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Mansour RM, El-Sayyad GS, Abulsoud AI, Hemdan M, Faraag AHI, Ali MA, Elsakka EGE, Abdelmaksoud NM, Abdallah AK, Mahdy A, Ashraf A, Zaki MB, Elrebehy MA, Mohammed OA, Abdel-Reheim MA, Abdel Mageed SS, Alam Eldein KM, Doghish AS. The role of miRNAs in pathogenesis, diagnosis, and therapy of Helicobacter pylori infection, gastric cancer-causing bacteria: Special highlights on nanotechnology-based therapy. Microb Pathog 2025; 205:107646. [PMID: 40348207 DOI: 10.1016/j.micpath.2025.107646] [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: 02/13/2025] [Revised: 04/24/2025] [Accepted: 04/28/2025] [Indexed: 05/14/2025]
Abstract
Helicobacter pylori (H. pylori) infection and consequent inflammation in the stomach are widely recognized as major contributors to gastric cancer (GC) development. Recent investigations have placed considerable emphasis on uncovering the controlling influence of small RNA molecules known as microRNAs (miRNAs) in H. pylori-related diseases, particularly gastric cancer. This review aims to offer a comprehensive understanding of the intricate roles fulfilled by miRNAs in conditions associated with H. pylori infection. Exploring miRNA biogenesis pathways reveals their intimate connection with H. pylori infection, shedding light on the underlying molecular mechanisms driving disease progression and identifying potential intervention targets. An examination of epidemiological data surrounding H. pylori infection, including prevalence, risk factors, and transmission routes, underscores the imperative for preventive measures and targeted interventions. Incorporating insights from miRNA-related research into these strategies holds promise for enhancing their efficacy in controlling H. pylori spread. The symptoms, underlying mechanisms, and virulent characteristics of the bacteria highlight the intricate relationship between H. pylori and host cells, influencing the course of diseases. Within this complex web, miRNAs play pivotal roles, regulating various facets of H. pylori's development. MicroRNAs intricately involved in directing the immune response against H. pylori infection serve as key players in molding host defense mechanisms and impacting the bacterium's evasion tactics. Utilizing this knowledge holds the potential to drive forward groundbreaking therapeutic strategies. The diagnostic and prognostic capabilities of miRNAs in H. pylori infection highlight their effectiveness as non-invasive indicators for identifying diseases and evaluating risk. Integration of miRNA signatures into diagnostic algorithms holds promise for enhancing early detection and management of H. pylori-related diseases. MiRNA-based therapeutics offer a promising avenue for combatting H. pylori-induced gastric cancer, targeting specific molecular pathways implicated in tumorigenesis. H. pylori infection induces dysregulation of several miRNAs that contribute to antibiotic resistance, inflammation, and gastric cancer progression, including downregulation of tumor-suppressive miR-7 and miR-153 and upregulation of oncogenic miR-671-5p and miR-155-5p, which promote carcinogenesis and inflammation. Additionally, H. pylori manipulates host immune responses by upregulating miRNAs such as let-7f-5p, let-7i-5p, miR-146b-5p, and miR-185-5p that suppress HLA class II expression and antigen presentation, facilitating immune evasion and chronic gastritis that predispose to gastric cancer. Future research endeavors should focus on refining these therapeutic modalities and identifying novel targets to optimize clinical outcomes. By elucidating the multifaceted roles of miRNAs in H. pylori infection, this review provides invaluable insights into disease pathogenesis, diagnostics, and therapeutics, and the role of some nanoparticles in combating the H. pylori infection. Continued research efforts are imperative for translating these insights into clinical practice and addressing the global burden of H. pylori-related diseases.
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Affiliation(s)
- Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Gharieb S El-Sayyad
- Department of Medical Analysis Technology, Faculty of Applied Health Sciences Technology, Badr University in Cairo (BUC), Cairo, Egypt; Drug Microbiology Lab., Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Mohamed Hemdan
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed H I Faraag
- Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Medical Department, School of Biotechnology, Badr University in Cairo, Badr City, Cairo, 11829, Egypt.
| | - Mohamed A Ali
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
| | - Nourhan M Abdelmaksoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Asmaa K Abdallah
- Botany and Microbiology Department, Faculty of Science, Benha University, 13518 Benha, Egypt.
| | - Ahmed Mahdy
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Alaa Ashraf
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt; Department of Biochemistry, Faculty of Pharmacy, Menoufia National University, km Cairo-Alexandria Agricultural Road, Menofia, Egypt.
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Galala University, New Galala City, 43713, Suez, Egypt.
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
| | | | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Khaled M Alam Eldein
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed S Doghish
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
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Sahlberg C, Salmela E, Rice DP, Nakano K, Nomura R, Alaluusua S. Effect of Helicobacter pylori on enamel and dentin development - an in vitro study in mice. J Oral Microbiol 2025; 17:2500670. [PMID: 40351552 PMCID: PMC12064110 DOI: 10.1080/20002297.2025.2500670] [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: 02/17/2025] [Revised: 04/25/2025] [Accepted: 04/26/2025] [Indexed: 05/14/2025] Open
Abstract
Objective A heavy infection in a primary molar tooth can impair the enamel formation of the underlying permanent successor. Helicobacter pylori colonizes primarily the stomach, but it has also been detected in oral samples, including in the dental pulp of infected primary teeth. Here, we aim to test if H. pylori can disturb enamel and dentin formation. Methods Mandibular molar explants of E18.5 mice were grown for 12 days in media containing 10% of H. pylori cell lysates. The presence and extent of enamel and dentin on the mesial surface of the first molar explants were evaluated from stereomicroscopic photographs and histologically. Results The statistical analyses revealed that less enamel was formed in the test (N = 47) than in the control first molars (N = 28, p < 0.001). Most severe disturbances were seen in explants grown in media containing H. pylori cell lysates, which were made from stationary growth-phase cultures, with high optical density. Histological findings showed that dentin mineralization was also impaired. Conclusion The results suggest that H. pylori disturbs enamel and dentin development in cultured mouse embryonic molar teeth. This provides new insight into the etiology of enamel disturbances in permanent teeth.
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Affiliation(s)
- Carin Sahlberg
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Eija Salmela
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - David P. Rice
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kazuhiko Nakano
- Department of Pediatric Dentistry, Graduate School of Dentistry, Osaka University, Osaka, Japan
| | - Ryota Nomura
- Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Satu Alaluusua
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Zhang S, Ma S, Hao S, Pan J, Li Y, Yuan G, Li P, Hu H, Yu S. Fucoidan-modified antibiotic-free nanovesicles: A multidimensional approach to eradicate intracellular and extracellular Helicobacter pylori and restore gastrointestinal homeostasis. Int J Biol Macromol 2025; 307:141786. [PMID: 40057100 DOI: 10.1016/j.ijbiomac.2025.141786] [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: 12/08/2024] [Revised: 02/11/2025] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
Helicobacter pylori (H. pylori) infection affects nearly half of the global population, with biofilm formation and immune evasion contributing to chronic and recurrent infections, posing significant public health challenges. The robust immune evasion mechanisms and gene mutations of H. pylori not only result in a progressive decrease in clinical treatment efficacy but also increase bacterial resistance. Furthermore, antibiotic regimens have been shown to disrupt the diversity and richness of the gut microbiota. Given the challenges of eradicating H. pylori and adverse effects of antibiotics on host microbiota, this study introduces an antibiotic-free alternative strategy: fucoidan-modified kaempferol-loaded glycyrrhizic acid lipid nanovesicles (Fu-GaLip@KP). Kaempferol, supported by the nanovesicles, penetrates the mucus barrier, disperses biofilms, and eradicates bacteria. Additionally, glycyrrhetinic acid, a critical stabilizer for nanovesicles, restores lysosomal acidification and enhances the host's ability to eliminate intracellular bacteria. Notably, nanovesicles also reduce oxidative free radicals and inflammatory factor secretion, exhibiting superior efficacy in repairing gastric mucosal damage and mitigating inflammation. In vivo studies have demonstrated that Fu-GaLip@KP achieves anti-H. pylori efficacy comparable to triple therapy, while simultaneously restoring gut microbiota diversity and preventing dysbiosis. In summary, the antibiotic-free approach of Fu-GaLip@KP offers a comprehensive strategy for addressing H. pylori infection and related diseases.
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Affiliation(s)
- Shuqi Zhang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Shijie Ma
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Suqi Hao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Jieyi Pan
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Yuanyuan Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Gang Yuan
- Department of Geriatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Pengyu Li
- Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China.
| | - Haiyan Hu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Shihui Yu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
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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] [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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Wu S, Luo Y, Wei F, Li Y, Fan J, Chen Y, Zhang W, Li X, Xu Y, Chen Z, Xia C, Hu M, Li P, Gu Q. Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation. Food Funct 2025; 16:3101-3119. [PMID: 40152095 DOI: 10.1039/d4fo06308b] [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: 03/29/2025]
Abstract
Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.
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Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yuenuo Luo
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yanan Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, China
| | - Jiayi Fan
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Wenjie Zhang
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Xuelong Li
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Yang Xu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Mingyang Hu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
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Asadi S, Rostamizadeh K, Bahrami H, Amanlou M, Salehabadi H. Enhanced urease inhibitory activity of quercetin via conjugation with silver nanoparticles: synthesis, characterization, and DFT study. Sci Rep 2025; 15:11892. [PMID: 40195446 PMCID: PMC11976935 DOI: 10.1038/s41598-025-96684-2] [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: 02/12/2025] [Accepted: 03/31/2025] [Indexed: 04/09/2025] Open
Abstract
Urease plays a crucial role in the survival and colonization of Helicobacter pylori (H. pylori). Consequently, urease inhibitors are important in managing various diseases associated with H. pylori infection. Given the widespread use of silver nanoparticles (AgNPs) as antibacterial agents and quercetin's known urease inhibitory properties, we sought to develop a potent urease inhibitor by conjugating quercetin onto AgNPs. In fact, this study aimed to enhance the urease inhibitory activity of quercetin through its conjugation with AgNPs. Quercetin-loaded silver nanoparticles (Ag@QNPs) were successfully synthesized using the Frens method and characterized using various techniques, including UV-Vis spectroscopy, FT-IR spectroscopy, XRD analysis, DLS, and TEM. The urease inhibitory activity of Ag@QNPs was significantly higher (approximately 250 times) than that of pure quercetin, demonstrating a synergistic effect. In contrast, AgNPs alone exhibited minimal inhibitory activity against urease. Density functional theory (DFT) calculations revealed a favorable interaction energy between quercetin and the silver surface. These findings suggest the potential of Ag@QNPs as promising nanomaterials for applications in urease-related diseases.
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Affiliation(s)
- Shayan Asadi
- Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
- Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Kobra Rostamizadeh
- Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hamed Bahrami
- Department of Chemistry, University of Zanjan, Zanjan, Iran
| | - Massoud Amanlou
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Hafezeh Salehabadi
- Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
- Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
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Lin M, Wang J, Yao X. Association between decreased p53 expression, elevated serum CagA levels, and oral squamous cell carcinoma. Clinics (Sao Paulo) 2025; 80:100632. [PMID: 40179525 PMCID: PMC11999629 DOI: 10.1016/j.clinsp.2025.100632] [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: 05/08/2024] [Revised: 02/18/2025] [Accepted: 03/23/2025] [Indexed: 04/05/2025] Open
Abstract
OBJECTIVE p53 is a key tumor suppressor, aCnd loss of p53 function promotes the progression of many cancers. Helicobacter Pylori (HP) is mainly involved in the progression of gastric carcinoma, but its role in Oral Squamous Cell Carcinoma (OSCC) is controversial. The primary objectives of this study were to investigate the expression levels of p53 in OSCC tissues and to examine the serum levels of CagA in OSCC patients. Additionally, the authors aimed to explore the potential association between p53 expression and CagA levels in OSCC. METHOD A total of 65 patients diagnosed with OSCC and 42 healthy volunteers were recruited in this study. The clinical pathological parameters of all patients were collected. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of p53 in tissues. Receiver Operating Characteristics Curve (ROC) analysis was used to assess the sensitivity of p53 for the diagnosis of OSCC. The concentration of Cytotoxin-Associated gene A (CagA) in serum was assessed by enzyme-linked immuno sorbent assay. RESULTS The results indicated that the p53 expression in oral mucosal tissues was downregulated while the concentration of CagA in serum was increased in OSCC patients. Besides, p53 expression was correlated with tumor stage. OSCC patients showed a higher HP positive rate than in healthy people. CONCLUSIONS In conclusion, this study demonstrated that decreased p53 expression and elevated serum CagA levels might be correlated with OSCC progression and diagnosis.
