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El-Seedi HR, Refaey MS, Abd El-Wahed AA, Albadawy A, Karav S, El-Seedi SH, Cheng G, Salem MF, Liu L, Tang J, Abolibda TZ, Zou X, Guo Z, Khalifa SAM. Bee products in the fight against Helicobacter pylori and molecular interactions. Microb Pathog 2025; 205:107707. [PMID: 40378976 DOI: 10.1016/j.micpath.2025.107707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 04/23/2025] [Accepted: 05/13/2025] [Indexed: 05/19/2025]
Abstract
Gastric or duodenal ulcers can lead to upper gastrointestinal (GI) bleeding. Infection with Helicobacter pylori (H. pylori) is one of the most common infections in the world and can cause both gastric ulcers and gastric cancer. The treatment aims to eradicate H. pylori and treatment with antibiotics has made it possible to cure gastric ulcers. The most common complication of untreated peptic ulcer disease is bleeding (hematemesis, melena, and anemia), while perforation occurs in a smaller proportion of patients. In some individuals, the infection causes mucosal changes with increasing age that lead to atrophy and intestinal metaplasia. It is believed that atrophy and especially intestinal metaplasia are a prerequisite for the most common form of gastric cancer, adenocarcinoma. There is presently a demand for an alternate treatment devoid of the current strategies drawbacks including recurrence, resistance and antibiotic abuse. The current workhighlights the possibility of bee product-based treatments for preventing and eliminating H. pylori infestation. Sci-finder, Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus were used for literature screening. Terms and keywords, i.e. "helicobacter pylori", "epidemiology", "chemotherapy", "honey", "propolis", "bee venom", "bioactive compounds", and "mechanism of action" were used in the search. Bee products are important alternatives that have been utilized for treating many ailments due to their diverse biochemical and biological characteristics. Various mechanisms, such as direct antibacterial, antioxidant, anti-inflammatory, and wound healing capacities, are proposed to explain the potential effect of bee products against H. pylori. The bee product's metabolites have a role in the adherence of H. pylori to stomach epithelial cells. The disruption of bacterial cell membranes and the inhibition of virulence factors are the two mechanisms behind the bee product's promising therapeutic applications against H. pylori.
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Affiliation(s)
- Hesham R El-Seedi
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Mohamed S Refaey
- Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia National University, Km Cairo-Alexandria Agricultural Road, Menoufia, Egypt.
| | - Aida A Abd El-Wahed
- Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, Giza 12627, Egypt.
| | - Aida Albadawy
- Translational Medicine Laboratory, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale, 17000, Turkey.
| | | | - Guiguang Cheng
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Mohamed F Salem
- Department of Environmental Biotechnology, Genetic Engineering and Biotechnology Research Institute, GEBRI, University of Sadat City, Sadat City, P.O. Box:79, Egypt.
| | - Lianliang Liu
- School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang, China.
| | - Jie Tang
- School of Food and Bioengineering, Xihua University, Chengdu, Si Chuan Province, China.
| | - Tariq Z Abolibda
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
| | - Xiaobo Zou
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Zhiming Guo
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China.
| | - Shaden A M Khalifa
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Neurology and Psychiatry Department, Capio Saint Göran's Hospital, Sankt Göransplan 1, 112 19, Stockholm, Sweden.
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Poria R, Lutomia D, Kaushal A, Ramasamy SK, Gupta S. Polyaniline-graphene oxide (PANI/GO)-grafted paper-based nanosensor for the detection of Helicobacterpylori. Anal Biochem 2025; 704:115891. [PMID: 40334770 DOI: 10.1016/j.ab.2025.115891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 05/03/2025] [Accepted: 05/04/2025] [Indexed: 05/09/2025]
Abstract
A polyaniline-graphene oxide (PANI-GO) nanocomposite-grafted DNA biosensor for detecting Helicobacter pylori-specific toxins, oncoprotein cytotoxin-associated gene A (CagA), has been reported. The nanocomposite was fabricated on Screen printed paper electrode (SPPE) and modified with a 5'NH2-labelled single-stranded DNA (ssDNA) probe specific to the CagA gene via an EDC/NHS cross-linker. Under optimized electrochemical experimental conditions, CV and DPV were used to analyse the performance of the developed biosensor. A linear dynamic range for H. pylori ssDNA was established between 0.00001 ng/μl and 0.1 ng/μl, with correlation coefficients of R2 = 0.9813 for the CV and R2 = 0.9343 for the DPV. The sensitivities of the developed sensor in the CV studies were 50.261 μA μL/ng∙mm2 and 66.5 μA μL/ng∙mm2 in the DPV studies. CV demonstrated an LOD of 0.0026 ng/μL, whereas the LOD of the DPV studies was 0.001 ng/μL. The developed sensor was validated using different concentrations of H. pylori ssDNA spiked in human stool samples. The results highlight the potential of the developed biosensor to detect and quantify H. pylori genomic DNA in a sensitive and reliable manner to aid in clinical diagnostics and pathogen detection applications.
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Affiliation(s)
- Rachna Poria
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Desmond Lutomia
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Ankur Kaushal
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Selva Kumar Ramasamy
- Department of Chemistry, M.M Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India
| | - Shagun Gupta
- Department of Bio-Sciences and Technology, M.M. Engineering College, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, (Haryana), 133207, India.
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Hu C, Liu H, Hong B, Wang L, Wu Z, Xie W, Luo B, Cao D, Zhong Y, Liu Y, Gong W. Helicobacter pylori reversing the landscape of neoadjuvant immunotherapy for microsatellite stable gastric cancer: a multicenter cohort study. BMC Med 2025; 23:230. [PMID: 40264112 PMCID: PMC12016324 DOI: 10.1186/s12916-025-04047-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 04/01/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Microsatellite stable (MSS) gastric cancer (GC) is largely unresponsive to immunotherapy, presenting a persistent and formidable challenge in the field. Patients with advanced GC and Helicobacter pylori (H. pylori) infection have shown benefits from immunotherapy. However, it remains unreported whether neoadjuvant immunotherapy is beneficial for H. pylori-positive MSS GC patients. METHODS This retrospective cohort study analyzed data from GC patients treated at three medical centers in China between January 1, 2014, and July 1, 2024. Patients with gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction underwent testing for H. pylori infection prior to receiving neoadjuvant therapy. RESULTS In this retrospective analysis, those positive for H. pylori had a higher objective response rate of 63.77% (95% CI, 51.98-74.11%) compared to 47.73% (95% CI, 39.39-56.19%) in H. pylori-negative patients. Pathological complete remission was higher in H. pylori-positive patients at 17.39% (95% CI, 10.24-27.98%) versus 15.91% (95% CI, 10.65-23.10%). Logistic regression analysis revealed a strong correlation between H. pylori positivity and increased objective remission rate (P = 0.031, OR = 1.928, 95% CI 1.06-3.51). In H. pylori-positive MSS GC patients receiving neoadjuvant immunotherapy pCR rates can reach 27.27% (95% CI, 15.07-44.21%), much higher than the 8.33% (95% CI, 2.87-21.82%) in neoadjuvant chemotherapy patients. Survival analysis showed a 3-year OS rate of 74.2% (95% CI, 56.75-86.30%) in the H. pylori-positive group and 64.3% (95% CI, 51.20-75.55%) in the H. pylori-negative group, and the hazard ratio (HR) of these two groups was 0.50 (95% CI, 0.28-0.87; P <.001). Multivariable analysis for OS further showed the survival benefit of H. pylori, with HRs of 0.51 (95% CI, 0.29-0.91; P = 0.02). CONCLUSIONS H. pylori infection has emerged as a favorable factor for neoadjuvant immunotherapy in MSS GC, underscoring the importance of considering H. pylori status in preoperative treatment strategies.
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Affiliation(s)
- Chengyu Hu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongming Liu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Bo Hong
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Wang
- Department of Emergency Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
| | - Zelai Wu
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Weixun Xie
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Bixian Luo
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Dong Cao
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
- Department of Gastrointestinal Surgery, Affiliated Hospital of Shaoxing University, Shaoxing City, China
| | - Yuxin Zhong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Yong Liu
- Department of Gastric Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
| | - Weihua Gong
- Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
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Yarahmadi A, Afkhami H. Potential relationship between Helicobacter pylori infection and autoimmune disorders: A narrative review. Microb Pathog 2025; 205:107572. [PMID: 40220801 DOI: 10.1016/j.micpath.2025.107572] [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: 04/11/2024] [Revised: 04/06/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative, flagellated bacteria that causes gastritis symptoms. This bacterium, particularly in individuals with a genetic predisposition, has been implicated in the pathogenesis of several autoimmune diseases (AD) through complex mechanisms involving the interaction of cellular and humoral immune responses. This review article tells you about the link between H. pylori infection and several types of AD, including systemic lupus erythematosus (SLE), autoimmune pancreatitis (AIP), rheumatoid arthritis (RA), Sjögren syndrome (SjS), psoriasis, and antiphospholipid syndrome (APS). We conducted a comprehensive analysis of the current literature to elucidate the potential role of H. pylori as a triggering factor for these disorders. Our findings suggest a significant correlation between H. pylori infection and the onset or exacerbation of specific ADs. This relationship is common mechanisms, including molecular mimicry, chronic inflammation, epitope spreading, and cytokine dysregulation. While H. pylori is implicated in AD, other factors such as genetic predisposition, environmental triggers, and other microbial agents also play crucial roles. Other pathogens, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and bacteria like Mycobacterium tuberculosis and Chlamydia pneumoniae have been linked to ADs. These shared pathways highlight the potential role of H. pylori as a unifying factor in the pathogenesis of diverse ADs. Further research is necessary to fully understand the interactions between H. pylori and the immune system in the context of autoimmunity. This review aims to provide a detailed overview of the knowledge on this topic, highlighting the need for additional studies to clarify these complex relationships.
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Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran; Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran; Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
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Gaonkar A, Zahiruddin QS, Shabil M, Menon SV, Kaur M, Kumari M, Sudan P, Naidu KS, Thapliyal S, Uikey J, Kathuria R, Chauhan SS, Verma L, Sidhu A, Bushi G, Yusoff RBM, Mehta R, Satapathy P, Sah S. Association of Helicobacter pylori Infection and Risk of Dyslipidemia: A Systematic Review and Meta-Analysis. JGH Open 2025; 9:e70128. [PMID: 40130085 PMCID: PMC11931453 DOI: 10.1002/jgh3.70128] [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: 12/01/2024] [Revised: 02/03/2025] [Accepted: 02/24/2025] [Indexed: 03/26/2025]
Abstract
Background Although Helicobacter pylori (H. pylori) infections are widespread throughout the world, it is yet unknown whether they are linked to systemic illnesses like dyslipidemia. The purpose of this systematic review and meta-analysis was to examine the connection between lipid metabolism and H. pylori infection, with a particular emphasis on how it affects dyslipidemia. Methods We conducted a thorough search up until October 10, 2024, across databases such as PubMed, Web of Science, and Embase. Studies that reported lipid profiles in both H. pylori-infected and non-infected patients were considered eligible. The primary outcomes were triglyceride, LDL-C, HDL-C, and total cholesterol levels, which were examined using a random-effects model in R software version 4.4. Results There were 17 studies with more than 150,000 participants from 681 screened publications. Higher levels of LDL (MD: 5.32 mg/dL; 95% CI: 1.315 to 9.319) and total cholesterol (MD: 6.28 mg/dL; 95% CI: 0.718 to 11.842), as well as lower levels of HDL (MD: -2.06 mg/dL; 95% CI: -3.212 to -0.915), were the results of the meta-analysis. Among those infected, triglyceride levels were likewise higher (MD: 7.93 mg/dL; 95% CI: 0.413 to 15.436), but the odds ratio (OR) did not show a significant increase in risk (OR: 1.002; 95% CI: 0.995 to 1.010). Conclusion H. pylori infection is associated with significant dyslipidemia, suggesting a potential link between chronic bacterial infection and lipid metabolism. The findings emphasize the need for further research to explore the mechanisms and potential therapeutic interventions.
