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Hosseini FS, Nikparast A, Etesami E, Javaheri-Tafti F, Asghari G. The association between empirical dietary inflammatory pattern and risk of cancer and cancer-specific mortality: a systematic review and meta-analysis of prospective cohort studies. Front Nutr 2024; 11:1462931. [PMID: 39494310 PMCID: PMC11527705 DOI: 10.3389/fnut.2024.1462931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 10/01/2024] [Indexed: 11/05/2024] Open
Abstract
Background/aim Current evidence indicates a correlation between the inflammatory potential of diet and the risk of cancer and cancer-specific mortality. This study aimed to assess the association between empirical dietary inflammatory pattern (EDIP), which has recently been designed based on the inflammatory potential of the diet, and the risk of cancer and cancer-specific mortality. Methods A systematic literature search was conducted across the PubMed/Medline, Scopus, and Web of Science databases from January 2016 to March 2024. A random effects model was used to calculate the pooled effect size (ES) and 95% confidence intervals (95% CI). Heterogeneity between studies was assessed using the Cochran Q test and the I 2 statistic. Results From the initial 229 records, 24 prospective cohort studies with 2,683,350 participants and 37,091 cancer incidence cases, as well as 20,819 cancer-specific mortality, were included in our study. Pooled results indicated a significant association between higher adherence to the EDIP and an increased risk of total cancer (ES: 1.10; 95% CI: 1.05-1.15; I 2 = 41.1), colorectal cancer (ES: 1.19; 95% CI: 1.11-1.27; I 2 = 41.1), and liver cancer (ES: 1.48; 95% CI: 1.14-1.94; I 2 = 36.9). However, no significant association between increased adherence to the EDIP and an increased risk of ovarian or endometrial cancer was found. Furthermore, greater adherence to the EDIP was significantly associated with an increased risk of cancer-specific mortality (ES: 1.18; 95% CI: 1.05-1.33; I 2 = 45.4). Conclusion Our results showed that a diet with higher inflammatory properties is associated with an increased risk of cancer and cancer-specific mortality. Systematic review registration PROSPERO registration no. CRD42024496912.
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Affiliation(s)
- Fatemeh S. Hosseini
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Ali Nikparast
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elahe Etesami
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Javaheri-Tafti
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golaleh Asghari
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Fei X, Li N, Xu X, Zhu Y. Macrophage biology in the pathogenesis of Helicobacter pylori infection. Crit Rev Microbiol 2024:1-18. [PMID: 39086061 DOI: 10.1080/1040841x.2024.2366944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 05/31/2024] [Accepted: 06/04/2024] [Indexed: 08/02/2024]
Abstract
Infection with H. pylori induces chronic gastric inflammation, progressing to peptic ulcer and stomach adenocarcinoma. Macrophages function as innate immune cells and play a vital role in host immune defense against bacterial infection. However, the distinctive mechanism by which H. pylori evades phagocytosis allows it to colonize the stomach and further aggravate gastric preneoplastic pathology. H. pylori exacerbates gastric inflammation by promoting oxidative stress, resisting macrophage phagocytosis, and inducing M1 macrophage polarization. M2 macrophages facilitate the proliferation, invasion, and migration of gastric cancer cells. Various molecular mechanisms governing macrophage function in the pathogenesis of H. pylori infection have been identified. In this review, we summarize recent findings of macrophage interactions with H. pylori infection, with an emphasis on the regulatory mechanisms that determine the clinical outcome of bacterial infection.
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Affiliation(s)
- Xiao Fei
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nianshuang Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Hsieh HL, Yu MC, Chang YC, Wu YH, Huang KH, Tsai MM. Lonicera japonica Thunb. Ethanol Extract Exerts a Protective Effect on Normal Human Gastric Epithelial Cells by Modulating the Activity of Tumor-Necrosis-Factor-α-Induced Inflammatory Cyclooxygenase 2/Prostaglandin E2 and Matrix Metalloproteinase 9. Curr Issues Mol Biol 2024; 46:7303-7323. [PMID: 39057074 PMCID: PMC11276375 DOI: 10.3390/cimb46070433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through the activation of TNFR-ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.
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Affiliation(s)
- Hsi-Lung Hsieh
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Chemical Engineering, R&D Center of Biochemical Engineering Technology, Ming Chi University of Technology, New Taipei City 301, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Yu-Chia Chang
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
| | - Yi-Hsuan Wu
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
| | - Kuo-Hsiung Huang
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan;
- Department of Laboratory Medicine, Section of Clinical Serology and Immunology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Ming Tsai
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan;
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan;
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Kuang Y, Yang K, Meng L, Mao Y, Xu F, Liu H. Identification and validation of ferroptosis-related biomarkers and the related pathogenesis in precancerous lesions of gastric cancer. Sci Rep 2023; 13:16074. [PMID: 37752199 PMCID: PMC10522668 DOI: 10.1038/s41598-023-43198-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/21/2023] [Indexed: 09/28/2023] Open
Abstract
Using advanced bioinformatics techniques, we conducted an analysis of ferroptosis-related genes (FRGs) in precancerous lesions of gastric cancer (PLGC). We also investigated their connection to immune cell infiltration and diagnostic value, ultimately identifying new molecular targets that could be used for PLGC patient treatment. The Gene Expression Omnibus (GEO) and FerrDb V2 databases were used to identify FRGs. These genes were analysed via ClueGO pathways and Gene Ontology (GO) enrichment analysis, as well as single-cell dataset GSE134520 analysis. A machine learning model was applied to identify hub genes associated with ferroptosis in PLGC patients. Receiver Operating Characteristics (ROC) curve analysis was conducted to verify the diagnostic efficacy of these genes, and a PLGC diagnosis model nomogram was established based on hub genes. R software was utilized to conduct functional, pathway, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) on the identified diagnostic genes. Hub gene expression levels and survival times in gastric cancer were analysed using online databases to determine the prognostic value of these genes. MCPcounter and single-sample gene set enrichment analysis (ssGSEA) algorithms were used to investigate the correlation between hub genes and immune cells. Finally, noncoding RNA regulatory mechanisms and transcription factor regulatory networks for hub genes were mapped using multiple databases. Eventually, we identified 23 ferroptosis-related genes in PLGC. Enrichment analyses showed that ferroptosis-related genes were closely associated with iron uptake and transport and ferroptosis in the development of PLGC. After differential analysis using machine learning algorithms, we identified four hub genes in PLGC patients, including MYB, CYB5R1, LIFR and DPP4. Consequently, we established a ferroptosis diagnosis model nomogram. GSVA and GSEA mutual verification analysis helped uncover potential regulatory mechanisms of hub genes. MCPcounter and ssGSEA analysed immune infiltration in the disease and indicated that B cells and parainflammation played an important role in disease progression. Finally, we constructed noncoding RNA regulatory networks and transcription factor regulatory networks. Our study identified ferroptosis-related diagnostic genes and therapeutic targets for PLGC, providing novel insights and a theoretical foundation for research into the molecular mechanisms, clinical diagnosis, and treatment of this disease.
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Affiliation(s)
- Yuhui Kuang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301608, China
| | - Kuo Yang
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China
| | - Lingkai Meng
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301608, China
| | - Yijia Mao
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China
| | - Fangbiao Xu
- Graduate School, Henan University of Chinese Medicine, Zhengzhou, 450046, China
| | - Huayi Liu
- Department of Digestive Diseases, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China.
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Zhang K, Han Y, Gu F, Gu Z, Zhao J, Chen J, Chen B, Gao M, Hou Z, Yu X, Cai T, Gao Y, Hu R, Xie J, Liu T. Association between dietary zinc intake and Helicobacter pylori seropositivity in US adults: National Health and Nutrition Examination Survey. Front Nutr 2023; 10:1243908. [PMID: 37810930 PMCID: PMC10551451 DOI: 10.3389/fnut.2023.1243908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 09/07/2023] [Indexed: 10/10/2023] Open
Abstract
Purpose Helicobacter pylori infection is a well-established etiological factor for gastric inflammation and a significant risk factor for the development of gastric cancer. However, the precise relationship between dietary zinc intake and seropositivity for Helicobacter pylori remains uncertain. Methods This cross-sectional observational study utilized data from the United States National Health and Nutrition Examination Survey conducted between 1999 and 2000. The study cohort comprised 2,884 adults aged 20 years or older who provided comprehensive 24-h dietary recall data. The presence of Helicobacter pylori infection was confirmed using serum analysis and lgG protein enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression models and generalized additive model (GAM) were employed to explore the potential association between dietary zinc intake and Helicobacter pylori seropositivity. Results Additionally, subgroup analysis was performed to evaluate the robustness of the primary findings. Of the 1,281 participants, 47.8% were male and the average age was 49.5 years. In the fully adjusted model, a statistically significant inverse association between dietary zinc intake and Helicobacter pylori seropositivity was observed [quartile variable, Q4 vs. Q1, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.57-0.91, p = 0.007]. Furthermore, the relationship between dietary zinc intake and Helicobacter pylori seropositivity exhibited an L-shaped pattern, indicating a saturation effect. The results of sensitivity analysis remained consistent and reliable. Conclusion Therefore, this study suggests that higher dietary zinc intake may be associated with a lower prevalence of Helicobacter pylori seropositivity. Notably, this association follows an L-shaped pattern, with a threshold point estimated at 24.925 mg/day.
