|
1
|
Xie J, Peng J, Wu S, Yang K, Liu D, Shen L, Gong X, Liu D, Xie Y. Efficacy and safety of tetracycline vs. amoxicillin in furazolidone-based rescue therapy for Helicobacter pylori: a real-world analysis. Ann Med 2025; 57:2464938. [PMID: 39950212 PMCID: PMC11834778 DOI: 10.1080/07853890.2025.2464938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 01/23/2025] [Accepted: 01/25/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND AND AIM Despite the increasing rates of antibiotic resistance, furazolidone-based regimens have demonstrated promise in Helicobacter pylori eradication. Therefore, this study aims to evaluate the comparative efficacy and safety of tetracycline versus amoxicillin in furazolidone-based quadruple therapy [bismuth quadruple therapy with furazolidone and tetracycline (BQFT) vs. bismuth quadruple therapy with furazolidone and amoxicillin (BQFA)] in rescue treatments. METHODS Patients who received BQFT or BQFA as rescue treatment were enrolled in this study. H. pylori status was determined using the 13C/14C urea breath test or histological examination. Eradication rates, adherence and side effects were carefully recorded. RESULTS A total of 342 participants were included. BQFT showed significantly higher eradication rates (modified intention-to-treat: 96.2% vs. 76%; per-protocol: 97.1% vs. 77.8%, P < 0.001), suggesting superior efficacy for patients with prior treatment failures. However, BQFA demonstrated fewer overall adverse effects (11.6% vs. 20.7%, P = 0.046), highlighting a tolerability advantage. Both groups showed similar symptom improvements and compliance rates. CONCLUSION BQFT exhibits superior efficacy with acceptable tolerability, making it a promising option for patients with refractory H. pylori infections. Clinicians should consider its benefits in cases of multiple prior eradication failures.
Collapse
Affiliation(s)
- Jinliang Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Jianxiang Peng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Shuang Wu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The Second People’s Hospital of Jingdezhen, Jingdezhen, China
| | - Kaijie Yang
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, People’s Hospital of Ganzhou, Ganzhou, China
| | - Dingwei Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Liting Shen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Xiaomin Gong
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Dongsheng Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Yong Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Nanchang, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, China
| |
Collapse
|
|
2
|
Zhao YR, Wang XJ, Zhu MJ, Chen AL, Zhang D, Du Q, Kim JJ, Hu WL. Efficacy and safety of low-dose tetracycline, amoxicillin quadruple therapy in Helicobacter pylori infection: A retrospective single center study. World J Gastroenterol 2024; 30:4295-4304. [PMID: 39492823 PMCID: PMC11525849 DOI: 10.3748/wjg.v30.i39.4295] [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: 05/14/2024] [Revised: 09/09/2024] [Accepted: 09/24/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) eradication rates have declined with the rise of antibiotic-resistant strains in recent years. Although highly effective with a low prevalence of resistance, standard dose tetracycline is associated with frequent adverse events. The efficacy and safety of low-dose tetracycline as part of tetracycline and amoxicillin-containing bismuth quadruple therapy are not well described. AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H. pylori infection. METHODS Consecutive patients with H. pylori infection receiving tetracycline, amoxicillin, proton pump inhibitor, and bismuth for 14 days at Sir Run Run Shaw Hospital (1/2022-6/2023) were evaluated. The low-dose tetracycline group received tetracycline 500 mg twice daily (bid) while the standard dose group received 750 mg bid or 500 mg three times daily (tid). Primary endpoints were H. pylori eradication rate and treatment-related adverse events. RESULTS The mean age of the 218 patients was 48.7 ± 14.0 years, 120 (55%) were male, and 118 (54.1%) received treatment as primary therapy. Furthermore, 73 (33%) patients received low-dose tetracycline (500 mg bid) and 145 (67%) received standard dose tetracycline including 500 mg tid in 74 (33%) and 750 mg bid in 71 (33%). On intention-to-treat analysis, H. pylori eradication rates were 89% [95% confidence interval (CI): 82%-96%] in the 500 mg bid group, 82% (95%CI: 74%-91%) in the 500 mg tid group, and 79% (95%CI: 69%-89%) in the 750 mg bid group without a statistically significant difference (P = 0.25). The incidence of adverse events was lower in the low-dose compared to the standard dose group (12.3% vs 31.1% or 23.9%; P = 0.02). CONCLUSION Low-dose tetracycline combined with amoxicillin quadruple therapy for 14 days achieved a high eradication rate and fewer adverse events compared to the standard dose tetracycline regimen in patients with H. pylori infection.
Collapse
Affiliation(s)
- Yi-Ru Zhao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Department of Gastroenterology, The First Affiliated Hospital, Medical School, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Xin-Jie Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Meng-Jia Zhu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Ang-Li Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Dian Zhang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Qin Du
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - John J Kim
- Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9021, United States
| | - Wei-Ling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| |
Collapse
|
|
3
|
Yamaguchi N, Sakaguchi T, Isomoto H, Inamine T, Ueda H, Fukuda D, Ohnita K, Kanda T, Kurumi H, Matsushima K, Hirayama T, Yashima K, Tsukamoto K. ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis. J Clin Med 2023; 12:5384. [PMID: 37629426 PMCID: PMC10455120 DOI: 10.3390/jcm12165384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/08/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337-1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.