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Affiliation(s)
- Minxiao Lin
- Department of Stomatology, the Second Affiliated Hospital of Shantou University Medical College, Guangdong, PR China
| | - Jing Wang
- Department of Otolaryngology, the Second Affiliated Hospital of Shantou University Medical College, Guangdong, PR China
| | - Xiaowu Yao
- Department of Stomatology, the Second Affiliated Hospital of Shantou University Medical College, Guangdong, PR China.
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8
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Qin C, Xu C, Zhu Z, Song X, Wang X, Xu W, Zhu M. A study of the association between Helicobacter pylori infection type and pancreatic cancer risk: A systematic review and meta‑analysis. Oncol Lett 2025; 29:174. [PMID: 39975953 PMCID: PMC11837465 DOI: 10.3892/ol.2025.14920] [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: 09/15/2024] [Accepted: 01/16/2025] [Indexed: 02/21/2025] Open
Abstract
Pancreatic cancer is a highly invasive malignant tumor with a complex pathogenesis that makes early diagnosis challenging. The potential association between Helicobacter pylori infection and pancreatic cancer risk has been noted; however, the available results are still highly divergent. The aim of the present study was to systematically evaluate the association between different types of H. pylori infection and pancreatic cancer risk as well as to explore the possible causes. A systematic search was conducted using the PubMed, Embase and Cochrane Library databases up to August 2023. The literature quality was evaluated using the Newcastle-Ottawa Scale. All studies that met the criteria were included in the overall meta-analysis to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, subgroup analyses were performed based on factors such as diagnostic criteria for H. pylori infection, study region, type of study design and CagA status. The effect of publication bias on the quantitative synthesis results was assessed using the trim-and-fill analysis, and sensitivity analyses were used to verify the robustness of the quantitative synthesis results. A total of 17 studies involving 67,910 participants, including 64,372 controls and 3,538 patients with pancreatic cancer, were included in the present study. The overall analysis showed that no significant association was observed between H. pylori infection and pancreatic cancer risk (OR, 1.15; 95% CI, 0.93-1.41). Further subgroup analyses, which did not consider the effects of study quality, diagnostic criteria, geographical distribution and the type of study design, did not produce new findings that contradicted the results of the overall analysis. CagA+ H. pylori infection did not significantly affect the risk of pancreatic cancer (OR, 0.95; 95% CI, 0.78-1.16), whereas CagA- H. pylori infection may be a possible risk factor for pancreatic cancer (OR, 1.24; 95% CI, 1.004-1.541). The H. pylori infection did not significantly increase the risk of pancreatic cancer. However, it is noteworthy that CagA- H. pylori infection could be a potential factor that elevated the risk of pancreatic cancer.
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Affiliation(s)
- Chao Qin
- Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui 238000, P.R. China
| | - Chonghe Xu
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
| | - Zhongqi Zhu
- Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui 238000, P.R. China
| | - Xixi Song
- Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui 238000, P.R. China
| | - Xin Wang
- Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui 238000, P.R. China
| | - Wei Xu
- Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
| | - Mei Zhu
- Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui 238000, P.R. China
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9
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Keikha M. Comments on 'Genotypic diversity of the Helicobacter pylori vacA c region and its correlation with gastric disease outcomes'. J Med Microbiol 2025; 74:002002. [PMID: 40193187 PMCID: PMC11975057 DOI: 10.1099/jmm.0.002002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Accepted: 03/17/2025] [Indexed: 04/10/2025] Open
Affiliation(s)
- Masoud Keikha
- Tropical and Communicable Diseases Research Center, Iranshahr University of Medical Sciences, Iranshahr, Iran
- Department of Medical Microbiology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
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10
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Feng W, Liu Q, Zhou S, Chen M, Xiao Y. Helicobacter pylori and Atrial Fibrillation: Insights into Their Inter-Relationship. Rev Cardiovasc Med 2025; 26:26911. [PMID: 40351687 PMCID: PMC12059773 DOI: 10.31083/rcm26911] [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: 10/11/2024] [Revised: 11/29/2024] [Accepted: 12/06/2024] [Indexed: 05/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection and atrial fibrillation (AF) are prevalent global health concerns that significantly impact societal and economic well-being. This study explored the potential associations between H. pylori infection and the incidence and progression of AF. Emerging research suggests that H. pylori may influence AF through various pathways, including systemic inflammation, metabolic disturbances, immune responses, and changes in the gut microbiota. These pathways provide a novel perspective on the etiology of AF, suggesting that chronic H. pylori infection could exacerbate or even initiate the arrhythmic events typical of AF. Current evidence, while preliminary, points to significant correlations, particularly through changes in markers such as C-reactive protein (CRP) and lipid metabolism, which are heightened in individuals with active H. pylori infection. However, the exact mechanisms and causal nature of this relationship remain elusive, with studies showing conflicting results. This inconsistency underscores the need for more comprehensive and rigorously designed clinical and experimental research to elucidate fully the interactions between H. pylori infection and AF. Understanding these connections is crucial for developing innovative treatments and management strategies targeting microbial influences in AF patients. Future research should focus on defining the role of H. pylori eradication in the clinical management of AF assessing its impact on disease progression and patient outcomes.
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Affiliation(s)
- Weiting Feng
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, 410011 Changsha, Hunan, China
- Department of Cardiovascular Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120 Guangzhou, Guangdong, China
| | - Qiming Liu
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, 410011 Changsha, Hunan, China
| | - Shenghua Zhou
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, 410011 Changsha, Hunan, China
| | - Mingxian Chen
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, 410011 Changsha, Hunan, China
| | - Yichao Xiao
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, 410011 Changsha, Hunan, China
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11
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Shen J, Zhou M, Xiao N, Tan Z, Liang X. Unveiling the Mystery of the Stimulatory Effects of Arecoline: Its Relevance to the Regulation of Neurotransmitters and the Microecosystem in Multi-Ecological Intestinal Sites. Int J Mol Sci 2025; 26:3150. [PMID: 40243919 PMCID: PMC11989758 DOI: 10.3390/ijms26073150] [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: 02/26/2025] [Revised: 03/17/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
The dried ripe seeds and pericarp of Areca catechu L., a palm species, possess significant economic value. Masticating betel nut is also a long-standing and widely prevalent lifestyle habit rooted in history, known for its stimulating effect. This effect stems primarily from arecoline, the principal active compound in betel nut. This study investigates the potential mechanisms underlying the stimulating effects of arecoline, focusing on neurotransmitters, neurotrophic factors, and the microecosystem in multi-ecological intestinal sites. After arecoline intervention in mice, significant changes were observed in locomotor activity. The levels of dopamine (DA) in liver tissue and 5-hydroxytryptamine (5-HT) in brain tissue were significantly reduced. There was a significant increase in microbial activity in the feces and in the level of n-valeric acid in the intestinal content. At the genus level, the relative abundance of Clostridium was significantly reduced, whereas the relative abundances of Helicobacter and Aquincola were markedly increased. Helicobacter, Aquincola, Faecalibaculum, and Liquorilactobacillus were signature genera in the arecoline-treated group. The 5-HT level was significantly negatively correlated with the abundance of the signature genera Aquincola, Helicobacter, and Liquorilactobacillus in the arecoline group. The ingestion of arecoline can alter the behavioral patterns of mice, causing significant changes in the 5-HT levels in brain tissue and exerting regulatory effects on the microecosystem in multi-ecological intestinal sites. These findings will provide a reference for the future development and utilization of betel nut.
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Affiliation(s)
- Junxi Shen
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China; (J.S.); (M.Z.)
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;
| | - Mengsi Zhou
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China; (J.S.); (M.Z.)
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;
| | - Nenqun Xiao
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;
| | - Zhoujin Tan
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China; (J.S.); (M.Z.)
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;
| | - Xuejuan Liang
- Institute of Innovative Traditional Chinese Medications, Hunan Academy of Chinese Medicine, Changsha 410013, China
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12
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Yu Z, Chen J, Chen M, Pan Q, Shao Y, Jin X, Wang C, Zhang Y, Lin G, Feng P, Teng X. Analysis between Helicobacter pylori infection and hepatobiliary diseases. Front Cell Infect Microbiol 2025; 15:1477699. [PMID: 40125519 PMCID: PMC11926543 DOI: 10.3389/fcimb.2025.1477699] [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: 08/08/2024] [Accepted: 02/06/2025] [Indexed: 03/25/2025] Open
Abstract
Objective Helicobacter pylori (H. pylori) represents a significant chronic health concern, affecting approximately half of the global population. While H. pylori infection has been closely linked to numerous extradigestive diseases, the relationship between H. pylori and lesions in the gallbladder and biliary tract remains under debate. Method We retrospectively collected data from patients who underwent H. pylori tests at the Physical Examination Center of Taizhou Central Hospital (Taizhou University Hospital) between 2018 and 2022. Logistic regression analysis and restricted cubic spline analysis were employed to investigate the correlation between parameters and H. pylori. Additionally, we utilized population data from the National Health and Nutrition Examination Survey (NHANES) database as an external validation cohort. Results A total of 30,612 patients were included in the training set, with 22,296 (72.8%) belonging to the H. pylori non-infection group and 8,316 (27.2%) to the H. pylori infection group. Compared to the non-infection group, patients in the infection group exhibited a significant decrease in albumin levels and a notable increase in total cholesterol and erythrocyte sedimentation rate levels. Furthermore, the infection group demonstrated significantly higher occurrences of gallbladder cholesterol crystals (6.0%), gallbladder polyps (20.2%), and atherosclerosis (25.6%) compared to the non-infection group, with respective rates of 5.1%, 19.1%, and 21.4% (average p < 0.05). However, no significant differences were observed between the two groups in terms of fatty liver, intrahepatic inflammation, gallstones, or cholecystitis. Additional regression analysis revealed that H. pylori, age, BMI, albumin, and total cholesterol were independent risk factors for the cholesterol crystals and atherosclerosis. Conclusion H. pylori infection is closely associated with the gallbladder cholesterol crystals and atherosclerosis, albeit not with conditions such as fatty liver, gallbladder stones, or cholecystitis. Future research necessitates multi-center, prospective studies to corroborate these findings.
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Affiliation(s)
- Zhenjun Yu
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Jie Chen
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Mengdie Chen
- Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Qiaoling Pan
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Yaojian Shao
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Xiaolong Jin
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Chaohui Wang
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Yuetao Zhang
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Gang Lin
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Ping Feng
- Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Xiaosheng Teng
- Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- Department of Endoscopy Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
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13
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Chen Y, Pan M, Yan K, Chen L, Li Z, Yu G, Zhang Q, Dai X. Efficacy and eradication effect of vonoprazan and high-dose amoxicillin dual therapy in CagA +VacA + Helicobacter pylori infected patients. Curr Med Res Opin 2025; 41:535-542. [PMID: 40181762 DOI: 10.1080/03007995.2025.2479791] [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: 06/10/2024] [Revised: 01/23/2025] [Accepted: 03/10/2025] [Indexed: 04/05/2025]
Abstract
OBJECTIVE Helicobacter pylori (HP) eradication rates are higher by treated with the potassium-competitive acid blocker vonorasan than with proton pump inhibitors (PPIs). Herein, this study analyzed the clinical efficacy of vonoprazan combined with high-dose amoxicillin for dual therapy in personalized eradication of HP. METHODS This retrospective analysis included 452 patients with type I HP who were assigned to the observation and control groups. Cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies were detected using the H. pylori antibody typing classification assay kit by Western blot. The control group underwent PPI quadruple therapy (oral administration of esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth subcitrate). The observation group was treated with vonoprazan combined with high-dose amoxicillin orally. The clinical efficacy was evaluated after 14 days of treatment, and adverse reactions during treatment were compared. The eradication rates for different HP types in the two groups were detected using a 13C-urea breath test. RESULTS There was no significant difference between the control and observation groups in sex, age, BMI, disease duration, smoking history, or drinking history. The observation group exhibited higher total effective rates and better eradication effects than the control group. The CagA+, VacA+, or CagA+VacA+ type patients showed no statistical difference in the incidence of adverse reactions, but the observation group showed a lower total incidence of adverse reactions than the control group. CONCLUSION Vonoprazan combined with high-dose amoxicillin has better clinical efficacy and eradication effect for patients with CagA+VacA+ HP, along with reduced adverse reactions.
