Intestinal metaplasia key molecules and UPP1 activation via Helicobacter pylori /NF-kB: drivers of malignant progression in gastric cancer DOI Creative Commons
Xuyu Chen,

Ben‐Gang Zhou,

Siying Wang

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Дек. 18, 2024

Gastric cancer (GC) remains a significant global health challenge due to its high morbidity and mortality rates. The development of GC is multi-hit process the exploration precancerous lesions crucial. To elucidate molecular cellular dynamics underlying gastric carcinogenesis, we conducted an integrative single-cell RNA sequencing analysis 26,028 high-quality cells from antral mucosa biopsies across various stages, including non-atrophic gastritis, chronic atrophic intestinal metaplasia, early cancer. By constructing detailed atlas, identified distinct epithelial cell subpopulations their corresponding signatures. We focused on biological link between cells. Notably, observed that gland mucous acquired intestinal-like stem phenotype during with MUC6, MUC2 OLFM4 emerging as specific markers for unique endocrine in malignant lesions. Additionally, our highlighted UPP1 key oncogene, expression progressively increasing normal upregulation was shown promote proliferation migration, implicating it oncogenic process. Further, explored impact Helicobacter pylori infection gene expression, revealing upregulates via NF-κB pathway. Our cell-cell communication underscored role Macrophage migration inhibitory factor pathway tumor microenvironment, contributing progression. Various molecules involved along pathway, collectively illustrate multifaceted nature complexity evolution, highlighting cumulative impacts drive tumorigenesis.

Язык: Английский

Organoid models: applications and research advances in colorectal cancer DOI Creative Commons

Yijie Wu,

Sha Yu,

Xingpo Guo

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 7, 2025

This review summarizes the applications and research progress of organoid models in colorectal cancer research. First, high incidence mortality rates are introduced, emphasizing importance organoids as a model. Second, this provides detailed introduction to concept, biological properties, organoids, including their strengths mimicking structural functional aspects organs. article further analyzes adult stem cell-derived pluripotent discusses advancements for basic research, drug development, personalized treatment evaluation prediction, regenerative medicine. Finally, prospects applying technology its significant value improving patient survival rates. In conclusion, systematically explains highlighting tremendous potential promising

Язык: Английский

Процитировано

0
SMYD4 promotes MYH9 ubiquitination through lysine monomethylation modification to inhibit breast cancer progression DOI Creative Commons
Junping Yang, Junming Cao, Rui Sun

и другие.

Breast Cancer Research, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

0
Promoting the transition from pyroptosis to apoptosis in endothelial cells: a novel approach to alleviate methylglyoxal-induced vascular damage DOI Creative Commons

Ruqiang Yuan,

Hu Xu, Mingqi Wang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 10, 2025

Methylglyoxal (MGO)-induced cell death in vascular endothelial cells (VECs) plays a critical role the progression of diabetic complications (DVCs). Previous studies have shown that MGO can induce inflammatory pyroptosis, leading to VEC damage. However, underlying mechanism remains unclear, and effective interventions are yet be developed. Human umbilical vein (HUVECs) were used for vitro experiments. Cell modes assessed through morphological observations. Mechanistic investigations performed using immunofluorescence, flow cytometry, Western blotting, ELISA. Inhibitors adenoviruses employed validate mechanisms. Vascular organoids conjunction with AngioTool plug-in assays evaluate damage angiogenic capacity. Mouse blood pressure was measured tail-cuff method, morphology examined hematoxylin eosin (H&E) staining as well immunofluorescence staining. Data analyzed GraphPad Prism software. Our study revealed induces pyroptosis VECs via Caspase3/gasdermin E (GSDME) pathway. Furthermore, saponin monomer 13 dwarf lilyturf tuber (DT-13), inhibited MGO-induced promoted generation apoptotic bodies, facilitating transition from apoptosis. Mechanistically, DT-13 suppressed Caspase3-mediated cleavage GSDME non-muscle myosin heavy chain IIA (NMMHC IIA), while increasing phosphorylation light 2 (MLC2), which facilitated body formation. Additionally, mitigate damage, inhibit angiogenesis, reduce remodeling, alleviate hypertension. This uncovers novel highlighting therapeutic significance apoptosis this process. These findings suggest potential strategies managing angiopathy. emerges promising compound intervention, offering new possibilities clinical applications.

Язык: Английский

Процитировано

0
A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors DOI Creative Commons
Robert J. Huang, Ignacio A. Wichmann, Andrew Su

и другие.

npj Precision Oncology, Год журнала: 2025, Номер 9(1)

Опубликована: Фев. 25, 2025

Abstract Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for compared lower-risk metaplasia. The biological differences between high- and low-risk lesions have been incompletely explored. In this study, we use several clinical cohorts characterize the microenvironment relative using bulk, spatial, single-cell gene expression assays. We identified a 26-gene panel which is associated lesions, localizes metaplastic glands on histopathology, expressed in aberrant mature immature cells not normally present healthy stomach. This signature suggests an important role lineages promoting carcinogenesis microenvironment. These findings help inform future biomarker development strategies prevention.