Collapse
Affiliation(s)
- Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Takuki Sakaguchi
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
| | - Hajime Isomoto
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
| | - Tatsuo Inamine
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Haruka Ueda
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Daisuke Fukuda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
- Department of Surgical Oncology, Nagasaki University Graduate School of Biological Science, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
- Fukuda Yutaka Clinic, 3-5 Hamaguchi-machi, Nagasaki 852-8107, Japan
| | - Ken Ohnita
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
- Shunkaikai Inoue Hospital, 6-12 Takara-machi, Nagasaki 850-0045, Japan
| | - Tsutomu Kanda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
| | - Hiroki Kurumi
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Tatsuro Hirayama
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Kazuo Yashima
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan
| | - Kazuhiro Tsukamoto
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| |
Collapse
|
|
4
|
Lupu A, Gavrilovici C, Lupu VV, Cianga AL, Cernomaz AT, Starcea IM, Mihai CM, Tarca E, Mocanu A, Fotea S. Helicobacter pylori Infection in Children: A Possible Reason for Headache? Diagnostics (Basel) 2023; 13:diagnostics13071293. [PMID: 37046511 PMCID: PMC10093035 DOI: 10.3390/diagnostics13071293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/25/2023] [Accepted: 03/27/2023] [Indexed: 04/14/2023] Open
Abstract
(1) Background: The correlation between infection with Helicobacter pylori (H. pylori) and headache has been argued and explored for a long time, but a clear association between the simultaneous presence of the two in children has not been established yet. In this study, we aimed to explore this relationship in children from the Northeast region of Romania. (2) Methods: A retrospective study exploring the correlation between children having H. pylori infection and headache or migraine was conducted on a batch of 1757 children, hospitalized over 3 years in a pediatric gastroenterology department in Northeast Romania. (3) Results: A total of 130 children of both sexes had headache. From 130 children, 54 children (41.5%) also presented H. pylori infection. A significant association between headache and H. pylori infection (χ2; p < 0.01) was noticed. (4) Conclusions: More studies are needed on this relationship, and we emphasize the importance of further analyses, as they present great clinical importance for both prompt diagnosis and treatment.
Collapse
Affiliation(s)
- Ancuta Lupu
- Pediatrics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Cristina Gavrilovici
- Pediatrics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Vasile Valeriu Lupu
- Pediatrics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Anca Lavinia Cianga
- Pediatrics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Andrei Tudor Cernomaz
- III-rd Medical Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | | | - Cristina Maria Mihai
- Pediatrics, Faculty of General Medicine, Ovidius University, 900470 Constanta, Romania
| | - Elena Tarca
- Department of Surgery II-Pediatric Surgery, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Adriana Mocanu
- Pediatrics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Silvia Fotea
- Medical Department, Faculty of Medicine and Pharmacy, "Dunarea de Jos" University of Galati, 800008 Galati, Romania
| |
Collapse
|
|
5
|
Ahmed SFM, Abdelrahman MM, Mohammed MH. Evaluation of Immunohistochemical Expression of Heparanase in Helicobacter pylori-Associated Chronic Gastritis. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2023; 16:2632010X231188937. [PMID: 37534373 PMCID: PMC10392192 DOI: 10.1177/2632010x231188937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/03/2023] [Indexed: 08/04/2023]
Abstract
Background Chronic gastritis (CG) is a very common disease. More than half of the worldwide population suffers from symptoms of CG. This disease has received great attention since the discovery of H. pylori as the most important cause of CG. Symptoms experienced by patients with CG are attributed to H. pylori-induced inflammatory reactions. Heparanase (HPSE) is a mammalian β-endoglucoronidase. In inflammation; HPSE degrades and remodels the extracellular matrix's heparan sulfate polysaccharide chains liberating heparan sulfate-bound cytokines and chemokines, HPSE also facilitates movement of inflammatory cells. Aims This study aimed to detect the function of HPSE in CG by correlating levels of HPSE expression with histopathological features of CG, including H. pylori infection, acute and chronic inflammatory cells, mucosal atrophic and/or metaplastic features. Methods Ninety-five upper endoscopic-guided gastric punch biopsies were enrolled in this study. From each specimen, formalin-fixed and paraffin-embedded tissue blocks were prepared. Tissue sections were stained by Hematoxylin and eosin, Giemsa, and anti-heparanase antibody. Results HPSE expression was statistically associated with H. pylori infection (P-value < .000), and intensity of chronic lymphocytic inflammatory infiltrate in the gastric mucosal tissues (P = .004). High levels of HPSE expression were also related to the presence of neutrophils in the gastric surface epithelium and lamina propria (P-value < .009). Conclusions HPSE expression was upregulated in H. pylori-associated chronic gastritis. Thus, future therapeutic agents that could specifically inhibit HPSE enzyme activity, may aid in the reduction of sequelae of H. pylori infection.
Collapse
Affiliation(s)
| | - Mona Mohammed Abdelrahman
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | | |
Collapse
|
|
6
|
Host Cell Antimicrobial Responses against Helicobacter pylori Infection: From Biological Aspects to Therapeutic Strategies. Int J Mol Sci 2022; 23:ijms231810941. [PMID: 36142852 PMCID: PMC9504325 DOI: 10.3390/ijms231810941] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/13/2022] [Accepted: 09/16/2022] [Indexed: 02/07/2023] Open
Abstract
The colonization of Helicobacter pylori (H. pylori) in human gastric mucosa is highly associated with the occurrence of gastritis, peptic ulcer, and gastric cancer. Antibiotics, including amoxicillin, clarithromycin, furazolidone, levofloxacin, metronidazole, and tetracycline, are commonly used and considered the major treatment regimens for H. pylori eradication, which is, however, becoming less effective by the increasing prevalence of H pylori resistance. Thus, it is urgent to understand the molecular mechanisms of H. pylori pathogenesis and develop alternative therapeutic strategies. In this review, we focus on the virulence factors for H. pylori colonization and survival within host gastric mucosa and the host antimicrobial responses against H. pylori infection. Moreover, we describe the current treatments for H. pylori eradication and provide some insights into new therapeutic strategies for H. pylori infection.
