Search Results (15)

Chronic atrophic gastritis (CAG) is a precancerous gastric condition with limited therapeutic interventions, and the mechanisms underlying the benefits of Coptis chinensis Franch. (CCF) remain insufficiently defined. This study employed an integrated computational strategy to clarify the molecular basis of CCF activity against CAG. Network pharmacology was used to identify potential targets of the major CCF constituents berberine, coptisine, and palmatine, followed by molecular docking, machine learning-based IC₅₀ prediction, and molecular dynamics simulations. Fifty-eight overlapping targets between CCF compounds and CAG-related genes were identified, highlighting SRC, STAT3, MAPK1, and NFKB1 as central nodes enriched in inflammatory and immune pathways, including TNF and MAPK signaling. Docking analyses revealed strong interactions between all three compounds and SRC kinase, and machine learning models predicted IC₅₀ values in the low micromolar range (1.38–1.82 μM). Molecular dynamics simulations further suggest that berberine may stabilize the crucial regulatory regions of SRC, specifically the activation loop. It is hypothesized that this stabilization maintains the inactive conformation of the kinase domain and potentially shields Tyr416 from phosphorylation, thus potentially influencing kinase activation. These findings suggest that CCF may modulate key inflammatory and immune pathways implicated in CAG progression, with SRC emerging as a central node for further investigation. Full article

Background: Gastric cancer (GC) is the fifth most common malignancy worldwide. Early detection of precancerous conditions—atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia—is vital for surveillance. Objectives: To assess the accuracy of single high-quality endoscopy (HQE) in detecting advanced GPCs and to identify risk factors for AG, IM, and dysplasia. Methods: A retrospective review of 442 gastroscopies (2017–2022) at a single center. Endoscopic findings were compared with histology, including OLGA/OLGIM staging, dysplasia, and Helicobacter pylori (H. pylori) status. Results: The study population comprised 319 women (72.17%) and 123 men (27.83%), with a mean age of 59 years (SD: 12.53). AG, as defined by OLGA and OLGIM staging, was identified in 90 patients (20.36%) and 50 patients (11.31%), respectively. A total of 44 cases of de novo gastric dysplasia were observed, while HP infection was confirmed in 37 individuals (8.37%). We observed similar low sensitivity for detection of advanced OLGA (32.5%), OLGIM (40%), and dysplasia (19.7%) with relatively high specificity (~89%). Advanced AG and IM peaked at ages 51–53. Risk factors for advanced OLGIM included male sex (OR 2.26; p < 0.001) and presence of dysplasia (OR 2.09; p = 0.02). Dysplasia was positively associated with AG (OR 2.03; p < 0.001) and IM (OR 2.21; p < 0.001) but inversely associated with a family history of GC (OR 0.44; p < 0.001). Conclusions: A single HQE can help exclude advanced GPCs, but due to low sensitivity, gastric mapping biopsies remain crucial. Males are at increased risk of extensive IM. Family history of GC was linked to lower OLGA/OLGIM stages. Full article

Chronic atrophic gastritis and intestinal metaplasia (IM) are gastric precancerous conditions (GPCs) associated with an increased risk of gastric cancer. Early detection and accurate characterization of GPC are therefore crucial for risk stratification and the implementation of preventive strategies. In the absence of clear mucosal changes observed through white-light imaging (WLI) or virtual chromoendoscopy, endocytoscopy can help unveil the presence of GPC by enabling in vivo assessment of nuclear and cellular structures at ultra-high magnification. Endocytoscopy is typically performed using WLI following dye-based staining of the mucosa. In this case, we demonstrate that combining endocytoscopy with the texture and color enhancement imaging (TXI) mode substantially improves the assessment of the gastric mucosa. In a 61-year-old man undergoing esophagogastroduodenoscopy, WLI showed multifocal erythema in the stomach, without clearly visible lesions on either WLI or narrow-band imaging. Conventional endocytoscopy revealed multiple small spots of IM with characteristic changes in glandular structures, which were even more evident when using the TXI mode. Histological analysis of targeted biopsies confirmed small foci of IM in both the antrum and corpus. The patient was enrolled in a surveillance program because of his clinical background. The combination of endocytoscopy with the TXI mode significantly enhances the delineation of mucosal and cellular architecture, supporting a more accurate optical diagnosis. Full article