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Affiliation(s)
- Yongkang Chen
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Manli Pan
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Kunfeng Yan
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Lei Chen
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Zhenxing Li
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Gongchao Yu
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Qingyu Zhang
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
| | - Xiaorong Dai
- Department of Gastroenterology, Taixing People's Hospital, The Affiliated Hospital of Bengbu Medical University, Taizhou, China
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14
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Unakal C, Blake LW, Farfan G, Justiz-Vaillant A, Pandit BR, Akpaka PE. Helicobacter pylori vacA genes associated with gastric diseases in Trinidad and Tobago. IJID REGIONS 2025; 14:100498. [PMID: 39717866 PMCID: PMC11664410 DOI: 10.1016/j.ijregi.2024.100498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/18/2024] [Accepted: 11/19/2024] [Indexed: 12/25/2024]
Abstract
Objectives To delineate and understand the genetic variations among Helicobacter pylori strains from Trinidad and Tobago associated with gastric diseases. Methods One hundred (n = 100) patients who routinely presented with clinical features suggestive of peptic disease were enrolled in the study and underwent gastroscopy procedures. Biopsy specimens were analyzed using serological and molecular methods. Amplification of the variable vacuolating cytotoxin gene A (vacA), urease C (ureC), and 16S ribosomal RNA regions was performed by polymerase chain reaction; and then followed by sequencing and alignment. Phylogenetic analysis and DNA fragment alignment were carried out using DNA MEGA 7 version 7. Results Overall, 70 of the patients tested positive for H. pylori infection using an enzyme immune assay. All were 16S ribosomal RNA positive, with 8.6% (6/70) testing positive for S1 and 91.4% (64/70) for S2. The most prevalent vacA allelic combination was S2M1, with 87.1% (61/70) cases. All S1M1 strains were ureC-positive, while S1M2 strains were ureC-negative. Conclusions H. pylori strain variations are seen in the Trinidad and Tobago isolates and are most closely related to the ones from the USA, India, and Indonesia. However, the factors contributing to the emergence of S2/M1 being more prevalent will need to be further investigated.
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Affiliation(s)
- Chandrashekhar Unakal
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Lemar Wayne Blake
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Gerard Farfan
- The Endoscopy Centre, Woodbrook, Port of Spain, Trinidad and Tobago
| | - Angel Justiz-Vaillant
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Bijay Raj Pandit
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
| | - Patrick Eberechi Akpaka
- Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago
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15
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Sandu R, Singh J. A comprehensive review on calcitonin gene-related peptide in the management of gastrointestinal disorders. Inflammopharmacology 2025; 33:1043-1059. [PMID: 39934537 DOI: 10.1007/s10787-025-01657-6] [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: 12/06/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
The prevalence of gastrointestinal disorders caused by alcohol, Helicobacter pylori, non-steroidal anti-inflammatory drugs, chronic stress and sedentary lifestyle is on the rise. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has emerged as a protective factor against various gastrointestinal issues. Despite its known benefits, the dual role of CGRP in gastrointestinal damage remains unclear. Discovered 30 years ago through alternative RNA processing of the calcitonin gene, CGRP is known to be a potent vasodilator involved in crucial defensive mechanisms for both physiological and pathological conditions. Promising evidences from preclinical research have attracted the interest of scientists for the exploration of CGRP as a therapeutic neuropeptide. Numerous evidences suggest that this neuropeptide is secreted by the neurons under the influence of endogenous as well as exogenous stimuli. CGRP repairs the gastric mucosal barrier and maintain mucosal integrity by suppressing NF-κB activation, thereby reducing tumour necrosis factor-alpha expression. In addition, recent studies suggest that CGRP modulates immune responses and enhances epithelial cell proliferation, further contributing to its cytoprotective effects. Consequently, CGRP and the CGRP secretagogues represent promising novel targets for clinical applications. This review aims to elucidate the role of CGRP and CGRP secretagogues in the management of gastrointestinal disorders, highlighting its potential as a therapeutic agent in the context of evidence-based modern gastroenterology.
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Affiliation(s)
- Rajesh Sandu
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India
| | - Jagtar Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India.
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16
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Yi M, Chen S, Yi X, Zhang F, Zhou X, Zeng M, Song H. Helicobacter pylori infection process: from the molecular world to clinical treatment. Front Microbiol 2025; 16:1541140. [PMID: 40083792 PMCID: PMC11903457 DOI: 10.3389/fmicb.2025.1541140] [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: 12/07/2024] [Accepted: 02/10/2025] [Indexed: 03/16/2025] Open
Abstract
Helicobacter pylori is a gram-negative microaerophilic microorganism intricately associated with chronic gastrointestinal disorders and gastric cancer. H. pylori can cause various upper digestive tract diseases, including chronic gastritis, peptic ulcer, gastroesophageal reflux disease, and gastric cancer. The bacterium exhibits a variety of pathogenic mechanisms, including colonization, the expression of virulence factors, and the development of drug resistance. This article presents a comprehensive review of H. pylori pathogenesis, emphasizing recent research advancements concerning the cytotoxin-associated gene A, vacuolating cytotoxin, outer membrane proteins, and other virulence factors. Additionally, it examines the molecular mechanisms underlying drug resistance and evaluates the efficacy of conventional therapeutic approaches. Recently, researchers have attempted novel therapeutic regimens, including probiotics and Chinese medicine-assisted therapies, to enhance therapeutic effects. This article aimed to offer an overview of the academic community's comprehension of H. pylori infection and to highlight the current treatment options.
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Affiliation(s)
- Meijing Yi
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Silan Chen
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Xinying Yi
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Fan Zhang
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Xuan Zhou
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
| | - Meiyan Zeng
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Houpan Song
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, China
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17
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Lu Q, Wang J, Tang Y, Li W, Li C. Phytochemical analysis of dried ginger extract and its inhibitory effect and mechanism on Helicobacter pylori and associated ureases. Food Funct 2025; 16:1100-1115. [PMID: 39831446 DOI: 10.1039/d4fo04991h] [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: 01/22/2025]
Abstract
Helicobacter pylori (H. pylori), one of the most common infectious pathogens in the world, can cause gastritis, digestive ulcers, and even gastric cancer. H. pylori urease (HPU) is a distinctive virulence factor of H. pylori that allows it to be distinguished from other pathogens. Dried ginger is a famous edible and medicinal herb that is commonly used to prevent and treat gastrointestinal tract-related diseases. In this study, phytochemical analysis of the aqueous extract of dried ginger (DGE) and the inhibition of DGE on H. pylori was investigated. Subsequently, we evaluated the inhibitory activity of DGE against enzymes including HPU and jack bean urease (JBU) and determined its potential mechanism of action. UPLC-ESI-MS/MS analysis indicated that a total of 63 compounds including seven glycosides, nine terpenoids, two esters, seven phenols, eight lignans, five phenylpropanoids, and four phenolic acids were identified in DGE. DGE was observed to inhibit the growth of four H. pylori strains (ATCC 43504, NCTC 26695, SS1, and ICDC 111001) with minimum inhibitory concentration (MIC) values spanning the range of 0.05 to 1.50 mg mL-1. Moreover, DGE has higher enzyme inhibitory activity on HPU (IC50 = 0.49 ± 0.01 mg mL-1) than on JBU (IC50 = 0.54 ± 0.01 mg mL-1). Enzyme inhibitory kinetic analysis revealed that the inhibition type of DGE against HPU was slow-binding and anti-competitive, whereas it was slow-binding and mixed type on JBU. A further mechanism study indicated that the protective effect of sulfhydryl-containing compounds on enzyme activity was significantly better than that of inorganic compounds, indicating that the action site of DGE inhibition of enzyme was the sulfhydryl residue. The results of DTT reactivation experiments showed that the DGE-urease complex was reversible. Furthermore, molecular docking investigation showed that the main components of DGE interacted with sulfhydryl groups and Ni2+. In conclusion, DGE effectively inhibited the growth of H. pylori and the activity of its key virulence factor urease. And the in-depth study of the kinetic characteristics and the mechanism of action showed that the active site sulfhydryl group and Ni2+ might be the targets of urease inhibition by DGE. Our study may provide experimental evidence for the traditional application of dried ginger in the treatment of H. pylori-associated gastric diseases.
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Affiliation(s)
- Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Jiahao Wang
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
| | - Ying Tang
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
| | - Wenna Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
| | - Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
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18
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Gou GE, Li T, Liu CR, Meng T, Li YP. Potential mechanisms and therapeutic prospects of the association between Helicobacter pylori infection and metabolic dysfunction-associated steatohepatitis. World J Hepatol 2025; 17:101798. [PMID: 39871896 PMCID: PMC11736473 DOI: 10.4254/wjh.v17.i1.101798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/13/2024] [Accepted: 11/22/2024] [Indexed: 01/06/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection is a known inducer of various gastrointestinal diseases, including gastritis, gastric ulcers, and gastric cancer. However, in recent years, research on the potential association between H. pylori infection and metabolic dysfunction-associated steatohepatitis (MASH) has been scarce. This large-scale multicenter study, covering more than 360 hospitals across 26 medical systems in the United States, systematically evaluated the association between H. pylori infection and MASH. This paper reviews the innovative aspects of this study, discusses its significance in the current research field of H. pylori and liver diseases, analyzes potential molecular mechanisms, and suggests future research directions and therapeutic prospects.
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Affiliation(s)
- Guo-E Gou
- Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710004, Shaanxi Province, China
| | - Ting Li
- Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710004, Shaanxi Province, China
| | - Chen-Rui Liu
- Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710004, Shaanxi Province, China
| | - Ting Meng
- Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710004, Shaanxi Province, China.
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19
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Amaral R, Concha T, Vítor J, Almeida AJ, Calado C, Gonçalves LM. Chitosan Nanoparticles for Enhanced Immune Response and Delivery of Multi-Epitope Helicobacter pylori Vaccines in a BALB/c Mouse Model. Pharmaceutics 2025; 17:132. [PMID: 39861778 PMCID: PMC11768296 DOI: 10.3390/pharmaceutics17010132] [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: 12/20/2024] [Revised: 01/13/2025] [Accepted: 01/16/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Helicobacter pylori is the leading cause of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosal-associated lymphoma. Due to the emerging problems with antibiotic treatment against H. pylori in clinical practice, H. pylori vaccination has gained more interest. Oral immunization is considered a promising approach for preventing initial colonization of this bacterium in the gastrointestinal tract, establishing a first line of defense at gastric mucosal surfaces. Chitosan nanoparticles can be exploited effectively for oral vaccine delivery due to their stability, simplicity of target accessibility, and beneficial mucoadhesive and immunogenic properties. Methods: In this study, new multi-epitope pDNA- and recombinant protein-based vaccines incorporating multiple H. pylori antigens were produced and encapsulated in chitosan nanoparticles for oral and intramuscular administration. The induced immune response was assessed through the levels of antigen-specific IgGs, secreted mucosal SIgA, and cytokines (IL-2, IL-10, and IFN-γ) in immunized BALB/C mice. Results: Intramuscular administration of both pDNA and recombinant protein-based vaccines efficiently stimulated the production of specific IgG2a and IgG1, which was supported by cytokines levels. Oral immunizations with either pDNA or recombinant protein vaccines revealed high SIgA levels, suggesting effective gastric mucosal immunization, contrasting with intramuscular immunizations, which did not induce SIgA. Conclusions: These findings indicate that both pDNA and recombinant protein vaccines encapsulated into chitosan nanoparticles are promising candidates for eradicating H. pylori and mitigating associated gastric diseases in humans.