Collapse
|
|
7
|
Wang L, Yi J, Yin XY, Hou JX, Chen J, Xie B, Chen G, Wang QF, Wang LN, Wang XY, Sun J, Huo LM, Che TJ, Wei HL. Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells. Front Oncol 2022; 12:881829. [PMID: 35912184 PMCID: PMC9329568 DOI: 10.3389/fonc.2022.881829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/20/2022] [Indexed: 11/30/2022] Open
Abstract
Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein–protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.
Collapse
Affiliation(s)
- Li Wang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Juan Yi
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Xiao-Yang Yin
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Jin-Xia Hou
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Jing Chen
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Bei Xie
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Gang Chen
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Qun-Feng Wang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Li-Na Wang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Xiao-Yuan Wang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Jing Sun
- Geriatrics Department, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Lei-Ming Huo
- Neurosurgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - Tuan-Jie Che
- Key Laboratory of Functional Genomics and Molecular Diagnosis of Gansu Province, Lanzhou Baiyuan Gene Technology Co., Ltd, Lanzhou, China
- *Correspondence: Tuan-Jie Che, ; Hu-Lai Wei,
| | - Hu-Lai Wei
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Functional Genomics and Molecular Diagnosis of Gansu Province, Lanzhou Baiyuan Gene Technology Co., Ltd, Lanzhou, China
- *Correspondence: Tuan-Jie Che, ; Hu-Lai Wei,
| |
Collapse
|
|
8
|
Öcal S, Öcal R, Suna N. Relationship between Helicobacter pylori infection and white matter lesions in patients with migraine. BMC Neurol 2022; 22:187. [PMID: 35597897 PMCID: PMC9123779 DOI: 10.1186/s12883-022-02715-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/16/2022] [Indexed: 11/28/2022] Open
Abstract
Background/aim White matter lesions (WML) are more frequently observed in migraine patients than in the average population. Associations between Helicobacter pylori (H. pylori) infection and different extraintestinal pathologies have been identified. Here, we aimed to investigate the association between H. pylori infection and WML in patients diagnosed with episodic migraine. Materials and methods A retrospective study was conducted with 526 subjects with a diagnosis of episodic migraine. Hyperintensity of WML had been previously evaluated in these patients with brain magnetic resonance imaging (MRI) examinations. Previous endoscopic gastric biopsy histopathological examination of the same patients and reports on H. pylori findings were recorded. The demographic characteristics of the patients, such as age, gender and chronic systemic diseases such as hypertension and diabetes mellitus (DM) were recorded. Statistical evaluation was made. Results Evaluation was made among 526 migraine patients who met the inclusion criteria, comprising 397 (75.5%) females and 129 (24.5%) males with a mean age of 45.57 ± 13.46 years (range, 18–69 years). WML was detected on brain MRI in 178 (33.8%) patients who were also positive for H. pylori (p < 0.05). Subjects who are H. pylori-positive with migraine, WML were observed at a 2.5-fold higher incidence on brain MRI (odds ratio: 2.562, 95% CI 1.784–3.680). WML was found to be more significant in patients with hypertension and migraine than those without (p < 0.001). Older age was also found to be associated with WML (OR = 1.07, 95% CI: 0.01–0.04, p < 0.001). The age (p < 0.001), H. pylori (p < 0.001), hypertension (p < 0.001), and hypertension + DM (p < 0.05), had significant associations in predicting WML according to the multivariate logistic regression analysis. The presence of hypertension had a higher odds ratio value than the other variables. Conclusion It was concluded that H. pylori infection, as a chronic infection, can be considered a risk factor in developing WML in subjects with migraine. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-022-02715-0.
Collapse
Affiliation(s)
- Serkan Öcal
- Department of Gastroenterology, University of Health Sciences Antalya Training and Research Hospital, Antalya, Turkey.
| | - Ruhsen Öcal
- Antalya Training and Research Hospital Department of Neurology, Antalya, Turkey
| | - Nuretdin Suna
- Department of Gastroenterology, Faculty of Medicine, Başkent University, Ankara, Turkey
| |
Collapse
|
|
9
|
miR-30c Increases the Intracellular Survival of Helicobacter pylori by Inhibiting Autophagy. Cell Microbiol 2022. [DOI: 10.1155/2022/4536450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Persistent Helicobacter pylori infection causes a variety of gastrointestinal diseases and even gastric cancer. H. pylori invades gastric epithelial cells to survive and proliferate, which is one of the key factors in persistent colonization. A Published study has confirmed that cells can eliminate intracellular H. pylori through xenophagy to maintain intracellular balance. However, a growing body of evidences indicate that H. pylori can inhibit xenophagy by miRNA through regulating the expression of key autophagy-related genes. Through western blot analysis, mRFP-GFP-LC3 transfection assay, and transmission electron microscopy, we found that H. pylori infection obstructed autophagy flux degradation stage in GES-1 cell lines. Gentamicin protection assay confirmed that inhibit xenophagy is benefit for intracellular H. pylori survive. miR-30c-1-3p and miR-30c-5p were upregulated in GES-1 cell lines after infecting with H. pylori, resulting in the negative regulation on xenophagy. Further studies through bioinformatics analysis and dual-luciferase reporter assays confirmed that ATG14 and ULK1 were the target genes of miR-30c-1-3p and that ATG12 was the target gene of miR-30c-5p. The overexpression of miR-30c-1-3p and miR-30c-5p reduces the expression of ATG14, ULK1, and ATG12 at mRNA level and also decreased intracellular H. pylori elimination in GES-1 cells. The above results suggested that the inhibition on xenophagy by miR-30c-1-3p and miR-30c-5p through ATG14, ULK1, and ATG12 targeting benefitted intracellular H. pylori in the evasion of xenophagy clearance.
