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Keywords = non-atrophic gastritis

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10 pages, 1317 KiB  
Review
Unraveling the Enigma: Food Cobalamin Malabsorption and the Persistent Shadow of Cobalamin Deficiency
by Emmanuel Andrès, Jean Edouard Terrade, María Belén Alonso Ortiz, Manuel Méndez-Bailón, Cosmina Ghiura, Chalène Habib, Thierry Lavigne, Xavier Jannot and Noel Lorenzo-Villalba
J. Clin. Med. 2025, 14(8), 2550; https://doi.org/10.3390/jcm14082550 - 8 Apr 2025
Viewed by 4434
Abstract
Food cobalamin malabsorption (FCM) represents a prevalent, often underdiagnosed, etiology of vitamin B12 deficiency, particularly within an aging population. Unlike pernicious anemia, an autoimmune disorder targeting intrinsic factor, FCM stems from the impaired release of cobalamin from food proteins, primarily due to age-related [...] Read more.
Food cobalamin malabsorption (FCM) represents a prevalent, often underdiagnosed, etiology of vitamin B12 deficiency, particularly within an aging population. Unlike pernicious anemia, an autoimmune disorder targeting intrinsic factor, FCM stems from the impaired release of cobalamin from food proteins, primarily due to age-related gastric changes, medication-induced gastric hypochlorhydria, metformin, or non-immune atrophic gastritis. The clinical presentation of FCM mirrors that of general cobalamin deficiency, encompassing a spectrum of neurological (peripheral neuropathy, cognitive decline), hematological (megaloblastic anemia), and gastrointestinal (glossitis, anorexia) manifestations. Given the potential for irreversible neurological sequelae, early detection and intervention are paramount. High-dose oral cobalamin (125–250 mcg daily) has demonstrated efficacy, offering a convenient and cost-effective alternative to parenteral administration. Full article
(This article belongs to the Section Hematology)
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15 pages, 1819 KiB  
Article
Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
by María José Maturana, Oslando Padilla, Pablo M. Santoro, Maria Alejandra Alarcón, Wilda Olivares, Alejandro Blanco, Ricardo Armisen, Marcelo Garrido, Edmundo Aravena, Carlos Barrientos, Alfonso Calvo-Belmar and Alejandro H. Corvalán
Int. J. Mol. Sci. 2025, 26(7), 3333; https://doi.org/10.3390/ijms26073333 - 3 Apr 2025
Viewed by 1009
Abstract
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated [...] Read more.
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response. Full article
(This article belongs to the Section Molecular Oncology)
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17 pages, 1559 KiB  
Article
Point-of-Care Diagnosis of Atrophic Gastritis by Serological Biomarker Test (GastroPanel® Quick Test) in Gastroscopy Referral Patients in India
by Mohinish Chhabra, Ajit Kolatkar, Suresh Chawla, Aniket Joshi, Marika Karjalainen, Heli Holopainen, Panu Hendolin and Kari Syrjänen
J. Clin. Med. 2025, 14(3), 787; https://doi.org/10.3390/jcm14030787 - 25 Jan 2025
Cited by 1 | Viewed by 1654
Abstract
Background: Increased demand of the serological biomarker test (GastroPanel®) in non-invasive diagnosis of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, prompted the design of GastroPanel® Quick test (GPQT) (Biohit Oyj, Helsinki, [...] Read more.
