OBJECTIVE: To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG). METHODS: Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083). RESULTS: m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5). CONCLUSION These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.
Humans ; RNA, Messenger/metabolism* ; Adenocarcinoma/pathology* ; Esophagogastric Junction/metabolism* ; Esophageal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Middle Aged ; DNA Methylation ; Methyltransferases/metabolism* ; Stomach Neoplasms/genetics*

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

OBJECTIVES: To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells. METHODS: The differentially expressed RNAs in ESCC were identified using the GSE149612 dataset from the GEO database. PCR was used to detect LINC00261 expression levels in clinical ESCC and normal esophageal tissue samples and in multiple ESCC cell lines and normal esophageal epithelial cells (HEEC). In ESCC cells, the effects of overexpression of LINC00261 on cell proliferation, invasion, metastasis and apoptosis were analyzed using CCK-8 assay, clone formation assay, Transwell assay and flow cytometry. The potential targets of LINC00261 were predicted using bioinformatics tools including ENCORI and verified using dual-luciferase reporter assay and Western blotting. The effects of LINC00261 overexpression on ESCC were confirmed in a nude mouse model bearing ESCC xenograft. RESULTS: Analysis of the GSE149612 dataset revealed significantly lower LINC00261 expression in ESCC tissues and cell lines. In cultured ESCC cells, LINC00261 overexpression markedly suppressed cell proliferation, invasion, and metastasis and promoted cell apoptosis. Dual-luciferase reporter assays confirmed that LINC00261 targets the miR-23a-3p/ZNF292 axis. In the tumor-bearing mouse model, LINC00261 overexpression significantly inhibited ESCC xenograft proliferation and metastasis. CONCLUSIONS LINC00261 suppresses ESCC progression by targeting the miR-23a-3p/ZNF292 axis, suggesting a potential therapeutic strategy for ESCC treatment.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Esophageal Neoplasms/genetics* ; Animals ; Esophageal Squamous Cell Carcinoma ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Cell Line, Tumor ; Neoplasm Invasiveness ; Mice ; Carcinoma, Squamous Cell/genetics* ; Apoptosis ; Gene Expression Regulation, Neoplastic ; Neoplasm Metastasis

OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

OBJECTIVE: To explore the research history, hotspots and development trends of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease（GERD）based on knowledge graph technology, and to provide references for clinical and basic research in this field. METHODS: The literature of acupuncture and moxibustion for gastroesophageal reflux disease was searched from the CNKI, Wanfang, VIP and SinoMed, from the establishment of the databases to December 31th, 2023. CiteSpace 6.2.R6 Advance was used to draw the knowledge graph of authors, institutions, keywords and other elements, and then perform the visual analysis. RESULTS: A total of 341 articles were included, with the number of publications showing an upward trend and the research types continually diversifying. A total of 832 authors and 308 institutions were analyzed, with XIE Sheng from the First Affiliated Hospital of Guangxi University of CM and BAI Xinghua from the Beijing University of CM as representative figures, forming core research teams. However, there was a lack of close collaboration between institutions, and no significant cross-regional research networks had been formed. A total of 192 keywords were included, forming 8 cluster labels, which mainly included 4 categories：treatment methods, disease types, TCM syndrome types, and literature types. The burst analysis showed that the methods of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease had gradually become more integrated, the treatment methods had transitioned from simple acupuncture therapy to combined therapies with proton pump inhibitors or TCM decoctions, the disease types had become more refined, the focus of mechanism research had shifted from lower esophageal sphincter pressure and esophageal motility to changes in gastrointestinal hormone levels, and the research hotspots had gradually shifted from improving clinical symptoms to considering both mental and psychological states. Twenty-three high-frequency acupoints were obtained, forming 8 clusters of "acupuncture techniques-acupoints" for the treatment of gastroesophageal reflux disease with acupuncture and moxibustion, indicating a gradual enrichment of acupuncture and acupoint treatment protocols. CONCLUSION The research on acupuncture and moxibustion in the treatment of gastroesophageal reflux disease has gradually deepened, in the future, the cooperation among research teams should be strengthened, the quality of clinical research should be improved, more multi-dimensional mechanism research and horizontal comparative research of different acupuncture and moxibustion methods should be made, to provide a basis for clinical promotion and deeper exploration.
Humans ; Moxibustion/trends* ; Gastroesophageal Reflux/therapy* ; Acupuncture Therapy/trends*

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

Esophageal squamous cell carcinoma (ESCC) poses a significant global health challenge, necessitating early detection, timely diagnosis, and prompt treatment to improve patient outcomes. Endoscopic examination plays a pivotal role in this regard. However, despite the availability of various endoscopic techniques, certain limitations can result in missed or misdiagnosed ESCCs. Currently, artificial intelligence (AI)-assisted endoscopic diagnosis has made significant strides in addressing these limitations and improving the diagnosis of ESCC and precancerous lesions. In this review, we provide an overview of the current state of AI applications for endoscopic diagnosis of ESCC and precancerous lesions in aspects including lesion characterization, margin delineation, invasion depth estimation, and microvascular subtype classification. Furthermore, we offer insights into the future direction of this field, highlighting potential advancements that can lead to more accurate diagnoses and ultimately better prognoses for patients.
Humans ; Artificial Intelligence ; Esophageal Squamous Cell Carcinoma/diagnosis* ; Esophageal Neoplasms/diagnosis* ; Precancerous Conditions/diagnosis*

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive tract that poses a significant threat to human health, with an incidence rate that continues to rise globally. Increasing research highlights the crucial role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating ferroptosis and contributing to the malignant progression of ESCC. These ncRNAs influence the proliferation, apoptosis, and invasion capabilities of ESCC cells by modulating iron metabolism and redox balance. miRNAs can regulate cellular iron accumulation and oxidative stress by targeting ferroptosis-related genes; lncRNAs may indirectly affect iron metabolic pathways by competitively binding to miRNAs; circRNAs, through a sponge effect, may regulate the activity of miRNAs. This review systematically summarizes the mechanisms of ncRNAs-mediated regulation of ferroptosis in ESCC, focusing on molecular mechanisms, regulatory networks, and their specific roles in the ferroptosis process. Additionally, the potential of ncRNAs in ESCC diagnosis, prognosis assessment, and therapeutic intervention is discussed, aiming to provide new insights and targets for ferroptosis-based tumor therapy.
Ferroptosis/genetics* ; Humans ; Esophageal Neoplasms/physiopathology* ; Esophageal Squamous Cell Carcinoma ; MicroRNAs/physiology* ; RNA, Long Noncoding/physiology* ; RNA, Circular ; RNA, Untranslated/physiology*