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Affiliation(s)
- Kai Zhang
- Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, China
| | - Yu Han
- Department of Ophthalmology, First Hospital of Jilin University, Changchun, China
| | - Fangming Gu
- Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, China
| | - Zhaoxuan Gu
- Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, China
| | - JiaYu Zhao
- Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, China
| | - Jianguo Chen
- Bethune First College of Clinical Medicine, Jilin University, Changchun, China
| | - Bowen Chen
- Bethune First College of Clinical Medicine, Jilin University, Changchun, China
| | - Min Gao
- Department of Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Zhengyan Hou
- Bethune Second School of Clinical Medicine, Jilin University, Changchun, China
| | - Xiaoqi Yu
- Bethune Second School of Clinical Medicine, Jilin University, Changchun, China
| | - Tianyi Cai
- Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, China
| | - Yafang Gao
- Bethune Second School of Clinical Medicine, Jilin University, Changchun, China
| | - Rui Hu
- Bethune Third College of Clinical Medicine, Jilin University, Changchun, China
| | - Jinyu Xie
- Bethune Second School of Clinical Medicine, Jilin University, Changchun, China
| | - Tianzhou Liu
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, China
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6
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Chibanda Y, Brookes M, Churchill D, Al-Hassi H. The Ferritin, Hepcidin and Cytokines Link in the Diagnoses of Iron Deficiency Anaemia during Pregnancy: A Review. Int J Mol Sci 2023; 24:13323. [PMID: 37686128 PMCID: PMC10488244 DOI: 10.3390/ijms241713323] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Following a diagnosis of iron deficiency anaemia in pregnancy, iron supplements are prescribed using UK guidelines; however, despite this, the condition remains highly prevalent, affecting up to 30% of pregnant women in the UK. According to the World Health Organisation, it globally accounts for 45% in the most vulnerable groups of pregnant women and infants (<5 years old). Recently, the efficacy of iron replacement therapy and the effectiveness of current standard testing of iron parameters have been reviewed in order to evaluate whether a more accurate diagnosis can be made using alternative and/or supplementary markers. Furthermore, many questions remain about the mechanisms involved in iron metabolism during pregnancy. The most recent studies have shed more light on serum hepcidin and raised questions on the significance of pregnancy related inflammatory markers including cytokines in iron deficiency anaemia. However, research into this is still scarce, and this review aims to contribute to further understanding and elucidating these areas.
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Affiliation(s)
- Yvonne Chibanda
- Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1LY, UK
| | - Matthew Brookes
- Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK
| | - David Churchill
- Obstetrics, The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK
| | - Hafid Al-Hassi
- Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1LY, UK
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Zhang L, Xia X, Wu H, Liu X, Zhu Q, Wang M, Hao H, Cui Y, Li DP, Chen SY, Martinez-Lemus LA, Hill MA, Xu C, Liu Z. Helicobacter pylori infection selectively attenuates endothelial function in male mice via exosomes-mediated ROS production. Front Cell Infect Microbiol 2023; 13:1142387. [PMID: 37274312 PMCID: PMC10233065 DOI: 10.3389/fcimb.2023.1142387] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 05/03/2023] [Indexed: 06/06/2023] Open
Abstract
Background Substantial sex differences exist in atherosclerosis. Excessive reactive oxygen species (ROS) formation could lead to endothelial dysfunction which is critical to atherosclerosis development and progression. Helicobacter pylori (H. pylori) infection has been shown to attenuate endothelial function via exosomes-mediated ROS formation. We have demonstrated that H. pylori infection selectively increases atherosclerosis risk in males with unknown mechanism(s). The present study was to test the hypothesis that H. pylori infection impaired endothelial function selectively in male mice through exosome-mediated ROS formation. Methods and results Age-matched male and female C57BL/6 mice were infected with CagA+ H. pylori to investigate sex differences in H. pylori infection-induced endothelial dysfunction. H. pylori infection attenuated acetylcholine (ACh)-induced endothelium-dependent aortic relaxation without changing nitroglycerine-induced endothelium-independent relaxation in male but not female mice, associated with increased ROS formation in aorta compared with controls, which could be reversed by N-acetylcysteine treatment. Treatment of cultured mouse brain microvascular endothelial cells with exosomes from H. pylori infected male, not female, mice significantly increased intracellular ROS production and impaired endothelial function with decreased migration, tube formation, and proliferation, which could be prevented with N-acetylcysteine treatment. Conclusions H. pylori infection selectively impairs endothelial function in male mice due to exosome-mediated ROS formation.
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Affiliation(s)
- Linfang Zhang
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xiujuan Xia
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Hao Wu
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Xuanyou Liu
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Qiang Zhu
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Meifang Wang
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Hong Hao
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Yuqi Cui
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - De-Pei Li
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
| | - Shi-You Chen
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, United States
| | - Luis A. Martinez-Lemus
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United States
| | - Michael A. Hill
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United States
| | - Canxia Xu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Zhenguo Liu
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States
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Di Fermo P, Di Lodovico S, Di Campli E, D'Arcangelo S, Diban F, D'Ercole S, Di Giulio M, Cellini L. Helicobacter pylori Dormant States Are Affected by Vitamin C. Int J Mol Sci 2023; 24:ijms24065776. [PMID: 36982855 PMCID: PMC10057322 DOI: 10.3390/ijms24065776] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/14/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
Helicobacter pylori colonizes human gastric mucosa, overcoming stressful conditions and entering in a dormant state. This study evaluated: (i) H. pylori's physiological changes from active to viable-but-non-culturable (VBNC) and persister (AP) states, establishing times/conditions; (ii) the ability of vitamin C to interfere with dormancy generation/resuscitation. A dormant state was induced in clinical MDR H. pylori 10A/13 by: nutrient starvation (for VBNC generation), incubating in an unenriched medium (Brucella broth) or saline solution (SS), and (for AP generation) treatment with 10xMIC amoxicillin (AMX). The samples were monitored after 24, 48, and 72 h, 8-14 days by OD600, CFUs/mL, Live/Dead staining, and an MTT viability test. Afterwards, vitamin C was added to the H. pylori suspension before/after the generation of dormant states, and monitoring took place at 24, 48, and 72 h. The VBNC state was generated after 8 days in SS, and the AP state in AMX for 48 h. Vitamin C reduced its entry into a VBNC state. In AP cells, Vitamin C delayed entry, decreasing viable coccal cells and increasing bacillary/U-shaped bacteria. Vitamin C increased resuscitation (60%) in the VBNC state and reduced the aggregates of the AP state. Vitamin C reduced the incidence of dormant states, promoting the resuscitation rate. Pretreatment with Vitamin C could favor the selection of microbial vegetative forms that are more susceptible to H. pylori therapeutical schemes.
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Affiliation(s)
- Paola Di Fermo
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Silvia Di Lodovico
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Emanuela Di Campli
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Sara D'Arcangelo
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Firas Diban
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Simonetta D'Ercole
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Mara Di Giulio
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Luigina Cellini
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
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9
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Yu B, Xiang L, Peppelenbosch MP, Fuhler GM. Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis. Front Immunol 2023; 14:1125658. [PMID: 37006300 PMCID: PMC10050690 DOI: 10.3389/fimmu.2023.1125658] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 03/06/2023] [Indexed: 03/17/2023] Open
Abstract
Background Previous evidence indicated that Helicobacter pylori-induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to H. pylori infection and GC and relate these to global GC risk. Methods We performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in H. pylori-infected cases vs. non-infected controls and gastric cancer cases vs. non-gastric cancer controls, with sub-analyses performed to identify global regional differences in cytokine induction and their correlation with GC incidence. Results Only levels of systemic IL-6 (standardized mean difference [SMD]:0.95, 95%CI [0.45;1.45]) and TNF-α (SMD:0.88, 95%CI [0.46; 1.29]) were significantly increased upon H. pylori infection. Sub-analysis showed that of IL-6 levels were increased upon H. pylori infection in East Asian, Middle Eastern and Southeast Asian cohorts, but not in North America, Europe, Russia and Africa. Serum levels of IL-6, IL-7, IL-10, IL-12, and TNF-α were significantly raised in GC. Exploration of the relationship between serum cytokines changes upon H. pylori infection and regional differences in risk of GC development indicated that the SMD of IL-6 serum levels presents a significant correlation with the relative incidence of GC (r=0.81, p=0.00014). Conclusion This study shows that H. pylori infection and GC are associated with increased IL-6 and TNF-α levels. Particularly, IL-6 shows region-specific increases that correlate with GC incidence, making it a key contender for the cause of this disease.
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Affiliation(s)
| | | | | | - Gwenny M. Fuhler
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
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10
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Xiao Q, Deng B, Akbari A, Liu Q, Zhu B. The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis. J Food Biochem 2022; 46:e14407. [PMID: 36219718 DOI: 10.1111/jfbc.14407] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 08/03/2022] [Accepted: 08/30/2022] [Indexed: 01/13/2023]
Abstract
The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.
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Affiliation(s)
- Qiuju Xiao
- Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Bo Deng
- Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Abolfazl Akbari
- Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Qisheng Liu
- Department of Gastroenterology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Bisheng Zhu
- Department of Oncology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
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11
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α-Lipoic Acid Inhibits Apoptosis by Suppressing the Loss of Ku Proteins in Helicobacter pylori-Infected Human Gastric Epithelial Cells. Nutrients 2022; 14:nu14153206. [PMID: 35956382 PMCID: PMC9370604 DOI: 10.3390/nu14153206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/02/2022] [Accepted: 08/03/2022] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku-DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku-DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin-proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.
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12
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Wei Y, Gao L, Yang X, Xiang X, Yi C. Inflammation-Related Genes Serve as Prognostic Biomarkers and Involve in Immunosuppressive Microenvironment to Promote Gastric Cancer Progression. Front Med (Lausanne) 2022; 9:801647. [PMID: 35372408 PMCID: PMC8965837 DOI: 10.3389/fmed.2022.801647] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/15/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is a typical inflammatory-related malignant tumor which is closely related to helicobacter pylori infection. Tumor inflammatory microenvironment plays a crucial role in tumor progression and affect the clinical benefit from immunotherapy. In recent years, immunotherapy for gastric cancer has achieved promising outcomes, but not all patients can benefit from immunotherapy due to tumor heterogeneity. In our study, we identified 29 differentially expressed and prognostic inflammation-related genes in GC and normal samples. Based on those genes, we constructed a prognostic model using a least absolute shrinkage and selection operator (LASSO) algorithm, which categorized patients with GC into two groups. The high-risk group have the characteristics of "cold tumor" and have a poorer prognosis. In contrast, low-risk group was "hot tumor" and had better prognosis. Targeting inflammatory-related genes and remodeling tumor microenvironment to turn "cold tumor" into "hot tumor" may be a promising solution to improve the efficacy of immunotherapy for patients with GC.
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Affiliation(s)
- Yuanfeng Wei
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Limin Gao
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Yang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyu Xiang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Cheng Yi
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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13
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Hsieh HL, Yu MC, Cheng LC, Chu MY, Huang TH, Yeh TS, Tsai MM. Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells. World J Gastroenterol 2022; 28:1139-1158. [PMID: 35431500 PMCID: PMC8985486 DOI: 10.3748/wjg.v28.i11.1139] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 12/23/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities. However, the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear.
AIM To assess whether tumor necrosis factor-α (TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells.