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Affiliation(s)
- Rita Amaral
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (R.A.); (T.C.); (J.V.); (A.J.A.)
| | - Tomás Concha
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (R.A.); (T.C.); (J.V.); (A.J.A.)
| | - Jorge Vítor
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (R.A.); (T.C.); (J.V.); (A.J.A.)
| | - António J. Almeida
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (R.A.); (T.C.); (J.V.); (A.J.A.)
| | - Cecília Calado
- ISEL—Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisbon, Portugal;
- iBB—Institute for Bioengineering and Biosciences, i4HB—Associate Laboratory, Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal
| | - Lídia M. Gonçalves
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (R.A.); (T.C.); (J.V.); (A.J.A.)
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Heidary M, Akrami S, Madanipour T, Shakib NH, Mahdizade Ari M, Beig M, Khoshnood S, Ghanavati R, Bazdar M. Effect of Helicobacter pylori-induced gastric cancer on gastrointestinal microbiota: a narrative review. Front Oncol 2025; 14:1495596. [PMID: 39868371 PMCID: PMC11757270 DOI: 10.3389/fonc.2024.1495596] [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: 09/12/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection is a typical microbial agent that interferes with the complex mechanisms of gastric homeostasis by disrupting the balance between the host gastric microbiota and mucosa-related factors, ultimately leading to inflammatory changes, dysbiosis, and gastric cancer (GC). We searched this field on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. Most studies show that H. pylori inhibits the colonization of other bacteria, resulting in a less variety of bacteria in the gastrointestinal (GI) tract. When comparing the patients with H. pylori-positive and H. pylori-negative GC, the composition of the gastric microbiome changes with increasing abundance of H. pylori (where present) in the gastritis stage, whereas, as the gastric carcinogenesis cascade progresses to GC, oral and intestinal-type pathogenic microbial strains predominate. H. pylori infection induces a premalignant milieu of atrophy and intestinal metaplasia, and the resulting change in gastric microbiota appears to play an important role in gastric carcinogenesis. The effect of H. pylori-induced GC on GI microbiota is discussed in this review.
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Affiliation(s)
- Mohsen Heidary
- Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Sousan Akrami
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Tohid Madanipour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nafiseh Hosseinzadeh Shakib
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzie Mahdizade Ari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Beig
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Roya Ghanavati
- School of Medicine, Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | - Monireh Bazdar
- School of Medicine, Razi Hospital, Ilam University of Medical Sciences, Ilam, Iran
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Elbehiry A, Marzouk E, Abalkhail A, Sindi W, Alzahrani Y, Alhifani S, Alshehri T, Anajirih NA, ALMutairi T, Alsaedi A, Alzaben F, Alqrni A, Draz A, Almuzaini AM, Aljarallah SN, Almujaidel A, Abu-Okail A. Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development. Front Med (Lausanne) 2025; 11:1523991. [PMID: 39850097 PMCID: PMC11756510 DOI: 10.3389/fmed.2024.1523991] [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: 11/06/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025] Open
Abstract
One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.
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Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Eman Marzouk
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Wael Sindi
- Department of Population, Public and Environmental Health, General Administration of Health Services, Ministry of Defense, Riyadh, Saudi Arabia
| | - Yasir Alzahrani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Salem Alhifani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Turki Alshehri
- Department of Dental, Alhada Armed Forces Hospital, Taif, Saudi Arabia
| | - Nuha Abdulaziz Anajirih
- Department of Medical Emergency Services, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah, Saudi Arabia
| | - Turki ALMutairi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ahmad Alsaedi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Abdullah Alqrni
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah, Saudi Arabia
| | - Abdelmaged Draz
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Abdulaziz M. Almuzaini
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Sahar N. Aljarallah
- Department of Pharmacy Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia
| | - Abdulrahman Almujaidel
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Akram Abu-Okail
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
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22
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Jung YS, Jung BW, Park CH. Comparative efficacy of Helicobacter pylori eradication therapy between tegoprazan-based concomitant and bismuth quadruple therapies: A real-world evidence. J Gastroenterol Hepatol 2025; 40:159-165. [PMID: 39557599 DOI: 10.1111/jgh.16798] [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: 08/31/2024] [Revised: 10/07/2024] [Accepted: 10/20/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND AND AIM Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies. METHODS We retrospectively analyzed data from patients with H. pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H. pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates. RESULTS Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P = 0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P = 0.424). The overall adverse event rates (49.6% vs 39.2%, P = 0.001) and insufficient medication rates (4.8% vs 2.4%, P = 0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group. CONCLUSIONS The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Wook Jung
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Chung-Ang University H.C.S. Hyundae Hospital, Namyangju, Korea
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23
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Elbehiry A, Abalkhail A, Anajirih N, Alkhamisi F, Aldamegh M, Alramzi A, AlShaqi R, Alotaibi N, Aljuaid A, Alzahrani H, Alzaben F, Rawway M, Ibrahem M, Abdelsalam MH, Rizk NI, Mostafa MEA, Alfaqir MR, Edrees HM, Alqahtani M. Helicobacter pylori: Routes of Infection, Antimicrobial Resistance, and Alternative Therapies as a Means to Develop Infection Control. Diseases 2024; 12:311. [PMID: 39727641 PMCID: PMC11727528 DOI: 10.3390/diseases12120311] [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: 10/14/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 12/28/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the gastric epithelium and is associated with a range of gastrointestinal disorders, exhibiting a global prevalence of approximately 50%. Despite the availability of treatment options, H. pylori frequently reemerges and demonstrates increasing antibiotic resistance, which diminishes the efficacy of conventional therapies. Consequently, it is imperative to explore non-antibiotic treatment alternatives to mitigate the inappropriate use of antibiotics. This review examines H. pylori infection, encompassing transmission pathways, treatment modalities, antibiotic resistance, and eradication strategies. Additionally, it discusses alternative therapeutic approaches such as probiotics, anti-biofilm agents, phytotherapy, phototherapy, phage therapy, lactoferrin therapy, and vaccine development. These strategies aim to reduce antimicrobial resistance and enhance treatment outcomes for H. pylori infections. While alternative therapies can maintain low bacterial levels, they do not achieve complete eradication of H. pylori. These therapies are designed to bolster the immune response, minimize side effects, and provide gastroprotective benefits, rendering them suitable for adjunctive use alongside conventional treatments. Probiotics may serve as adjunctive therapy for H. pylori; however, their effectiveness as a monotherapy is limited. Photodynamic and phage therapies exhibit potential in targeting H. pylori infections, including those caused by drug-resistant strains, without the use of antibiotics. The development of a reliable vaccine is also critical for the eradication of H. pylori. This review identifies candidate antigens such as VacA, CagA, and HspA, along with various vaccine formulations, including vector-based and subunit vaccines. Some vaccines have demonstrated efficacy in clinical trials, while others have shown robust immune protection in preclinical studies. Nevertheless, each of the aforementioned alternative therapies requires thorough preclinical and clinical evaluation to ascertain their efficacy, side effects, cost-effectiveness, and patient compliance.
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Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia
| | - Nuha Anajirih
- Medical Emergency Services Department, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah P.O. Box 1109, Saudi Arabia
| | - Fahad Alkhamisi
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah 23311, Saudi Arabia
| | - Mohammed Aldamegh
- Pathology and Laboratory Medicine Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Abdullah Alramzi
- Medical Radiology Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Riyad AlShaqi
- Biomedical Engineer, Armed Forces Medical Services, Riyadh 12426, Saudi Arabia
| | - Naif Alotaibi
- Medical Hospital Administration Department, Armed Forces Hospital-Jubail, Jubail 31951, Saudi Arabia
| | - Abdullah Aljuaid
- Medical Hospital Administration Department, Armed Forces Hospitals in Al Kharj, AL Kharj 16278, Saudi Arabia
| | - Hilal Alzahrani
- Physical Medicine and Rehabilitation Department, Armed Forces Center for Health Rehabilitation, Taif 21944, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah 23311, Saudi Arabia
| | - Mohammed Rawway
- Biology Department, College of Science, Jouf University, Sakaka 42421, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt
| | - Mai Ibrahem
- Department of Public Health, College of Applied Medical Science, King Khalid University, Abha 61421, Saudi Arabia
| | - Moustafa H. Abdelsalam
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Nermin I. Rizk
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Mohamed E. A. Mostafa
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Moneef Rohail Alfaqir
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Husam M. Edrees
- Department of Physiology, Faculty of Medicine, University of Tabuk, Tabuk 74191, Saudi Arabia
| | - Mubarak Alqahtani
- Department of Radiology, King Fahd Armed Forces Hospital, Jeddah 23311, Saudi Arabia
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Zhai S, Gao Y, Jiang Y, Li Y, Fan Q, Tie S, Wu Y, Gu S. Weizmannia coagulans BC99 affects valeric acid production via regulating gut microbiota to ameliorate inflammation and oxidative stress responses in Helicobacter pylori mice. J Food Sci 2024; 89:9985-10002. [PMID: 39556495 DOI: 10.1111/1750-3841.17514] [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: 08/13/2024] [Revised: 10/11/2024] [Accepted: 10/17/2024] [Indexed: 11/20/2024]
Abstract
Helicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin-10, transforming growth factor-β, and interferon-γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short-chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota.
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Affiliation(s)
- Shirui Zhai
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
| | - Yinyin Gao
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
| | - Yiru Jiang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
| | - Yuwan Li
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
- National Demonstration Center for Experimental Food Processing and Safety Education, Luoyang, China
| | - Qiuxia Fan
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
| | - Shanshan Tie
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
- National Demonstration Center for Experimental Food Processing and Safety Education, Luoyang, China
| | - Ying Wu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
- Henan Engineering Research Center of Food Microbiology, Luoyang, China
| | - Shaobin Gu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China
- Henan Engineering Research Center of Food Microbiology, Luoyang, China
- National Demonstration Center for Experimental Food Processing and Safety Education, Luoyang, China
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25
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Hasanzadeh Haghighi F, Menbari S, Mohammadzadeh R, Pishdadian A, Farsiani H. Developing a potent vaccine against Helicobacter pylori: critical considerations and challenges. Expert Rev Mol Med 2024; 27:e12. [PMID: 39584502 PMCID: PMC11964096 DOI: 10.1017/erm.2024.19] [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: 06/27/2023] [Revised: 01/13/2024] [Accepted: 08/07/2024] [Indexed: 11/26/2024]
Abstract
Helicobacter pylori (H. pylori) is closely associated with gastric cancer and peptic ulcers. The effectiveness of antibiotic treatment against H. pylori is diminished by the emergence of drug-resistant strains, side effects, high cost and reinfections. Given the circumstances, it is imperative to develop a potent vaccination targeting H. pylori. Understanding H. pylori's pathogenicity and the host's immune response is essential to developing a vaccine. Furthermore, vaccine evaluation necessitates the careful selection of design formulation. This review article aims to provide a concise overview of the considerations involved in selecting the optimal antigen, adjuvant, vaccine delivery system and laboratory animal model for vaccine formulation. Furthermore, we will discuss some significant obstacles in the realm of developing a potent vaccination against H. pylori.
