goal, we combined the elongation of the N-substituent of Ebselen from phenyl to benzyl with halogenation of the aromatic fragment. The modifications implemented provided compounds with activities that were several times better compared to that of the lead compound. In particular, 3-fluoro-4-trifluoromethyl and 2-chloro-5-fluoro derivatives of N-benzyl-1,2-benzisoselenazol-3(2H)-one achieved a remarkable antiureolytic effect in live H. pylori cells (IC50 < 100 nM) that outperformed the data reported so far. This activity was reflected in the antiurease potential measured for the Sporosarcina pasteurii model enzyme, with the highest affinity observed for 2-chloro-5-fluoro and 2,4-dichloro derivatives (K i < 0.6 nM). The best inhibitor demonstrated considerable antibacterial properties on a multidrug-resistant clinical H. pylori isolate in additive combination with clarithromycin (MIC = 0.073 μg/mL).
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Affiliation(s)
- Marta Grabarek
- Department
of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego
27, 50-370 Wrocław, Poland
| | - Wojciech Tabor
- Department
of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego
27, 50-370 Wrocław, Poland
| | - Paweł Krzyżek
- Department
of Microbiology, Faculty of Medicine, Wrocław
Medical University, Chałubińskiego
4, 50-368 Wrocław, Poland
| | - Agnieszka Grabowiecka
- Department
of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego
27, 50-370 Wrocław, Poland
| | - Łukasz Berlicki
- Department
of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego
27, 50-370 Wrocław, Poland
| | - Artur Mucha
- Department
of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego
27, 50-370 Wrocław, Poland
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46
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Ye L, Yan K, Tian Z, Xiao ZH, Xie RY, Xie ZY, Tao L. Helicobacter pylori infection is linked to metabolic dysfunction and associated steatotic liver disease: A large cross-sectional study. World J Gastroenterol 2025; 31:102563. [PMID: 40248064 PMCID: PMC12001171 DOI: 10.3748/wjg.v31.i13.102563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 02/19/2025] [Accepted: 03/12/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori), a globally widespread pathogen affecting half of the global population, has been increasingly implicated in metabolic disorders, including obesity, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is a common condition, impacting nearly one in four adults globally. It also shares significant pathophysiological links with metabolic syndrome. Despite the fact that mechanistic hypotheses (such as oxidative stress and inflammation) have been proposed to explain these relationships, large-scale studies comprehensively assessing multifactorial metabolic associations are lacking. We proposed that H. pylori infection may independently correlate with unfavorable metabolic profiles and the presence of MASLD among adults in a large cohort. AIM To investigate the associations of H. pylori infection with obesity, glucose, lipids, blood pressure, and MASLD in Chinese adults. METHODS This study included 28624 adults recruited from the Physical Examination Center at Nanchang University's Second Affiliated Hospital. The 13C-urea breath test was used to identify H. pylori infection, while abdominal ultrasound was employed for MASLD diagnosis. The relationships between H. pylori infection and metabolic factors were analyzed via multivariate logistic regression. RESULTS The overall H. pylori infection incidence was 26.8%, with higher rates observed in older adults (≥ 70 years: 26.1% vs 18-29 years: 24.6%, P < 0.001) and obese individuals [body mass index (BMI) ≥ 28 kg/m²: 30.0% vs normal BMI: 25.3%, P < 0.001]. H. pylori-positive individuals exhibited elevated blood glucose (5.43 ± 1.55 mmol/L vs 5.27 ± 1.23 mmol/L, P < 0.001), low-density lipoprotein cholesterol (2.97 ± 0.76 mmol/L vs 2.94 ± 0.75 mmol/L, P < 0.001), and blood pressure (systolic: 123.49 ± 19.06 mmHg vs 122.85 ± 18.33 mmHg, P = 0.009; diastolic: 75.48 ± 12.37 vs 74.9 mmHg ± 11.9 mmHg, P < 0.001) levels. Among MASLD patients, infection was associated with increased glucose (5.82 ± 1.95 mmol/L vs 5.60 ± 1.60 mmol/L, P < 0.001), total cholesterol (5.05 ± 1.03 mmol/L vs 5.00 ± 1.00 mmol/L, P = 0.039), BMI (26.23 ± 3.00 kg/m² vs 26.04 ± 2.96 kg/m², P = 0.004), and blood pressure (systolic: 129.5 ± 20.00 mmHg vs 128.49 ± 17.62 mmHg, P = 0.009; diastolic: 79.87 ± 12.07 mmHg vs 79.04 ± 11.76 mmHg, P = 0.002) levels. Multivariate analysis demonstrated elevated glucose [odds ratio (OR) = 1.079, P < 0.001], BMI (OR = 1.016, P = 0.002), and diastolic pressure (OR = 1.003, P = 0.048) levels as independent risk factors, with high-density lipoprotein (HDL) being observed as a protective factor (OR = 0.837, P < 0.001). CONCLUSION H. pylori infection correlates with older age, obesity, elevated glucose levels, and elevated diastolic blood pressure, whereas HDL protects against H. pylori infection, thus underscoring its role in metabolic disturbances and MASLD.