METHODS The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the anti-inflammatory effects of quercetin. The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line. Cell migration was measured using Transwell assay. The expression of proto-oncogene tyrosine-protein kinase Src (c-Src), phospho (p)-c-Src, extracellular-signal-regulated kinase 2 (ERK2), p-ERK1/2, c-Fos, p-c-Fos, nuclear factor kappa B (NF-κB/p65), and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity. p65 expression was detected by immunofluorescence. MMP-9 mRNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction (qRT–PCR) and gelatin zymography, respectively.
RESULTS qRT-PCR and gelatin zymography showed that TNF-α induced MMP-9 mRNA and protein expression in a dose- and time-dependent manner. These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-α antagonist (TNFR inhibitor) in a dose- and time-dependent manner. Quercetin and TNF-α antagonists decreased the TNF-α-induced phosphorylation of c-Src, ERK1/2, c-Fos, and p65 in a dose- and time-dependent manner. Quercetin, TNF-α antagonist, PP1, U0126, and tanshinone IIA (TSIIA) reduced TNF-α-induced c-Fos phosphorylation and AP-1–Luciferase (Luc) activity in a dose- and time-dependent manner. Pretreatment with quercetin, TNF-α antagonist, PP1, U0126, or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65–Luc activity in a dose- and time-dependent manner. TNF-α significantly increased GES-1 cell migration, and these results were reduced by pretreatment with quercetin or a TNF-α antagonist.
CONCLUSION Quercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src–ERK1/2 and c-Fos or NF-κB pathways.
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Affiliation(s)
- Hsi-Lung Hsieh
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Li-Ching Cheng
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Mei-Yi Chu
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
| | - Tzu-Hao Huang
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
| | - Ta-Sen Yeh
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Ming Tsai
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
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Paul D, Mahanta S, Tag H, Das SK, Das Gupta D, Tanti B, Ananthan R, Das R, Jambhulkar S, Hui PK. Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK-HER2 and VEGFR2 receptors, by in silico approach. Mol Divers 2021; 26:1933-1955. [PMID: 34554395 DOI: 10.1007/s11030-021-10304-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/24/2021] [Indexed: 11/26/2022]
Abstract
Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.
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Affiliation(s)
- Dipayan Paul
- Department of Biotechnology, National Institute of Technology Arunachal Pradesh, Yupia, Papum Pare, Arunachal Pradesh, 791112, India
| | - Saurov Mahanta
- National Institute of Electronics and Information Technology, Guwahati, Assam, 781008, India
| | - Hui Tag
- Pharmacognosy and Phytochemistry Research Laboratory, Department of Botany, Rajiv Gandhi University, Rono Hills, Doimukh, Arunachal Pradesh, 791112, India.
| | - Sanjib Kumar Das
- Department of Biotechnology, National Institute of Technology Arunachal Pradesh, Yupia, Papum Pare, Arunachal Pradesh, 791112, India
| | - Debmalya Das Gupta
- Department of Biotechnology, National Institute of Technology Arunachal Pradesh, Yupia, Papum Pare, Arunachal Pradesh, 791112, India
| | - Bhaben Tanti
- Department of Botany, Gauhati University, Guwahati, Assam, 781014, India
| | - Rajendran Ananthan
- Food Chemistry Division, ICMR National Institute of Nutrition, Jamai-Osmania PO, Hyderabad, Telangana, 500007, India
| | - Ranjan Das
- Department of Crop Physiology, Assam Agricultural University, Jorhat, Assam, 785013, India
| | - Sanjay Jambhulkar
- Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, 400085, India
| | - Pallabi Kalita Hui
- Department of Biotechnology, National Institute of Technology Arunachal Pradesh, Yupia, Papum Pare, Arunachal Pradesh, 791112, India.
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15
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Barekzai AM, Aminianfar A, Mousavi SM, Esmaillzadeh A. The Association between Dietary Inflammatory Potential and Gastric Cancer: A Case Control Study. Nutr Cancer 2021; 74:463-471. [PMID: 33560151 DOI: 10.1080/01635581.2021.1883682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
OBJECTIVE No report is available about diet-disease associations in the understudied region of Afghanistan. Although the inflammatory potential of diet has been linked with several cancers, information about gastric cancer is scarce. The present study aimed to investigate the relationship between the inflammatory potential of the diet and odds of gastric cancer in Afghanistan. METHODS In this hospital-based case-control study, we enrolled 90 newly-diagnosed cases of gastric cancer and 180 age (±5) and sex-matched controls. All cases were pathologically confirmed gastric cancer patients, with no history of any type of other pathologically confirmed cancers. Controls were healthy individuals and relatives of patients in the hospital. Dietary assessment was done by a pre-tested food frequency questionnaire. DII was calculated based on energy-adjusted amounts of several foods and nutrients with inflammatory or anti-inflammatory potential, as introduced by earlier studies. RESULTS Mean age of study participants was 54 years, of them 73% were males. After adjustment for age and sex, individuals in the highest tertile of the inflammatory potential of the diet were 2.47 times (95% CI: 1.31-4.66) more likely to have gastric cancer compared with those in the lowest tertile. Further adjustment for other potential confounders did not substantially affect the association; such that participants with the greatest inflammatory potential of the diet had approximately 3.59 times (95% CI: 1.16-11.02) increased odds of gastric cancer than those with the lowest adherence. Additional adjustment for BMI strengthened the association (OR: 3.75; 95% CI: 1.14-12.30). CONCLUSION We found a significant positive association between inflammatory potential of the diet and risk of gastric cancer. Further studies with prospective nature are required to confirm this association.
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Affiliation(s)
- Ahmad Mujtaba Barekzai
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Azadeh Aminianfar
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Science, Kashan, Iran
| | - Seyed Mohammad Mousavi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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16
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TNF genetic polymorphism (rs1799964) may modify the effect of the dietary inflammatory index on gastric cancer in a case-control study. Sci Rep 2020; 10:14590. [PMID: 32883994 PMCID: PMC7471946 DOI: 10.1038/s41598-020-71433-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/22/2020] [Indexed: 12/26/2022] Open
Abstract
The inflammatory process is known to increase the risk of gastric carcinogenesis, and both genetic and dietary factors are associated with inflammation. In the present study of 1,125 participants (373 cases and 752 controls), we determined whether the dietary inflammatory index (DII) is associated with the risk of gastric cancer (GC) and investigated whether a TNF polymorphism (rs1799964) modifies this association. Semi-quantitative food frequency questionnaire derived data were used to calculate the DII scores. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic models adjusted for confounders. When we stratified the data by sex, the association between GC and the DII was significant only among the women (OR, 2.27; 95% CI 1.25-4.19), and the DII effect on the risk of GC differed depending on the TNF genotype (OR, 2.30; 95% CI 1.27-4.24 in TT genotype; OR, 0.78; 95% CI 0.37-1.65 in CC + CT, p for interaction = 0.035). Furthermore, the association between the DII and GC was significant in the Helicobacter pylori-positive group; similarly, the effect differed based on the TNF genotype (OR, 1.76; 95% CI 1.13-2.73 in TT genotype; OR,0.98; 95% CI 0.54-1.77 in CT + CC, p for interaction = 0.034). In conclusion, rs1799964 may modify the effect of the DII on GC.
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17
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Hajiasgharzadeh K, Somi MH, Sadigh-Eteghad S, Mokhtarzadeh A, Shanehbandi D, Mansoori B, Mohammadi A, Doustvandi MA, Baradaran B. The dual role of alpha7 nicotinic acetylcholine receptor in inflammation-associated gastrointestinal cancers. Heliyon 2020; 6:e03611. [PMID: 32215331 PMCID: PMC7090353 DOI: 10.1016/j.heliyon.2020.e03611] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 12/10/2019] [Accepted: 02/10/2020] [Indexed: 02/07/2023] Open
Abstract
Alpha7 nicotinic acetylcholine receptor (α7nAChR) is one of the main subtypes of nAChRs that modulates various cancer-related properties including proliferative, anti-apoptotic, pro-angiogenic and pro-metastatic activities in most of the cancers. It also plays a crucial role in inflammation control through the cholinergic anti-inflammatory pathway in numerous pathophysiological contexts. Such diverse physiological and pathological functions that initiate from this receptor may have significant impacts in determining the outcome of different cancers. Various tissues of gastrointestinal (GI) cancers such as gastric, colorectal, pancreatic and liver cancers have shown the up-regulated expression of α7nAChR as compared to normal adjacent tissues. According to the well-established connection between inflammation and tumorigenesis in the digestive system, there are mounting studies demonstrated either stimulatory or inhibitory effects of α7nAChR signaling in the development of GI cancers. To date, the precise underlying mechanisms related to this receptor in patients with GI cancers have not been fully elucidated. Regarding the paradoxical modulatory effects of this receptor in carcinogenesis, in this review, we aim to summarize the accumulated evidence about the involvement of α7nAChR in inflammation-associated GI cancers. It seems that the complex influences of α7nAChR may be a promising target in designing novel strategies in the treatment of such pathologic conditions.
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Affiliation(s)
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Sadigh-Eteghad
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Dariush Shanehbandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Mansoori
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Mohammadi
- Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Wang N, Lu K, Qu H, Wang H, Chen Y, Shan T, Ge X, Wei Y, Zhou P, Xia J. CircRBM33 regulates IL-6 to promote gastric cancer progression through targeting miR-149. Biomed Pharmacother 2020; 125:109876. [PMID: 32044717 DOI: 10.1016/j.biopha.2020.109876] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/16/2022] Open
Abstract
There is increasing evidence of the vital role played by circular RNAs (circRNAs) in the progression of gastric cancer (GC). A circRNA, hsa_circ_0001772, was generated from the RBM33 gene and named circRBM33. The aim of this study was to investigate the role of circRBM33 in GC. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of circRBM33 in 79 pairs of GC tissues and paracancerous tissues and 4 GC cell lines (MGC-803, BGC-823, SGC-7901, and AGS). Bioinformatics databases were used to predict downstream targets of circRNA and micro RNA (miRNA). Dual luciferase reporter assay was used to verify whether miR-149 was a direct binding target for circRBM33. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2´-deoxyuridine (EDU) assay, transwell assay, and flow-cytometric analyses were performed to determine the role of circRBM33 in the biological functioning of GC cells. Western blot technique was used to quantify the levels of interleukin-6 (IL-6). CircRBM33 was distinctly upregulated in GC specimens and cell lines and a close correlation between circRBM33 expression and clinical characteristics of GC was observed. After silencing circRBM33, the apoptosis of GC cells increased, while proliferation, migration, and invasion decreased. Rescue experiments indicated that circRBM33 manipulates biological function in GC cells through the circRBM33/miR-149/IL-6 axis. CircRBM33 can be used as a tumor biomarker and a possible therapeutic target in the future.
