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Ortiz PS, Young M, Mahmud T, Sohag MMH, Kearney CM. Generation of VacA-targeting guide peptides to increase specific antimicrobial peptide toxicity against Helicobacter pylori. J Biotechnol 2025; 403:17-29. [PMID: 40157455 DOI: 10.1016/j.jbiotec.2025.03.018] [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: 06/01/2024] [Revised: 03/20/2025] [Accepted: 03/24/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND The H. pylori virulence factors VacA and CagA are the primary determinants of gastric cancer globally. In this study we increased the activity of antimicrobial peptides (AMPs) against H. pylori by using phage display against VacA to rapidly generate peptides targeting VacA, subsequently fusing these peptides to the AMP N-terminus to confer specificity. RESULTS After four rounds of phage display, 36 phage clones were ranked for whole cell H. pylori binding by ELISA. The displayed 12-mer peptides of the top nine candidate clones were fused to GFP as guide peptides and analyzed for binding to wild type H. pylori 60190 and a ∆vacA strain. The three guides with the best differential binding were fused to the AMP pexiganan using two different linker peptides. All guide/linker combinations led to increased toxicity against H. pylori and most also decreased off-target toxicity. Guide P5 linked to pexiganan was the top configuration, delivering 64- to > 256-fold differential toxicity against H. pylori compared to off-target bacteria and a therapeutic window exceeding 128-fold when tested against cultured gastric cells. CONCLUSIONS Guide peptide biopanning provides an effective, scalable method to increase specific activity of antimicrobial peptides based on attraction to a key virulence factor.
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Affiliation(s)
- Patrick S Ortiz
- Baylor University, Department of Biology, 101 Bagby Ave., Waco, TX 76706, USA
| | - Mikaeel Young
- Baylor University, Department of Biology, 101 Bagby Ave., Waco, TX 76706, USA
| | - Toslim Mahmud
- Baylor University, Department of Biology, 101 Bagby Ave., Waco, TX 76706, USA
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Jiang J, Li D, Li F, Li H, Zhang X, Feng L. Catechin promotes endoplasmic reticulum stress-mediated gastric cancer cell apoptosis via NOX4-induced reactive oxygen species. Mol Cell Biochem 2025; 480:3201-3215. [PMID: 39565530 DOI: 10.1007/s11010-024-05138-2] [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: 06/24/2024] [Accepted: 10/07/2024] [Indexed: 11/21/2024]
Abstract
Catechin, a polyphenolic compound in various foods and beverages, shows strong anti-cancer effects against gastric cancer (GC) cells. This study explored the effect of catechin on GC cell apoptosis and endoplasmic reticulum (ER) stress. GC cells were treated with different catechin concentrations to assess effects on cell viability, LDH release, invasion, migration, apoptosis, intracellular calcium (Ca2⁺), ER stress markers, and reactive oxygen species (ROS). siRNA knockdown targeted GRP78, PERK, CHOP, and NOX4 to examine their roles in catechin-induced ER stress and apoptosis. Catechin treatment significantly reduced GC cell viability, increased LDH release, and induced apoptosis dose-dependently. Catechins elevated intracellular Ca2⁺ and ER stress markers. Co-treatment with thapsigargin (TG) intensified these effects, implicating ER stress in apoptosis. Knocking down GRP78, PERK, and CHOP mitigated catechin-induced apoptosis and restored viability. Additionally, catechins raised ROS levels, while co-treatment with Diphenyleneiodonium (DPI) or N-acetylcysteine (NAC) lowered ROS, cell damage, and ER stress markers. NOX4 knockdown countered catechin-induced viability loss and upregulated CHOP and cleaved caspase-3. Catechin induces apoptosis in GC cells through ER stress and ROS generation. Key mediators include GRP78, PERK, CHOP, and NOX4, suggesting potential therapeutic targets for enhancing catechin efficacy in GC treatment.
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Affiliation(s)
- Jun Jiang
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Deming Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Fan Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Huanqing Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
| | - Xiaohong Zhang
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
| | - Li Feng
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
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Chen D, Wu L, Liu X, Wang Q, Gui S, Bao L, Wang Z, He X, Zhao Y, Zhou J, Xie Y. Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells. Sci Rep 2024; 14:21648. [PMID: 39289452 PMCID: PMC11408507 DOI: 10.1038/s41598-024-72534-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 09/09/2024] [Indexed: 09/19/2024] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.
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Affiliation(s)
- Dingyu Chen
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Lixia Wu
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
| | - Xi Liu
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
| | - Qinrong Wang
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
| | - Shuqin Gui
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
| | - Liya Bao
- Hepatitis Laboratory, Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Zhengrong Wang
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China
| | - Xiaofeng He
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China
| | - Yan Zhao
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.
| | - Jianjiang Zhou
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.
| | - Yuan Xie
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.
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Naing C, Aung HH, Aye SN, Poovorawan Y, Whittaker MA. CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies. PLoS One 2024; 19:e0307172. [PMID: 39173001 PMCID: PMC11341061 DOI: 10.1371/journal.pone.0307172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 07/01/2024] [Indexed: 08/24/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region. METHODS Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders. RESULTS Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73-91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67-90%) in H. pylori-infected gastritis, 86% (95%CI = 73-96%) in peptic ulcer disease, and 83% (95%CI = 51-100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15-5.55). CONCLUSION Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease.
