[Astragali Radix-Curcumae Rhizoma combination inhibits proliferation, migration, and invasion of colon cancer HT-29 cells by regulating EMT].

This study aims to investigate the effect of Astragali Radix-Curcumae Rhizoma(AC) combination on the proliferation, migration, and invasion of colon cancer HT-29 cells based on epithelial-mesenchymal transition(EMT). HT-29 cells were respectively treated with 0, 3, 6 and 12 g·kg~(-1) AC-containing serum for 48 h. The survival and growth of cells were measured by thiazole blue(MTT) colorimetry, and the proliferation, migration, and invasion of cells were detected by 5-ethynyl-2'-deoxyuridine(EdU) test and Transwell assay. Cell apoptosis was examined by flow cytometry. The BALB/c nude mouse model of subcutaneous colon cancer xenograft was established, and then model mice were classified into blank control group, 6 g·kg~(-1) AC group, and 12 g·kg~(-1) AC group. The tumor weight and volume of mice were recorded, and the histopathological morphology of the tumor was observed based on hematoxylin-eosin(HE) staining. The expression of apoptosis-associated proteins B-cell lymphoma-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), and cleaved caspase-3, and EMT-associated proteins E-cadherin, MMP9, MMP2 and vimentin in HT-29 cells and mouse tumor tissues after the treatment of AC was determined by Western blot. The results showed that cell survival rate and the number of cells at proliferation stage decreased compared with those in the blank control group. The number of migrating and invading cells reduced and the number of apoptotic cells increased in the administration groups compared with those in the blank control group. As for the in vivo experiment, compared with the blank control group, the administration groups had small tumors with low mass and shrinkage of cells and karyopycnosis in the tumor tissue, indicating that the AC combination may improve EMT. In addition, the expression of Bcl2 and E-cadherin increased and the expression of Bax, caspase-3, cleaved caspase-3, MMP9, MMP2, and vimentin decreased in HT-29 cells and tumor tissues in each administration group. In summary, the AC combination can significantly inhibit the proliferation, invasion, migration, and EMT of HT-29 cells in vivo and in vitro and promote the apoptosis of colon cancer cells.

Internet and WeChat used by patients with Crohn's disease in China: a multi-center questionnaire survey.

BACKGROUND: Currently, WeChat is widely used in disease education for patients with Crohn's disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. METHODS: In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. RESULTS: Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn's and Colitis Foundation (CCCF) (73%), "IBD Academic Officer" (21%) and "IBD in love" (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients' expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). CONCLUSIONS: WeChat has become a major source of information for IBD education in China, but the content of WeChat didn't fully meet patients' expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients' demands.

Combination of Paris and Vienna classifications may optimize follow-up of gastric epithelial neoplasia patients.

BACKGROUND: The aim of this study was to evaluate the efficiency of the combination of Paris and Vienna classifications in a follow-up study of gastric epithelial neoplasia (GEN) patients. MATERIAL AND METHODS: This study was conducted between January 2003 and September 2010, during which 170 biopsy-proven GEN patients were followed up by gastroenterologists and pathologists according to our follow-up regimen (modified Vienna classification). RESULTS: In total, 161 patients with low-grade neoplasia (LGN) and 9 patients with high-grade neoplasia (HGN) were randomly enrolled in our study. Eighteen patients with depressed appearance were observed, of which 9 patients had HGN and 9 patients had low-grade dysplasia (LGD). Three patients with type 0-IIa were observed with low-grade adenoma (LGA), and type 0-I was observed in 2 patients with LGN. Endoscopic or surgical treatments were performed to avoid potential malignancy or bleeding. Two patients with ulcer lesions, 2 patients with non-depressed type 0 appearance, and 3 patients without visible lesions were shown to have higher-grade lesions during follow-up. The misdiagnosis rate of forceps biopsy - 62.07% - was determined by comparing pre- and post-resection diagnoses of 29 patients. CONCLUSIONS: The combination of the Paris and Vienna classifications for GEN may optimize the follow-up routines for patients with suspicious precancerous lesions and may significantly improve the detection of early gastric cancer (EGC) while helping gastroenterologists select the best therapy option.