Background: Increased demand of the serological biomarker test (GastroPanel®) in non-invasive diagnosis of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, prompted the design of GastroPanel® Quick test (GPQT) (Biohit Oyj, Helsinki, Finland) for point-of-care (POC) settings. Objective: This study validated the diagnostic accuracy (DA) of GPQT in diagnosis of AG and Hp among gastroscopy referral patients. Methods: Altogether, 266 patients were enrolled among the consecutive gastroscopy referrals at the Department of Gastroenterology, Fortis Hospital (Punjab, India). All patients underwent gastroscopy with biopsies (n = 249) classified using the Updated Sydney System (USS) and finger prick blood sampling for GPQT testing. Results: Biopsy-confirmed AG was found in 15.3% (38/249) of the patients. The overall agreement between the GPQT and the USS classification was 71.4% (95% CI 65.4–77.0%), with the weighted kappa (κw) of 0.823 (95% CI 0.773–0.862). In ROC analysis for moderate/severe AG of the corpus (AGC) endpoint, AUC = 0.990 (95% CI 0.979–1.000) and AUC = 0.971 (95% CI 0.948–0.995) for PGI and PGI/PGII, respectively. Hp IgG Ab test detected biopsy-confirmed Hp with AUC = 0.836 (95% CI 0.783–0.889). Conclusions: The GPQT favourably competes in accuracy with the ELISA test version (unified-GP) in diagnosis of AG and Hp in patients referred for diagnostic gastroscopy. Full article
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11 pages, 1039 KiB  
Article
The C/C Genotype of rs1231760 in RGS2 Is a Risk Factor for the Progression of H. pylori-Positive Atrophic Gastritis by Increasing RGS2 Expression
by Naoyuki Yamaguchi, Takuki Sakaguchi, Jing-Jing Wei, Yuna Tazoe, Tatsuo Inamine, Daisuke Fukuda, Ken Ohnita, Tatsuro Hirayama, Hajime Isomoto, Kayoko Matsushima and Kazuhiro Tsukamoto
Diagnostics 2024, 14(22), 2563; https://doi.org/10.3390/diagnostics14222563 - 15 Nov 2024
Cited by 1 | Viewed by 1097
Abstract
Background: Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can progress to gastric cancer through atrophic gastritis (AG). The risk of gastric cancer increases with the progression of AG. Therefore, investigating the risk factors for the progression of AG is [...] Read more.
Background: Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can progress to gastric cancer through atrophic gastritis (AG). The risk of gastric cancer increases with the progression of AG. Therefore, investigating the risk factors for the progression of AG is important. Methods: Using the GTEx and GEO databases, we extracted thirty-four candidate genes involved in the progression of AG. Then, with in silico analysis using HaploReg v4.1 and JASPAR (Matrix ID: MA0113.3), we extracted rs1231760 of RGS2 as a key single-nucleotide polymorphism (SNP) that could be involved in the functional change in the candidate gene. A correlation analysis between the selected SNP and AG in 200 H. pylori-positive and 302 H. pylori-negative participants was conducted. For functional analysis of the SNP, a dual-luciferase assay using reporter plasmids with a major or minor allele sequence was carried out. Results: The frequency of the C/C genotype of rs1231760 was higher in the AG group than in the non-AG group (p = 0.0471). Functional analysis showed that the transcriptional activities were higher at the dexamethasone-stimulating C allele than at the others (p < 0.05). Conclusions: The C/C genotype of rs1231760 in RGS2 could be a biomarker of high-risk H. pylori-positive AG because of an increase in RGS2 expression. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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31 pages, 893 KiB  
Review
Protein Biomarkers of Gastric Preneoplasia and Cancer Lesions in Blood: A Comprehensive Review
by Thomas Bazin, Karine Nozeret, Catherine Julié, Dominique Lamarque and Eliette Touati
Cancers 2024, 16(17), 3019; https://doi.org/10.3390/cancers16173019 - 29 Aug 2024
Cited by 2 | Viewed by 2080
Abstract
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence [...] Read more.
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC. Full article
(This article belongs to the Collection The Biomarkers for the Diagnosis and Prognosis in Cancer)
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13 pages, 3652 KiB  
Article
Research on Predictive Auxiliary Diagnosis Method for Gastric Cancer Based on Non-Invasive Indicator Detection
by Xia Zhang, Mao Zhang, Gang Wei and Jia Wang
Appl. Sci. 2024, 14(16), 6858; https://doi.org/10.3390/app14166858 - 6 Aug 2024
Viewed by 1658
Abstract
Chronic atrophic gastritis is a serious health issue beyond the stomach health problems that affect normal life. This study aimed to explore the influencing factors related to chronic atrophic gastritis (CAG) using non-invasive indicators and establish an optimal prediction model to aid in [...] Read more.