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Affiliation(s)
- Faria Hasanzadeh Haghighi
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shaho Menbari
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Laboratory Sciences, Faculty of Paramedical Sciences, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Roghayeh Mohammadzadeh
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abbas Pishdadian
- Department of Immunology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran
| | - Hadi Farsiani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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26
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Jung K, Bae H, Kim JK, Jeong B, Park MI, Lee JY. Comparison of three methods for generating the coccoid form of Helicobacter pylori and proteomic analysis. BMC Microbiol 2024; 24:448. [PMID: 39501162 PMCID: PMC11536543 DOI: 10.1186/s12866-024-03599-5] [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: 05/24/2024] [Accepted: 10/23/2024] [Indexed: 11/09/2024] Open
Abstract
BACKGROUND Helicobacter pylori changes from spiral to coccoid depending on the host state, environmental factors, and surrounding microbial communities. The coccoid form of H. pylori still maintains its complete cellular structure, retains virulence genes, and thus plays a role in pathogenicity. To understand the coccoid form, it is crucial to establish the in vitro generation of the coccoid H. pylori. Although some conditions have been studied for the generation of the coccoid form, few studies have compared these conditions for coccoid generation. Here, we generated coccoid forms via three methods and compared the differences in morphology, viability, culturability, and protein expression. RESULTS The coccoid H. pylori was generated in vitro via three methods: a starvation method, a method using amoxicillin, and a method using the culture supernatant of Streptococcus mitis. The morphology and viability of the cells were examined by fluorescence microscopy after staining with SYTO9 and propidium iodide. The culturability of H. pylori was examined by counting colony-forming units on chocolate agar plates. In the starvation group, no colonies formed after 7 days, but viable coccoids were continuously observed. In the amoxicillin-treated group, the culturability decreased rapidly after 12 h, and showed a viable but non culturable (VBNC) state after the third day. Most cells treated with S. mitis supernatant changed to coccoid forms after 7 days, but colonies were continuously formed, probably due to living spiral forms. We performed proteomics to analyse the differences in protein profiles between the spiral and coccoid forms and protein profiles among the coccoid forms generated by the three methods. CONCLUSION Amoxicillin treatment changed H. pylori to VBNC cells faster than starvation. Treatment with the S. mitis supernatant prolonged the culturability of H. pylori, suggesting that the S. mitis supernatant may contain substances that support spiral form maintenance. Proteomic analysis revealed that the expression of proteins differed between the spiral form and coccoid form of H. pylori, and this variation was observed among the coccoid forms produced via three different methods. The proteins in the coccoid forms produced by the three methods differed from each other, but common proteins were also observed among them.
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Affiliation(s)
- Kyoungwon Jung
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, 49267, Republic of Korea
| | - Haram Bae
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyeun Kate Kim
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Bohyun Jeong
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, 49267, Republic of Korea
| | - Jee Young Lee
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea.
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27
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Jung BW, Park CH, Jung YS. Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence. J Gastroenterol Hepatol 2024; 39:2409-2416. [PMID: 39188111 DOI: 10.1111/jgh.16719] [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: 05/23/2024] [Revised: 07/13/2024] [Accepted: 07/30/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND AND AIM Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication in real-world clinical practice. METHODS We retrospectively analyzed data from patients with H. pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H. pylori eradication rate. The secondary endpoint was adverse events. RESULTS Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P = 0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P = 0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P = 0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P = 0.001). CONCLUSIONS Tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.
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Affiliation(s)
- Byung Wook Jung
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
- Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Chung-Ang University H.C.S. Hyundae Hospital, Namyangju, Republic of Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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28
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Jung BW, Kim YJ, Park CH. Nationwide Trends in Helicobacter pylori Eradication Therapies in Korea: Impact of Guideline Updates on Treatment Practices. Helicobacter 2024; 29:e13152. [PMID: 39538435 DOI: 10.1111/hel.13152] [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: 09/04/2024] [Revised: 10/15/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Helicobacter pylori infects over 50% of the global population, prompting the issuance of guidelines for effective diagnosis and treatment. However, research on guideline dissemination and adherence is limited. Therefore, we assessed the nationwide status of H. pylori eradication therapies in Korea before and after guideline updates. METHODS Using data from the Korean National Health Insurance Service, this retrospective cohort study analyzed changes in H. pylori eradication therapies across three periods: Phase I (2006-2007), Phase II (2014-2015), and Phase III (2021-2022). It examined therapy regimens, confirmation tests, and retreatment rates. RESULTS Among 1,657,746 patients included, the number undergoing eradication therapy increased across the phases (Phase I: 234,365; Phase II: 493,889; Phase III: 929,492). The use of conventional triple therapy declined from 96.1% in Phase I to 88.3% in Phase III, while non-bismuth and bismuth quadruple therapies increased to 6.8% and 3.3%, respectively, in Phase III. The proportion of patients following a 1-week regimen of conventional triple therapy decreased from 90.3% in Phase I to 54.2% in Phase III, while a 2-week regimen increased to 36.1% in Phase III. Confirmation testing within 1 year of therapy increased from 21.3% in Phase I to 43.0% in Phase III, whereas retreatment rates increased from 3.8% in Phase I to 8.8% in Phase III. CONCLUSIONS Guideline updates have influenced H. pylori eradication practices in Korea, leading to increased use of quadruple therapies with longer treatment durations. However, further improvements in confirmatory tests and retreatment following failed initial therapy are required.
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Affiliation(s)
- Byung Wook Jung
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Republic of Korea
- Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yun Jin Kim
- Department of Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea
- Biostatistics Lab, Medical Research Collaborating Center, Hanyang University, Seoul, Republic of Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Chung-Ang University H.C.S. Hyundae Hospital, Namyangju, Republic of Korea
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Abdel-Razeq R, Bitar L, Bitar ER, Onwuzo C, Abu-Hammour MN, Eren B, Mohamed I, Johnson A, Boustany A, Onwuzo S, Asaad I. Prevalence and risk factors associated with metabolic dysfunction-associated steatohepatitis in patients with Helicobacter pylori infection: A population-based study. World J Hepatol 2024; 16:1349-1356. [DOI: 10.4254/wjh.v16.i10.1349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/03/2024] [Accepted: 09/23/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is associated with the development of gastrointestinal disorders ranging from gastritis to gastric cancer. The evidence of the association between metabolic dysfunction-associated steatohepatitis (MASH) and H. pylori infection in the literature is scarce. Therefore, we aim to evaluate the risk of developing MASH in patients who have had a diagnosis of H. pylori infection independently of any confounding variables.
AIM To evaluate the risk of developing MASH in patients who have had a diagnosis of H. pylori infection.
METHODS This study used a validated multicenter research database of over 360 hospitals across 26 healthcare systems across the United States from 1999 to 2022. Multivariate regression analysis assessed the risk of developing MASH, adjusting for confounders including H. pylori infection, obesity, type 2 diabetes, hypertension, dyslipidemia, and male gender. A two-sided P value < 0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008).
RESULTS A total of 79476132 individuals were screened in the database and 69232620 were selected in the final analysis after accounting for inclusion and exclusion criteria. Smokers (14.30%), patients with hyperlipidemia (70.35%), hypertension (73.86%), diabetes mellitus type 2 (56.46%), and obese patients (58.15%) were more common in patients with MASH compared to control. Using a multivariate regression analysis, the risk of MASH was increased in diabetics [odds ratio (OR): 3.55; 95%CI: 3.48-3.62], obese (OR: 5.93; 95%CI: 5.81-6.04), males (OR: 1.49; 95%CI: 1.46-1.52), individuals with hyperlipidemia (OR: 2.43; 95%CI: 2.38-2.49) and H. pylori infection (OR: 2.51; 95%CI: 2.31-2.73).
CONCLUSION This is the largest population-based study in the United States illustrating an increased prevalence and odds of developing MASH in patients with H. pylori infection after adjusting for risk factors.
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Affiliation(s)
- Rashid Abdel-Razeq
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Lynn Bitar
- Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1104 2020, Lebanon
| | - Elio R Bitar
- Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Chidera Onwuzo
- Department of Medicine & Surgery, General Hospital Lagos Island, Lagos Island 101223, Lagos, Nigeria
| | - Mohamad-Noor Abu-Hammour
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Barish Eren
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Islam Mohamed
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Adejoke Johnson
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, Bronx, NY 10461, United States
| | - Antoine Boustany
- Division of Gastroenterology, Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL 32209, United States
| | - Somtochukwu Onwuzo
- Department of Gastroenterology, Allegheny General Hospital, Pittsburgh, PA 15212, United States
| | - Imad Asaad
- Department of Gastroenterology, Firelands Health, Sandusky, OH 44870, United States
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Abdel-Razeq R, Bitar L, Bitar ER, Onwuzo C, Abu-Hammour MN, Eren B, Mohamed I, Johnson A, Boustany A, Onwuzo S, Asaad I. Prevalence and risk factors associated with metabolic dysfunction-associated steatohepatitis in patients with Helicobacter pylori infection: A population-based study. World J Hepatol 2024; 16:1169-1176. [PMID: 39474577 PMCID: PMC11514611 DOI: 10.4254/wjh.v16.i10.1169] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/03/2024] [Accepted: 09/23/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is associated with the development of gastrointestinal disorders ranging from gastritis to gastric cancer. The evidence of the association between metabolic dysfunction-associated steatohepatitis (MASH) and H. pylori infection in the literature is scarce. Therefore, we aim to evaluate the risk of developing MASH in patients who have had a diagnosis of H. pylori infection independently of any confounding variables.
AIM To evaluate the risk of developing MASH in patients who have had a diagnosis of H. pylori infection.
METHODS This study used a validated multicenter research database of over 360 hospitals across 26 healthcare systems across the United States from 1999 to 2022. Multivariate regression analysis assessed the risk of developing MASH, adjusting for confounders including H. pylori infection, obesity, type 2 diabetes, hypertension, dyslipidemia, and male gender. A two-sided P value < 0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008).
RESULTS A total of 79476132 individuals were screened in the database and 69232620 were selected in the final analysis after accounting for inclusion and exclusion criteria. Smokers (14.30%), patients with hyperlipidemia (70.35%), hypertension (73.86%), diabetes mellitus type 2 (56.46%), and obese patients (58.15%) were more common in patients with MASH compared to control. Using a multivariate regression analysis, the risk of MASH was increased in diabetics [odds ratio (OR): 3.55; 95%CI: 3.48-3.62], obese (OR: 5.93; 95%CI: 5.81-6.04), males (OR: 1.49; 95%CI: 1.46-1.52), individuals with hyperlipidemia (OR: 2.43; 95%CI: 2.38-2.49) and H. pylori infection (OR: 2.51; 95%CI: 2.31-2.73).
CONCLUSION This is the largest population-based study in the United States illustrating an increased prevalence and odds of developing MASH in patients with H. pylori infection after adjusting for risk factors.
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Affiliation(s)
- Rashid Abdel-Razeq
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Lynn Bitar
- Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1104 2020, Lebanon
| | - Elio R Bitar
- Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Chidera Onwuzo
- Department of Medicine & Surgery, General Hospital Lagos Island, Lagos Island 101223, Lagos, Nigeria
| | - Mohamad-Noor Abu-Hammour
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Barish Eren
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Islam Mohamed
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Adejoke Johnson
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, Bronx, NY 10461, United States
| | - Antoine Boustany
- Division of Gastroenterology, Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL 32209, United States
| | - Somtochukwu Onwuzo
- Department of Gastroenterology, Allegheny General Hospital, Pittsburgh, PA 15212, United States
| | - Imad Asaad
- Department of Gastroenterology, Firelands Health, Sandusky, OH 44870, United States
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Wang J, Qiao D, Wang Y, Xiong R, Ding X, Zhang W, Wang T, Tang K. Effects of Infection with Different Types of Helicobacter pylori on Gastric Secretion Function: A Cross-Sectional Clinical Study. Int J Gen Med 2024; 17:4539-4549. [PMID: 39398484 PMCID: PMC11471097 DOI: 10.2147/ijgm.s477480] [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: 05/12/2024] [Accepted: 08/30/2024] [Indexed: 10/15/2024] Open
Abstract
Purpose Helicobacter pylori (Hp)-related gastropathies are accompanied by alterations in gastric secretion function, but the effects of infection of different Hp strains on gastric function are not yet well-elucidated. Our cross-sectional clinical study aim to research the effects of infection with different Hp types on gastric function. Patients and Methods We analyzed 525 patients' serum cytotoxin-associated protein gene A (CagA), vacuolating cytotoxin-associated protein gene A (VacA), urease (Ure), Gastrin-17 (G-17), Pepsinogen I (PGI), Pepsinogen II (PGII) and PGI/PGII ratio (PGR). Results The PGII levels (8.19 ± 5.44 vs 5.98 ± 10.75, P = 0.013) were higher in the Hp infected group than in the uninfected, while the PGR levels (16.81 ± 8.22 vs 23.23 ± 8.36, P < 0.001) were lower. The PGR levels were higher in the uninfected group (23.23 ± 8.36, P < 0.001) than in Hp-I (16.47 ± 7.45) and Hp-II infected groups (17.39 ± 8.98). In the uninfected group, the G-17 level was positively correlated with the levels of PGI (Pearson coefficient = 0.177, P = 0.001), PGII (Pearson coefficient = 0.140, P = 0.008) and age (Pearson coefficient = 0.121, P = 0.022), negatively with the PGR levels (Pearson coefficient = -0.201, P < 0.001). In the Hp-I (Pearson coefficient = -0.003, P = 0.975) and Hp-II (Pearson coefficient = 0.018, P = 0.161) infected groups, the G-17 levels were not correlated with age. Conclusion Hp-I with CagA and/or VacA positive and Hp-II without cytotoxicity can reduce gastric secretion function regardless of age and sex. Gastric function in patients with Hp eradication was similar to that in those without Hp infection. G-17 rises physiologically with age, but infection with Hp will affect it.
