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Pantic I, Lugonja S, Jerotic D, Pljesa-Ercegovac M, Matic M, Bakovic N, Vojnovic M, Simic T, Milovanovic T, Savic-Radojevic A. GSTP1 and GSTO1 Variant Alleles Affect Susceptibility to Helicobacter pylori Infection and Severity of Helicobacter pylori-Associated Clinical Manifestations. Int J Mol Sci 2025; 26:488. [PMID: 39859205 PMCID: PMC11764725 DOI: 10.3390/ijms26020488] [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: 11/20/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Considering the mutual relationship between redox disbalance and inflammation in Helicobacter pylori (HP) infection, we aimed to evaluate whether the polymorphisms in antioxidant glutathione transferases genes (GSTP1 rs1695, GSTP1rs1138272, GSTO1 rs4925 and GSTO2 rs156697) modify susceptibility to HP infection, as well as the severity of HP-associated gastric manifestation development. Therefore, GST gene polymorphisms were determined via the appropriate PCR in 101 HP-positive and 107 HP-negative patients. Our results show that carriers of the GSTP1*G/G variant genotype (rs1695) or at least one GSTP1*T variant allele (rs1138272) were more prone to the development of HP-positive gastritis compared with reference allele carriers (OR = 3.21, 95%CI = 1.15-8.91, p = 0.025 and OR = 2.31, 95%CI = 1.14-4.89, p = 0.021, respectively), which was confirmed by haplotype analysis. HP-positive carriers of the GSTO1*A variant allele showed increased risk of developing gastric atrophy and precancerous gastric lesions compared with the reference one (OR = 2.49, 95%CI:1.04-5.96, p = 0.04 and OR = 2.98, 95%CI = 1.21-7.34, p = 0.018, respectively). HP-positive carriers of the GSTO2*G variant allele were less prone to developing moderate/severe inflammatory infiltration (OR = 0.35, 95%CI = 1.04-5.96, p = 0.04), whereas the GSTP1*T variant allele was significantly associated with active inflammation (OR = 4.09, 95%CI = 1.04-5.96, p = 0.042). In conclusion, antioxidant GST genetic propensity seems to have an important impact on both acute and chronic forms of HP infection.
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Affiliation(s)
- Ivana Pantic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (N.B.); (M.V.)
| | - Sofija Lugonja
- Division of Gastroenterology, Department of Internal Medicine, General Hospital “Djordje Joanovic”, 23000 Zrenjanin, Serbia;
| | - Djurdja Jerotic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center for Excellence for Redox Medicine, 11000 Belgrade, Serbia
| | - Marija Pljesa-Ercegovac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center for Excellence for Redox Medicine, 11000 Belgrade, Serbia
| | - Marija Matic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center for Excellence for Redox Medicine, 11000 Belgrade, Serbia
| | - Nikola Bakovic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (N.B.); (M.V.)
| | - Marko Vojnovic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (N.B.); (M.V.)