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Affiliation(s)
- Cho Naing
- College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia
| | - Htar Htar Aung
- School of Medicine, IMU University, Kuala Lumpur, Malaysia
| | - Saint Nway Aye
- School of Medicine, IMU University, Kuala Lumpur, Malaysia
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Maxine A. Whittaker
- College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia
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5
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Li G, Miao Z, Liu X, Wang Q, Zheng X. Four novel anti-adhesive activity peptides against Helicobacter pylori derived from rice bran protein: release, identification and anti-adhesive mechanisms elucidation. Food Funct 2024; 15:8418-8431. [PMID: 39042096 DOI: 10.1039/d4fo01734j] [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: 07/24/2024]
Abstract
H. pylori is a highly pathogenic and prevalent pathogen that is a class I carcinogen. More than 50% of the world's population is infected with H. pylori. An anti-adhesive strategy is an effective way to antagonize H. pylori infection, which does not cause H. pylori resistance and is safer compared to antibiotic therapy. In the present study, to obtain rice bran protein-derived anti-adhesive activity peptides against H. pylori, an efficient enzymatic hydrolysis system was established, and it was found that rice bran protein hydrolysate prepared under specific conditions possessed anti-adhesive activity against H. pylori. The anti-adhesive activity of rice bran protein hydrolysate (RPH) was 43.74 ± 1.12% (4 mg mL-1), and gastric digestion (RPHA) had no significant effect on its activity. Hydrophobic amino acids and aromatic amino acids were important for its anti-adhesive activity. Further, 284 peptide sequences with potential anti-adhesive activity were isolated and identified from RPHA. Combined with molecular docking results, four novel anti-adhesive activity peptides were finally screened, namely LS5 (LSFRL), SN8 (SNTPGMVY), VV7 (VVNFGNL) and PV9 (PVLWGVPKG). Among them, PV9 showed the highest anti-adhesive activity of 59.64 ± 2.00% (4 mg mL-1). These four peptides could bind H. pylori adhesins BabA and SabA, occupying the binding sites of cell receptors and acting as anti-adhesion agents. In conclusion, four rice bran protein-derived anti-adhesive activity peptides against H. pylori can be used for the development of novel functional foods antagonizing H. pylori infection.
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Affiliation(s)
- Guanlong Li
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, PR China.
| | - Zhengfei Miao
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, PR China.
| | - Xiaolan Liu
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, PR China.
| | - QuanXin Wang
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, PR China.
| | - Xiqun Zheng
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China.
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6
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Aydinlou ZH, Rajabi A, Emami A, Tayefeh-Gholami S, Teimourian S, Nargesi MM, Banan-Khojasteh SM, Safaralizadeh R. Three possible diagnostic biomarkers for gastric cancer: miR-362-3p, miR-362-5p and miR-363-5p. Biomark Med 2024; 18:567-579. [PMID: 39072355 PMCID: PMC11364078 DOI: 10.1080/17520363.2024.2352419] [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: 02/05/2024] [Accepted: 04/22/2024] [Indexed: 07/30/2024] Open
Abstract
Aim: MicroRNAs can be regarded as biomarkers for gastric cancer (GC) diagnosis in the early stages. This study assesses the expression levels of miR-362-3p, miR-362-5p and miR-363-5p as potential biomarkers for GC.Materials & methods: The expression levels of the miRNAs in 90 pairs of GC and adjacent normal tissue samples were analyzed by quantitative real-time reverse transcription PCR (qRT-PCR) and some bioinformatics tools were utilized for analyzing the target genes and possible molecular pathways in which these miRNAs participate.Results & conclusion: There was a significant overexpression of the miRNAs in GC cells and an outstanding correlation between their overexpression with some clinicopathological features of the patients.
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Affiliation(s)
| | - Ali Rajabi
- Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
| | - Ali Emami
- Medical School Department of Biochemistry & Molecular Medicine, Université de Montréal, Montreal, Québec
| | | | - Shahram Teimourian
- Department of Medical Genetics, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mirsaed Miri Nargesi
- Department of Pathology & Laboratory Medicine, Auckland City Hospital, Te Whatu Ora Health, New Zealand
| | | | - Reza Safaralizadeh
- Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
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7
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He X, Huang T, Wang Q, Bao L, Wang Z, Song H, Li Y, Zhou J, Zhao Y, Xie Y. A prominent role of LncRNA H19 in H. pylori CagA induced DNA damage response and cell malignancy. Sci Rep 2024; 14:14185. [PMID: 38902391 PMCID: PMC11190245 DOI: 10.1038/s41598-024-65221-y] [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: 03/05/2024] [Accepted: 06/18/2024] [Indexed: 06/22/2024] Open
Abstract
Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.
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Affiliation(s)
- Xiaofeng He
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China
- Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, People's Republic of China
| | - Tingting Huang
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China
| | - Qinrong Wang
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China
| | - Liya Bao
- Hepatitis Laboratory, Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou, People's Republic of China
| | - Zhengrong Wang
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, Guizhou, People's Republic of China
| | - Hui Song
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China
| | - Yanhong Li
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China
| | - Jianjiang Zhou
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China.
| | - Yan Zhao
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China.
| | - Yuan Xie
- Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, 550004, Guizhou, People's Republic of China.
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8
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Chang ZY, Gao WX, Zhang Y, Zhao W, Wu D, Chen L. Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases. World J Clin Cases 2024; 12:2182-2193. [PMID: 38808342 PMCID: PMC11129128 DOI: 10.12998/wjcc.v12.i13.2182] [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: 02/01/2024] [Revised: 03/08/2024] [Accepted: 03/28/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.
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Affiliation(s)
- Zheng-Yao Chang
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Wen-Xing Gao
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Yue Zhang
- Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Wen Zhao
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Di Wu
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Lin Chen
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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9
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Zhang J, Wang P, Wang J, Wei X, Wang M. Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy. Pharmacol Res 2024; 203:107185. [PMID: 38615875 DOI: 10.1016/j.phrs.2024.107185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/01/2024] [Accepted: 04/11/2024] [Indexed: 04/16/2024]
Abstract
Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.
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Affiliation(s)
- Jinjing Zhang
- Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, China
| | - Penghui Wang
- Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, China
| | - Jiafeng Wang
- Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Xiaojie Wei
- Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, China.
| | - Mengchuan Wang
- Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, China.
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10
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Zhou W, Yu X, Zhang Z, Zou X, Song H, Zheng W. Preparation and evaluation of luteolin-loaded PLA-based shape memory gastroretentive drug delivery systems. Int J Pharm 2024; 650:123670. [PMID: 38056794 DOI: 10.1016/j.ijpharm.2023.123670] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/26/2023] [Accepted: 12/02/2023] [Indexed: 12/08/2023]
Abstract
Luteolin, a natural flavonoid, is gaining growing attention for its potential in the treatment of gastric cancer. However, its clinical application is limited by factors such as poor aqueous solubility. This study aimed to develop a novel gastroretentive drug delivery system (GRDDS) to both enhance the oral bioavailability of luteolin and prolong its release and in vivo circulation time. Out of 10 luteolin-loaded PLA-based shape memory films prepared in this study, the LPC-PLA/PEG(7/3) formulation incorporated with PEG, HPMC, and NaHCO3 exhibited optimal properties in terms of drug release and inhibitory activity against SGC-7901 cells. Moreover, small-animal imaging revealed that LPC-PLA/PEG(7/3) exhibited a prolonged gastric retention time of approximately 8 h. Furthermore, the pharmacokinetic studies indicated a 354 % increase in the oral bioavailability of LPC-PLA/PEG(7/3) in rats compared to luteolin. In sum, a novel GRDDS was developed to enhance the relative bioavailability of luteolin, offering a potential strategy for practical oral administration.