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Affiliation(s)
- Ankita Gaonkar
- Noida Institute of Engineering and Technology (Pharmacy Institute)Greater NoidaIndia
| | - Quazi Syed Zahiruddin
- South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and ResearchDatta Meghe Institute of Higher EducationWardhaIndia
| | - Muhammed Shabil
- University Center for Research and Development, Chandigarh UniversityMohaliPunjabIndia
- Medical Laboratories Techniques Department, AL‐Mustaqbal UniversityBabilIraq
| | - Soumya V. Menon
- Department of Chemistry and BiochemistrySchool of Sciences JAIN (Deemed to be University)BangaloreKarnatakaIndia
| | - Mandeep Kaur
- Department of Allied Healthcare and SciencesVivekananda Global UniversityJaipurRajasthanIndia
| | - Mukesh Kumari
- Department of Applied Sciences‐ChemistryNIMS Institute of Engineering & Technology, NIMS University RajasthanJaipurIndia
| | - Puneet Sudan
- Department of Pharmacy Chandigarh Pharmacy CollegeChandigarh Group of Colleges‐JhanjeriMohaliPunjabIndia
| | - K. Satyam Naidu
- Department of ChemistryRaghu Engineering CollegeVisakhapatnamAndhra PradeshIndia
| | - Shailendra Thapliyal
- Uttaranchal Institute of ManagementUttaranchal UniversityDehradunUttarakhandIndia
| | - Jyoti Uikey
- IES Institute of PharmacyIES UniversityBhopalMadhya PradeshIndia
| | - Rachna Kathuria
- New Delhi Institute of Management, Tughlakabad Institutional AreaNew DelhiIndia
| | | | - Lokesh Verma
- Centre of Research Impact and OutcomeChitkara UniversityRajpuraPunjabIndia
| | - Amritpal Sidhu
- Chitkara Centre for Research and DevelopmentChitkara UniversityRajpuraHimachal PradeshIndia
| | - Ganesh Bushi
- School of Pharmaceutical SciencesLovely Professional UniversityPhagwaraIndia
| | | | - Rachana Mehta
- Clinical MicrobiologyRDC, Manav Rachna International Institute of Research and StudiesFaridabadHaryanaIndia
| | - Prakasini Satapathy
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical SciencesSaveetha UniversityChennaiIndia
- University of Cyberjaya, Persiaran BestariCyberjayaSelangor Darul EhsanMalaysia
| | - Sanjit Sah
- SR Sanjeevani HospitalKalyanpurNepal
- Department of PaediatricsDr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil VidyapeethPuneMaharashtraIndia
- Department of Public Health DentistryDr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil VidyapeethPuneMaharashtraIndia
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Lin L, Huang T, Li L, Lin Y, Chen F, Zheng Z, Zhou J, Wang Y, You W, Duan Y, An Y, He S, Ye W. Single-cell profiling reveals a reduced epithelial defense system, decreased immune responses and the immune regulatory roles of different fibroblast subpopulations in chronic atrophic gastritis. J Transl Med 2025; 23:159. [PMID: 39905493 PMCID: PMC11796052 DOI: 10.1186/s12967-025-06150-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 01/18/2025] [Indexed: 02/06/2025] Open
Abstract
PURPOSE To identify key cellular changes and molecular events in atrophic mucosa, we aimed to elucidate the molecular mechanisms driving the occurrence of chronic atrophic gastritis (CAG). METHODS We used single-cell RNA sequencing (scRNA-seq) to characterize changes in the epithelial state and tissue microenvironment associated with CAG. The molecular changes were identified by comparing differentially expressed genes (DEGs) between the two mucosa states. Gene Ontology (GO) pathway enrichment analysis was used to explore the potential functional changes in each cell subtype in atrophic mucosa. Gene set score analysis was conducted to compare the functional roles of different fibroblast subtypes and functional changes in cell subtypes between the CAG and control groups. Metabolic analysis was performed to compare the metabolic activity of C1Q+ macrophages under different conditions. NichNet analysis was used to analyze the regulatory relationships between CCL11+APOE+ fibroblasts and C1Q+ macrophages and between CCL11+APOE+ fibroblasts and CD8+ effector T cells. Transcription factor (TF) analysis was performed to determine the transcription status of different T-cell subtypes in atrophic and normal mucosa. RESULTS We generated a single-cell transcriptomic atlas from 3 CAG biopsy samples and paired adjacent normal tissues. Our analysis revealed that chief cells and parietal cells exhibited a loss of detoxification ability and that surface mucous cells displayed a reduced antimicrobial defense ability in CAG lesions. The mucous neck cells in CAG lesions showed upregulation of genes related to cell cycle transition, which may lead to aberrant DNA replication. Additionally, cells with the T exhaustion phenotype infiltrated under CAG condition. C1Q+ macrophages exhibited reduced phagocytosis, downregulated expression of pattern recognition receptors and decreased metabolic activity. NichNet analysis revealed that a subpopulation of CXCL11+APOE+ fibroblasts regulated the inflammatory response in the pathogenesis of atrophic gastritis. APSN+CXCL11+APOE+ fibroblasts were found to be associated with gastric cancer (GC) development. CONCLUSIONS The main goal of this study was to comprehensively elucidate the cellular changes in CAG lesions. We observed an immune decline in the mucosal microenvironment during the development of CAG, including a reduced immune response of C1Q+ macrophages, reduced cytotoxicity of T cells, and increased infiltration of exhausted T cells. Specifically, we demonstrated that different epithelial subtypes aberrantly express genes related to susceptibility to external bacterial infection and aberrant cell cycle progression. Our study provides new insights into the functions of epithelial changes and immune alterations during the development of CAG.
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Affiliation(s)
- Lin Lin
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China
| | - Tingxuan Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
- Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, 350001, China
| | - Lizhi Li
- Department of Pediatric Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
| | - Yang Lin
- Department of Pediatric Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China
| | - Feng Chen
- Department of Pediatric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Ziyi Zheng
- Department of Pediatric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jie Zhou
- Department of Pediatric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Yizhe Wang
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China
| | - Weihao You
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China
| | - Yujie Duan
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China
| | - Yawen An
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China
| | - Shiwei He
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China.
| | - Weimin Ye
- Institute of Population Medicine, School of Public Health, Fujian Medical University, 1 Xuefu North Road, Fuzhou, 350122, China.
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, China.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden.
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Santacroce L, Topi S, Cafiero C, Palmirotta R, Jirillo E. The Role of the Immune Response to Helicobacter pylori Antigens and Its Relevance in Gastric Disorders. GASTROINTESTINAL DISORDERS 2025; 7:6. [DOI: 10.3390/gidisord7010006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/03/2025] Open
Abstract
Helicobacter pylori (H.p.) is a Gram-negative bacterium endowed with gastric tropism. H.p. infection is widely spread throughout the world, accounting for various pathologies, such as peptic ulcer, gastric cancer, mucosa-associated lymphoid tissue lymphoma, and extra-gastric manifestations. This bacterium possesses several virulence factors, e.g., lipopolysaccharides (LPS), the toxins CagA and VacA, and adhesins, which elicit a robust immune response during the initial phase of the infection. Of note, the lipid A moiety of the LPS exhibits a lower endotoxic potency than that of other LPSs, thus facilitating infection through a mechanism of immune escape. H.p. colonization of the gastric mucosa induces an initial protective immune response with innate immune cells, e.g., neutrophils, monocytes, and macrophages, which engulf and kill bacteria. Moreover, the same cells, along with gastric epithelial cells, secrete cytokines and chemokines, which recruit T cells [T helper (h)1 and Th17 cells] to the site of infection, thus leading to H.p. eradication. In a large subset of individuals, the perturbation of such an immune equilibrium leads to a harmful response, with an expansion of T regulatory (TREG) cells, which suppress the protective immune response. In fact, TREG cells, via the production of interleukin (IL)-10, downregulate Th1- and Th17-related cytokines, thus allowing H.p. survival and the perpetuation of inflammation. As far as the humoral immune response is concerned, B cells, upon H.p. stimulation, produce autoreactive antibodies, and IgG anti-Lex antibodies are harmful to the gastric mucosa. In this review, the structure and function of H.p. antigenic components and immune mechanisms elicited by this bacterium will be described in relation to gastric damage.
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Affiliation(s)
- Luigi Santacroce
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania
| | - Skender Topi
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania
| | | | - Raffaele Palmirotta
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania
| | - Emilio Jirillo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
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Wang X, Wang J, Mao L, Yao Y. Helicobacter pylori outer membrane vesicles and infected cell exosomes: new players in host immune modulation and pathogenesis. Front Immunol 2024; 15:1512935. [PMID: 39726601 PMCID: PMC11670821 DOI: 10.3389/fimmu.2024.1512935] [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: 10/17/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024] Open
Abstract
Outer membrane vesicles (OMVs) and exosomes are essential mediators of host-pathogen interactions. Elucidating their mechanisms of action offers valuable insights into diagnosing and treating infectious diseases and cancers. However, the specific interactions of Helicobacter pylori (H. pylori) with host cells via OMVs and exosomes in modulating host immune responses have not been thoroughly investigated. This review explores how these vesicles elicit inflammatory and immunosuppressive responses in the host environment, facilitate pathogen invasion of host cells, and enable evasion of host defenses, thereby contributing to the progression of gastric diseases and extra-gastric diseases disseminated through the bloodstream. Furthermore, the review discusses the challenges and future directions for investigating OMVs and exosomes, underscoring their potential as therapeutic targets in H. pylori-associated diseases.
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Affiliation(s)
- Xiuping Wang
- Department of Clinical Laboratory, The First People’s Hospital of
Kunshan, Kunshan, Jiangsu, China
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Tu Z, Wang Y, Liang J, Liu J. Helicobacter pylori-targeted AI-driven vaccines: a paradigm shift in gastric cancer prevention. Front Immunol 2024; 15:1500921. [PMID: 39669583 PMCID: PMC11634812 DOI: 10.3389/fimmu.2024.1500921] [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: 09/24/2024] [Accepted: 11/08/2024] [Indexed: 12/14/2024] Open
Abstract
Helicobacter pylori (H. pylori), a globally prevalent pathogen Group I carcinogen, presents a formidable challenge in gastric cancer prevention due to its increasing antimicrobial resistance and strain diversity. This comprehensive review critically analyzes the limitations of conventional antibiotic-based therapies and explores cutting-edge approaches to combat H. pylori infections and associated gastric carcinogenesis. We emphasize the pressing need for innovative therapeutic strategies, with a particular focus on precision medicine and tailored vaccine development. Despite promising advancements in enhancing host immunity, current Helicobacter pylori vaccine clinical trials have yet to achieve long-term efficacy or gain approval regulatory approval. We propose a paradigm-shifting approach leveraging artificial intelligence (AI) to design precision-targeted, multiepitope vaccines tailored to multiple H. pylori subtypes. This AI-driven strategy has the potential to revolutionize antigen selection and optimize vaccine efficacy, addressing the critical need for personalized interventions in H. pylori eradication efforts. By leveraging AI in vaccine design, we propose a revolutionary approach to precision therapy that could significantly reduce H. pylori -associated gastric cancer burden.
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Affiliation(s)
| | | | | | - Jinping Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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10
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Xu H, Huang K, Shi M, Gong H, Han M, Tian W, Wang X, Zhang D. MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application. Pharmacol Res 2024; 205:107216. [PMID: 38761883 DOI: 10.1016/j.phrs.2024.107216] [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: 02/27/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/20/2024]
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Ke Huang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Mingxuan Shi
- Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Hang Gong
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Mengyu Han
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Wenji Tian
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Xiaoying Wang
- Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
| | - Dekui Zhang
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
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Liu N, Sun W, Gao W, Yan S, Yang C, Zhang J, Ni B, Zhang L, Zang J, Zhang S, Xu D. CD300e: Emerging role and mechanism as an immune-activating receptor. Int Immunopharmacol 2024; 133:112055. [PMID: 38677094 DOI: 10.1016/j.intimp.2024.112055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 04/06/2024] [Accepted: 04/07/2024] [Indexed: 04/29/2024]
Abstract
As a transmembrane protein, CD300e is primarily expressed in myeloid cells. It belongs to the CD300 glycoprotein family, functioning as an immune-activating receptor. Dysfunction of CD300e has been suggested in many diseases, such as infections, immune disorders, obesity, and diabetes, signifying its potential as a key biomarker for disease diagnosis and treatment. This review is aimed to explore the roles and potential mechanisms of CD300e in regulating oxidative stress, immune cell activation, tissue damage and repair, and lipid metabolism, shedding light on its role as a diagnostic marker or a therapeutic target, particularly for infections and autoimmune disorders.