A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

BACKGROUND: The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes. MATERIAL/METHODS: Serum liver enzymes of the samples including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were measured. The cumulative incidences of IFG between different quartiles of liver enzymes were compared by the chi-square test. A logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95% CI). RESULTS: The total incidence of IFG was 20.3% and the cumulative incidence of IFG was higher in men compared to women. In both sexes, IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), the cumulative incidences of IFG were significantly higher in the highest quartiles of liver enzymes than in the lowest quartiles. A significantly higher cumulative incidence of IFG was found in the highest GGT quartile than in the lowest quartile for woman. CONCLUSIONS: The results of this study suggest that serum liver enzymes are related to the risk of IFG in Chinese adults. We infer that preserving the hepatic function may be an efficient way to prevent the development of IFG, especially in males.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report.

BACKGROUND: Intestinal natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive non-Hodgkin's lymphoma, and its occurrence is closely related to Epstein-Barr virus infection. In addition, the clinical symptoms of NKTCL are not obvious, and the specific pathogenesis is still uncertain. While NKTCL may occur in any segment of the intestinal tract, its distinct location in the periampullary region, which leads clinicians to consider mimics of a pancreatic head mass, should also be addressed. Therefore, there remain huge challenges in the diagnosis and treatment of intestinal NKTCL. CASE SUMMARY: In this case, we introduce a male who presented to the clinic with edema of both lower limbs, accompanied by diarrhea, and abdominal pain. Endoscopic ultrasound (EUS) showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas. Under the guidance of EUS- fine needle biopsy (FNB) with 19 gauge or 22 gauge needles, combined with multicolor flow cytometry immunophenotyping (MFCI) helped us diagnose NKTCL. During treatments, the patient was prescribed the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy regimen. Unfortunately, he died of leukopenia and severe septic shock in a local hospital. CONCLUSION: Clinicians should enhance their understanding of NKTCL. Some key factors, including EUS characteristics, the right choice of FNB needle, and combination with MFCI, are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Curdione induces ferroptosis mediated by m6A methylation via METTL14 and YTHDF2 in colorectal cancer.

BACKGROUND: Curdione is a sesquiterpene isolated from Curcumae Rhizoma that possesses high biological activity and extensive pharmacological effects. As a traditional Chinese medicine, Curcumae Rhizoma can inhibit the development of many types of cancer, especially colorectal cancer. However, the anti-colorectal mechanism of its monomer curdione remains unclear. METHODS: Colorectal cancer (CRC) cells were treated with curdione at doses of 12.5 µM, 25 µM, and 50 µM, and then the cells' activity was measured with methyl thiazolyl tetrazolium (MTT). Nude mice were administered different doses of curdione subcutaneously and oxaliplatin by tail vein injection, and then hematoxylin-eosin (HE) staining was adopted to examine tumor histology. Moreover, flow cytometry was applied to detect reactive oxygen species in cells and tissues. Kits were employed to detect the levels of iron ions, malondialdehyde, lipid hydroperoxide, and glutathione. Polymerase chain reaction (PCR) and Western blotting were adopted to detect ferroptosis and m6A modification-related factors. A methylation spot hybridization assay was performed to measure changes in overall methylation. SLC7A11 and HOXA13 were measured by MeRIP-qPCR. The shRNA-METTL14 plasmid was constructed to verify the inhibitory effect of curdione on CRC. RESULTS: A dose-dependent decrease in activity was observed in curdione-treated cells. Curdione increased the accumulation of reactive oxygen species in CRC cells and tumor tissues, greatly enhanced the levels of malondialdehyde, lipid hydroperoxide and Fe2+, and lowered the activity of glutathione. According to the qPCR and Western blot results, curdione promoted the expression of METTL14 and YTHDF2 in CRC cells and tissues, respectively, and decreased the expression of SLC7A11, SLC3A2, HOXA13, and glutathione peroxidase 4. Additionally, in animal experiments, the curdione-treated group showed severe necrosis of tumor cells, as displayed by HE staining. Furthermore, compared with the control group, levels of m6A modifying factors (namely, SLC7A11 and HOXA13) were increased in the tissues after drug intervention. METTL14 knockdown was followed by an increase in CRC cell activity and glutathione levels. However, the levels of reactive oxygen species, malondialdehyde, and iron ions decreased. The expression levels of SLC7A11, SLC3A2, HOXA13, and GPX4 were all increased after METTL14 knockdown. CONCLUSION: The results suggest that curdione induces ferroptosis in CRC by virtue of m6A methylation.

