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Sousa C, Ferreira R, Azevedo NF, Oleastro M, Azeredo J, Figueiredo C, Melo LDR. Helicobacter pylori infection: from standard to alternative treatment strategies. Crit Rev Microbiol 2021; 48:376-396. [PMID: 34569892 DOI: 10.1080/1040841x.2021.1975643] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is the major component of the gastric microbiome of infected individuals and one of the aetiological factors of chronic gastritis, peptic ulcer disease and gastric cancer. The increasing resistance to antibiotics worldwide has made the treatment of H. pylori infection a challenge. As a way to overhaul the efficacy of currently used H. pylori antibiotic-based eradication therapies, alternative treatment strategies are being devised. These include probiotics and prebiotics as adjuvants in H. pylori treatment, antimicrobial peptides as alternatives to antibiotics, photodynamic therapy ingestible devices, microparticles and nanoparticles applied as drug delivery systems, vaccines, natural products, and phage therapy. This review provides an updated synopsis of these emerging H. pylori control strategies and discusses the advantages, hurdles, and challenges associated with their development and implementation. An effective human vaccine would be a major achievement although, until now, projects regarding vaccine development have failed or were discontinued. Numerous natural products have demonstrated anti-H. pylori activity, mostly in vitro, but further clinical studies are needed to fully disclose their role in H. pylori eradication. Finally, phage therapy has the potential to emerge as a valid alternative, but major challenges remain, namely the isolation of more H. pylori strictly virulent bacterio(phages).
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Affiliation(s)
- Cláudia Sousa
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Rute Ferreira
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Nuno F Azevedo
- Faculty of Engineering, LEPABE - Department of Chemical Engineering, University of Porto, Porto, Portugal
| | - Mónica Oleastro
- Department of Infectious Diseases, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal
| | - Joana Azeredo
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.,Ipatimup - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.,Faculty of Medicine, Department of Pathology, University of Porto, Porto, Portugal
| | - Luís D R Melo
- Centre of Biological Engineering, University of Minho, Braga, Portugal
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Tiwari SK, Shaik AS, Shaik AP, Alyousef AA, Bardia A, Habeeb MA, Khan AA. Gene expression patterns of COX-1, COX-2 and iNOS in H. Pylori infected histopathological conditions. Microb Pathog 2019; 135:103634. [PMID: 31325568 DOI: 10.1016/j.micpath.2019.103634] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 07/17/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Research indicates that Helicobacter pylori can inflict severe histological damage through the modulation of host-related genes. The current study investigated the effect of H. pylori genotypes in the outcome of disease, and the expression of anti-apoptotic related genes, COX-1, COX-2, and iNOS genes in benign, pre-malignant, and malignant lesions of gastric carcinogenesis. MATERIALS AND METHODS Tissue samples from H. pylori positive patients were graded based on the genotype of the infected H. pylori strain. Expression of COX-1, COX-2 and iNOS was assessed using a combination of real-time PCR and immunohistochemistry. RESULTS Gene expression studies confirmed that COX-2 and iNOS expression was highly and selectively induced in epithelium with premalignant changes such as atrophic conditions, metaplasia and dysplasia, suggesting an important role of these genes in the sequence to gastric carcinoma of the intestinal type. Furthermore, the expression of COX-2 and iNOS was also dependent on the genotype of H. pylori and subjects with genotype-1 exhibited significantly higher expressions of COX-2 and iNOS compared to other genotypes. Comparison of the expression levels among infected and uninfected individuals demonstrated significant difference in the expression pattern of COX-2 gene whereas iNOS expression was found only in subjects infected H. pylori (p < 0.001). Immunohistochemical staining showed 1.5619 folds higher propensity of COX-2 and 3.2941 folds higher intensity of iNOS expression in subjects infected with H. pylori genotype 1. CONCLUSION The up-regulation of COX-2 and iNOS was associated with the genotype of the H. pylori strain and the presence of certain genotype may greatly affect early events during carcinogenesis.