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Affiliation(s)
- Na Liu
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Wenchang Sun
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Weixing Gao
- Office of the First Clinical Medical College, Shandong Second Medical University, Weifang 261000, China
| | - Shushan Yan
- Department of Colorectal and Anal Surgery of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Chunjuan Yang
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China; Department of Rheumatology of the Affiliated Hospital, Shandong Second Medical University, Weifang, 261053, China
| | - Jin Zhang
- Department of Colorectal and Anal Surgery of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Biao Ni
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Lili Zhang
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Jie Zang
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China
| | - Sue Zhang
- Department of Anesthesiology, Weifang People's Hospital, Weifang 261000, China.
| | - Donghua Xu
- Central Laboratory of the First Affiliated Hospital & the First Clinical College, Shandong Second Medical University, Weifang 261000, China; Department of Rheumatology of the Affiliated Hospital, Shandong Second Medical University, Weifang, 261053, China; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
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12
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Lei C, Xu Y, Zhang S, Huang C, Qin J. The role of microbiota in gastric cancer: A comprehensive review. Helicobacter 2024; 29:e13071. [PMID: 38643366 DOI: 10.1111/hel.13071] [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: 12/13/2023] [Revised: 02/19/2024] [Accepted: 03/25/2024] [Indexed: 04/22/2024]
Abstract
BACKGROUND Gastric cancer (GC) continues to pose a significant global threat in terms of cancer-related fatalities. Despite notable advancements in medical research and therapies, further investigation is warranted to elucidate its underlying etiology and risk factors. Recent times have witnessed an escalated emphasis on comprehending the role of the microbiota in cancer development. METHODS This review briefly delves into recent developments in microbiome-related research pertaining to gastric cancer. RESULTS According to studies, the microbiota can influence GC growth by inciting inflammation, disrupting immunological processes, and generating harmful microbial metabolites. Furthermore, there is ongoing research into how the microbiome can impact a patient's response to chemotherapy and immunotherapy. CONCLUSION The utilization of the microbiome for detecting, preventing, and managing stomach cancer remains an active area of exploration.
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Affiliation(s)
- Changzhen Lei
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yitian Xu
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shaopeng Zhang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing Qin
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Oktem-Okullu S, Karaman T, Akcelik-Deveci S, Timucin E, Sezerman OU, Mansur-Ozen N, Buyukcolak Y, Tiftikci A. Effect of the switch status of Helicobacter pylori outer inflammatory protein A on gastric diseases. AMB Express 2023; 13:109. [PMID: 37817013 PMCID: PMC10564699 DOI: 10.1186/s13568-023-01621-z] [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: 06/29/2023] [Accepted: 10/03/2023] [Indexed: 10/12/2023] Open
Abstract
Helicobacter pylori OipA (Outer Inflammatory Protein A) is an outer membrane protein that takes role in the adherence and colonization to the stomach. oipA gene expression is regulated by the slipped-strand mispairing mechanism through a hypermutable CT dinucleotide repeat motif in the 5΄ region. Alterations in the CT number repeats cause frame-shift mutations to result in phase variation of oipA expression. While a functional "On" status has been recognized as a risk factor for peptic ulcer diseases and gastric cancer in many studies, some controversial findings still exist. To this end, this study compiled the sequence data of oipA from 10 different studies between 2000-2019 and 50 oipA DNA sequences from our own research that examined the relationship between the phase On/Off status of oipA and gastric diseases based on CT repeat number. Overall, we have reached 536 oipA DNA sequences from patients. This large collection of oipA sequences first clarified the absolute conservation of the peptide-pentamer of FWLHA for phase ''On'' status, suggesting this pentamer as a superior marker for the determination of oipA status than counting the number of CT repeats. Combining the sequence and patient data, we have re-analyzed the association between the ''On'' status of oipA and gastric diseases. Our results showed a strong association between oipA ''On'' status and gastric cancer supporting previous findings. We also investigated the AlphaFold2 computed structure of OipA that adopts a beta-barrel fold closely resembling to the autotransporter family of H. pylori. Altogether, this study confirms a strong association between oipA ''On'' statuses and severe gastrointestinal diseases like cancer and provides useful insights into the FWLHA pentamer as an indicator of "On" status of oipA putative autotransporter function rather than CT repeats number.
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Affiliation(s)
- Sinem Oktem-Okullu
- Department of Medical Microbiology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey.
| | - Tayyip Karaman
- Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Sümeyye Akcelik-Deveci
- Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Emel Timucin
- Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Osman Ugur Sezerman
- Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Nesteren Mansur-Ozen
- Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Yaren Buyukcolak
- Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
| | - Arzu Tiftikci
- Department of Internal Medicine, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34752, Turkey
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Ahmed AAQ, Besio R, Xiao L, Forlino A. Outer Membrane Vesicles (OMVs) as Biomedical Tools and Their Relevance as Immune-Modulating Agents against H. pylori Infections: Current Status and Future Prospects. Int J Mol Sci 2023; 24:ijms24108542. [PMID: 37239888 DOI: 10.3390/ijms24108542] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/26/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
Outer membrane vesicles (OMVs) are lipid-membrane-bounded nanoparticles that are released from Gram-negative bacteria via vesiculation of the outer membrane. They have vital roles in different biological processes and recently, they have received increasing attention as possible candidates for a broad variety of biomedical applications. In particular, OMVs have several characteristics that enable them to be promising candidates for immune modulation against pathogens, such as their ability to induce the host immune responses given their resemblance to the parental bacterial cell. Helicobacter pylori (H. pylori) is a common Gram-negative bacterium that infects half of the world's population and causes several gastrointestinal diseases such as peptic ulcer, gastritis, gastric lymphoma, and gastric carcinoma. The current H. pylori treatment/prevention regimens are poorly effective and have limited success. This review explores the current status and future prospects of OMVs in biomedicine with a special focus on their use as a potential candidate in immune modulation against H. pylori and its associated diseases. The emerging strategies that can be used to design OMVs as viable immunogenic candidates are discussed.
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Affiliation(s)
- Abeer Ahmed Qaed Ahmed
- Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy
| | - Roberta Besio
- Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy
| | - Lin Xiao
- School of Biomedical Engineering, Shenzhen Campus, Sun Yat-sen University, Shenzhen 518107, China
| | - Antonella Forlino
- Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy
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Zaib S, Javed H, Ogaly HA, Khan I. Evaluating the Anti‐Gastric Ulcer Activity of
Aegle marmelos
: A Brief Review. ChemistrySelect 2023. [DOI: 10.1002/slct.202204193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Affiliation(s)
- Sumera Zaib
- Department of Basic and Applied Chemistry, Faculty of Science and Technology University of Central Punjab Lahore 54590 Pakistan
| | - Hira Javed
- Department of Basic and Applied Chemistry, Faculty of Science and Technology University of Central Punjab Lahore 54590 Pakistan
| | - Hanan A. Ogaly
- Chemistry Department, College of Science King Khalid University Abha 61421 Saudi Arabia
- Biochemistry and Molecular Biology Department Faculty of Veterinary Medicine, Cairo University Giza 12211 Egypt
| | - Imtiaz Khan
- Manchester Institute of Biotechnology The University of Manchester, 131 Princess Street Manchester M1 7DN United Kingdom
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Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions. Cancers (Basel) 2023; 15:cancers15061662. [PMID: 36980548 PMCID: PMC10046233 DOI: 10.3390/cancers15061662] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/28/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023] Open
Abstract
Background: Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.
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El Filaly H, Outlioua A, Desterke C, Echarki Z, Badre W, Rabhi M, Riyad M, Arnoult D, Khalil A, Akarid K. IL-1 Polymorphism and Helicobacter pylori Infection Features: Highlighting VNTR's Potential in Predicting the Susceptibility to Infection-Associated Disease Development. Microorganisms 2023; 11:microorganisms11020353. [PMID: 36838318 PMCID: PMC9961292 DOI: 10.3390/microorganisms11020353] [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: 12/10/2022] [Revised: 01/05/2023] [Accepted: 01/13/2023] [Indexed: 02/04/2023] Open
Abstract
Genetic polymorphisms at the IL-1 cluster are associated with increased Helicobacter pylori (H. pylori)-associated disease risk in an ethnically dependent manner. Due to the corroborated role of IL-1β in H. pylori infection progression, our aim is to depict the impact of IL1B rs1143627 and rs16944 as well as the IL1RN variable number of identical tandem repeats (VNTR) on the clinical and biological features of Moroccan H. pylori-infected patients. A total of 58 patients with epigastralgic pain were referred to the gastroenterology department for histopathological and clinical analysis. DNA extraction from antrum and fundus biopsies and PCR-RFLP were performed to detect polymorphisms. As a result, VNTR was significantly associated with IL-1β antrum levels (p-value = 0.029), where the *1/*4 genotype showed a positive association with upregulated cytokine levels in the antrum and was clustered with H. pylori-infected patients' features and higher levels of IL-1β in the antrum and fundus. Likewise, *1/*1 genotype carriers clustered with severe gastritis activity and H. pylori density scores along with low levels of IL-1β in the antrum and fundus, while the *1/*2 genotype was clustered with non-infected-patient features and normal IL-1β levels. In conclusion, VNTR might be an interesting predictor to identify patients at risk of developing H. pylori-associated pathologies.
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Affiliation(s)
- Hajar El Filaly
- Biochemistry, Biotechnology and Immunophysiopathology Research Team, Health and Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20100, Morocco
- Correspondence:
| | - Ahmed Outlioua
- Biochemistry, Biotechnology and Immunophysiopathology Research Team, Health and Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20100, Morocco
| | - Christophe Desterke
- INSERM UMRS-1311, Faculty of Medicine, University of Paris-Saclay, 94270 Villejuif, France
| | - Zerif Echarki
- Research Center on Aging, Faculty of Medicine and Health Sciences, Department of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Wafaa Badre
- Gastroenterology Department, CHU Ibn Rochd, Casablanca 20100, Morocco
| | - Moncef Rabhi
- Diagnostic Center, Hôpital Militaire d’Instruction Mohammed V, Mohammed V University, Rabat 10045, Morocco
| | - Myriam Riyad
- Research Team on Immunopathology of Infectious and Systemic Diseases, Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy, UH2C, Casablanca 20250, Morocco
| | - Damien Arnoult
- INSERM, UMR_S 1197, Hôpital Paul Brousse, Université Paris-Saclay, 94270 Villejuif, France
| | - Abdelouahed Khalil
- Research Center on Aging, Faculty of Medicine and Health Sciences, Department of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Khadija Akarid
- Biochemistry, Biotechnology and Immunophysiopathology Research Team, Health and Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Casablanca 20100, Morocco
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Mirza WA, Zhang K, Zhang R, Duan G, Khan MSN, Ni P. Vitamin D deficiency in dengue fever patients' coinfected with H. pylori in Pakistan. A case-control study. Front Public Health 2022; 10:1035560. [PMID: 36388314 PMCID: PMC9659955 DOI: 10.3389/fpubh.2022.1035560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/14/2022] [Indexed: 01/29/2023] Open
Abstract
INTRODUCTION Dengue fever is a vector-borne disease with an estimate of 390 million persons getting the infection each year with a significant public health impact. It has been reported DENV patients with vitamin D deficiency led to severe form of dengue infection; while H. pylori coinfection alters vitamin D receptors leading to vitamin D deficiency. We hypothesize that DENV patient's having low vitamin D along with H. pylori coinfection could have worsen dengue severity as well as vitamin D deficiency. In this case-control study, we compared (I) the vitamin D deficiency in dengue fever cases with or without H. pylori coinfection, and (II) negative dengue fever as a control with or without H. pylori coinfection. We have also assessed the correlation between vitamin D levels and its effect on warning signs of the dengue fever. Further, we have investigated whether coinfection with H. pylori has any effect on warning signs in the dengue fever patients and the vitamin D deficiency in all serotypes of the dengue virus infected patients. METHODS In this case control study the association of the vitamin D levels with age, gender and H. pylori coinfection in dengue fever hospitalized patients was assessed using chi-square and multivariate logistic regression analysis. RESULTS Four hundred dengue fever patients with H. pylori coinfection were compared with 400 dengue negative controls with H. pylori coinfection. The mean age was 29.96 ± 10.5 and 29.88 ± 10.7 years among cases and controls, respectively. Most dengue fever patients with H. pylori coinfection were deficient in vitamin D compared with negative dengue controls with H. pylori coinfection. In multivariate logistic regression, the dengue cases with H. pylori coinfection were.056 times (95% CI: 0.024, 0.128, P = 0.000) more likely to have vitamin D "deficiency', while compared with the cases who did not have H. pylori coinfection. CONCLUSION The present study proposes that vitamin D deficiency in dengue fever patients coinfected with H. pylori is much higher than the dengue fever negative controls coinfected with H. pylori. As hypothesized the DENV patient with H. pylori coinfection has vitamin D deficiency as well as increased dengue severity.