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Affiliation(s)
- Wanmei Zhou
- School of Pharmacy, Harbin University of Commerce, Harbin 150076, People' s Republic of China
| | - Xuefei Yu
- School of Library, Harbin University of Commerce, Harbin 150076, People' s Republic of China
| | - Ziwei Zhang
- School of Pharmacy, Harbin University of Commerce, Harbin 150076, People' s Republic of China
| | - Xiang Zou
- School of Pharmacy, Harbin University of Commerce, Harbin 150076, People' s Republic of China
| | - Hui Song
- School of Pharmacy, Harbin University of Commerce, Harbin 150076, People' s Republic of China
| | - Wei Zheng
- School of Pharmacy, Harbin University of Commerce, Harbin 150076, People' s Republic of China.
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11
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An W, Bao L, Wang C, Zheng M, Zhao Y. Analysis of Related Risk Factors and Prognostic Factors of Gastric Cancer with Liver Metastasis: A SEER and External Validation Based Study. Int J Gen Med 2023; 16:5969-5978. [PMID: 38144441 PMCID: PMC10748731 DOI: 10.2147/ijgm.s434952] [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] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 12/12/2023] [Indexed: 12/26/2023] Open
Abstract
Background Gastric cancer (GC) has a poor prognosis, particularly in patients with liver metastasis (LM). This study aims to identify relevant factors associated with the occurrence of LM in GC patients and factors influencing the prognosis of gastric cancer with liver metastasis (GCLM) patients, in addition to developing diagnostic and prognostic nomograms specifically. Patients and Methods Overall, 6184 training data were from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2015. 1527 validation data were from our hospital between January 2018 and December 2022. Logistic regression was used to identify the risk factors associated with the occurrence of LM in GC patients, Cox regression was used to confirm the prognostic factors of GCLM patients. Two nomogram models were established to predict the risk and overall survival (OS) of patients with GCLM. The performance of the two models was evaluated using the area under the curve (AUC), concordance index (C-index), and calibration curves. Results A nomogram included five independent factors from multivariate logistic regression: sex, lymph node removal, chemotherapy, T stage and N stage were constructed to calculate the possibility of LM. Internal and external verifications of AUC were 0.786 and 0.885, respectively. The other nomogram included four independent factors from multivariate Cox regression: surgery at primary site, surgery at other site, chemotherapy, and N stage were constructed to predict OS. C-index for internal and external validations were 0.714 and 0.702, respectively, and the calibration curves demonstrated the robust discriminative ability of the models. Conclusion Based on the SEER database and validation data, we defined effective nomogram models to predict risk and OS in patients with GCLM. They have important value in clinical decision-making and personalized treatment.
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Affiliation(s)
- Wenxiu An
- Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang City, Liaoning Province, People’s Republic of China
- Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang City, Liaoning Province, People’s Republic of China
| | - Lijie Bao
- Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang City, Liaoning Province, People’s Republic of China
- Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang City, Liaoning Province, People’s Republic of China
| | - Chenyu Wang
- Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang City, Liaoning Province, People’s Republic of China
- Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang City, Liaoning Province, People’s Republic of China
| | - Mingxin Zheng
- Neusoft Research of Intelligent Healthcare Technology, Co. Ltd, Shenyang City, Liaoning Province, People’s Republic of China
| | - Yan Zhao
- Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang City, Liaoning Province, People’s Republic of China
- Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang City, Liaoning Province, People’s Republic of China
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12
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Zhang J, Hu C, Zhang R, Xu J, Zhang Y, Yuan L, Zhang S, Pan S, Cao M, Qin J, Cheng X, Xu Z. The role of macrophages in gastric cancer. Front Immunol 2023; 14:1282176. [PMID: 38143746 PMCID: PMC10746385 DOI: 10.3389/fimmu.2023.1282176] [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: 08/23/2023] [Accepted: 11/24/2023] [Indexed: 12/26/2023] Open
Abstract
As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma. These cells engage in crosstalk with cancer cells, adipocytes and other stromal cells to regulate metabolic, inflammatory and immune status, generating an immunosuppressive tumour microenvironment (TME) and ultimately promoting tumour initiation and progression. In this review, we summarise recent advances in our understanding of the origin of macrophages and their types and polarisation in cancer and provide an overview of the role of macrophages in GC carcinogenesis and development and their interaction with the GC immune microenvironment and flora. In addition, we explore the role of macrophages in preclinical and clinical trials on drug resistance and in treatment of GC to assess their potential therapeutic value in this disease.
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Affiliation(s)
- Jiaqing Zhang
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Can Hu
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Ruolan Zhang
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Jingli Xu
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Yanqiang Zhang
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Li Yuan
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Shengjie Zhang
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Siwei Pan
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Mengxuan Cao
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jiangjiang Qin
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Zhiyuan Xu
- Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
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13
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Krzysiek-Maczka G, Brzozowski T, Ptak-Belowska A. Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development. Cancer Metastasis Rev 2023; 42:1219-1256. [PMID: 37460910 PMCID: PMC10713772 DOI: 10.1007/s10555-023-10122-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 06/20/2023] [Indexed: 12/18/2023]
Abstract
The discovery of Helicobacter pylori (Hp) infection of gastric mucosa leading to active chronic gastritis, gastroduodenal ulcers, and MALT lymphoma laid the groundwork for understanding of the general relationship between chronic infection, inflammation, and cancer. Nevertheless, this sequence of events is still far from full understanding with new players and mediators being constantly identified. Originally, the Hp virulence factors affecting mainly gastric epithelium were proposed to contribute considerably to gastric inflammation, ulceration, and cancer. Furthermore, it has been shown that Hp possesses the ability to penetrate the mucus layer and directly interact with stroma components including fibroblasts and myofibroblasts. These cells, which are the source of biophysical and biochemical signals providing the proper balance between cell proliferation and differentiation within gastric epithelial stem cell compartment, when exposed to Hp, can convert into cancer-associated fibroblast (CAF) phenotype. The crosstalk between fibroblasts and myofibroblasts with gastric epithelial cells including stem/progenitor cell niche involves several pathways mediated by non-coding RNAs, Wnt, BMP, TGF-β, and Notch signaling ligands. The current review concentrates on the consequences of Hp-induced increase in gastric fibroblast and myofibroblast number, and their activation towards CAFs with the emphasis to the altered communication between mesenchymal and epithelial cell compartment, which may lead to inflammation, epithelial stem cell overproliferation, disturbed differentiation, and gradual gastric cancer development. Thus, Hp-activated fibroblasts may constitute the target for anti-cancer treatment and, importantly, for the pharmacotherapies diminishing their activation particularly at the early stages of Hp infection.
