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1.
Hum Genomics ; 18(1): 3, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38200573

ABSTRACT

INTRODUCTION: Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3'- and 5'- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. MATERIALS AND METHODS: 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis  predicted binding affinity of circRNA/miRNA/mRNA axis. RESULTS: After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. CONCLUSION: We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , MicroRNAs , Humans , RNA, Circular/genetics , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Neoplasms/genetics , Carcinogenesis/genetics , MicroRNAs/genetics , RNA, Small Interfering , Minichromosome Maintenance Complex Component 3
2.
Biochim Biophys Acta Mol Cell Res ; 1870(5): 119447, 2023 06.
Article in English | MEDLINE | ID: mdl-36990227

ABSTRACT

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Mouth Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Squamous Cell/metabolism , Esophageal Squamous Cell Carcinoma/genetics , Mouth Neoplasms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Esophageal Neoplasms/genetics
3.
Cell Mol Biol Lett ; 27(1): 89, 2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36221055

ABSTRACT

BACKGROUND: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS: The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , RNA, Long Noncoding , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , DEAD-box RNA Helicases , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/genetics , Eukaryotic Initiation Factor-4A/genetics , Gene Expression Regulation, Neoplastic , Humans , Peptide Initiation Factors/genetics , Peptide Initiation Factors/metabolism , RNA Stability/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , rho GTP-Binding Proteins/genetics , rho GTP-Binding Proteins/metabolism
4.
World J Gastrointest Oncol ; 14(9): 1758-1770, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36187386

ABSTRACT

BACKGROUND: There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) who are not eligible to undergo surgical treatment. AIM: To introduce a novel therapy called endoscopic debulking resection (EdR) followed by additive chemoradiotherapy (CRT) and evaluate its efficacy and safety. METHODS: Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received EdR followed by CRT were deemed the EdR + CRT group and those without CRT were deemed the EdR group. Overall survival (OS), progression-free survival (PFS), and adverse events were evaluated. RESULTS: A total of 41 patients were enrolled. At a median follow-up of 36 mo (range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent EdR plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent EdR alone (1-year OS, 83.3%; 2-year OS, 58.3%; 3-year OS, 50%; P = 0.05). The estimated 2-year cumulative PFS rate after EdR + CRT was 85.7%, while it was 61.5% after EdR (P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage (stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the EdR procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after EdR. CONCLUSION: EdR plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.

5.
Eur J Gastroenterol Hepatol ; 34(2): 128-136, 2022 02 01.
Article in English | MEDLINE | ID: mdl-33252417

ABSTRACT

Peroral endoscopic myotomy (POEM) is a rapidly evolving technique for the treatment of esophageal diverticulum. The aim of this study was to perform a systematic review and meta-analysis of the literature focusing on POEM for symptomatic esophageal diverticula, including an in-depth evaluation of its efficacy, safety, and limitations. A comprehensive literature search was completed to identify articles that examined the efficacy and safety of POEM for esophageal diverticula. Heterogeneity among studies was assessed using the I2 statistic. Meta-regression and sensitivity analyses were performed to explore the sources of heterogeneity and assess potentially important covariates influencing the main outcomes. Primary endpoints such as rates of success, adverse events, and recurrences were evaluated. P values of ≤0.05 were considered statistically significant. Nine studies with a total of 153 patients were enrolled. Pooled technical success, clinical success, adverse events, and recurrence rates were 99% [95% confidence interval (CI), 97-100%; I2 = 0%), 94% (95% CI, 89-97%; I2 = 24%), 2% (95% CI, 0-6%, I2 = 0%), and 0% (95% CI, 0-1%; I2 = 0%), respectively. The pooled perforation rate was 6% (95% CI, 1-11%; I2 = 0%). Meta-regression analysis indicated that esophageal diverticula types and motility disorders were not associated with the clinical success rate (P > 0.05). POEM is a feasible, safe, and effective treatment for symptomatic esophageal diverticula, with low adverse events and recurrence rates.