Collapse
|
|
10
|
Guo R, Wu S, Guan L, Xie Y, Yang X, Li Z, Zhang Z. Dietary multivalent anti-Helicobacter pylori immunoglobulin Y significantly increase the H. pylori eradication and improve the clinical symptoms in patients. Helicobacter 2021; 26:e12843. [PMID: 34382297 DOI: 10.1111/hel.12843] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/28/2021] [Accepted: 07/30/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The oral chicken immunoglobulin Y (IgY) as a novel model of immunotherapy to control Helicobacter pylori (H. pylori, Hp) infection has gained much interest in recent years. However, none of the current IgY therapies showed a total eradication of H. pylori on patients. METHODS In this report, the recombinant antigens of H. pylori, including UreB (1710 bp), BabA2 (1269 bp), and FlaA (399 bp), were, respectively, expressed and purified, and then mixed and subjected to immunize laying hens for the preparation of multivalent anti-H. pylori immunoglobulin Y (anti-Hp mIgY). Next, the biological activities of anti-Hp mIgY, including the recognition to antigens and the inhibition on H. pylori growth, were tested. Moreover, to perform a clinical trial, 94 Hp-infected patients, according to the values of 13 C urea breath test and the characteristics of gastroscopy of volunteers, were enrolled to evaluate the effects of dietary anti-Hp mIgY against H. pylori infection. After continuous dietary of anti-Hp mIgY for 2 weeks, the oral administration was terminated. The clinical symptoms of the patients were followed up at 2nd, 4th, and 6th week, respectively, and the 13 C urea breath test were re-examined at 6th week. RESULTS The anti-Hp mIgY could bind to recombinant antigens very well, and the titers of anti-Hp mIgY to UreB, Baba2, and FlaA, are 62.5, 125, and 250 μg/ml, respectively. The in vitro antibacterial test showed that the 2 mg/ml of anti-Hp mIgY could completely inhibit the H. pylori growth for 36 h. After a 2-week dietary of anti-Hp mIgY, the value of 13 C urea breath test was significantly decreased by 56.0% (25.9 ± 14.1 vs 11.4 ± 9.78, p < 0.001), the total improvement rate of clinical symptoms in volunteers was 87.3%, and the H. pylori eradication rate was 30.6%. CONCLUSION Two-week dietary of anti-Hp mIgY greatly improved the clinical symptoms and the quality of life of Hp-infected patients, and the H. pylori eradication rate reached up to 30.6%.
Collapse
Affiliation(s)
- Rong Guo
- Department of Gastroenterology, FuShun People's Hospital, Zigong, China
| | - Shan Wu
- Department of Gastroenterology, FuShun People's Hospital, Zigong, China
| | - Li Guan
- Department of Gastroenterology, FuShun People's Hospital, Zigong, China
| | - Yongmei Xie
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xifei Yang
- Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Medical Key Subject of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Zaixin Li
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, China
| | - Zhi Zhang
- Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, China
| |
Collapse
|
|
11
|
Golubinskaya EP, Sataieva TP, Fomochkina II, Kubyshkin AV, Makalish TP, Shkolyar NA, Galyshevskaya AA, Varghese DV. Predictive potential of macrophage population phenotyping in malignization of H. pylori-associated chronic gastritis. BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY 2021. [DOI: 10.24075/brsmu.2021.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Tumor-associated macrophages are able to regulate the tumor cell proliferation and to affect the tumor cell dissemination. The study was aimed to assess the predictive potential of the macrophage population immunohistochemical phenotyping in early malignization of H. pylori-associated chronic gastritis. Gastic biopsy samples of male and female patients aged 48 ± 7.2 infected with Helicobacter pylori were used as the research material. The patients were divided into three groups: non-atrophic chronic gastritis (NACG, n = 10), atrophic chronic gastritis (ACG, n = 10), G1/G2 gastric adenocarcinoma (GAC, n = 10). The macrophage population was visualized using the CD68 pan-macrophage marker and the type 2 monocyte/macrophage marker CD163. Intensity of neoangiogenesis was defined using the CD31 endothelial marker by assessing the total cross sectional area of blood vessels. It was found that chronic gastritis was accompanied by the dynamic increase in the size of the general macrophage population with the progression of atrophic and metaplastic processes. According to immunohistochemical study of biopsies obtained from patients with NCG, the CD163 : CD68 ratio was 0.67 ± 0.02, and the total cross sectional area of blood vessels was 3590.92 ± 356.27 µm2. Atrophic gastritis and adenocarcinoma were characterized by vector redistribution of monocytes/macrophages into the 2nd functional phenotype. The CD163 : CD68 expression index in the group with ACG was 0.81 ± 0.04, and in the group with GAC it was 0.88 ± 0.03. Microvascular area was significantly increased in the groups with ACG and GAC, which reflected tumor neoangiogenesis intensification under the influence of М2 monocytes/macrophages. The increased expression of CD163 can serve as a predictor of chronic gastritis malignization together with evaluation of the glandular epithelium atrophy and metaplasia degree.
