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Yao SY, Li XM, Cai T, Li Y, Liang LX, Liu XM, Lei YF, Zhu Y, Wang F. Helicobacter pylori infection is associated with the risk and phenotypes of cholelithiasis: A multi-center study and meta-analysis. World J Gastroenterol 2024; 30:4991-5006. [PMID: 39713162 PMCID: PMC11612862 DOI: 10.3748/wjg.v30.i47.4991] [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: 07/20/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a prevalent pathogen associated with various diseases. Cholelithiasis is also a common condition. H. pylori infection has been identified in the biliary system, suggesting its potential involvement in biliary diseases. However, the specific role of H. pylori in the development of cholelithiasis remains inconclusive. AIM To investigate the potential association between H. pylori infection and the development of cholelithiasis. METHODS We performed a retrospective study in more than 70000 subjects in health examination center from 3 institutions in the middle, northern and eastern China, from October 2018 to December 2021, to explore the potential association between H. pylori and cholelithiasis through univariate and multivariate analysis. Meanwhile, the influence of H. pylori on biliary-related parameters was investigated. A comprehensive analysis of previous studies concerned about H. pylori and cholelithiasis was also executed. RESULTS In our multi-center study, H. pylori was positively associated with cholelithiasis [odds ratio (OR) = 1.103, 95% confidence interval (CI): 1.001-1.216, P = 0.049]. Furthermore, H. pylori patients had less total and direct bilirubin than uninfected patients, while the total cholesterol and low-density lipoprotein cholesterol were more in H. pylori-positive participants (P < 0.05). In the published articles, the cohort studies indicated H. pylori was a risk factor of cholelithiasis (hazard ratio =1.3280, 95%CI: 1.1810-1.4933, P < 0.0001). The pooled results of case-control and cross-sectional studies showed positive association between H. pylori and cholelithiasis in Asia (OR = 1.5993, 95%CI: 1.0353-2.4706, P = 0.034) but not in Europe (OR = 1.2770, 95%CI: 0.8446-1.9308, P = 0.246). Besides, H. pylori was related to a higher choledocholithiasis/cholecystolithiasis ratio (OR = 3.3215, 95%CI: 1.1034-9.9986, P = 0.033). CONCLUSION H. pylori is positively correlated with cholelithiasis, choledocholithiasis phenotype particularly, especially in Asia, which may be relevant to bilirubin/cholesterol metabolism. Cohort studies confirm an increased risk of cholelithiasis in H. pylori patients.
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Affiliation(s)
- Shuo-Yi Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xin-Meng Li
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Ying Li
- Health Management Center, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Lun-Xi Liang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xiao-Ming Liu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Yu-Feng Lei
- Department of Gastroenterology, Shanxi Coal Central Hospital, Taiyuan 030006, Shanxi Province, China
| | - Yong Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
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Weisy OKM, Kedia RA, Mahmoud I, Abu Odeh RO, Mussa BM, Abusnana S, Soliman SSM, Muhammad JS, Hamad M, Ghemrawi R, Khoder G. Assessment of Helicobacter pylori cytotoxin-associated Gene A (Cag A) protein and its association with ferritin and vitamin B12 deficiencies among adult healthy asymptomatic residents in Sharjah, United Arab Emirates. Heliyon 2024; 10:e32141. [PMID: 38882276 PMCID: PMC11180313 DOI: 10.1016/j.heliyon.2024.e32141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 05/28/2024] [Accepted: 05/29/2024] [Indexed: 06/18/2024] Open
Abstract
The United Arab Emirates (UAE) serves as an effective epidemiological site for assessing Helicobacter pylori (H. pylori) infection due to its diverse population. However, comprehensive studies on the prevalence of H. pylori in the UAE are notably scarce. In depth prevalence studies are needed as a preventive measure against gastric cancer and other emerging extra gastric diseases associated with H. pylori infection. Aim: This study aimed to assess H. pylori infection and its virulent oncoprotein, the Cytotoxin-Associated Gene (Cag A) and its association with ferritin and vitamin B12 deficiencies. Methods: The study was conducted on 1094 healthy asymptomatic volunteers residents in the Sharjah Emirate, UAE. Enzyme-linked immunosorbent assay (ELISA) was performed to assess H. pylori infection using H. pylori antibodies (IgG), and detection of CagA protein using Cag A antibody (IgG) in the human serum. Ferritin and vitamin B12 serum levels were assessed and correlated to H. pylori infection. Results: This study focuses mainly on the assessment of H. pylori and its virulent factor CagA, in relation to vitamin B12 and ferritin deficiencies. Remarkably, 49.6 % of the participants were detected positive for H. pylori, with over half of these cases involving CagA positive strains. Notably, among Emirati participants, 76.11 % of those with H. pylori infection were CagA positive. Statistical analysis revealed a significant correlation between H. pylori, CagA level, and ferritin/vitamin B12 deficiencies. Conclusion: These findings emphasize the importance of timely detection and eradication of H. pylori not only as a preventive strategy against gastric cancer but also as an effective strategy to rescue the adverse effects from ferritin and vitamin B12 deficiencies, thereby improving the overall health outcomes of individuals affected by H. pylori infection.
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Affiliation(s)
- Om Kolthoom M Weisy
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Reena A Kedia
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
| | - Ibrahim Mahmoud
- Department of Family and Community Medicine and Behavioral Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Raed O Abu Odeh
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Bashair M Mussa
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Salah Abusnana
- Diabetes and Endocrinology Department, University Hospital Sharjah, Sharjah, United Arab Emirates
- Clinical Science Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Sameh S M Soliman
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Jibran Sualeh Muhammad
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohamad Hamad
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Rose Ghemrawi
- College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
| | - Ghalia Khoder
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
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Sun L, Zheng H, Qiu M, Hao S, Liu X, Zhu X, Cai X, Huang Y. Helicobacter pylori infection and risk of cardiovascular disease. Helicobacter 2023; 28:e12967. [PMID: 36974892 DOI: 10.1111/hel.12967] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/23/2023] [Accepted: 02/25/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Whether Helicobacter pylori (H. pylori) infection is associated with an increased risk of cardiovascular disease (CVD) remains controversial. This study aimed to investigate the association between H. pylori infection and the risk of CVD. METHODS Potentially related studies were searched in the electronic databases, including PubMed, EMBASE and Cochrane Library, from inception to 31 August 2022. Observational cohort studies that reported the multivariable-adjusted relative risks (RRs) for composite CVD, CHD, stroke, or all-cause mortality associated with H. pylori infection were included in the meta-analysis, using random-effects models. RESULTS Forty-one cohort studies with 230,288 participants were included. After a median follow-up duration of 6.3 years, H. pylori infection was associated with a mildly increased risk of composite CVD (RR 1.10, 95% CI 1.03, 1.18) and coronary heart disease (RR 1.10, 95% CI 1.02, 1.18) compared with those without H. pylori infection. No significant association was observed between H. pylori infection and risk of stroke (RR 1.08, 95% CI 0.94, 1.23) or all-cause mortality (RR 1.02, 95% CI 0.90, 1.16). Compared with cytotoxin-associated gene-A (CagA) negative H. pylori infection, the risk of CVD was significantly increased in patients with CagA positive H. pylori infection (RR 1.58, 95% CI 1.03, 2.41). CONCLUSIONS Helicobacter pylori infection is associated with a mildly increased risk of CVD. It may be of great public health and clinical significance to screen H. pylori infection in patients with a high risk of CVD.
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Affiliation(s)
- Lichang Sun
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Haoxiao Zheng
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Min Qiu
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Shali Hao
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Xiong Liu
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Xiaolin Zhu
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Xiaoyan Cai
- Department of Scientific Research and Education, Shunde Hospital, Southern Medical University, Foshan, China
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
- The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
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Castagnini LA, Gilger MA. Helicobacter pylori. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:954-959.e5. [DOI: 10.1016/b978-0-323-75608-2.00174-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Hashim M, Mohammed O, G/Egzeabeher T, Wolde M. The association of Helicobacter Pylori infection with dyslipidaemia and other atherogenic factors in dyspeptic patients at St. Paul's Hospital Millennium Medical College. Heliyon 2022; 8:e09430. [PMID: 35600431 PMCID: PMC9120239 DOI: 10.1016/j.heliyon.2022.e09430] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/15/2022] [Accepted: 05/11/2022] [Indexed: 11/20/2022] Open
Abstract
Background Studies showed that more than half of Ethiopians were presumed to be chronically infected with H. pylori. Nowadays, evidence has come to the literature strongly suggesting the potential association between H. pylori and extra gastric disorders including atherosclerosis. Objective To assess the association of helicobacter pylori infection with dyslipidaemia and other atherogenic factors in dyspeptic patients at St. Paul's Hospital Millennium Medical College, from November 2019 to June 2020. Materials and methods This institution-based cross-sectional study was examining 346 dyspeptic patients at SPHMMC from November 2019 to June 2020. A structured questionnaire was used to collect socio-demography data and anthropometric measurement was taken. Biochemical parameters were measured in serum samples by using Cobas 6000 clinical chemistry analyzer. Data were coded and entered into a statistical package for social sciences (SPSS) version 23 for analysis. Risk factors were identified using logistic regression. Hence, a bivariate logistic regression analysis test was conducted and variables with a p < 0.25 were included in the multivariate logistic regression model. P-values ≤0.05 were considered as a cut point for statistical significance in the final model. Results An overall prevalence of dyslipidemia among study participants was 253 (73.12 %). Among those who tested positive for H. pylori, 119/174 (68.39 %) had dyslipidemia in at least one lipid profile, while 8 (4.60%) had dyslipidemia in all four lipid profiles. After adjusting for traditional dyslipidemia risk factors, age >45 (AOR 4.864, 95% CI 2.281-4.080, P < 0.001), systolic blood pressure >120mmHg (AOR 1.036, 95% CI 1.009-1.065, P = 0.036) and being H. Pylori seropositive (AOR 0.555, 95% CI 0.318-0.967, P = 0.038) were an independent predictors of dyslipidemia. Conclusion This study reported that more than two-thirds of the H. pylori seropositive groups had exhibited dyslipidemia in at least one lipid profile, which can accelerate the incidence of atherosclerosis process.