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Affiliation(s)
- Ning Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Keyu Lu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Huiheng Qu
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Hao Wang
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Yigang Chen
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Ting Shan
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Xuhui Ge
- Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yunyu Wei
- Department of Laboratory, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Peng Zhou
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China
| | - Jiazeng Xia
- Department of Genernal Surgery, The Affiliated Wuxi NO.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China.
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Pyo JH, Lee H, Choi SC, Cho SJ, Choi YH, Min YW, Min BH, Lee JH, Yoo H, Kim K, Kim JJ. Lack of Association between Past Helicobacter pylori Infection and Diabetes: A Two-Cohort Study. Nutrients 2019; 11:nu11081874. [PMID: 31409000 PMCID: PMC6723734 DOI: 10.3390/nu11081874] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/06/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) may be involved in diabetes and other insulin-related processes. This study aimed to investigate the associations between H. pylori infection and the risks of type 2 diabetes, impaired glucose tolerance (IGT), diabetic nephropathy, and poor glycemic control. We retrospectively evaluated 16,091 subjects without diabetes at baseline who underwent repeated health examinations. Subjects were categorized according to whether they were seropositive and seronegative for H. pylori infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The serological results were validated using an independent cohort (n = 42,351) based on a histological diagnosis of H. pylori infection. During 108,614 person-years of follow-up, 1338 subjects (8.3%) developed newly diagnosed diabetes, although the cumulative incidence of diabetes was not significantly related to serological H. pylori status. The multivariate Cox proportional-hazards regression models revealed that H. pylori seropositivity was not significantly associated with diabetes (HR: 1.01, 95% CI: 0.88–1.16; p = 0.854), IGT (HR: 0.98, 95% CI: 0.93–1.04; p = 0.566), diabetic nephropathy (HR: 0.99, 95% CI: 0.82–1.21; p = 0.952), or poor glycemic control (HR: 1.05, 95% CI: 0.90–1.22; p = 0.535). Similarly, histopathological findings of H. pylori infection were not significantly associated with diabetes (p = 0.311), diabetic nephropathy (p = 0.888), or poor glycemic control (p = 0.989). The findings from these large Korean cohorts indicate that there does not appear to be a role for past H. pylori infection in the development of diabetes, IGT, diabetic nephropathy, or poor glycemic control.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Soo Jin Cho
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Heejin Yoo
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Kyunga Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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20
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Zhou W, Ma L, Yang J, Qiao H, Li L, Guo Q, Ma J, Zhao L, Wang J, Jiang G, Wan X, Adam Goscinski M, Ding L, Zheng Y, Li W, Liu H, Suo Z, Zhao W. Potent and specific MTH1 inhibitors targeting gastric cancer. Cell Death Dis 2019; 10:434. [PMID: 31164636 PMCID: PMC6547740 DOI: 10.1038/s41419-019-1665-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 05/13/2019] [Accepted: 05/15/2019] [Indexed: 01/22/2023]
Abstract
Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.
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Affiliation(s)
- Wenjuan Zhou
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
- Department of Pathology, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo, 0379, Norway
| | - Liying Ma
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Jing Yang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Hui Qiao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Lingyu Li
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Qian Guo
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Jinlian Ma
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Lijuan Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Junwei Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Guozhong Jiang
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Xiangbin Wan
- Department of General Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450001, China
| | - Mariusz Adam Goscinski
- Department of Urology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway
| | - Lina Ding
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Yichao Zheng
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Wencai Li
- Department of Pathology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450001, China
| | - Hongmin Liu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
| | - Zhenhe Suo
- Department of Pathology, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo, 0379, Norway.
| | - Wen Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment; Key Laboratory of Advanced Pharmaceutical Technology Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China.
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21
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Gantuya B, El-Serag HB, Matsumoto T, Ajami NJ, Oyuntsetseg K, Azzaya D, Uchida T, Yamaoka Y. Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area. Cancers (Basel) 2019; 11:E504. [PMID: 30974798 PMCID: PMC6520852 DOI: 10.3390/cancers11040504] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 04/02/2019] [Accepted: 04/04/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.
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Affiliation(s)
- Boldbaatar Gantuya
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
- Department of Internal Medicine, Gastroenterology Unit, Mongolian National University of Medical Sciences, Zorig Street, Ulaanbaatar-14210, Mongolia.
| | - Hashem B El-Serag
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX 77030, USA.
| | - Takashi Matsumoto
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
| | - Nadim J Ajami
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
| | - Khasag Oyuntsetseg
- Department of Internal Medicine, Gastroenterology Unit, Mongolian National University of Medical Sciences, Zorig Street, Ulaanbaatar-14210, Mongolia.
| | - Dashdorj Azzaya
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
- Department of Internal Medicine, Gastroenterology Unit, Mongolian National University of Medical Sciences, Zorig Street, Ulaanbaatar-14210, Mongolia.
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX 77030, USA.
- Global Oita Medical Advanced Research Center for Health, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan.
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22
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Velazquez-Caldelas TE, Alcalá-Corona SA, Espinal-Enríquez J, Hernandez-Lemus E. Unveiling the Link Between Inflammation and Adaptive Immunity in Breast Cancer. Front Immunol 2019; 10:56. [PMID: 30761130 PMCID: PMC6362261 DOI: 10.3389/fimmu.2019.00056] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 01/10/2019] [Indexed: 12/21/2022] Open
Abstract
Inflammation has been recognized as an important driver in the development and growth of malignancies. Inflammatory signaling in cancer emerges from the combinatorial interaction of several deregulated pathways. Pathway deregulation is often driven by changes in the underlying gene regulatory networks. Confronted with such complex scenario, it can be argued that a closer analysis of the structure of such regulatory networks will shed some light on how gene deregulation led to sustained inflammation in cancer. Here, we inferred an inflammation-associated gene regulatory network from 641 breast cancer and 78 healthy samples. A modular structure analysis of the regulatory network was carried out, revealing a hierarchical modular structure. Modules show significant overrepresentation score p-values for biological processes unveiling a definite association between inflammatory processes and adaptive immunity. Other modules are enriched for T-cell activation, differentiation of CD8+ lymphocytes and immune cell migration, thus reinforcing the aforementioned association. These analyses suggest that in breast cancer tumors, the balance between antitumor response and immune tolerance involving CD8+ T cells is tipped in favor of the tumor. One possible mechanism is the induction of tolerance and anergization of these cells by persistent antigen exposure.
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Affiliation(s)
| | - Sergio Antonio Alcalá-Corona
- Computational Genomics Division, National Institute of Genomic Medicine, Mexico City, Mexico.,Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico.,Department of Ecology and Evolution, Erman Biology Center, The University of Chicago, Chicago, IL, United States
| | - Jesús Espinal-Enríquez
- Computational Genomics Division, National Institute of Genomic Medicine, Mexico City, Mexico.,Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Enrique Hernandez-Lemus
- Computational Genomics Division, National Institute of Genomic Medicine, Mexico City, Mexico.,Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico
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23
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Ren WK, Xu YF, Wei WH, Huang P, Lian DW, Fu LJ, Yang XF, Chen FJ, Wang J, Cao HY, Deng YH. Effect of patchouli alcohol on Helicobacter pylori-induced neutrophil recruitment and activation. Int Immunopharmacol 2018; 68:7-16. [PMID: 30599446 DOI: 10.1016/j.intimp.2018.12.044] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/15/2018] [Accepted: 12/18/2018] [Indexed: 01/12/2023]
Abstract
Neutrophil infiltration typically occurs in Helicobacter pylori (H. pylori)-induced acute gastritis; however, this immune response fails to eradicate H. pylori in vivo. Moreover, reactive oxygen species (ROS), which are generated by neutrophils, cause severe damage to gastric mucosa. Patchouli alcohol (PA) has been reported to have effective anti-oxidative and anti-H. pylori activities, and we investigated its effects on H. pylori-induced neutrophil recruitment and activation in this research. In neutrophil recruitment experiment, H. pylori was injected into rat air pouch to explore the effects of PA (10, 20 and 40 mg/kg) on acute inflammatory response. The results revealed that PA significantly reduced the weight of exudate and the number of neutrophils in the air pouch. Meanwhile, remarkable decrements in TNF-α and IL-8 levels in exudates were observed. In neutrophil activation experiment, rat neutrophils were isolated and activated by using 50 μg/mL H. pylori water-soluble surface protein with or without the treatment of PA (5, 10 or 20 μmol/L). Results indicated that PA not only significantly inhibited the production of ROS, but also reduced the gene and protein expressions of p22/p47-phoxes, and the binding of p22/p47-phoxes. Furthermore, the influence of PA on the neutrophil activation genes of H. pylori (h-nap and sabA) was investigated, and the results showed that expressions of h-nap and sabA were remarkably decreased after PA treatment. In conclusion, PA reduced the recruitment and activation of neutrophils induced by H. pylori, as shown by its inhibition of pro-inflammatory factor generation, p22/p47-phoxes function and H. pylori neutrophil activation-related gene expression.
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Affiliation(s)
- Wen-Kang Ren
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Yi-Fei Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Wen-Hui Wei
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
| | - Ping Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan 523808, PR China
| | - Da-Wei Lian
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Li-Jun Fu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xu-Feng Yang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Fang-Jun Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Jing Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Hong-Ying Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
| | - Yuan-Hui Deng
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
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24
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Luo X, Wang GH, Bian ZL, Li XW, Zhu BY, Jin CJ, Ju SQ. Long non-coding RNA CCAL/miR-149/FOXM1 axis promotes metastasis in gastric cancer. Cell Death Dis 2018; 9:993. [PMID: 30250169 PMCID: PMC6155366 DOI: 10.1038/s41419-018-0969-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 08/05/2018] [Accepted: 08/20/2018] [Indexed: 12/13/2022]
Abstract
Early evidence indicates that the long non-coding RNA CCAL plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of CCAL in gastric tumourigenesis and progression remain largely unknown. We observed that CCAL was upregulated in gastric cancer tissues and was associated with the tumour-node-metastasis stage. Functional experiments showed that CCAL promoted gastric cancer cell proliferation and metastasis in vitro and in vivo. Luciferase reporter assay indicated that CCAL directly bind to miR-149. Moreover, knockdown of CCAL significantly reduced the expression of FOXM1, a direct target of miR-149. We also showed that FOXM1 suppression by miR-149 could be partially rescued by CCAL overexpression. In addition, we identified a negative correlation between the mRNA expression of CCAL and miR-149 in gastric cancer tissues. Furthermore, we observed a negative correlation between the expression of miR-149 and FOXM1 and a positive correlation between CCAL and FOXM1 levels. These results demonstrated that the CCAL/miR-149/FOXM1 axis functions as a key regulator in gastric cancer metastasis and CCAL potentially represents a biomarker for diagnosis and potential target for therapy in the future.