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Affiliation(s)
- Jinglei Wang
- Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Dehong Qiao
- Minimally Invasive Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Yunzhu Wang
- Endoscopy Center, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Rui Xiong
- Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Xinyi Ding
- Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Wei Zhang
- Endoscopy Center, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Tingting Wang
- Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
| | - Kai Tang
- Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China
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Zhao SQ, Zheng HL, Zhong XT, Wang ZY, Su Y, Shi YY. Effects and mechanisms of Helicobacter pylori infection on the occurrence of extra-gastric tumors. World J Gastroenterol 2024; 30:4090-4103. [DOI: 10.3748/wjg.v30.i37.4090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/23/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024] Open
Abstract
Helicobacter pylori (H. pylori) colonizes the human stomach and many studies have discussed the mechanisms of H. pylori infection leading to gastric diseases, including gastric cancer. Additionally, increasing data have shown that the infection of H. pylori may contribute to the development of extra-gastric diseases and tumors. Inflammation, systemic immune responses, microbiome disorders, and hypergastrinemia caused by H. pylori infection are associated with many extra-gastric malignancies. This review highlights recent discoveries; discusses the relationship between H. pylori and various extra-gastric tumors, such as colorectal cancer, lung cancer, cholangiocarcinoma, and gallbladder carcinoma; and explores the mechanisms of extra-gastric carcinogenesis by H. pylori. Overall, these findings refine our understanding of the pathogenic processes of H. pylori, provide guidance for the clinical treatment and management of H. pylori-related extra-gastric tumors, and help improve prognosis.
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Affiliation(s)
- Shi-Qing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Hui-Ling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xiao-Tian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Zi-Ye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yan-Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
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33
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Peng L, Sun Y, Zhu Z, Li Y. Association of oxidative balance score with Helicobacter pylori infection and mortality among US population. Eur J Nutr 2024; 63:2499-2509. [PMID: 38847866 DOI: 10.1007/s00394-024-03445-4] [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: 01/13/2024] [Accepted: 05/30/2024] [Indexed: 10/20/2024]
Abstract
BACKGROUND Antioxidant and pro-oxidant dietary patterns and lifestyle changes have been considered to play a crucial role in Helicobacter pylori (H. pylori) infection. We conducted this study to investigate the underlying association between oxidative balance score (OBS) and H. pylori infection in the US population. METHODS This was a cross-sectional study according to data from the National Health and Nutrition Examination Survey (1999-2000), and included individuals with complete information about dietary intake and H. pylori serologic testing results. In the present study, we used multivariate logistic regression analysis, smoothed curve fitting, subgroup analyses, and Cox proportional hazards modeling based on demographic and clinical variables to examine the relationship between OBS and H. pylori infection. RESULTS A total of 3413 individuals participated in our analysis with an average age of 32.31 years. The prevalence of H. pylori infection in the study population was 29.77%. By performing smooth curve fitting analysis, we observed an approximately linear relationship between OBS and H. pylori infection, indicating that lower OBS was associated with higher risk of H. pylori infection, especially in over 60 years of age and non-Hispanic white populations. All-cause mortality was also found lower in individuals with higher OBS levels. CONCLUSION In the US population, increased levels of OBS were associated with a reduced risk of H. pylori infection and decreased all-cause mortality. More and further work is still needed to elucidate the precise mechanism of the association between OBS and H. pylori infection.
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Affiliation(s)
- Lei Peng
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yongping Sun
- Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Zhenghui Zhu
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuanyuan Li
- Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.
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Huang Y, Chen Y, Ma L, Guo H, Chen H, Qiu B, Yao M, Huang W, Zhu L. The toxic effects of Helicobacter pylori and benzo(a)pyrene in inducing atrophic gastritis and gut microbiota dysbiosis in Mongolian gerbils. Food Sci Nutr 2024; 12:7568-7580. [PMID: 39479696 PMCID: PMC11521681 DOI: 10.1002/fsn3.4368] [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: 04/09/2024] [Revised: 07/09/2024] [Accepted: 07/15/2024] [Indexed: 11/02/2024] Open
Abstract
Food chemical and microbiological contamination are major global food safety issues. This study investigated the combined effects of the food-borne pathogen Helicobacter pylori (H. pylori) and the pollutant benzo(a)pyrene (Bap) on atrophic gastritis and gut microbiota in Mongolian gerbils. The results demonstrated that simultaneous administration of H. pylori and Bap caused more severe weight loss, DNA damage, and gastritis in Mongolian gerbils compared with those exposed to H. pylori or Bap alone. The combination also significantly increased the serum level of proinflammatory cytokines, including IL-1β (p < .05), IL-6 (p < .0001), and TNF-α (p < .05). Additionally, the H. pylori and Bap combination altered the composition of gut microbiota in Mongolian gerbils: the relative abundance of Lactobacillus and Ligilactobacillus at the genus level (p < .05) was significantly reduced while the relative abundance of Allobaculum and Erysipelotrichaceae enhanced (p < .0001, p < .05). Our study revealed that the synergy of H. pylori and Bap can boost the development of atrophic gastritis and lead to gut microbiota dysbiosis in Mongolian gerbils, which provides essential implications for preventing contaminated foods to sustain life and promote well-being.
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Affiliation(s)
- Yilun Huang
- Alberta Institute, Wenzhou Medical UniversityWenzhouChina
| | - Yunxiang Chen
- Center for Safety Evaluation and ResearchHangzhou Medical CollegeHangzhouChina
| | - Lingfei Ma
- Institute for Health PolicyHangzhou Medical CollegeHangzhouChina
| | - Honggang Guo
- Center of Laboratory AnimalHangzhou Medical CollegeHangzhouChina
| | - Hao Chen
- Center for Safety Evaluation and ResearchHangzhou Medical CollegeHangzhouChina
| | - Bo Qiu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
| | - Mingfei Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
| | - Weixin Huang
- Shaoxing Tongchuang Biotechnology Co., LtdShaoxingChina
| | - Lian Zhu
- School of Basic Medical Sciences and Forensic MedicineHangzhou Medical CollegeHangzhouChina
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Kazantseva EP, Frolov AM, Frolov MA, Novikova EA, Mugulov KS, Kozlova KS, Volchanskiy KI, Maximova SA, Pilipenko MO. The role of Helicobacter pylori in the development of inflammatory eyelid diseases. ACTA BIOMEDICA SCIENTIFICA 2024; 9:108-116. [DOI: 10.29413/abs.2024-9.4.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Background. Blepharitis is one of the most common eye diseases: it accounts for 23.3 % of the total number of patients with inflammatory eye diseases worldwide. 40.2 % of these patients seek outpatient care. The incidence of blepharitis is 1.5–2 times higher in women than in men. The leading factors in the development of blepharitis are both general (gastrointestinal tract diseases, diabetes mellitus, hypertension, systemic use of corticosteroids, etc.) and local (atopic and seborrheic dermatitis or rosacea). The main causative agents of this disease are Staphylococcus spp. (S. aureus, S. epidermidis). As a rule, the disease manifests itself in patients aged 30–50 years, while in women aged 40 to 45 years, 80 % of blepharitis are of staphylococcal origin. Currently, there are reports in the literature about apotential link between Helicobacter pylori infection and the development of chronic blepharitis, but the data are very contradictory.The aim of the study. To analyze the features of the relationship between Helicobacter pylori and inflammatory eyelid diseases.Materials and methods. We conducted a search and analysis of literary sources in the Web of Science, PubMed and Google Scholar databases, as well as in the Russian Science Citation Index database for the period from 2000 to 2022.Conclusion. The review analyzes and summarizes the pathogenic mechanisms of the relationship between chronic blepharitis and Helicobacter pylori. We carried out an analysis of numerous studies, which give grounds to assume a possible role of Helicobacter pylori infection in the development and course of inflammatory eyelid diseases (blepharitis). The main pathogenic aspects in these studies are: chronic inflammation of the eyelids and gastrointestinal tract (antigenic mimicry); excretion of toxic substances from the oral cavity (ammonia, hydrogen nitrite, hydrogen cyanide and other substances causing indirect inflammation of the conjunctiva and eyelid cartilage); the presence of Helicobacter pylori in tears.
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Affiliation(s)
- E. P. Kazantseva
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - A. M. Frolov
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - M. A. Frolov
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - E. A. Novikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. S. Mugulov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. S. Kozlova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. I. Volchanskiy
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. A. Maximova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. O. Pilipenko
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Casado J, Olivan-Muro I, Algarate S, Chueca E, Salillas S, Velázquez-Campoy A, Piazuelo E, Fillat MF, Sancho J, Lanas Á, González A. Novel Drug-like HsrA Inhibitors Exhibit Potent Narrow-Spectrum Antimicrobial Activities against Helicobacter pylori. Int J Mol Sci 2024; 25:10175. [PMID: 39337660 PMCID: PMC11432330 DOI: 10.3390/ijms251810175] [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: 09/03/2024] [Revised: 09/20/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase in multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide. By using a high-throughput screening strategy, in combination with in vitro DNA binding assays and antibacterial activity testing, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against several antibiotic-resistant strains of H. pylori, and minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, an additive effect in combination with metronidazole and clarithromycin as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggests that the in vivo inhibition of HsrA triggers lethal global disturbances in H. pylori physiology including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.
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Affiliation(s)
- Javier Casado
- Group of Translational Research in Digestive Disease, Institute for Health Research Aragón (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Irene Olivan-Muro
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
| | - Sonia Algarate
- Microbiology Service, University Clinic Hospital Lozano Blesa, San Juan Bosco 15, 50009 Zaragoza, Spain
| | - Eduardo Chueca
- Group of Translational Research in Digestive Disease, Institute for Health Research Aragón (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Biomedical Research Networking Centre in Hepatic and Digestive Diseases (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Sandra Salillas
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
| | - Adrián Velázquez-Campoy
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Biomedical Research Networking Centre in Hepatic and Digestive Diseases (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Elena Piazuelo
- Group of Translational Research in Digestive Disease, Institute for Health Research Aragón (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Biomedical Research Networking Centre in Hepatic and Digestive Diseases (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
- Aragón Health Sciences Institute (IACS), San Juan Bosco 13, 50009 Zaragoza, Spain
| | - María F Fillat
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
| | - Javier Sancho
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
| | - Ángel Lanas
- Group of Translational Research in Digestive Disease, Institute for Health Research Aragón (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Biomedical Research Networking Centre in Hepatic and Digestive Diseases (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Digestive Diseases Service, University Clinic Hospital Lozano Blesa, San Juan Bosco 15, 50009 Zaragoza, Spain
| | - Andrés González
- Group of Translational Research in Digestive Disease, Institute for Health Research Aragón (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Biomedical Research Networking Centre in Hepatic and Digestive Diseases (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
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Bezerra TMDO, Xavier KVM, Luz ACDO, Cavalcanti IMF, Brito CAAD, Balbino TCL. Prevalence of cagA, cagM, vacA and oipA genes in isolates of Helicobacter pylori obtained from hospital patients in Northeast Brazil. Braz J Microbiol 2024; 55:2631-2641. [PMID: 38802685 PMCID: PMC11405591 DOI: 10.1007/s42770-024-01380-4] [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: 03/11/2024] [Accepted: 05/13/2024] [Indexed: 05/29/2024] Open
Abstract
Helicobacter pylori is a major cause of gastrointestinal disorders such as chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. It is estimated that around half of the world's population is infected with this pathogen, with underdeveloped countries reporting the highest frequencies. The genes cagA, cagM, vacA, and oipA are some of the most important virulence factors of H. pylori; however, there are no recent studies from Recife-PE demonstrating their frequency, and their relationship with severe gastric modifications. This work aims to use qualitative PCR to detect the virulence genes cagA, cagM, vacA, and oipA in H. pylori isolates obtained from patients in a public hospital in Recife (PE). We collected samples from the stomach's body and antrum of 147 patients, from which 71 (48%) tested positive for H. pylori. Among positive samples, the most frequently infected gender was female (44/71, 62%), and the most frequently infected age group was those above the age of 46 (31/71, 44%). Histological examination of H. pylori-positive samples revealed alterations other than chronic gastritis, including metaplasia and atrophy. The frequency of cagA, cagM, and oipA genes were identified in 84%, 56%, and 69% of the samples tested, respectively, as well as the vacA-s1m1 allelic combination (77%). However, there was no statistically significant variation in the occurrence of these genes, therefore they cannot be considered unique markers of severity in our setting. New research with larger samples and investigations of other genetic markers can aid uncover local risk factors and lead to a better understanding of H. pylori's pathogenesis.