Chronic atrophic gastritis is a serious health issue beyond the stomach health problems that affect normal life. This study aimed to explore the influencing factors related to chronic atrophic gastritis (CAG) using non-invasive indicators and establish an optimal prediction model to aid in the clinical diagnosis of CAG. Electronic medical record data from 20,615 patients with CAG were analyzed, including routine blood tests, liver function tests, and coagulation tests. The logistic regression algorithm revealed that age, hematocrit, and platelet distribution width were significant influences suggesting chronic atrophic gastritis in the Chongqing population (p < 0.05), with an area under the curve (AUC) of 0.879. The predictive model constructed based on the Random Forest algorithm exhibited an accuracy of 83.15%, precision of 97.38%, recall of 77.36%, and an F1-score of 70.86%, outperforming the models constructed using XGBoost, KNN, and SVC algorithms in a comprehensive comparison. The prediction model derived from this study serves as a valuable tool for future studies and can aid in the prediction and screening of chronic atrophic gastritis. Full article
(This article belongs to the Section Computing and Artificial Intelligence)
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11 pages, 1429 KiB  
Article
Gastric Carcinogenesis and Potential Role of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptor: An Observational Histopathological Study
by Sylvester R. Groen, Daniel Keszthelyi, Arpad Szallasi, Jara A. van Veghel, Annick M. E. Alleleyn, Kata Csekő, Zsuzsanna Helyes, Iryna Samarska, Heike I. Grabsch, Ad A. M. Masclee and Zsa Zsa R. M. Weerts
Int. J. Mol. Sci. 2024, 25(15), 8294; https://doi.org/10.3390/ijms25158294 - 30 Jul 2024
Viewed by 1880
Abstract
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was [...] Read more.
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis. Full article
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22 pages, 690 KiB  
Review
Non-Invasive Markers for the Detection of Gastric Precancerous Conditions
by Marcin Romańczyk, Malgorzata Osmola, Alexander Link, Amaury Druet, Caroline Hémont, Jerome Martin, Nicolas Chapelle and Tamara Matysiak-Budnik
Cancers 2024, 16(12), 2254; https://doi.org/10.3390/cancers16122254 - 18 Jun 2024
Cited by 10 | Viewed by 3079
Abstract
Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, [...] Read more.
Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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11 pages, 296 KiB  
Article
Helicobacter pylori cagA, vacA, iceA and babA Genotypes from Peruvian Patients with Gastric Intestinal Metaplasia
by Jesús Guzmán, Denis Castillo, Anabel D. González-Siccha, Alejandro Bussalleu, Alba A. Trespalacios-Rangel, Andres G. Lescano and Michel Sauvain
Cancers 2024, 16(8), 1476; https://doi.org/10.3390/cancers16081476 - 12 Apr 2024
Cited by 4 | Viewed by 4917
Abstract
We explored the clinical-stage association of gastric intestinal metaplasia (IM) compared to cases of chronic non-atrophic gastritis (CNAG) and its relationship with virulence genotypes of Helicobacter pylori (H. pylori) clinical isolates from patients with dyspepsia in Peru. This study was cross-sectional [...] Read more.