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Affiliation(s)
- Xi Luo
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China.,Department of Clinical Laboratory, The Third People's Hospital of Nantong, No.60 Middle Qingnian Road, 226006, Nantong, Jiangsu Province, China
| | - Gui-Hua Wang
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China
| | - Zhao-Lian Bian
- Nantong Institute of Liver Diseases, The Third People's Hospital of Nantong, No.60 Middle Qingnian Road, 226006, Nantong, Jiangsu Province, China
| | - Xi-Wen Li
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China
| | - Bing-Ying Zhu
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China
| | - Chun-Jing Jin
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China
| | - Shao-Qing Ju
- Laboratory Medicine Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, 226001, Nantong, Jiangsu Province, China.
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25
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van der Poorten DK, McLeod D, Ahlenstiel G, Read S, Kwok A, Santhakumar C, Bassan M, Culican S, Campbell D, Wong SWJ, Evans L, Jideh B, Kane A, Katelaris CH, Keat K, Ko Y, Lee JA, Limaye S, Lin MW, Murad A, Rafferty M, Suan D, Swaminathan S, Riminton SD, Toong C, Berglund LJ. Gastric Cancer Screening in Common Variable Immunodeficiency. J Clin Immunol 2018; 38:768-777. [PMID: 30219982 DOI: 10.1007/s10875-018-0546-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 09/06/2018] [Indexed: 12/22/2022]
Abstract
Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.
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Affiliation(s)
- David K van der Poorten
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, NSW, Australia.,Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Duncan McLeod
- Department of Anatomical Pathology, Westmead Hospital, Sydney, NSW, Australia.,NSW Health Pathology, Sydney, NSW, Australia
| | - Golo Ahlenstiel
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Blacktown Clinical School, School of Medicine, Western Sydney University, Penrith, NSW, Australia.,Department of Gastroenterology and Hepatology, Blacktown Hospital, Blacktown, NSW, Australia.,Storr Liver Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia
| | - Scott Read
- Storr Liver Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia
| | - Avelyn Kwok
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Cositha Santhakumar
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Milan Bassan
- Department of Gastroenterology and Hepatology, Liverpool hospital, Sydney, NSW, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia
| | | | | | | | - Louise Evans
- Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia.,Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Bilel Jideh
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, NSW, Australia
| | - Alisa Kane
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Constance H Katelaris
- Department of Immunology, Campbelltown Hospital, Campbelltown, NSW, Australia.,Faculty of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Karuna Keat
- Department of Immunology, Campbelltown Hospital, Campbelltown, NSW, Australia.,Faculty of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Yanna Ko
- Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Jessie A Lee
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Sandhya Limaye
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Ming Wei Lin
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia
| | - Ari Murad
- Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia
| | - Martina Rafferty
- Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Dan Suan
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia.,Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Sanjay Swaminathan
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia
| | - Sean D Riminton
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Catherine Toong
- NSW Health Pathology, Sydney, NSW, Australia.,Faculty of Medicine, The University of New South Wales, Sydney, NSW, Australia.,Department of Immunology, Liverpool Hospital, Sydney, NSW, Australia.,Department of Immunology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Lucinda J Berglund
- Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia. .,NSW Health Pathology, Sydney, NSW, Australia. .,Departments of Immunology and Immunopathology, Westmead Hospital, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Australia.
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26
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Jayedi A, Emadi A, Shab-Bidar S. Dietary Inflammatory Index and Site-Specific Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis. Adv Nutr 2018; 9:388-403. [PMID: 30032224 PMCID: PMC6054175 DOI: 10.1093/advances/nmy015] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 03/06/2018] [Indexed: 12/12/2022] Open
Abstract
Existing evidence suggests a link between the inflammatory potential of diet and risk of cancer. This study aimed to test the linear and potential nonlinear dose-response associations of the Dietary Inflammatory Index (DII), as being representative of inflammatory features of the diet, and site-specific cancer risk. A systematic search was conducted with the use of PubMed and Scopus from 2014 to November 2017. Prospective cohort or case-control studies reporting the risk estimates of any cancer type for ≥3 categories of the DII were selected. Studies that reported the association between continuous DII score and cancer risk were also included. Pooled RRs were calculated by using a random-effects model. Eleven prospective cohort studies (total n = 1,187,474) with 28,614 incident cases and 29 case-control studies with 19,718 cases and 33,229 controls were identified. The pooled RRs for a 1-unit increment in the DII were as follows: colorectal cancer, 1.06 (95% CI: 1.04, 1.08; I2 = 72.5%; n = 9); breast cancer, 1.03 (95% CI: 1.00, 1.07; I2 = 84.0%; n = 7); prostate cancer, 1.06 (95% CI: 0.97, 1.15; I2 = 56.2%; n = 6); pancreatic cancer, 1.16 (95% CI: 1.05, 1.28; I2 = 61.6%; n = 2); ovarian cancer, 1.08 (95% CI: 1.03, 1.13; I2 = 0%; n = 2); esophageal squamous cell carcinoma, 1.24 (95% CI: 1.10, 1.38; I2 = 64.3%; n = 2); renal cell carcinoma, 1.08 (95% CI: 1.02, 1.13; I2 = 0%; n = 2); and esophageal adenocarcinoma, 1.26 (95% CI: 1.13, 1.39; I2 = 0%; n = 2). A nonlinear dose-response meta-analysis showed that, after a somewhat unchanged risk within initial scores of the DII, the risk of colorectal cancer increased linearly with increasing DII score. In the analyses of breast and prostate cancers, the risk increased with a very slight trend with increasing DII score. In conclusion, the results showed that dietary habits with high inflammatory features might increase the risk of site-specific cancers.
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Affiliation(s)
- Ahmad Jayedi
- Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Emadi
- Department of Information Technologies, Semnan University of Medical Sciences, Semnan, Iran
| | - Sakineh Shab-Bidar
- Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran,Address correspondence to SS-B (e-mail: )
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27
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García-Heredia JM, Carnero A. Dr. Jekyll and Mr. Hyde: MAP17's up-regulation, a crosspoint in cancer and inflammatory diseases. Mol Cancer 2018; 17:80. [PMID: 29650022 PMCID: PMC5896160 DOI: 10.1186/s12943-018-0828-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 03/28/2018] [Indexed: 12/14/2022] Open
Affiliation(s)
- José M García-Heredia
- Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain.,Department of Vegetal Biochemistry and Molecular Biology, University of Seville, Seville, Spain.,CIBER de Cáncer, Instituto de Salud Carlos III, Pabellón 11, Madrid, Spain
| | - Amancio Carnero
- Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain. .,CIBER de Cáncer, Instituto de Salud Carlos III, Pabellón 11, Madrid, Spain.
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28
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Sahan AZ, Hazra TK, Das S. The Pivotal Role of DNA Repair in Infection Mediated-Inflammation and Cancer. Front Microbiol 2018; 9:663. [PMID: 29696001 PMCID: PMC5904280 DOI: 10.3389/fmicb.2018.00663] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Accepted: 03/21/2018] [Indexed: 12/19/2022] Open
Abstract
Pathogenic and commensal microbes induce various levels of inflammation and metabolic disease in the host. Inflammation caused by infection leads to increased production of reactive oxygen species (ROS) and subsequent oxidative DNA damage. These in turn cause further inflammation and exacerbation of DNA damage, and pose a risk for cancer development. Helicobacter pylori-mediated inflammation has been implicated in gastric cancer in many previously established studies, and Fusobacterium nucleatum presence has been observed with greater intensity in colorectal cancer patients. Despite ambiguity in the exact mechanism, infection-mediated inflammation may have a link to cancer development through an accumulation of potentially mutagenic DNA damage in surrounding cells. The multiple DNA repair pathways such as base excision, nucleotide excision, and mismatch repair that are employed by cells are vital in the abatement of accumulated mutations that can lead to carcinogenesis. For this reason, understanding the role of DNA repair as an important cellular mechanism in combatting the development of cancer will be essential to characterizing the effect of infection on DNA repair proteins and to identifying early cancer biomarkers that may be targeted for cancer therapies and treatments.
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Affiliation(s)
- Ayse Z Sahan
- Department of Pathology, University of California, San Diego, San Diego, CA, United States
| | - Tapas K Hazra
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States
| | - Soumita Das
- Department of Pathology, University of California, San Diego, San Diego, CA, United States
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29
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Gastric cancer associated with refractory cytomegalovirus gastritis. Clin J Gastroenterol 2017; 10:498-502. [DOI: 10.1007/s12328-017-0773-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 08/31/2017] [Indexed: 12/20/2022]
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30
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Molecular signaling cascades involved in nonmelanoma skin carcinogenesis. Biochem J 2017; 473:2973-94. [PMID: 27679857 DOI: 10.1042/bcj20160471] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 06/10/2016] [Indexed: 12/17/2022]
Abstract
Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the incidence continues to rise, in part due to increasing numbers in high-risk groups such as organ transplant recipients and those taking photosensitizing medications. The most significant risk factor for NMSC is ultraviolet radiation (UVR) from sunlight, specifically UVB, which is the leading cause of DNA damage, photoaging, and malignant transformation in the skin. Activation of apoptosis following UVR exposure allows the elimination of irreversibly damaged cells that may harbor oncogenic mutations. However, UVR also activates signaling cascades that promote the survival of these potentially cancerous cells, resulting in tumor initiation. Thus, the UVR-induced stress response in the skin is multifaceted and requires coordinated activation of numerous pathways controlling DNA damage repair, inflammation, and kinase-mediated signal transduction that lead to either cell survival or cell death. This review focuses on the central signaling mechanisms that respond to UVR and the subsequent cellular changes. Given the prevalence of NMSC and the resulting health care burden, many of these pathways provide promising targets for continued study aimed at both chemoprevention and chemotherapy.