| | - Tatjana Simic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center for Excellence for Redox Medicine, 11000 Belgrade, Serbia
- Department of Medical Sciences, Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (I.P.); (N.B.); (M.V.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
| | - Ana Savic-Radojevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (M.P.-E.); (M.M.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center for Excellence for Redox Medicine, 11000 Belgrade, Serbia
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Nasier-Hussain M, Samanje JN, Mokhtari K, Nabi-Afjadi M, Fathi Z, Hoseini A, Bahreini E. Serum levels of oxidative stress, IL-8, and pepsinogen I/II ratio in Helicobacter pylori and gastric cancer patients: potential diagnostic biomarkers. BMC Gastroenterol 2025; 25:2. [PMID: 39748276 PMCID: PMC11697901 DOI: 10.1186/s12876-024-03564-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 12/13/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND AND AIM Helicobacter pylori (H.pylori), a gram-negative bacterial pathogen associated with an increased risk of gastric cancer. This study investigates potential factors in the incidence of gastric cancer in patients with H.pylori, including oxidative stress, inflammatory biomarkers, serum pepsinogens (PG) of I and II, and PG-I/PG-II ratio. METHODS The study comprised individuals with Helicobacter pylori (H.pylori) infection, gastric cancer patients, and healthy individuals. Biochemical parameters such as FBS (fasting blood sugar), lipid profile, and liver and kidney functional factors were evaluated using colorimetric techniques. Oxidative markers such as total oxidant status (TOS) and malondialdehyde (MDA) were quantified through colorimetric methods. IL-8, PG-II, and PG-II levels were also determined using the ELISA technique. RESULTS Individuals with H. pylori infection exhibited elevated levels of IL-8 (940.5 ± 249.7 vs. 603.4 ± 89.1 pg/ml, P < 0.0001) and oxidative species (5.47 ± 0.7 vs. 1.64 ± 0.7 nM, P < 0.05) compared to gastric cancer patients, who, despite having lower levels of IL-8 and oxidative species, showed higher levels of MDA. H.pylori patients exhibited significantly higher levels of PG-I (7.28 ± 2.1 vs. 2.61 ± 1.4 ng/ml, P < 0.001), PG-II (3.21 ± 1 vs. 2.6 ± 0.6 ng/ml, P < 0.001), and the PG-I/PG-II ratio (2.27 ± 1.2 vs. 1 ± 0.4, P < 0.001) compared to gastric cancer patients. The findings were substantiated using various data analysis platforms such as Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN (The University of ALabama at Birmingham CANcer data analysis), cBioPortal, and TIMER (Tumor IMmune Estimation Resource). These parameters could serve as potential diagnostic biomarkers for screening and therapeutic interventions based on the cut-off values derived from ROC (receiver operating characteristic) curves for IL-8, PGI, PGII, and PGI/PGII across the three groups. CONCLUSIONS IL-8, PGI, PGII, and PGI/PGII parameters could serve as potential diagnostic markers for the screening and treatment of gastric conditions.
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Affiliation(s)
- Marwa Nasier-Hussain
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran
| | - Jaleel Najah Samanje
- Collage of Health and Medical Technology, Middle Technical University, Baghdad, Iraq
| | - Khatere Mokhtari
- Department of Modern Biology, ACECR Institute of Higher Education (Isfahan Branch), Isfahan, Iran
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zeinab Fathi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Asieh Hoseini
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Elham Bahreini
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran.
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Wang JH, Han SY, Kim J, Lim S, Jeong C, Wu L, Kim H. Comparative Assessment of the Anti- Helicobacter pylori Activity and Gastroprotective Effects of Three Herbal Formulas for Functional Dyspepsia In Vitro. Cells 2024; 13:901. [PMID: 38891033 PMCID: PMC11172274 DOI: 10.3390/cells13110901] [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: 04/23/2024] [Revised: 05/16/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024] Open
Abstract
Helicobacter pylori has been implicated in various gastrointestinal disorders, including functional dyspepsia. This study aimed to compare the anti-H. pylori activity and gastroprotective effects of three typical herbal formulas used for gastrointestinal disorders in Korea: Shihosogan-tang (ST), Yijung-tang (YT), and Pyeongwi-san (PS). Firstly, we assessed the total phenolic and flavonoid contents, as well as the antioxidative capacity. Additionally, we evaluated the antibacterial effect on H. pylori using an ammonia assay, minimum inhibitory concentration (MIC) test, and the disk agar diffusion method. Furthermore, we examined alterations in the gene expression of tight junction proteins, pro-inflammatory cytokines, and cellular vacuolation using an AGS cell model infected with H. pylori. While ST exhibited a higher total phenolic content, superior free radical scavenging, and inhibition of H. pylori compared to YT and PS, YT more evidently inhibited gastric cellular morphological changes such as vacuolation. All formulations significantly ameliorated changes in inflammatory and gastric inflammation-related genes and cellular morphological alterations induced by H. pylori infection. Overall, the present in vitro study suggests that all three herbal formulas possess potential for ameliorating gastrointestinal disorders, with ST relatively excelling in inhibiting H. pylori infection and inflammation, while YT potentially shows greater efficacy in directly protecting the gastric mucosa.