Collapse
Affiliation(s)
- EP Golubinskaya
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - TP Sataieva
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - II Fomochkina
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - AV Kubyshkin
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - TP Makalish
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | | | | | - DV Varghese
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| |
Collapse
|
|
12
|
Tang L, Tang B, Lei Y, Yang M, Wang S, Hu S, Xie Z, Liu Y, Vlodavsky I, Yang S. Helicobacter pylori-Induced Heparanase Promotes H. pylori Colonization and Gastritis. Front Immunol 2021; 12:675747. [PMID: 34220822 PMCID: PMC8248549 DOI: 10.3389/fimmu.2021.675747] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/31/2021] [Indexed: 11/13/2022] Open
Abstract
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection has been widely recognized as the most important risk factor for gastric cancer. Analysis of the interaction between the key participants in gastric mucosal immunity and H. pylori infection is expected to provide important insights for the treatment of chronic gastritis and the prevention of gastric cancer. Heparanase is an endoglycosidase that degrades heparan sulfate, resulting in remodeling of the extracellular matrix thereby facilitating the extravasation and migration of immune cells towards sites of inflammation. Heparanase also releases heparan sulfate-bound cytokines and chemokines that further promote directed motility and recruitment of immune cells. Heparanase is highly expressed in a variety of inflammatory conditions and diseases, but its role in chronic gastritis has not been sufficiently explored. In this study, we report that H. pylori infection promotes up-regulation of heparanase in gastritis, which in turn facilitates the colonization of H. pylori in the gastric mucosa, thereby aggravating gastritis. By sustaining continuous activation, polarization and recruitment of macrophages that supply pro-inflammatory and pro-tumorigenic cytokines (i.e., IL-1, IL-6, IL-1β, TNF-α, MIP-2, iNOS), heparanase participates in the generation of a vicious circle, driven by enhanced NFκB and p38-MAPK signaling, that supports the development and progression of gastric cancer. These results suggest that inhibition of heparanase may block this self-sustaining cycle, and thereby reduce the risk of gastritis and gastric cancer.
Collapse
Affiliation(s)
- Li Tang
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Min Yang
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Sumin Wang
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Shiping Hu
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Zhuo Xie
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Yaojiang Liu
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| | - Israel Vlodavsky
- Technion Integrated Cancer Center (TICC), Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, The Army Medical University, Chongqing, China
| |
Collapse
|
|
13
|
Zhong Y, Tang L, Deng Q, Jing L, Zhang J, Zhang Y, Yu F, Ou Y, Guo S, Huang B, Cao H, Huang P, Xu Y. Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of Helicobacter pylori. Front Microbiol 2021; 12:674560. [PMID: 34149664 PMCID: PMC8206506 DOI: 10.3389/fmicb.2021.674560] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/20/2021] [Indexed: 12/17/2022] Open
Abstract
The long-term colonization of Helicobacter pylori can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of H. pylori. Patchouli alcohol (PA) shows a highly efficient activity against H. pylori in vitro and in vivo. And this study aims to explore whether PA can reduce the resistance of H. pylori and determine the underlying mechanism. Checkerboard and time-kill bactericidal curve assay reveal that the combination of PA and clarithromycin (CLR) promoted the inhibition and bactericidal effect against H. pylori. Stimulation of CLR leads to the internalization of H. pylori, but PA can effectively inhibit the invasion induced by CLR. Compared with antibiotics, PA remarkably eradicated the intracellular H. pylori, and this intracellular sterilized ability was further improved in combination with antibiotics (CLR and metronidazole). The expression of H. pylori efflux pump genes (hp0605, hp1327, and hp1489) was dose-dependently downregulated by PA. Digital droplet PCR indicated that the H. pylori mutant of A2143G can be inhibited by PA. Cellular uptake and transport assays showed that PA is rapidly absorbed, which promotes its activity against intracellular bacteria. Therefore, PA can act synergistically with CLR as a candidate treatment against drug-resistant H. pylori.
Collapse
Affiliation(s)
- Yuanzun Zhong
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liyao Tang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiuhua Deng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li Jing
- School of Basic Medical Science, Tianjin Medical University, Tianjin, China
| | - Jiao Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yao Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Feng Yu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yijun Ou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shaoju Guo
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Bin Huang
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Hongying Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ping Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yifei Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| |
Collapse
|
|
14
|
|
|
15
|
Antibiotics as a Stressing Factor Triggering the Harboring of Helicobacter pylori J99 within Candida albicans ATCC10231. Pathogens 2021; 10:pathogens10030382. [PMID: 33806815 PMCID: PMC8004595 DOI: 10.3390/pathogens10030382] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/12/2021] [Accepted: 03/16/2021] [Indexed: 12/18/2022] Open
Abstract
First-line treatment for Helicobacter pylori includes amoxicillin and clarithromycin or metronidazole plus a proton pump inhibitor. Treatment failure is associated with antibiotic resistance and possibly also with internalization of H. pylori into eukaryotic cells, such as yeasts. Factors triggering the entry of H. pylori into yeast are poorly understood. Therefore, the aim of this study was to evaluate whether clarithromycin or amoxicillin trigger the entry of H. pylori into C. albicans cells. METHODS H. pylori J99 and C. albicans ATCC 10231 were co-cultured in the presence of subinhibitory concentrations of amoxicillin and clarithromycin as stressors. Bacterial-bearing yeasts were observed by fresh examination. The viability of bacteria within yeasts was evaluated, confirming the entry of bacteria into Candida, amplifying, by PCR, the H. pylori16S rRNA gene in total yeast DNA. RESULTS Amoxicillin significantly increased the entry of H. pylori into C. albicans compared to the control. CONCLUSION the internalization of H. pylori into C. albicans in the presence of antibiotics is dependent on the type of antibiotic used, and it suggests that a therapy including amoxicillin may stimulate the entry of the bacterium into Candida, thus negatively affecting the success of the treatment.
Collapse
|
|
16
|
Hwang JY, Kim C, Kwon YH, Lee JE, Jeon SW, Nam SY, Seo AN, Han MH, Park JH. Dual Clarithromycin and Metronidazole Resistance Is the Main Cause of Failure in Ultimate Helicobacter pylori Eradication. Dig Dis 2021; 39:451-461. [PMID: 33429397 DOI: 10.1159/000514278] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 01/10/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND/AIM Antimicrobial resistance significantly affects the cure rate of Helicobacter pylori (H. pylori) eradication. We evaluated the risk factor of failure in ultimate H. pylori eradication and assessed the efficacy of current regimens to overcome antibiotic resistance. METHODS Patients with H. pylori infection were prospectively enrolled in a single center. They were classified into 3 groups according to the previous history of H. pylori eradication, and antibiotic susceptibility was evaluated by culture and minimum inhibitory concentrations (MICs). RESULTS Ninety-seven patients were successfully cultured for H. pylori and 81 (83.5%), 7 (7.2%), and 9 (9.3%) were classified into primary resistance, 1st eradication failure, and 2nd or more eradication failure groups; the resistance to clarithromycin (CLA), metronidazole (MET), and levofloxacin increased in the 1st eradication failure (85.7, 57.1, and 42.9%) and 2nd or more eradication failure (88.9, 88.9, and 55.6%) groups. The prevalence of MDR was 21.0% (17/81), 57.1% (4/7), and 88.9% (8/9) in the primary, 1st eradication failure, and 2nd or more eradication failure groups, respectively. In multivariate analysis, dual CLA/MET resistance (CLA/MET-R) (OR = 31.432, 95% CI: 3.094-319.266, p = 0.004) was an independent risk factor for ultimate H. pylori eradication failure. In patients with dual CLA/MET-R, the eradication ratio of concomitant therapy was 57.1% (4/7), whereas that of bismuth-containing quadruple therapy was 27.3% (3/11) (p = 0.350). CONCLUSIONS Dual CLA/MET-R was the main cause of failure in ultimate H. pylori eradication, and 7-day bismuth quadruple or concomitant regimen would not be suitable for H. pylori eradication in the dual CLA/MET-R group.
Collapse
Affiliation(s)
- Ji Yong Hwang
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Changho Kim
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yong Hwan Kwon
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.,School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Ji Eun Lee
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seong Woo Jeon
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.,School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Su Youn Nam
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - An Na Seo
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea.,Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Man-Hoon Han
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea.,Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Ji Hye Park
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| |
Collapse
|
|
17
|
Courtois S, Haykal M, Bodineau C, Sifré E, Azzi-Martin L, Ménard A, Mégraud F, Lehours P, Durán RV, Varon C, Bessède E. Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence. Gastric Cancer 2021; 24:133-144. [PMID: 32940810 DOI: 10.1007/s10120-020-01118-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The main cause of gastric cancer is the infection by the bacterium Helicobacter pylori which induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover, H. pylori modulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whether H. pylori-induced autophagy has a role in CSC emergence. METHODS Autophagic flux in response to H. pylori infection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed. RESULTS First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected with H. pylori was observed. Then, we demonstrated in vitro that H. pylori was able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties. CONCLUSION In conclusion, all these data show that H. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.
Collapse
Affiliation(s)
- Sarah Courtois
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Maria Haykal
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Clément Bodineau
- Centro Andaluz de Biología Molecular Y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Américo Vespucio 24, 41092, Sevilla, Spain.,Institut Européen de Chimie et Biologie, INSERM U1218, University of Bordeaux, Pessac, France
| | - Elodie Sifré
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | | | - Armelle Ménard
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Francis Mégraud
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France.,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France
| | - Philippe Lehours
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France.,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France
| | - Raúl V Durán
- Centro Andaluz de Biología Molecular Y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Américo Vespucio 24, 41092, Sevilla, Spain
| | - Christine Varon
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France
| | - Emilie Bessède
- Univ. Bordeaux, INSERM, BaRITOn, U1053, F-33000, Bordeaux, France. .,French National Reference Center for Campylobacters and Helicobacters (CNRCH), University Hospital of Bordeaux, Place Amelie Raba Leon, 33076, Bordeaux, France.
| |
Collapse
|
|
18
|
Prospective comparative study between two first-line regimens for Helicobacter pylori eradication: Non-bismuth quadruple versus bismuth quadruple therapy. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:301-309. [PMID: 32253018 DOI: 10.1016/j.gastrohep.2019.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 11/26/2019] [Accepted: 12/05/2019] [Indexed: 12/15/2022]
|
|
19
|
Szymczak A, Ferenc S, Majewska J, Miernikiewicz P, Gnus J, Witkiewicz W, Dąbrowska K. Application of 16S rRNA gene sequencing in Helicobacter pylori detection. PeerJ 2020; 8:e9099. [PMID: 32440373 PMCID: PMC7229771 DOI: 10.7717/peerj.9099] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 04/09/2020] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori is one of the major stomach microbiome components, promoting development of inflammation and gastric cancer in humans. H. pylori has a unique ability to transform into a coccoidal form which is difficult to detect by many diagnostic methods, such as urease activity detection, and even histopathological examination. Here we present a comparison of three methods for H. pylori identification: histological assessment (with eosin, hematoxylin, and Giemsa staining), polymerase chain reaction (PCR) detection of urease (ureA specific primers), and detection by 16S rRNA gene sequencing. The study employed biopsies from the antral part of the stomach (N = 40). All samples were assessed histologically which revealed H. pylori in eight patients. Bacterial DNA isolated from the bioptates was used as a template for PCR reaction and 16S rRNA gene sequencing that revealed H. pylori in 13 and in 20 patients, respectively. Thus, 16S rRNA gene sequencing was the most sensitive method for detection of H. pylori in stomach biopsy samples.
Collapse
Affiliation(s)
- Aleksander Szymczak
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Stanisław Ferenc
- Regional Specialist Hospital in Wrocław, Research and Development Center, Wrocław, Poland
| | - Joanna Majewska
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Paulina Miernikiewicz
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Jan Gnus
- Medical Academy in Wroclaw, Wrocław, Poland
| | - Wojciech Witkiewicz
- Regional Specialist Hospital in Wrocław, Research and Development Center, Wrocław, Poland
| | - Krystyna Dąbrowska
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| |
Collapse
|
|
20
|
Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens. Int J Mol Sci 2020; 21:ijms21051881. [PMID: 32164177 PMCID: PMC7084853 DOI: 10.3390/ijms21051881] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/04/2020] [Accepted: 03/06/2020] [Indexed: 02/06/2023] Open
Abstract
Flavodoxins are small soluble electron transfer proteins widely present in bacteria and absent in vertebrates. Flavodoxins participate in different metabolic pathways and, in some bacteria, they have been shown to be essential proteins representing promising therapeutic targets to fight bacterial infections. Using purified flavodoxin and chemical libraries, leads can be identified that block flavodoxin function and act as bactericidal molecules, as it has been demonstrated for Helicobacter pylori (Hp), the most prevalent human gastric pathogen. Increasing antimicrobial resistance by this bacterium has led current therapies to lose effectiveness, so alternative treatments are urgently required. Here, we summarize, with a focus on flavodoxin, opportunities for pharmacological intervention offered by the potential protein targets described for this bacterium and provide information on other gastrointestinal pathogens and also on bacteria from the gut microbiota that contain flavodoxin. The process of discovery and development of novel antimicrobials specific for Hp flavodoxin that is being carried out in our group is explained, as it can be extrapolated to the discovery of inhibitors specific for other gastric pathogens. The high specificity for Hp of the antimicrobials developed may be of help to reduce damage to the gut microbiota and to slow down the development of resistant Hp mutants.
Collapse
|
|
21
|
Bravo J, Díaz P, Corvalán AH, Quest AFG. A Novel Role for Helicobacter pylori Gamma-Glutamyltranspeptidase in Regulating Autophagy and Bacterial Internalization in Human Gastric Cells. Cancers (Basel) 2019; 11:cancers11060801. [PMID: 31185677 PMCID: PMC6627848 DOI: 10.3390/cancers11060801] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/23/2019] [Accepted: 04/26/2019] [Indexed: 12/12/2022] Open
Abstract
The risk of developing gastric cancer is strongly linked to Helicobacter pylori (H. pylori) infection. Alternatively, autophagy is a conserved response that is important in cellular homeostasis and provides protection against bacterial infections. Although H. pylori is typically considered an extracellular bacterium, several reports indicate that it internalizes, possibly to avoid exposure to antibiotics. Mechanisms by which H. pylori manipulates host cell autophagic processes remain unclear and, importantly, none of the available studies consider a role for the secreted H. pylori virulence factor gamma-glutamyltranspeptidase (HpGGT) in this context. Here, we identify HpGGT as a novel autophagy inhibitor in gastric cells. Our experiments revealed that deletion of HpGGT increased autophagic flux following H. pylori infection of AGS and GES-1 gastric cells. In AGS cells, HpGGT disrupted the late stages of autophagy by preventing degradation in lysosomes without affecting lysosomal acidification. Specifically, HpGGT impaired autophagic flux by disrupting lysosomal membrane integrity, which leads to a decrease in lysosomal cathepsin B activity. Moreover, HpGGT was necessary for efficient internalization of the bacteria into gastric cells. This important role of HpGGT in internalization together with the ability to inhibit autophagy posits HpGGT as a key virulence factor in the development of gastric cancer.
Collapse
Affiliation(s)
- Jimena Bravo
- Laboratory of Cellular Communication, Center for the Study of Exercise, Metabolism and Cancer (CEMC), Program in Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380492, Chile.
| | - Paula Díaz
- Laboratory of Cellular Communication, Center for the Study of Exercise, Metabolism and Cancer (CEMC), Program in Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380492, Chile.
| | - Alejandro H Corvalán
- Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380492, Chile.
- Laboratory of Oncology, Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago 8330034, Chile.
| | - Andrew F G Quest
- Laboratory of Cellular Communication, Center for the Study of Exercise, Metabolism and Cancer (CEMC), Program in Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380492, Chile.
| |
Collapse
|
|
22
|
Chen X, Li P, Shen Y, Zou Y, Yuan G, Hu H. Rhamnolipid-involved antibiotics combinations improve the eradication of Helicobacter pylori biofilm in vitro: A comparison with conventional triple therapy. Microb Pathog 2019; 131:112-119. [DOI: 10.1016/j.micpath.2019.04.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 03/29/2019] [Accepted: 04/01/2019] [Indexed: 02/07/2023]
|
|
23
|
Liu L, Zhao Y, Fan G, Shuai T, Li B, Li Y. Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogen‑activated protein kinase signalling in human gastric cancer cells. Mol Med Rep 2018; 18:5733-5741. [PMID: 30320396 DOI: 10.3892/mmr.2018.9558] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 09/18/2018] [Indexed: 01/08/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is the most important factor in the development of gastric cancer. Heparanase (HPA) is involved in tissue remodelling and cell migration, which leads to inflammation and tumour metastasis. The current study aimed was to explore whether a H. pylori infection leads to an increase in the level of HPA in gastric cancer and to investigate the specific mechanism underlying this association. Reverse transcription‑polymerase chain reaction and western blotting were used to detect HPA mRNA and protein expression, respectively, in MKN‑45 cells infected by H. pylori, MKN‑45 cells treated with the mitogen‑activated protein kinase (MAPK) inhibitor SB203580 and MKN‑45 cells transfected with small interfering RNA against HPA. MAPK and nuclear factor (NF)‑κB expression were determined by western blotting in the different cells group. Cell Counting Kit‑8, Transwell method, and Scratch and Clone tests were conducted to detect proliferation, invasion, migration and clone formation ability of gastric cancer cells. It was demonstrated that HPA mRNA expression was highest at 6 h post‑infection, while the expression of the HPA protein was highest at 24 h post‑infection in H. pylori‑infected gastric cancer cells. Furthermore, it was demonstrated that H. pylori infection significantly enhanced the expression of MAPK and NF‑κB in MKN‑45 cells at the mRNA and protein levels. SB203580 significantly decreased the expression of NF‑κB in MKN‑45 cells infected with H. pylori. Exposure to SB203580 also significantly decreased the expression of HPA. In the present study, the inhibition of HPA significantly lowered H. pylori‑induced cell proliferation, suggesting that H. pylori infection induces the proliferation of gastric cancer cells through the upregulation of HPA. Taken together, the results of the present study demonstrated that HPA serves a critical role in the development of gastric cancer in H. pylori‑infected cells, which may be an important mechanism through which H. pylori infection leads to gastric cancer. In addition, H. pylori infection promotes the proliferation, invasion and metastasis of gastric cancer cells through the upregulation of HPA expression, and this is likely mediated via the MAPK and NF‑κB signalling pathways. These data suggest that HPA can be used as a therapeutic target in gastric cancer, particularly in cases induced by H. pylori infection.