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Affiliation(s)
- Mujahid Hashim
- St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Ousman Mohammed
- Department of Medical Laboratory Sciences, College of Health Sciences, Wollo University, Dessie, Ethiopia
| | - Tatek G/Egzeabeher
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Mistire Wolde
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Galal AMF, Mohamed HS, Abdel-Aziz MM, Hanna AG. Development, synthesis, and biological evaluation of sulfonyl-α-l-amino acids as potential anti-Helicobacter pylori and IMPDH inhibitors. Arch Pharm (Weinheim) 2021; 354:e2000385. [PMID: 33576040 DOI: 10.1002/ardp.202000385] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/10/2021] [Accepted: 01/15/2021] [Indexed: 12/16/2022]
Abstract
Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of DNA and RNA, and it has been exploited as a promising target for antimicrobial therapy. The present study discusses the development and synthesis of a series of sulfonyl-α-l-amino acids coupled with the anisamide scaffold and evaluates their activities as anti-Helicobacter pylori and IMPDH inhibitors. Twenty derivatives were synthesized and their structures were established by high-resolution mass spectrometry and 1 H and 13 C nuclear magnetic resonance measurements. Four compounds (6, 10, 11, and 21) were found to be the most potent and selective molecules in the series with minimum inhibitory concentration (MIC) values <17 µM, which were selected to test their inhibitory activities against HpIMPDH and human (h)IMPDH2 enzymes. In all tests, amoxicillin and clarithromycin were used as reference drugs. Compounds 6 and 10 were found to have a promising activity against the HpIMPDH enzyme, with IC50 = 2.42 and 2.56 µM, respectively. Moreover, the four compounds were found to be less active and safer against hIMPDH2 than the reference drugs, with IC50 > 17.17 µM, which makes sure that their selectivity is toward HpIMPDH and reverse to that of amoxicillin and clarithromycin. Also, the synergistic antibacterial activity of compounds 6, 10, amoxicillin, and clarithromycin was investigated in vitro. The combination of amoxicillin/compound 6 (2:1 by weight) exhibited a significant antibacterial activity against H. pylori, with MIC = 0.12 µg/ml. The molecular docking study and ADMET analysis of the most active compounds were used to elucidate the mode-of-action mechanism.
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Affiliation(s)
- Alaaeldin M F Galal
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Hanaa S Mohamed
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Centre, Cairo, Egypt
| | - Marwa M Abdel-Aziz
- Regional Center for Mycology and Biotechnology (RCMB), Al-Azhar University, Cairo, Egypt
| | - Atef G Hanna
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza, Egypt
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7
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Darvishi M, Noori M, Nazer MR, Soleiman-Meigooni S, Forootan M. The Relationship between Helicobacter Pylori and Extra-Gastrointestinal Infections. IRANIAN JOURNAL OF MEDICAL MICROBIOLOGY 2020; 14:543-565. [DOI: 10.30699/ijmm.14.6.543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
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Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
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Chen QF, Zhou XD, Fang DH, Zhang EG, Lin CJ, Feng XZ, Wang N, Wu JS, Wang D, Lin WH. Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas. World J Gastroenterol 2020; 26:5682-5692. [PMID: 33088161 PMCID: PMC7545385 DOI: 10.3748/wjg.v26.i37.5682] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/29/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.
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Affiliation(s)
- Qin-Fen Chen
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xiao-Dong Zhou
- Department of Cardiovascular Medicine, The Key Laboratory of Cardiovascular Diseases of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Dan-Hong Fang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - En-Guang Zhang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Chun-Jing Lin
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xiao-Zhen Feng
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Na Wang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Jian-Sheng Wu
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Dan Wang
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Wei-Hong Lin
- Department of Physical Examination Medical Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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Doulberis M, Kountouras J, Rogler G. Reconsidering the "protective" hypothesis of Helicobacter pylori infection in eosinophilic esophagitis. Ann N Y Acad Sci 2020; 1481:59-71. [PMID: 32770542 DOI: 10.1111/nyas.14449] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/12/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
Since its discovery, Helicobacter pylori (H. pylori) has attracted attention in the biomedical world with its numerous pathophysiologic implications, both gastrointestinal and systemic. Beyond its well-established carcinogenic properties, emerging evidence also supports "harmful" proinflammatory and neurodegenerative roles of H. pylori. On the other hand, H. pylori infection has been proposed to be "protective" against several diseases, such as asthma and gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) is a relatively new, allergen/immune-mediated disease, which has also been linked to these considerations. Main arguments are a postulated shift of immune responses by H. pylori from T helper 2 (TH 2) to TH 1 polarization, as well as a potential decline of the H. pylori burden with the dramatic parallel rise of ΕοΕ: a series of observational studies reported an inverse association. In this review, we counter these arguments by providing further epidemiological data, which point out that this generalization might be rather incomplete. We also discuss the limitations of the existing studies evaluating a possible association. Furthermore, we provide current evidence on common pathogenetic components, which share both entities. In summary, the claim that H. pylori is protective against EoE is rather incomplete, and further mechanistic studies are necessary to elucidate a possible association.
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Affiliation(s)
- Michael Doulberis
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.,Second Medical Clinic, Faculty of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Jannis Kountouras
- Second Medical Clinic, Faculty of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
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11
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Li S, Wu D, Cao M, Yu Z, Wu M, Liu Y, Zhou J, Yan S, Chen J, Huang M, Zhao J. Effects of choline supplementation on liver biology, gut microbiota, and inflammation in Helicobacter pylori-infected mice. Life Sci 2020; 259:118200. [PMID: 32758621 DOI: 10.1016/j.lfs.2020.118200] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 07/31/2020] [Accepted: 07/31/2020] [Indexed: 02/07/2023]
Abstract
AIMS Diet is one of the factors affecting the pathogenicity of Helicobacter pylori (H. pylori) infection. Choline is a dietary component that is crucial for normal cellular function. However, choline intake imbalance can lead to liver injury, inflammation, and changes of the gut microbiota composition. The study aimed to explore the effects of choline supplementation on liver biology, gut microbiota, and inflammation in H. pylori-infected mice. MAIN METHODS Liver function was detected by biochemical and histopathological analysis. Serum inflammatory markers were measured using ELISA. Fecal microbial profiles were determined via 16S rRNA sequencing. KEY FINDINGS The results showed that choline supplementation decreased serum LDL level, while increased the activities of serum AST and ALT in normal BALB/c mice. Besides, choline also reduced hepatic SOD and GSH-Px activities, and elevated hepatic MDA level of H. pylori-infected mice. Moreover, choline markedly enhanced the concentrations of inflammatory factors including LPS, CRP, IL-6, TNF-α, and CXCL1 in H. pylori-infected mice. Meanwhile, choline and H. pylori cotreatment altered the richness and diversity of the mice gut microbiota, and increased the relative abundance of Escherichia_Shigella, which had a significant positive correlation with the levels of LPS, CRP, IL-6, TNF-α and CXCL1. SIGNIFICANCE Our data suggest, for the first time, that choline can aggravate H. pylori-induced inflammation, which may be associated with the alterations of gut microbiota. This study may provide novel insights into the possible effects of food-derived choline on H. pylori infection-related diseases.
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Affiliation(s)
- Shu Li
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Daoyan Wu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Mei Cao
- Core Laboratory, School of Medicine, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu 610072, PR China
| | - Zhihao Yu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Mengmeng Wu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Yi Liu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Jie Zhou
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Shiying Yan
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Jieyun Chen
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China
| | - Min Huang
- Irradiation Preservation Technology Key Laboratory of Sichuan Province, Sichuan Institute of Atomic Energy, Chengdu 610101, PR China
| | - Jian Zhao
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
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12
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Zou Y, Qian X, Liu X, Song Y, Song C, Wu S, An Y, Yuan R, Wang Y, Xie Y. The effect of antibiotic resistance on Helicobacter pylori eradication efficacy: A systematic review and meta-analysis. Helicobacter 2020; 25:e12714. [PMID: 32533599 DOI: 10.1111/hel.12714] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/22/2020] [Accepted: 05/25/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The occurrence of antibiotic-resistant strains has been rapidly increasing due to the wide use of antibiotics. To evaluate the current effects of antibiotic resistance on Helicobacter pylori eradication efficacy, we conducted this systematic review and meta-analysis. METHODS Literature searches were conducted in the following databases: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Statistical analysis was performed using STATA version 12.0 (StataCorp LP, College Station, TX, USA). RESULTS A total of 120 studies, including 28 707 patients, were assessed. Only first-line therapy was considered. The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to clarithromycin was 0.682 (95% CI: 0.636-0.731). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to metronidazole was 0.843 (95% CI: 0.810-0.877). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to levofloxacin was 0.794 (95% CI: 0.669-0.941). The pooled RR of eradication rate in patients with Helicobacter pylori strains sensitive versus resistant to dual clarithromycin and metronidazole was 0.674 (95% CI: 0.590-0.770). CONCLUSION Antibiotic resistance causes a decrease in the eradication rate of H pylori today. Quadruple concomitant therapy may overcome the declining H pylori eradication rate caused by metronidazole-only resistance.
