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Almarmouri C, El-Gamal MI, Haider M, Hamad M, Qumar S, Sebastian M, Ghemrawi R, Muhammad JS, Burucoa C, Khoder G. Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora. Gut Pathog 2025; 17:37. [PMID: 40437630 PMCID: PMC12121022 DOI: 10.1186/s13099-025-00708-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 05/07/2025] [Indexed: 06/01/2025] Open
Abstract
The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant challenges, such as increasing antibiotic resistance, high recurrence rates, and adverse effects such as gut microflora dysbiosis. These limitations have driven the exploration of alternative antibiotic-free therapies, including the use of plant-based compounds, probiotics, nanoparticles, phage therapy, antimicrobial peptides, and H. pylori vaccines. Among these, urease-targeted therapy has shown particular promise. Urease enables the survival and colonization of H. pylori by neutralizing stomach acidity. Targeting this urease without disrupting beneficial gut microflora offers a selective mechanism to impair H. pylori, due to the absence of this enzyme in most of the human gut microbiome. In this review, we highlight advancements and limitations in the field of antibiotic-free therapies, with a particular focus on anti-urease strategies. We explore the structural and functional characteristics of urease, its role in H. pylori pathogenesis, and its potential as a therapeutic target. For the first time, we provide a comprehensive analysis of natural, semisynthetic, and synthetic anti-urease compounds, emphasizing their mechanisms of action, efficacy, and safety profiles. Advances in silico, in vitro, and in vivo studies have identified several promising anti-urease compounds with high specificity and minimal toxicity. By focusing on urease inhibition as a targeted strategy, this review underscores its potential to overcome antibiotic resistance while minimizing gut dysbiosis and improving the outcomes of H. pylori infection treatment.
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Affiliation(s)
- Christina Almarmouri
- Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohammed I El-Gamal
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Mohamed Haider
- 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, Sharjah, United Arab Emirates
| | - Mohamad Hamad
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Shamsul Qumar
- Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Merylin Sebastian
- Research Institute for Medical & 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
| | - Jibran Sualeh Muhammad
- Department of Biomedical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Christophe Burucoa
- Laboratoire de Bactériologie, U1070 INSERM, CHU de Poitiers, Université de Poitiers, 86000, Poitiers, France
| | - 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, Sharjah, United Arab Emirates.
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Wang X, Zhou N, Gao XJ, Zhu Z, Sun M, Wang Q, Cao H, Wu X, Zhou C, Zheng Q, Yuan Y, Liu Y, Chen L, Jiang J, Bu P, Gao L. Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide. SCIENCE CHINA. LIFE SCIENCES 2025; 68:1158-1173. [PMID: 39821832 DOI: 10.1007/s11427-024-2775-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/07/2024] [Indexed: 01/19/2025]
Abstract
Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide (H2Sn, n⩾2), not organic polysulfides. Studies on the mechanism of action (MoA) show that H2Sn specifically inactivates H. pylori glucose-6-phosphate dehydrogenase (G6PDH) by interfering with electron transfer from glucose-6-phosphate (G6P) to nicotinamide adenine dinucleotide phosphate (NADP+). However, low H2Sn yield makes garlic derivatives hard to be a reliable donor of H2Sn to treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4 that generates H2Sn with a 25-58 times increase in yield. Through chitosan encapsulation, we designed a gastric-adaptive H2Sn microreactor (GAPSR) that eradicates H. pylori with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid H. pylori eradication than combined antibiotics therapy without disturbing the gut microbiota. These findings indicate a distinct MoA transformation mediated by polysulfide as an alternative candidate to treat H. pylori infection.
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Affiliation(s)
- Xiaonan Wang
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
| | - Ning Zhou
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Xuejiao J Gao
- College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, China
| | - Zijing Zhu
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
- Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Minmin Sun
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Qian Wang
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
| | - Haolin Cao
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
| | - Xuetong Wu
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
| | - Caiyu Zhou
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China
| | - Qingkang Zheng
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Ye Yuan
- Nanozyme Laboratory in Zhongyuan, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Yuan Liu
- Nanozyme Laboratory in Zhongyuan, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Lei Chen
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Jing Jiang
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Pengcheng Bu
- Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Lizeng Gao
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Nanozyme Laboratory in Zhongyuan, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
- Nanozyme Laboratory in Zhongyuan, Henan Academy of Innovations in Medical Science, Zhengzhou, 451163, China.
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [PMID: 40061592 PMCID: PMC11886037 DOI: 10.3748/wjg.v31.i9.102053] [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: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Al-Shuhaib MBS, Hashim HO, Al-Shuhaib JMB. D-Glucosamine is a Potential Urease Inhibitor from Middle Eastern Medicinal Plants for Combatting Helicobacter Pylori Infections; a Molecular Docking and Simulation Approach. Biochem Genet 2025; 63:239-260. [PMID: 38430447 DOI: 10.1007/s10528-024-10709-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 01/19/2024] [Indexed: 03/03/2024]
Abstract
Helicobacter pylori stands as a significant risk factor for both peptic and stomach ulcers. Their resistance to the highly acidic host environment primarily stems from their capability to produce urease, an enzyme that rapidly converts urea into NH3 and CO2. These byproducts are crucial for the bacterium's survival under such harsh conditions. Given the pivotal role of medicinal plants in treating various ailments with minimal side effects, there is an urgent need for a natural drug that can effectively eliminate H. pylori by inhibiting urease. Hence, the current study aims to identify the most potent urease inhibitor among the natural compounds found in Middle Eastern medicinal plants, taking into consideration factors such as optimal affinity, drug-like properties, pharmacokinetic characteristics, and thermodynamic attributes. In total, 5599 ligand conformers from 151 medicinal plants were subjected to docking against the urease's active site. The top-ranking natural compounds, as determined by their high docking scores, were selected for further analysis. Among these compounds, D-glucosamine (PubChem code 439,213) exhibited the most interactions with the crucial amino acid residues in the urease's active site. Furthermore, D-glucosamine demonstrated superior absorption, distribution, metabolism, excretion, and toxicity properties compared to other top-ranked candidates. Molecular dynamics simulations conducted over 100 nanoseconds revealed stable root mean square deviations and fluctuations of the protein upon complexation with D-glucosamine. Additionally, the radius of gyration and solvent-accessible surface area values for the D-glucosamine-urease complex were notably lower than those observed in other typical urease-inhibitor complexes. In conclusion, this study provides valuable insights into the potential development of D-glucosamine as a novel urease inhibitor. This promising compound holds the potential to serve as an effective drug for combating H. pylori infections in the near future.
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Affiliation(s)
- Mohammed Baqur S Al-Shuhaib
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, 8, Al-Qasim, Babil, 51013, Iraq.
| | - Hayder O Hashim
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Babylon, Hillah, Babil, 51001, Iraq
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Wang X, Wang J, Mao L, Yao Y. Helicobacter pylori outer membrane vesicles and infected cell exosomes: new players in host immune modulation and pathogenesis. Front Immunol 2024; 15:1512935. [PMID: 39726601 PMCID: PMC11670821 DOI: 10.3389/fimmu.2024.1512935] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 11/27/2024] [Indexed: 12/28/2024] Open
Abstract
Outer membrane vesicles (OMVs) and exosomes are essential mediators of host-pathogen interactions. Elucidating their mechanisms of action offers valuable insights into diagnosing and treating infectious diseases and cancers. However, the specific interactions of Helicobacter pylori (H. pylori) with host cells via OMVs and exosomes in modulating host immune responses have not been thoroughly investigated. This review explores how these vesicles elicit inflammatory and immunosuppressive responses in the host environment, facilitate pathogen invasion of host cells, and enable evasion of host defenses, thereby contributing to the progression of gastric diseases and extra-gastric diseases disseminated through the bloodstream. Furthermore, the review discusses the challenges and future directions for investigating OMVs and exosomes, underscoring their potential as therapeutic targets in H. pylori-associated diseases.
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Affiliation(s)
- Xiuping Wang
- Department of Clinical Laboratory, The First People’s Hospital of
Kunshan, Kunshan, Jiangsu, China
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Hameed H, Hussain J, Cláudia Paiva-Santos A, Zaman M, Hamza A, Sajjad I, Asad F. Comprehensive insights on treatment modalities with conventional and herbal drugs for the treatment of duodenal ulcers. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:8211-8229. [PMID: 38837070 DOI: 10.1007/s00210-024-03178-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/21/2024] [Indexed: 06/06/2024]
Abstract
Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal tract mucosa. Peptic ulcer disease is the term for this illness (PUD). About 80% of peptic ulcers are duodenal ulcers, with stomach ulcers accounting for the remaining 20%. Duodenal ulcers are linked to the two primary results about Helicobacter pylori infection and COX inhibitor users. Additional causes might include drinking, smoking, stress, and coffee consumption. The indications and symptoms of a duodenal ulcer depend on the patient's age and the lesion's location. For duodenal ulcers, proton pump inhibitors (PPIs) are the usual course of treatment. This comprehensive study included an in-depth literature search in the literature and methods section using electronic databases such as PubMed, ScienceDirect, and Google Scholar. The search method included publications published from the inception of the relevant database to the present. Inclusion criteria included studies investigating different treatment options for duodenal ulcer disease, including traditional pharmacotherapy and naturopathic treatments. Data mining includes information on treatment techniques, treatment outcomes, and possible synergies between conventional and herbal treatments. In addition, this review critically examines the available information on the effectiveness, safety, and possible side effects of different treatments. The inclusion of conventional and herbal treatments is intended to provide a comprehensive overview of the many treatment options available for duodenal ulcer disease. A more comprehensive and personalized treatment plan can be achieved by incorporating dietary changes, lifestyle modifications, and, if necessary, herbal therapies to complement other treatments normally.
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Affiliation(s)
- Huma Hameed
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan.
| | - Jahangir Hussain
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, 3000-548, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, 3000-548, Portugal
| | - Muhammad Zaman
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan
| | - Ali Hamza
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan
| | - Irsa Sajjad
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan
| | - Faria Asad
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan
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Chitas R, Fonseca DR, Parreira P, Martins MCL. Targeted nanotherapeutics for the treatment of Helicobacter pylori infection. J Biomed Sci 2024; 31:78. [PMID: 39128983 DOI: 10.1186/s12929-024-01068-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/16/2024] [Indexed: 08/13/2024] Open
Abstract
Helicobacter pylori infection is involved in gastric diseases such as peptic ulcer and adenocarcinoma. Approved antibiotherapies still fail in 10 to 40% of the infected patients and, in this scenario, targeted nanotherapeutics emerged as powerful allies for H. pylori eradication. Nano/microparticles conjugated with H. pylori binding molecules were developed to eliminate H. pylori by either (i) blocking essential mechanisms of infection, such as adhesion to gastric mucosa or (ii) binding and killing H. pylori through the release of drugs within the bacteria or at the site of infection. Glycan antigens (as Lewis B and sialyl-Lewis X), pectins, lectins, phosphatidylethanolamine and epithelial cell membranes were conjugated with nano/microparticles to successfully block H. pylori adhesion. Urea-coated nanoparticles were used to improve drug delivery inside bacteria through H. pylori UreI channel. Moreover, nanoparticles coated with antibodies against H. pylori and loaded with sono/photosensitizers, were promising for their application as targeted sono/photodynamic therapies. Further, non-specific H. pylori nano/microparticles, but only active in the acidic gastric environment, coated with binders to bacterial membrane, extracellular polymeric substances or to high temperature requirement A protease, were evaluated. In this review, an overview of the existing nanotherapeutics targeting H. pylori will be given and their rational, potential to counteract infection, as well as level of development will be presented and discussed.
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Affiliation(s)
- Rute Chitas
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Diana R Fonseca
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- FEUP - Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e de Materiais, Universidade do Porto, Porto, Portugal
| | - Paula Parreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
| | - M Cristina L Martins
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
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Emmanuel BN, Peter DA, Peter MO, Adedayo IS, Olaifa K. Helicobacter pylori infection in Africa: comprehensive insight into its pathogenesis, management, and future perspectives. JOURNAL OF UMM AL-QURA UNIVERSITY FOR APPLIED SCIENCES 2024. [DOI: 10.1007/s43994-024-00166-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 05/22/2024] [Indexed: 01/04/2025]
Abstract
AbstractHelicobacter pylori is a widespread bacterium that has effectively colonized half of the global population, with Africa having over 70% of the total burden of H. pylori infections (HPI). Considering its acknowledged classification of as bacterial carcinogens and their significant contribution to the development of gastrointestinal disorders such as gastritis, peptic ulcers, and gastric neoplasia, together with their growing resistance to antibiotics. Gaining insight into the etiology of this organism is crucial in order to investigate and develop appropriate treatment strategies. Furthermore, the rise of bacteria that are resistant to antibiotics presents an extra danger in managing this detrimental bacterium. Our review focuses on investigating the presence of H. pylori in Africa and analyzing the various factors that contribute to its extensive prevalence. We simplified the complex mechanisms that H. pylori utilizes to flourish in the human body, with a specific emphasis on its virulence factors and antibiotic resistance. These variables pose significant challenges to conventional treatment strategies. In addition, we analyze both conventional and developing diagnostic methods, as well as the current treatment approaches implemented in various African nations. In addition, we tackle the distinct healthcare obstacles of the region and put-up practical remedies. The main goal of this review is to improve the formulation of more efficient methods for the management and treatment of HPI in Africa.
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Xiao L, Zou X, Tian G, Qin C, Zhao H, Fu J, Hu J, Yin J. Antigenicity evaluation of synthetic α-(1,3)-linked D, D-heptoglycan of
Helicobacter pylori
serotype O6 lipopolysaccharide. J Carbohydr Chem 2024:1-28. [DOI: 10.1080/07328303.2024.2341716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/06/2024] [Indexed: 01/04/2025]
Affiliation(s)
- Lei Xiao
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Xiaopeng Zou
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Guangzong Tian
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Chunjun Qin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Hui Zhao
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Junjie Fu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
| | - Jing Hu
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China
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Li L, Yin XC, Jiang YY, Xia YF, Wang X, Li J, Li H, Qin Y, Yang JS. Chemical Synthesis of a Branched Nonasaccharide Fragment from Helicobacter pylori Lipopolysaccharide. Org Lett 2024; 26:2103-2107. [PMID: 38443201 DOI: 10.1021/acs.orglett.4c00271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of β-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired β-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.
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Affiliation(s)
- Ling Li
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Xiao-Chen Yin
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Yuan-Yuan Jiang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Yi-Fei Xia
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Xia Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Jiao Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yong Qin
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Jin-Song Yang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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Zaman T, Haq A, Ahmad R, Sinha S, Chowdhury K, Parvin S, Imran M, Humayra ZU, Kumar S, Haque M. The Role of Probiotics in the Eradication of Helicobacter pylori and Overall Impact on Management of Peptic Ulcer: A Study Involving Patients Undergoing Triple Therapy in Bangladesh. Cureus 2024; 16:e56283. [PMID: 38495972 PMCID: PMC10944298 DOI: 10.7759/cureus.56283] [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] [Accepted: 03/16/2024] [Indexed: 03/19/2024] Open
Abstract
Background Helicobacter pylori infection has been identified to cause constantly recurring inflammation, leading to gastrointestinal tract disorders, including carcinoma. The standard triple therapy (STT), used to eradicate H. pylori, includes two antimicrobials and a proton pump inhibitor for two weeks. Other drug regimens have also been developed since H. pylori exhibits antimicrobial resistance. These regimens, including probiotics, have been shown to lower adverse drug reactions (ADR), improve drug adherence, exert bacteriostatic effect, and reduce inflammation. Objective This study intended to explore probiotic intervention for improving eradication rates and mitigating adverse effects while administrating STT. Methods This prospective study was conducted from May to December, 2021, in the Department of Gastroenterology of Ship International Hospital, Dhaka, Bangladesh, to observe the effects of probiotics inclusion along with STT on H. pylori eradication. A total of 100 patients aged ≥18 years who tested positive for H. pylori were included. The experimental group (n=50) was given STT and probiotics, and the control group (n=50) was given only STT without probiotics for 14 days. Necessary follow-up was done six weeks after treatment. An independent sample t-test, chi-square test, and multiple regression analysis were used for statistical analysis. Result The odds of getting rapid urease test (RUT) negative results from positive were 2.06 times higher (95%CI= 0.95, 3.22, p=0.054) in the experimental group. ADRs were crucially towering in the control group (p=0.045) compared to the probiotics group. The probiotics group had a lower risk of having adverse effects by 0.54 times (95%CI=0.19, 0.84, p=0.032) than the control group. Conclusion Using probiotics and STT together to eradicate H. pylori may lower ADR and improve treatment adherence. It may also help terminate H. pylori infection more effectively. More research is required as H. pylori is very contagious and can ultimately cause life-threatening gastric cancer.
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Affiliation(s)
- Taslima Zaman
- Department of Gastroenterology, United Hospital Ltd, Dhaka, BGD
| | - Ahsanul Haq
- Department of Biostatistics, RNA Biotech Limited, Dhaka, BGD
| | - Rahnuma Ahmad
- Department of Physiology, Medical College for Women & Hospital, Dhaka, BGD
| | - Susmita Sinha
- Department of Physiology, Khulna City Medical College and Hospital, Khulna, BGD
| | - Kona Chowdhury
- Department of Pediatrics, Gonoshasthaya Samaj Vittik Medical College, Dhaka, BGD
| | - Sultana Parvin
- Department of Medical Gastroenterology, Sheikh Russel National Gastroliver Institute & Hospital, Dhaka, BGD
| | - Mostofa Imran
- Department of Gastroenterology, Ibn Sina Medical College & Hospital, Dhaka, BGD
| | - Zaman U Humayra
- Department of Plastic and Reconstructive Surgery, Ship International Hospital, Dhaka, BGD
| | - Santosh Kumar
- Department of Periodontology and Implantology, Karnavati School of Dentistry, Karnavati University, Gandhinagar, IND
| | - Mainul Haque
- Karnavati Scientific Research Center (KSRC), Karnavati School of Dentistry, Karnavati University, Gandhinagar, IND
- Unit of Pharmacology and Therapeutics, National Defence University of Malaysia, Kuala Lumpur, MYS
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12
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Wang C, Yao M, Zhong H, Meena SS, Shu F, Nie S, Xie M. Natural foods resources and dietary ingredients for the amelioration of Helicobacter pylori infection. Front Med (Lausanne) 2023; 10:1324473. [PMID: 38131043 PMCID: PMC10734694 DOI: 10.3389/fmed.2023.1324473] [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: 10/21/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric-persistent pathogen that can cause peptic ulcer disease, gastric cancer, and mucosal-associated lymphoid tissue lymphoma. This pathogen is commonly treated with antibiotic-based triple or quadruple therapy. However, antibiotic therapy could result in the bacterial resistance, imbalance of gut microbiota, and damage to the liver and kidneys, etc. Therefore, there is an urgent need for alternative therapeutic strategies. Interestingly, natural food resources, like vegetables, fruits, spices, and edible herbs, have potent inhibitory effects on H. pylori. In this review, we systematically summarized these foods with supporting evidence from both animal and clinical studies. The results have indicated that natural foods may possess temporary inhibition effect on H. pylori rather than durable eradication, and may help to reduce H. pylori colonization, enhance the effect of antibiotics and modulate the host's immune response.
