Research trends on nanomaterials in gastric cancer: a bibliometric analysis from 2004 to 2023

Abstract Background Gastric cancer is one of the leading causes of cancer-related deaths worldwide. In recent years, an increasing number of studies aimed at designing and developing nanomaterials for use in diagnosing and treating gastric cancer have been conducted. In this study, we aimed to comprehensively assess the current status and trends of the research on the application of nanomaterials in gastric cancer through a bibliometric analysis. Methods Studies focusing on nanomaterials and gastric cancer were retrieved from the Web of Science Core Collection database and relevant articles were selected for inclusion in the study according to the inclusion criteria. Bibliometric and visual analysis of the included publications was performed using VOSviewer and CiteSpace. Results A total of 793 studies were included. An increase in annual publications was observed from 2004 to 2023. China, Iran and the USA were the dominant countries in this field, accounting for 66.1%, 11.5% and 7.2% of publications, respectively. Shanghai Jiao Tong University and Cui DX were the most influential institution and author, respectively. The International Journal of Nanomedicine was the most prolific journal; Biomaterials was the most cited and most cocited journal. Nanomaterial-related drug delivery and anticancer mechanisms were found to be the most widely researched aspects, and green synthesis and anticancer mechanisms are recent research hotspots. Conclusion In this study, we summarized the characteristics of publications and identified the most influential countries, institutions, authors, journals, hot topics and trends regarding the application of nanomaterials in gastric cancer. Graphical Abstrac

Tel-Aviv Univ.

Figure 1: Composing parts, possibly with sharp features and non-overlapping boundaries, presents challenges to both part alignment and blending. Our field-guided approach (see middle for a visualization of the fields) leads to alignment of parts away from each other and feature-conforming surface blending. The bridging surfaces generated (colored yellow on the right) are piecewise smooth. We present an automatic shape composition method to fuse two shape parts which may not overlap and possibly contain sharp features, a scenario often encountered when modeling man-made objects. At the core of our method is a novel field-guided approach to automatically align two input parts in a feature-conforming manner. The key to our field-guided shape registration is a natural continuation of one part into the ambient field as a means to introduce an overlap with the distant part, which then allows a surface-tofield registration. The ambient vector field we compute is featureconforming; it characterizes a piecewise smooth field which respects and naturally extrapolates the surface features. Once the two parts are aligned, gap filling is carried out by spline interpolation between matching feature curves followed by piecewise smooth least-squares surface reconstruction. We apply our algorithm to obtain feature-conforming shape composition on a variety of models and demonstrate generality of the method with results on parts with or without overlap and with or without salient features

Helicobacter pylori CagA promotes epithelial mesenchymal transition in gastric carcinogenesis via triggering oncogenic YAP pathway

Background Helicobacter pylori (H. pylori) delivers oncoprotein CagA into gastric epithelial cells via the T4SS and drives activation of multiple oncogenic signalling pathways. YAP, a core effector of the Hippo tumour suppressor pathway, is frequently overexpressed in human cancers, suggesting its potential tumor-promoting role. Although CagA is a casual factor in H. pylori induced gastric carcinogenesis, the link between CagA and YAP pathway has not been identified. In this work, we investigated the regulation of oncogenic YAP pathway by H. pylori CagA. Methods Expression of YAP and E-cadherin protein in human gastric biopsies were assessed by immunohistochemistry. H. pylori PMSS1 cagA− isogenic mutant strains were generated. Gastric epithelial cells were co-cultured with H. pylori wild-type cagA+ strains or isogenic mutants and were also treated by recombinant CagA expression. Immunofluorescence was performed for YAP localization. Immunoblot and quantitative PCR were performed for examining levels of YAP, downstream effectors and markers of epithelial-mesenchymal transition. Verteporfin and siRNA silencing were used to inhibit YAP activity. Results YAP is significantly upregulated in human gastric carcinogenesis. We generated PMSS1 CagA isogenic mutant strains with chloramphenicol resistance successfully. Our analysis indicated that H. pylori infection induced YAP and downstream effectors in gastric epithelial cells. Importantly, knockout of CagA in 7.13 and PMSS1 strains reduced the expression of YAP by H. pylori infection. Moreover, Inhibition of YAP suppressed H. pylori infection-induced Epithelial-mesenchymal transition (EMT). Conclusion Our results indicated that H. pylori CagA as a pathogenic protein promotes oncogenic YAP pathway, which contributes to EMT and gastric tumorigenesis. This study provided a novel mechanistic insight into why cagA+ H. pylori infection is associated with a higher risk for the development of gastric cancer. Keywords: H. pyloriCagA; YAP; Epithelial-mesenchymal transition; Gastric carcinogenesi

Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis

Abstract Background A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear. Methods We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured. Results Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG. Conclusion Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF

YAP and β-catenin cooperate to drive H. pylori-induced gastric tumorigenesis

ABSTRACTH. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and β-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and β-catenin pathways in H. pylori-associated gastric tumorigenesis. Immunohistochemical analysis of YAP and β-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and β-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori-induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and β-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and β-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin–gastrin (INS-GAS) mice, whereas silencing of both YAP and β-catenin synergistically inhibited H. pylori-induced cell proliferation and expansion. In addition, YAP was found to directly interact with β-catenin and knockdown of YAP suppressed H. pylori-induced nuclear translocation of β-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and β-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or β-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori-infected mice. Finally, the elevation of gastric YAP was positively correlated with β-catenin expression in human gastric cancer tissues. These findings indicate that YAP and β-catenin synergistically promote H. pylori-induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and β-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis