Search Results (854)

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Gastric cancer traditionally affects older adults, and its precursor lesions and risk factors are well-documented in this population. Helicobacter pylori (H. pylori) infection remains highly prevalent in Saudi Arabia and contributes to gastric pathology. However, early-onset gastric cancer (EOGC), diagnosed in individuals aged ≤ 45 years, presents unique challenges and remains poorly understood in young populations. Therefore, we conducted an observational cohort study using a prospective longitudinal design (2021–2024) involving 1823 Saudi nationals aged 18–45 years who underwent zoom high-definition chromoendoscopy to evaluate the prevalence of premalignant gastric lesions (PGLs) and EOGC. We found a high H. pylori prevalence (78.0%) with PGLs in 1.9% of participants and EOGC-adenocarcinoma in 0.7% of patients. All EOGC cases arose from dysplasia, with most PGLs being classified as OLGA/OLGIM stage II/III. Multiple risk factorswere significantly associated with PGLs and EOGC, including H. pylori infection (p = 0.022), increasing age (p < 0.001), a family history of gastric cancer (p < 0.001), poor dietary habits (p < 0.001), obesity (p < 0.001), and smoking (p < 0.001). Additional EOGC risk factors include dage of 36–45 years (p = 0.018), EBV infection (p = 0.016), and diabetes mellitus (p = 0.001). These findings demonstrate the notable presence of PGLs and EOGC in young Saudi adults and emphasize the importance of early detection and risk factor management in this vulnerable population. Full article

Helicobacter pylori, a spiral-shaped bacterium found in the stomach, is associated with various gastrointestinal and systemic health conditions. Effective suppression of H. pylori is therefore critical for managing gastrointestinal diseases. In a search for natural products with anti-H. pylori activity, the extract of Atractylodes macrocephala rhizoma showed significant inhibitory effects. Chromatographic purification of A. macrocephala extract yielded thirteen compounds, which were identified as ten sesquiterpenes and three polyacetylenes by spectroscopic analysis. The sesquiterpene compounds belong to the eudesmane or eudesmane lactone types and exhibited structure-dependent efficacy. The major eudesmane lactone sesquiterpene, atractylenolide I (1), showed strong inhibitory activity comparable to metronidazole, a positive control, and atractylenolide III (3) also showed good efficacy. However, structural modification such as hydroxylation, methylation, or acetylation of the sesquiterpenes led to reduced activity. In contrast, polyacetylene derivatives displayed only mild inhibitory effects. Further evaluation of the active compounds against three H. pylori strains such as 51, 43504, and 26695 showed that atractylenolide I (1) had potent inhibitory effects against all three strains, with MIC₅₀ values of ranging from 27.3 to 48.6 μM and MIC₉₀ values from 45.4 to 87.2 μM. Atractylenolide III (3) exhibited selective activity against strain 51 with MIC₅₀ value of 89.9 μM. Both compounds also exhibited anti-inflammatory activity with IC₉₀ values of 23.3 and 31.1 μM, respectively, although they showed little effect on urease. This is the first report on the anti-H. pylori efficacy of various constituents of A. macrocephala and comparative analysis of inhibitory effects against several strains, which will provide scientific evidence supporting its potential as therapeutic agent for H. pylori-related infection. Full article

Helicobacter pylori infection represents one of the most prevalent and persistent bacterial infections worldwide, closely linked to a spectrum of gastroduodenal diseases, including chronic gastritis, peptic ulceration, and gastric cancer. Recent advances have shed light on the critical role of endogenous lectins, particularly galectins, in modulating host–pathogen interactions within the gastric mucosa. Galectins are β-galactoside-binding proteins with highly conserved structures but diverse biological functions, ranging from regulation of innate and adaptive immunity to modulation of cell signaling, apoptosis, and epithelial integrity. This review provides a comprehensive synthesis of current knowledge on the involvement of key galectin family members—especially Galectin-1, -2, -3, -8, and -9—in the context of H. pylori infection. Their dual roles in enhancing mucosal defense and facilitating bacterial persistence are examined along with their contributions to immune evasion, inflammation, and gastric carcinogenesis. Understanding the interplay between galectins and H. pylori enhances our knowledge of mucosal immunity. This interaction may also reveal potential biomarkers for disease progression and identify novel therapeutic targets. Modulating galectin-mediated pathways could improve outcomes in H. pylori-associated diseases. Full article