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31
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Bagheri V, Memar B, Momtazi AA, Sahebkar A, Gholamin M, Abbaszadegan MR. Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma. J Cell Physiol 2017; 233:2791-2803. [PMID: 28121015 DOI: 10.1002/jcp.25822] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 12/16/2016] [Indexed: 12/20/2022]
Abstract
Cytokine networks as dynamic networks are pivotal aspects of tumor immunology, especially in gastric cancer (GC), in which infection, inflammation, and antitumor immunity are key elements of disease progression. In this review, we describe functional roles of well-known GC-modulatory cytokines, highlight the functions of cytokines with more recently described roles in GC, and emphasize the therapeutic potential of targeting the complex cytokine milieu. We also focus on the role of Helicobacter pylori (HP)-induced inflammation in GC and discuss how HP-induced chronic inflammation can lead to the induction of stem cell hyperplasia, morphological changes in gastric mucosa and GC development.
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Affiliation(s)
- Vahid Bagheri
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bahram Memar
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pathology, Faculty of Medicine, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Momtazi
- Department of Medical Biotechnology, Student Research Committee, Nanotechnology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehran Gholamin
- Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Abbaszadegan
- Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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32
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Jiang Y, Xu H, Jiang H, Ding S, Zheng T. Pretreatment neutrophil-lymphocyte count ratio may associate with gastric cancer presence. Cancer Biomark 2017; 16:523-8. [PMID: 27062567 DOI: 10.3233/cbm-160593] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Inflammation plays a pivotal role in cancer development and progression. Neutrophil-lymphocyte count ratio (NLR) is an indicator of systemic inflammatory response which is supposedly associated with gastric cancer (GC) development and progression. Since this parameter can be easily obtained from routine blood examination, it will be a great economic relief to gastric patients if we can bring it into clinical application. OBJECTIVE The current study aims to evaluate the pretreatment NLR in gastric cancer patients through retrospectively reviewing the medical records. METHODS A total of 327 patients hospitalized on a tertiary care hospital were retrospectively investigated and divided into two groups. Gastric cancer group were composed of patients with newly diagnosed, pathologically confirmed GC and the control group were patients with gastric polyp or benign gastric stromal tumor. The value of NLR in the presence and stage of gastric cancer was investigated in the entire gastric cancer group. RESULTS Our study showed levels of NLR were significantly higher in gastric cancer cohort (2.17 (1.63-3.09) versus 1.62 (0.85-2.32), p< 0.001). After all the known confounders were excluded, NLR was an independent predicator of GC (OR = 1.446, 95%CI (1.121-1.866), and P= 0.005). Area under ROC curve (AUC) of NLR was 0.694. In addition, the results of Spearman's correlation showed NLR may have a positive correlation with size of tumor, N-stage, distant metastasis, and overall stage (r = 0.256, 0.256, 0.161 and 0.171, resp., all p < 0.05). CONCLUSIONS The current study demonstrated that pre-treatment NLR may be a useful biomarker in the health care of gastric cancer patients.
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Affiliation(s)
- Yuanyuan Jiang
- Department of Clinical Laboratory, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Huan Xu
- Department of Clinical Laboratory, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Hongmin Jiang
- Department of Clinical Laboratory, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Siyi Ding
- Department of Clinical Laboratory, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Taiqing Zheng
- Department of Clinical Laboratory, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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33
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Patel TN, Roy S, Ravi R. Gastric cancer and related epigenetic alterations. Ecancermedicalscience 2017; 11:714. [PMID: 28144288 PMCID: PMC5243136 DOI: 10.3332/ecancer.2017.714] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer, a malignant and highly proliferative condition, has significantly affected a large population around the globe and is known to be caused by various factors including genetic, epigenetic, and environmental influences. Though the global trend of these cancers is declining, an increase in its frequency is still a threat because of changing lifestyles and dietary habits. However, genetic and epigenetic alterations related to gastric cancers also have an equivalent contribution towards carcinogenic development. DNA methylation is one of the major forms of epigenetic modification which plays a significant role in gastric carcinogenesis. Methylation leads to inactivation of some of the most important genes like DNA repair genes, cell cycle regulators, apoptotic genes, transcriptional regulators, and signalling pathway regulators; which subsequently cause uncontrolled proliferation of cells. Mutations in these genes can be used as suitable prognostic markers for early diagnosis of the disease, since late diagnosis of gastric cancers has a huge negative impact on overall patient survival. In this review, we focus on the important epigenetic mutations that contribute to the development of gastric cancer and the molecular pathogenesis underlying each of them. Methylation, acetylation, and histone modifications play an integral role in the onset of genomic instability, one of the many contributory factors to gastric cancer. This article also covers the constraints of incomplete knowledge of epigenetic factors influencing gastric cancer, thus throwing light on our understanding of the disease.
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Affiliation(s)
- Trupti N Patel
- Department of Medical Biotechnology, VIT University, Vellore 632014, Tamil Nadu, India
| | - Soumyadipta Roy
- Department of Medical Biotechnology, VIT University, Vellore 632014, Tamil Nadu, India
| | - Revathi Ravi
- Department of Medical Biotechnology, VIT University, Vellore 632014, Tamil Nadu, India
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34
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Serum Cytokinome Profile Evaluation: A Tool to Define New Diagnostic and Prognostic Markers of Cancer Using Multiplexed Bead-Based Immunoassays. Mediators Inflamm 2016; 2016:3064643. [PMID: 28050120 PMCID: PMC5168457 DOI: 10.1155/2016/3064643] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Revised: 09/19/2016] [Accepted: 10/27/2016] [Indexed: 12/15/2022] Open
Abstract
In recent years, many researchers are focusing their attention on the link between inflammation and cancer. The inflammation is involved in the tumor development and suppression, by stimulating the immune response. In particular, the transition from chronic inflammation to cancer produces angiogenic and growth factors able to repair the tissue and to promote cancer cell survival, implantation, and growth. In this contest, the cytokines contribute to the development of these processes becoming active before and during the inflammatory process and playing an important function at the various disease levels. Thus, these proteins can represent specific markers of tumor development and progression. Therefore the "cytokinome" term is used to indicate the evaluation of cytokine pattern by using an "omics" approach. Newly, specific protein chips of considerable and improved sensitivity are being developed to determine simultaneously several and different cytokines. This can be achieved by a multiplex technology that, through the use of small amounts of serum or other fluids, is used to determine the presence and the levels of underrepresented cytokines. Since this method is an accurate, sensitive, and reproducible cytokine assay, it is already used in many different studies. Thus, this review focuses on the more latest aspects related to cytokinome profile evaluation in different cancers.
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35
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Shivappa N, Hébert JR, Ferraroni M, La Vecchia C, Rossi M. Association between Dietary Inflammatory Index and Gastric Cancer Risk in an Italian Case-Control Study. Nutr Cancer 2016; 68:1262-1268. [PMID: 27636679 PMCID: PMC5154551 DOI: 10.1080/01635581.2016.1224367] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND In this study, we explored the association between the dietary inflammatory index (DII) and gastric cancer risk in an Italian case-control study. MATERIALS AND METHODS Cases were 230 patients with incident, histologically confirmed cases of gastric cancer from the Greater Milan area, Northern Italy. Controls were 547 frequency-matched subjects admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. The DII was computed using a reproducible and valid 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models conditioned on age and sex and adjusted for recognized confounding factors, including total energy intake. RESULTS Subjects with the most pro-inflammatory diet had a higher risk of gastric cancer compared to subjects with the most anti-inflammatory diet (ORQuartile4vs1 = 2.35, 95% confidence interval, 1.32, 4.20; P-trend = 0.004). CONCLUSION These results indicate that a pro-inflammatory diet, as indicated by higher DII score, was associated with increased risk of gastric cancer.
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Affiliation(s)
- Nitin Shivappa
- Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
- Connecting Health Innovations LLC, Columbia, SC, 29229, USA
| | - James R. Hébert
- Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
- Connecting Health Innovations LLC, Columbia, SC, 29229, USA
- Department of Family and Preventive Medicine, University of South Carolina School of Medicine, Columbia, South Carolina, 29208, USA
| | - Monica Ferraroni
- Department of Clinical Sciences and Community Health. Universitá degli Studi di Milano, Milan, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health. Universitá degli Studi di Milano, Milan, Italy
| | - Marta Rossi
- Department of Clinical Sciences and Community Health. Universitá degli Studi di Milano, Milan, Italy
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Saeed MT, Ahmad J, Kanwal S, Holowatyj AN, Sheikh IA, Zafar Paracha R, Shafi A, Siddiqa A, Bibi Z, Khan M, Ali A. Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression. PeerJ 2016; 4:e2348. [PMID: 27703839 PMCID: PMC5047222 DOI: 10.7717/peerj.2348] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 07/19/2016] [Indexed: 12/21/2022] Open
Abstract
The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT), an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.