We explored the clinical-stage association of gastric intestinal metaplasia (IM) compared to cases of chronic non-atrophic gastritis (CNAG) and its relationship with virulence genotypes of Helicobacter pylori (H. pylori) clinical isolates from patients with dyspepsia in Peru. This study was cross-sectional and included 158 H. pylori clinical isolates; each isolate corresponded to a different Peruvian patient, genotyped by polymerase chain reaction to detect cagA gene and EPIYA motifs, the vacA gene (alleles s1, s2, i1, i2, d1, d2, m1, m2 and subtypes s1a, s1b and s1c), the iceA gene (alleles 1 and 2), and the babA gene (allele 2). We observed that 38.6% presented with IM and that all clinical isolates were CagA positive. The EPIYA-ABC motif was predominant (68.4%), and we observed a high frequency for the vacA gene alleles s1 (94.9%), m1 (81.7%), i1 (63.9%), and d1 (70.9%). Strains with both iceA alleles were also detected (69.6%) and 52.2% were babA2 positive. In addition, it was observed that the cagA+/vacAs1m1 (PR: 2.42, 1.14 to 5.13, p < 0.05) and cagA+/vacAs1am1 (PR: 1.67, 1.13 to 2.45, p < 0.01) genotypes were associated with IM. Our findings revealed the cagA and vacA risk genotypes predominance, and we provided clinically relevant associations between Peruvian patients with H. pylori infection and IM clinical stage. Full article
(This article belongs to the Section Clinical Research of Cancer)
11 pages, 1155 KiB  
Article
Autophagy-Related Gene ATG7 Polymorphism Could Potentially Serve as a Biomarker of the Progression of Atrophic Gastritis
by Naoyuki Yamaguchi, Takuki Sakaguchi, Miki Taira, Daisuke Fukuda, Ken Ohnita, Tatsuro Hirayama, Kazuo Yashima, Hajime Isomoto and Kazuhiro Tsukamoto
J. Clin. Med. 2024, 13(2), 629; https://doi.org/10.3390/jcm13020629 - 22 Jan 2024
Cited by 4 | Viewed by 2310
Abstract
Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host’s gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1β. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. [...] Read more.
Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host’s gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1β. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. On the other hand, host cells degrade CagA using autophagy systems. However, few studies exist about the single nucleotide polymorphisms (SNPs) in MAP1LC3A, MAP1LC3B, ATG4A, ATG4B, ATG4C, ATG7, and ATG13, which belong to the autophagy-related genes concerning AG. This study aimed to detect biomarkers associated with AG. Herein, H. pylori-positive subjects (n = 200) were divided into the AG (n = 94) and non-AG (n = 106) groups. Thirty tag SNPs were selected from the above seven candidate genes. The SNP frequency between the two groups was analyzed. The frequency of the C/T or T/T genotype at rs4683787 of ATG7 was significantly lower in the AG group than in the non-AG group (p = 0.034, odds ratio = 0.535). Based on multivariate analysis, the C/C genotype of rs4684787 and age were independently associated with gastric mucosal atrophy. This finding helps stratify the patients needing timely endoscopic screening or early eradication of H. pylori. Full article
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15 pages, 5731 KiB  
Article
High Hepcidin Levels Promote Abnormal Iron Metabolism and Ferroptosis in Chronic Atrophic Gastritis
by Yashuo Zhao, Jianing Zhao, Hongyu Ma, Yan Han, Weichao Xu, Jie Wang, Yanru Cai, Xuemei Jia, Qingzhong Jia and Qian Yang
Biomedicines 2023, 11(9), 2338; https://doi.org/10.3390/biomedicines11092338 - 22 Aug 2023
Cited by 25 | Viewed by 3287
Abstract
Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is [...] Read more.
Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. Methods: Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. Results: CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. Conclusion: Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future. Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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12 pages, 929 KiB  
Article
ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis
by Naoyuki Yamaguchi, Takuki Sakaguchi, Hajime Isomoto, Tatsuo Inamine, Haruka Ueda, Daisuke Fukuda, Ken Ohnita, Tsutomu Kanda, Hiroki Kurumi, Kayoko Matsushima, Tatsuro Hirayama, Kazuo Yashima and Kazuhiro Tsukamoto
J. Clin. Med. 2023, 12(16), 5384; https://doi.org/10.3390/jcm12165384 - 19 Aug 2023
Cited by 8 | Viewed by 1841
Abstract
Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On [...] Read more.
Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337–1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required. Full article
(This article belongs to the Special Issue Gastric Cancer: Diagnosis, Treatment and Prevention)
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15 pages, 2573 KiB  
Article
The Translational Impact of Plant-Derived Xeno-miRNA miR-168 in Gastrointestinal Cancers and Preneoplastic Conditions
by Jastin Link, Cosima Thon, Vytenis Petkevicius, Ruta Steponaitiene, Peter Malfertheiner, Juozas Kupcinskas and Alexander Link
Diagnostics 2023, 13(16), 2701; https://doi.org/10.3390/diagnostics13162701 - 18 Aug 2023
Cited by 8 | Viewed by 1852
Abstract
Introduction: Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the [...] Read more.