Background/Objectives: Tegoprazan (TPZ) is a potassium-competitive acid blocker (P-CAB) used to treat conditions such as gastroesophageal reflux disease, peptic ulcer, and Helicobacter pylori infection. It exists in three solid forms: amorphous, Polymorph A, and Polymorph B. This study investigates the molecular basis of polymorph selection, focusing on conformational bias and solvent-mediated phase transformations (SMPTs). Methods: The conformational energy landscapes of two TPZ tautomers were constructed using relaxed torsion scans with the OPLS4 force field and validated by nuclear Overhauser effect (NOE)-based nuclear magnetic resonance (NMR). Hydrogen-bonded dimers were analyzed using DFT-D. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility, and slurry tests were conducted using methanol, acetone, and water. Kinetic profiles were modeled with the Kolmogorov–Johnson–Mehl–Avrami (KJMA) equation. Results: Polymorph A was thermodynamically stable across all analyses. Both amorphous TPZ and Polymorph B converted to A in a solvent-dependent manner. Methanol induced direct A formation, while acetone showed a B → A transition. Crystallization was guided by solution conformers and hydrogen bonding. Conclusions: TPZ polymorph selection is governed by solution-phase conformational preferences, tautomerism, and solvent-mediated hydrogen bonding. DFT-D and NMR analyses showed that protic solvents favor the direct crystallization of stable Polymorph A, while aprotic solvents promote the transient formation of metastable Polymorph B. Elevated temperatures and humidity accelerate polymorphic transitions. This crystal structure prediction (CSP)-independent strategy offers a practical framework for rational polymorph control and the mitigation of disappearing polymorph risks in tautomeric drugs. Full article

H. pylori infects over half of the global population and is associated with various gastric and extra-gastric diseases. Other species, such as zoonotic non-Helicobacter pylori Helicobacters (NHPHs), have shown similar associations with gastritis and MALT lymphoma and H. pylori-negative cases with gastric disease have been identified, including gastric MALT lymphoma, chronic gastritis, and gastroduodenal ulcers. Accurate identification of these species is of great relevance but remains challenging using conventional diagnostic methods. This cross-sectional study aimed to determine the prevalence of H. pylori and NHPH infections, comparing standard histological protocols with molecular techniques. Between December 2024 and February 2025, 54 adult patients undergoing upper gastrointestinal endoscopy (UGE) with gastric biopsy in three hospitals in Algarve, Portugal were recruited. Endoscopic assessment was performed, and gastric biopsies were collected for histological and molecular analysis. DNA was extracted from antral biopsies and analyzed by conventional PCR to detect H. pylori and NHPH. H. pylori diagnostic techniques were compared, descriptive plus statistical analysis was performed, and p-values < 0.05 were considered to be statistically significant. Fifty-four patients were included in the study, with 51.9% of them presenting symptoms. Endoscopic gastritis was observed in 66.7% of patients, while histological gastritis was present in 88.9%, with statistically significant differences between the two diagnostic techniques (p = 0.004). Helicobacter spp. were identified in 44.4% (24/54) of the patients. H. pylori was detected in 42.6% of the patients by Modified Giemsa stain and in 33.3% by PCR. H. bizzozeronii was found in 35.9% of the patients, with 22.2% showing mixed infections. This study reveals a significant prevalence of Helicobacter spp. in patients from the Algarve region, with both H. pylori and zoonotic H. bizzozeronii detected. This is the first report of H. bizzozeronii DNA detection in gastric biopsies via PCR from patients undergoing UGE in Portugal, highlighting the need to consider NHPH in clinical diagnosis. It is important to include molecular methods in routine diagnostics and the need for broader studies to assess regional and national trends in Helicobacter infections besides H. pylori. Full article

Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. The bacterium leverages several unique virulence factors to its advantage in order to colonize the human host. Among these, T4SS-delivered cytotoxin-associated gene A (CagA) has the most well-established links to severe forms of disease. To explore the effect of lactobacilli in disrupting CagA functions within host cells, we expressed HA-tagged humanized cagA in the human gastric epithelial AGS cell line and studied both the phosphorylation levels of CagA and its downstream binding partners. We found that gastric-specific Lactobacillus gasseri Kx110 A1 suppressed the phosphorylation of CagA and inhibited phosphorylation-dependent downstream signaling, resulting in the suppression of CagA-induced cell elongation of AGS cells, commonly known as the hummingbird phenotype. Surprisingly, phosphorylation-independent signaling was unaffected by L. gasseri. Furthermore, our confocal microscopy analysis revealed that CagA was mislocalized to the cytoplasm, suggesting that L. gasseri interferes with its membrane localization and thereby hinders its phosphorylation. Live L. gasseri that had direct contact with host cells was found to be necessary to suppress the hummingbird phenotype. In summary, the data suggest that a L. gasseri strain can inhibit CagA phosphorylation and suppress cell elongation. Full article

Background: Helicobacter pylori infection is widely prevalent across the globe and is a major etiological agent of various gastric pathologies. This bacterium colonizes the human stomach, where it induces a range of mucosal abnormalities observable upon clinical examination. Accordingly, the present study aimed to assess the prevalence and clinical implications of H. pylori infection among patients undergoing endoscopic evaluation. Method: A cross-sectional study was conducted from January to May 2019 at endoscopy service-providing health institutions. Sociodemographic and clinical data were collected. Gastric biopsies were collected during endoscopic procedures and immediately inoculated into brain–heart infusion broth and plated out. Then, phenotypic bacterial identification was done. The collected data have been analyzed using SPSS version 23. A logistic regression model was used for association determination. Result: Among the 135 individuals enrolled in the study, 59.3% are male, and 40.7% are female, with a mean age of 45 years. H. pylori is isolated in 17.8% of participants (24/135). Notably, the majority of these isolates 71% (17/24) are from male participants, while 29% (7/24) are from females. A statistically significant association is identified between H. pylori infection and both high salt intake [AOR = 3.3; 95% CI: 1.5–10.8; p = 0.04] and the presence of duodenal ulcers [AOR = 3.8; 95% CI: 1.2–11.9; p = 0.02]. The highest prevalence of H. pylori is observed among patients diagnosed with atrophic pangastritis. Conclusions: The prevalence of H. pylori among the study participants is comparatively low. However, a significant association was observed between H. pylori infection and both high dietary salt intake and the presence of duodenal ulcers. Full article

Traditionally, Helicobacter pylori (HP) gastritis has been diagnosed by pathologists through the examination of gastric biopsies using optical microscopy with standard hematoxylin and eosin (H&E) staining. However, with the adoption of digital pathology, the identification of HP faces certain limitations, particularly due to insufficient resolution in some scanned images. Moreover, interobserver variability has been well documented in the traditional diagnostic approach, which may further complicate consistent interpretation. In this context, deep convolutional neural network (DCNN) models are showing promising results in the automated detection of this infection in whole-slide images (WSIs). The aim of the present article is to detect the presence of HP infection from our own institutional dataset of histopathological gastric biopsy samples using different pretrained and recognized DCNN and AutoML approaches. The dataset comprises 100 H&E-stained WSIs of gastric biopsies. HP infection was confirmed previously using immunohistochemical confirmation. A total of 45,795 patches were selected for model development. InceptionV3, Resnet50, and VGG16 achieved AUC (area under the curve) values of 1. However, InceptionV3 showed superior metrics such as accuracy (97%), recall (100%), F1 score (97%), and MCC (93%). BoostedNet and AutoKeras achieved accuracy, precision, recall, specificity, and F1 scores less than 85%. The InceptionV3 model was used for external validation, and the predictions across all patches yielded a global accuracy of 78%. In conclusion, DCNN models showed stronger potential for diagnosing HP in gastric biopsies compared with the auto ML approach. However, due to variability across pathology applications, no single model is universally optimal. A problem-specific approach is essential. With growing WSI adoption, DL can improve diagnostic accuracy, reduce variability, and streamline pathology workflows using automation. Full article

Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, immune evasion, and persistent inflammation. A major challenge in vaccine development is the bacterium’s ability to manipulate both innate and adaptive immune responses, resulting in limited natural clearance and long-term persistence. This review synthesizes H. pylori pathogenesis and host immune dynamics, highlighting their implications for vaccine design. By elucidating the molecular and cellular mechanisms underlying host–pathogen interactions, we explore how these insights inform antigen selection, adjuvant optimization, and delivery strategies. By integrating basic science with translational objectives, this review aims to support the development of an effective H. pylori vaccine, addressing global health needs, particularly in regions with a high infection burden and limited access to treatment. Full article