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Affiliation(s)
- Santosh K Tiwari
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Asma Sultana Shaik
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abjal Pasha Shaik
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah A Alyousef
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Avinash Bardia
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Md Aejaz Habeeb
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Aleem A Khan
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India.
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Phull AR, Hassan M, Abbas Q, Raza H, Haq IU, Seo SY, Kim SJ. In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX-2 Inhibitory Efficacy of Coagulansin A of Withania coagulans. Chem Biodivers 2018; 15. [PMID: 29121447 DOI: 10.1002/cbdv.201700427] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 11/06/2017] [Indexed: 11/08/2022]
Abstract
Urease enzyme plays a crucial role in the survival of Helicobacter pylori that contributes to different diseases, including peptic ulcer (gastric and duodenal ulcers). Coagulansin A is the steroidal lactone (withanolide) found in plants of solanaceae family such Withania coagulans. The current study was carried out to examine the in vitro urease, COX-2 inhibitory activity and effect on type II collagen expression of coagulansin A. Moreover, we investigated cytotoxic effects on rabbit articular chondrocytes through MTT assay. COX-2 and type II collagen expressions were determined through a Western blot method. Molecular docking and simulation studies of urease (PDBID 4H9M) and COX-2 (PDBID 5F1A) proteins were also performed as an in silico approach. Results showed that COX-2 expression was decreased dose dependably, significantly higher expression of type II collagen was observed at higher doses. In the current study, coagulansin A was found as non-toxic, and showed notable urease inhibitory activity in non-competitive manner with IC50 23.14 μm in comparison to reference drug thiourea 17.81 μm. Significant decrease in COX-2 expression (40%) and increase in type II collagen (20%) were observed as compared to control. In silico results unveiled the strong binding affinities of coagulansin A with both of these urease and COX-2 proteins. Therefore, herein we proposed the significant antiurease potential of this compound that could be used in treating different diseases such as ulcers. Moreover, detailed in vivo studies and molecular mechanism based studies are suggested.
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Affiliation(s)
- Abdul Rehman Phull
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
| | - Mubshir Hassan
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
| | - Qamar Abbas
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
- Department of Physiology, University of Sindh, Jamshoro, 76080, Pakistan
| | - Hussain Raza
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
| | - Ihsan Ul Haq
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan
| | - Sung Yum Seo
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
| | - Song Ja Kim
- Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea
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CD14 overexpression upregulates TNF-α-mediated inflammatory responses and suppresses the malignancy of gastric carcinoma cells. Mol Cell Biochem 2013; 376:137-43. [PMID: 23338226 PMCID: PMC3576562 DOI: 10.1007/s11010-013-1559-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 01/09/2013] [Indexed: 01/07/2023]
Abstract
CD14 mediates the inflammatory response via recognition of lipopolysaccharide, which has been implicated in Helicobacter pylori (H. pylori) infections. Increasing evidence has suggested that CD14 status significantly influences the clinical outcome of H. pylori infection, which can result in gastric carcinoma. However, there is little evidence regarding the cellular impact and associated molecular basis of CD14 on gastric carcinoma cells. To address this question, we generated a CD14-overexpressing SGC-7901 gastric carcinoma cell line and analyzed the impact of CD14 expression. Our results revealed that cells overexpressing CD14 exhibited antitumor potential, including significantly decreased clonogenic ability, proliferation, metastatic invasion, as well as enhanced apoptosis, suggesting a tumor-suppressive role of CD14 in the cells. Intriguingly, we further discovered that CD14 overexpression activated NF-κB via upregulating its expression and simultaneously stimulating DNA binding activity. Upregulated NF-κB transcriptionally elevated a series of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-12. Together, the current study utilized a CD14-overexpressing gastric cell model to determine the impacts of CD14 upregulation on cell viability, apoptosis, and migration and NF-κB-mediated inflammation.