High prevalence of hepatitis B virus infection in HIV-negative Castleman's disease.

Castleman's disease (CD) is a rare non-neoplastic lymphoproliferative disorder with ambiguous etiology. This study aimed to evaluate the potential association between hepatitis B virus (HBV) and CD and to characterize the HBV-positive CD patients in China, an endemic area for HBV infection. We compared the prevalence of HBV infection in 35 consecutive CD patients initially diagnosed in our hospitals over a 10-year period with an age- and sex-matched healthy control, a national population-based control, and a non-Hodgkin's lymphoma (NHL) control. We found that the prevalence of HBV infection in CD was 17.1% (6/35), which was as high as the NHL control (19.9%, P = 0.693), but significantly higher than the age- and sex-matched healthy control (6.9%, P = 0.033) and the national population-based control (7.2%, P = 0.037). Next, we compared the clinicopathological characteristics between HBV-positive and HBV-negative CD patients. We found that HBV-positive CD patients had a significantly higher NHL malignant transformation rate (33.3% vs. 0%, P = 0.025), higher splenomegaly rate (83.3% vs. 27.6%, P = 0.019), and much poorer prognosis (estimated mean overall survival time (50.83 vs. 64.34 months, P = 0.016). In conclusion, our findings suggest an association between HBV infection and development of CD. CD patients with HBV infection have their own distinguished features.

Role of COVID-19 Vaccines in SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a threat to the health of the global population. As the result of a global effort in the determination of origin, structure, and pathogenesis of SARS-CoV-2 and its variants, particularly such the variant of concern as Delta Variant and Omicron Variant, the understanding of SARS-CoV-2 are deepening and the development of vaccines against SARS-CoV-2 are ongoing. Currently, AstraZeneca-Vaxzevria/SII-Covishield vaccine, Janssen-Ad26.COV2.S vaccine, Moderna-mRNA-1273 vaccine, Pfizer BioNTech-Comirnaty vaccine and Sinovac-CoronaVac vaccine have been listed as WHO Emergency Use Listing (EUL) Qualified Vaccines by WHO. Because of the antigen escape caused by the mutation in variants, the effectiveness of vaccines, which are currently the main means of prevention and treatment, has been affected by varying degrees. Herein, we review the current status of mutations of SARS-CoV-2 variants, the different approaches used in the development of COVID-19 vaccines, and COVID-19 vaccine effectiveness against SARS-CoV-2 variants.

Identification of three immune subtypes characterized by distinct tumor immune microenvironment and therapeutic response in stomach adenocarcinoma.