Subject(s)
Digestive System Surgical Procedures , Diverticulum, Esophageal , Esophageal Achalasia , Myotomy , Natural Orifice Endoscopic Surgery , Diverticulum, Esophageal/etiology , Diverticulum, Esophageal/surgery , Humans , Myotomy/adverse effects , Myotomy/methods , Natural Orifice Endoscopic Surgery/methods , Treatment Outcome
6.
Surg Endosc ; 36(2): 1385-1393, 2022 02.
Article in English | MEDLINE | ID: mdl-33721092

ABSTRACT

BACKGROUND: Refractory esophageal stricture is difficult to deal with. Some refractory stricture shows little response to now-existing endoscopic techniques. We assessed the efficacy of modified endoscopic radial incision and cutting method (M-RIC) for the treatment of refractory esophageal stricture. METHODS: This was a retrospective study. Patients with refractory esophageal stricture who underwent M-RIC or dilation from June 2016 to June 2020 were included. Outcomes measured included technical and clinical success, restenosis rate, time to restenosis and complications. Risk factors for restenosis after M-RIC were assessed. RESULTS: 67 patients were enrolled (M-RIC group, n = 29; dilation group, n = 38). After propensity score matching, each group include 28 patients. There were no significant differences in technical success (96.4% vs 100%, p = 1.00) or clinical success (89.3% vs 100%, p = 0.23) between groups. Patients in M-RIC group had lower rates of restenosis (75% vs. 100%, p = 0.02) and longer time to restenosis (110 days vs 31.5 days, p = 0.00) compared with dilation group. 4 patients did not require any additional treatment after M-RIC and maintained food intake until the end of follow-up. Complications of M-RIC include perforation, fever and retrosternal pain, and no difference was found in total complication rate when compared with dilation group (25% vs 7.1%, p = 0.07). Although 3 out of 28 patients (10.7%) in M-RIC group had perforation, the perforation rate was not significantly different between groups (p = 0.11). Multivariate analyze suggested stricture length ≥ 5 cm (HR 7.25, p = 0.00) was a risk factor to restenosis while oral prednisone (HR 0.29, p = 0.02) was associated with preventing restenosis after M-RIC. CONCLUSION: M-RIC is a feasible and effective technique for refractory esophageal stricture with lower rate and longer time to restenosis. Stricture length ≥ 5 cm is a risk factor to restenosis while oral prednisone is helpful in remitting restenosis after M-RIC.


Subject(s)
Endoscopic Mucosal Resection , Esophageal Stenosis , Constriction, Pathologic/etiology , Dilatation/adverse effects , Endoscopic Mucosal Resection/adverse effects , Esophageal Stenosis/etiology , Esophageal Stenosis/surgery , Humans , Retrospective Studies , Treatment Outcome
7.
Biomed Res Int ; 2021: 7430315, 2021.
Article in English | MEDLINE | ID: mdl-34722771

ABSTRACT

Immune checkpoint inhibitor (ICI) therapy may benefit patients with advanced esophageal squamous cell carcinoma (ESCC); however, novel biomarkers are needed to help predict the response of patients to treatment. Differentially expressed immune-related genes within The Cancer Genome Atlas ESCC dataset were selected using the weighted gene coexpression network and lasso Cox regression analyses. Based on these data, an immune-related gene prognostic index (IRGPI) was constructed. The molecular characteristics of the different IRGPI subgroups were assessed using mutation information and gene set enrichment analysis. Differences in immune cell infiltration and the response to ICI therapy and other drugs were also analyzed. Additionally, tumor and adjacent control tissues were collected from six patients with ESCC and the expression of these genes was verified using real-time quantitative polymerase chain reaction. IRGPI was designed based on CLDN1, HCAR3, FNBP1L, and BRCA2, the expression of which was confirmed in ESCC samples. The prognosis of patients in the high-IRGPI group was poor, as verified using publicly available expression data. KMT2D mutations were more common in the high-IRGPI group. Enrichment analysis revealed an active immune response, and immune infiltration assessment showed that the high-IRGPI group had an increased infiltration degree of CD8 T cells, which contributed to the improved response to ICI treatment. Collectively, these data demonstrate that IRGPI is a robust biomarker for predicting the prognosis and response to therapy of patients with ESCC.