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Affiliation(s)
- Yunzhi Zou
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
- Medical College of Nanchang University, Nanchang, China
| | - Xing Qian
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, First People's Hospital of Fuzhou, Fuzhou, China
| | - Xiaoqun Liu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
- Affiliated Hospital of Jiujiang University, Jiujiang, China
| | - YanPing Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Conghua Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shuang Wu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ying An
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Rui Yuan
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
- Fuzhou Medical College of Nanchang University, Fuzhou, China
| | - Youhua Wang
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yong Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
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Rahman N, Ajmal A, Ali F, Rastrelli L. Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori. Genomics 2020; 112:3473-3483. [PMID: 32562830 DOI: 10.1016/j.ygeno.2020.06.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/13/2020] [Accepted: 06/15/2020] [Indexed: 01/18/2023]
Abstract
Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects half of the human population worldwide and causes chronic inflammation. In the present study, we used the art of computational biology for therapeutic drug targets identification and a multi-epitope vaccine against multi-strains of H. pylori. For drug target identification, we used different tools and softwares to identify human non-homologous but pathogen essential proteins, with virulent properties and involved in unique metabolic pathways of H. pylori. For this purpose, the core proteome of 84 strains of H. pylori was retrieved from EDGAR 2.3 database. There were 59,808 proteins sequences in these strains. Duplicates and paralogous protein sequence removal was followed by human non-homologous protein miningPathogen essential and virulent proteins were subjected to pathway analysis Subcellular localization of the virulent proteins was predicted and druggability was also checked, leading to 30 druggable targets based on their similarity with the approved drug targets in Drugbank. For immunoinformatics analysis, we selected two outer membrane proteins (HPAKL86_RS06305 and HPSNT_RS00950) and subjected to determined immunogenic B and T-Cell epitopes. The B and T-Cell overlapped epitopes were selected to design 9 different vaccine constructs by using linkers and adjuvants. Least allergenic and most antigenic construct (C-8) was selected as a promiscuous vaccine to elicit host immune response. Cloning and in silico expression of the constructed vaccine (C-8) was done to produce a clone having the desired (gene) vaccine construct. In conclusion, the prioritized therapeutic targets for 84 strains of H.pylori will be useful for future therapy design. Vaccine design may also prove useful in the quest for targeting multi-strains of H. pylori in patients.
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Affiliation(s)
- Noor Rahman
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
| | - Amar Ajmal
- Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, KP, Pakistan
| | - Fawad Ali
- Department of Biochemistry, Hazara University, Mansehra, Pakistan
| | - Luca Rastrelli
- Dipartimento di Farmacia, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy
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14
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Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis. Microorganisms 2020; 8:microorganisms8060894. [PMID: 32545826 PMCID: PMC7355761 DOI: 10.3390/microorganisms8060894] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48–2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17–9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09–27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.
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15
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Doheim MF, Altaweel AA, Elgendy MG, Elshanbary AA, Dibas M, Ali AAHA, Dahy TM, Sharaf AK, Hassan AE. Association between Helicobacter Pylori infection and stroke: a meta-analysis of 273,135 patients. J Neurol 2020; 268:3238-3248. [PMID: 32447554 DOI: 10.1007/s00415-020-09933-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 05/16/2020] [Accepted: 05/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Stroke stands among the most leading causes of mortality worldwide. Although modifiable risk factors for stroke have been identified, current risk factors do not sufficiently explain the risk in young patients. Previous studies have postulated an association between infection by Helicobacter pylori (HP) and stroke. OBJECTIVE To investigate the association between HP infection and stroke by using a systematic review and meta-analysis approach. METHODS Four electronic search engines/libraries were systematically searched for relevant observational studies. Studies were screened for eligibility and data were extracted. The odds ratio (OR) and 95% confidence interval (95% CI) were combined under the random-effect model. The protocol was registered in PROSPERO (CRD42019123689). RESULTS Among the included studies, 25 studies were analyzed for anti-HP IgG, 9 studies were for anti-Cag A, and 6 studies were for the C-urea breath test. The results showed that positive anti-HP IgG was significantly associated with an increased risk of stroke [OR (95% CI) = 1.43 (1.25-1.46)]. Similarly, both antiCag A and C-urea breath test were significantly associated with an increased risk of stroke with [OR (95% CI) = 1.77 (1.25-2.49)], and [OR (95% CI) = 2.21 (1.33-3.66)], respectively. Furthermore, our results indicated that positive anti-HP IgG was associated with stroke caused by atherothrombosis and small artery disease. CONCLUSIONS This study suggests that HP infection is significantly associated with increased risk of stroke. However, more well-designed studies are required to investigate if early HP eradication might decrease the incidence of stroke.
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Affiliation(s)
| | | | | | | | - Mahmoud Dibas
- College of Medicine, Sulaiman Al Rajhi University, Qassim, Saudi Arabia
| | | | | | | | - Ameer E Hassan
- Department of Neurology, University of Texas Rio Grande Valley, Valley Baptist Medical Center, Harlingen, TX, USA.
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16
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Song C, Xie C, Zhu Y, Liu W, Zhang G, He S, Zheng P, Lan C, Zhang Z, Hu R, Du Q, Xu J, Chen Y, Zeng Z, Cheng H, Wang X, Zuo X, Lu H, Guo T, Chen Z, Xie Y, Lu N. Management of Helicobacter pylori infection by clinicians: A nationwide survey in a developing country. Helicobacter 2019; 24:e12656. [PMID: 31571330 DOI: 10.1111/hel.12656] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 07/02/2019] [Accepted: 07/18/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND & AIMS Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective. METHODS An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion. RESULTS A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05). CONCLUSIONS Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.
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Affiliation(s)
- Conghua Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,Department of Gastroenterology, Affiliated Hospital of Putian University, Putian, Fujian Province, China
| | - Chuan Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yin Zhu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Wenzhong Liu
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China
| | - Guoxin Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shuixiang He
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Pengyuan Zheng
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Chunhui Lan
- Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing City, China
| | - Zhenyu Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Qin Du
- Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Jianming Xu
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Zhirong Zeng
- Division of Gastroenterology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Hong Cheng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xuehong Wang
- Department of Gastroenterology, Qinghai University Affiliated Hospital, Xining, Qinghai Province, China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Hong Lu
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China
| | - Tao Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing City, China
| | - Zhifen Chen
- Department of Gastroenterology, Zhongnan Hospital Affiliated to Wuhan University, Wuhan, Hubei Province, China
| | - Yong Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Nonghua Lu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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17
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Afsharpooyan S, Mohammadian T. Seroepidemiology Study ofHelicobacter pyloriInfection and Its Effect on Cardiovascular Diseases in Karaj, Iran. Monoclon Antib Immunodiagn Immunother 2019; 38:277-281. [DOI: 10.1089/mab.2019.0039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Affiliation(s)
- Shadi Afsharpooyan
- Department of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
| | - Taher Mohammadian
- Department of Microbiology, Shahr-e-Qods-Branch, Islamic Azad University, Tehran, Iran
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18
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Pyo JH, Lee H, Choi SC, Cho SJ, Choi YH, Min YW, Min BH, Lee JH, Yoo H, Kim K, Kim JJ. Lack of Association between Past Helicobacter pylori Infection and Diabetes: A Two-Cohort Study. Nutrients 2019; 11:nu11081874. [PMID: 31409000 PMCID: PMC6723734 DOI: 10.3390/nu11081874] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/06/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) may be involved in diabetes and other insulin-related processes. This study aimed to investigate the associations between H. pylori infection and the risks of type 2 diabetes, impaired glucose tolerance (IGT), diabetic nephropathy, and poor glycemic control. We retrospectively evaluated 16,091 subjects without diabetes at baseline who underwent repeated health examinations. Subjects were categorized according to whether they were seropositive and seronegative for H. pylori infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The serological results were validated using an independent cohort (n = 42,351) based on a histological diagnosis of H. pylori infection. During 108,614 person-years of follow-up, 1338 subjects (8.3%) developed newly diagnosed diabetes, although the cumulative incidence of diabetes was not significantly related to serological H. pylori status. The multivariate Cox proportional-hazards regression models revealed that H. pylori seropositivity was not significantly associated with diabetes (HR: 1.01, 95% CI: 0.88–1.16; p = 0.854), IGT (HR: 0.98, 95% CI: 0.93–1.04; p = 0.566), diabetic nephropathy (HR: 0.99, 95% CI: 0.82–1.21; p = 0.952), or poor glycemic control (HR: 1.05, 95% CI: 0.90–1.22; p = 0.535). Similarly, histopathological findings of H. pylori infection were not significantly associated with diabetes (p = 0.311), diabetic nephropathy (p = 0.888), or poor glycemic control (p = 0.989). The findings from these large Korean cohorts indicate that there does not appear to be a role for past H. pylori infection in the development of diabetes, IGT, diabetic nephropathy, or poor glycemic control.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Soo Jin Cho
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Heejin Yoo
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Kyunga Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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Abstract
Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.
