Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori ...Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.展开更多
Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer,while gastric organoid technology,especially region-specific modeling,provides a mor...Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer,while gastric organoid technology,especially region-specific modeling,provides a more precise in vitro platform for studying this carcinogenic mechanism.Helicobacter pylori activates carcinogenic signaling pathways through virulence factors,inducing DNA damage,epigenetic dysregulation,and immune microenvironment imbalance,driving inflammation-cancer conversion.Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions,gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion.The immune suppression,metabolic reprogramming,and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammationcarcinogenesis transformation.The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis,and its future integration with single-cell omics,real-time imaging technologies,and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies.These advances position gastric organoids as pivotal tools for clinical translation,enabling personalized risk stratification,early intervention targeting precancerous transitions,and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.展开更多
BACKGROUND Spasmolytic polypeptide-expressing metaplasia(SPEM)is a potential preneoplastic lesion.AIM To elucidate the microRNA(miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules(YWXY)in SPEM l...BACKGROUND Spasmolytic polypeptide-expressing metaplasia(SPEM)is a potential preneoplastic lesion.AIM To elucidate the microRNA(miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules(YWXY)in SPEM lesions.METHODS Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent.YWXY was administered to the mice with induced SPEM by tamoxifen,and the gastric mucosa was harvested on the tenth day of the experiment.Then immunohistochemistry and immunofluorescence were performed to validate the SPEM,lesions and the potential mechanism was investigated.RNA transcripts were detected with reverse transcriptionquantitative polymerase chain reaction.RESULTS The expression of miR-7 was downregulated in the SPEM lesions,and expression of trefoil factor 2(TFF2)and clusterin was high in the human gastric mucosa.In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67.Simultaneously,YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction,indicating its potential mechanism of targeting miR-7 by mediating TFF2.The expression of vascular endothelial growth factor-βand gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions,speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-βand gastric intrinsic factor.CONCLUSION miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa.YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.展开更多
The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer(GC)development.Chinese medicine(CM)exhibits unique advantages and holds significant promise in ...The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer(GC)development.Chinese medicine(CM)exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa.This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation(GMICT),with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia(SPEM).Moreover,it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC.Furthermore,the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions,and innovative studies related to CM are presented.We offer a highly succinct yet optimistic outlook on future developmental trends.This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM.It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.展开更多
基金Supported by the Guangdong Basic and Applied Basic Research Foundation,No.2020A1515110947the National Natural Science Foundation of China,No.82104747+1 种基金the Scientific Research Project of Guangdong Bureau of Traditional Chinese Medicine,No.20231303the Guangdong Provincial Key Research and Development Plan,No.2020B1111100011.
文摘Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.
基金Supported by National Traditional Chinese Medicine Advantageous Specialty Project of National Administration of Traditional Chinese MedicineShuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304.
文摘Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer,while gastric organoid technology,especially region-specific modeling,provides a more precise in vitro platform for studying this carcinogenic mechanism.Helicobacter pylori activates carcinogenic signaling pathways through virulence factors,inducing DNA damage,epigenetic dysregulation,and immune microenvironment imbalance,driving inflammation-cancer conversion.Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions,gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion.The immune suppression,metabolic reprogramming,and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammationcarcinogenesis transformation.The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis,and its future integration with single-cell omics,real-time imaging technologies,and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies.These advances position gastric organoids as pivotal tools for clinical translation,enabling personalized risk stratification,early intervention targeting precancerous transitions,and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.
基金Supported by National Natural Science Foundation of China,No.81904175Natural Science Foundation of Chongqing,China,No.cstc2018jcyjAX0756Chongqing Health Planning Commission Project,No.ZY201802063 and No.2019ZY013111.
文摘BACKGROUND Spasmolytic polypeptide-expressing metaplasia(SPEM)is a potential preneoplastic lesion.AIM To elucidate the microRNA(miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules(YWXY)in SPEM lesions.METHODS Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent.YWXY was administered to the mice with induced SPEM by tamoxifen,and the gastric mucosa was harvested on the tenth day of the experiment.Then immunohistochemistry and immunofluorescence were performed to validate the SPEM,lesions and the potential mechanism was investigated.RNA transcripts were detected with reverse transcriptionquantitative polymerase chain reaction.RESULTS The expression of miR-7 was downregulated in the SPEM lesions,and expression of trefoil factor 2(TFF2)and clusterin was high in the human gastric mucosa.In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67.Simultaneously,YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction,indicating its potential mechanism of targeting miR-7 by mediating TFF2.The expression of vascular endothelial growth factor-βand gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions,speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-βand gastric intrinsic factor.CONCLUSION miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa.YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.
基金Supported by the National Natural Science Foundation of China(No.82274511)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021A01004)+1 种基金the China Postdoctoral Science Foundation General Project(No.2021M693541)China Postdoctoral Science Foundation Special Project(No.2022T150731)。
文摘The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer(GC)development.Chinese medicine(CM)exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa.This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation(GMICT),with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia(SPEM).Moreover,it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC.Furthermore,the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions,and innovative studies related to CM are presented.We offer a highly succinct yet optimistic outlook on future developmental trends.This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM.It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.