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Affiliation(s)
- Chengyuan Wang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Meixiang Yao
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Hongguang Zhong
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Stephene S. Meena
- Jiangzhong Cancer Research, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Fuxing Shu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
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13
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Luo X, Li H, He L. Correlation analysis of endoscopic manifestations and eradication effect of Helicobacter pylori. Front Med (Lausanne) 2023; 10:1259728. [PMID: 37706023 PMCID: PMC10495841 DOI: 10.3389/fmed.2023.1259728] [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: 07/16/2023] [Accepted: 08/08/2023] [Indexed: 09/15/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer. Eradication of H. pylori significantly reduces the incidence and mortality of gastric cancer. H. pylori resistance to antibiotics and a gradual decline in eradication rates are gaining more and more attention. Our study aimed to address the correlation between endoscopic manifestations and the eradication effect of H. pylori. Methods We retrospectively reviewed outpatients in our hospital with H. pylori infection undergoing eradication therapy from January 2022 to March 2023. Both the primary diagnosis and eradication of H. pylori after treatment were confirmed by a 13C urea breath test. Patients were treated with a proton pump inhibitor (PPI)-based quadruple therapy. Clinical characteristics and endoscopy manifestations within 7 days before or after patients were diagnosed with H. pylori infection were analyzed. Results From January 2022 to March 2023, a total of 323 patients were enrolled in this study. There were 138 male patients and 185 female patients. The mean age of patients was 45.62 ± 13.04 years. The H. pylori initial eradication rate was 82.0%. Univariate analysis of factors affecting H. pylori eradication showed that sex, age, and endoscopic manifestations including diffuse redness, multiple white, and flat elevated lesions, and atrophy were significantly associated with the failure of H. pylori eradication therapy. A multivariable logistic regression model analysis of these five factors showed that patients aged over 60 years with multiple white and flat elevated lesions in the endoscopic examination are significantly less likely to eradicate H. pylori with empirical quadruple therapy. On the other hand, patients with diffuse redness were significantly more likely to eradicate H. pylori infection with empirical quadruple therapy. Conclusion Our study shows that age over 60 years old, multiple white and flat elevated lesions in endoscopic examination are independent risk factors of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor. For patients with these risk factors, a drug sensitivity test or H. pylori resistance gene mutation detection may be more appropriate. However, further mechanism studies or prospective studies are needed to prove our findings.
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Affiliation(s)
- Xin Luo
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hui Li
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li He
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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14
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Aziz S, König S, Umer M, Akhter TS, Iqbal S, Ibrar M, Ur-Rehman T, Ahmad T, Hanafiah A, Zahra R, Rasheed F. Risk factor profiles for gastric cancer prediction with respect to Helicobacter pylori: A study of a tertiary care hospital in Pakistan. Artif Intell Gastroenterol 2023; 4:10-27. [DOI: 10.35712/aig.v4.i1.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 04/01/2023] [Accepted: 04/20/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Diagnosis relies on histopathology and the number of endoscopies is increasing. Helicobacter pylori (H. pylori) infection is a major risk factor.
AIM To develop an in-silico GC prediction model to reduce the number of diagnostic surgical procedures. The meta-data of patients with gastroduodenal symptoms, risk factors associated with GC, and H. pylori infection status from Holy Family Hospital Rawalpindi, Pakistan, were used with machine learning.
METHODS A cohort of 341 patients was divided into three groups [normal gastric mucosa (NGM), gastroduodenal diseases (GDD), and GC]. Information associated with socioeconomic and demographic conditions and GC risk factors was collected using a questionnaire. H. pylori infection status was determined based on urea breath test. The association of these factors and histopathological grades was assessed statistically. K-Nearest Neighbors and Random Forest (RF) machine learning models were tested.
RESULTS This study reported an overall frequency of 64.2% (219/341) of H. pylori infection among enrolled subjects. It was higher in GC (74.2%, 23/31) as compared to NGM and GDD and higher in males (54.3%, 119/219) as compared to females. More abdominal pain (72.4%, 247/341) was observed than other clinical symptoms including vomiting, bloating, acid reflux and heartburn. The majority of the GC patients experienced symptoms of vomiting (91%, 20/22) with abdominal pain (100%, 22/22). The multinomial logistic regression model was statistically significant and correctly classified 80% of the GDD/GC cases. Age, income level, vomiting, bloating and medication had significant association with GDD and GC. A dynamic RF GC-predictive model was developed, which achieved > 80% test accuracy.
CONCLUSION GC risk factors were incorporated into a computer model to predict the likelihood of developing GC with high sensitivity and specificity. The model is dynamic and will be further improved and validated by including new data in future research studies. Its use may reduce unnecessary endoscopic procedures. It is freely available.
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Affiliation(s)
- Shahid Aziz
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology, Islamabad 44000, Pakistan
- Department of Microbiology, Quaid-i-Azam University, Islamabad 45320, Pakistan
- Interdisciplinary Center for Clinical Research, Core Unit Proteomics, University of Münster, Münster 48149, Germany
| | - Simone König
- Interdisciplinary Center for Clinical Research, Core Unit Proteomics, University of Münster, Münster 48149, Germany
| | - Muhammad Umer
- Management Information System Division, Pakistan Institute of Nuclear Science and Technology, Islamabad 44000, Pakistan
| | - Tayyab Saeed Akhter
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi 46300, Pakistan
| | - Shafqat Iqbal
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi 46300, Pakistan
| | - Maryum Ibrar
- Pakistan Scientific and Technological Information Centre, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Tofeeq Ur-Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Tanvir Ahmad
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology, Islamabad 44000, Pakistan
| | - Alfizah Hanafiah
- Faculty of Medicine, Department of Medical Microbiology and Immunology, Universiti Kebangsan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
| | - Rabaab Zahra
- Department of Microbiology, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Faisal Rasheed
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology, Islamabad 44000, Pakistan
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15
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Hasna B, Houari H, Koula D, Marina S, Emilia U, Assia B. In Vitro and In Vivo Study of Combined Effect of Some Algerian Medicinal Plants and Probiotics against Helicobacter pylori. Microorganisms 2023; 11:1242. [PMID: 37317215 DOI: 10.3390/microorganisms11051242] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/27/2023] [Accepted: 05/05/2023] [Indexed: 06/16/2023] Open
Abstract
Helicobacter pylori causes gastritis, peptic ulcers and gastric cancer and affects more than half of the world's population. Although this infection can have serious consequences, no novel cure or remedy have been discovered, the present therapy still relies on a variety of known antibiotics and anti-secretory agents. In the present study, the potential effect of combinations between methanolic extracts of four Algerian medicinal plants, garlic (Allium sativum), red onion (Allium cepa), cumin (Cuminum cyminum L.) and fenugreek (T. foenum-graecum L.), with different strains of lactic acid bacteria against H. pylori, was investigated. Similarly, the in vivo antibacterial effect of fenugreek extract combined with Bifidobacterium breve on H. pylori colonization potential to confirm the enhanced effect of the mixture was explored. Helicobacter pylori was inhibited by all combined mixtures of extracts and probiotics with varying results. The highest anti-H. pylori activities were found in fenugreek/B. breve, cumin/B. breve, garlic/B. breve and onion/B. breve combinations with inhibition diameters of 29, 26, 23 and 25 mm, respectively. Preliminary studies on the effect of probiotics against H. pylori revealed that the inhibition was due to lactic acid and bacteriocins and it was also related to the presence of phenolic compounds in the studied plants, such as gallic acid, caffeic acid, quercetin and vanillic acid. Fenugreek extract was found to inhibit the growth of H. pylori in a concentration-dependent manner. When H. pylori-infected rats were administered B. breve, the infection rate of H. pylori was significantly reduced, while the combination of B. breve and fenugreek extract effectively inhibited H. pylori. In addition, the B. breve and fenugreek extract mixture significantly reduced gastritis in H. pylori-infected rats. These results suggest that this complex mixture may be an alternative to treating diseases caused by H. pylori infection.
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Affiliation(s)
- Bouhenni Hasna
- Faculty of Nature and Life Sciences, University of Tiaret, Tiaret 14000, Algeria
| | - Hemida Houari
- Institute of Veterinary Sciences, University of Tiaret, Tiaret 14000, Algeria
| | - Doukani Koula
- Faculty of Nature and Life Sciences, University of Tiaret, Tiaret 14000, Algeria
| | - Spinu Marina
- Department of Infectious Diseases, Clinical Sciences, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Ungureanu Emilia
- Department of Infectious Diseases, Clinical Sciences, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Boumezrag Assia
- Institute of Veterinary Sciences, University of Tiaret, Tiaret 14000, Algeria
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16
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Chemical synthesis of oligosaccharides and their application in new drug research. Eur J Med Chem 2023; 249:115164. [PMID: 36758451 DOI: 10.1016/j.ejmech.2023.115164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/16/2023] [Accepted: 01/25/2023] [Indexed: 02/04/2023]
Abstract
Oligosaccharides are the ubiquitous molecules of life. In order to translate human bioglycosylation into clinical applications, homogeneous samples of oligosaccharides and glycoconjugates can be obtained by chemical, enzymatic or other biological methods for systematic studies. However, the structural complexity and diversity of glycans and their conjugates present a major challenge for the synthesis of such molecules. This review summarizes the chemical synthesis methods of oligosaccharides, the application of oligosaccharides in the field of medicinal chemistry according to their related biological activities, and shows the great prospect of oligosaccharides in the field of pharmaceutical chemistry.
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17
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Nikolić I, Chua EG, Tay ACY, Kostrešević A, Pavlović B, Jončić Savić K. Savory, Oregano and Thyme Essential Oil Mixture (HerbELICO ®) Counteracts Helicobacter pylori. Molecules 2023; 28:molecules28052138. [PMID: 36903396 PMCID: PMC10003975 DOI: 10.3390/molecules28052138] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/13/2023] [Accepted: 02/22/2023] [Indexed: 03/02/2023] Open
Abstract
Fifty percent of the world's population is infected with Helicobacter pylori, which can trigger many gastrointestinal disorders. H. pylori eradication therapy consists of two to three antimicrobial medicinal products, but they exhibit limited efficacy and may cause adverse side effects. Alternative therapies are urgent. It was assumed that an essential oil mixture, obtained from species from genera Satureja L., Origanum L. and Thymus L. and called the HerbELICO® essential oil mixture, could be useful in H. pylori infection treatment. HerbELICO® was analyzed by GC-MS and assessed in vitro against twenty H. pylori clinical strains isolated from patients of different geographical origins and with different antimicrobial medicinal products resistance profiles, and for its ability to penetrate the artificial mucin barrier. A customer case study included 15 users of HerbELICO®liquid/HerbELICO®solid dietary supplements (capsulated HerbELICO® mixture in liquid/solid form). Carvacrol and thymol were the most dominant compounds (47.44% and 11.62%, respectively), together with p-cymene (13.35%) and γ-terpinene (18.20%). The minimum concentration required to inhibit in vitro H. pylori growth by HerbELICO® was 4-5% (v/v); 10 min exposure to HerbELICO® was enough to kill off the examined H. pylori strains, while HerbELICO® was able to penetrate through mucin. A high eradication rate (up to 90%) and acceptance by consumers was observed.
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Affiliation(s)
- Ivan Nikolić
- Oncology Institute of Vojvodina, Faculty of Medicine Novi Sad, University of Novi Sad, Put Doktora Goldmana 4, 21204 Sremska Kamenica, Serbia
| | - Eng Guan Chua
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA 6009, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA 6009, Australia
| | | | - Bojan Pavlović
- Phytonet Ltd., Science Technology Park, Veljka Dugoševića 54, 11000 Belgrade, Serbia
| | - Katarina Jončić Savić
- Phytonet Ltd., Science Technology Park, Veljka Dugoševića 54, 11000 Belgrade, Serbia
- Correspondence: ; Tel.: +381-11-4085118
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18
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Correlation between Chemical Profile of Georgian Propolis Extracts and Their Activity against Helicobacter pylori. Molecules 2023; 28:molecules28031374. [PMID: 36771040 PMCID: PMC9921474 DOI: 10.3390/molecules28031374] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/20/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
Helicobacter pylori (H. pylori) is considered the most common bacterial pathogen colonizing stomach mucosa of almost half the world's population and is associated with various gastrointestinal diseases (from digestive problems and ulcers to gastric cancer). A lack of new drugs and a growing number of H. pylori antibiotic-resistant strains is a serious therapeutic problem.As a mixture of natural compounds, propolis has antimicrobial activity based on high concentrations of bioactive polyphenols (mainly flavonoids and phenolic acid derivates). The chemical composition of tested Georgian propolis is characterized by the presence of flavonoids aglycones, and phenolic acid monoesters, e.g., pinobanksin-5-methyl ether, pinobanksin, chrysin, pinocembrin, galangin, pinobanksin-3-O-acetate, pinostrobin and pinobanksin-3-O-butanoate, or isobutanoate and methoxycinnamic acid cinnamyl ester. The anti-H. pylori activity of 70% ethanol water extracts of 10 Georgian propolis samples was evaluated in vitro by MIC (minimal inhibitory concentration) against the reference strain (H. pylori ATCC 43504) and 10 clinical strains with different antibiotic-resistance patterns. The strongest anti-Helicobacter activity (MIC and MBC = 31.3 µg/mL) was observed for propolis from Orgora, Ota, and Vardzia and two from Khaheti. Lower levels of activity (MIC = 62.5 µg/mL) were found in propolis obtained from Qvakhreli and Pasanauri, while the lowest effect was observed for Norio and Mestia (MIC = 125.0 µg/mL). However, despite differences in MIC, all evaluated samples exhibited bactericidal activity. We selected the most active propolis samples for assessment of urease inhibition property. Enzyme activity was inhibited by propolis extracts, with IC50 ranging from 4.01 to 1484.8 µg/mL. Principal component analysis (PCA) and hierarchical fuzzy clustering (dendrograms) coupled with matrix correlation analysis exhibited that the strongest anti-Helicobacter activity was connected with black poplar origin and high flavonoid content of propolis. Samples with lower activity contained higher presence of aspen markers and/or dominance of non-flavonoid polyphenols over flavonoids. In summary, Georgian propolis can be regarded as a source bioactive compounds that can be used as adjuvant in therapy of H. pylori infection.
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Dinat S, Orchard A, Van Vuuren S. A scoping review of African natural products against gastric ulcers and Helicobacter pylori. JOURNAL OF ETHNOPHARMACOLOGY 2023; 301:115698. [PMID: 36174808 DOI: 10.1016/j.jep.2022.115698] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE African traditional medicine is one of the oldest and most diverse practices for treating ailments and numerous natural products have been recommended for gastric ulcer treatment. Helicobacter pylori is the main causative organism implicated in several diseases, most notably in causing inflammation and the onset of gastric ulcers. Current H. pylori treatment methods are losing efficacy as H. pylori rapidly gains resistance to antibiotics. Hence, a search into natural products and their historical traditional efficacy for the treatment of gastric ulcers is of interest. AIM OF THE STUDY This review aimed to summarise the African use of natural products, including medicinal plants noted in ethnobotanical reviews, used traditionally to treat gastric ulcers, and highlights the investigations into the anti-H. pylori activity of medicinal plants and bee products found in Africa. METHODOLOGY A systematic review was carried out to identify natural products, including those used traditionally in Africa to treat gastric ulcers, and to correlate this with scientific investigations into the anti-H. pylori activity of natural products used in Africa. RESULTS A total of 107 literature sources describing the traditional use of medicinal plants in gastric ulcer treatment were found, from which 360 medicinal plants were identified. Of the plants used traditionally for gastric ulcer treatment, 11% were investigated either in vitro or in vivo for anti-ulcer and anti-H. pylori activity. Of the 122 medicinal plants eliciting antimicrobial or anti-ulcer activity, Hibiscus sabdariffa L. calyx extract and Terminalia macroptera Guill. & Perr. root extract were found to have the most noteworthy antimicrobial activity, with minimum inhibitory concentrations (MICs) of 0.01 mg/mL and 0.03 mg/mL respectively. The essential oils of Piper longum L. and Pachira aquatica Aubl. displayed the most notable in vitro anti-H. pylori activity (MIC of 0.01 mg/mL and 0.02 mg/mL). Several in vivo studies found medicinal plant extracts effective in reducing the H. pylori load along the gastric mucosa. The South African honey variants, Pure Honey and Champagne Royal Train (common names given by supplier) were the most antimicrobially effective (MIC of 0.01-10.0%, 0.63-10.00% v/v) in inhibiting H. pylori when assessed in vitro. CONCLUSION These results highlight the potential of natural products to inhibit H. pylori growth and serve as a possible stepping-stone in understanding the management of ulcers. Furthermore, effective natural product treatment or prophylactic use for preventing H. pylori growth may provide a more affordable option for African populations.
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Affiliation(s)
- S Dinat
- Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa
| | - A Orchard
- Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa
| | - S Van Vuuren
- Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa.
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Tao H, Meng F, Zhou Y, Fan J, Liu J, Han Y, Sun BB, Wang G. Transcriptomic and Functional Approaches Unveil the Role of tmRNA in Zinc Acetate Mediated Levofloxacin Sensitivity in Helicobacter pylori. Microbiol Spectr 2022; 10:e0115222. [PMID: 36354329 PMCID: PMC9769675 DOI: 10.1128/spectrum.01152-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 10/17/2022] [Indexed: 11/12/2022] Open
Abstract
Rapid increase in resistance of Helicobacter pylori (H. pylori) has hindered antibiotics-based eradication efforts worldwide and raises the need for additional approaches. Here, we investigate the role of zinc-based compounds in inhibiting H. pylori growth and modulating antibiotic sensitivities, interrogate their downstream transcriptomic changes, and highlight the potential mechanism driving the observed effects. We showed that zinc acetate inhibited H. pylori growth and increased H. pylori sensitivity to levofloxacin. Transcriptomic profiling showed distinct gene expression patterns between zinc acetate treated groups versus controls. In particular, we independently replicated the association between zinc acetate treatment and increased ssrA expression. Knockdown of ssrA restored levofloxacin resistance to levels of the control group. In this study, we first demonstrated the role of zinc acetate in H. pylori growth and antibiotic sensitivities. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results provide alternative and complementary strategies for H. pylori treatment and shed light on the underlying mechanisms driving these effects. IMPORTANCE Helicobacter pylori (H. pylori) eradication plays an important role in gastric cancer prevention, but the antimicrobial resistance of H. pylori is fast becoming a growing concern. In this study, we investigated the role of zinc acetate in inhibiting H. pylori growth and modulating antibiotic sensitivities in vitro. Additionally, we explored the transcriptomic perturbations of zinc acetate followed by functional knockdown follow-up of differentially expressed ssrA, highlighting the role of tmRNA and trans-translation in H. pylori levofloxacin resistance. Our results open up a new horizon for the treatment of antibiotic-resistant H. pylori.
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Affiliation(s)
- Hongjin Tao
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
- Medical School of Chinese PLA, Beijing, People’s Republic of China
| | - Fansen Meng
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yu Zhou
- Department of Laboratory Medicine, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jiao Fan
- Institute of Geriatrics, National Clinical Research Center of Geriatrics Disease, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jing Liu
- Institute of Geriatrics, National Clinical Research Center of Geriatrics Disease, Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yingjie Han
- Department of Oncology, Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Benjamin B. Sun
- MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Gangshi Wang
- Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Mascellino MT, Pontone S, Vega AE, Malfertheiner P. Editorial: Helicobacter pylori infection: pathogenesis, antibiotic resistance, advances and therapy, new treatment strategies. Front Microbiol 2022; 13:1102144. [PMID: 36569072 PMCID: PMC9775295 DOI: 10.3389/fmicb.2022.1102144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 11/21/2022] [Indexed: 12/13/2022] Open
Affiliation(s)
- Maria Teresa Mascellino
- Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy,*Correspondence: Maria Teresa Mascellino
| | - Stefano Pontone
- Department of Surgical Sciences, Sapienza University, Rome, Italy
| | - Alba Edith Vega
- Faculty of Biochemical Chemistry and Pharmacy, National University of San Luis, San Luis, Argentina
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-v-Guericke-University, Magdeburg, Germany
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22
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Pilat TL, Minushkin ON, Lazebnik LB, Zverkov IV, Kuznetsova YG, Khanferyan RA. Features of diet therapy for H. pylori associated diseases of the gastrointestinal tract. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2022:46-61. [DOI: 10.21518/2079-701x-2022-16-15-46-61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
This review of the literature is devoted to the importance of nutritional support in the treatment and prevention of diseases of the gastrointestinal tract associated with Helicobacter pylori. Modern data on the biological properties of H. pylori and the mechanisms of colonization of the microorganism in the gastrointestinal mucosa are presented. Information is provided on the virulence factors and factors that promote adhesion, depolymerization and dissolution of protective mucus, damage and circulatory disorders of the gastrointestinal mucosa, secreted by H. pylori (lipopolysaccharides and proteins of the outer shell of the bacterium, enzymes – mucinase, protease, phospholipase, urease, VacA cytotoxin). The article pays special attention to the issues of diet therapy, the role of various foods and their components in the dietary correction of disorders in gastrointestinal diseases associated with H. pylori. The causes of nutritional disorders in patients with gastrointestinal diseases are described and a detailed description of food products and their biologically active components with anti-Helicobacter activity is given. A special section is devoted to the use and effectiveness of specialized dietary products for therapeutic and preventive nutrition of domestic production (LLC “Leovit nutria”) and the features of use in diseases of the gastrointestinal tract mediated by H. pylori. The authors provide information on the composition of dietary products, their anti-inflammatory, antioxidant, immunotropic and other activities that underlie clinical efficacy. The article provides detailed recommendations on the use of specialized dietary foods for this pathology.
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Affiliation(s)
- T. L. Pilat
- Izmerov Research Institute of Occupational Health
| | - O. N. Minushkin
- Central State Medical Academy of Department for Presidential Affairs of the Russian Federation
| | - L. B. Lazebnik
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - I. V. Zverkov
- Central State Medical Academy of Department for Presidential Affairs of the Russian Federation
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Consumption of a Gelatin Supplemented with the Probiotic Strain Limosilactobacillus fermentum UCO-979C Prevents Helicobacter pylori Infection in a Young Adult Population Achieved. Foods 2022; 11:foods11121668. [PMID: 35741866 PMCID: PMC9222482 DOI: 10.3390/foods11121668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 05/20/2022] [Accepted: 05/28/2022] [Indexed: 12/10/2022] Open
Abstract
Helicobacter pylori is a bacterium associated with various gastrointestinal diseases of high worldwide prevalence. Since probiotics are an emerging alternative to managing infection by this pathogenic bacterium, the present work evaluated, in a randomized double-blind study controlled by a placebo, if consuming Limosilactobacillus fermentum UCO-979C prevents H. pylori infection in humans. Participants consumed either L. fermentum UCO-979C-supplemented gelatin (67 participants) or placebo-supplemented gelatin (64 participants) once a day, five days per week for 12 weeks. H. pylori infection in the participants was controlled before and after the intervention detecting H. pylori antigens in stools. Regarding H. pylori-infected participants before the study, 100% remained infected at the end of the study in the placebo group, while 96.7% of those receiving the probiotic remained infected after the intervention. Most importantly, of the non-infected participants, 34.2% became infected and 65.8% remained non-infected in the placebo group, while 2.7% became infected and 97.3% remained as non-infected individuals in the intervened group. Therefore, consuming the L. fermentum UCO-979C strain significantly reduced H. pylori infection, demonstrating a 92.6% efficacy in avoiding infection by this pathogen in non-infected individuals; thus, this probiotic is an excellent candidate to prevent H. pylori infections in non-infected individuals.
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A new approach against Helicobacter pylori using plants and its constituents: A review study. Microb Pathog 2022; 168:105594. [PMID: 35605740 DOI: 10.1016/j.micpath.2022.105594] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 05/11/2022] [Accepted: 05/15/2022] [Indexed: 02/07/2023]
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Sultan AM, Shenouda R, Sultan AM, Shehta A, Nabiel Y. The Relation Between Host TLR9 -1486T/C, rs187084 Gene Polymorphisms and Helicobacter pylori cagA, sodB, hsp60, and vacA Virulence Genes among Gastric Cancer Patients. Pol J Microbiol 2022; 71:35-42. [PMID: 35635169 PMCID: PMC9152911 DOI: 10.33073/pjm-2022-003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/19/2021] [Indexed: 12/26/2022] Open
Abstract
To identify the associations between different genotypes of TLR9 -1486T/C (rs187084) with gastric cancer patients and reveal their relation to Helicobacter pylori virulence genes (cagA, sodB, hsp60 and vacA). Patients with gastric cancer were recruited to our study, diagnosed both endoscopically and histopathologically. H. pylori were isolated from gastric samples by culture and PCR amplification of the glmM gene. Virulence genes cagA, sodB, hsp60, and vacA were detected by multiplex PCR. Blood samples were used for genotyping of TLR9 -1486T/C (rs187084) by PCR-RFLP. Out of 132 patients with gastric cancer, 106 (80.3%) were positive for H. pylori. A similar number of healthy participants was recruited as controls. The prevalence of cagA, sodB, hsp60, and vacA genes among H. pylori was 90.6%, 70.8%, 83.0%, and 95.3%, respectively. The vacA gene alleles had a prevalence of 95.3% for vacAs1/s2, 52.8% for vacAm1, and 42.5% for vacAm2. The CC genotype of TLR9 -1486T/C had a significantly higher frequency in gastric cancer patients when compared to healthy participants (p = 0.045). Furthermore, the CC genotype demonstrated a significant association with H. pylori strains carrying sodB, hsp60, and vacAm1 virulence genes (p = 0.021, p = 0.049, and p = 0.048 respectively). Patients with CC genotype of TLR9 -1486T/C (rs187084) might be at higher risk for the development of gastric cancer, and its co-existence with H. pylori strains carrying sodB, hsp60, or vacAm1 virulence genes might have a synergistic effect in the development of gastric cancer. Further studies on a wider scale are recommended.
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Affiliation(s)
- Amira M. Sultan
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ragy Shenouda
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad M. Sultan
- Gastroenterology Surgical Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Shehta
- Gastroenterology Surgical Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Yasmin Nabiel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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26
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Paucar-Carrión C, Espinoza-Monje M, Gutiérrez-Zamorano C, Sánchez-Alonzo K, Carvajal RI, Rogel-Castillo C, Sáez-Carrillo K, García-Cancino A. Incorporation of Limosilactobacillus fermentum UCO-979C with Anti- Helicobacter pylori and Immunomodulatory Activities in Various Ice Cream Bases. Foods 2022; 11:foods11030333. [PMID: 35159484 PMCID: PMC8834266 DOI: 10.3390/foods11030333] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/17/2022] [Accepted: 01/17/2022] [Indexed: 12/15/2022] Open
Abstract
Limosilactobacillus fermentum UCO-979C is a probiotic strain possessing anti-Helicobacter pylori and immunomodulatory activity. The aim of this work was to examine if this strain maintains its probiotic properties and its viability when added to dairy-based ice creams (cookies and cream, Greek yogurt, and chocolate with brownie) or to fruit-based ice creams (pineapple and raspberry) stored at −18 °C for 90 days. The probiotic anti-H. pylori activity using the well diffusion test, its immunomodulatory activity was measured using transforming growth factor beta 1 (TGF-β1) cytokine production by human gastric adenocarcinoma (AGS) cells, and its viability was measured using the microdrop technique. Assays were performed in triplicate. The L. fermentum UCO-979C strain maintained strong anti-H. pylori activity in dairy-based ice creams and mild activity in fruit-based ice cream. The production of pro-inflammatory cytokine TGF-β1 on AGS cells was higher in the probiotic recovered from Greek yogurt ice cream, maintaining a viability exceeding 107 colony-forming units/mL. The addition of the probiotic to ice creams did not significantly influence the physicochemical properties of the product. These data show the great potential of the L. fermentum UCO-979C strain in producing probiotic dairy-based and fruit-based ice creams.
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Affiliation(s)
- Cristina Paucar-Carrión
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
| | - Marcela Espinoza-Monje
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
| | - Cristian Gutiérrez-Zamorano
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
| | - Kimberly Sánchez-Alonzo
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
| | - Romina I. Carvajal
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
| | - Cristian Rogel-Castillo
- Department of Food Science and Technology, Faculty of Pharmacy, Universidad de Concepción, Concepción 4070386, Chile;
| | - Katia Sáez-Carrillo
- Department of Statistics, Faculty of Physical and Mathematical Sciences, Universidad de Concepción, Concepción 4070386, Chile;
| | - Apolinaria García-Cancino
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile; (C.P.-C.); (M.E.-M.); (C.G.-Z.); (K.S.-A.); (R.I.C.)
- Correspondence: ; Tel.: +56-41-2204144; Fax: +56-41-2245975
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27
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Duque-Buitrago LF, Tornero-Martínez A, Loera-Castañeda V, Mora-Escobedo R. Use of food and food-derived products in the treatment of gastritis: A systematic review. Crit Rev Food Sci Nutr 2022; 63:5771-5782. [PMID: 34989280 DOI: 10.1080/10408398.2021.2024131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Gastritis is the acute or chronic inflammation of gastric mucosa and is triggered by diverse factors. Treatments used for non-bacterial gastritis include proton pump inhibitors, histamine H2 receptor inhibitors, and antacids, and their use is linked to various side effects. Research on alternative therapeutics using food or food-based products is extensive, mostly in preclinical research. We aimed at documenting the clinical advances in food-based therapies as alternative therapeutics for gastritis. Articles with information on the treatment of gastritis with food or food-based products published until December 1, 2020 were identified through a systematic search in PubMed Medline Database. Additionally, references of retrieved articles were screened for relevant reviews and meta-analyses. Two investigators independently selected and reviewed the titles and abstracts of articles and extracted the study characteristics (PICO framework) and key findings. Dual quality assessment and data extraction were performed. We found 28 clinical studies evaluating garlic, turmeric, red peppers, broccoli sprouts, cranberry juice, honey, oils, and probiotics contained in different foods, such as juices, yogurt, and cheese. The existing literature presents a high risk of bias, and results of the same should be evaluated and replicated with precaution; more rigorous clinical studies are lacking.
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Affiliation(s)
- Luisa F Duque-Buitrago
- Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Unidad Profesional "Adolfo López Mateos", Instituto Politécnico Nacional, Calle Wilfrido Massieu esquina Calzada, Manuel Stampa. C.P, Ciudad de México, 07738, México
| | - Antonio Tornero-Martínez
- Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Unidad Profesional "Adolfo López Mateos", Instituto Politécnico Nacional, Calle Wilfrido Massieu esquina Calzada, Manuel Stampa. C.P, Ciudad de México, 07738, México
| | - Verónica Loera-Castañeda
- Centro Interdisciplinario de Investigación para el Desarrollo Regional Unidad Durango, Instituto Politécnico Nacional, Calle Sigma #119, Fraccionamiento 20 de noviembre II, C.P.34220, Durango, México
| | - Rosalva Mora-Escobedo
- Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Unidad Profesional "Adolfo López Mateos", Instituto Politécnico Nacional, Calle Wilfrido Massieu esquina Calzada, Manuel Stampa. C.P, Ciudad de México, 07738, México
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28
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Basu N, Ghosh R. Recent chemical syntheses of bacteria related oligosaccharides using modern expeditious approaches. Carbohydr Res 2021; 507:108295. [PMID: 34271477 DOI: 10.1016/j.carres.2021.108295] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/15/2021] [Accepted: 03/16/2021] [Indexed: 12/22/2022]
Abstract
Apart from some essential and crucial roles in life processes carbohydrates also are involved in a few detrimental courses of action related to human health, like infections by pathogenic microbes, cancer metastasis, transplanted tissue rejection, etc. Regarding management of pathogenesis by microbes, keeping in mind of multi drug-resistant bacteria and epidemic or endemic incidents, preventive measure by vaccination is the best pathway as also recommended by the WHO; by vaccination, eradication of bacterial diseases is also possible. Although some valid vaccines based on attenuated bacterial cells or isolated pure polysaccharide-antigens or the corresponding conjugates thereof are available in the market for prevention of several bacterial diseases, but these are not devoid of some disadvantages also. In order to develop improved conjugate T-cell dependent vaccines oligosaccharides related to bacterial antigens are synthesized and converted to the corresponding carrier protein conjugates. Marketed Cuban Quimi-Hib is such a vaccine being used since 2004 to resist Haemophilus influenza b infections. During nearly the past two decades research is going on worldwide for improved synthesis of bacteria related oligosaccharides or polysaccharides towards development of such semisynthetic or synthetic glycoconjugate vaccines. The present dissertation is an endeavour to encompass the recent syntheses of several pathogenic bacterial oligosaccharides or polysaccharides, made during the past ten-eleven years with special reference to modern expeditious syntheses.
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Affiliation(s)
- Nabamita Basu
- Department of Chemistry, Nabagram Hiralal Paul College, Konnagar, Hoogly, West Bengal, 712246, India
| | - Rina Ghosh
- Department of Chemistry, Jadavpur University, Kolkata, 700 032, India.
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29
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Mirzaei S, Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran, Keshavarzi F, Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran, Karami P, Department of Medical Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. The Prevalence of H. Pylori cagA Gene in Patients with Gastric Ulcer. IRANIAN JOURNAL OF MEDICAL MICROBIOLOGY 2021; 15:345-351. [DOI: 10.30699/ijmm.15.3.345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2024]
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30
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Ullah H, Di Minno A, Santarcangelo C, Khan H, Xiao J, Arciola CR, Daglia M. Vegetable Extracts and Nutrients Useful in the Recovery from Helicobacter pylori Infection: A Systematic Review on Clinical Trials. Molecules 2021; 26:2272. [PMID: 33919894 PMCID: PMC8070974 DOI: 10.3390/molecules26082272] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/10/2021] [Accepted: 04/11/2021] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infections affect almost half of the world's population, with gradually increasing incidence in developed countries. Eradication of H. pylori may provide significant benefits to the affected individual by healing a number of gastrointestinal and extra-digestive disorders. But due to increased microbial resistance and lack of patient adherence to the therapy, the eradication rate of H. pylori is below 80% with current pharmacological therapies. The usage of botanicals for their therapeutic purposes and medicinal properties have been increased in last decades. They can be use as alternative H. pylori treatments, especially against drug-resistant strains. Epidemiological studies have revealed that people with lower vegetable and micronutrient intake may be at increased risk of H. pylori infection. We have undertaken a review of clinical trials to evaluate the efficacy of vegetable extracts and micronutrients in patients with H. pylori. Various databases, such as Google Scholar, PubMed, Scopus, Web of Science, and the Cochrane Library, were searched for the articles published in English. A total of 24 clinical studies (15 for vegetable extracts and 9 for micronutrients) were selected to be reviewed and summarized in this article. Vegetable extracts (Broccoli sprouts, curcumin, Burdock complex, and Nigella sativa) and micronutrients (vitamin C and E) were not found to be as effective as single agents in H. pylori eradication, rather their efficacy synergized with conventional pharmacological therapies. Conversely, GutGard was found to be significantly effective as a single agent when compared to placebo control.
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Affiliation(s)
- Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (A.D.M.); (C.S.)
| | - Alessandro Di Minno
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (A.D.M.); (C.S.)
- CEINGE-Biotecnologie Avanzate, 80131 Naples, Italy
| | - Cristina Santarcangelo
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (A.D.M.); (C.S.)
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; or
| | - Jianbo Xiao
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China;
| | - Carla Renata Arciola
- Department of Experimental, Diagnostic and Specially Medicine, University of Bologna, via San Giacomo 14, 40126 Bologna, Italy;
- Laboratorio di Patologia delle Infezioni Associate all’Impianto, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (A.D.M.); (C.S.)
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China;
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Byeon JY, Park D, Kim TW, Ko CH, Choi JI. Impregnation of probiotics into porous TiO2 support for enhanced viability. KOREAN J CHEM ENG 2021. [DOI: 10.1007/s11814-020-0728-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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32
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Cen Q, Gao T, Ren Y, Lu X, Lei H. Immune evaluation of a Saccharomyces cerevisiae-based oral vaccine against Helicobacter pylori in mice. Helicobacter 2021; 26:e12772. [PMID: 33219579 DOI: 10.1111/hel.12772] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 10/23/2020] [Accepted: 10/26/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a common human pathogenic bacterium that is associated with gastric diseases. The current leading clinical therapy is combination antibiotics, but this treatment has safety issues, especially the induction of drug resistance. Therefore, developing a safe and effective vaccine against H. pylori is one of the best alternatives. OBJECTIVE To develop Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines and then demonstrate the feasibility of this platform for preventing H. pylori infection in the absence of a mucosal adjuvant. MATERIALS AND METHODS Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines, including EBY100/pYD1-UreB and EBY100/pYD1-VacA, were generated and analyzed by Western blot, Immunofluorescence analysis, flow cytometric assay, and indirect enzyme-link immunosorbent assay (ELISA). Further, antibody responses induced by oral administration of EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA were measured in a mouse model. Lastly, the vaccinated mice were infected with H. pylori SS1, and colonization in the stomach were evaluated. RESULTS Saccharomyces cerevisiae-based H. pylori oral vaccines were successfully constructed. Mice orally administered with EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA exhibited a significant humoral immune response as well as a mucosal immune response. Importantly, S. cerevisiae-based oral vaccines could effectively reduce bacterial loads with statistical significance after H. pylori infection. CONCLUSIONS Our study shows that S. cerevisiae-based platforms can serve as an alternative approach for the future development of promising bacterial oral vaccine candidates.
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Affiliation(s)
- Qianhong Cen
- College of Medicine, Southwest Jiaotong University, Chengdu, China
| | - Tong Gao
- College of Medicine, Southwest Jiaotong University, Chengdu, China
| | - Yi Ren
- College of Medicine, Southwest Jiaotong University, Chengdu, China
| | - Xin Lu
- College of Medicine, Southwest Jiaotong University, Chengdu, China
| | - Han Lei
- College of Medicine, Southwest Jiaotong University, Chengdu, China
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3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti- Helicobacter pylori Activity In Vivo. Pharmaceuticals (Basel) 2020; 13:ph13110384. [PMID: 33202739 PMCID: PMC7697961 DOI: 10.3390/ph13110384] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/11/2020] [Accepted: 11/11/2020] [Indexed: 12/19/2022] Open
Abstract
We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.
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34
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Park HS, Jeong HY, Kim YS, Seo CS, Ha H, Kwon HJ. Anti-microbial and anti-inflammatory effects of Cheonwangbosim-dan against Helicobacter pylori-induced gastritis. J Vet Sci 2020; 21:e39. [PMID: 32476313 PMCID: PMC7263912 DOI: 10.4142/jvs.2020.21.e39] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 01/26/2020] [Accepted: 01/26/2020] [Indexed: 12/11/2022] Open
Abstract
Background There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. Objectives The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. Methods AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. Results Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. Conclusions This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.
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Affiliation(s)
- Hee Seon Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
| | - Hye Yun Jeong
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
| | - Young Suk Kim
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea
| | - Chang Seob Seo
- Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
| | - Hyekyung Ha
- Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
| | - Hyo Jung Kwon
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.
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Stojković D, Kostić M, Smiljković M, Aleksić M, Vasiljević P, Nikolić M, Soković M. Linking Antimicrobial Potential of Natural Products Derived from Aquatic Organisms and Microbes Involved in Alzheimer's Disease - A Review. Curr Med Chem 2020. [PMID: 29521212 DOI: 10.2174/0929867325666180309103645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The following review is oriented towards microbes linked to Alzheimer's disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high-risk factors for AD occurrence.