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Affiliation(s)
- Gracjana Krzysiek-Maczka
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland.
| | - Agata Ptak-Belowska
- Department of Physiology, the Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Kraków, Poland
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14
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Luo L, Wu A, Shu X, Liu L, Feng Z, Zeng Q, Wang Z, Hu T, Cao Y, Tu Y, Li Z. Hub gene identification and molecular subtype construction for Helicobacter pylori in gastric cancer via machine learning methods and NMF algorithm. Aging (Albany NY) 2023; 15:11782-11810. [PMID: 37768204 PMCID: PMC10683617 DOI: 10.18632/aging.205053] [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: 02/28/2023] [Accepted: 07/19/2023] [Indexed: 09/29/2023]
Abstract
Helicobacter pylori (HP) is a gram-negative and spiral-shaped bacterium colonizing the human stomach and has been recognized as the risk factor of gastritis, peptic ulcer disease, and gastric cancer (GC). Moreover, it was recently identified as a class I carcinogen, which affects the occurrence and progression of GC via inducing various oncogenic pathways. Therefore, identifying the HP-related key genes is crucial for understanding the oncogenic mechanisms and improving the outcomes of GC patients. We retrieved the list of HP-related gene sets from the Molecular Signatures Database. Based on the HP-related genes, unsupervised non-negative matrix factorization (NMF) clustering method was conducted to stratify TCGA-STAD, GSE15459, GSE84433 samples into two clusters with distinct clinical outcomes and immune infiltration characterization. Subsequently, two machine learning (ML) strategies, including support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), were employed to determine twelve hub HP-related genes. Beyond that, receiver operating characteristic and Kaplan-Meier curves further confirmed the diagnostic value and prognostic significance of hub genes. Finally, expression of HP-related hub genes was tested by qRT-PCR array and immunohistochemical images. Additionally, functional pathway enrichment analysis indicated that these hub genes were implicated in the genesis and progression of GC by activating or inhibiting the classical cancer-associated pathways, such as epithelial-mesenchymal transition, cell cycle, apoptosis, RAS/MAPK, etc. In the present study, we constructed a novel HP-related tumor classification in different datasets, and screened out twelve hub genes via performing the ML algorithms, which may contribute to the molecular diagnosis and personalized therapy of GC.
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Affiliation(s)
- Lianghua Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ahao Wu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xufeng Shu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Li Liu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zongfeng Feng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Qingwen Zeng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhonghao Wang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Tengcheng Hu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yi Cao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yi Tu
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhengrong Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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15
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Huang BS, Chen CT, Yeh CC, Fan TY, Chen FY, Liou JM, Shun CT, Wu MS, Chow LP. miR-21 Targets ASPP2 to Inhibit Apoptosis via CHOP-Mediated Signaling in Helicobacter pylori-Infected Gastric Cancer Cells. JOURNAL OF ONCOLOGY 2023; 2023:6675265. [PMID: 37547633 PMCID: PMC10403333 DOI: 10.1155/2023/6675265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 06/05/2023] [Accepted: 06/21/2023] [Indexed: 08/08/2023]
Abstract
Helicobacter pylori (H. pylori) infection affects cell survival pathways, including apoptosis and proliferation in host cells, and disruption of this balance is the key event in the development of H. pylori-induced gastric cancer (HPGC). H. pylori infection induces alterations in microRNAs expression that may be involved in GC development. Bioinformatic analysis showed that microRNA-21 (miR-21) is significantly upregulated in HPGC. Furthermore, quantitative proteomics and in silico prediction were employed to identify potential targets of miR-21. Following functional enrichment and clustered interaction network analyses, five candidates of miR-21 targets, PDCD4, ASPP2, DAXX, PIK3R1, and MAP3K1, were found across three functional clusters in association with cell death and survival, cellular movement, and cellular growth and proliferation. ASPP2 is inhibited by H. pylori-induced miR-21 overexpression. Moreover, ASPP2 levels are inversely correlated with miR-21 levels in HPGC tumor tissues. Thus, ASPP2 was identified as a miR-21 target in HPGC. Here, we observed that H. pylori-induced ASPP2 suppression enhances resistance to apoptosis in GC cells using apoptosis assays. Using protein interaction network and coimmunoprecipitation assay, we identified CHOP as a direct mediator of the ASPP2 proapoptotic activity in H. pylori-infected GC cells. Mechanistically, ASPP2 suppression promotes p300-mediated CHOP degradation, in turn inhibiting CHOP-mediated transcription of Noxa, Bak, and suppression of Bcl-2 to enact antiapoptosis in the GC cells after H. pylori infection. Clinicopathological analysis revealed correlations between decreased ASPP2 expression and higher HPGC risk and poor prognosis. In summary, the discovery of H. pylori-induced antiapoptosis via miR-21-mediated suppression of ASPP2/CHOP-mediated signaling provides a novel perspective for developing HPGC management and treatment.
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Affiliation(s)
- Bo-Shih Huang
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Ta Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chao-Chi Yeh
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ting-Yu Fan
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Fang-Yun Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Lu-Ping Chow
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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Bucci P, Barbaglia Y, Tedeschi F, Zalazar F. Helicobacter pylori infection: A balance between bacteria and host. Rev Argent Microbiol 2023; 55:60-67. [PMID: 35773060 DOI: 10.1016/j.ram.2022.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 01/14/2022] [Accepted: 04/07/2022] [Indexed: 12/12/2022] Open
Abstract
In Argentina, despite the important studies conducted on the prevalence of infection and the antibiotic resistance of Helicobacter pylori, there are no reports simultaneously analyzing a profile of virulence factors of the bacterium and polymorphisms in cytokine genes in patients with different alterations in the gastric mucosa (including intestinal metaplasia, IM). Our aim was to evaluate H. pylori genotypes in 132 adult patients with chronic gastritis presenting three different histological findings (inactive chronic gastritis, active chronic gastritis IM- and active chronic gastritis IM+) along with SNP-174 G>C in the IL-6 gene. cagA, vacA and babA2 genes were analyzed by multiplex PCR. The -174 G>C SNP IL-6 gene was analyzed by PCR-RFLP. Patients with active chronic gastritis IM+ showed the highest proportion of the cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG and cagA(+)/vacAm1s1/babA2(+)/IL-6GG combinations (p<0.05). There was 4-5 times greater probability of finding patients presenting the GG genotype for SNP-174 G>C IL-6, which in turn were infected with the most virulent H. pylori genotypes -cagA(+), cagA(+)/vacAm1s1 and cagA(+)/vacAm1s1/babA2- in the ACGIM+ group in comparison to the ICG group. Our results provide regional data to the idea that the transition towards severe alterations in the gastric mucosa would be the result of a balance between specific factors of H. pylori and inherent host factors. This fact can be useful to identify patients at greater risk and to select those individuals requiring appropriate eradication treatment to prevent progression to gastric cancer.