BACKGROUND: In primary stomach adenocarcinoma (STAD), the tumor immune microenvironment (TIME) is important for cancer occurrence and progression; however, its clinical significance remains unclear. This study investigated the association between patient survival, TIME, and therapeutic response to STAD. METHODS: Gene expression profiles of STAD cases were collected from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus. Molecular subtypes were explored with consistent clustering methods according to 119 immune signatures and the infiltrating scores of 22 immune cells using the Multi-Omics Immuno-Oncology Biological Research algorithm. We determined IFNγ scores and immune cytolytic activity (CYT) scores on the basis of corresponding gene signatures via single-sample Gene Set Enrichment Analysis. Comparisons of survival, TIME, 10 immunity-related oncogenic pathways, immune checkpoint expression, and therapeutic response were conducted among the three subtypes. We further applied linear discriminant analysis to construct a characteristic index to classify the subtypes, and the Pearson correlation coefficient for the relationship between the index and immune checkpoint genes. Weighted Correlation Network Analysis (WGCNA) was used to mine the associated modules and specific genes. RESULTS: We collected gene expression profiles from 352 STAD cases in the TCGA database, 300 in GSE62254, and 344 in GSE84437. Three STAD subtypes (IS1-IS3) were established according to the TIME signatures. The IS3 subtype had the highest immune score and the best prognosis, as well as markedly increased immune T-cell CYT, Th1/IFNγ scores, and immune checkpoint gene expression, compared to the other two subtypes. It was highly similar to the PD-1 response group in the previous study samples of GSE91061. The established TIME classification index performed well in classifying subtypes and was directly proportional to immune checkpoint-related gene expression levels. WGCNA explored 6 modules and 14 genes, namely DYSF, MAN1C1, HTRA3, EMCN, RFLNB, KANK3, MAGEH1, CD93, PCAT19, FUT11, BMP1, FOSB, DCHS1, and TCF3, which were associated with the established TIME classification index and STAD patient prognosis. CONCLUSION: TIME phenotypes of STAD patients could be divided into three different molecular subtypes, which displayed different prognoses, immune features, and therapeutic responses. Our results shed new light on predicting patient outcomes and the discovery of new anti-STAD therapeutic strategies according to the TIME.

A novel prognostic 6-gene signature for osteoporosis.

Introduction: The incidence of osteoporosis (OP) keeps increasing due to global aging of the population. Therefore, identifying the diagnostic and prognostic biomarkers of OP is of great significance. Methods: mRNA data from OP and non-OP samples were obtained from GEO database, which were divided into training set (GSE35959) and testing sets (GSE7158, GSE62402, GSE7429 and GSE56815). Gene modules most significantly related to OP were revealed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) between OP and normal samples in training set were identified using limma R package. Thereafter, above two gene sets were intersected to obtain the genes potentially related to OP. Protein-protein interaction (PPI) pairs were screened by STRING database and visualized using Cytoscape, while the plug-in cytoHubba was used to screen hub genes by determining their topological parameters. Afterwards, a diagnostic model was constructed using those hub genes, whose creditability was further evaluated by testing sets. Results: The results of WGCNA analysis found the Black module was most significantly related to OP, which included altogether 1286 genes. Meanwhile, 2771 DEGs were discovered between OP patients and the normal controls. After taking the intersection, 479 genes were identified potentially correlated with the development of OP. Subsequently, six hub genes were discovered through PPI network construction and node topological analysis. Finally, we constructed a support vector machine model based on these six genes, which can accurately classified training and testing set samples into OP and normal groups. Conclusion: Our current study constructed a six hub genes-based diagnostic model for OP. Our findings may shed some light on the research of the early diagnosis for OP and had certain practical significance.

Spontaneous expulsion of a duodenal lipoma after endoscopic biopsy: A case report.

BACKGROUND: Gastrointestinal (GI) lipomas are benign submucosal tumors of mature adipocytes that arise mainly in the colon and stomach, sometimes in the ileum and jejunum, and rarely in the duodenum. Patients with symptomatic lipomas require endoscopic or surgical treatment. Spontaneous expulsion of lipomas after biopsy is a rare condition that has limited case reports. CASE SUMMARY: A 56-year-old man presented to our hospital with intermittent postprandial epigastric fullness. Esophagogastroduodenoscopy (EGD) revealed a 10-mm soft yellowish submucosal lesion with the "pillow sign," located in the second portion of duodenum. Endoscopic ultrasonography (EUS) using a 12-MHz catheter probe showed a hyperechoic, homogenous, and round solid lesion (OLYMPUS EUS EU-ME2, UM-DP12-25R, 12-MHz radial miniprobe, Olympus Corporation, Tokyo, Japan). Deep biopsy was performed using the bite-on-bite technique with forceps. Histological examination was compatible with submucosal lipoma. The lesion spontaneously expelled 12 d after the biopsy. Follow-up EUS performed after 2 mo confirmed this condition. CONCLUSION: Deep biopsy could lead to spontaneous GI lipoma expulsion. This might be the first step in lipoma diagnosis and treatment.