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Affiliation(s)
| | | | | | | | | | | | - Hojun Kim
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 814 Siksa-dong, Ilsandong-gu, Goyang-si 10326, Republic of Korea; (J.-H.W.); (S.-Y.H.); (J.K.); (S.L.); (C.J.); (L.W.)
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Li G, Tanaka T, Ouchida T, Kaneko MK, Suzuki H, Kato Y. Cx 1Mab-1: A Novel Anti-mouse CXCR1 Monoclonal Antibody for Flow Cytometry. Monoclon Antib Immunodiagn Immunother 2024; 43:59-66. [PMID: 38593439 DOI: 10.1089/mab.2023.0031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024] Open
Abstract
The C-X-C motif chemokine receptor-1 (CXCR1) is a rhodopsin-like G-protein-coupled receptor, expressed on the cell surface of immune cells and tumors. CXCR1 interacts with some C-X-C chemokines, such as CXCL6, CXCL7, and CXCL8/interleukin-8, which are produced by various cells. Since CXCR1 is involved in several diseases including tumors and diabetes mellitus, drugs targeting CXCR1 have been developed. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CXCR1 has been desired for the diagnosis and treatment. This study established a novel anti-mouse CXCR1 (mCXCR1) mAb, Cx1Mab-1 (rat IgG1, kappa), using the Cell-Based Immunization and Screening method. Cx1Mab-1 reacted with mCXCR1-overexpressed Chinese hamster ovary-K1 (CHO/mCXCR1) and mCXCR1-overexpressed LN229 glioblastoma (LN229/mCXCR1) in flow cytometry. Cx1Mab-1 demonstrated a high binding affinity for CHO/mCXCR1 and LN229/mCXCR1 with a dissociation constant of 2.6 × 10-9 M and 2.1 × 10-8 M, respectively. Furthermore, Cx1Mab-1 could detect mCXCR1 by Western blot analysis. These results indicated that Cx1Mab-1 is useful for detecting mCXCR1, and provides a possibility for targeting mCXCR1-expressing cells in vivo experiments.
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Affiliation(s)
- Guanjie Li
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomohiro Tanaka
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tsunenori Ouchida
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Mika K Kaneko
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hiroyuki Suzuki
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yukinari Kato
- Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan
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Cen C, Du Q, Luo B, Wang T, Su J, Qin X, Zhang W, Lu L, Liao Y, Huang Y, Liang Y. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients. Open Life Sci 2024; 19:20220839. [PMID: 38585629 PMCID: PMC10997148 DOI: 10.1515/biol-2022-0839] [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: 09/19/2023] [Revised: 01/25/2024] [Accepted: 02/06/2024] [Indexed: 04/09/2024] Open
Abstract
Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori (H. pylori) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group, Helicobacter, Bacteroides, Klebsiella, and Pseudomonas. In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori-positive (HP_Pos) and H. pylori-negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.
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Affiliation(s)
- Chao Cen
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Qiuying Du
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Bin Luo
- Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Tonghua Wang
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Jianwei Su
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Xiaoshan Qin
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Wenyan Zhang
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Lijing Lu
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Yang Liao
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Yanqiang Huang
- Department of Pathogen Biology and Immunology, Youjiang Medical University for Nationalities School of Basic Medical Sciences, Baise, Guangxi 533000, China
| | - Yumei Liang
- Department of Neonatology, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan Second Road, Youjiang District, Baise, Guangxi 533000, China
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Chen H, Zhang GX, Zhou XY. Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus: A pilot bioinformatics study. World J Diabetes 2024; 15:170-185. [PMID: 38464370 PMCID: PMC10921168 DOI: 10.4239/wjd.v15.i2.170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/21/2023] [Accepted: 12/27/2023] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown. AIM To explore potential molecular connections between H. pylori infection and T2DM. METHODS We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed. RESULTS A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4, ITGAM, C5AR1, FCER1G, and FCGR2A, were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes. CONCLUSION We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori-induced onset of T2DM.
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Affiliation(s)
- Han Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210003, Jiangsu Province, China
| | - Guo-Xin Zhang
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing 210029, Jiangsu Province, China
| | - Xiao-Ying Zhou
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing 210029, Jiangsu Province, China
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