Introduction: Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the xeno-miRNA miR-168 in the gastric mucosa along the preneoplastic conditions and gastric carcinogenesis. Methods: For a systematic analysis, we included stomach tissues from patients with different pathologies, including normal mucosa (N), chronic non-atrophic (CNAG) and atrophic gastritis (CAG) and intestinal metaplasia (IM) (n = 72), matched non-tumorous (NT) and tumorous (T) gastric cancer (GC) tissues (n = 81), matched colorectal cancer (CRC) tissues (n = 40), and colon mucosa and faeces from controls and IBD patients. Results: miR-168 was reproducibly detectable in all samples studied, with the highest levels in the proximal upper GI and in non-tumorous compared to tumorous tissues in both GC and CRC. There was no difference related to H. pylori positivity or inflammation grade, while higher miR-168 levels were observed in patients with moderate or severe AG/IM or OLGIM3/4. Survival analysis showed only a small, non-significant trend towards worse overall survival for patients with the highest to lowest miR-168 levels, while no differences were related to Lauren‘s classification. Conclusions: Food-derived xeno miRNAs are reproducibly detectable in the gastric and colonic mucosa. Although the clinically relevant function remains to be elucidated, higher levels of miR-168 in patients with moderate and severe IM merit further investigation. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gastrointestinal Inflammation)
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12 pages, 1766 KiB  
Article
Gastric Microbiota Gender Differences in Subjects with Healthy Stomachs and Autoimmune Atrophic Gastritis
by Giulia Pivetta, Ludovica Dottori, Federico Fontana, Sophia Cingolani, Irene Ligato, Emanuele Dilaghi, Christian Milani, Marco Ventura, Marina Borro, Gianluca Esposito, Bruno Annibale and Edith Lahner
Microorganisms 2023, 11(8), 1938; https://doi.org/10.3390/microorganisms11081938 - 29 Jul 2023
Cited by 9 | Viewed by 1921
Abstract
Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia [...] Read more.
Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia (57.7% healthy stomach, 42.3% autoimmune atrophic gastritis). Gastric biopsies were obtained for histopathology and genomic DNA extraction. Gastric microbiota were assessed by sequencing the hypervariable regions of the 16SrRNA gene. The bacterial profile at the phylum level was reported as being in relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for the female and male gender. Results showed that women with healthy stomachs had a higher gastric bacterial abundance and less microbial diversity compared to men. Likely due to hypochlorhydria and the non-acid intragastric environment, autoimmune atrophic gastritis seems to reset gender differences in gastric bacterial abundance and reduce biodiversity in males, showing a greater extent of dysbiosis in terms of reduced biodiversity in men. Differences between gender on taxa frequency at the phylum and genus level in healthy subjects and autoimmune atrophic gastritis were observed. The impact of these findings on the gender-specific natural history of autoimmune atrophic gastritis remains to be elucidated; in any case, gender differences should deserve attention in gastric microbiota studies. Full article
(This article belongs to the Special Issue Gut Microbiota in Disease, Second Edition)
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10 pages, 631 KiB  
Article
Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study
by Malgorzata Osmola, Caroline Hemont, Nicolas Chapelle, Marie-Anne Vibet, David Tougeron, Driffa Moussata, Dominique Lamarque, Edith Bigot-Corbel, Damien Masson, Justine Blin, Maxime Leroy, Regis Josien, Jean-François Mosnier, Jérôme Martin and Tamara Matysiak-Budnik
Diagnostics 2023, 13(9), 1599; https://doi.org/10.3390/diagnostics13091599 - 30 Apr 2023
Cited by 10 | Viewed by 3101
Abstract
Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning [...] Read more.
Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31–0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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