Subject(s)
Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/immunology , BRCA2 Protein/genetics , Biomarkers, Pharmacological , Carrier Proteins/genetics , Claudin-1/genetics , Computational Biology/methods , Databases, Genetic , Esophageal Neoplasms/genetics , Esophageal Neoplasms/immunology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/genetics , Gene Regulatory Networks/genetics , Humans , Prognosis , Receptors, G-Protein-Coupled/genetics , Receptors, Nicotinic/genetics , Transcriptome/genetics
8.
Ann Transl Med ; 9(16): 1343, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34532480

ABSTRACT

BACKGROUND: To diagnose gastroparesis, it is necessary to assess gastric emptying accurately. This study aims to investigate the role of three-dimensional ultrasonography (3-D US) on the measurement of gastric volume to evaluate gastric accommodation in healthy patients. METHODS: In this study, 21 volunteers, 46 patients with diabetic gastroparesis (DG), and 22 patients with postsurgical gastroparesis (PSG) underwent 3-D US after oral administration of 250 mL gastrointestinal contrast at 2, 30, 60, and 90 min. The volume of the contrast agent in the stomach was then calculated using the virtual organ computer-aided analysis (VOCAL) (Virtual Organ Computer-aided AnaLysis, General Electric Medical Systems, Kretztechnik, Zipf, Austria). RESULTS: In the DG group, the gastric residue volumes at postprandial 60 and 90 min were significantly higher than those in the healthy group (P<0.05), and the areas under the receiver operating characteristic (ROC) curve of these parameters were 0.830 and 0.957, respectively. There were significant differences between the PSG and healthy groups at 60 and 90 min; however, the AUC of gastric residue at 90 min (0.955) was higher than the AUC at 60 min (0.697). CONCLUSIONS: Therefore, this study showed that the 3-D US is a powerful tool for assessing gastric emptying and provides a new strategy for diagnosing gastroparesis.

9.
FEBS Open Bio ; 11(11): 2870-2887, 2021 11.
Article in English | MEDLINE | ID: mdl-34510785

ABSTRACT

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.


Subject(s)
Esophageal Squamous Cell Carcinoma/genetics , RNA, Circular/genetics , RNA, Circular/physiology , Apoptosis/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Cell Transformation, Neoplastic/genetics , Epithelial-Mesenchymal Transition , Esophageal Neoplasms/genetics , Gene Expression/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Mouth Neoplasms/genetics , Neoplastic Processes , Signal Transduction/genetics
10.
Clin J Gastroenterol ; 14(4): 1250-1254, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34109527

ABSTRACT

Castleman's disease (CD) is a highly heterogeneous clinico-pathological entity belonging to the lymphoproliferative disorders. CD can occur in any part of the human body where lymph nodes are present. In addition, very few cases have been reported in hepatic hilum. Here, we present a case of a middle-aged female patient who was presented with abdominal pain and diagnosed as localized Castleman's disease of hepatic hilar and retroperitoneal origin. Diagnosing CD is complex due to its resemblance to many other diseases. EUS and FNA may play a more important role in differential diagnosis of CD and other disease in digestive system.


Subject(s)
Castleman Disease , Castleman Disease/diagnostic imaging , Diagnosis, Differential , Endosonography , Female , Human Body , Humans , Lymph Nodes , Middle Aged
11.
Int J Mol Med ; 47(4)2021 04.
Article in English | MEDLINE | ID: mdl-33537830

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in the human digestive system, which affects the physical and mental health of the patient. Long non­coding (lnc)RNAs have been revealed to play an important role in human malignant tumors. Moreover, long intergenic non­protein coding RNA 491 (LINC00491) is a newly discovered lncRNA that can affect the prognosis of cancer. The present study aimed to explore the expression of LINC00491 in ESCC tissues and cells. The reverse transcription­quantitative PCR results suggested that LINC00491 was upregulated in ESCC tissues and cells. LINC00491 expression in esophageal squamous cell carcinoma cells were knocked down. Cell Counting Kit­8, wound healing, Transwell and apoptosis assays were performed to detect the effects of LINC00491 knockdown on cell biological behavior. The results showed that lower expression of LINC00491 resulted in decreased cell proliferation and migration and increased the apoptosis rate. Therefore, the present results indicated that lncRNA LINC00491 promoted the biological processes of ESCC, and thus LINC00491 may be a potential therapeutic target for ESCC.