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Affiliation(s)
- Wajid Ameen Mirza
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Ke Zhang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Rongguang Zhang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
- The First Affiliated Hospital and International College of Public Health and One Health, Hainan Medical University, Haikou, China
| | - Guangcai Duan
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | | | - Peng Ni
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
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Zhou Q, Qureshi N, Xue B, Xie Z, Li P, Gu Q. Preventive and therapeutic effect of Lactobacillus paracasei ZFM54 on Helicobacter pylori-induced gastritis by ameliorating inflammation and restoring gastric microbiota in mice model. Front Nutr 2022; 9:972569. [PMID: 36091249 PMCID: PMC9449542 DOI: 10.3389/fnut.2022.972569] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 08/02/2022] [Indexed: 11/13/2022] Open
Abstract
Helicobacter pylori is the most prevalent pathogen causing chronic gastritis, gastroduodenal ulcers, and gastric tumors and is asymptomatically present in 50% of the world's population. This research is focused on investigating the effect of Lactobacillus paracasei ZFM 54 (CCTCC NO:2016667) on attenuating H. pylori-induced gastritis. H. pylori ZJC03 isolated from a patient with gastritis harbored the virulence genes of vacA and cagA and was highly resistant to metronidazole (MIC > 256 μg/mL). In vitro analysis revealed that the potential anti-H. pylori characteristics of L. paracasei ZFM54 in terms of 65.57 ± 1.87% survival rate in simulated gastric juices at a pH of 2.0, 69.00 ± 2.73% auto-aggregation, 30.28 ± 2.24% co-aggregation, 70.27 ± 2.23% urease inhibition, and 57.89 ± 1.27% radical scavenging. In H. pylori infectious mice, L. paracasei ZFM54 pre- and post-treatment reduced the levels of malondialdehyde in liver tissues to 0.71 ± 0.04 nmol/mgprot (p < 0.05) and 0.70 ± 0.06 nmol/mgprot (p < 0.05), respectively. Glutathione levels were increased to 1.78 ± 0.02 μmol/gprot (p < 0.05) and 1.76 ± 0.52 μmol/gprot (p < 0.05), respectively. L. paracasei ZFM54 significantly inhibited H. pylori-mediated inflammation observed in gastric mucosal repair and downregulated the mRNA expression of pro-inflammatory cytokines IFN-γ, IL-1β, and IL-6 (p < 0.01). Importantly, L. paracasei ZFM54 increased Firmicutes and Actinobacteriota and decreased the relative abundance of bacterial taxa belonging to Campilobacterota and Proteobacteria. With the preventive and therapeutic administration of L. paracasei ZFM54, significant reductions in the average relative abundance of genera Helicobacter, Muribaculum, Staphylococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, Alloprevotella, and Oscillibacter were observed compared to infected mice. These findings suggest that L. paracasei ZFM 54 has the potential to protect against H. pylori infection by ameliorating inflammation and restoring the gastric microbiota.
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Majewski M, Mertowska P, Mertowski S, Smolak K, Grywalska E, Torres K. Microbiota and the Immune System-Actors in the Gastric Cancer Story. Cancers (Basel) 2022; 14:cancers14153832. [PMID: 35954495 PMCID: PMC9367521 DOI: 10.3390/cancers14153832] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/04/2022] [Accepted: 08/06/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Stomach cancer is one of the most commonly diagnosed cancers in the world. Although the number of new cases is decreasing year by year, the death rate for this type of cancer is still high. The heterogeneous course and the lack of symptoms in the early stages of the disease mean that the diagnosis is made late, which translates into a worse prognosis for such patients. That is why it is so important to analyze potential risk factors that may increase the risk of developing gastric cancer and to search for new effective methods of treatment. These requirements are met by the analysis of the composition of the gastric microbiota and its relationship with the immune system, which is a key element in the human anti-cancer fight. This publication was created to systematize the current knowledge on the impact of dysbiosis of human microbiota on the development and progression of gastric cancer. Particular emphasis was placed on taking into account the role of the immune system in this process. Abstract Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis for patients. That is why it is so important to understand the mechanisms underlying the development and progression of this cancer, with particular emphasis on the role of risk factors. According to the literature data, risk factors include: changes in the composition of the stomach and intestinal microbiota (microbiological dysbiosis and the participation of Helicobacter pylori), improper diet, environmental and genetic factors, and disorders of the body’s immune homeostasis. Therefore, the aim of this review is to systematize the knowledge on the influence of human microbiota dysbiosis on the development and progression of gastric cancer, with particular emphasis on the role of the immune system in this process.
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Affiliation(s)
- Marek Majewski
- 2nd Department of General, Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, 20-081 Lublin, Poland
| | - Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
- Correspondence:
| | - Sebastian Mertowski
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Konrad Smolak
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Kamil Torres
- Chair and Department of Didactics and Medical Simulation, Medical University of Lublin, 20-093 Lublin, Poland
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21
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Hiengrach P, Panpetch W, Chindamporn A, Leelahavanichkul A. Helicobacter pylori, Protected from Antibiotics and Stresses Inside Candida albicans Vacuoles, Cause Gastritis in Mice. Int J Mol Sci 2022; 23:8568. [PMID: 35955701 PMCID: PMC9368807 DOI: 10.3390/ijms23158568] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 12/10/2022] Open
Abstract
Due to (i) the simultaneous presence of Helicobacter pylori (ulcer-induced bacteria) and Candida albicans in the stomach and (ii) the possibility of prokaryotic-eukaryotic endosymbiosis (intravacuolar H. pylori in the yeast cells) under stresses, we tested this symbiosis in vitro and in vivo. To that end, intravacuolar H. pylori were induced by the co-incubation of C. albicans with H. pylori under several stresses (acidic pH, non-H. pylori-enrichment media, and aerobic environments); the results were detectable by direct microscopy (wet mount) and real-time polymerase chain reaction (PCR). Indeed, intravacuolar H. pylori were predominant under all stresses, especially the lower pH level (pH 2-3). Interestingly, the H. pylori (an amoxicillin-sensitive strain) inside C. albicans were protected from the antibiotic (amoxicillin), while extracellular H. pylori were neutralizable, as indicated by the culture. In parallel, the oral administration of intravacuolar H. pylori in mice caused H. pylori colonization in the stomach resulting in gastritis, as indicated by gastric histopathology and tissue cytokines, similar to the administration of free H. pylori (extra-Candida bacteria). In conclusion, Candida protected H. pylori from stresses and antibiotics, and the intravacuolar H. pylori were able to be released from the yeast cells, causing gastric inflammation with neutrophil accumulations.
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Affiliation(s)
- Pratsanee Hiengrach
- Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand; (P.H.); (W.P.)
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Wimonrat Panpetch
- Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand; (P.H.); (W.P.)
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Ariya Chindamporn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Antimicrobial Resistance and Stewardship Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Asada Leelahavanichkul
- Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok 10330, Thailand; (P.H.); (W.P.)
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Nephrology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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22
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Mărginean CO, Meliț LE, Săsăran MO. Traditional and Modern Diagnostic Approaches in Diagnosing Pediatric Helicobacter pylori Infection. CHILDREN 2022; 9:children9070994. [PMID: 35883980 PMCID: PMC9316053 DOI: 10.3390/children9070994] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 01/10/2023]
Abstract
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, is usually acquired during childhood and is related to gastric carcinogenesis during adulthood. Therefore, its early proper diagnosis and subsequent successful eradication represent the cornerstones of gastric cancer prevention. The aim of this narrative review was to assess traditional and modern diagnostic methods in terms of H. pylori diagnosis. Several invasive and non-invasive methods were described, each with its pros and cons. The invasive diagnostic methods comprise endoscopy with biopsy, rapid urease tests, histopathological exams, cultures and biopsy-based molecular tests. Among these, probably the most available, accurate and cost-effective test remains histology, albeit molecular tests definitely remain the most accurate despite their high costs. The non-invasive tests consist of urea breath tests, serology, stool antigens and non-invasive molecular tests. Urea breath tests and stool antigens are the most useful in clinical practice both for the diagnosis of H. pylori infection and for monitoring the eradication of this infection after therapy. The challenges related to accurate diagnosis lead to a choice that must be based on H. pylori virulence, environmental factors and host peculiarities.
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Affiliation(s)
- Cristina Oana Mărginean
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
| | - Lorena Elena Meliț
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
- Correspondence:
| | - Maria Oana Săsăran
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
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23
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Rossi AFT, da Silva Manoel-Caetano F, Biselli JM, Cabral ÁS, Saiki MDFC, Ribeiro ML, Silva AE. Downregulation of TNFR2 decreases survival gene expression, promotes apoptosis and affects the cell cycle of gastric cancer cells. World J Gastroenterol 2022; 28:2689-2704. [PMID: 35979166 PMCID: PMC9260869 DOI: 10.3748/wjg.v28.i24.2689] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/21/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic inflammation due to Helicobacter pylori (H. pylori) infection promotes gastric carcinogenesis. Tumour necrosis factor-α (TNF-α), a key mediator of inflammation, induces cell survival or apoptosis by binding to two receptors (TNFR1 and TNFR2). TNFR1 can induce both survival and apoptosis, while TNFR2 results only in cell survival. The dysregulation of these processes may contribute to carcinogenesis.
AIM To evaluate the effects of TNFR1 and TNFR2 downregulation in AGS cells treated with H. pylori extract on the TNF-α pathway.
METHODS AGS cell lines containing TNFR1 and TNFR2 receptors downregulated by specific shRNAs and nonsilenced AGS cells were treated with H. pylori extract for 6 h. Subsequently, quantitative polymerase chain reaction with TaqMan® assays was used for the relative quantification of the mRNAs (TNFA, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) related to the TNF-α signalling pathway. Flow cytometry was employed for cell cycle analysis and apoptosis assays.
RESULTS In nonsilenced AGS cells, H. pylori extract treatment increased the expression of genes involved in cell survival and inhibited both apoptosis (NFKB1, NFKB2 and CFLIP) and the TNFR1 receptor. TNFR1 downregulation significantly decreased the expression of the TRADD and CFLIP genes, although no change was observed in the cellular process or miRNA expression. In contrast, TNFR2 downregulation decreased the expression of the TRADD and TRAF2 genes, which are both important downstream mediators of the TNFR1-mediated pathway, as well as that of the NFKB1 and CFLIP genes, while upregulating the expression of miR-19a and miR-34a. Consequently, a reduction in the number of cells in the G0/G1 phase and an increase in the number of cells in the S phase were observed, as well as the promotion of early apoptosis.
CONCLUSION Our findings mainly highlight the important role of TNFR2 in the TNF-α pathway in gastric cancer, indicating that silencing it can reduce the expression of survival and anti-apoptotic genes.
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Affiliation(s)
- Ana Flávia Teixeira Rossi
- Department of Biological Sciences, Sao Paulo State University (UNESP), São José do Rio Preto 15054-000, São Paulo, Brazil
| | | | - Joice Matos Biselli
- Department of Biological Sciences, Sao Paulo State University (UNESP), São José do Rio Preto 15054-000, São Paulo, Brazil
| | - Ágata Silva Cabral
- Department of Biological Sciences, Sao Paulo State University (UNESP), São José do Rio Preto 15054-000, São Paulo, Brazil
| | | | - Marcelo Lima Ribeiro
- Clinical Pharmacology and Gastroenterology Unit, São Francisco University (USF), Bragança Paulista 12916-900, São Paulo, Brazil
| | - Ana Elizabete Silva
- Department of Biological Sciences, Sao Paulo State University (UNESP), São José do Rio Preto 15054-000, São Paulo, Brazil
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24
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Öcal S, Öcal R, Suna N. Relationship between Helicobacter pylori infection and white matter lesions in patients with migraine. BMC Neurol 2022; 22:187. [PMID: 35597897 PMCID: PMC9123779 DOI: 10.1186/s12883-022-02715-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/16/2022] [Indexed: 11/28/2022] Open
Abstract
Background/aim White matter lesions (WML) are more frequently observed in migraine patients than in the average population. Associations between Helicobacter pylori (H. pylori) infection and different extraintestinal pathologies have been identified. Here, we aimed to investigate the association between H. pylori infection and WML in patients diagnosed with episodic migraine. Materials and methods A retrospective study was conducted with 526 subjects with a diagnosis of episodic migraine. Hyperintensity of WML had been previously evaluated in these patients with brain magnetic resonance imaging (MRI) examinations. Previous endoscopic gastric biopsy histopathological examination of the same patients and reports on H. pylori findings were recorded. The demographic characteristics of the patients, such as age, gender and chronic systemic diseases such as hypertension and diabetes mellitus (DM) were recorded. Statistical evaluation was made. Results Evaluation was made among 526 migraine patients who met the inclusion criteria, comprising 397 (75.5%) females and 129 (24.5%) males with a mean age of 45.57 ± 13.46 years (range, 18–69 years). WML was detected on brain MRI in 178 (33.8%) patients who were also positive for H. pylori (p < 0.05). Subjects who are H. pylori-positive with migraine, WML were observed at a 2.5-fold higher incidence on brain MRI (odds ratio: 2.562, 95% CI 1.784–3.680). WML was found to be more significant in patients with hypertension and migraine than those without (p < 0.001). Older age was also found to be associated with WML (OR = 1.07, 95% CI: 0.01–0.04, p < 0.001). The age (p < 0.001), H. pylori (p < 0.001), hypertension (p < 0.001), and hypertension + DM (p < 0.05), had significant associations in predicting WML according to the multivariate logistic regression analysis. The presence of hypertension had a higher odds ratio value than the other variables. Conclusion It was concluded that H. pylori infection, as a chronic infection, can be considered a risk factor in developing WML in subjects with migraine. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-022-02715-0.
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Affiliation(s)
- Serkan Öcal
- Department of Gastroenterology, University of Health Sciences Antalya Training and Research Hospital, Antalya, Turkey.
| | - Ruhsen Öcal
- Antalya Training and Research Hospital Department of Neurology, Antalya, Turkey
| | - Nuretdin Suna
- Department of Gastroenterology, Faculty of Medicine, Başkent University, Ankara, Turkey
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25
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Herrera-Uribe J, Zaldívar-López S, Aguilar C, Entrenas-García C, Bautista R, Claros MG, Garrido JJ. Study of microRNA expression in Salmonella Typhimurium-infected porcine ileum reveals miR-194a-5p as an important regulator of the TLR4-mediated inflammatory response. Vet Res 2022; 53:35. [PMID: 35598011 PMCID: PMC9123658 DOI: 10.1186/s13567-022-01056-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/08/2022] [Indexed: 12/12/2022] Open
Abstract
Infection with Salmonella Typhimurium (S. Typhimurium) is a common cause of food-borne zoonosis leading to acute gastroenteritis in humans and pigs, causing economic losses to producers and farmers, and generating a food security risk. In a previous study, we demonstrated that S. Typhimurium infection produces a severe transcriptional activation of inflammatory processes in ileum. However, little is known regarding how microRNAs regulate this response during infection. Here, small RNA sequencing was used to identify 28 miRNAs differentially expressed (DE) in ileum of S. Typhimurium-infected pigs, which potentially regulate 14 target genes involved in immune system processes such as regulation of cytokine production, monocyte chemotaxis, or cellular response to interferon gamma. Using in vitro functional and gain/loss of function (mimics/CRISPR-Cas system) approaches, we show that porcine miR-194a-5p (homologous to human miR-194-5p) regulates TLR4 gene expression, an important molecule involved in pathogen virulence, recognition and activation of innate immunity in Salmonella infection.
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Affiliation(s)
- Juber Herrera-Uribe
- Immunogenomics and Molecular Pathogenesis Group, Department of Genetics, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain.,Viral Immunology Group, School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland
| | - Sara Zaldívar-López
- Immunogenomics and Molecular Pathogenesis Group, Department of Genetics, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain. .,Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Research Group GA-14, Córdoba, Spain.
| | - Carmen Aguilar
- Immunogenomics and Molecular Pathogenesis Group, Department of Genetics, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain.,Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
| | - Carmen Entrenas-García
- Immunogenomics and Molecular Pathogenesis Group, Department of Genetics, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain.,Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Research Group GA-14, Córdoba, Spain
| | - Rocío Bautista
- Andalusian Platform of Bioinformatics-SCBI, University of Málaga, Málaga, Spain
| | - M Gonzalo Claros
- Andalusian Platform of Bioinformatics-SCBI, University of Málaga, Málaga, Spain.,Department of Molecular Biology and Biochemistry, University of Málaga, Málaga, Spain
| | - Juan J Garrido
- Immunogenomics and Molecular Pathogenesis Group, Department of Genetics, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain.,Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Research Group GA-14, Córdoba, Spain
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26
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Mohammadi A, Khanbabaei H, Zandi F, Ahmadi A, Haftcheshmeh SM, Johnston TP, Sahebkar A. Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases. Microb Pathog 2022; 166:105552. [DOI: 10.1016/j.micpath.2022.105552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 04/16/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022]
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27
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Nabavi-Rad A, Azizi M, Jamshidizadeh S, Sadeghi A, Aghdaei HA, Yadegar A, Zali MR. The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System. J Immunol Res 2022; 2022:4713684. [PMID: 35340586 PMCID: PMC8942682 DOI: 10.1155/2022/4713684] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/19/2022] [Accepted: 02/25/2022] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori as a class I carcinogen is correlated with a variety of severe gastroduodenal diseases; therefore, H. pylori eradication has become a priority to prevent gastric carcinogenesis. However, due to the emergence and spread of multidrug and single drug resistance mechanisms in H. pylori, as well as serious side effects of currently used antibiotic interventions, achieving successful H. pylori eradication has become exceedingly difficult. Recent studies expressed the intention of seeking novel strategies to improve H. pylori management and reduce the risk of H. pylori-associated intestinal and extragastrointestinal disorders. For which, vitamin supplementation has been demonstrated in many studies to have a tight interaction with H. pylori infection, either directly through the regulation of the host inflammatory pathways or indirectly by promoting the host immune response. On the other hand, H. pylori infection is reported to result in micronutrient malabsorption or deficiency. Furthermore, serum levels of particular micronutrients, especially vitamin D, are inversely correlated to the risk of H. pylori infection and eradication failure. Accordingly, vitamin supplementation might increase the efficiency of H. pylori eradication and reduce the risk of drug-related adverse effects. Therefore, this review aims at highlighting the regulatory role of micronutrients in H. pylori-induced host immune response and their potential capacity, as intrinsic antioxidants, for reducing oxidative stress and inflammation. We also discuss the uncovered mechanisms underlying the molecular and serological interactions between micronutrients and H. pylori infection to present a perspective for innovative in vitro investigations, as well as novel clinical implications.
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Affiliation(s)
- Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Azizi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Jamshidizadeh
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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28
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Sultan AM, Shenouda R, Sultan AM, Shehta A, Nabiel Y. The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and Helicobacter pylori cagA, sodB, hsp60, and vacA Virulence Genes among Gastric Cancer Patients. Pol J Microbiol 2022; 71:35-42. [PMID: 35635169 PMCID: PMC9152911 DOI: 10.33073/pjm-2022-003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/19/2021] [Indexed: 12/26/2022] Open
Abstract
To identify the associations between different genotypes of TLR9 -1486T/C (rs187084) with gastric cancer patients and reveal their relation to Helicobacter pylori virulence genes (cagA, sodB, hsp60 and vacA). Patients with gastric cancer were recruited to our study, diagnosed both endoscopically and histopathologically. H. pylori were isolated from gastric samples by culture and PCR amplification of the glmM gene. Virulence genes cagA, sodB, hsp60, and vacA were detected by multiplex PCR. Blood samples were used for genotyping of TLR9 -1486T/C (rs187084) by PCR-RFLP. Out of 132 patients with gastric cancer, 106 (80.3%) were positive for H. pylori. A similar number of healthy participants was recruited as controls. The prevalence of cagA, sodB, hsp60, and vacA genes among H. pylori was 90.6%, 70.8%, 83.0%, and 95.3%, respectively. The vacA gene alleles had a prevalence of 95.3% for vacAs1/s2, 52.8% for vacAm1, and 42.5% for vacAm2. The CC genotype of TLR9 -1486T/C had a significantly higher frequency in gastric cancer patients when compared to healthy participants (p = 0.045). Furthermore, the CC genotype demonstrated a significant association with H. pylori strains carrying sodB, hsp60, and vacAm1 virulence genes (p = 0.021, p = 0.049, and p = 0.048 respectively). Patients with CC genotype of TLR9 -1486T/C (rs187084) might be at higher risk for the development of gastric cancer, and its co-existence with H. pylori strains carrying sodB, hsp60, or vacAm1 virulence genes might have a synergistic effect in the development of gastric cancer. Further studies on a wider scale are recommended.
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Affiliation(s)
- Amira M. Sultan
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ragy Shenouda
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad M. Sultan
- Gastroenterology Surgical Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Shehta
- Gastroenterology Surgical Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Yasmin Nabiel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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29
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Sekar R, Preethi M, Mohammed J. Quantification of Helicobacter pylori and its oncoproteins in oral cavity. A cross sectional study. Oral Dis 2022; 29:1868-1874. [PMID: 35092112 DOI: 10.1111/odi.14141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 12/30/2021] [Accepted: 01/20/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To identify Helicobacter pylori (H.pylori) and related oncogenic and virulent proteins (CagA and VacA) in patients with gingivitis, periodontitis, oral cancer and gastric cancer. METHODS Subgingival plaque samples were collected from 90 individuals with either gingivitis/ periodontitis (group A, n=30), oral cancer (group B, n=30) and gastric cancer (group C, n=30). H.pylori was identified by real time- polymerase chain reaction (RT-PCR). The virulent organisms were detected by identification of proteins CagA and VacA through Enzyme Linked Immuno Sorbent Assay (ELISA). RESULTS We identified the presence of H.pylori in subgingival plaque samples among a large majority (76/90) of our study cohort. The proportions of CagA and VacA identified among H.pylori individuals with periodontal inflammation and oral cancer were lower than those diagnosed with gastric cancer. Furthermore, the relative risk of oral cancer based on the presence of the organism was no different to those with gingivitis/periodontitis. CONCLUSION The findings of our study does not indicate significant association between the organism and oral cancer but preludes that the oral cavity could act as a potential niche for H.pylori. The possibility for CagA and VacA proteins to be pathogenic in oral cavity is highly possible and to be researched extensively.
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Affiliation(s)
- Ramya Sekar
- Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College and Hospital, Maduravoyal, Chennai, 600 095, India
| | - Murali Preethi
- Department of Oral and Maxillofacial Pathology, Meenakshi Ammal Dental College and Hospital, Maduravoyal, Chennai, 600 095, India
| | - Junaid Mohammed
- School of Population and Global Health, University of Western Australia, Clifton Street Building, Clifton street, Nedlands, 6009, Western Australia, Australia.,Telethon Kids Institute, University of Western Australia, Nedlands, 6009, Western Australia, Australia
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30
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Idris AB, Idris AB, Gumaa MA, Idris MB, Elgoraish A, Mansour M, Allam D, Arbab BMO, Beirag N, Ibrahim EAM, Hassan MA. Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach. World J Gastroenterol 2022; 28:242-262. [PMID: 35110948 PMCID: PMC8776532 DOI: 10.3748/wjg.v28.i2.242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/13/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.