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Affiliation(s)
- Thaynara Millena de Oliveira Bezerra
- Laboratory of Microbiology of Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, Brazil.
| | - Keyla Vitória Marques Xavier
- Laboratory of Microbiology of Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, Brazil
| | - Ana Carolina de Oliveira Luz
- Laboratory of Microbiology of Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, Brazil
- Department of Internal Medicine, Federal University of Pernambuco (UFPE), Recife, PE, Brazil
| | - Isabella Macário Ferro Cavalcanti
- Keizo AsamiInstitute (iLIKA), Federal University of Pernambuco (UFPE), Recife, PE, Brazil
- Laboratory of Microbiology and Immunology, Academic Center of Vitoria (CAV), Federal University of Pernambuco (UFPE), Vitoria de Santo Antao, PE, Brazil
| | - Carlos Alexandre Antunes de Brito
- Keizo AsamiInstitute (iLIKA), Federal University of Pernambuco (UFPE), Recife, PE, Brazil
- Department of Immunology, Autoimune Research Institute, Recife, PE, Brazil
| | - Tereza Cristina Leal- Balbino
- Laboratory of Microbiology of Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, Brazil
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Qian J, Li Z, Wang J, Lin Y, Yu Y. 6-gingerol and its derivatives inhibit Helicobacter pylori-induced gastric mucosal inflammation and improve gastrin and somatostatin secretion. Front Microbiol 2024; 15:1451563. [PMID: 39234535 PMCID: PMC11371576 DOI: 10.3389/fmicb.2024.1451563] [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: 06/19/2024] [Accepted: 07/17/2024] [Indexed: 09/06/2024] Open
Abstract
The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 μg/mL for JF-1, 40 μg/mL for JF-2, 30 μg/mL for JF-3, 40 μg/mL for JF-4, 60 μg/mL for 6-gingerol standard (SS), and 0.03 μg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.
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Affiliation(s)
- Jiali Qian
- The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhennan Li
- The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
- School of Medicine, Shanghai University, Shanghai, China
| | - Jinhui Wang
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yuxian Lin
- The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, China
| | - Yingcong Yu
- The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
- School of Medicine, Shanghai University, Shanghai, China
- The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China
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39
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Huanjie Z, Bukhari I, Fazhan L, Wen H, Wang J, Wanqing W, Yuming F, Youcai T, AlJowaie RM, Aziz IM, Xiufeng C, Yang M, Pengyuan Z. P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer. Heliyon 2024; 10:e35228. [PMID: 39166030 PMCID: PMC11334848 DOI: 10.1016/j.heliyon.2024.e35228] [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: 02/01/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/22/2024] Open
Abstract
TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.
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Affiliation(s)
- Zhao Huanjie
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Ihtisham Bukhari
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Li Fazhan
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Huijuan Wen
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Jingyun Wang
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Wu Wanqing
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Fu Yuming
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Tang Youcai
- Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Reem M. AlJowaie
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Ibrahim M. Aziz
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Chu Xiufeng
- Department of Oncology, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Mi Yang
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
- Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China
- Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China
| | - Zheng Pengyuan
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
- Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China
- Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China
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Chitas R, Fonseca DR, Parreira P, Martins MCL. Targeted nanotherapeutics for the treatment of Helicobacter pylori infection. J Biomed Sci 2024; 31:78. [PMID: 39128983 DOI: 10.1186/s12929-024-01068-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/16/2024] [Indexed: 08/13/2024] Open
Abstract
Helicobacter pylori infection is involved in gastric diseases such as peptic ulcer and adenocarcinoma. Approved antibiotherapies still fail in 10 to 40% of the infected patients and, in this scenario, targeted nanotherapeutics emerged as powerful allies for H. pylori eradication. Nano/microparticles conjugated with H. pylori binding molecules were developed to eliminate H. pylori by either (i) blocking essential mechanisms of infection, such as adhesion to gastric mucosa or (ii) binding and killing H. pylori through the release of drugs within the bacteria or at the site of infection. Glycan antigens (as Lewis B and sialyl-Lewis X), pectins, lectins, phosphatidylethanolamine and epithelial cell membranes were conjugated with nano/microparticles to successfully block H. pylori adhesion. Urea-coated nanoparticles were used to improve drug delivery inside bacteria through H. pylori UreI channel. Moreover, nanoparticles coated with antibodies against H. pylori and loaded with sono/photosensitizers, were promising for their application as targeted sono/photodynamic therapies. Further, non-specific H. pylori nano/microparticles, but only active in the acidic gastric environment, coated with binders to bacterial membrane, extracellular polymeric substances or to high temperature requirement A protease, were evaluated. In this review, an overview of the existing nanotherapeutics targeting H. pylori will be given and their rational, potential to counteract infection, as well as level of development will be presented and discussed.
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Affiliation(s)
- Rute Chitas
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Diana R Fonseca
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- FEUP - Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e de Materiais, Universidade do Porto, Porto, Portugal
| | - Paula Parreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
| | - M Cristina L Martins
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
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Santiago MB, Tanimoto MH, Ambrosio MALV, Veneziani RCS, Bastos JK, Sabino-Silva R, Martins CHG. The Antibacterial Potential of Brazilian Red Propolis against the Formation and Eradication of Biofilm of Helicobacter pylori. Antibiotics (Basel) 2024; 13:719. [PMID: 39200019 PMCID: PMC11350797 DOI: 10.3390/antibiotics13080719] [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] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 09/01/2024] Open
Abstract
Helicobacter pylori is associated with gastrointestinal diseases, and its treatment is challenging due to antibiotic-resistant strains, necessitating alternative therapies. Brazilian red propolis (BRP), known for its diverse bioactive compounds with pharmaceutical properties, was investigated for its anti-H. pylori activity, focusing on biofilm formation inhibition and eradication. BRP was tested against H. pylori (ATCC 43526) using several assays: time-kill, nucleotide leakage, biofilm formation inhibition (determining the minimum inhibitory concentration of biofilm of 50%-MICB50, and cell viability), and biofilm eradication (determining the minimum eradication concentration of biofilm of 99.9%-MBEC). Standardization of H. pylori biofilm formation was also conducted. In the time-kill assay, BRP at 50 µg/mL eliminated all H. pylori cells after 24 h. The nucleotide leakage assay showed no significant differences between control groups and BRP-treated groups at 25 µg/mL and 50 µg/mL. H. pylori formed biofilms in vitro at 109 CFU/mL after 72 h. The MICB50 of BRP was 15.6 µg/mL, and at 500, 1000, and 2000 µg/mL, BRP eradicated all bacterial cells. The MBEC was 2000 µg/mL. These findings suggest that BRP has promising anti-H. pylori activity, effectively inhibiting and eradicating biofilms. Further studies are necessary to elucidate BRP's mechanisms of action against H. pylori.
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Affiliation(s)
- Mariana B. Santiago
- Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38405-320, Brazil;
| | - Matheus H. Tanimoto
- Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, Brazil; (M.H.T.); (J.K.B.)
| | - Maria Anita L. V. Ambrosio
- Nucleus of Research in Sciences and Technology, University of Franca, Franca 14404-600, Brazil; (M.A.L.V.A.); (R.C.S.V.)
| | - Rodrigo Cassio S. Veneziani
- Nucleus of Research in Sciences and Technology, University of Franca, Franca 14404-600, Brazil; (M.A.L.V.A.); (R.C.S.V.)
| | - Jairo K. Bastos
- Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-900, Brazil; (M.H.T.); (J.K.B.)
| | - Robinson Sabino-Silva
- Innovation Center in Salivary Diagnostic and Nanobiotechnology, Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlândia 38408-100, Brazil;
| | - Carlos Henrique G. Martins
- Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38405-320, Brazil;
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Zhu X, Ma C, Sa R, Wang Y, Zhu C, Zhao Y, Luo J, Liu X. CagA 3' region polymorphism of Helicobacter pylori and its association with chronic gastritis in the Chinese population. J Med Microbiol 2024; 73. [PMID: 39171760 DOI: 10.1099/jmm.0.001880] [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: 08/23/2024] Open
Abstract
Introduction. Cytotoxin-associated gene A (CagA) from Helicobacter pylori is highly related to chronic gastritis. Tyrosine phosphorylation of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs from CagA determines the pathogenicity of H. pylori.Gap statement. The precise amino acid variations surrounding the EPIYA motifs and their correlation with clinical outcomes have been poorly explored.Aim. The purpose of this study was to examine the CagA 3' region polymorphism of H. pylori and its association with chronic gastritis in the Chinese population.Method. A total of 86 cagA-positive H. pylori strains were isolated from patients with chronic gastritis in two different hospitals in Beijing, PR China. Genomic DNA was extracted commercial kits, and the cagA 3' variable region of H. pylori was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analysed using the CLC Sequence Viewer, BioEdit, and WebLogo 3.Results. Two hundred and fifty-nine EPIYA motifs were identified from cagA-positive H. pylori strains. Notably, EPIYA-B exhibited a higher frequency of variation in comparison to EPIYA-A, EPIYA-C, and EPIYA-D. The prevalent sequences for East-Asian-type CagA were QVNK and TIDF, while KVNK and TIDD were most commonly observed for Western-type CagA. The CRPIA motifs of East-Asian-type CagA and Western-type CagA varied at positions 4, 6, 7, 8, and 10. CagA-ABD (73.2%) was the most prevalent type, followed by CagA-ABC (18.6%) and CagA-AB (3.4%). The ratio of CagA-ABD was observed to be higher in cases of chronic non-atrophic gastritis with erosive (NAGE) or chronic atrophic gastritis (AG) compared to chronic non-atrophic gastritis (NAG), and the difference was found to be statistically significant (χ2=59.000/64.000, P<0.001).Conclusions. The EPIYA segments of Western-type CagA and East-Asian-type CagA differ significantly and the presence of CagA-ABD may be associated with severe chronic gastritis from this study.
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Affiliation(s)
- Xiaoyan Zhu
- Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China
- Yunnan Province Clinical Research Center for Laboratory Medicine, Kunming, PR China
- Yunnan Key Laboratory of Laboratory Medicine, Kunming, PR China
| | - Chao Ma
- Beijing Institute of Occupational Disease Prevention and Treatment, Beijing, PR China
- Department of Clinical Laboratory, The Beijing Prevention and Treatment Hospital of Occupational Disease for Chemical Industry, Beijing, PR China
| | - Rina Sa
- General internal medicine, Jingdong Medical Area, General Hospital of Chinese PLA, Beijing, PR China
| | - Yaxuan Wang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, PR China
| | - Chaohui Zhu
- Department of Gastroenterology, The Eighth Medical Center of PLA General Hospital, Beijing, PR China
| | - Yajiao Zhao
- Department of Gastroenterology, Emergency General Hospital, Beijing, PR China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China
- Yunnan Institute of Digestive Diseases, Kunming, PR China
| | - Xiaochuan Liu
- Department of Gastroenterology, Emergency General Hospital, Beijing, PR China
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Wang F, Yao Z, Jin T, Mao B, Shao S, Shao C. Research progress on Helicobacter pylori infection related neurological diseases. Ageing Res Rev 2024; 99:102399. [PMID: 38955263 DOI: 10.1016/j.arr.2024.102399] [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: 11/19/2023] [Revised: 06/25/2024] [Accepted: 06/25/2024] [Indexed: 07/04/2024]
Abstract
Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.