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Affiliation(s)
- Dejan Stojković
- Department of Plant Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
| | - Marina Kostić
- Department of Plant Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
| | - Marija Smiljković
- Department of Plant Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
| | - Milena Aleksić
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Nis, Visegradska 33, 18000 Nis, Serbia
| | - Perica Vasiljević
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Nis, Visegradska 33, 18000 Nis, Serbia
| | - Miloš Nikolić
- Department of Plant Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
| | - Marina Soković
- Department of Plant Physiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
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Henriques PC, Costa LM, Seabra CL, Antunes B, Silva-Carvalho R, Junqueira-Neto S, Maia AF, Oliveira P, Magalhães A, Reis CA, Gartner F, Touati E, Gomes J, Costa P, Martins MCL, Gonçalves IC. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice. Acta Biomater 2020; 114:206-220. [PMID: 32622054 DOI: 10.1016/j.actbio.2020.06.035] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 06/22/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
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Affiliation(s)
- Patrícia C Henriques
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Lia M Costa
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Catarina L Seabra
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Bernardo Antunes
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Ricardo Silva-Carvalho
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Susana Junqueira-Neto
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - André F Maia
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
| | - Pedro Oliveira
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Ana Magalhães
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Celso A Reis
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Faculdade de Medicina, Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Fátima Gartner
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Eliette Touati
- Unit of Helicobacter Pathogenesis, Department of Microbiology, CNRS UMR2001, Institut Pasteur, 25-28 Rue du Dr. Roux, 75015, Paris, France
| | - Joana Gomes
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
| | - Paulo Costa
- UCIBIO/REQUIMTE, MedTech-Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4150-755 Porto, Portugal
| | - M Cristina L Martins
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Inês C Gonçalves
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
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Tian G, Hu J, Qin C, Li L, Zou X, Cai J, Seeberger PH, Yin J. Chemical Synthesis and Immunological Evaluation of
Helicobacter pylori
Serotype O6 Tridecasaccharide O‐Antigen Containing a
dd
‐Heptoglycan. Angew Chem Int Ed Engl 2020; 59:13362-13370. [PMID: 32363752 DOI: 10.1002/anie.202004267] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/29/2020] [Indexed: 12/31/2022]
Affiliation(s)
- Guangzong Tian
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Jing Hu
- Wuxi School of Medicine Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Chunjun Qin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Lingxin Li
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Xiaopeng Zou
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Juntao Cai
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Peter H. Seeberger
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
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Tian G, Hu J, Qin C, Li L, Zou X, Cai J, Seeberger PH, Yin J. Chemical Synthesis and Immunological Evaluation of
Helicobacter pylori
Serotype O6 Tridecasaccharide O‐Antigen Containing a
dd
‐Heptoglycan. Angew Chem Int Ed Engl 2020. [DOI: 10.1002/ange.202004267] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Guangzong Tian
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Jing Hu
- Wuxi School of Medicine Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Chunjun Qin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Lingxin Li
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
| | - Xiaopeng Zou
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Juntao Cai
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Peter H. Seeberger
- Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of Biotechnology Jiangnan University Lihu Avenue 1800 Wuxi Jiangsu Province 214122 P. R. China
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Garcia-Castillo V, Marcial G, Albarracín L, Tomokiyo M, Clua P, Takahashi H, Kitazawa H, Garcia-Cancino A, Villena J. The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection. Microorganisms 2020; 8:microorganisms8040479. [PMID: 32230910 PMCID: PMC7232353 DOI: 10.3390/microorganisms8040479] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/18/2020] [Accepted: 03/22/2020] [Indexed: 02/07/2023] Open
Abstract
Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.
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Affiliation(s)
- Valeria Garcia-Castillo
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepcion Bio Bio 4030000, Chile;
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman CP4000, Argentina; (G.M.); (L.A.); (P.C.)
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
| | - Guillermo Marcial
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman CP4000, Argentina; (G.M.); (L.A.); (P.C.)
| | - Leonardo Albarracín
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman CP4000, Argentina; (G.M.); (L.A.); (P.C.)
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
- Laboratory of Computing Science. Faculty of Exact Sciences and Technology. Tucuman University, Tucuman CP4000, Argentina
| | - Mikado Tomokiyo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
| | - Patricia Clua
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman CP4000, Argentina; (G.M.); (L.A.); (P.C.)
| | - Hideki Takahashi
- Laboratory of Plant Pathology, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
- Plant Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
- Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
- Correspondence: (H.K.); (A.G.-C.); (J.V.)
| | - Apolinaria Garcia-Cancino
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepcion Bio Bio 4030000, Chile;
- Correspondence: (H.K.); (A.G.-C.); (J.V.)
| | - Julio Villena
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman CP4000, Argentina; (G.M.); (L.A.); (P.C.)
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;
- Correspondence: (H.K.); (A.G.-C.); (J.V.)
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40
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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.
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Nemattalab M, Shenagari M, Taheri M, Mahjoob M, Nazari Chamaki F, Mojtahedi A, Hasan-Alizadeh E, Ashrafkhani B, Mousavi Niri N. Co-expression of Interleukin-17A molecular adjuvant and prophylactic Helicobacter pylori genetic vaccine could cause sterile immunity in Treg suppressed mice. Cytokine 2020; 126:154866. [PMID: 31629103 DOI: 10.1016/j.cyto.2019.154866] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 09/15/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023]
Abstract
The increasing clinical significance of Helicobacter pylori (H. pylori) in human stomach cancer has led to global efforts to eradicate this pathogen. Recent studies have confirmed the importance of some cytokines such as Interleukin-18 (IL-18), Interleukin-8 (IL-8), Interleukin-17A (IL-17A) and Interleukin-22 (IL-22) in the pathogenesis of the so-called bacterium. This study was designed to compare the effects of Type 1T helper (Th1), Type 2T helper (Th2) cells, Regulatory T cells (Treg) and T helper 17 (Th17) modulatory effects on the efficacy of designed H. pylori vaccine by incorporating some molecular adjuvants in Treg competent and Treg suppressed groups. A bicistronic vector was used for simultaneous expression of codon-optimized Outer inflammatory protein a (OipA) gene and modified mice IL-18, IL-17A, IL-22 and Foxp3 (forkhead box P3) cytokines from four cassettes. Immunization of mice groups was performed using produced plasmids intradermally. Specific IgG1 and IgG2 and IgA antibody titers produced in mice were confirmed by enzyme-linked immunosorbent assay (ELISA) in sera and intestine obtained four weeks after the last immunization. After being stimulated with a mixture of both anti-CD28 mAb and H. pylori lysate, frequencies of single Interferon-Gamma (IFN-γ), single IL-17 and dual IFN-γ/IL-17-secreting T-cells were documented using dual-color FluoroSpot. The kinetics of Th1, Th2 and Th17 in the immunized animals was determined by relative quantification of IL-17A, IL-22, IFN-γ, IL-8, IL-2 and IL-4 specific mRNAs. Four weeks after bacterial challenge, quantitative colony count in the isolated and homogenized stomachs was utilized to assess the level of protective immunity among all groups. The results of immunologic assays showed that the highest cell-mediated immunity cytokines were produced in IL-17 receiving group in which the Treg responses were suppressed previously by the administration of the Foxp3 as an immunogen. In addition, potent clearance of Helicobacter pylori infection was seen in this group as well.
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Affiliation(s)
- Mehran Nemattalab
- Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Shenagari
- Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mojtaba Taheri
- Department of Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohammad Mahjoob
- Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Ali Mojtahedi
- Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Babak Ashrafkhani
- Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Neda Mousavi Niri
- Department of Biotechnology, Faculty of Advanced Medical Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
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Tian G, Qin C, Liu Z, Shen D, Zou X, Fu J, Hu J, Seeberger PH, Yin J. Total synthesis of theHelicobacter pyloriserotype O2 O-antigen α-(1 → 2)- and α-(1 → 3)-linked oligoglucosides. Chem Commun (Camb) 2020; 56:344-347. [DOI: 10.1039/c9cc07915g] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Unique α-(1 → 2)- and α-(1 → 3)-linked oligoglucosides from theH. pyloriserotype O2 O-antigen were synthesized with exclusive α-selectivity using remote participation effects.
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Affiliation(s)
- Guangzong Tian
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Chunjun Qin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Zhonghua Liu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Dacheng Shen
- Department of Biomolecular Systems
- Max-Plank Institute of Colloids and Interfaces
- 14476 Potsdam
- Germany
| | - Xiaopeng Zou
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Junjie Fu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Jing Hu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
| | - Peter H. Seeberger
- Department of Biomolecular Systems
- Max-Plank Institute of Colloids and Interfaces
- 14476 Potsdam
- Germany
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology
- Ministry of Education
- School of Biotechnology
- Jiangnan University
- Wuxi 214122
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Xia M, Chen H, Liu S. The synergy of resveratrol and alcohol against Helicobacter pylori and underlying anti-Helicobacter pylori mechanism of resveratrol. J Appl Microbiol 2019; 128:1179-1190. [PMID: 31774610 DOI: 10.1111/jam.14531] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 11/10/2019] [Accepted: 11/23/2019] [Indexed: 12/13/2022]
Abstract
AIMS To determine individual antibacterial and synergistic antibacterial effects of resveratrol and alcohol against Helicobacter pylori 26695 in vitro, and to elucidate the underlying mechanism of action of resveratrol against H. pylori. METHODS AND RESULTS The minimum inhibitory concentrations (MICs) and time-killing curve of resveratrol and alcohol were determined. Transcriptome analysis by RNA sequencing was used to elucidate the underlying mechanism of action of resveratrol against H. pylori. Our results showed that the MICs of resveratrol and alcohol against H. pylori 26695 are about 64 μg ml-1 and 4% (v/v) respectively. The synergy was found: resveratrol at concentration of 64 μg ml-1 in combination with alcohol at concentration of 4% (v/v) showed >10 000-fold decrease in the mount of viable bacteria compared with resveratrol and alcohol used alone. Transcriptome analysis showed 152 genes were downregulated and 111 genes were upregulated in the presence of resveratrol. Genes involved in protein translation (17·1%), outer membrane proteins (OMPs) (9·9%) and transports (11·2%) comprise 38·2% of the downregulated genes. In comparison, genes involved in redox (13·5%), pathogenesis and motility (9·9%) and iron homeostasis (4·5%) comprise 27·9% of the upregulated genes. CONCLUSIONS The synergy of resveratrol and alcohol against H. pylori was found in this study. The underlying mechanism of action of resveratrol against H. pylori may be mainly attributed to its inhibitory effect on translation, OMPs, transports, ATP synthase and possible oxidative damage. SIGNIFICANCE AND IMPACT OF THIS STUDY Our study provides a global insight into the anti-H. pylori mechanism of resveratrol. Both resveratrol and alcohol can contribute to inhibition of ribosomes, changes in OMPs and oxidative damage, which may be the explanations of synergistic effect against H. pylori elicited by resveratrol and alcohol.