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Affiliation(s)
- Muhammad Tariq Saeed
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Jamil Ahmad
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan; School of Computer Science and IT, Stratford University, VA, United States
| | - Shahzina Kanwal
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou , China
| | - Andreana N Holowatyj
- Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute , Detroit , MI , United States
| | - Iftikhar A Sheikh
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Rehan Zafar Paracha
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Aamir Shafi
- School of Electrical Engineering and Computer Science (SEECS), National University of Sciences and Technology (NUST), Islamabad, Pakistan; College of Computer Science and Information Technology, University of Dammam, Al Khobar, Kingdom of Saudi Arabia
| | - Amnah Siddiqa
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Zurah Bibi
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Mukaram Khan
- Research Centre for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
| | - Amjad Ali
- Atta-ur-Rehman School of Applied Bio-science (ASAB), National University of Sciences and Technology (NUST) , Islamabad , Pakistan
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Kachuei A, Amini M, Sebghatollahi V, Feizi A, Hamedani P, Iraj B. Effect of Helicobacter pylori eradication on insulin resistance among prediabetic patients: A pilot study and single-blind randomized controlled clinical trial. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2016; 21:8. [PMID: 27904554 PMCID: PMC5121998 DOI: 10.4103/1735-1995.177355] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Revised: 11/24/2015] [Accepted: 02/03/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Type II diabetes mellitus (T2DM) is the prevalent type of diabetes in the world. Prediabetic patients are the most probable group to get diabetes. Several studies have mentioned the role of inflammation in the incidence of diabetes. The origin of inflammation can be infection such as Helicobacter pylori (HP) infection. This study was designed to explore the effect of HP eradication on insulin resistance. MATERIALS AND METHODS This single-blind randomized controlled clinical trial was conducted in 2014-2015. The sample size consisted of 49 individuals who were in prediabetes stage with HP infection. Patients with positive stool antigen were allocated randomly into two groups. The treatment group took medication to eradicate HP infection by the routine method of four-drug eradication. However, placebo capsules and tablets were given to the patients in the placebo group. Then fasting plasma glucose (FPG), fasting plasma insulin (FPI), and quantitative C-reactive protein (CRP) levels were measured and homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-B), Matsuda index, insulinogenic index, and disposition index were calculated. RESULTS Results of this study showed that FPI and HOMA-IR increased significantly (P value of FPI = 0.023 and P value of HOMA-IR = 0.019) after HP eradication in the treatment group. On the other hand, comparison of differences at the baseline and after 6 weeks in FPG (P value = 0.045), FPI (P value = 0.013), and HOMA-B (P value = 0.038) revealed significant differences between the placebo group and treatment group. CONCLUSION Results showed that HP eradication by a 2-week antibiotic medication did not decrease insulin resistance and even increased FPI and insulin resistance indices. So HP eradication among prediabetic patients is not recommended for the decrease of insulin resistance and postponement of the development of diabetes mellitus.
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Affiliation(s)
- Ali Kachuei
- Department of Endocrinology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoud Amini
- Department of Endocrinology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vahid Sebghatollahi
- Department of Gastroenterology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Pooria Hamedani
- Department of Endocrinology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Bijan Iraj
- Department of Endocrinology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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38
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Güneş M, Bulut M, Demir S, İbiloğlu AO, Kaya MC, Atlı A, Kaplan İ, Camkurt MA, Sir A. Diagnostic performance of increased prolidase activity in schizophrenia. Neurosci Lett 2016; 613:36-40. [DOI: 10.1016/j.neulet.2015.12.036] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 11/22/2015] [Accepted: 12/17/2015] [Indexed: 12/22/2022]
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39
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Ramakrishna YG, Savithri K, Kist M, Devaraj SN. Aegle marmelos fruit extract attenuates Helicobacter pylori Lipopolysaccharide induced oxidative stress in Sprague Dawley rats. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:375. [PMID: 26482072 PMCID: PMC4615325 DOI: 10.1186/s12906-015-0915-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 10/13/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Bael (Aegle marmelos (L.) Corr.) has been widely used in indigenous systems of Indian medicine to exploit its medicinal properties including astringent, antidiarrheal, antidysenteric, demulcent, antipyretic, antiulcer, anti-inflammatory and anti cancer activities. The present study aims to evaluate the antioxidative and antiulcer effect of methanolic extract of unripe fruit of Aegle marmelos (MEAM) against Helicobacter pylori-Lipopolysaccharide (HP-LPS) induced gastric ulcer in Sprague Dawley (SD) rats. METHODS Dose and duration of HP-LPS and MEAM were fixed based on ulcer index of gastric tissue of experimental animals. Various gastric secretory parameters such as volume of gastric juice, free and total acidity, acid output, pepsin concentration were analyzed. The activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase), non-enzymatic antioxidants (reduced glutathione, vitamin C and vitamin E) and the levels of lipid peroxidation products were measured. Histological analysis was performed to evaluate the effect of Aegle marmelos on HP-LPS induced gastric ulcer. RESULTS Oral administration of HP-LPS (50 μg per animal) for four consecutive days resulted in induction of ulcer with the increase in gastric secretory parameters such as volume of gastric juice, free and total acidity, acid output, pepsin concentration. Oral administration of methanolic extract of Aegle marmelos fruit (MEAM) (25, 50, 100, 250 and 500 mg/kg) reduced the gastric ulcer by 2.8 %, 52.4 %, 73 %, 93 % and 93.98 %, respectively, compared to 89.2 % reduction by sucralfate (100 mg/kg). MEAM treatment significantly (p < 0.05) inhibited the increase in gastric secretory parameters in ulcerated rats, and it also prevented the reduction of enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione transferase) and non-enzymatic antioxidants (reduced glutathione, vitamin C and vitamin E) after HP-LPS induction. In addition, lipid peroxidation was inhibited by MEAM in HP-LPS induced rats. Results of histological analysis correlated well with biochemical parameters. CONCLUSION These observations explored the antioxidant properties of MEAM contributing to the gastroprotective effect in HP-LPS induced gastric ulcer model.
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Affiliation(s)
| | - Kumarasamy Savithri
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
| | - Manfred Kist
- Institut fur Medizinische, Mekrobiologie und Hygiene, Freiburg, Germany.
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An Additive Effect of Oral N-Acetyl Cysteine on Eradication of Helicobacter pylori. J Pathog 2015; 2015:540271. [PMID: 26421191 PMCID: PMC4572430 DOI: 10.1155/2015/540271] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Revised: 08/08/2015] [Accepted: 08/24/2015] [Indexed: 12/16/2022] Open
Abstract
Background. Helicobacter pylori is highly adapted to the gastric environment where it lives within or beneath the gastric mucous layer. The aim of this study was to evaluate whether the addition of N-acetyl cysteine to the treatment regimen of H. pylori infection would affect eradication rates of the disease. Methods. A total of 79 H. pylori positive patients were randomized to two therapeutic groups. Both groups received a 14-day course of three-drug regimen including amoxicillin/clarithromycin/omeprazole. Experimental group (38 subjects) received NAC, and control group (41 subjects) received placebo, besides three-drug regimen. H. pylori eradication was evaluated by urea breath test at least 4 weeks after the cessation of therapy. Results. The rate of H. pylori eradication was 72.9% and 60.9% in experimental and control groups, respectively (P = 0.005). By logistic regression modeling, female gender (OR 3.68, 95% CI: 1.06–5.79; P = 0.040) and treatment including NAC (OR 1.88, 95% CI: 0.68–3.15; P = 0.021) were independent factors associated with H. pylori eradication. Conclusion. The results of the present study show that NAC has an additive effect on the eradication rates of H. pylori obtained with three-drug regimen and appears to be a promising means of eradicating H. pylori infection.
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Park JS, Yeom JS, Seo JH, Lim JY, Park CH, Woo HO, Youn HS, Jun JS, Park JH, Ko GH, Baik SC, Lee WK, Cho MJ, Rhee KH. Immunohistochemical Expressions of MUC2, MUC5AC, and MUC6 in Normal, Helicobacter pylori Infected and Metaplastic Gastric Mucosa of Children and Adolescents. Helicobacter 2015; 20:260-8. [PMID: 25704078 DOI: 10.1111/hel.12198] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The aim of this study was to investigate expression of gastric mucins in children and adolescents and to assess their relations with age and Helicobacter pylori (H. pylori) infection. METHODS Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical stains. A semiquantitative approach was used to score the staining extent of tissue slide. RESULTS Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2 and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted in children without intestinal metaplasia. CONCLUSIONS MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role, based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.
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Affiliation(s)
- Ji Sook Park
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Jung-Sook Yeom
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Ji-Hyun Seo
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Jae-Young Lim
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Chan-Hoo Park
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Hyang-Ok Woo
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Hee-Shang Youn
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Jin-Su Jun
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Ji-Hoe Park
- Department of Pediatrics, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Gyung-Hyuck Ko
- Department of Pathology, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Seung-Chul Baik
- Department of Microbiology, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Woo-Kon Lee
- Department of Microbiology, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Myung-Je Cho
- Department of Microbiology, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
| | - Kwang-Ho Rhee
- Department of Microbiology, Gyeonsang National University School of Medicine, Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsangnam-do, Korea
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Choi MK, Kang MH, Kim MH. Dietary intake assessment and biochemical characteristics of blood and urine in patients with chronic gastritis. Clin Nutr Res 2015; 4:90-6. [PMID: 25954729 PMCID: PMC4418420 DOI: 10.7762/cnr.2015.4.2.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Revised: 04/09/2015] [Accepted: 04/10/2015] [Indexed: 01/07/2023] Open
Abstract
Chronic gastritis is a prevalent gastroentestinal disease in Korea. The purpose of this study was to investigate status of foods and nutrients intake and health related biochemical indicators in the patients with chronic gastritis. Daily food and nutrient intake, blood lipids, and antioxidant indicators in the urine, were compared between a group of 19 patients diagnosed with chronic gastritis and a control group of 27 subjects having normal gastroscopy. No significant differences were found in age, height, weight, body mass index, and blood pressure between the two groups. Daily energy intakes were 1900.6 kcal for the chronic gastritis patient group, and 1931.8 kcal for the normal control group without significant difference. No significant difference was found between the two groups in all nutrient intakes except for cholesterol. The chronic gastritis patients consumed lower amount of sugars and sweeteners but greater amount of starchy food groups such as potatoes and legumes than subjects of control group consumed. Also the chronic gastritis patients showed higher serum triglyceride concentration than the normal subjects. These results indicate that the dietary pattern of chronic gastritis patients may have relation to a change in the serum lipid level; however, more systematic research with a larger samples size is required.
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Affiliation(s)
- Mi-Kyeong Choi
- Division of Food Science, Kongju National University, Yesan 340-702, Korea
| | - Myung-Hwa Kang
- Department of Food and Nutrition, Hoseo University, Asan 336-795, Korea
| | - Mi-Hyun Kim
- Department of Food and Nutrition, Korea National University of Transportation, Jeungpyeong 368-701, Korea
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Zhao L, Zhang Z, Lin J, Cao L, He B, Han S, Zhang X. Complement receptor 1 genetic variants contribute to the susceptibility to gastric cancer in chinese population. J Cancer 2015; 6:525-30. [PMID: 26000043 PMCID: PMC4439937 DOI: 10.7150/jca.10749] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 11/26/2014] [Indexed: 12/21/2022] Open
Abstract
As the receptor for C3b/C4b, type 1 complement receptor (CR1/CD35) plays an important role in the regulation of complement activity and is further involved in carcinogenesis. This study aimed to elucidate the association of CR1 genetic variants with the susceptibility to gastric cancer in Chinese population. Based on the NCBI database, totally 13 tag single nucleotide polymorphisms (SNPs) were selected by Haploview program and genotyped using iPlex Gold Genotyping Assay and Sequenom MassArray among 500 gastric cancer cases and 500 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression to evaluate the association of each SNP with gastric cancer. Of all selected Tag SNPs , CR1 rs9429942 T > C was found to confer to the risk of developing gastric cancer. Compared with the carriers with rs9429942 TT genotype, those with CT genotype had 88% decreased risk of developing gastric cancer with OR (95%CI) of 0.12 (0.03-0.50). Generalized multifactor dimensionality reduction (GMDR) analysis revealed a significant three-way interaction among rs75422544 C > A, rs10494885 C > T and rs7525160 G > C in the development of gastric cancer with a maximum testing balance accuracy of 56.07% and a cross-validation consistency of 7/10 (P = 0.011). In conclusion, our findings demonstrated the genetic role of CR1 gene in the development of gastric cancer in Chinese population.