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Affiliation(s)
- Pamela Bucci
- Laboratorio de Práctica Profesional de Bioquímica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Subsuelo Hospital "Dr. José María Cullen", Avda. Freyre 2150, (S3000EOZ) Santa Fe, Argentina
| | - Yanina Barbaglia
- Servicio de Gastroenterologia, Subsuelo Hospital "Dr. José María Cullen", Avda. Freyre 2150 (S3000EOZ) Santa Fe, Argentina
| | - Fabián Tedeschi
- Laboratorio de Práctica Profesional de Bioquímica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Subsuelo Hospital "Dr. José María Cullen", Avda. Freyre 2150, (S3000EOZ) Santa Fe, Argentina
| | - Fabián Zalazar
- Laboratorio de Práctica Profesional de Bioquímica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Subsuelo Hospital "Dr. José María Cullen", Avda. Freyre 2150, (S3000EOZ) Santa Fe, Argentina.
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Wang XY, Wang LL, Liang SZ, Yang C, Xu L, Yu MC, Wang YX, Dong QJ. Prediction of gastric cancer risk by a polygenic risk score of Helicobacter pylori. World J Gastrointest Oncol 2022; 14:1844-1855. [PMID: 36187384 PMCID: PMC9516638 DOI: 10.4251/wjgo.v14.i9.1844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/29/2022] [Accepted: 08/15/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Genetic variants of Helicobacter pylori (H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms (SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear. AIM To assess the performance of a polygenic risk score (PRS) based on H. pylori SNPs in predicting the risk of gastric cancer. METHODS A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest (RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined. RESULTS Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio (OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76 (95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve (AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hpEurope strains, with an AUC value of 0.78. CONCLUSION The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.
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Affiliation(s)
- Xiao-Yu Wang
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Li-Li Wang
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Shu-Zhen Liang
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Chao Yang
- The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200000, China
| | - Lin Xu
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Meng-Chao Yu
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Yi-Xuan Wang
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Quan-Jiang Dong
- Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China
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Moghim S, Estaji F, Nasr Esfahani B, Zibaee S, Sanei M. EPIYA motif genetic characterization from Helicobacter pylori isolates in distinct geographical regions of Iran. Adv Biomed Res 2022; 11:77. [DOI: 10.4103/abr.abr_283_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/03/2021] [Accepted: 11/06/2021] [Indexed: 12/09/2022] Open
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19
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王 鑫, 孙 丽, 杨 志, 宋 顺, 李 南, 刘 悦, 田 婉, 赵 云. [Combined detection of Helicobacter pylori 16S rRNA and cagA gene in saliva specimens using multiplex PCR]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:1816-1821. [PMID: 35012913 PMCID: PMC8752427 DOI: 10.12122/j.issn.1673-4254.2021.12.09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To establish a multiplex PCR-based method for detecting Helicobacter pylori (Hp) 16S rRNA gene and cagA gene in saliva samples for investigating the prevalence of Hp in the oral cavity of Hp-infected patients with digestive tract diseases. METHODS Bioinformatics technique was used to design specific primers for Hp 16S rRNA and cagA genes for Hp detection using multiplex PCR, with recombinant cloning plasmids serving as the standard positive control. Oral saliva samples were collected from 156 patients with digestive tract diseases, and Hp 16S rRNA and cagA genes were detected using the established multiplex PCR system. RESULTS The established multiplex PCR system showed a strong specificity and a high sensitivity for detecting Hp 16S rRNA gene and cagA gene, with the lowest detection limit of 103 copies/μL. The recombinant plasmids pGMT-16s and pGMT-cagA could be used as standard positive controls for the identification of Hp. Among the 156 saliva samples, 87.2% were positive for Hp 16S rRNA gene and 23.1% for Hp cagA gene. CONCLUSION Hp is highly prevalent in saliva specimens of Hp-infected patients with digestive tract diseases. The presence of Hp in the oral cavity may importantly contribute to Hp infection in the digestive tract and recurrence after treatment.
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Affiliation(s)
- 鑫莹 王
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
- 吉林大学白求恩第一医院生殖中心-产前诊断中心,吉林 长春 130021Reproductive Medicine Prenatal Genetics Center, Bethune First Hospital of Jilin University, Changchun 130021, China
| | - 丽媛 孙
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
| | - 志平 杨
- 北华大学附属医院消化内科,吉林 吉林 132013Department of Gastroenterology of Beihua University Affiliated Hospital, Beihua University, Jilin 132013, China
| | - 顺佳 宋
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
| | - 南 李
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
| | - 悦 刘
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
| | - 婉佳 田
- 北华大学附属医院消化内科,吉林 吉林 132013Department of Gastroenterology of Beihua University Affiliated Hospital, Beihua University, Jilin 132013, China
| | - 云冬 赵
- 北华大学医学技术学院,吉林 吉林 132013College of Medical Technology, Beihua University, Jilin 132013, China
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20
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Raei N, Safaralizadeh R, Hesseinpourfeizi M, Yazdanbod A, Pourfarzi F, Latifi-Navid S. Crosstalk between lncRNAs and miRNAs in gastrointestinal cancer drug resistance. Life Sci 2021; 284:119933. [PMID: 34508759 DOI: 10.1016/j.lfs.2021.119933] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 02/09/2023]
Abstract
Gastrointestinal cancers are one of the most prevalent malignancies worldwide. Dysregulation of lncRNAs by epigenetic alteration is crucial in gastrointestinal carcinogenesis. Epigenetic alteration includes DNA methylation, chromatin remodeling, histone modifications, and deregulated-gene expression by miRNAs. LncRNAs are involved in biological processes, including, uncontrolled cell division, migration, invasion, and resistance to apoptosis and drugs. Multiple-drug resistance (MDR) is a crucial obstacle in effective chemotherapy for gastrointestinal cancers. MDR can be associated with the prognosis and diagnosis of patients receiving chemotherapeutic agents (i.e. cisplatin, oxaliplatin, platinum, 5-fluorouracil, gefitinib, methotrexate, taxol, cetuximab, docetaxel, and gemcitabine). In this review, we focused on recently known lncRNAs and their relation with miRNAs and chemotherapeutic drugs, and their modulation in gastrointestinal cancers. Moreover, we mentioned the future prospective and clinical application of lncRNAs as a critical indicator and biomarker in diagnosis, prognosis, staging, grading, and treatment of gastrointestinal cancers.