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Affiliation(s)
- Abeer Babiker Idris
- Department of Agricultural Science and Technology, Institute of Natural and Applied Sciences, Erciyes University, Kayseri 38039, Turkey
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan.
| | - Alaa B Idris
- Department of Neurosurgery, Ribat University Hospital, Khartoum 11111, Sudan
| | - Manal A Gumaa
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan
| | - Mohammed Babiker Idris
- BioMérieux Clinical and Application Advisor, Al-Jeel Medical Co., Riyadh 11422, Saudi Arabia
| | - Amanda Elgoraish
- Department of Epidemiology, Tropical Medicine Research Institute, Khartoum 11111, Sudan
| | - Mohamed Mansour
- Department of Gastroenterology, Ibn Sina Specialized Hospital, Khartoum 11111, Sudan
| | - Dalia Allam
- Department of Gastroenterology, Ibn Sina Specialized Hospital, Khartoum 11111, Sudan
| | - Bashir MO Arbab
- Department of Gastroenterology, Modern Medical Centre, Khartoum 11111, Sudan
| | - Nazar Beirag
- Biosciences, College of Health, Medicine and Life Sciences, Brunel University, London UB8 3PH, Uxbridge, United Kingdom
| | - El-Amin M Ibrahim
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum 11111, Sudan
| | - Mohamed A Hassan
- Department of Bioinformatics, Africa city of technology, Khartoum 11111, Sudan
- Department of Bioinformatics, DETAGEN Genetic Diagnostics Center, Kayseri 38350, Turkey
- Department of Translation Bioinformatics, Detavax Biotech, Kayseri 38350, Turkey
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Kim HS, Kim S, Shin SJ, Park YH, Nam Y, Kim CW, Lee KW, Kim SM, Jung ID, Yang HD, Park YM, Moon M. Gram-negative bacteria and their lipopolysaccharides in Alzheimer's disease: pathologic roles and therapeutic implications. Transl Neurodegener 2021; 10:49. [PMID: 34876226 PMCID: PMC8650380 DOI: 10.1186/s40035-021-00273-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 11/09/2021] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD) is the most serious age-related neurodegenerative disease and causes destructive and irreversible cognitive decline. Failures in the development of therapeutics targeting amyloid-β (Aβ) and tau, principal proteins inducing pathology in AD, suggest a paradigm shift towards the development of new therapeutic targets. The gram-negative bacteria and lipopolysaccharides (LPS) are attractive new targets for AD treatment. Surprisingly, an altered distribution of gram-negative bacteria and their LPS has been reported in AD patients. Moreover, gram-negative bacteria and their LPS have been shown to affect a variety of AD-related pathologies, such as Aβ homeostasis, tau pathology, neuroinflammation, and neurodegeneration. Moreover, therapeutic approaches targeting gram-negative bacteria or gram-negative bacterial molecules have significantly alleviated AD-related pathology and cognitive dysfunction. Despite multiple evidence showing that the gram-negative bacteria and their LPS play a crucial role in AD pathogenesis, the pathogenic mechanisms of gram-negative bacteria and their LPS have not been clarified. Here, we summarize the roles and pathomechanisms of gram-negative bacteria and LPS in AD. Furthermore, we discuss the possibility of using gram-negative bacteria and gram-negative bacterial molecules as novel therapeutic targets and new pathological characteristics for AD.
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Affiliation(s)
- Hyeon Soo Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Sujin Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
- Research Institute for Dementia Science, Konyang University, Daejeon, 35365, Republic of Korea
| | - Soo Jung Shin
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Yong Ho Park
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Yunkwon Nam
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Chae Won Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Kang Won Lee
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea
| | - Sung-Min Kim
- Dandi Bioscience Inc, 6th Floor of Real Company Building, 66, Achasan-ro, Sungdong-gu, Seoul, Republic of Korea
| | - In Duk Jung
- Dandi Bioscience Inc, 6th Floor of Real Company Building, 66, Achasan-ro, Sungdong-gu, Seoul, Republic of Korea
| | - Hyun Duk Yang
- Harvard Neurology Clinic, 294 Gwanggyojungang-ro, Suji-gu, Yongin, 16943, Republic of Korea.
| | - Yeong-Min Park
- Dandi Bioscience Inc, 6th Floor of Real Company Building, 66, Achasan-ro, Sungdong-gu, Seoul, Republic of Korea.
- Department of Immunology, School of Medicine, Konkuk University, 268, Chungwondaero, Chungju-si, Chungcheongbuk-do, Republic of Korea.
| | - Minho Moon
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
- Research Institute for Dementia Science, Konyang University, Daejeon, 35365, Republic of Korea.
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Bian Y, Chen X, Cao H, Xie D, Zhu M, Yuan N, Lu L, Lu B, Wu C, Bahaji Azami NL, Wang Z, Wang H, Zhang Y, Li K, Ye G, Sun M. A correlational study of Weifuchun and its clinical effect on intestinal flora in precancerous lesions of gastric cancer. Chin Med 2021; 16:120. [PMID: 34801051 PMCID: PMC8605594 DOI: 10.1186/s13020-021-00529-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 10/31/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Weifuchun (WFC), a Chinese herbal prescription consisting of Red Ginseng, Isodon amethystoides and Fructus Aurantii, is commonly used in China to treat a variety of chronic stomach disorders. The aim of the paper was to determine the effect of WFC on intestinal microbiota changes in precancerous lesions of gastric cancer (PLGC) patients. METHODS PLGC patients of H. pylori negative were randomly divided into two groups and received either WFC tablets for a dose of 1.44 g three times a day or vitacoenzyme (Vit) tablets for a dose of 0.8 g three times a day. All patients were treated for 6 months consecutively. Gastroscopy and histopathology were used to assess the histopathological changes in gastric tissues before and after treatment. 16S rRNA gene sequencing was carried out to assess the effects WFC on intestinal microbiota changes in PLGC patients. Receiver Operating Characteristics (ROC) analysis was used to assess the sensitivity and specificity of different intestinal microbiota in distinguishing between PLGC patients and healthy control group. RESULTS Gastroscopy and histopathological results indicated that WFC could improve the pathological condition of PLGC patients, especially in the case of atrophy or intestinal metaplasia. The results of 16S rRNA gene sequencing indicated that WFC could regulate microbial diversity, microbial composition, and abundance of the intestinal microbiota of PLGC patients. Following WFC treatment, the relative abundance of Parabacteroides decreased in WFC group when compared with the Vit group. ROC analysis found that the Parabacteroides could effectively distinguish PLGC patients from healthy individuals with sensitivity of 0.79 and specificity of 0.8. CONCLUSIONS WFC could slow down the progression of PLGC by regulating intestinal microbiota abundance. Trial registration NCT03814629. Name of registry: Randomized Clinical Trial: Weifuchun Treatment on Precancerous Lesions of Gastric Cancer. Registered 3 August 2018-Retrospectively registered, https://register.clinicaltrials.gov/ NCT03814629.
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Affiliation(s)
- Yanqin Bian
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
- Arthritis Institute of Integrated Traditional Chinese and Western Medicine, Shanghai Academy of Traditional Chinese Medicine, Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200052, China
| | - Xi Chen
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
- Department of Infectious Disease and Gastroenterology, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200080, China
| | - Hongyan Cao
- Department of Infectious Disease and Gastroenterology, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200080, China
| | - Dong Xie
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Meiping Zhu
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Nong Yuan
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Lu Lu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Bingjie Lu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Chao Wu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Nisma Lena Bahaji Azami
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Zheng Wang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China
| | - Huijun Wang
- Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 4, No. 898, Halei Road, Pudong New Area, Shanghai, 201203, China
| | - Yeqing Zhang
- Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 4, No. 898, Halei Road, Pudong New Area, Shanghai, 201203, China
| | - Kun Li
- Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 4, No. 898, Halei Road, Pudong New Area, Shanghai, 201203, China
| | - Guan Ye
- Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 4, No. 898, Halei Road, Pudong New Area, Shanghai, 201203, China.
| | - Mingyu Sun
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, 201203, China.
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Cieślik M, Bagińska N, Górski A, Jończyk-Matysiak E. Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response. Cells 2021; 10:cells10112991. [PMID: 34831214 PMCID: PMC8616480 DOI: 10.3390/cells10112991] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/28/2021] [Accepted: 10/30/2021] [Indexed: 12/17/2022] Open
Abstract
Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.
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Affiliation(s)
- Martyna Cieślik
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland; (M.C.); (N.B.); (E.J.-M.)
| | - Natalia Bagińska
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland; (M.C.); (N.B.); (E.J.-M.)
| | - Andrzej Górski
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland; (M.C.); (N.B.); (E.J.-M.)
- Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland
- Infant Jesus Hospital, The Medical University of Warsaw, 02-006 Warsaw, Poland
- Correspondence:
| | - Ewa Jończyk-Matysiak
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland; (M.C.); (N.B.); (E.J.-M.)
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Bakhti SZ, Latifi-Navid S. Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis. BMC Microbiol 2021; 21:258. [PMID: 34556055 PMCID: PMC8461988 DOI: 10.1186/s12866-021-02315-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/07/2021] [Indexed: 01/10/2023] Open
Abstract
Chronic Helicobacter pylori infection is a critical risk factor for gastric cancer (GC). However, only 1-3 % of people with H. pylori develop GC. In gastric carcinogenesis, non-H. pylori bacteria in the stomach might interact with H. pylori. Bacterial dysbiosis in the stomach can strengthen gastric neoplasia development via generating tumor-promoting metabolites, DNA damaging, suppressing antitumor immunity, and activating oncogenic signaling pathways. Other bacterial species may generate short-chain fatty acids like butyrate that may inhibit carcinogenesis and inflammation in the human stomach. The present article aimed at providing a comprehensive overview of the effects of gut microbiota and H. pylori on the development of GC. Next, the potential mechanisms of intestinal microbiota were discussed in gastric carcinogenesis. We also disserted the complicated interactions between H. pylori, intestinal microbiota, and host in gastric carcinogenesis, thus helping us to design new strategies for preventing, diagnosing, and treating GC.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 56199-11367, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 56199-11367, Ardabil, Iran.
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Jafarzadeh A, Marzban H, Nemati M, Jafarzadeh S, Mahjoubin-Tehran M, Hamblin MR, Mirzaei H, Mirzaei HR. Dysregulated expression of miRNAs in immune thrombocytopenia. Epigenomics 2021; 13:1315-1325. [PMID: 34498489 DOI: 10.2217/epi-2021-0092] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In recent years the critical role of miRNAs has been established in many diseases, including autoimmune disorders. Immune thrombocytopenia purpura (ITP) is a predominant autoimmune disease, in which aberrant expression of miRNAs has been observed, suggesting that miRNAs are involved in its development. miRNAs could induce an imbalance in the T helper (Th)1/Th2 cell and Th17/Treg cell-related responses. Moreover, they could also cause alterations in Th9 and Th22 cell responses, and activate Tfh (T follicular helper) cell-dependent auto-reactive B cells, thus influencing megakaryogenesis. Herein, we summarize the role of immune-related miRNAs in ITP pathogenesis, and look forward to clinical applications.
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Affiliation(s)
- Abdollah Jafarzadeh
- Department of Immunology, School of Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran.,Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, 7718175911, Rafsanjan, Iran
| | - Havva Marzban
- Department of Pathology & Experimental Animals, Razi Vaccine & Serum Research Institute, Agricultural Research, Education & Extension Organization (AREEO), 31975/148 Karaj, Iran
| | - Maryam Nemati
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, 77181/75911, Rafsanjan, Iran.,Department of Hematology & Laboratory Sciences, School of Para-Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran
| | - Sara Jafarzadeh
- Student Research Committee, School of Medicine, Kerman University of Medical Sciences, 76169-13555, Kerman, Iran
| | - Maryam Mahjoubin-Tehran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, 13131- 99137, Mashhad, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, 2028 Doornfontein, South Africa
| | - Hamed Mirzaei
- Research Center for Biochemistry & Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, 87159-88141, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, 87159-88141, Kashan, Iran
| | - Hamid Reza Mirzaei
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, 1417613151, Tehran, Iran
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Ailloud F, Estibariz I, Suerbaum S. Evolved to vary: genome and epigenome variation in the human pathogen Helicobacter pylori. FEMS Microbiol Rev 2021; 45:5900976. [PMID: 32880636 DOI: 10.1093/femsre/fuaa042] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is a Gram-negative, spiral shaped bacterium that selectively and chronically infects the gastric mucosa of humans. The clinical course of this infection can range from lifelong asymptomatic infection to severe disease, including peptic ulcers or gastric cancer. The high mutation rate and natural competence typical of this species are responsible for massive inter-strain genetic variation exceeding that observed in all other bacterial human pathogens. The adaptive value of such a plastic genome is thought to derive from a rapid exploration of the fitness landscape resulting in fast adaptation to the changing conditions of the gastric environment. Nevertheless, diversity is also lost through recurrent bottlenecks and H. pylori's lifestyle is thus a perpetual race to maintain an appropriate pool of standing genetic variation able to withstand selection events. Another aspect of H. pylori's diversity is a large and variable repertoire of restriction-modification systems. While not yet completely understood, methylome evolution could generate enough transcriptomic variation to provide another intricate layer of adaptive potential. This review provides an up to date synopsis of this rapidly emerging area of H. pylori research that has been enabled by the ever-increasing throughput of Omics technologies and a multitude of other technological advances.