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Mu HM, Wu C, Zhang L, Pan KF, Ma JL, Zhang Y, Li WQ, Tu HK, Zeng HM, Liu WD, Zhou T, Lin DX, You WC. Genetic polymorphism of PSCA and risk of advanced precancerous gastric lesions in a Chinese population. Chin J Cancer Res 2010. [DOI: 10.1007/s11670-010-0099-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Zhao D, Sun T, Zhang X, Guo Y, Yu D, Yang M, Tan W, Wang G, Lin D. Role of CD14 promoter polymorphisms in Helicobacter pylori infection--related gastric carcinoma. Clin Cancer Res 2007; 13:2362-8. [PMID: 17438094 DOI: 10.1158/1078-0432.ccr-06-2612] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Genetic variation in CD14 may affect CD14 expression and susceptibility to Helicobacter pylori infection-related cancers. This study examined functional single nucleotide polymorphisms (SNP) in the CD14 promoter and their associations with risk of developing gastric carcinoma in relation to H. pylori infection. EXPERIMENTAL DESIGN Thirty individual DNAs were sequenced to identify variants, and the function of the variants was examined by reporter gene assays. Genotypes and haplotypes were analyzed in 470 patients and 470 controls, and odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Serologic H. pylori antibody and soluble CD14 (sCD14) levels were measured by ELISA. RESULTS Two SNPs (-651C>T and -260C>T) were identified, of which the -260CT and -260TT genotypes were associated with elevated risk of gastric carcinoma (OR, 1.77; 95% CI, 1.09-2.85 and OR, 1.95; 95% CI, 1.20-3.16, respectively). Haplotype analysis suggested a synergistic effect of the two SNPs (OR for the T(-651)-T(-260) haplotype, 3.39 versus OR for the C(-651)-T(-260) haplotype, 1.45; P = 0.02), which is consistent with reporter gene assays. A multiplicative joint effect between H. pylori infection and -260C>T polymorphism was observed (OR for the presence of both -260TT genotype and H. pylori infection, 4.03; 95% CI, 1.80-9.04). Patients had significantly higher sCD14 than controls (1,866 +/- 2,535 ng/mL versus 1,343 +/- 2,119 ng/mL; P < 0.001), and this difference was associated with the CD14 -260 polymorphism and H. pylori infection. CONCLUSIONS Functional polymorphism in CD14 is associated with greater risk of H. pylori-related gastric carcinoma, which might be mediated by elevated sCD14.
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Affiliation(s)
- Dan Zhao
- Department of Etiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Ouburg S, Bart A Crusius J, Klinkenberg-Knol EC, Mulder CJJ, Salvador Peña A, Morré SA. A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections. Eur J Gastroenterol Hepatol 2005; 17:1213-24. [PMID: 16215434 DOI: 10.1097/00042737-200511000-00010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.
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Affiliation(s)
- Sander Ouburg
- Department of Gastroenterology, Laboratory of Immunogenetics VU University Medical Centre, Amsterdam, The Netherlands
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Chang YJ, Wu MS, Lin JT, Sheu BS, Muta T, Inoue H, Chen CC. Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. Mol Pharmacol 2004; 66:1465-77. [PMID: 15456896 DOI: 10.1124/mol.104.005199] [Citation(s) in RCA: 123] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
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Affiliation(s)
- Ya Jen Chang
- Department of Pharmacology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
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Abstract
Symptoms of gastro-oesophageal reflux disease are highly prevalent in Western countries; however, it is less certain how many individuals with heartburn have clinically relevant disease. Although the prevalence of gastro-oesophageal reflux disease in Asia is substantially lower, the incidence may be increasing. How much of this increase is explained by the increasing recognition of heartburn in clinical practice, dietary changes and increasing obesity, or the eradication of Helicobacter pylori, remains unclear. There has been speculation that endoscopy-negative reflux disease represents a separate entity from reflux oesophagitis (as defined by the Los Angeles classification), but the evidence that might support this proposal is unconvincing. Patients with chronic reflux symptoms have a higher risk of Barrett's oesophagus, and the increased risk of developing oesophageal adenocarcinoma in individuals with a long history of heartburn is also well documented, but whether this always occurs via Barrett's oesophagus is debatable. Moreover, treatment with standard-dose antisecretory therapies and anti-reflux surgery seems unlikely, based on current evidence, to reduce the cancer risk in patients with Barrett's oesophagus. Gastro-oesophageal reflux disease has also been implicated in an increasing array of other conditions, but arguably in these settings it is often over-diagnosed.