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20
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Treatment of Helicobacter pylori-associated gastritis using traditional Chinese medicine. INFECTION INTERNATIONAL 2018. [DOI: 10.2478/ii-2018-0009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Abstract
Helicobacter pylori is a pathogenic bacterium with strong pathogenicity, which can induce chronic gastritis and peptic ulcer in addition to causing gastric mucosal atrophy and intestinal metaplasia after longterm infection. It is even associated closely with the occurrence of gastric cancer and mucosa-associated lymphoid tissue lymphoma. Recently, the incidence of H.pylori-associated gastritis has increased rapidly worldwide, especially in China. The prevention and treatment of H. pylori infection has become an urgent issue to be resolved by the medical community. Traditional Chinese medicine and the combination of traditional Chinese medicine and Western medicine have recently shown unique advantages in the treatment of H.pylori–associated gastritis. The progress in this area is summarized in this review.
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21
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Helicobacter pylori-induced autoimmune thyroiditis: is the pathogenic link concluded or still a hypothesis? ACTA ACUST UNITED AC 2018. [DOI: 10.1097/mrm.0000000000000133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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22
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Refaeli R, Chodick G, Haj S, Goren S, Shalev V, Muhsen K. Relationships of H. pylori infection and its related gastroduodenal morbidity with metabolic syndrome: a large cross-sectional study. Sci Rep 2018; 8:4088. [PMID: 29511278 PMCID: PMC5840265 DOI: 10.1038/s41598-018-22198-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 02/12/2018] [Indexed: 12/14/2022] Open
Abstract
The few published studies on the relationship between Helicobacter pylori infection and metabolic homeostasis were relatively small and yielded inconsistent results. We examined the prevalence of metabolic syndrome in relation to H. pylori infection and its symptoms in a large and unselected population. Coded data from the computerised database of a large health maintenance organisation in Israel were accessed for 147,936 individuals 25–95 years of age who performed the urea breath test during 2002–2012. The classification of metabolic syndrome followed a modified definition of the international diabetes federation. Prevalences of H. pylori infection and metabolic syndrome were 52.0% and 11.4% respectively. H. pylori infected patients had increased likelihood of metabolic syndrome: adjusted odds ratio (aOR) 1.15 (95% confidence intervals (CI) 1.10–1.19), as did patients with gastric ulcer: aOR 1.15 (95% CI 1.03–1.28) vs patients without these conditions. Duodenal ulcer was associated with metabolic syndrome only in persons aged 25–34 years: aOR 1.59 (95% CI 1.19-2.13), but not in older persons (P = 0.001 for heterogeneity). In conclusion, the likelihood of metabolic syndrome appeared significantly increased in relation to H. pylori infection and gastric and duodenal ulcers. These findings suggest that H. pylori long-term gastric inflammation might play a role in metabolic homeostasis.
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Affiliation(s)
- Rotem Refaeli
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gabriel Chodick
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Medical division, Maccabi Health Services, Tel Aviv, Israel
| | - Saeda Haj
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sophy Goren
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Varda Shalev
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Medical division, Maccabi Health Services, Tel Aviv, Israel
| | - Khitam Muhsen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Liu Y, Shen C, Zhang X, Yu H, Wang F, Wang Y, Zhang LW. Exposure and nephrotoxicity concern of bismuth with the occurrence of autophagy. Toxicol Ind Health 2018; 34:188-199. [PMID: 29506455 DOI: 10.1177/0748233717746810] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Metal nanoparticles or metal-based compounds have drawn attention in various fields ranging from industry to medicine because of their unique physicochemical properties. Bismuth (Bi) compounds and nanomaterials have been commonly used in alloys, electronic industry, batteries, and as flame retardants as well as for anti- Helicobacter pylori therapy, while the nanomaterial form has great potential for computed tomography imaging and thermotherapy, both of which will be introduced in this review. Although Bi was used for several decades, there is a lack of detailed information concerning their toxicity and mechanisms on human health. We described the toxicity of Bi on the kidney that seemed to be relatively known by researchers, while the mechanisms remain unclear. Recently, our group has found that Bi compounds, including bismuth nitrate (BN) and Bi nanomaterials, can induce autophagy in kidney cells. We also extended our findings by selecting five Bi compounds, and the results showed that BN, bismuth oxychloride, bismuth citrate, colloidal bismuth subcitrate, and Bi nanomaterials all induced slight cytotoxicity accompanied with autophagy. Although the role of autophagy in Bi-induced cytotoxicity and kidney injury is under investigation by us, autophagy may help with the exploration of the mechanisms of nephrotoxicity by Bi.
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Affiliation(s)
- Yongming Liu
- 1 School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China
| | - Chen Shen
- 2 Department of Oncology, No.100 Hospital of PLA, Suzhou, Jiangsu, China
| | - Xihui Zhang
- 1 School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China
| | - Huan Yu
- 1 School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China
| | - Fujun Wang
- 3 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yangyun Wang
- 1 School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China
| | - Leshuai W Zhang
- 1 School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS PROTEOMICS & BIOINFORMATICS 2018. [PMID: 29474889 DOI: 10.1016/j.gpb.2017.06.002.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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25
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS, PROTEOMICS & BIOINFORMATICS 2018; 16:33-49. [PMID: 29474889 PMCID: PMC6000254 DOI: 10.1016/j.gpb.2017.06.002] [Citation(s) in RCA: 270] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 06/08/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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26
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Fan N, Peng L, Xia Z, Zhang L, Wang Y, Peng Y. Helicobacter pylori Infection Is Not Associated with Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in China. Front Microbiol 2018; 9:73. [PMID: 29445363 PMCID: PMC5797778 DOI: 10.3389/fmicb.2018.00073] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 01/11/2018] [Indexed: 12/14/2022] Open
Abstract
Background and Aim:Helicobacter pylori infection has been reported to promote the development of a variety of extra-digestive manifestations, including type 2 diabetes, cardiovascular and liver diseases. Recently, the association between H. pylori infection and non-alcoholic fatty liver disease (NAFLD) was also proposed. However, evidence from different studies was controversial. We therefore performed this study to investigate the relationship between them in a large population of apparently healthy subjects in China. Methods: A total of 21,456 subjects underwent a healthy checkup program were included. H. pylori infection was detected by 14C urea breath test (14C-UBT) and NAFLD was diagnosed by ultrasonography. Results: Subjects infected with H. pylori had a more unfavorable metabolic profile, including higher levels of body mass index (BMI), blood pressure, triglycerides (TG) and lower levels of high-density lipoprotein cholesterol (HDL-C), as compared with those without H. pylori infection (all P < 0.05). Moreover, the prevalence rate of NAFLD was significantly increased in subjects with H. pylori infection when compared with those without H. pylori in women (23.6% vs. 21.5%, P < 0.05), but not in men (46.5% vs. 45.5%, P > 0.05). After adjusting for confounding factors including age, sex, BMI, blood pressure and lipid profiles, multivariate logistic analysis revealed that H. pylori infection was not independently associated with the risk of NAFLD in the total population (OR = 0.9, 95% CI = 0.9–1.0, P = 0.097). Also, subgroup analysis (stratified by age, sex, BMI, and diabetes status) showed no independent association between H. pylori infection and NAFLD. Conclusion: Our data suggests that H. pylori infection is not independently associated with the risk of NAFLD in apparently healthy subjects.
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Affiliation(s)
- Nengguang Fan
- Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Liang Peng
- Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, Shanghai, China
| | - Zhenhua Xia
- Department of Endocrinology, Shanghai Songjiang Center Hospital, Shanghai, China
| | - Lijuan Zhang
- Department of Endocrinology, Shanghai Songjiang Center Hospital, Shanghai, China
| | - Yufan Wang
- Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yongde Peng
- Department of Endocrinology and Metabolism, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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27
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Xu MY, Cao B, Yuan BS, Yin J, Liu L, Lu QB. Association of anaemia with Helicobacter pylori infection: a retrospective study. Sci Rep 2017; 7:13434. [PMID: 29044219 PMCID: PMC5647388 DOI: 10.1038/s41598-017-13955-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 10/03/2017] [Indexed: 02/07/2023] Open
Abstract
The role of Helicobacter pylori (H. pylori) infection in haematological system diseases is not well understood. We conducted this retrospective study to explore the association between H. pylori infection and anaemia in the Chinese population. This retrospective study was performed in Aerospace Center Hospital in Beijing. We derived the data from the registration system of the physical population between 2012-2016. Logistic regression models were used to explore the association between H. pylori infection and anaemia. Among 17,791 subjects, there were 7,804 (43.9%) subjects with H. pylori infection and 950 (5.3%) with anaemia. The prevalence of anaemia in the H. pylori (+) group was significantly higher than in the H. pylori (-) group after adjusting for age, sex, marriage, underlying diseases and body mass index. Compared to H. pylori (-), the OR of H. pylori (+) was 1.39 for moderate-to-severe anaemia and 1.05 for mild anaemia. The level of haemoglobin was lower in the H. pylori (+) group than in the H. pylori (-) group. This study indicates that H. pylori infection may be related to anaemia and haemoglobin level in the Chinese population.
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Affiliation(s)
- Mei-Yan Xu
- Department of Nutrition, Aerospace Center Hospital, Beijing, 100049, P. R. China
| | - Bing Cao
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, P. R. China
| | - Bao-Shi Yuan
- Department of Health Management, Aerospace Center Hospital, Beijing, 100049, P. R. China
| | - Jian Yin
- Department of Nutrition, Aerospace Center Hospital, Beijing, 100049, P. R. China
| | - Lan Liu
- Department of Health Management, Aerospace Center Hospital, Beijing, 100049, P. R. China.
| | - Qing-Bin Lu
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, P. R. China.
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, P. R. China.
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Nammi D, Yarla NS, Chubarev VN, Tarasov VV, Barreto GE, Pasupulati AMC, Aliev G, Neelapu NRR. A Systematic In-silico Analysis of Helicobacter pylori Pathogenic Islands for Identification of Novel Drug Target Candidates. Curr Genomics 2017; 18:450-465. [PMID: 29081700 PMCID: PMC5635650 DOI: 10.2174/1389202918666170705160615] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 01/22/2016] [Accepted: 01/25/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori is associated with inflammation of different areas, such as the duodenum and stomach, causing gastritis and gastric ulcers leading to lymphoma and cancer. Pathogenic islands are a type of clustered mobile elements ranging from 10-200 Kb contributing to the virulence of the respective pathogen coding for one or more virulence factors. Virulence factors are molecules expressed and secreted by pathogen and are responsible for causing disease in the host. Bacterial genes/virulence factors of the pathogenic islands represent a promising source for identifying novel drug targets. OBJECTIVE The study aimed at identifying novel drug targets from pathogenic islands in H. pylori. MATERIAL & METHODS The genome of 23 H. pylori strains were screened for pathogenic islands and bacterial genes/virulence factors to identify drug targets. Protein-protein interactions of drug targets were predicted for identifying interacting partners. Further, host-pathogen interactions of interacting partners were predicted to identify important molecules which are closely associated with gastric cancer. RESULTS Screening the genome of 23 H. pylori strains revealed 642 bacterial genes/virulence factors in 31 pathogenic islands. Further analysis identified 101 genes which were non-homologous to human and essential for the survival of the pathogen, among them 31 are potential drug targets. Protein-protein interactions for 31 drug targets predicted 609 interacting partners. Predicted interacting partners were further subjected to host-pathogen interactions leading to identification of important molecules like TNF receptor associated factor 6, (TRAF6) and MAPKKK7 which are closely associated with gastric cancer. CONCLUSION These provocative studies enabled us to identify important molecules in H. pylori and their counter interacting molecules in the host leading to gastric cancer and also a pool of novel drug targets for therapeutic intervention of gastric cancer.
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Affiliation(s)
- Deepthi Nammi
- Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), India
| | - Nagendra S. Yarla
- Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), India
| | - Vladimir N. Chubarev
- Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 19991Moscow, Russia
| | - Vadim V. Tarasov
- Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 19991Moscow, Russia
| | - George E. Barreto
- Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriama, BogotáD.C., Colombia
| | - Amita Martin Corolina Pasupulati
- Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), India
| | - Gjumrakch Aliev
- Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 19991Moscow, Russia
- Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia
| | - Nageswara Rao Reddy Neelapu
- Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), India
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Haj S, Chodick G, Refaeli R, Goren S, Shalev V, Muhsen K. Associations of Helicobacter pylori infection and peptic disease with diabetic mellitus: Results from a large population-based study. PLoS One 2017; 12:e0183687. [PMID: 28850590 PMCID: PMC5574557 DOI: 10.1371/journal.pone.0183687] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 08/09/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Evidence is conflicting regarding the association between Helicobacter pylori infection and diabetes mellitus. The study objective was to examine associations of H. pylori infection, gastric ulcers and duodenal ulcers, with diabetes mellitus. METHODS This cross-sectional study was undertaken using coded data from the computerized database of Maccabi Health Services in Israel, on 147,936 individuals aged 25-95 years who underwent the urea breath test during 2002-2012. Multiple logistic regression models were conducted, while adjusting for known risk factors for diabetes mellitus. RESULTS A H. pylori positive test was recorded for 76,992 (52.0%) individuals and diabetes for 12,207 (8.3%). The prevalence of diabetes was similar in individuals with and without H. pylori infection, but this association was modified (P for heterogeneity 0.049) by body mass index (BMI): adjusted odds ratio (aOR) 1.16 (95% confidence intervals (CI) 1.04-1.29) in persons with BMI<25 kg/m2 versus aOR 1.03 (95% CI 0.98-1.08) in persons with BMI≥25 kg/m2. Diabetes mellitus prevalence was higher in persons with gastric (aOR 1.20 (95% CI 1.06-1.34)) and duodenal ulcers (aOR 1.20 (95% CI 1.12-1.28)) compared to persons without these diagnoses. CONCLUSIONS In this large population-based study, we demonstrated significant positive associations, albeit of small magnitude, of H. pylori infection and peptic disease with diabetes. The long-term gastric inflammation and associated-damage to the gastric mucosa might play a role in such associations.
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Affiliation(s)
- Saeda Haj
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gabriel Chodick
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Medical division, Maccabi Health Services, Tel Aviv, Israel
| | - Rotem Refaeli
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sophy Goren
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Varda Shalev
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Medical division, Maccabi Health Services, Tel Aviv, Israel
| | - Khitam Muhsen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- * E-mail:
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Lee JY, Park HW, Choi JY, Lee JS, Koo JE, Chung EJ, Chang HS, Choe J, Yang DH, Myung SJ, Jung HY, Yang SK, Byeon JS. Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm. Gut Liver 2017; 10:902-909. [PMID: 27458180 PMCID: PMC5087929 DOI: 10.5009/gnl15340] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 11/05/2015] [Accepted: 02/02/2016] [Indexed: 12/14/2022] Open
Abstract
Background/Aims Helicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN. Methods This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy. Results A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not. Conclusions H. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.
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Affiliation(s)
- Ji Young Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye Won Park
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Young Choi
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong-Soo Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ja Eun Koo
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Ju Chung
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye-Sook Chang
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaewon Choe
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters. Infect Immun 2017; 85:IAI.00009-17. [PMID: 28138021 DOI: 10.1128/iai.00009-17] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 01/22/2017] [Indexed: 12/21/2022] Open
Abstract
Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii) H. pylori infected (HP), (iii) O. viverrini infected (OV), and (iv) O. viverrini and H. pylori infected (OV+HP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of H. pylori in the stomach, gallbladder, and liver. In the liver, H. pylori was detected in the following order: OV+HP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%). H. pylori was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) were also observed in the OV+HP group. These results suggest that coinfection with H. pylori and O. viverrini increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did.
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Branquinho D, Almeida N, Gregório C, Cabral JEP, Casela A, Donato MM, Tomé L. Levofloxacin or Clarithromycin-based quadruple regimens: what is the best alternative as first-line treatment for Helicobacter pylori eradication in a country with high resistance rates for both antibiotics? BMC Gastroenterol 2017; 17:31. [PMID: 28202013 PMCID: PMC5312567 DOI: 10.1186/s12876-017-0589-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 02/11/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Helicobacter pylori eradication rates in Portugal are declining, due to increased resistance of this bacterium to antimicrobial agents, especially Clarithromycin. Quadruple Levofloxacin-containing regimens could be an option for first-line treatment, but its efficacy should be evaluated as fluoroquinolone resistance is rapidly increasing. Our aim was to compare the efficacy of Clarithromycin and Levofloxacin-based sequential quadruple therapies as first-line treatment options and determine factors associated with treatment failure. METHODS A total of 200 Helicobacter pylori infected patients were retrospectively included (female 57.5%; average age: 53.2 ± 15.7) and received either 10-day sequential therapy (Proton-Pump Inhibitor + Amoxicillin 1 g bid for 5 days and Proton-Pump Inhibitor + Clarithromycin 500 mg + Metronidazole/Tinidazole 500 mg bid/tid in the following 5 days; group A) or a 10-day modified sequential therapy with Levofloxacin 500 mg id instead of Clarithromycin (group B). Eradication was confirmed with urea breath test. Variables that could influence success rate were analyzed. RESULTS There were no differences between groups in terms of gender, age, smoking habits and indications for treatment. The eradication rate obtained with Clarithromycin-based sequential treatment was significantly higher than with Levofloxacin-based therapy (90%, CI95%: 84-96% vs. 79%, CI95%: 71-87%, p = 0.001). Using full-dose proton-pump inhibitor and high-dose Metronidazole in group A, and full-dose proton-pump inhibitor and prescription from a Gastroenterologist in group B were associated with eradication success. CONCLUSIONS Ten-day Levofloxacin-based sequential treatment achieved inadequate efficacy rate (<80%) and should not be adopted as first-line therapy. Standard sequential therapy showed significantly better results in this naïve population. Using full-dose proton-pump inhibitor and higher doses of Metronidazole is essential to achieve such results.