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Affiliation(s)
- Negin Raei
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Reza Safaralizadeh
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
| | | | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
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21
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Bakhti SZ, Latifi-Navid S. Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis. BMC Microbiol 2021; 21:258. [PMID: 34556055 PMCID: PMC8461988 DOI: 10.1186/s12866-021-02315-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/07/2021] [Indexed: 01/10/2023] Open
Abstract
Chronic Helicobacter pylori infection is a critical risk factor for gastric cancer (GC). However, only 1-3 % of people with H. pylori develop GC. In gastric carcinogenesis, non-H. pylori bacteria in the stomach might interact with H. pylori. Bacterial dysbiosis in the stomach can strengthen gastric neoplasia development via generating tumor-promoting metabolites, DNA damaging, suppressing antitumor immunity, and activating oncogenic signaling pathways. Other bacterial species may generate short-chain fatty acids like butyrate that may inhibit carcinogenesis and inflammation in the human stomach. The present article aimed at providing a comprehensive overview of the effects of gut microbiota and H. pylori on the development of GC. Next, the potential mechanisms of intestinal microbiota were discussed in gastric carcinogenesis. We also disserted the complicated interactions between H. pylori, intestinal microbiota, and host in gastric carcinogenesis, thus helping us to design new strategies for preventing, diagnosing, and treating GC.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 56199-11367, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 56199-11367, Ardabil, Iran.
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22
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Zheng J, Zheng C, Song B, Guo Q, Zhong Y, Zhang S, Zhang L, Duan G, Li F, Duan Y. HMB Improves Lipid Metabolism of Bama Xiang Mini-Pigs via Modulating the Bacteroidetes-Acetic Acid-AMPKα Axis. Front Microbiol 2021; 12:736997. [PMID: 34484171 PMCID: PMC8415715 DOI: 10.3389/fmicb.2021.736997] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 07/28/2021] [Indexed: 12/29/2022] Open
Abstract
Here, we used Bama Xiang mini-pigs to explore the effects of different dietary β-hydroxy-β-methylbutyrate (HMB) levels (0, 0.13, 0.64 or 1.28%) on lipid metabolism of adipose tissue. Results showed that HMB decreased the fat percentage of pigs (linearly, P < 0.05), and the lowest value was observed in the 0.13% HMB group. Moreover, the colonic acetic acid concentration and the relative Bacteroidetes abundance were increased in response to HMB supplementation (P < 0.05). Correlation analysis identified a positive correlation between the relative Bacteroidetes abundance and acetic acid production, and a negative correlation between fat percentage and the relative Bacteroidetes abundance or acetic acid production. HMB also upregulated the phosphorylation (p) of AMPKα, Sirt1, and FoxO1, and downregulated the p-mTOR expression. Collectively, these findings indicate that reduced fat percentage in Bama Xiang mini-pigs could be induced by HMB supplementation and the mechanism might be associated with the Bacteroidetes-acetic acid-AMPKα axis.
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Affiliation(s)
- Jie Zheng
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Changbing Zheng
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Bo Song
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Qiuping Guo
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Yinzhao Zhong
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Shiyu Zhang
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Lingyu Zhang
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Geyan Duan
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Fengna Li
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Yehui Duan
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
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23
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Abdi E, Latifi-Navid S, Abedi Sarvestani F, Esmailnejad MH. Emerging therapeutic targets for gastric cancer from a host- Helicobacter pylori interaction perspective. Expert Opin Ther Targets 2021; 25:685-699. [PMID: 34410200 DOI: 10.1080/14728222.2021.1971195] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Gastric cancer (GC) has the higher genetic, cytologic, and architectural heterogeneity compared to other gastrointestinal cancers. By inducing gastric inflammation, Helicobacter pylori (HP) may lead to GC through combining bacterial factors with host factors. In this regard, identification of the major therapeutic targets against the host-HP interactions plays a critical role in GC prevention, diagnosis, and treatment. AREAS COVERED This study offers new insights into the promising therapeutic targets against the angiogenesis, invasion, or metastasis of GC from a host-HP interaction perspective. To this end, MEDLINE, EMBASE, LILACS, AIM, and IndMed databases were searched for relevant articles since 1992. EXPERT OPINION Wnt signaling and COX pathway have a well-documented history in the genesis of GC by HP and might be considered as the most promising targets for early GC treatment. Destroying HP may decrease the risk of GC, but it cannot fully hinder the GC development induced by HP infection. Therefore, targeting HP-activated pathways, especially COX-2/Wnt/beta-catenin/VEGF, TLR2/TLR9/COX-2, COX2-PGE2, and NF-κB/COX-2, as well as EPHA2, MMPs, and miR-543/SIRT1 axis, can be an effective measure in the early treatment of GC. However, different clinical trials and large, multi-center cohorts are required to validate these potentially effective targets for GC therapy.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
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24
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Xin Z, Zhang L, Liu M, Wang Y, Zhang Y, Zhao W, Sun Y, Shi L, Xu N, Zhang N, Xu H. Helicobacter pylori Infection-Related Long Non-Coding RNA Signatures Predict the Prognostic Status for Gastric Cancer Patients. Front Oncol 2021; 11:709796. [PMID: 34386426 PMCID: PMC8353258 DOI: 10.3389/fonc.2021.709796] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/06/2021] [Indexed: 12/24/2022] Open
Abstract
Background Helicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori. Method We screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model. Results We identified 115 H. pylori infection-related genes were differentially expressed among H. pylori-infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection-related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters. Conclusion We successfully constructed a H. pylori-related lncRNA risk signature and nomogram associated with H. pylori-infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.