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Affiliation(s)
- Lina Zhao
- 1. Institute of Molecular Genetics, College of Life Sciences, Hebei United University, Tangshan, China
| | - Zhi Zhang
- 2. Affiliated Tangshan Gongren Hospital, Hebei United University, Tangshan, China
| | - Jia Lin
- 1. Institute of Molecular Genetics, College of Life Sciences, Hebei United University, Tangshan, China
| | - Lei Cao
- 1. Institute of Molecular Genetics, College of Life Sciences, Hebei United University, Tangshan, China
| | - Bing He
- 1. Institute of Molecular Genetics, College of Life Sciences, Hebei United University, Tangshan, China
| | - Sugui Han
- 3. Department of Clinical laboratory, Tangshan Renmin Hospital, Tangshan, China
| | - Xuemei Zhang
- 1. Institute of Molecular Genetics, College of Life Sciences, Hebei United University, Tangshan, China
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YE XIAOLEI, ZHAO YARONG, WENG GUOBIN, CHEN YICHEN, WEI XUENI, SHAO JINGPING, JI HUI. IL-33-induced JNK pathway activation confers gastric cancer chemotherapy resistance. Oncol Rep 2015; 33:2746-52. [DOI: 10.3892/or.2015.3898] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 12/15/2014] [Indexed: 02/06/2023] Open
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Marwaha S, Schumacher MA, Zavros Y, Eghbalnia HR. Crosstalks between cytokines and Sonic Hedgehog in Helicobacter pylori infection: a mathematical model. PLoS One 2014; 9:e111338. [PMID: 25364910 PMCID: PMC4218723 DOI: 10.1371/journal.pone.0111338] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 09/23/2014] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori infection of gastric tissue results in an immune response dominated by Th1 cytokines and has also been linked with dysregulation of Sonic Hedgehog (SHH) signaling pathway in gastric tissue. However, since interactions between the cytokines and SHH during H. pylori infection are not well understood, any mechanistic understanding achieved through interpretation of the statistical analysis of experimental results in the context of currently known circuit must be carefully scrutinized. Here, we use mathematical modeling aided by restraints of experimental data to evaluate the consistency between experimental results and temporal behavior of H. pylori activated cytokine circuit model. Statistical analysis of qPCR data from uninfected and H. pylori infected wild-type and parietal cell-specific SHH knockout (PC-SHHKO) mice for day 7 and 180 indicate significant changes that suggest role of SHH in cytokine regulation. The experimentally observed changes are further investigated using a mathematical model that examines dynamic crosstalks among pro-inflammatory (IL1β, IL-12, IFNγ, MIP-2) cytokines, anti-inflammatory (IL-10) cytokines and SHH during H. pylori infection. Response analysis of the resulting model demonstrates that circuitry, as currently known, is inadequate for explaining of the experimental observations; suggesting the need for additional specific regulatory interactions. A key advantage of a computational model is the ability to propose putative circuit models for in-silico experimentation. We use this approach to propose a parsimonious model that incorporates crosstalks between NFĸB, SHH, IL-1β and IL-10, resulting in a feedback loop capable of exhibiting cyclic behavior. Separately, we show that analysis of an independent time-series GEO microarray data for IL-1β, IFNγ and IL-10 in mock and H. pylori infected mice further supports the proposed hypothesis that these cytokines may follow a cyclic trend. Predictions from the in-silico model provide useful insights for generating new hypothesis and design of subsequent experimental studies.
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Affiliation(s)
- Shruti Marwaha
- Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, United States of America
- * E-mail:
| | - Michael A. Schumacher
- Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, United States of America
| | - Yana Zavros
- Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, United States of America
| | - Hamid R. Eghbalnia
- Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, United States of America
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Dogan Z, Sarikaya M, Ergul B, Filik L. The effect of Helicobacter pylori eradication on insulin resistance and HbA1c level in people with normal glucose levels: a prospective study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 159:242-5. [PMID: 24993741 DOI: 10.5507/bp.2014.036] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 06/10/2014] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection is reported to be associated with various extragastrointestinal conditions such as insulin resistance, diabetes mellitus and metabolic syndrome. These conditions are attributed to systemic inflammation, leptin or ghrelin changes due to H. pylori infection. Therefore, increasing trends in the management of H. pylori infection are ordered to maintain glycemic control. In this study, we evaluated the effect of H. pylori eradication on insulin resistance in patients with normal blood glucose concentrations. METHOD A total of 370 patients with successful eradication were included in the study. Patients with H. pylori were given triple eradication treatment. All patients with H. pylori infection were tested for fasting glucose, fasting insulin, glicated hemoglobin (HbA1c) at baseline and 6 months after eradication treatment. Also, insulin resistance was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Body mass index was also determined as a metabolic syndrome criteria effecting insulin resistance. RESULTS There were significant differences in fasting glucose, fasting insulin, HbA1c, and HOMA-IR values between before treatment and after treatment(P <0.04, <0.01, <0.01, <0.01). The favorable effect of eradication was more significant in patients with BMI≥25 mg/m(2)(P<0.05). CONCLUSION Eradication treatment has beneficial effects on insulin resistance in patients with normal glucose concentrations.
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Affiliation(s)
- Zeynal Dogan
- Ankara Education and Research Hospital, Gastroenterology, Turkey
| | - Murat Sarikaya
- Ankara Education and Research Hospital, Gastroenterology, Turkey
| | - Bilal Ergul
- Ankara Education and Research Hospital, Gastroenterology, Turkey
| | - Levent Filik
- Ankara Education and Research Hospital, Gastroenterology, Turkey
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Yan F, Fu Q. PLCε1: A potential target of RNA interference therapy for gastric cancer. Biochem Biophys Res Commun 2014; 448:409-13. [DOI: 10.1016/j.bbrc.2014.04.119] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 04/23/2014] [Indexed: 01/01/2023]
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Thiraworawong T, Spinler JK, Werawatganon D, Klaikeaw N, Venable SF, Versalovic J, Tumwasorn S. Anti-inflammatory properties of gastric-derived Lactobacillus plantarum XB7 in the context of Helicobacter pylori infection. Helicobacter 2014; 19:144-55. [PMID: 24387083 DOI: 10.1111/hel.12105] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Helicobacter pylori colonization of the gastric epithelium induces interleukin-8 (IL-8) production and inflammation leading to host cell damage. We searched for gastric-derived Lactobacillus with the ability to suppress H. pylori-induced inflammation. MATERIALS AND METHODS Conditioned media from gastric-derived Lactobacillus spp. were tested for the ability to suppress H. pylori-induced IL-8 production in AGS gastric epithelial cells. IL-8 protein and mRNA levels were measured by ELISA and qPCR, respectively. The changes on host cell signaling pathway were analyzed by Western blotting and the anti-inflammatory effect was tested in a Sprague-Dawley rat model. RESULTS Conditioned media from L. salivarius B101, L. rhamnosus B103, and L. plantarum XB7 suppressed IL-8 production and IL-8 mRNA expression in H. pylori-induced AGS cells without inhibiting H. pylori growth. Conditioned media from LS-B101, LR-B103, and LP-XB7 suppressed the activation of NF-κB in AGS cells, while strain LP-XB7 also suppressed c-Jun activation. The anti-inflammatory effect of LP-XB7 was further assessed in vivo using a H. pylori-infected Sprague-Dawley rat model. Strain LP-XB7 contributed to a delay in the detection and colonization of H. pylori in rat stomachs, attenuated gastric inflammation, and ameliorated gastric histopathology. Additionally, the administration of LP-XB7 correlated with the suppression of TNF-α and CINC-1 in sera, and suppression of CINC-1 in the gastric mucosa of H. pylori-infected rats. CONCLUSIONS These results suggest that L. plantarum XB7 produces secreted factors capable of modulating inflammation during H. pylori infection, and this probiotic Lactobacillus strain shows promise as an adjunctive therapy for treating H. pylori-associated disease.
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Affiliation(s)
- Thien Thiraworawong
- Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand
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Ainslie-Waldman CE, Koh WP, Jin A, Yeoh KG, Zhu F, Wang R, Yuan JM, Butler LM. Coffee intake and gastric cancer risk: the Singapore Chinese health study. Cancer Epidemiol Biomarkers Prev 2014; 23:638-47. [PMID: 24608187 DOI: 10.1158/1055-9965.epi-13-0886] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. METHODS We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women ages 45 to 74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n = 647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected before cancer diagnosis and their matched controls. RESULTS In the total cohort, daily versus nondaily coffee intake was associated with a statistically nonsignificant decrease in gastric cancer risk [HR = 0.85; 95% confidence interval (CI), 0.69-1.04]. In women, the inverse association strengthened and reached statistical significance (HR = 0.63; 95% CI, 0.46-0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR = 0.69; 95% CI, 0.52-0.91) and in women (HR = 0.52; 95% CI, 0.37-0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. CONCLUSION Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. IMPACT Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted.
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Affiliation(s)
- Cheryl E Ainslie-Waldman
- Authors' Affiliations: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis; Department of Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota; Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Duke-NUS Graduate Medical School Singapore, Singapore; Saw Swee Hock School of Public Health and Department of Medicine, National University of Singapore, Singapore; National Registry of Diseases Office, Health Promotion Board; and Department of Gastroenterology and Hepatology, National University Health System, Singapore
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Abstract
An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies.
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Affiliation(s)
- Meredith A J Hullar
- Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, PO Box 19024, Seattle, WA, 98109, USA
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