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Affiliation(s)
- N J Talley
- Mayo Clinic College of Medicine and Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA.
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Bai Y, Zhang YL, Wang JD, Zhang ZS, Zhou DY. Construction of attenuated Salmonella typhimurium Strain expressing Helicobacter pylori conservative region of adhesin antigen and its immunogenicity. World J Gastroenterol 2004; 10:2498-502. [PMID: 15300892 PMCID: PMC4572149 DOI: 10.3748/wjg.v10.i17.2498] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To construct a non-resistant and attenuated Salmonella typhimurium (S. typhimurium) strain which expresses conservative region of adhesion AB of Helicobacter pylori (H pylori) and evaluate its immunogenicity.
METHODS: The AB gene amplified by PCR was inserted into the expression vector pYA248 containing asd gene and through two transformations introduced into the delta Cya, delta Crp, delta Asd attenuated Salmonella typhimurium strain, constructing balanced lethal attenuated Salmonella typhimurium strains X4072 (pYA248-AB). Bridged ELISA method was used to measure the expression of AB antigen in sonicate and culture supernatant. According to the method described by Meacock, stability of the recombinant was evaluated. Semi-lethal capacity test was used to evaluate the safety of recombinant. The immunogenicity of recombinant was evaluated with animal experiments.
RESULTS: The attenuated S. typhimurium X4072 (pYA248-AB) which expresses AB was successfully constructed. Furthermore, bridged ELISA assay showed that the content of AB in recombinant X4072 (pYA248- AB) culture supernatant was higher than that was in thallus lytic liquor. And after recombinant X4072 (pYA248- AB) was cultured for 100 generations without selection pressure, the entire recombinant bacteria selected randomly could grow, and the AB antigen was defected positive by ELISA. The growth curve of the recombinant bacteria showed that the growth states of X4072 (pYA248) and X4072 (pYA248-AB) were basically consistent. The survival rate of C57BL/6 was still 100%, at 30 d after mice taking X4072 (pYA248-AB) 1.0 × 1010 cfu orally. Oral immunization of mice with X4072 (pYA248-AB) induced a specific immune response.
CONCLUSION: In vitro recombinant plasmid appears to be stable and experiments on animals showed that the recombinant strains were safe and immunogenic in vitro, which providing a new live oral vaccine candidate for protection and care of H pylori infection.
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Affiliation(s)
- Yang Bai
- PLA Institute for Digestive Medicine, Nanfang Hospital, the First Military Medical University, Guangzhou 510515, Guangdong Province, China.
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Ruby E, Henderson B, McFall-Ngai M. Microbiology. We get by with a little help from our (little) friends. Science 2004; 303:1305-7. [PMID: 14988540 DOI: 10.1126/science.1094662] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Affiliation(s)
- Edward Ruby
- Pacific Biomedical Research Center, Kewalo Marine Laboratory, University of Hawaii, Honolulu, HI 96813, USA
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Kamangar F, Limburg P, Taylor P, Dawsey S. Re: Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 2003; 95:760; author reply 760-1. [PMID: 12759399 DOI: 10.1093/jnci/95.10.760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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Figueiredo C, Machado JC. RESPONSE: Re: Helicobacter pylori and Interleukin 1 Genotyping: An Opportunity to Identify High-Risk Individuals for Gastric Carcinoma. J Natl Cancer Inst 2003. [DOI: 10.1093/jnci/95.10.760-a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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