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Affiliation(s)
- Florent Ailloud
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Iratxe Estibariz
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany
| | - Sebastian Suerbaum
- Max von Pettenkofer Institute, Faculty of Medicine, LMU München, Pettenkoferstr. 9a, 80336 München, Germany.,DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Pettenkoferstr. 9a, 80336 München, Germany.,National Reference Center for Helicobacter pylori, Pettenkoferstr. 9a, 80336 München, Germany
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Yousefi L, Osquee HO, Ghotaslou R, Rezaee MA, Pirzadeh T, Sadeghi J, Hemmati F, Yousefi B, Moaddab SY, Yousefi M, Shirmohammadi M, Somi MH, Ganbarov K, Kafil HS. Dysregulation of lncRNA in Helicobacter pylori-Infected Gastric Cancer Cells. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6911734. [PMID: 34337048 PMCID: PMC8286195 DOI: 10.1155/2021/6911734] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/25/2021] [Accepted: 06/30/2021] [Indexed: 12/31/2022]
Abstract
Helicobacter pylori (H. pylori) infection is the most common cause of gastric cancer (GC). This microorganism is genetically diverse; GC is caused by several genetic deregulations in addition to environmental factors and bacterial virulence factors. lncRNAs (long noncoding RNAs) are significant biological macromolecules in GC, have specific functions in diseases, and could be therapeutic targets. Altered lncRNAs can lead to the abnormal expression of adjacent protein-coding genes, which may be important in cancer development. Their mechanisms have not been well understood, so we are going to investigate the risk of GC in a population with both high lncRNA and H. pylori infection.
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Affiliation(s)
- Leila Yousefi
- Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Owaysee Osquee
- Pharmaceutical Nanotechnology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Ghotaslou
- Pharmaceutical Nanotechnology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Tahereh Pirzadeh
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javid Sadeghi
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Hemmati
- Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahman Yousefi
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyed Yaghoub Moaddab
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Shirmohammadi
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Hossein Samadi Kafil
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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de Brito BB, Lemos FFB, Carneiro CDM, Viana AS, Barreto NMPV, Assis GADS, Braga BDC, Santos MLC, Silva FAFD, Marques HS, Silva NOE, de Melo FF. Immune response to Helicobacter pylori infection and gastric cancer development. World J Meta-Anal 2021; 9:257-276. [DOI: 10.13105/wjma.v9.i3.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
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Raj R, Agarwal N, Raghavan S, Chakraborti T, Poluri KM, Pande G, Kumar D. Epigallocatechin Gallate with Potent Anti- Helicobacter pylori Activity Binds Efficiently to Its Histone-like DNA Binding Protein. ACS OMEGA 2021; 6:3548-3570. [PMID: 33585739 PMCID: PMC7876696 DOI: 10.1021/acsomega.0c04763] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/21/2021] [Indexed: 05/10/2023]
Abstract
Helicobacter pylori (H. pylori)-a human gastric pathogen-forms a major risk factor for the development of various gastric pathologies such as chronic inflammatory gastritis, peptic ulcer, lymphomas of mucosa-associated lymphoid tissues, and gastric carcinoma. The complete eradication of infection is the primary objective of treating any H. pylori-associated gastric condition. However, declining eradication efficiencies, off-target effects, and patient noncompliance to prolong and broad-spectrum antibiotic treatments has spurred the clinical interest to search for alternative effective and safer therapeutic options. As natural compounds are safe and privileged with high levels of antibacterial-activity, previous studies have tested and reported a plethora of such compounds with potential in vitro/in vivo anti-H. pylori activity. However, the mode of action of majority of these natural compounds is unclear. The present study has been envisaged to compile the information of various such natural compounds and to evaluate their binding with histone-like DNA-binding proteins of H. pylori (referred here as Hup) using in silico molecular docking-based virtual screening experiments. Hup-being a major nucleoid-associated protein expressed by H. pylori-plays a strategic role in its survival and persistent colonization under hostile stress conditions. The ligand with highest binding energy with Hup-that is, epigallocatechin-(-)gallate (EGCG)-was rationally selected for further computational and experimental testing. The best docking poses of EGCG with Hup were first evaluated for their solution stability using long run molecular dynamics simulations and then using fluorescence and nuclear magnetic resonance titration experiments which demonstrated that the binding of EGCG with Hup is fairly strong (the resultant apparent dissociation constant (k D) values were equal to 2.61 and 3.29 ± 0.42 μM, respectively).
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Affiliation(s)
- Ritu Raj
- Centre
of Biomedical Research (CBMR), SGPGIMS Campus, Raibareli Road, Lucknow 226014, Uttar Pradesh, India
- Department
of Biochemistry & Biophysics, University
of Kalyani, Kalyani 741235, West Bengal, India
| | - Nipanshu Agarwal
- Department
of Biotechnology and Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
| | - Sriram Raghavan
- Computational
Structural Biology Team, RIKEN Center for
Computational Science (R-CCS), Kobe 650-0047, Japan
| | - Tapati Chakraborti
- Department
of Biochemistry & Biophysics, University
of Kalyani, Kalyani 741235, West Bengal, India
| | - Krishna Mohan Poluri
- Department
of Biotechnology and Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
| | - Gaurav Pande
- Department
of Gastroeneterology, SGPGIMS, Lucknow 226014, Uttar Pradesh, India
- . Phone: +91-9170689999
| | - Dinesh Kumar
- Centre
of Biomedical Research (CBMR), SGPGIMS Campus, Raibareli Road, Lucknow 226014, Uttar Pradesh, India
- . Phone: +91-8953261506
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40
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Idris AB, Idris EB, Ataelmanan AE, Mohamed AEA, Osman Arbab BM, Ibrahim EAM, Hassan MA. First insights into the molecular basis association between promoter polymorphisms of the IL1B gene and Helicobacter pylori infection in the Sudanese population: computational approach. BMC Microbiol 2021; 21:16. [PMID: 33413117 PMCID: PMC7792167 DOI: 10.1186/s12866-020-02072-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infects nearly half of the world's population with a variation in incidence among different geographic regions. Genetic variants in the promoter regions of the IL1B gene can affect cytokine expression and creates a condition of hypoacidity which favors the survival and colonization of H. pylori. Therefore, the aim of this study was to characterize the polymorphic sites in the 5'- region [-687_ + 297] of IL1B in H. pylori infection using in silico tools. RESULTS A total of five nucleotide variations were detected in the 5'-regulatory region [-687_ + 297] of IL1B which led to the addition or alteration of transcription factor binding sites (TFBSs) or composite regulatory elements (CEs). Genotyping of IL1B - 31 C > T revealed a significant association between -31 T and susceptibility to H. pylori infection in the studied population (P = 0.0363). Comparative analysis showed conservation rates of IL1B upstream [-368_ + 10] region above 70% in chimpanzee, rhesus monkey, a domesticated dog, cow and rat. CONCLUSIONS In H. pylori-infected patients, three detected SNPs (- 338, - 155 and - 31) located in the IL1B promoter were predicted to alter TFBSs and CE, which might affect the gene expression. These in silico predictions provide insight for further experimental in vitro and in vivo studies of the regulation of IL1B expression and its relationship to H. pylori infection. However, the recognition of regulatory motifs by computer algorithms is fundamental for understanding gene expression patterns.
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Affiliation(s)
- Abeer Babiker Idris
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Einas Babiker Idris
- Medical Laboratory Specialist, Department of Medical Microbiology, Rashid Medical Complex, Riyadh, Saudi Arabia
| | - Amany Eltayib Ataelmanan
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Al-Gazirah, Wad Madani, Sudan
| | | | | | - El-Amin Mohamed Ibrahim
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Mohamed A. Hassan
- Department of Bioinformatics, Africa city of technology, Khartoum, Sudan
- Department of Bioinformatics, DETAGEN Genetic Diagnostics Center, Kayseri, Turkey
- Department of Translation Bioinformatics, Detavax Biotech, Kayseri, Turkey
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41
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Kim N. Reversal of the Methylation-Associated Regulation of miR-200a/b by Helicobacter pylori Eradication Contributes to the Chemoprevention of Gastric Carcinogenesis. Gut Liver 2020; 14:533-534. [PMID: 32921637 PMCID: PMC7492488 DOI: 10.5009/gnl20251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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42
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Gohir W, Klement W, Singer LG, Palmer SM, Mazzulli T, Keshavjee S, Husain S. Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus. J Heart Lung Transplant 2020; 39:1228-1237. [PMID: 32771440 DOI: 10.1016/j.healun.2020.07.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 07/06/2020] [Accepted: 07/17/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs of ∼22 nucleotides that play a crucial role in post-transcriptional regulation of gene expression. Dysregulation of miRNA expression has been shown during microbial infections. We sought to identify miRNAs that distinguish invasive aspergillosis (IA) from non-IA in lung transplant recipients (LTRs). METHODS We used NanoString nCounter Human miRNA, version 3, panel to measure miRNAs in bronchoalveolar lavage (BAL) samples from LTRs with Aspergillus colonization (ASP group) (n = 10), those with Aspergillus colonization and chronic lung allograft dysfunction (CLAD) (ASPCLAD group) (n = 7), those with IA without CLAD (IA group) (n = 10), those who developed IA with CLAD (IACLAD group) (n = 9), and control patients (controls) (n = 9). The miRNA profile was compared using the permutation test of 100,000 trials for each of the comparisons. We used mirDIP to obtain their gene targets and pathDIP to determine the pathway enrichment. RESULTS We performed pairwise comparisons between patient groups to identify differentially expressed miRNAs. A total of 5 miRNAs were found to be specific to IA, including 4 (miR-145-5p, miR-424-5p, miR-99b-5p, and miR-4488) that were upregulated and the pair (miR-4454 + miR-7975) that was downregulated in IA group vs controls. The expression change for these miRNAs was specific to patients with IA; they were not significantly differentiated between IACLAD and IA groups. Signaling pathways associated with an immunologic response to IA were found to be significantly enriched. CONCLUSIONS We report a set of 5 differentially expressed miRNAs in the BAL of LTRs with IA that might help in the development of diagnostic and prognostic tools for IA in LTRs. However, further investigation is needed in a larger cohort to validate the findings.
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Affiliation(s)
- Wajiha Gohir
- Transplant Infectious Diseases, Ajmera Family Transplant Centre
| | - William Klement
- Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Lianne G Singer
- Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Scott M Palmer
- Division of Pulmonary and Critical Care Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina
| | - Tony Mazzulli
- Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Shaf Keshavjee
- Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Shahid Husain
- Transplant Infectious Diseases, Ajmera Family Transplant Centre.
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Zendehdel A, Roham M. Role of Helicobacter pylori infection in the manifestation of old age-related diseases. Mol Genet Genomic Med 2020; 8:e1157. [PMID: 32067423 PMCID: PMC7196471 DOI: 10.1002/mgg3.1157] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 11/10/2019] [Accepted: 01/11/2020] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori is one of the most prevalent infection worldwide. It affects individuals of different age groups. Elderly people tend to resist eradication treatment and worsening of infection can lead to several gastric and non-gastric pathologies. Aging-associated cellular and molecular alteration can increase the risk of other pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, respiratory and renal dysfunction, and cancer in geriatric patients, more than other age groups. This review article highlights some of the most common old age diseases and the role of H. pylori infection as a risk factor to worsen the conditions, presented by the molecular evidences of these associations. These studies can help clinicians to understand the underlying pathogenesis of the disease and identify high-risk patients, aiding clearer diagnosis and treatment.