Background and Objectives: Chronic mucosal infection with Helicobacter pylori (H. pylori) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic and inflammatory conditions in the gastric mucosa. This study aims to evaluate the potential diagnostic value of hypoxia-inducible factors HIF-1α and HIF-2α, along with transmembrane prolyl 4-hydroxylase (P4H-TM), as biomarkers in H. pylori-positive patients. Additionally, the study investigates the association between these markers and alterations in lipid profiles, as well as their involvement in the molecular mechanisms underlying gastric conditions like gastritis, particularly in the context of H. pylori infection. Materials and Methods: This study was conducted at Istanbul Avcılar Murat Kölük State Hospital’s General Surgery Outpatient Clinic. A total of 60 participants were included: 40 patients diagnosed with chronic gastritis (20 H. pylori-positive and 20 H. pylori-negative) and 20 healthy controls confirmed negative by 13C-urea breath test. Blood samples were collected for ELISA analysis of HIF-1α, HIF-2α, and P4H-TM levels. Additionally, lipid profiles were measured and compared among the groups. Results: No significant differences were found among the groups in terms of demographic factors such as age, sex, or body mass index (BMI). However, significant variations were observed in the levels of HIF-1α, HIF-2α, and P4H-TM across all groups (p < 0.001 for each marker). These markers were substantially elevated in the H. pylori-positive gastritis group compared to both the H. pylori-negative and healthy control groups. Receiver Operating Characteristic (ROC) curve analysis revealed that all evaluated markers exhibited strong diagnostic accuracy in differentiating H. pylori-positive individuals from other groups. HIF-1α (AUC: 0.983) and HIF-2α (AUC: 0.981) both achieved 100% sensitivity with specificities of 93.3% and 91.1%, respectively. P4H-TM showed an AUC of 0.927, with 85% sensitivity and 95.6% specificity. Conclusions: These findings indicate that HIF-1α, HIF-2α, and P4H-TM may serve as effective biomarkers for diagnosing H. pylori-positive patients and may be linked to changes in lipid metabolism. The elevated expression of these markers in response to H. pylori infection highlights their potential roles in the inflammatory and hypoxic pathways that contribute to the pathogenesis of gastric diseases such as gastritis. Full article

Aging is associated with structural and functional changes in the gastrointestinal tract; however, its impact on gastric secretion remains unclear. This scoping review examines whether gastric secretion declines with age and explores its clinical implications. Following the PRISMA guidelines, PubMed, Web of Science, Embase, and Google Scholar were systematically searched from inception to December 2024. Fifteen studies (both animal and human) met the inclusion criteria: they were written in English, directly relevant to aging and gastric secretion, and had a clearly stated methodology. Evidence strength was assessed using the GRADE framework, revealing predominantly low to moderate certainty due to small sample sizes and observational study designs. Animal studies have demonstrated reduced acid secretion in older rats, which is attributed to mucosal atrophy and diminished responsiveness to gastrin. Recent human studies suggest that aging does not directly reduce acid output, as reduced acid secretion may result from a higher prevalence of atrophic gastritis, Helicobacter pylori infection, and the widespread use of proton pump inhibitors. Antisecretory therapy may lack benefits in older adult patients with hypochlorhydria/achlorhydria and increase the risk of adverse effects. Pepsin output declines with aging due to reduced chief cell function, although its clinical impact on digestion is unclear. Since intrinsic factor secretion far exceeds the amount necessary for its physiological function, even low amounts seem to be sufficient to prevent cobalamin deficiency. Age-related decline in gastric secretion is mostly attributed to age-associated disorders; however, impairment of secretory function in older people is frequent. Future research should prioritise longitudinal studies, larger cohorts, and histology-stratified analysis. Full article