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Affiliation(s)
- Diogo Branquinho
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. .,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal.
| | - Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
| | - Carlos Gregório
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - José Eduardo Pina Cabral
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - Adriano Casela
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - Maria Manuel Donato
- Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
| | - Luís Tomé
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
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Dore MP, Pes GM, Sferlazzo G, Marras G, Bassotti G. Role of Helicobacter pylori Infection in Body Height of Adult Dyspeptic Patients. Helicobacter 2016; 21:575-580. [PMID: 27098759 DOI: 10.1111/hel.12314] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION The prevalence of H. pylori infection is high in underdeveloped countries and is associated with growth retardation. In the first half of the 20th century, Sardinia was an underdeveloped region; however, more recent development resulted in a decline in H. pylori infection. Because body height is correlated with health and nutritional status in childhood, the association among H. pylori infection and height was explored. MATERIALS AND METHODS A retrospective observational study was conducted involving patients undergoing endoscopy for dyspepsia from 2002 to 2012. H. pylori status was assessed by histology plus the rapid urease test or 13Carbon-urea breath test. RESULTS Body height and H. pylori status were assessed in 5045 adult patients: 3257 (64.6%) were women. Patients born after 1950 showed a significant increase in height (average 3.22 cm) compared to patients born before 1950 (163.93 vs 160 cm; 95% confidence interval, CI = 2.74-3.70 cm) (p < .0001). H. pylori-infected patients were nearly 1 cm shorter than uninfected patients (95% CI = -1.35 to·-0.09 cm) (p = .012). The multivariate linear regression analysis showed male gender, birth cohort, and occupational categories to be strongly associated with height, while the weak effect of H. pylori infection disappeared. CONCLUSIONS Our results demonstrate a strong secular trend related to body height in Sardinia with a minimal influence of H. pylori infection.
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Affiliation(s)
- Maria P Dore
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
- Baylor College of Medicine, Houston, Texas, USA
| | - Giovanni M Pes
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Giovanni Sferlazzo
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Giuseppina Marras
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Gabrio Bassotti
- Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy
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Keogan DM, Twamley B, Fitzgerald-Hughes D, Griffith DM. Novel class of Bi(iii) hydroxamato complexes: synthesis, urease inhibitory activity and activity against H. pylori. Dalton Trans 2016; 45:11008-11014. [PMID: 27314129 DOI: 10.1039/c5dt05061h] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Reaction of Bi(NO3)3 with benzohydroxamic acid (Bha) and salicylhydroxamic acid (Sha) gives the novel Bi(iii) complexes [Bi2(Bha-1H)2(μ-Bha-1H)2(η(2)-NO3)2] () and [Bi6(CH3OH)2(η(1)-NO3)2(η(2)-NO3)(OH2)2(Sha-1H)12](NO3)2 (). X-ray crystal structure of reveals two hydroxamato coordination modes; bidentate bridging (O, O') and bidentate non-bridging (O, O') and of reveals one coordination mode; bidentate bridging (O, O'). , specifically designed to and demonstrated to inhibit the activity of urease, exhibits excellent antibacterial activity against three strains of Helicobacter pylori with MIC ≥ 16 μg mL(-1).
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Affiliation(s)
- D M Keogan
- Centre for Synthesis & Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
| | - B Twamley
- School of Chemistry, Chemistry Building, Trinity College Dublin, Dublin 2, Ireland
| | - D Fitzgerald-Hughes
- RCSI Microbiology, Royal College of Surgeons in Ireland, RCSI Education & Research Centre, Beaumont Hospital, Beaumont, Dublin 9, Ireland
| | - D M Griffith
- Centre for Synthesis & Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
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Augmentation of Autoantibodies by Helicobacter pylori in Parkinson's Disease Patients May Be Linked to Greater Severity. PLoS One 2016; 11:e0153725. [PMID: 27100827 PMCID: PMC4839651 DOI: 10.1371/journal.pone.0153725] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 04/01/2016] [Indexed: 12/20/2022] Open
Abstract
Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.
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Miklossy J, McGeer PL. Common mechanisms involved in Alzheimer's disease and type 2 diabetes: a key role of chronic bacterial infection and inflammation. Aging (Albany NY) 2016; 8:575-88. [PMID: 26961231 PMCID: PMC4925815 DOI: 10.18632/aging.100921] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Accepted: 02/20/2016] [Indexed: 12/30/2022]
Abstract
Strong epidemiologic evidence and common molecular mechanisms support an association between Alzheimer's disease (AD) and type 2-diabetes. Local inflammation and amyloidosis occur in both diseases and are associated with periodontitis and various infectious agents. This article reviews the evidence for the presence of local inflammation and bacteria in type 2 diabetes and discusses host pathogen interactions in chronic inflammatory disorders. Chlamydophyla pneumoniae, Helicobacter pylori and spirochetes are demonstrated in association with dementia and brain lesions in AD and islet lesions in type 2 diabetes. The presence of pathogens in host tissues activates immune responses through Toll-like receptor signaling pathways. Evasion of pathogens from complement-mediated attack results in persistent infection, inflammation and amyloidosis. Amyloid beta and the pancreatic amyloid called amylin bind to lipid bilayers and produce Ca(2+) influx and bacteriolysis. Similarly to AD, accumulation of amylin deposits in type 2 diabetes may result from an innate immune response to chronic bacterial infections, which are known to be associated with amyloidosis. Further research based on an infectious origin of both AD and type 2 diabetes may lead to novel treatment strategies.
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Affiliation(s)
- Judith Miklossy
- International Alzheimer Research Centre, Prevention Alzheimer International Foundation, Martigny-Croix, Switzerland
| | - Patrick L. McGeer
- Kinsmen Laboratory of Neurological Research, The University of British Columbia, Vancouver, B.C, Canada
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Kell DB, Kenny LC. A Dormant Microbial Component in the Development of Preeclampsia. Front Med (Lausanne) 2016; 3:60. [PMID: 27965958 PMCID: PMC5126693 DOI: 10.3389/fmed.2016.00060] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 11/04/2016] [Indexed: 12/12/2022] Open
Abstract
Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of "preeclampsia" that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.
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Affiliation(s)
- Douglas B. Kell
- School of Chemistry, The University of Manchester, Manchester, UK
- The Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK
- Centre for Synthetic Biology of Fine and Speciality Chemicals, The University of Manchester, Manchester, UK
- *Correspondence: Douglas B. Kell,
| | - Louise C. Kenny
- The Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland
- Department of Obstetrics and Gynecology, University College Cork, Cork, Ireland
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Rabelo-Gonçalves EMA, Roesler BM, Zeitune JMR. Extragastric manifestations of Helicobacter pylori infection: Possible role of bacterium in liver and pancreas diseases. World J Hepatol 2015; 7:2968-2979. [PMID: 26730276 PMCID: PMC4691700 DOI: 10.4254/wjh.v7.i30.2968] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 12/15/2015] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.
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Yang Z, Li W, He C, Xie C, Zhu Y, Lu NH. Potential effect of chronic Helicobacter pylori infection on glucose metabolism of Mongolian gerbils. World J Gastroenterol 2015; 21:12593-12604. [PMID: 26640335 PMCID: PMC4658613 DOI: 10.3748/wjg.v21.i44.12593] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 06/19/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effect of Helicobacter pylori (H. pylori) infection on metabolic parameters in Mongolian gerbils.
METHODS: A total of 40 male, 5- to 8-wk-old, specific-pathogen-free Mongolian gerbils (30-50 g) were randomly allocated into two groups: a control group (n = 20) and an H. pylori group (n = 20). After a two-week acclimation period, the control group was administered Brucella broth and the H. pylori group was challenged intra-gastrically five times every other day with approximately 109/CFU H. pylori ATCC43504 (CagA+, VacA+). Each group was then divided into two subgroups, which were sacrificed at either 6 or 12 mo. The control and H. pylori subgroups each contained 10 Mongolian gerbils. Body weight, abdominal circumference, and body length were measured, and body mass index (BMI) and Lee’s index were calculated. Biochemical assays were used to detect serum indexes, including glucose, glycated hemoglobin (GHb), glycated hemoglobin A1c (HbA1c), triacylglycerol, and total cholesterol, using an automatic biochemistry analyzer. Inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-10, IL-12, tumor necrosis factor-α (TNF-α) and interferon (IFN)-γ, were assayed using ELISA. The expression of insulin and insulin-like growth factor 1 (IGF-1) was detected by immunohistochemistry, and islet apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
RESULTS: At each time point, body weight, abdominal circumference, BMI, and Lee’s index were increased after H. pylori infection. However, these differences were not significant. H. pylori infection significantly increased the GHb (5.45 ± 0.53 vs 4.98 ± 0.22, P < 0.05) and HbA1c (4.91 ± 0.61 vs 4.61 ± 0.15, P < 0.05) levels at 12 mo. We observed no significant differences in serum biochemical indexes, including fasting blood glucose, triacylglycerol and total cholesterol, at 6 or 12 mo after infection. H. pylori infection significantly increased the expression of IGF-1 (P < 0.05). Insulin levels from the pancreas and the apoptotic rate of islet β-cells remained unchanged. Also, we observed no significant differences among cytokines levels, including IL-1β, IL-2, IL-4, IL-10, IL-12, TNF-α and IFN-γ. IL-4 was the only exception, which increased at 6 (44.36 ± 25.17 vs 17.38 ± 3.47, P < 0.05) and 12 mo (33.41 ± 10.00 vs 18.91 ± 5.31, P < 0.05) after H. pylori infection.