Subject(s)
Apoptosis/genetics , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Ontology , Gene Silencing , Humans , Neoplasm Invasiveness , Neoplasm Metastasis , RNA, Long Noncoding/genetics , Wound Healing
12.
Surg Endosc ; 35(7): 3459-3470, 2021 07.
Article in English | MEDLINE | ID: mdl-32880749

ABSTRACT

BACKGROUND: Postsurgical gastroparesis is recognized as a gastrointestinal dysfunction syndrome following foregut surgery. Gastric peroral endoscopic myotomy (G-POEM) is suggested as a minimally invasive therapy for gastroparesis. But the long-term efficacy and safety of G-POEM in treating postsurgical gastroparesis are rarely explored. METHODS: The primary outcomes included the symptomatic improvement based on gastroparesis cardinal symptoms index (GCSI) and the improvement of gastric emptying. The secondary outcomes included the improvement of gastroesophageal reflux symptoms and complications of G-POEM. RESULTS: The severity of postsurgical gastroparesis was not associated with the onset time and the course of the disease. G-POEM significantly reduced GCSI throughout the follow-up period (p < 0.0001). For different anastomotic site, a significant improvement of GCSI was found at 6 month post-G-POEM (F4,165 = 74.18, p < 0.0001). Subscale analysis of GCSI showed that nausea/vomiting, post-prandial fullness/early satiety, and bloating were improved significantly at 6-month post-G-POEM (p < 0.0001, respectively). Half-emptying and whole-emptying time were significantly shortened in patients with different anastomotic site post-G-POEM (half-emptying time: F3,174 = 65.44, p < 0.0001; whole-emptying time: F3,174 = 54.85, p < 0.0001). The emptying of ioversol was obviously accelerated after G-POEM. GCSI wasn't related to pyloric length, pyloric diameter, and thickness of pyloric wall. GERDQ was also used to evaluate the clinical efficacy of G-POEM. For each time points, GERDQ didn't differ significantly in patients with different anastomotic site (F4,104 = 0.8075, p = 0.5231). For patients with different anastomotic site, GERDQ was improved significantly at different time points (F4,104 = 59.11, p < 0.0001). The higher the esophageal anastomotic site was, the faster G-POEM improved the symptoms of gastroesophageal reflux. No one required re-hospitalization for any complication. CONCLUSION: G-POEM is a minimally invasive therapy with long-term effectiveness and safety in treating postsurgical gastroparesis.


Subject(s)
Esophageal Achalasia , Gastroparesis , Pyloromyotomy , Esophageal Sphincter, Lower , Feasibility Studies , Gastric Emptying , Gastroparesis/etiology , Gastroparesis/surgery , Humans , Pyloromyotomy/adverse effects , Pylorus/surgery , Retrospective Studies , Treatment Outcome
13.
Eur J Gastroenterol Hepatol ; 33(4): 470-478, 2021 04 01.
Article in English | MEDLINE | ID: mdl-32675780

ABSTRACT

Diagnosis of gastric intestinal metaplasia (GIM) under digital chromoendoscopy presents various markers. The diagnostic yield of each marker has shown variable results. A systematic review and meta-analysis were performed to evaluate the following markers: light blue crest (LBC), marginal turbid band (MTB), groove type (GT), white opaque substance (WOS). Discussion of their joint diagnosis, reliability, assessment of local GIM severity and influencing factors was also provided. PubMed, EMBASE, Cochrane Library and Web of science were searched. The Meta-DiSc and Stata software were used to analyze the data. Fourteen studies were included with a total of 3081 lesions. There were 12 studies for LBC, six for GT, four for MTB and one for WOS, respectively. The pooled results showed that the diagnostic sensitivity and specificity of LBC were 0.79 [95% confidence interval (CI) 0.76-0.81] and 0.95 (95% CI 0.94-0.96). The sensitivity of GT and MTB were 0.49 (95% CI 0.43-0.54) and 0.47 (95% CI 0.40-0.53), and the specificity were 0.92 (95% CI 0.89-0.94) and 0.92 (95% CI 0.89-0.95). The area under the summary receiver operating characteristic curve was 0.9532, 0.7791 and 0.9553 for LBC, GT and MTB, respectively. LBC resulted the most classic marker. Proper combined diagnosis can improve the diagnostic efficiency. Reliability of these markers was acceptable. These markers can help endoscopic to assess the severity of local GIM. Besides intestinal metaplasia, many factors can potentially interfere with the diagnosis.