Язык: Английский

Процитировано

0
Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia DOI Creative Commons
Gøran Andersen, Aleksandr Ianevski,

Mathilde Resell

и другие.

npj Systems Biology and Applications, Год журнала: 2024, Номер 10(1)

Опубликована: Ноя. 4, 2024

Abstract Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to adenocarcinoma (GA), i.e., GA-related GIM, could provide valuable insights into identifying patients increased risk for GA. The aim of this study was utilize multi-bioinformatics reveal potential biomarkers GIM and predict drug repurposing GA prevention in patients. included gene expression matrix (GEM) by microarray (MGE), ScType (a fully automated ultra-fast cell-type identification based solely on a given scRNA-seq data), Ingenuity Pathway Analysis, PageRank centrality, GO MSigDB enrichments, Cytoscape, Human Protein Atlas molecular docking analysis combination immunohistochemistry. To identify paired surgical biopsies were collected 16 GIM-GA who underwent gastrectomy, yielding 64 samples (4 per stomach x patients) MGE. Co-analysis performed including scRNAseq immunohistochemistry datasets endoscopic 37 results present showed GEM individual patients, genes (such as RBP2 CD44), signaling pathways, network molecules, pathways key topological nodes. Accordingly, treatment targets repurposed drugs identified epidermal growth factor receptor, proto-oncogene tyrosine-protein kinase Src, paxillin, transcription Jun, breast cancer type 1 susceptibility protein, cellular tumor antigen p53, mouse double minute 2, CD44.

Язык: Английский

Процитировано

2
Refining the diagnostic utility of OLFM4 in gastric cancer precursors: a call for rigorous methodologies DOI Creative Commons
Tai Zhang, Xudong Tang

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 8, 2024

This commentary offers a thoughtful discussion of the study by Wei et al. published in journal on role Olfactomedin 4 (OLFM4) incomplete intestinal metaplasia, gastric precancerous condition. The original paper introduces OLFM4 as novel biomarker with potential enhanced diagnostic efficacy compared to established markers. However, several methodological and interpretive considerations are noted. histopathological findings could be refined using higher magnification better elucidate cellular localization OLFM4. Including high-resolution images for key stainings would enhance study's robustness expression profiling. statistical approach strengthened employing more rigorous, quantitative methodologies. Additionally, integrating immunofluorescence double-staining may improve reliability results. Discrepancies immunohistochemical signals across datasets suggest need further investigation into tissue section representativeness. Clarifying term "precancerous lesions carcinoma cells" align widely accepted definitions clarity. choice GES-1 cell model treated MNNG reconsidered favor models such organoids, air-liquid interface models, cancer-specific lines. vivo MNNG-alcohol combination might require additional empirical support, given limited conflicting literature this approach, ensure an accurate portrayal IM pathogenesis. concludes call stringent standardized methodologies research clinical applicability studies, particularly context cancer detection intervention.

Язык: Английский

Процитировано

0
Intestinal metaplasia key molecules and UPP1 activation via Helicobacter pylori /NF-kB: drivers of malignant progression in gastric cancer DOI Creative Commons
Xuyu Chen,

Ben‐Gang Zhou,

Siying Wang

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Дек. 18, 2024

Gastric cancer (GC) remains a significant global health challenge due to its high morbidity and mortality rates. The development of GC is multi-hit process the exploration precancerous lesions crucial. To elucidate molecular cellular dynamics underlying gastric carcinogenesis, we conducted an integrative single-cell RNA sequencing analysis 26,028 high-quality cells from antral mucosa biopsies across various stages, including non-atrophic gastritis, chronic atrophic intestinal metaplasia, early cancer. By constructing detailed atlas, identified distinct epithelial cell subpopulations their corresponding signatures. We focused on biological link between cells. Notably, observed that gland mucous acquired intestinal-like stem phenotype during with MUC6, MUC2 OLFM4 emerging as specific markers for unique endocrine in malignant lesions. Additionally, our highlighted UPP1 key oncogene, expression progressively increasing normal upregulation was shown promote proliferation migration, implicating it oncogenic process. Further, explored impact Helicobacter pylori infection gene expression, revealing upregulates via NF-κB pathway. Our cell-cell communication underscored role Macrophage migration inhibitory factor pathway tumor microenvironment, contributing progression. Various molecules involved along pathway, collectively illustrate multifaceted nature complexity evolution, highlighting cumulative impacts drive tumorigenesis.

Язык: Английский

Процитировано

0