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Affiliation(s)
- Abolfazl Zendehdel
- Department of Geriatric MedicineZiaeian HospitalTehran University of Medical SciencesTehranIran
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Park H, Cho D, Huang E, Seo JY, Kim WG, Todorov SD, Ji Y, Holzapfel WH. Amelioration of Alcohol Induced Gastric Ulcers Through the Administration of Lactobacillus plantarum APSulloc 331261 Isolated From Green Tea. Front Microbiol 2020; 11:420. [PMID: 32256476 PMCID: PMC7090068 DOI: 10.3389/fmicb.2020.00420] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/27/2020] [Indexed: 12/12/2022] Open
Abstract
Gastric inflammation is an indication of gastric ulcers and possible other underlying gastric malignancies. Epidemiological studies have revealed that several Asian countries, including South Korea, suffer from a high incidence of gastric diseases derived from high levels of stress, alcoholic consumption, pyloric infection and usage of non-steroidal anti-inflammatory drugs (NSAIDs). Clinical treatments of gastric ulcers are generally limited to proton pump inhibitors that neutralize the stomach acid, and the application of antibiotics for Helicobacter pylori eradication, both of which are known to have a negative effect on the gut microbiota. The potential of probiotics for alleviating gastrointestinal diseases such as intestinal bowel syndrome and intestinal bowel disease receives increasing scientific interest. Probiotics may support the amelioration of disease-related symptoms through modulation of the gut microbiota without causing dysbiosis. In this study the potential of Lactobacillus plantarum APSulloc 331261 (GTB1TM), isolated from green tea, was investigated for alleviating gastric inflammation in an alcohol induced gastric ulcer murine model (positive control). Treatment with the test strain significantly influenced the expression of pro-inflammatory and anti-inflammatory biomarkers, interleukin 6 (IL6) and interleukin 10 (IL10), of which the former was down- and the latter up-regulated when the alcohol induced mice were treated with the test strain. This positive effect was also indicated by less severe gastric morphological changes and the histological score of the gastric tissues. A significant increase in the abundance of Akkermansia within the GTB1TM treated group compared to the positive control group also correlated with a decrease in the ratio of acetate over propionate. The increased levels of propionate in the GTB1TM group appear to result from the impact of the test strain on the microbial population and the resulting metabolic activities. Moreover, there was a significant increase in beta-diversity in the group that received GTB1TM over that of the alcohol induced control group.
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Affiliation(s)
- Haryung Park
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
| | - Donghyun Cho
- Vital Beautie Research Division, Amore Pacific R&D Unit, Gyeonggi-do, South Korea
| | - Eunchong Huang
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
| | - Ju Yeon Seo
- Vital Beautie Research Division, Amore Pacific R&D Unit, Gyeonggi-do, South Korea
| | - Wan Gi Kim
- Vital Beautie Research Division, Amore Pacific R&D Unit, Gyeonggi-do, South Korea
| | | | - Yosep Ji
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
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Kumar V, Das S, Kumar A, Tiwari N, Kumar A, Abhishek K, Mandal A, Kumar M, Shafi T, Bamra T, Singh RK, Vijayakumar S, Sen A, Das P. Leishmania donovani infection induce differential miRNA expression in CD4+ T cells. Sci Rep 2020; 10:3523. [PMID: 32103111 PMCID: PMC7044172 DOI: 10.1038/s41598-020-60435-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 01/20/2020] [Indexed: 12/12/2022] Open
Abstract
Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host upon Leishmania infection. However, the regulatory mechanism for Th1/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells with Leishmania donovani infected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p < 0.05), which were validated by qPCR. Further, using insilco approach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1/2 dichotomy upon Leishmania donovani infection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in Leishmania donovani infection.
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Affiliation(s)
- Vinod Kumar
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Sushmita Das
- Department of Microbiology, All India Institute of Medical Sciences, Phulwarisharif, Patna, Bihar, India
| | - Ajay Kumar
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Neeraj Tiwari
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Ashish Kumar
- Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Kumar Abhishek
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Abhishek Mandal
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Manjay Kumar
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Taj Shafi
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Tanvir Bamra
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Rakesh Kumar Singh
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Saravanan Vijayakumar
- Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Abhik Sen
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India
| | - Pradeep Das
- Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India.
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H.pylori Infection Alleviates Acute and Chronic Colitis with the Expansion of Regulatory B Cells in Mice. Inflammation 2020; 42:1611-1621. [PMID: 31377948 DOI: 10.1007/s10753-019-01022-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Epidemiological studies showed that there was an inverse relationship between Helicobacter pylori (H. pylori) infection and the incidence of inflammatory bowel diseases (IBD). Our previous research indicated that the regulatory immune responses induced by H. pylori infection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, mice were infected with H. pylori SS1, and then colitis was induced by 3% dextran sulphate sodium (DSS), to investigate the role of the regulatory B cells in the effects of H. pylori infection on acute and chronic colitis. In acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less, the proinflammatory cytokines mRNA expression downregulated in colonic mucosa, and the percentages of CD19+IL-10+Breg cells were higher in the H. pylori/DSS co-treated groups compared with the DSS-treated groups. Our study suggests that H. pylori infection can alleviate the acute and chronic colitis induced by DSS, and CD19+IL-10+Breg cells may play a critical role in the alleviation of acute and chronic colitis following H. pylori infection.
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Yousefi B, Mohammadlou M, Abdollahi M, Salek Farrokhi A, Karbalaei M, Keikha M, Kokhaei P, Valizadeh S, Rezaiemanesh A, Arabkari V, Eslami M. Epigenetic changes in gastric cancer induction by Helicobacter pylori. J Cell Physiol 2019; 234:21770-21784. [PMID: 31169314 DOI: 10.1002/jcp.28925] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 05/06/2019] [Accepted: 05/07/2019] [Indexed: 02/05/2023]
Abstract
Epigenetic disorder mechanisms are one of the causes of cancer. The most important of these changes is the DNA methylation, which leads to the spread of Helicobacter pylori and inflammatory processes followed by induction of DNA methylation disorder. Mutations and epigenetic changes are the two main agents of neoplasia. Epithelial cells infection by H. pylori associated with activating several intracellular pathways including: MAPK, NF-κB, Wnt/β-catenin, and PI3K are affects a variety of cells and caused to an increase in the production of inflammatory cytokines, changes in apoptosis, proliferation, differentiation, and ultimately leads to the transformation of epithelial cells into oncogenic. The arose of free radicals impose the DNA cytosine methylation, and NO can increase the activity of DNA methyltransferase. H. pylori infection causes an environment that mediates inflammation and signaling pathways that probably caused to stomach tumorigenicity. The main processes that change by decreasing or increasing the expression of various microRNAs expressions include immune responses, apoptosis, cell cycle, and autophagy. In this review will be describe a probably H. pylori roles in infection and mechanisms that have contribution in epigenetic changes in the promoter of genes.
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Affiliation(s)
- Bahman Yousefi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Maryam Mohammadlou
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Maryam Abdollahi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Amir Salek Farrokhi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Masoud Keikha
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parviz Kokhaei
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
- Immune and Gene Therapy Lab, Cancer Centre Karolinska, Karolinska University Hospital, Stockholm, Sweden
| | - Saeid Valizadeh
- Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran
| | - Alireza Rezaiemanesh
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Vahid Arabkari
- Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland
| | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
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Susi MD, Lourenço CDM, Rasmussen LT, Payão SLM, Rossi AFT, Silva AE, Oliveira-Cucolo JGD. Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population. World J Gastrointest Oncol 2019. [DOI: 10.4251/wjgo.v11.i11.0000] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Susi MD, Lourenço Caroline DM, Rasmussen LT, Payão SLM, Rossi AFT, Silva AE, Oliveira-Cucolo JGD. Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population. World J Gastrointest Oncol 2019; 11:998-1010. [PMID: 31798780 PMCID: PMC6883180 DOI: 10.4251/wjgo.v11.i11.998] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 07/26/2019] [Accepted: 08/28/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Toll-like receptors (TLRs) are the first line of host defense, and are involved in Helicobacter pylori (H. pylori) recognition and activation of both inflammatory and carcinogenic processes. The presence of single nucleotide polymorphisms (SNPs) in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer (GC). Among them, Toll-like receptor 9 (TLR9) polymorphisms have emerged with a risk factor of infectious diseases and cancer, however the studies are still inconclusive.
AIM To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis, and its influence on mRNA expression.
METHODS A case-control study was conducted to evaluate two TLR9 SNPs (TLR9-1237 TC-rs5743836 and TLR9-1486 CT-rs187084) in chronic gastritis (CG) and GC patients. A total of 609 DNA samples of peripheral blood [248 CG, 161 GC, and 200 samples from healthy individuals (C)] were genotyped by polymerase chain reaction-restriction fragment length polymorphism. All samples were tested for the H. pylori infection using Hpx1 and Hpx2 primers. Quantitative polymerase chain reaction by TaqMan® assay was used to quantify TLR9 mRNA from fresh gastric tissues (48 GC, 26 CG, and 14 C).
RESULTS For TLR9-1237, the TC + CC or CC genotypes were associated with a higher risk of GC than C [recessive model odds ratio (OR) = 5.01, 95% confidence interval (CI): 2.52-9.94, P < 0.0001], and the CG (recessive model OR =4.63; 95%CI: 2.44-8.79, P < 0.0001) groups. For TLR9-1486, an association between the CT + TT genotypes and increased risk of both GC (dominant model OR = 2.72, 95%CI: 1.57-4.72, P < 0.0001) and CG (dominant model OR = 1.79, 95%CI: 1.15-2.79, P = 0.0094) was observed when compared to the C group. Moreover, the presence of TLR9-1237 TC/CC + TLR9-1486 CC genotypes potentiate the risk for this neoplasm (OR = 18.57; 95%CI: 5.06-68.15, P < 0.0001). The TLR9 mRNA level was significantly higher in the GC group (RQ = 9.24, P < 0.0001) in relation to the CG group (RQ = 1.55, P = 0.0010) and normal mucosa (RQ = 1.0). When the samples were grouped according to the polymorphic genotypes and the presence of H. pylori infection, an influence of TLR9-1237 TC + CC polymorphic genotypes (P = 0.0083) and H. pylori infection (P < 0.0001) was observed on the upregulation of mRNA expression.
CONCLUSION Our findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric, and that TLR9 mRNA levels can be modulated by TLR9-1237 TC + CC variant genotypes and H. pylori infection.
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Affiliation(s)
- Manoela Dias Susi
- Department of Graduate-Level Research, USC-Sacred Heart University, Bauru 17011-970, SP, Brazil
| | | | - Lucas Trevizani Rasmussen
- Department of Genetics and Molecular Biology, FAMEMA-Marilia Medical School, Marília 17519-030, SP, Brazil
| | - Spencer Luis Marques Payão
- Department of Genetics and Molecular Biology, FAMEMA-Marilia Medical School, Marília 17519-030, SP, Brazil
| | - Ana Flávia Teixeira Rossi
- Department of Biology, São Paulo State University-UNESP, São José do Rio Preto 15054-000, SP, Brazil
| | - Ana Elizabete Silva
- Department of Biology, São Paulo State University-UNESP, São José do Rio Preto 15054-000, SP, Brazil
| | - Juliana Garcia de Oliveira-Cucolo
- Department of Molecular, Biological and Genetics and Molecular Biology Research Unit – UPGEM, Faculty of Medicine of São José do Rio Preto – FAMERP, São José do Rio Preto 15090-000, SP, Brazil
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Su T, Li F, Guan J, Liu L, Huang P, Wang Y, Qi X, Liu Z, Lu L, Wang D. Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 63:152968. [PMID: 31280140 DOI: 10.1016/j.phymed.2019.152968] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 04/30/2019] [Accepted: 05/21/2019] [Indexed: 05/21/2023]
Abstract
BACKGROUND Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.
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Key Words
- ARTS, artesunate
- Abbreviations: ART, artemisinin
- Artemisinin
- Artesunate
- CFU, colony forming units
- COX-2, cyclooxygenase-2
- DHA, dehydroartemisinin
- DMSO, dimethyl sulfoxide
- Dihydroartemisinin
- ELISA, enzyme-linked immunosorbent assay
- Gastric cancer
- Helicobacter pylori
- IARC, International Agency for Research on Cancer
- IL-8, interleukin-8
- MNU, N-methyl-N-nitroso-urea
- MOI, multiplicity of infection
- NF-κB signaling
- NF-κB, nuclear factor-κB
- PBS, phosphate buffer solution
- ROS, reactive oxygen species
- TNF-α, tumor necrosis factor-α
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Affiliation(s)
- Tao Su
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Fangyuan Li
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Jiaji Guan
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Linxin Liu
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ping Huang
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ying Wang
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xiaoxiao Qi
- Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhongqiu Liu
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Linlin Lu
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
| | - Dawei Wang
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, Guangdong, China.
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