Subject(s)
Precancerous Conditions , Stomach Diseases , Endoscopy , Humans , Metaplasia , Reproducibility of Results
14.
Drug Des Devel Ther ; 14: 5599-5610, 2020.
Article in English | MEDLINE | ID: mdl-33376304

ABSTRACT

AIM: Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury. METHODS: We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A (VEGF-A) and CD34 were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker CHOP, angiogenic markers VEGF-A and its receptor VEGFR1, and endothelial NO synthase (eNOS) were all analyzed by Western blot. RESULTS: This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and eNOS. Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B (AKT) and p38 mitogen-activated protein kinase (p38/MAPK). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa. CONCLUSION: In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via VEGF-A/VEGFR1 mediated-AKT/p38/MAPK signaling pathways.


Subject(s)
Peptide Fragments/therapeutic use , Protective Agents/therapeutic use , Proteins/therapeutic use , Stomach Ulcer/drug therapy , Acetic Acid/administration & dosage , Administration, Oral , Animals , Clopidogrel/administration & dosage , Injections, Intraperitoneal , Male , Peptide Fragments/administration & dosage , Protective Agents/administration & dosage , Proteins/administration & dosage , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced
15.
Gastroenterol Res Pract ; 2020: 4152453, 2020.
Article in English | MEDLINE | ID: mdl-32508911

ABSTRACT

Esophageal squamous cell carcinoma comprises the majority of esophageal carcinoma in the Eastern Asia. The need of early detection of precancerous neoplastic lesions and cancer has been necessitated due to the probability of progression to the advanced stage and its poor prognosis. In recent times, many endoscopic modalities have come into practice for early detection and treatment. Endoscopic radiofrequency ablation (RFA) has been recommended as an efficient therapy in treating the dysplastic mucosa in Barrett's esophagus (BE). Its potential in reversing neoplastic lesions in squamous epithelium has been gradually explored. This article is aimed at reviewing the current evidence regarding the use of RFA on esophageal squamous cell neoplasia.

16.
Am J Transl Res ; 12(5): 1741-1753, 2020.
Article in English | MEDLINE | ID: mdl-32509173

ABSTRACT

Bleeding and delayed healing of gastric ulcer are well-recognized in patients following Clopidorgrel treatment. Our previous studies have shown that endoplasmic reticulum stress (ER) is involved in Clopidogrel-induced gastric mucosal damage through activating p38 mitogen-activated protein kinases (MAPK) pathway. This present study aims to further investigate the role of MAP kinase phosphatase 5 (MKP-5), a MKP known to dephosphorylate and inactivate p38/MAPK, in Clopidogrel-induced gastric mucosal injury and the underlying mechanisms. It shows that MKP-5 is down-regulated at both mRNA and protein levels in the gastric mucosa from bleeding patients who took Clopidogrel over one year. In vitro study using human gastric epithelial cell line GES-1 demonstrates that exposure to Clopidorgrel (1.0-2.0 mM) increases phosphorylation of p38/MAPK and decreases MKP-5 expression simultaneously. Overexpression of MKP-5 promotes GES-1 cell proliferation and reduces apoptosis following Clopidogrel exposure. Interestingly, overexpression of MKP-5 also attenuates Clopidorgrel-induced tight junction (TJ) destruction by down-regulating expression of ER stress-related protein C/EBP homologous protein (CHOP) and tribbles pseudokinase 3 (TRIB3). These three effects, increased proliferation, reduced apoptosis and attenuated TJ destruction, are regulated through inhibited phosphorylation of p38/MAPK signaling pathway. We conclude that MKP-5 is down-regulated in Clopidogrel-induced gastric mucosa injury in vivo and in vitro via phosphorylation and activation of p38/MAPK signaling pathway. Overexpression of MKP-5 reverses Clopidogrel-induced gastric mucosal injury. These findings imply that MKP-5 may be a potential therapeutic target in Clopidogrel-induced gastric mucosal injury and bleeding.

17.
Biomed Res Int ; 2018: 3201940, 2018.
Article in English | MEDLINE | ID: mdl-29682534

ABSTRACT

Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+ T cell, memory cell, and so on, and each of them has special function on antitumor response or tumor immune escape which is revealed in lung cancer, colorectal cancer, breast cancer, ovarian cancer, and so on. But its correlation with gastric cancer is not clear. Our review was preformed to explore the relationship between the progress and prognosis of gastric cancer (GC) and T cell immunity. According to recent researches, T cell immunity may have an important role in the progress and prognosis of GCs, but its function is affected by location, category, related molecule, and interaction between the cells, and some effects still are controversial. More researches are needed to clarify this correlation.