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Affiliation(s)
- Lin Ye
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Kai Yan
- Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Ze Tian
- Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Zhi-Hua Xiao
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Ru-Yi Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Zheng-Yuan Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
| | - Li Tao
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330008, Jiangxi Province, China
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Cao W, Jin F, Liu B, Xu G, Jin S, Jia Z, Peng P, Song W, Li F, Gao D, Feng K. Synthesis and evaluation of novel ebselen derivatives as urease inhibitors for combating Helicobacter pylori infections. Eur J Med Chem 2025; 287:117359. [PMID: 39919439 DOI: 10.1016/j.ejmech.2025.117359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/23/2025] [Accepted: 01/31/2025] [Indexed: 02/09/2025]
Abstract
The development of novel inhibitors targeting urease that affects the colonization of Helicobacter pylori (H. pylori) is a promising strategy to address the growing challenge of antibiotic resistance. In this study, a novel urease covalent inhibitor, XBP2 (IC50 = 0.14 ± 0.01 μM and MIC = 8 μg/mL), was identified through structure-based design using Ebselen as a template. XBP2 binds to a newly identified site, forming stable dipole interaction with residues ASP223 and HIS322, which enhances both stability and inhibitory activity against urease. It exhibits potent in vitro antibacterial activity, reducing cell apoptosis rates and significantly decreasing the fluorescence intensity of ROS and γH2AX in GES-1 cells infected with H. pylori. In the mouse gastritis model infected with H. pylori, XBP2 exhibits significant gastric mucosal protective effects. High-dose XBP2 (50 mg/kg) effectively prevented pathological changes such as bleeding and hyperplasia. Furthermore, acute toxicity test revealed that XBP2 does not display any detectable toxicity. These findings not only expand the structural diversity of Ebselen derivatives but also provide valuable insights for developing targeted therapies for eradicating H. pylori.
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Affiliation(s)
- Weilong Cao
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Feng Jin
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Binzhuo Liu
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Guangzhao Xu
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Shanshan Jin
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Zongqing Jia
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China
| | - Peng Peng
- School of Pharmacy, East China Normal University, Shanghai, 200241, China
| | - Weiguo Song
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China.
| | - Fahui Li
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China.
| | - Dingding Gao
- The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Kairui Feng
- School of Pharmacy, Shandong Second Medical University, Weifang, 261053, China.
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48
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Hu C, Zhao Z, Zhu D, Li R, Jiang X, Ren Y, Ma X, Zhao X. A Comparative Analysis of the Clinical Application of a Novel Helicobacter pylori Serum Antibody Typing Test and the 13C-Urea Breath Test. Diagnostics (Basel) 2025; 15:934. [PMID: 40218284 PMCID: PMC11988664 DOI: 10.3390/diagnostics15070934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/26/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: To compare and analyze the application of a Helicobacter pylori (H. pylori, Hp) serum antibody typing test (Hp-sATT) and the 13C-urea breath test (13C-UBT) in the diagnosis of Hp infection against an empirical therapy background. Methods: The detection of Hp-sATT using a combination of the quantum dot immunofluorescence method and the 13C-UBT was carried out in 237 patients who visited the Department of Gastroenterology at Beijing Tsinghua Changgung Hospital. The diagnostic consistency and correlation with gastric lesions of the two detection methods were analyzed by integrating the detection results, clinical information, and special staining of Hp in histopathological tissues (SS-Hp). Results: For the 13C-UBT, 104 (43.88%) cases were positive and 133 (56.12%) were negative. Positive results were found in 127 (53.59%) patients by using the Hp-sATT, with 67 (28.27%) cases of Type I Hp infection and 60 (25.32%) cases of Type II Hp infection. The consistency analysis between the Hp-sATT and 13C-UBT for all the patients showed a Kappa value of 0.339 (p < 0.001); the consistency analysis between the Hp-sATT and the 127 patients with SS-Hp showed a Kappa value of 0.427 (p < 0.001); and the consistency analysis between the 13C-UBT and the 127 patients with SS-Hp indicated a Kappa value of 0.621 (p < 0.001). However, in 191 patients without a history of Hp eradication, the consistency analysis results for the three methods improved, with Kappa values of 0.467 (p < 0.001) and 0.457 (p < 0.001) for the Hp-sATT with the 13C-UBT and SS-Hp, respectively, and 0.646 (p < 0.001) for the 13C-UBT with SS-Hp. In addition, a positive correlation was found between the signal values of anti-urease antibodies and the Delta Over Baseline (DOB) values of the 13C-UBT. The results also indicated that Hp-infected patients exhibited more pronounced gastric lesions, while cases with Type I Hp infection did not. Conclusions: In patients without a history of Hp eradication, the consistency between the Hp-sATT and 13C-UBT is moderate. However, Hp eradication therapy can reduce the consistency of the test results. When screening for Hp infection using the Hp-sATT, it is necessary to consider the patient's history of Hp eradication.
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Affiliation(s)
- Chonghui Hu
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
| | - Zhipeng Zhao
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
| | - Dong Zhu
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
| | - Runqing Li
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
| | - Xuan Jiang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (X.J.); (Y.R.)
| | - Yutang Ren
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (X.J.); (Y.R.)
| | - Xin Ma
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
| | - Xiuying Zhao
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China; (C.H.); (Z.Z.); (D.Z.); (R.L.); (X.M.)
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Mu X, Fan Y, Xu J, Xie R. Exploration of the optimal regimen of gastric mucosal cleansing medication for the H. pylori population before ME-NBI screening: study protocol for a single-center, single-blind, randomized controlled trial. Front Med (Lausanne) 2025; 12:1516271. [PMID: 40241907 PMCID: PMC12000017 DOI: 10.3389/fmed.2025.1516271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
Objective Magnifying endoscopy combined with narrow-band imaging endoscopy is an emerging method for early gastric cancer screening and diagnosis However, its effectiveness is closely related to the cleaning quality of the gastric mucosal preparation. H. pylori infection is a major risk factor for inadequate gastric mucosa cleaning quality preparation. Multiple medications are useful in helping patients with gastric mucosal cleansing preparations. This randomized controlled trial study protocol aims to investigate the effect of different combinations of medications on the quality of gastric mucosal cleansing in an H. pylori-infected population. Methods This study is a prospective, randomized, single-blind, single-center trial. The subjects are patients who require magnifying endoscopy combined with narrow-band imaging and have evidence of H. pylori infection (a non-invasive diagnostic 13C urea breath test was used to examine the study subjects). These patients will be randomly assigned to the control group (Group A) and the experimental groups (Groups B, C, D, E, and F). Each group will consist of 44 patients, with a total of 264 patients expected to be enrolled. The core content of the drug preparation regimen for each group is as follows: Group A (control group) will take 10 ml of simethicone before the examination; Group B (experimental group) will take 20,000 units of pronase before the examination; Group C (experimental group) will take 600 mg of N-acetylcysteine before the examination; Group D (experimental group) will take 10 ml of simethicone +20,000 units of pronase before the examination; Group E (experimental group) will take 10 ml of simethicone + 600 mg of N-acetylcysteine before the examination; Group F (experimental group) will take 10 ml of simethicone + 20,000 units of pronase + 1 g of sodium bicarbonate before the examination. All group medications will be dissolved in 50 ml of warm water at 20-40°C. All patients will fast for ≥6 h and abstain from drinking for 2 h before the examination. The primary endpoint is the gastric mucosa cleanliness score. Secondary endpoints include the early detection rate of gastric cancer, polyp detection rate, adenoma detection rate, procedure time, number of irrigations, patient medication compliance, preoperative anxiety, incidence of adverse reactions, overall patient satisfaction, and willingness to undergo the examination again. Implications The results of this research project are aimed at improving the quality of gastric mucosal cleansing preparations in the H. pylori population to meet the demand for early diagnosis and treatment prevention screening for early gastric cancer screening. The implementation of the results of the study and their inclusion in the guidelines may reduce economic expenditures by reflecting a reduced need for social and health care services. Clinical Trial registration Chinese Clinical Trial Registry (ChiCTR). Number of identification: (ChiCTR2400087510).