CONCLUSION: Long-term H. pylori infection is significantly associated with high levels of HbA1c in Mongolian gerbils, indicating a potential role of H. pylori infection in glucose dysregulation.
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40
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Losurdo G, Leandro G, Principi M, Giorgio F, Montenegro L, Sorrentino C, Ierardi E, Di Leo A. Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'. Int J Clin Pract 2015; 69:1112-1120. [PMID: 26138290 DOI: 10.1111/ijcp.12687] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Sequential therapy is a first-line regimen obtaining satisfactory Helicobacter pylori eradication. Triple therapy prolongation improves the success rate even if a recent meta-analysis showed satisfying results only for the 14-day regimen. Studies from Africa and North America were unavailable in previous meta-analyses. AIM To perform a meta-analysis comparing sequential vs. prolonged 14-day triple therapy with regard to 'geographic weighting' by considering subgroups analysis according to metronidazole/clarithromycin low and high resistance areas. METHODS Based on PRISMA recommendations, we considered all first-line clinical studies from 2003 to November 2014. Randomised clinical trials (RCTs) were included by a search on PubMed, MEDLINE, Science Direct, EMBASE. Data on eradication rates were expressed as ITT. Risk ratio (RR), pooled RR and 95% confidence intervals were calculated by the Mantel-Haenszel method. Data were entered into RevMan 5.2 software (Nordic Cochrane Centre) using a random-effects model. RESULTS Databases identified 194 studies; seven met the inclusion criteria. Overall results showed a similar effectiveness of the two regimens considered (RR = 0.99; 95% CI = 0.94-1.05; p = 0.75). In areas with high resistance to clarithromycin, sequential was superior to 14-day triple therapy (RR = 0.95; 95% CI = 0.90-1.00; p = 0.03). In areas with high metronidazole resistance, sequential and 14-day triple therapy were equivalent (RR = 0.99; 95% CI = 0.91-1.08; p = 0.82). CONCLUSIONS 'Geographic weighting' could be the main factor affecting the lack of differences between sequential and 14-day triple therapy outcomes.
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Affiliation(s)
- G Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - G Leandro
- Gastroenterological Department, IRCCS "De Bellis" Hospital, Castellana Grotte, Italy
| | - M Principi
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - F Giorgio
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - L Montenegro
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - C Sorrentino
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - E Ierardi
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - A Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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Kim HS, Im HN, An DR, Yoon JY, Jang JY, Mobashery S, Hesek D, Lee M, Yoo J, Cui M, Choi S, Kim C, Lee NK, Kim SJ, Kim JY, Bang G, Han BW, Lee BI, Yoon HJ, Suh SW. The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase. J Biol Chem 2015; 290:25103-17. [PMID: 26306031 PMCID: PMC4599014 DOI: 10.1074/jbc.m115.658781] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Indexed: 01/01/2023] Open
Abstract
Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H. pylori, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of l,d-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known l,d-transpeptidases. Mass analyses confirm that Csd6 functions only as an l,d-carboxypeptidase and not as an l,d-transpeptidase. The d-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and in silico docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that H. pylori Csd6 and its homologs constitute a new family of l,d-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of H. pylori.
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Affiliation(s)
- Hyoun Sook Kim
- From the Departments of Chemistry and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
| | - Ha Na Im
- Biophysics and Chemical Biology, College of Natural Sciences, and
| | - Doo Ri An
- Biophysics and Chemical Biology, College of Natural Sciences, and
| | - Ji Young Yoon
- Biophysics and Chemical Biology, College of Natural Sciences, and
| | | | - Shahriar Mobashery
- the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
| | - Dusan Hesek
- the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
| | - Mijoon Lee
- the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
| | - Jakyung Yoo
- the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea
| | - Minghua Cui
- the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea
| | - Sun Choi
- the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea
| | - Cheolhee Kim
- the Department of Physics, POSTECH, Pohang 790-784, Republic of Korea
| | - Nam Ki Lee
- the Department of Physics, POSTECH, Pohang 790-784, Republic of Korea
| | - Soon-Jong Kim
- the Department of Chemistry, Mokpo National University, Chonnam 534-729, Republic of Korea
| | - Jin Young Kim
- the Division of Mass Spectrometry, Korea Basic Science Institute, Chungbuk 363-883, Republic of Korea, and
| | - Geul Bang
- the Division of Mass Spectrometry, Korea Basic Science Institute, Chungbuk 363-883, Republic of Korea, and
| | - Byung Woo Han
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
| | - Byung Il Lee
- the Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea
| | | | - Se Won Suh
- From the Departments of Chemistry and Biophysics and Chemical Biology, College of Natural Sciences, and
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42
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Frydman GH, Davis N, Beck PL, Fox JG. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography. Helicobacter 2015; 20:239-51. [PMID: 25728540 PMCID: PMC4506733 DOI: 10.1111/hel.12200] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.
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Affiliation(s)
- Galit H. Frydman
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Nick Davis
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Paul L. Beck
- The Gastrointestinal Research Group, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada
| | - James G. Fox
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
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43
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Yu M, Zhang Y, Yang Z, Ding J, Xie C, Lu N. Association between Helicobacter pylori infection and stroke: a meta-analysis of prospective observational studies. J Stroke Cerebrovasc Dis 2015; 23:2233-9. [PMID: 25263434 DOI: 10.1016/j.jstrokecerebrovasdis.2014.04.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Accepted: 04/03/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Some studies have suggested an association between Helicobacter pylori infection and the risk of stroke, but the relationship remains controversial. The aim of this study was to obtain a more comprehensive estimate of H. pylori on the risk of stroke by performing a meta-analysis. METHODS A computerized search of PubMed, EMBASE, and the Cochrane library (including CENTRAL) up to February 2014 was performed to identify eligible studies. Prospective studies reported that a multivariate-adjusted estimate for the association between H. pylori and stroke were included. A random-effects model was used to calculate the overall combined risk. RESULTS Ten prospective observational studies (6 cohort studies, 4 nested case-control, or case-cohort studies within cohort studies) were included in the meta-analysis. The overall combined odds ratio for H. infection and stroke was .96 (95% confidence interval, .78-1.14). Similar results were yielded in patients with cytotoxin-associated gene-A seropositive strains. The combined estimates were robust across sensitivity analyses and had no observed publication bias. CONCLUSIONS In conclusion, our formal meta-analysis indicated no strong association between H. pylori infection and stroke, neither in those with cytotoxin-associated gene-A-positive infection. We believe that future epidemiologic studies of H. pylori and stroke are unlikely to be fruitful.
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Affiliation(s)
- Min Yu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Yangbo Zhang
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Guangzhou, People's Republic of China
| | - Zhen Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Jiangwu Ding
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
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Dai YN, Yu WL, Zhu HT, Ding JX, Yu CH, Li YM. Is Helicobacter pylori infection associated with glycemic control in diabetics? World J Gastroenterol 2015; 21:5407-5416. [PMID: 25954115 PMCID: PMC4419082 DOI: 10.3748/wjg.v21.i17.5407] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 10/31/2014] [Accepted: 12/08/2014] [Indexed: 02/07/2023] Open
Abstract
AIM To investigate whether Helicobacter pylori (H. pylori) infection is associated with glycemic control and whether hyperglycemia is modified by eradication therapy. METHODS The databases of PubMed, Cochrane Library, Chinese BioMedicine Web Base and Chinese Science and Technology Journals were searched from inception to June 2014. Studies examining the association between H. pylori infection and glycemic control and/or the effect of eradication treatment on glycemic control in diabetic humans were eligible for inclusion. Meta-analyses were conducted using the Review Manager software version 5.2. The outcome measures are presented as weighed mean differences (WMDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed by the Cochran Q test and the I(2) statistic. RESULTS A total of 21 relevant publications were identified. A meta-analysis of 11 studies with 513 patients with diabetes mellitus (DM) showed significantly lower glycosylated hemoglobin (HbA1c) levels in the H. pylori-negative than H. pylori-positive DM participants (WMD = 0.43, 95%CI: 0.07-0.79; P = 0.02). In children and adolescents with type 1 DM (T1DM), there was a positive association between H. pylori infection and HbA1c level (WMD = 0.35, 95%CI: 0.05-0.64; P = 0.02), but there was no difference in those with type 2 DM (T2DM, WMD = 0.51, 95%CI: -0.63-1.65; P = 0.38). A meta-analysis of six studies with 325 T2DM participants showed a significant difference in the fasting plasma glucose levels between H. pylori-positive and H. pylori-negative participants (WMD = 1.20, 95%CI: 0.17-2.23; P = 0.02). Eradication of H. pylori did not improve glycemic control in the T2DM participants in a three-month follow-up period (HbA1c decrease: WMD = -0.03, 95%CI = -0.14-0.08; P = 0.57; fasting plasma glucose decrease: WMD = -0.06, 95%CI: -0.36-0.23; P = 0.68). Glycemic control was significantly better in T1DM participants who were not reinfected than in those who were reinfected (HbA1c: WMD = 0.72, 95%CI: 0.32-1.13: P = 0.00). CONCLUSION H. pylori infection is associated with poorer glycemic control in T1DM patients, but eradication may not improve glycemic control in DM in a short-term follow-up period.