Background: Intestinal metaplasia (IM) is a precancerous gastric condition that requires accurate histopathological diagnosis to enable early intervention and cancer prevention. Traditional evaluation of H&E-stained tissue slides can be labor-intensive and prone to interobserver variability. Recent advances in deep learning, particularly transformer-based models, offer promising tools for improving diagnostic accuracy. Methods: We propose ViSwNeXtNet, a novel patch-wise ensemble framework that integrates three transformer-based architectures—ConvNeXt-Tiny, Swin-Tiny, and ViT-Base—for deep feature extraction. Features from each model (12,288 per model) were concatenated into a 36,864-dimensional vector and refined using iterative neighborhood component analysis (INCA) to select the most discriminative 565 features. A quadratic SVM classifier was trained using these selected features. The model was evaluated on two datasets: (1) a custom-collected dataset consisting of 516 intestinal metaplasia cases and 521 control cases, and (2) the public GasHisSDB dataset, which includes 20,160 normal and 13,124 abnormal H&E-stained image patches of size 160 × 160 pixels. Results: On the collected dataset, the proposed method achieved 94.41% accuracy, 94.63% sensitivity, and 94.40% F1 score. On the GasHisSDB dataset, it reached 99.20% accuracy, 99.39% sensitivity, and 99.16% F1 score, outperforming individual backbone models and demonstrating strong generalizability across datasets. Conclusions: ViSwNeXtNet successfully combines local, regional, and global representations of tissue structure through an ensemble of transformer-based models. The addition of INCA-based feature selection significantly enhances classification performance while reducing dimensionality. These findings suggest the method’s potential for integration into clinical pathology workflows. Future work will focus on multiclass classification, multicenter validation, and integration of explainable AI techniques. Full article

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions. Full article

Background: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Chinese medicine (TCM), has demonstrated significant therapeutic effects on CAG and IM; however, its underlying mechanisms remain poorly understood. Methods: This study utilized chromatography-mass spectrometry to identify the major compounds in QLXP. Network pharmacology was used to predict the associated targets of these components. Thermal proteome profiling (TPP) pinpointed the potential binding proteins of QLXP, which were validated by bioinformatic analyses. Bio-layer interferometry (BLI) was used to analyze the interactions between QLXP and its key target proteins, thereby determining their binding components. Molecular docking predicted the binding modes between the components and proteins. Results: ADAM17 was identified as a key binding protein for QLXP. Further investigation revealed that QLXP inhibits the enzymatic activity of ADAM17, thereby reducing the secretion of the pro-inflammatory cytokine TNF-α, contributing to the anti-inflammatory properties of QLXP. BLI confirmed direct and reversible binding interactions between QLXP and ADAM17. Narirutin, isolated from the ADAM17 binding fraction, displayed the highest affinity for QLXP. Conclusions: This study highlights ADAM17 as a key molecular target of QLXP and narirutin as its principal binding component. The integrated approach combining chromatography-mass spectrometry, network pharmacology, TPP, BLI, and molecular docking provides a robust framework for elucidating the mechanisms of action of TCM. Full article

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

Gastric cancer (GC) is a significant healthcare concern, and the identification of high-risk patients is crucial. Indeed, gastric precancerous conditions present significant diagnostic challenges, particularly early intestinal metaplasia (IM) detection. This study developed a deep learning system to assist in IM detection using image patches from gastric corpus examined using virtual chromoendoscopy in a Western country. Utilizing a retrospective dataset of endoscopic images from Sant’Andrea University Hospital of Rome, collected between January 2020 and December 2023, the system extracted 200 × 200 pixel patches, classifying them with a voting scheme. The specificity and sensitivity on the patch test set were 76% and 72%, respectively. The optimization of a learnable voting scheme on a validation set achieved a specificity of 70% and sensitivity of 100% for entire images. Despite data limitations and the absence of pre-trained models, the system shows promising results for preliminary screening in gastric precancerous condition diagnostics, providing an explainable and robust Artificial Intelligence approach. Full article

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

Image-enhanced endoscopy (IEE) plays an important role in the detection and further examination of gastritis and early gastric cancer (EGC). Linked color imaging (LCI) is also useful for detecting and evaluating gastritis, gastric intestinal metaplasia as a pre-cancerous lesion, and EGC. LCI provides a clear excellent endoscopic view of the atrophic border and the demarcation line under various conditions of gastritis. We could recognize gastritis as the lesions of the diffuse redness to purple color area with LCI. On the other hand, EGCs are recognized as the lesions of the orange-red, orange, or orange-white color area in the lesion of the purple color area, which is the surround atrophic mucosa with LCI. With further prospective randomized studies, we will be able to evaluate the diagnosis ability for EGC by IEE, and it will be necessary to evaluate the role of WLI/IEE and the additional effects of the diagnostic ability by adding IEE to WLI in future. Full article

Gastric cancer (GC) is a relevant public health issue as its incidence and mortality rates are growing worldwide. There are recognized carcinogen agents, such as obesity, tobacco, meat, alcohol consumption and some dietary protective factors. Strategies of early diagnosis through population-based surveillance programs have been demonstrated to be effective in lowering the morbidity and mortality related to GC in some countries. Indeed, the detection of early lesions is very important in order to offer minimally invasive treatments. Endoscopic resection is the gold standard for lesions with a low risk of lymph node metastasis, whereas surgical mini-invasive approaches can be considered in early lesions when endoscopy is not curative. This review outlines the role of lifestyle and prevention strategies for GC, in order to reduce the patients’ risk factors, implement the surveillance of precancerous conditions and, therefore, improve the diagnosis of early lesions. Furthermore, we summarize the available treatments for early gastric cancer. Full article

Stomach cancer is the third deadliest type of cancer in the world (0.86 million deaths in 2017). In 2035, a 20% increase will be observed both in incidence and mortality due to demographic effects if no interventions are foreseen. Upper GI endoscopy (UGIE) plays a paramount role in early diagnosis and, therefore, improved survival rates. On the other hand, human and technical factors can contribute to misdiagnosis while performing UGIE. In this scenario, artificial intelligence (AI) has recently shown its potential in compensating for the pitfalls of UGIE, by leveraging deep learning architectures able to efficiently recognize endoscopic patterns from UGIE video data. This work presents a review of the current state-of-the-art algorithms in the application of AI to gastroscopy. It focuses specifically on the threefold tasks of assuring exam completeness (i.e., detecting the presence of blind spots) and assisting in the detection and characterization of clinical findings, both gastric precancerous conditions and neoplastic lesion changes. Early and promising results have already been obtained using well-known deep learning architectures for computer vision, but many algorithmic challenges remain in achieving the vision of AI-assisted UGIE. Future challenges in the roadmap for the effective integration of AI tools within the UGIE clinical practice are discussed, namely the adoption of more robust deep learning architectures and methods able to embed domain knowledge into image/video classifiers as well as the availability of large, annotated datasets. Full article

The adult gastric mucosa is characterised by deep invaginations of the epithelium called glands. These tissue architectural elements are maintained with the contribution of morphogen signals. Morphogens are expressed in specific areas of the tissue, and their diffusion generates gradients in the microenvironment. Cells at different positions in the gland sense a specific combination of signals that instruct them to differentiate, proliferate, regenerate, or migrate. Differentiated cells perform specific functions involved in digestion, such as the production of protective mucus and the secretion of digestive enzymes or gastric acid. Biopsies from gastric precancerous conditions usually display tissue aberrations and change the shape of the glands. Alteration of the morphogen signalling microenvironment is likely to underlie those conditions. Furthermore, genes involved in morphogen signalling pathways are found to be frequently mutated in gastric cancer. We summarise the most recent findings regarding alterations of morphogen signalling during gastric carcinogenesis, and we highlight the new stem cell technologies that are improving our understanding of the regulation of human tissue shape. Full article