Helicobacter pylori (H. pylori) infection is a leading cause of gastritis, peptic ulcers, and gastric cancer, affecting more than half of the global population. Its persistence in the acidic gastric environment and its ability to evade host immunity present major treatment challenges. Although antibiotics remain the standard therapy, rising antimicrobial resistance has reduced treatment efficacy, prompting the search for alternative and adjunct approaches. Emerging therapies include probiotics, antimicrobial peptides (AMPs), and plant-derived compounds, which target H. pylori through membrane disruption, immunomodulation, or direct antimicrobial activity. Novel drug delivery systems and microbiota-sparing interventions are also being investigated. Additionally, vaccine development offers a promising strategy for long-term protection, though challenges related to antigenic variability and host-specific responses remain. Despite these advances, treatment variability and the limited clinical validation of alternatives hinder progress. A multifaceted approach integrating microbiome research, host–pathogen interactions, and new therapeutic agents is essential for future success. Full article

Gastric cancer (GC) remains a major global health burden, with high morbidity and mortality rates, particularly in regions with prevalent Helicobacter pylori (H. pylori) infection. While H. pylori has long been recognized as a primary carcinogenic agent, recent research has underscored the broader contribution of the gastric microbiota to gastric carcinogenesis. Alterations in the microbial community, or dysbiosis, contribute to chronic inflammation, immune modulation, and epithelial transformation through a range of mechanisms, including disruption of mucosal integrity, activation of oncogenic signaling pathways (e.g., PI3K/Akt, NF-κB, STAT3), and epigenetic alterations. Furthermore, microbial metabolites, such as short-chain fatty acids, secondary bile acids, and lactate, play dual roles in either promoting or suppressing tumorigenesis. Oral and gut-derived microbes, translocated to the gastric niche, have been implicated in reshaping the gastric microenvironment and exacerbating disease progression. The composition of the microbiota also influences responses to cancer immunotherapy, suggesting that microbial profiles can serve as both prognostic biomarkers and therapeutic targets. Emerging strategies, such as probiotics, dietary interventions, and fecal microbiota transplantation (FMT), offer new avenues for restoring microbial balance and enhancing therapy response. This review synthesizes current knowledge on the complex interplay between microbiota and gastric cancer development and emphasizes the potential of microbiome modulation in both preventive and therapeutic frameworks. Full article

Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, with approximately one million new cases diagnosed annually. While Helicobacter pylori infection remains a primary etiological factor, mounting evidence implicates obesity and lipid metabolic dysregulation, particularly in hypercholesterolemia, as emerging drivers of gastric tumorigenesis. This study investigates the molecular intersections between gastric cancer, obesity, and hypercholesterolemia through a comprehensive multi-omics and systems biology approach. Methods: We conducted integrative transcriptomic analysis of gastric adenocarcinoma using The Cancer Genome Atlas (TCGA) RNA-sequencing dataset (n = 623, 8863 genes), matched with standardized clinical metadata (n = 413). Differential gene expression between survival groups was assessed using Welch’s t-test with Benjamini–Hochberg correction (FDR < 0.05, |log₂FC| ≥ 1). High-confidence gene sets for obesity (n = 128) and hypercholesterolemia (n = 97) were curated from the OMIM, STRING (confidence ≥ 0.7), and KEGG databases using hierarchical evidence-based prioritization. Overlapping gene signatures were identified, followed by pathway enrichment via Enrichr (KEGG 2021 Human) and protein–protein interaction (PPI) analysis using STRING v11.5 and Cytoscape v3.9.0. CD36’s prognostic value was evaluated via Kaplan–Meier and log-rank testing alongside clinicopathological correlations. Results: We identified 36 genes shared between obesity and gastric cancer, and 31 genes shared between hypercholesterolemia and gastric cancer. CD36 emerged as the only gene intersecting all three conditions, marking it as a unique molecular integrator. Enrichment analyses implicated dysregulated fatty acid uptake, adipocytokine signaling, cholesterol metabolism, and NF-κB-mediated inflammation as key pathways. Elevated CD36 expression was significantly correlated with higher tumor stage (p = 0.016), reduced overall survival (p = 0.001), and race-specific expression differences (p = 0.007). No sex-based differences in CD36 expression or survival were observed. Conclusions: CD36 is a central metabolic–oncogenic node linking obesity, hypercholesterolemia, and gastric cancer. It functions as both a mechanistic driver of tumor progression and a clinically actionable biomarker, particularly in metabolically comorbid patients. These findings provide a rationale for targeting CD36-driven pathways as part of a precision oncology strategy and highlight the need to incorporate metabolic profiling into gastric cancer risk assessment and treatment paradigms. Full article