Subject(s)
Immunity/immunology , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , T-Lymphocytes/immunology , Disease Progression , Humans , Lymphatic Metastasis/immunology , Prognosis
18.
J Nurs Educ ; 56(11): 670-674, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29091236

ABSTRACT

BACKGROUND: There is a need to better understand the demographic and academic characteristics of individuals enrolled in online Master of Science in Nursing (MSN) programs. METHOD: This article reports a retrospective analysis of 4,079 students enrolled in one of three MSN programs: family nurse practitioner (FNP), nurse educator, and nursing administration. Demographic characteristics (i.e., gender, race, age) and academic variables (i.e., academic load, past undergraduate/graduate enrollment at the university) were examined for all enrollees. RESULTS: Students in the MSN programs were younger than the national mean age for RNs, were primarily White, and were enrolled part time. The sample was composed of a disproportionately higher percentage of students from ethnic minority backgrounds than national RN profiles. CONCLUSION: Study implications indicate that understanding the commonalities, differences, and educational experiences of students in on-campus and online MSN programs is important. The finding that almost 90% of online graduate nursing students enroll as part time has significant financial, family, and career implications. [J Nurs Educ. 2017;56(11):670-674.].


Subject(s)
Education, Distance/statistics & numerical data , Education, Nursing, Graduate/statistics & numerical data , Students, Nursing/statistics & numerical data , Adult , Ethnicity/statistics & numerical data , Female , Humans , Male , Middle Aged , Nursing Education Research , Retrospective Studies
19.
J Nurs Educ ; 56(9): 522-526, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28876437

ABSTRACT

BACKGROUND: To meet the increasing demand for RNs to further their education, many colleges of nursing have developed RN-to-baccalaureate nursing (BSN) programs, many of which are delivered online. A better understanding of the demographic and academic characteristics and outcomes of individuals enrolled in online RN-to-BSN programs is needed. METHOD: This article reports a retrospective predictive analysis of 9,567 students enrolled in an online RN-to-BSN program. Outcome variables examined were graduation, timely graduation, and discontinuation. RESULTS: Younger students who received financial aid and had a previous baccalaureate degree reflected the demographic profile associated with the highest likelihood of graduating and graduating sooner. Fewer failed and withdrawn courses also predicted graduation and retention. CONCLUSION: Implications of these findings are that when online programs are designed with persistence in mind, progression to graduation in such programs can be consistent with national benchmarks. The creation of an early identification process for at-risk students would have the potential to enhance educational outcomes even further. [J Nurs Educ. 2017;56(9):522-526.].


Subject(s)
Academic Success , Education, Distance , Education, Nursing, Baccalaureate , Adult , Curriculum , Education, Nursing, Associate , Female , Humans , Male , Retrospective Studies , Texas
20.
Medicine (Baltimore) ; 96(51): e9313, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29390503

ABSTRACT

RATIONALE: Gastrointestinal solitary extramedullary plasmacytoma (EMP) is rare, just occupies about 5% of all EMPs. The most common site is small intestine followed by stomach. The colorectal incidence is much rare. PATIENT CONCERNS: A 63-year-old female had an episodic pain around the umbilicus for about one week. The hyperemia and edema in the ileocecal mucosa were found in colonoscopy, and the endoscopy could not cross the ileocecal valve. The pathology specimens showed a high index suspicion of plasmacytoma. DIAGNOSES: The patient was diagnosed with extramedullary plasmacytoma. INTERVENTIONS: A right hemicolectomy surgery was performed to treat the disease. OUTCOMES: Post surgery pathologic report showed low grade malignant mucosa associated marginal zone B cell lymphoma. LESSONS: We report a case of an extramedullary plasmacytoma in ileocecum with abdominal pain and a review of extramedullary plasmacytoma.


Subject(s)
Cecal Neoplasms/pathology , Ileal Neoplasms/pathology , Plasmacytoma/pathology , Cecal Neoplasms/surgery , Colectomy , Female , Humans , Ileal Neoplasms/surgery , Middle Aged , Plasmacytoma/surgery
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