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Affiliation(s)
- Xinyi Mu
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yi Fan
- Department of Endoscopy, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Jingyu Xu
- Nursing College, Zunyi Medical University, Zunyi, Guizhou, China
| | - Rui Xie
- Department of Endoscopy and Digestive System, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
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50
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Bogiel T, Szaflarska-Popławska A, Krawczyk A. Prevalence and Variability of Helicobacter pylori Clarithromycin Resistance Mutations in Pediatric Patients in Poland: A Genotypic Analysis Using the Bosphore Genotyping Kit. Antibiotics (Basel) 2025; 14:352. [PMID: 40298526 PMCID: PMC12024284 DOI: 10.3390/antibiotics14040352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 03/23/2025] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Helicobacter pylori is a Gram-negative bacterium responsible for various gastrointestinal diseases, including peptic ulcers and gastric cancer. Despite available antibiotic therapies, increasing resistance to clarithromycin-a key antibiotic in eradication regimens-poses a significant challenge. This resistance is primarily linked to point mutations in the 23S rRNA gene, particularly A2143G, A2142G, and A2142C, which hinder clarithromycin binding, reducing its bacteriostatic efficacy. This study aimed to assess the prevalence and variability of clarithromycin resistance mutations in pediatric patients from Bydgoszcz, Poland. Methods: A total of 45 gastric biopsy samples from pediatric patients were analyzed using the Bosphore®Helicobacter pylori Genotyping Kit v1 to detect clarithromycin resistance-associated mutations. Results: Among the 45 tested samples, 30 were classified as wild-type, while 12 contained resistance-associated mutations. The most frequently detected mutation was A2143G (58.3%), followed by A2142G (33.3%). One sample exhibited both A2142G and A2143G mutations, and another contained a mixture of wild-type and mutant strains. The A2142C mutation was not detected in any sample. Conclusions: Our findings confirm the predominance of A2143G among clarithromycin-resistant H. pylori strains, consistent with global trends. The detection of both mutant and wild-type strains in a single patient highlights potential co-infections or subpopulations with varying resistance profiles. Continuous surveillance and improved diagnostic tools are crucial for optimizing treatment strategies. Tailored eradication protocols based on resistance profiling are necessary to enhance treatment efficacy and mitigate the spread of resistant strains. Further research is needed to understand the clinical implications of mixed infections and double mutations in H. pylori resistance development.
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Affiliation(s)
- Tomasz Bogiel
- Department of Propaedeutics of Medicine and Infection Prevention Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University and Clinical Microbiology Laboratory, Dr. Antoni Jurasz University Hospital No. 1 in Bydgoszcz, 9 Maria Skłodowska-Curie Street, 85-094 Bydgoszcz, Poland
| | - Anna Szaflarska-Popławska
- Department of Pediatric Endoscopy and Gastrointestinal Function Testing Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland;
| | - Agnieszka Krawczyk
- Department of Molecular Medical Microbiology, Chair of Microbiology, Jagiellonian Univeristy Medical College, 31-007 Cracow, Poland
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