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Affiliation(s)
- M Xia
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - H Chen
- College of Life Science, Sichuan Agricultural University, Ya'an, China
| | - S Liu
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
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In Vitro Activity of Sertraline, an Antidepressant, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains. Pathogens 2019; 8:pathogens8040228. [PMID: 31717683 PMCID: PMC6963513 DOI: 10.3390/pathogens8040228] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 11/02/2019] [Accepted: 11/08/2019] [Indexed: 12/19/2022] Open
Abstract
Antibiotic resistance of Helicobacter pylori, a spiral bacterium associated with gastric diseases, is a topic that has been intensively discussed in last decades. Recent discoveries indicate promising antimicrobial and antibiotic-potentiating properties of sertraline (SER), an antidepressant substance. The aim of the study, therefore, was to determine the antibacterial activity of SER in relation to antibiotic-sensitive and antibiotic-resistant H. pylori strains. The antimicrobial tests were performed using a diffusion-disk method, microdilution method, and time-killing assay. The interaction between SER and antibiotics (amoxicillin, clarithromycin, tetracycline, and metronidazole) was determined by using a checkerboard method. In addition, the study was expanded to include observations by light, fluorescence, and scanning electron microscopy. The growth inhibition zones were in the range of 19–37 mm for discs impregnated with 2 mg of SER. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) counted for 2–8 µg/mL and 4–8 µg/mL, respectively. The time-killing assay showed the time-dependent and concentration-dependent bactericidal activity of SER. Bacteria exposed to MBCs (but not sub-MICs and MICs ≠ MBCs) underwent morphological transformation into coccoid forms. This mechanism, however, was not protective because these cells after a 24-h incubation had a several-fold reduced green/red fluorescence ratio compared to the control. Using the checkerboard assay, a synergistic/additive interaction of SER with all four antibiotics tested was demonstrated. These results indicate that SER may be a promising anti-H. pylori compound.
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Si XB, Zhang XM, Wang S, Lan Y, Zhang S, Huo LY. Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis. World J Gastroenterol 2019; 25:6025-6040. [PMID: 31660038 PMCID: PMC6815797 DOI: 10.3748/wjg.v25.i39.6025] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 09/16/2019] [Accepted: 09/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against Helicobacter pylori (H. Pylori) infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported. AIM To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials (RCTs). METHODS Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including "allicin", "Helicobacter pylori", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality". RESULTS A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [I 2 = 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35, P < 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group (86.17%, 349/405) was significantly higher than that of the control group (75.87%, 305/402) [I 2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P < 0.001]. The total remission rate of peptic ulcers across all allicin groups was 97.16%, which was significantly higher than that of controls [96.05% (389/405) vs 86.55% (360/402), I 2 = 0, OR = 3.04, 95%CI: 1.51-6.12, P = 0.015]. No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low" due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias". CONCLUSION Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality.
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Affiliation(s)
- Xiao-Bei Si
- Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Xu-Min Zhang
- Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Shuai Wang
- Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Yu Lan
- Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Shuo Zhang
- Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing 100037, China
| | - Lin-Yu Huo
- Department of Neurology, Beijing Haidian Hospital, Beijing 100080, China
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de Brito BB, da Silva FAF, Soares AS, Pereira VA, Santos MLC, Sampaio MM, Neves PHM, de Melo FF. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J Gastroenterol 2019; 25:5578-5589. [PMID: 31602159 PMCID: PMC6785516 DOI: 10.3748/wjg.v25.i37.5578] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/14/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Aline Silva Soares
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Vinícius Afonso Pereira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Maria Luísa Cordeiro Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Mariana Miranda Sampaio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Pedro Henrique Moreira Neves
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Häfner SJ. High hopes and high honours for cancer immunotherapy. Biomed J 2019; 42:293-298. [PMID: 31783989 PMCID: PMC6889242 DOI: 10.1016/j.bj.2019.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 10/14/2019] [Indexed: 02/07/2023] Open
Abstract
This issue of the Biomedical Journal honours the laureates of the 2018 Nobel Prize in Physiology and Medicine for their ground-breaking contributions to cancer immunotherapy and unveils the identification of essential intermediates between microtubule-targeting agents and apoptosis. Subsequently, we learn about the hypoglycemic properties of natural phenolic acids, how cone-beam computed tomography assists dental implant surgery and which factors should be taken into account for salvage liver transplantation after recurrent hepatocellular carcinoma. Further readings discuss the negative impact of bismuth shields on computed tomography image quality, the predictive value of warning headaches for aneurysmal subarachnoid haemorrhage and the great long-term performance of zirconia implant abutments.
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Affiliation(s)
- Sophia Julia Häfner
- University of Copenhagen, BRIC Biotech Research & Innovation Centre, Anders Lund Group, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
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Sharifi A, Azizi M, Moradi-Choghakabodi P, Aghaei S, Azizi A. In vitro anti-Helicobacter pylori activity of aqueous extract from Persian Oak testa. CHINESE HERBAL MEDICINES 2019. [DOI: 10.1016/j.chmed.2019.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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González A, Salillas S, Velázquez-Campoy A, Espinosa Angarica V, Fillat MF, Sancho J, Lanas Á. Identifying potential novel drugs against Helicobacter pylori by targeting the essential response regulator HsrA. Sci Rep 2019; 9:11294. [PMID: 31383920 PMCID: PMC6683298 DOI: 10.1038/s41598-019-47746-9] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 07/23/2019] [Indexed: 02/06/2023] Open
Abstract
The increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome the current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. pylori infection. We screened 1120 FDA-approved drugs for molecules that bind to the essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as HsrA binders. All of these compounds noticeably inhibited the in vitro DNA binding activity of HsrA, but only four of them, apigenin, chrysin, kaempferol and hesperetin, exhibited high bactericidal activities against H. pylori. Chrysin showed the most potent bactericidal activity and the most synergistic effect in combination with clarithromycin or metronidazole. Flavonoid binding to HsrA occurs preferably at its C-terminal effector domain, interacting with amino acid residues specifically involved in forming the helix-turn-helix DNA binding motif. Our results validate the use of HsrA as a novel and effective therapeutic target in H. pylori infection and provide molecular evidence of a novel antibacterial mechanism of some natural flavonoids against H. pylori. The results further support the valuable potential of natural flavonoids as candidate drugs for novel antibacterial strategies.
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Affiliation(s)
- Andrés González
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009, Zaragoza, Spain.
- Institute for Biocomputation and Physics of Complex Systems, Mariano Esquillor (Edif. I + D), 50018, Zaragoza, Spain.
| | - Sandra Salillas
- Institute for Biocomputation and Physics of Complex Systems, Mariano Esquillor (Edif. I + D), 50018, Zaragoza, Spain
- Department of Biochemistry & Molecular and Cell Biology, University of Zaragoza, Pedro Cerbuna 12, 50009, Zaragoza, Spain
| | - Adrián Velázquez-Campoy
- Institute for Biocomputation and Physics of Complex Systems, Mariano Esquillor (Edif. I + D), 50018, Zaragoza, Spain
- CIBERehd, Monforte de Lemos 3-5, 28029, Madrid, Spain
- ARAID Foundation, Ranillas 1-D, 500018, Zaragoza, Spain
| | - Vladimir Espinosa Angarica
- Cancer Science Institute, National University of Singapore, 14 Medical Drive, #12-01, 117599, Singapore, Singapore
| | - María F Fillat
- Institute for Biocomputation and Physics of Complex Systems, Mariano Esquillor (Edif. I + D), 50018, Zaragoza, Spain
- Department of Biochemistry & Molecular and Cell Biology, University of Zaragoza, Pedro Cerbuna 12, 50009, Zaragoza, Spain
| | - Javier Sancho
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems, Mariano Esquillor (Edif. I + D), 50018, Zaragoza, Spain
- Department of Biochemistry & Molecular and Cell Biology, University of Zaragoza, Pedro Cerbuna 12, 50009, Zaragoza, Spain
| | - Ángel Lanas
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009, Zaragoza, Spain
- CIBERehd, Monforte de Lemos 3-5, 28029, Madrid, Spain
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Pedro Cerbuna 12, 50009, Zaragoza, Spain
- Digestive Diseases Service, University Clinic Hospital Lozano Blesa, San Juan Bosco 15, 50009, Zaragoza, Spain
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Yoon JY, Cha JM, Hong SS, Kim HK, Kwak MS, Jeon JW, Shin HP. Fermented milk containing Lactobacillus paracasei and Glycyrrhiza glabra has a beneficial effect in patients with Helicobacter pylori infection: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore) 2019; 98:e16601. [PMID: 31464895 PMCID: PMC6736393 DOI: 10.1097/md.0000000000016601] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Lactobacillus paracasei and Glycyrrhiza glabra have been reported as having beneficial effects on Helicobacter pylori infection. We aimed to assess the efficacy and safety of fermented milk containing L paracasei HP7 and G glabra in patients with H pylori infection. METHODS This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted in 2 hospitals from April to December 2017. Patients with H pylori infection were randomized into either the treatment group (fermented milk with L paracasei HP7 and G glabra) or placebo group (fermented milk only) once daily for 8 weeks. The primary endpoint was the gastric load of H pylori measured by C-urea breath test (UBT). Secondary endpoints were histologic and clinical improvement. RESULTS A total of 142 patients were randomly allocated to the treatment (n = 71) or placebo groups (n = 71). Compared to baseline data, the quantitative value of C-UBT at 8 weeks was significantly reduced in the treatment group (from 20.8 ± 13.2% to 16.9 ± 10.8%, P = .035), but not in the placebo group (P = .130). Chronic inflammation improved significantly only in the treatment group (P = .013), whereas the neutrophil activity deteriorated significantly only in the placebo group (P = .003). Moreover, the treatment group had significant improvement in gastrointestinal symptoms (P = .049) and quality of life (P = .029). No serious adverse events were observed. CONCLUSION The combination of fermented milk containing L paracasei and G glabra reduced H pylori density and improved histologic inflammation. However, their mechanisms of action should be elucidated in further studies.
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Affiliation(s)
- Jin Young Yoon
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine
| | - Jae Myung Cha
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine
| | | | - Hyung Kyung Kim
- Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea
| | - Min Seob Kwak
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine
| | - Jung Won Jeon
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine
| | - Hyun Phil Shin
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong, Kyung Hee University School of Medicine
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