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Affiliation(s)
- Zhuoyuan Xin
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China.,The Key Laboratory of Zoonosis Research, Chinese Ministry of Education, College of Basic Medical Science, Jilin University, Changchun, China.,Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Luping Zhang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Mingqing Liu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Yachen Wang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Yingli Zhang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Weidan Zhao
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Yongxiao Sun
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Lei Shi
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Na Xu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Nan Zhang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Hong Xu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
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25
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Feili O, Bakhti SZ, Latifi-Navid S, Zahri S, Yazdanbod A. Contrasting association of Helicobacter pylori oipA genotype with risk of peptic ulceration and gastric cancer. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2021; 89:104720. [PMID: 33440259 DOI: 10.1016/j.meegid.2021.104720] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/18/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori OipA (outer inflammatory protein A) is an outer membrane protein that involves in the binding and colonization of the bacterium in the stomach. The oipA status is associated with the risk of peptic ulcerations (PUs) and gastric cancer (GC) diseases. However, the association trend with PUs compared to GC is often different and highly challenging. We therefore aimed to determine the presence of this genotype in Iranian strains and assess its association with the risk of PUs and GC in a larger number of samples. A total of 319 strains were obtained from 172 patients with non-atrophic gastritis (NAG), 52 with PUs and 95 with GC. The prevalence of the oipA+vs. oipA- genotype was 67.7% (216/319). The total frequency of the oipA+vs. oipA- genotypes in NAG, PUs, GC, non-peptic ulceration (including NAG and GC), and non-tumor (including NAG and PUs) groups was 121/172 (70.3%), 50/52 (96.2%), 45/95 (47.4%), 166/267 (62.2%), and 171/224 (76.3%), respectively. In multiple logistic regression analysis, the oipA+vs. oipA- genotype showed a strong direct association with PUs; the ORadj (95% CI) was 18.751 (4.421-79.531), (p = 0.00007). In contrast, it had a significant reverse association with GC; the ORadj (95% CI) was 0.330 (0.179-0.607), (p = 0.00036). In the present study, we interestingly found a contrasting association of the H. pylori oipA genotype with the risk of PUs and GC in Iran. Therefore, the contrasting effect of this genotype may emphasize its independent role in predicting clinical outcomes.
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Affiliation(s)
- Omolbanin Feili
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran.
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil 5618953141, Iran
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26
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Bakhti SZ, Latifi-Navid S. Oral microbiota and Helicobacter pylori in gastric carcinogenesis: what do we know and where next? BMC Microbiol 2021; 21:71. [PMID: 33663382 PMCID: PMC7934379 DOI: 10.1186/s12866-021-02130-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 02/21/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies causing death worldwide, and Helicobacter pylori is a powerful inducer of precancerous lesions and GC. The oral microbiota is a complex ecosystem and is responsible for maintaining homeostasis, modulating the immune system, and resisting pathogens. It has been proposed that the gastric microbiota of oral origin is involved in the development and progression of GC. Nevertheless, the causal relationship between oral microbiota and GC and the role of H. pylori in this relationship is still controversial. This study was set to review the investigations done on oral microbiota and analyze various lines of evidence regarding the role of oral microbiota in GC, to date. Also, we discussed the interaction and relationship between H. pylori and oral microbiota in GC and the current understanding with regard to the underlying mechanisms of oral microbiota in carcinogenesis. More importantly, detecting the patterns of interaction between the oral cavity microbiota and H. pylori may render new clues for the diagnosis or screening of cancer. Integration of oral microbiota and H. pylori might manifest a potential method for the assessment of GC risk. Hence it needs to be specified the patterns of bacterial transmission from the oral cavity to the stomach and their interaction. Further evidence on the mechanisms underlying the oral microbiota communities and how they trigger GC may contribute to the identification of new prevention methods for GC. We may then modulate the oral microbiota by intervening with oral-gastric bacterial transmission or controlling certain bacteria in the oral cavity.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran.
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27
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Abdi E, Latifi-Navid S, Latifi-Navid H, Safaralizadeh R. LncRNA polymorphisms and upper gastrointestinal cancer risk. Pathol Res Pract 2021; 218:153324. [DOI: 10.1016/j.prp.2020.153324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
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28
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Abstract
Since the description of Helicobacter pylori (HP) as the most common cause of gastritis and its neoplastic complications, numerous articles have been written about the epidemiology, clinical features, diagnostic methods, histopathology, pathogenesis, molecular biology and treatment of this infection. This review focuses on those aspects of the infection that challenge the universality of the medical implications through the lens of evolutionary science applied to medicine. The divergent epidemiological and clinical outcomes observed in different populations and the possible beneficial aspects of the infection are discussed. Also reviewed are Correa's seminal contributions to our understanding of gastric cancer in particular and postinflammatory tumours in general, and the renewed interest in intestinal metaplasia and its clinical implications.
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Affiliation(s)
- Jose Jessurun
- Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA
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29
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Liu Y, Yuan X, Chen K, Zhou F, Yang H, Yang H, Qi Y, Kong J, Sun W, Gao S. Clinical significance and prognostic value of Porphyromonas gingivalis infection in lung cancer. Transl Oncol 2020; 14:100972. [PMID: 33279803 PMCID: PMC7718477 DOI: 10.1016/j.tranon.2020.100972] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/15/2020] [Accepted: 11/20/2020] [Indexed: 02/07/2023] Open
Abstract
A variety of pathogenic microorganisms can promote the occurrence and development of malignant tumors by colonizing in the body. It has been shown that Porphyromonas gingivalis (P. gingivalis) can be colonized for a long time in upper gastrointestinal tumors and is closely related to the occurrence and development of esophageal cancer in previous studies of our team. Because the esophagus and trachea are closely adjacent and P. gingivalis can instantly enter and colonize in cells, we speculate that P. gingivalis may be colonized in lung cancer cells through oral or blood, promoting the malignant progression of lung cancer. In this study, we investigated P. gingivalis infection in lung carcinoma tissues and adjacent lung tissues, and found that the colonization rate of P. gingivalis in carcinoma tissues was significantly higher than that in adjacent lung tissues. Therefore, we propose that the microenvironment of cancer cells is more conducive to the survival of P. gingivalis. Then, we analyzed the correlation between P. gingivalis infection and clinicopathological features and survival prognosis of patients with lung cancer. It was found that P. gingivalis infection was closely related to smoking, drinking, lymph node metastasis and clinical stage. Moreover, the survival rate and median survival time of patients with P. gingivalis infection were significantly shortened. Therefore, we put forward the view that long term smoking and drinking will cause a bad oral environment, increasing the risk of P. gingivalis infection, then P. gingivalis infection will promote the malignant progression of lung cancer.