Background: Various microorganisms such as bacteria, virus, and fungi can infect humans and cause not just a simple infection but septic conditions, organ dysfunction, and precancerous conditions or cancer involving various organ systems. After the discovery of the microscope, it was easier to discover and study such microorganisms, as in the case of Helicobacter pylori, a pathogen that was seen in the distant era of the nineteenth century but without being recognized as such. It took 100 years to later discover the pathogenesis and the cancer that this bacterium can cause. Since it was discovered, until today, there has been a continuous search for the understanding of its pathogenetic mechanisms, and the therapeutic approach is continuously updated. Methods: We investigated how diagnosis and therapy were dealt with in the past and how researchers sought to understand, exactly, the pathogenetic biomolecular mechanisms of H. pylori, from the genesis of the infection to the current knowledge, with an analysis of carcinogenic mechanisms in the stomach. We have examined the scientific evolution of the knowledge of the disease over these 40 years in the gastroenterological and pharmacological fields. This was possible through a search in the databases of Medline, the WHO website, the Centers for Disease Control and Prevention (CDC) website, PubMed, and Web of Science to analyze the earlier and the latest data regarding H. pylori. Results: With the scientific discoveries over time, thanks to an increasing number of progressions in scientific research in the analysis of the gastric mucosa, the role of Helicobacter pylori in peptic ulcer, carcinogenesis, and in some forms of gastric lymphoma was revealed. Furthermore, over the years, the biomolecular mechanism involvement in some diseases has also been noted (such as cardiovascular ones), which could affect patients positive for H. pylori. Conclusions: Thanks to scientific and technological advances, the role of the bacterium H. pylori in carcinogenesis has been discovered and demonstrated, and new prospective research is currently attempting to investigate the role of other factors in the stomach and other organs. Cancer from H. pylori infection had a high incidence rate compared to various types of cancer, but in recent years, it is improving thanks to the techniques developed in the detection of the bacterium and the evolution of therapies. Thus, although it has become an increasingly treatable disease, there is still continuous ongoing research in the field of treatment for resistance and pharma compliance. Furthermore, in this field, probiotic therapy is considered a valid adjuvant. Full article

The aim of the study was to compare the prevalence and severity of precancerous condition – gastric atrophy and intestinal metaplasia (IM) between Eastern European (Lithuania and Latvia) and Asian (Taiwan) countries in population older than 55 years.
Methods. Patients aged 55 years and older, referred for upper endoscopy due to dyspeptic symptoms, were included in the study. Gastric biopsies were histological investigated according modified Sydney classification. Helicobacter pylori (H. pylori) was detected if any two of three methods (urease test, histology, and serology) were positive.
Results. Overall 322 patients included: 52 from Taiwan (TW), 171 from Latvia (LV) and 99 from Lithuania (LT). There were 227 (70%) females and 95 (30%) males. The mean age of TW patients was significantly lower (61.0±5.8 years), than of LV (68.1±7.3 years) and LT (66.5±7.5 years) patients. H. pylori was established in 224 (69.6%) patients. H. pylori positivity was established in 43 (82.7%) TW patients, in 112 (65.5%) LV patients, and in 69 (69.7%) LT patients (P>0.05). In H. pylori-infected patients, any atrophy either in the corpus or in the antrum of the stomach was detected in 26 (60.5%) TW patients, in 40 (35.7%) LV patients, and in 36 (52.2%) LT patients (between TW and LV patients P<0.005). Severe atrophy (grade 2 or 3) detected in 8 (18.6%) TW patients, in 17 (15.2%) LV patients, and in 18 (26.1%) LT patients (P>0.05). Intestinal metaplasia was detected in 22 (51.2%) TW patients, in 37 (33.0%) LV patients and in 31 (44.9%) LT patients among countries (P>0.05). There were no significant differences in proportions of different degrees of both atrophy and intestinal metaplasia among countries. Intestinal metaplasia was found in 79 (77.5%) of 102 patients with any degree of atrophy and in 11 (9.0%) of 122 patients without atrophy (P<0.0001). We found strong statistically significant correlations between atrophy and intestinal metaplasia in antrum (r=0.89), P<0.01, and corpus (r= 0.73), P<0.01.
Conclusions. The prevalence of H. pylori in the elderly population is still high in LT, LV, and TW. There are no significant differences in prevalence of gastric atrophy and intestinal metaplasia among TW, LT, and LV. There is a strong correlation between gastric atrophy and intestinal metaplasia. Full article