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Affiliation(s)
- Fan Wang
- School of Medicine, Jiangsu University, Zhenjiang 212013, China; Yixing Hospital Affiliated to Jiangsu University, Yixing 214200, China
| | - Zhendong Yao
- Yixing Hospital Affiliated to Jiangsu University, Yixing 214200, China
| | - Tao Jin
- Yixing Hospital Affiliated to Jiangsu University, Yixing 214200, China
| | - Boneng Mao
- Yixing Hospital Affiliated to Jiangsu University, Yixing 214200, China.
| | - Shihe Shao
- School of Medicine, Jiangsu University, Zhenjiang 212013, China; Yixing Hospital Affiliated to Jiangsu University, Yixing 214200, China; Affiliated Hospital of Jiangsu University, Zhenjiang 212013, China.
| | - Chen Shao
- Affiliated Hospital of Jiangsu University, Zhenjiang 212013, China.
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Yao M, Cao J, Zhang L, Wang K, Lin H, Qin L, Zhang Q, Qu C, Miao J, Xue C. Indole-3-Lactic Acid Derived from Lacticaseibacillus paracasei Inhibits Helicobacter pylori Infection via Destruction of Bacteria Cells, Protection of Gastric Mucosa Epithelial Cells, and Alleviation of Inflammation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:15725-15739. [PMID: 38973111 DOI: 10.1021/acs.jafc.4c02868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.
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Affiliation(s)
- Mengke Yao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Junhan Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Liping Zhang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Kai Wang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Huan Lin
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Ling Qin
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Qing Zhang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Changfeng Qu
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China
- Marine Natural Products R&D Laboratory, Qingdao Key Laboratory, Qingdao 266061, China
| | - Jinlai Miao
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China
- Marine Natural Products R&D Laboratory, Qingdao Key Laboratory, Qingdao 266061, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
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Fan C, Li Z, Zhai L, Wang H, Zhao X, Xie D, Cai Y, Huang K, Bai Q, Ding H, Cheng J. Clinical evaluation of a real-time PCR assay for diagnosis of Helicobacter pylori infection and antibiotic resistance. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2024; 17:219-226. [PMID: 39114501 PMCID: PMC11301412 DOI: 10.62347/clcl4783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 06/11/2024] [Indexed: 08/10/2024]
Abstract
OBJECTIVES Helicobacter pylori (H. pylori) is a globally prevalent bacterium that increases the risk of developing various gastrointestinal diseases, including gastric adenocarcinoma. This study aimed to evaluate the performances of real-time PCR assay in detecting H. pylori infection, as well as clarithromycin and levofloxacin resistance, in both stool and gastric biopsy specimens. METHODS Stool and gastric biopsy specimens were collected from patients within one to three days post-hospitalization. All patients were analyzed for H. pylori infection and resistance to clarithromycin and levofloxacin using a real-time PCR based molecular assay. RESULTS 169 patients (83 males) with a mean age of 43.6±13.1 years were included in the study. The prevalence of H. pylori was 89.9% (152/169) in stool and 90.5% (153/169) in gastric biopsy samples. The molecular diagnostics employed in this study exhibited a sensitivity of 99.3% and a specificity of 100%, resulting in a diagnostic accuracy rate of 99.6%. Resistance to clarithromycin was 36.1% (61/169) in stool and 44.4% (75/169) in gastric biopsy samples. The molecular tests for clarithromycin resistance demonstrated a sensitivity of 96.8% and a specificity of 86.8%, with an overall diagnostic accuracy of 90.5%. Furthermore, resistance to levofloxacin was 22.5% (38/169) and 26.6% (45/169) in stool and gastric biopsy samples, respectively. The molecular test demonstrated a sensitivity of 80.9% and a specificity of 94.3%, resulting in a diagnostic accuracy of 90.5%. CONCLUSION The implementation of real-time PCR-based screening for H. pylori infection and resistance to clarithromycin and levofloxacin in the stool may enhance the success rate of eradication therapy.
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Affiliation(s)
- Chanjuan Fan
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Zhen Li
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Lili Zhai
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Hui Wang
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Xiaolin Zhao
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Dongling Xie
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Yong Cai
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Kun Huang
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Qixuan Bai
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Haiou Ding
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
| | - Jianping Cheng
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital Beijing 100123, China
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Chen D, Wang S, Yang W, Lu H, Ren Q. Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000. BMC Infect Dis 2024; 24:676. [PMID: 38971751 PMCID: PMC11227695 DOI: 10.1186/s12879-024-09409-7] [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: 09/16/2023] [Accepted: 05/15/2024] [Indexed: 07/08/2024] Open
Abstract
BACKGROUND Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.
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Affiliation(s)
- Danni Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Shiling Wang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Wei Yang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Hong Lu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, 730000, China
- Gansu Province Clinical Research Center for Digestive Diseases, Lanzhou, China
| | - Qian Ren
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China.
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
- Gansu Province Clinical Research Center for Digestive Diseases, Lanzhou, China.
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47
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Trautmann D, Suazo F, Torres K, Simón L. Antitumor Effects of Resveratrol Opposing Mechanisms of Helicobacter pylori in Gastric Cancer. Nutrients 2024; 16:2141. [PMID: 38999888 PMCID: PMC11243391 DOI: 10.3390/nu16132141] [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: 06/18/2024] [Revised: 07/02/2024] [Accepted: 07/02/2024] [Indexed: 07/14/2024] Open
Abstract
Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.
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Affiliation(s)
- Daniela Trautmann
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
| | - Francesca Suazo
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
| | - Keila Torres
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
- Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
| | - Layla Simón
- Nutrition and Dietetic School, Universidad Finis Terrae, Santiago 7501015, Chile
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48
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Liu Z, Li H, Huang X, Liu Q. Animal Models of Helicobacter pylori Infection and Vaccines: Current Status and Future Prospects. Helicobacter 2024; 29:e13119. [PMID: 39108210 DOI: 10.1111/hel.13119] [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: 04/27/2024] [Revised: 07/10/2024] [Accepted: 07/23/2024] [Indexed: 01/02/2025]
Abstract
Helicobacter pylori infection causes chronic gastritis, ulcers, and gastric cancer, making it a threat to human health. Despite the use of antibiotic therapy, the global prevalence of H. pylori infection remains high, necessitating early eradication measures. Immunotherapy, especially vaccine development, is a promising solution in this direction, albeit the selection of an appropriate animal model is critical in efficient vaccine production. Accordingly, we conducted a literature, search and summarized the commonly used H. pylori strains, H. pylori infection-related animal models, and models for evaluating H. pylori vaccines. Based on factors such as the ability to replicate human diseases, strain compatibility, vaccine types, and eliciting of immune responses, we systematically compared the advantages and disadvantages of different animal models, to obtain the informed recommendations. In addition, we have proposed novel perspectives on H. pylori-related animal models to advance research and vaccine evaluation for the prevention and treatment of diseases such as gastric cancer.
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Affiliation(s)
- Zhili Liu
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
- HuanKui Academy, Nanchang University, Nanchang, China
| | - He Li
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaotian Huang
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qiong Liu
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
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Weisy OKM, Kedia RA, Mahmoud I, Abu Odeh RO, Mussa BM, Abusnana S, Soliman SSM, Muhammad JS, Hamad M, Ghemrawi R, Khoder G. Assessment of Helicobacter pylori cytotoxin-associated Gene A (Cag A) protein and its association with ferritin and vitamin B12 deficiencies among adult healthy asymptomatic residents in Sharjah, United Arab Emirates. Heliyon 2024; 10:e32141. [PMID: 38882276 PMCID: PMC11180313 DOI: 10.1016/j.heliyon.2024.e32141] [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: 01/04/2024] [Revised: 05/28/2024] [Accepted: 05/29/2024] [Indexed: 06/18/2024] Open
Abstract
The United Arab Emirates (UAE) serves as an effective epidemiological site for assessing Helicobacter pylori (H. pylori) infection due to its diverse population. However, comprehensive studies on the prevalence of H. pylori in the UAE are notably scarce. In depth prevalence studies are needed as a preventive measure against gastric cancer and other emerging extra gastric diseases associated with H. pylori infection. Aim: This study aimed to assess H. pylori infection and its virulent oncoprotein, the Cytotoxin-Associated Gene (Cag A) and its association with ferritin and vitamin B12 deficiencies. Methods: The study was conducted on 1094 healthy asymptomatic volunteers residents in the Sharjah Emirate, UAE. Enzyme-linked immunosorbent assay (ELISA) was performed to assess H. pylori infection using H. pylori antibodies (IgG), and detection of CagA protein using Cag A antibody (IgG) in the human serum. Ferritin and vitamin B12 serum levels were assessed and correlated to H. pylori infection. Results: This study focuses mainly on the assessment of H. pylori and its virulent factor CagA, in relation to vitamin B12 and ferritin deficiencies. Remarkably, 49.6 % of the participants were detected positive for H. pylori, with over half of these cases involving CagA positive strains. Notably, among Emirati participants, 76.11 % of those with H. pylori infection were CagA positive. Statistical analysis revealed a significant correlation between H. pylori, CagA level, and ferritin/vitamin B12 deficiencies. Conclusion: These findings emphasize the importance of timely detection and eradication of H. pylori not only as a preventive strategy against gastric cancer but also as an effective strategy to rescue the adverse effects from ferritin and vitamin B12 deficiencies, thereby improving the overall health outcomes of individuals affected by H. pylori infection.
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Affiliation(s)
- Om Kolthoom M Weisy
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Reena A Kedia
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
| | - Ibrahim Mahmoud
- Department of Family and Community Medicine and Behavioral Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Raed O Abu Odeh
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Bashair M Mussa
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Salah Abusnana
- Diabetes and Endocrinology Department, University Hospital Sharjah, Sharjah, United Arab Emirates
- Clinical Science Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Sameh S M Soliman
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Jibran Sualeh Muhammad
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohamad Hamad
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of 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
| | - 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, United Arab Emirates
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50
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Morin C, Verma VT, Arya T, Casu B, Jolicoeur E, Ruel R, Marinier A, Sygusch J, Baron C. Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori. Biochem Cell Biol 2024; 102:226-237. [PMID: 38377487 DOI: 10.1139/bcb-2023-0331] [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: 02/22/2024] Open
Abstract
We here describe the structure-based design of small molecule inhibitors of the type IV secretion system of Helicobacter pylori. The secretion system is encoded by the cag pathogenicity island, and we chose Cagα, a hexameric ATPase and member of the family of VirB11-like proteins, as target for inhibitor design. We first solved the crystal structure of Cagα in a complex with the previously identified small molecule inhibitor 1G2. The molecule binds at the interface between two Cagα subunits and mutagenesis of the binding site identified Cagα residues F39 and R73 as critical for 1G2 binding. Based on the inhibitor binding site we synthesized 98 small molecule derivates of 1G2 to improve binding of the inhibitor. We used the production of interleukin-8 of gastric cancer cells during H. pylori infection to screen the potency of inhibitors and we identified five molecules (1G2_1313, 1G2_1338, 1G2_2886, 1G2_2889, and 1G2_2902) that have similar or higher potency than 1G2. Differential scanning fluorimetry suggested that these five molecules bind Cagα, and enzyme assays demonstrated that some are more potent ATPase inhibitors than 1G2. Finally, scanning electron microscopy revealed that 1G2 and its derivatives inhibit the assembly of T4SS-determined extracellular pili suggesting a mechanism for their anti-virulence effect.
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Affiliation(s)
- Claire Morin
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
| | - Vijay Tailor Verma
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
| | - Tarun Arya
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
| | - Bastien Casu
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
| | - Eric Jolicoeur
- Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Québec, Canada
| | - Réjean Ruel
- Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Québec, Canada
| | - Anne Marinier
- Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Québec, Canada
- Department of Chemistry, Faculty of Arts and Sciences, Université de Montréal, Québec, Canada
| | - Jurgen Sygusch
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
| | - Christian Baron
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Québec, Canada
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