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Affiliation(s)
- Yiwen Liu
- School of Information Engineering, Henan University of Science and Technology, Luoyang 471023, China; Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Xiang Yuan
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Kuisheng Chen
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Fuyou Zhou
- Department of Thoracic Surgery, Department of Pathology, Anyang Tumor Hospital, Anyang 455000, China
| | - Haijun Yang
- Department of Thoracic Surgery, Department of Pathology, Anyang Tumor Hospital, Anyang 455000, China
| | - Hong Yang
- School of PE, Henan University of Science and Technology, Luoyang 471023, China
| | - Yijun Qi
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Jinyu Kong
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Wei Sun
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Shegan Gao
- School of Information Engineering, Henan University of Science and Technology, Luoyang 471023, China; Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
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30
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Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
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Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
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31
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Li H, Zhao L, Liu S, Zhang Z, Wang X, Lin H. Propionate inhibits fat deposition via affecting feed intake and modulating gut microbiota in broilers. Poult Sci 2020; 100:235-245. [PMID: 33357686 PMCID: PMC7772713 DOI: 10.1016/j.psj.2020.10.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 09/03/2020] [Accepted: 10/06/2020] [Indexed: 12/14/2022] Open
Abstract
As one of the 3 main short-chain fatty acids, the role of propionate in chicken fat metabolism is largely unknown. In this study, we demonstrated that dietary supplementation of coated sodium propionate (SP) moderately inhibits fat deposition in broiler chickens, as evidenced by the decreased adipocyte mean area (P < 0.01), the lowered triglyceride content in abdominal fat tissue (P < 0.01), and the reduced transcription of several lipogenic genes in liver and abdominal fat tissues (P < 0.05). Surprisingly, the propionate content was not significantly elevated either in serum or in the cecal chyme by SP administration (P > 0.05). However, SP application significantly decreased the average daily feed intake of broilers (P < 0.05). In addition, the composition of the cecal microbial communities was altered, with the ratio of Firmicutes to Bacteroidetes decreasing in particular (P < 0.05). At the genus level, SP application increased the richness of Alistipes, Lactobacillus, and Bifidobacterium, while reduced the abundance of Lachnospiraceae and Helicobacter significantly (P < 0.05). Moreover, in vitro experiments indicated that, although physiological concentrations of propionate (0.01 to 0.1 mmol) upregulated or downregulated the transcription of some fat synthesis-associated genes (P < 0.05), they did not significantly affect the triglyceride accumulation in hepatocytes and adipocytes (P > 0.05). These results suggest that feed supplementation with SP inhibits fat deposition in broilers by reducing feed and caloric intake, but not via direct regulation on hepatic fat synthesis or adipocytic fat deposition. Alteration in the relative populations of the gut microflora suggests that SP may have gut health implications.
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Affiliation(s)
- Haifang Li
- College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China
| | - Liqin Zhao
- College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China
| | - Shuang Liu
- College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China
| | - Zhihao Zhang
- College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China
| | - Xiaojuan Wang
- College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China
| | - Hai Lin
- College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.
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32
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Abdi E, Latifi-Navid S, Zahri S, Kholghi-Oskooei V, Mostafaiy B, Yazdanbod A, Pourfarzi F. SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility. Sci Rep 2020; 10:16763. [PMID: 33028884 PMCID: PMC7541458 DOI: 10.1038/s41598-020-73682-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil-a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) 'tag' single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 5619911367, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 5619911367, Ardabil, Iran.
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, 5619911367, Ardabil, Iran
| | - Vahid Kholghi-Oskooei
- Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, 9516915169, Torbat Heydariyeh, Iran
- Health Sciences Research Center, Torbat Heydariyeh University of Medical Sciences, 9516915169, Torbat Heydariyeh, Iran
| | - Behdad Mostafaiy
- Department of Statistics, Faculty of Sciences, University of Mohaghegh Ardabili, 5619911367, Ardabil, Iran
| | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran
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33
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Bakhti SZ, Latifi‐Navid S, Safaralizadeh R. Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects. Cancer Med 2020; 9:4808-4822. [PMID: 32363738 PMCID: PMC7333836 DOI: 10.1002/cam4.3068] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Saeid Latifi‐Navid
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Reza Safaralizadeh
- Department of Animal BiologyFaculty of Natural SciencesUniversity of TabrizTabrizIran
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34
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Bilski K, Dobruch J, Kozikowski M, Skrzypczyk MA, Oszczudłowski M, Ostrowski J. Urobiome in Gender-Related Diversities of Bladder Cancer. Int J Mol Sci 2020; 21:ijms21124488. [PMID: 32599810 PMCID: PMC7349933 DOI: 10.3390/ijms21124488] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 06/20/2020] [Accepted: 06/22/2020] [Indexed: 12/18/2022] Open
Abstract
Bladder cancer (BC) remains the most common malignancy of urinary tract. Sex-related differences in BC epidemiology, diagnosis, therapy, and outcomes have been reported. Throughout the recent years, extensive research has been devoted to genetic and molecular alterations in BC. Apart from the molecular background, another related concept which has been speculated to contribute to gender diversities in BC is the role of urinary pathogens in bladder carcinogenesis. Microbiome studies, fueled by the availability of high-throughput DNA-based techniques, have shown that perturbation in the microbiome is associated with various human diseases. The aim of this review is to comprehensively analyze the current literature according to sex-related differences in the microbiome composition in BC.
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Affiliation(s)
- Konrad Bilski
- Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland; (J.D.); (M.K.); (M.A.S.); (M.O.)
- Correspondence:
| | - Jakub Dobruch
- Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland; (J.D.); (M.K.); (M.A.S.); (M.O.)
| | - Mieszko Kozikowski
- Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland; (J.D.); (M.K.); (M.A.S.); (M.O.)
| | - Michał A. Skrzypczyk
- Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland; (J.D.); (M.K.); (M.A.S.); (M.O.)
| | - Maciej Oszczudłowski
- Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland; (J.D.); (M.K.); (M.A.S.); (M.O.)
| | - Jerzy Ostrowski
- Department of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland;
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