Collapse
Affiliation(s)
- Liping Liu
- The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
| | - Yongxun Zhao
- Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Guangrui Fan
- The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
| | - Tiankui Shuai
- Department of Critical Care Medicine, The Donggang Branch of The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
| | - Bin Li
- Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yumin Li
- Department of General Surgery, The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China
| |
Collapse
|
|
24
|
Liu LP, Sheng XP, Shuai TK, Zhao YX, Li B, Li YM. Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression. World J Gastroenterol 2018; 24:4565-4577. [PMID: 30386106 PMCID: PMC6209574 DOI: 10.3748/wjg.v24.i40.4565] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 09/02/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC). METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.
Collapse
Affiliation(s)
- Li-Ping Liu
- The Second Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Critical Care Medicine, The Donggang District of First Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Xi-Ping Sheng
- Institute of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Tian-Kui Shuai
- Department of Critical Care Medicine, The Donggang District of First Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Yong-Xun Zhao
- Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Bin Li
- Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yu-Min Li
- Key Laboratory of Digestive System Tumors of Gansu Province, The Second Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
25
|
Lee JH, Choi JK, Jeong SN, Choi SH. Charlson comorbidity index as a predictor of periodontal disease in elderly participants. J Periodontal Implant Sci 2018; 48:92-102. [PMID: 29770238 PMCID: PMC5944227 DOI: 10.5051/jpis.2018.48.2.92] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 04/22/2018] [Indexed: 12/14/2022] Open
Abstract
Purpose This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods Nationwide representative samples of 149,785 adults aged ≥60 years with PD (International Classification of Disease, 10th revision [ICD-10], K052-K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002-2013. The degree of comorbidity was measured using the CCI (grade 0-6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ≥2: HR, 1.12, P<0.001). Conclusions We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population.
Collapse
Affiliation(s)
- Jae-Hong Lee
- Department of Periodontology, Daejeon Dental Hospital, Institute of Wonkwang Dental Research, Wonkwang University College of Dentistry, Daejeon, Korea
| | - Jung-Kyu Choi
- Department of Health Insurance Research, Ilsan Hospital, National Health Insurance Service, Goyang, Korea
| | - Seong-Nyum Jeong
- Department of Periodontology, Daejeon Dental Hospital, Institute of Wonkwang Dental Research, Wonkwang University College of Dentistry, Daejeon, Korea
| | - Seong-Ho Choi
- Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, Korea
| |
Collapse
|
|
26
|
Gong Y, Yuan Y. Resistance mechanisms of Helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol 2018; 44:371-392. [PMID: 29293032 DOI: 10.1080/1040841x.2017.1418285] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.
Collapse
Affiliation(s)
- Yuehua Gong
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| | - Yuan Yuan
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| |
Collapse
|
|
27
|
Hu Y, Zhu Y, Lu NH. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance. Front Cell Infect Microbiol 2017; 7:168. [PMID: 28529929 PMCID: PMC5418237 DOI: 10.3389/fcimb.2017.00168] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 04/18/2017] [Indexed: 01/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.
Collapse
Affiliation(s)
- Yi Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang UniversityNanchang, China
| |
Collapse
|
|
28
|
Hu Y, Zhu Y, Lu NH. Primary Antibiotic Resistance of Helicobacter pylori in China. Dig Dis Sci 2017; 62:1146-1154. [PMID: 28315035 DOI: 10.1007/s10620-017-4536-8] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 03/08/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China. METHODS We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed. RESULTS Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively. CONCLUSIONS In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.
Collapse
Affiliation(s)
- Yi Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 YongWaizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 YongWaizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China.
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 YongWaizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China.
| |
Collapse
|
|
29
|
Huang Y, Wang QL, Cheng DD, Xu WT, Lu NH. Adhesion and Invasion of Gastric Mucosa Epithelial Cells by Helicobacter pylori. Front Cell Infect Microbiol 2016; 6:159. [PMID: 27921009 PMCID: PMC5118847 DOI: 10.3389/fcimb.2016.00159] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 11/04/2016] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori is the main pathogenic bacterium involved in chronic gastritis and peptic ulcer and a class 1 carcinogen in gastric cancer. Current research focuses on the pathogenicity of H. pylori and the mechanism by which it colonizes the gastric mucosa. An increasing number of in vivo and in vitro studies demonstrate that H. pylori can invade and proliferate in epithelial cells, suggesting that this process might play an important role in disease induction, immune escape and chronic infection. Therefore, to explore the process and mechanism of adhesion and invasion of gastric mucosa epithelial cells by H. pylori is particularly important. This review examines the relevant studies and describes evidence regarding the adhesion to and invasion of gastric mucosa epithelial cells by H. pylori.
Collapse
Affiliation(s)
- Ying Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Qi-Long Wang
- Department of General Surgery, Tianjin Haihe Hospital Tianjin, China
| | - Dan-Dan Cheng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Wen-Ting Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| |
Collapse
|