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MESH Headings
- Adolescent
- Adult
- Anti-Bacterial Agents/therapeutic use
- Biomarkers/blood
- Blood Glucose/drug effects
- Blood Glucose/metabolism
- Chi-Square Distribution
- Child
- Diabetes Mellitus, Type 1/blood
- Diabetes Mellitus, Type 1/diagnosis
- Diabetes Mellitus, Type 1/drug therapy
- Diabetes Mellitus, Type 1/epidemiology
- Diabetes Mellitus, Type 1/microbiology
- Diabetes Mellitus, Type 2/blood
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/epidemiology
- Diabetes Mellitus, Type 2/microbiology
- Drug Therapy, Combination
- Female
- Glycated Hemoglobin/metabolism
- Helicobacter Infections/diagnosis
- Helicobacter Infections/drug therapy
- Helicobacter Infections/epidemiology
- Helicobacter Infections/microbiology
- Helicobacter pylori/drug effects
- Helicobacter pylori/pathogenicity
- Humans
- Hypoglycemic Agents/therapeutic use
- Male
- Middle Aged
- Odds Ratio
- Proton Pump Inhibitors/therapeutic use
- Risk Factors
- Treatment Outcome
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45
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Besednova NN, Zaporozhets TS, Somova LM, Kuznetsova TA. Review: prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by Helicobacter pylori. Helicobacter 2015; 20:89-97. [PMID: 25660579 DOI: 10.1111/hel.12177] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Helicobacter pylori possesses a broad spectrum of pathogenic factors that allow it to survive and colonize the gastric mucosa, and thus, the pathogenetic targets, which have the same diversity, require search for and the development of alternative, effective, and innocuous means for the eradication of H. pylori. In recent years, fucoidans have been extensively studied due to the numerous interesting biological activities, including the anti-adhesive, anti-oxidative, antitoxic, immunomodulatory, anticoagulant, and anti-infection effects. This review summarizes the data on the effects of extracts and sulfated polysaccharides of marine algae, mainly fucoidans, on pathogenic targets in Helicobacter infection. The pathogenetic targets for therapeutic agents after H. pylori infection, such as flagellas, urease, and other enzymes, including adhesins, cytotoxin A (VacA), phospholipase, and L-8, are characterized here. The main target for the sulfated polysaccharides of seaweed is cell receptors of the gastric mucosa. This review presents the published data about the pleiotropic anti-inflammatory effects of polysaccharides on the gastric mucosa. It is known that fucoidan and other sulfated polysaccharides from algae have anti-ulcer effects, prevent the adhesion of H. pylori to, and reduce the formation of biofilm. The authors speculate that the effect of sulfated polysaccharides on the infectious process caused by H. pylori is related to their action on innate and adaptive immunity cells, and also anti-oxidant and antitoxic potential. Presented in the review are materials indicated for the study of extracts and sulfated polysaccharides from seaweed during H. pylori infection, as these compounds are characterized by multimodality actions. Based on the analysis of literary materials in recent years, the authors concluded that fucoidan can be attributed to the generation of new candidates to create drugs intended for the inclusion in the scheme of eradication therapy of H. pylori infection.
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Affiliation(s)
- Natalya N Besednova
- G.P. Somov Research Institute of Epidemiology and Microbiology, Siberian Branch of the Russian Academy of Medical Sciences, Vladivostok, Russia
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Effects of H. pylori infection on carotid intima-media thickness, serum glucose, serum uric acid, liver and kidney function in subjects with chronic alcohol ingestion. Int J Cardiol 2015; 187:470-1. [PMID: 25846655 DOI: 10.1016/j.ijcard.2015.03.338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 03/21/2015] [Indexed: 02/07/2023]
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47
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Dietary and anthropometric indicators of nutritional status in relation to Helicobacter pylori infection in a paediatric population. Br J Nutr 2015; 113:1113-9. [PMID: 25761510 DOI: 10.1017/s0007114515000483] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
It has been postulated that Helicobacter pylori infection could affect growth and appetite, consequently influencing body weight. Therefore, the association between H. pylori infection and the dietary and anthropometric indicators of nutritional status of a paediatric population were investigated. A total of 525 children (aged 4-16 years) who were referred to the gastroenterology unit of the Sor Maria Ludovica Children's Hospital from Buenos Aires, Argentina, were enrolled and completed an epidemiological questionnaire. H. pylori infection was diagnosed using the ¹³C-urea breath test (¹³C-UBT). Height and weight were assessed for calculation of anthropometric indicators. Energy and macronutrient intakes were estimated by 24 h dietary recall. Data analysis was performed using a χ² test, a Student's t test, a Mann-Whitney U test and linear and logistic regressions. The prevalence of H. pylori infection was 25·1 % (with a mean age of 10·1 (SD 3·1) years). A tendency towards lower energy, carbohydrate, protein and fat intakes was observed in infected patients; however, it was not associated with H. pylori infection in any of the evaluated age groups (4-8, 9-13 and 14-16 years). Underweight, stunting, overweight and obesity were also not associated with the infection. Although height-for-age and BMI-for-age Z scores tended to be lower in infected patients, the differences between H. pylori-positive and H. pylori-negative children were not statistically significant. In conclusion, H. pylori infection was not associated with dietary intake or with anthropometric indicators in the present population of children with gastrointestinal symptoms; however, an increased sample size would be needed to confirm the observed tendency towards lower dietary intake and lower anthropometric indicators of nutritional status in H. pylori-infected children.
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Zhao Y, Dua P, Lukiw WJ. Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's Disease (AD). JOURNAL OF ALZHEIMER'S DISEASE & PARKINSONISM 2015; 5:177. [PMID: 25977840 PMCID: PMC4428612 DOI: 10.4172/2161-0460.1000177] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~1014 microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest 'diffuse organ system' in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer's disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.
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Affiliation(s)
- Y Zhao
- LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans LA 70112 USA ; Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans LA 70112 USA
| | - P Dua
- Department of Health Information Management, Louisiana State University Ruston LA 71270 USA
| | - W J Lukiw
- LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans LA 70112 USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans LA 70112 USA ; Department of Neurology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112 USA
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An DR, Kim HS, Kim J, Im HN, Yoon HJ, Yoon JY, Jang JY, Hesek D, Lee M, Mobashery S, Kim SJ, Lee BI, Suh SW. Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase. ACTA CRYSTALLOGRAPHICA. SECTION D, BIOLOGICAL CRYSTALLOGRAPHY 2015; 71:675-86. [PMID: 25760614 PMCID: PMC4356371 DOI: 10.1107/s1399004715000152] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 01/06/2015] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its D,D-endopeptidase activity cleaves the D-Ala(4)-mDAP(3) peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a D,D-carboxypeptidase that cleaves off the terminal D-Ala(5) from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn(2+) ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.
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Affiliation(s)
- Doo Ri An
- Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Hyoun Sook Kim
- Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
| | - Jieun Kim
- Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Ha Na Im
- Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Hye Jin Yoon
- Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Ji Young Yoon
- Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Jun Young Jang
- Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
| | - Dusan Hesek
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Mijoon Lee
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Shahriar Mobashery
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Soon-Jong Kim
- Department of Chemistry, Mokpo National University, Chonnam 534-729, Republic of Korea
| | - Byung Il Lee
- Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea
| | - Se Won Suh
- Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
- Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea
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50
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Yilmaz I, Erkul E, Berber U, Kucukodaci Z, Narli G, Haholu A, Demirel D. The presence of Helicobacter pylori in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2015; 273:761-5. [PMID: 25721196 DOI: 10.1007/s00405-015-3566-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2014] [Accepted: 02/16/2015] [Indexed: 02/07/2023]
Abstract
A definitive relationship between Helicobacter pylori (HP) and upper respiratory tract disorders has not been established. In this case-control study, we investigated the relationship between HP and laryngeal carcinoma by real-time PCR method in Turkey. 74 subjects were enrolled from patients who were admitted to the Otolaryngology Department. Formalin-fixed-paraffin-embedded tissue samples with laryngeal cancer were used and all samples were evaluated by real-time PCR method. Our study population included 72 males and 2 females with a mean age range of 62.7 years. Helicobacter Pylori was detected in only one case. The positive case was also investigated with histopathologic evaluation and HP immunohistochemistry. However, we could not detect HP in this case with both methods. This study revealed that HP might not contribute to the pathogenesis of laryngeal carcinoma. A definitive relationship between HP and upper respiratory tract disorders has not been established.
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Affiliation(s)
- Ismail Yilmaz
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
| | - E Erkul
- Department of Otorhinolaryngology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
| | - U Berber
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
| | - Z Kucukodaci
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
| | - G Narli
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
| | - A Haholu
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
| | - D Demirel
- Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
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