Association between RUNX3 promoter methylation and gastric cancer: a meta-analysis.

BACKGROUND: Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer. However, the association between RUNX3 promoter methylation and gastric cancer remains unclear. METHODS: We systematically reviewed studies of RUNX3 promoter methylation and gastric cancer published in English or Chinese from January 2000 to January 2011, and quantified the association between RUNX3 promoter methylation and gastric cancer using meta-analysis methods. RESULTS: A total of 1740 samples in 974 participants from seventeen studies were included in the meta-analysis. A significant association was observed between RUNX3 promoter methylation and gastric cancer, with an aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07). There was obvious heterogeneity among studies. Subgroup analyses (including by tissue origin, country and age), meta-regression were performed to determine the source of the heterogeneity. Meta-regression showed that the trend in ORs was inversely correlated with age. No publication bias was detected. The ORs for RUNX3 methylation in well-differentiated vs undifferentiated gastric cancers, and in intestinal-type vs diffuse-type carcinomas were 0.59 (95%CI: 0.30, 1.16) and 2.62 (95%CI: 1.33, 5.14), respectively. There were no significant differences in RUNX3 methylation in cancer tissues in relation to age, gender, TNM stage, invasion of tumors into blood vessel or lymphatic ducts, or tumor stage. CONCLUSIONS: This meta-analysis identified a strong association between methylation of the RUNX3 promoter and gastric cancer, confirming the role of RUNX3 as a tumor suppressor gene.

Erythropoietin, as a biological macromolecule in modification of tissue engineered constructs: A review.

In recent years, tissue engineering has emerged as a promising approach to address limitations of organ transplantation. The ultimate goal of tissue engineering is to provide scaffolds that closely mimic the physicochemical and biological cues of native tissues' extracellular matrix. In this endeavor, new generation of scaffolds have been designed that utilize the incorporation of signaling molecules in order to improve cell recruitment, enhance angiogenesis, exert healing activities, and increase the engraftment of the scaffolds. Among different signaling molecules, the role of erythropoietin (EPO) in regenerative medicine is increasingly being appreciated. It is a biological macromolecule which can prevent programed cell death, modulate inflammation, induce cell proliferation, and provide tissue protection in different disease models. In this review, we have outlined and critically analyzed different techniques of scaffolds' modification with EPO or EPO-loaded nanoparticles. We have also explored different strategies for the incorporation of EPO into scaffolds. Non-hematopoietic functions of EPO have also been discussed. Finalizing with detailed discussion surrounding the applications, challenges, and future perspectives of EPO-modified scaffolds in regenerative medicine.

Association of Timing of Biliary Drainage with Clinical Outcomes in Severe Acute Cholangitis: A Retrospective Cohort Study.

PURPOSE: The guidelines recommend urgent biliary drainage (BD) for severe acute cholangitis, without a clear definition of "urgent". To explore the optimal time, we identified the impact of timing of BD on clinical outcomes in severe acute cholangitis. PATIENTS AND METHODS: A retrospective study of patients with severe acute cholangitis was conducted based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Multivariable regressions were used to identified the effect of timing of BD on in-hospital mortality, 30-day mortality, and the length of stay (LOS) in hospital and the intensive care unit (ICU) with adjustment for confounding factors. RESULTS: A total of 106 severe acute cholangitis patients underwent BD with a median time of 14.14 hours (IQR: 7.60-32.59). Among them, 67.9% were performed within 24 hours and 80.2% within 48 hours. Median length of stay was 2.65 days (IQR: 1.70-5.12) in the ICU and 7.54 days (IQR: 4.49-17.17) in hospital. The in-hospital and 30-day mortality rates were 13.2% and 14.2%, respectively. On multivariate analysis, every 1-day delay of BD increased 1.49 days of stay in hospital (P<0.0001). Delayed BD (>48 hours) was linked with 5.56 days longer ICU LOS (P = 0.0096), while urgent BD (<24 hours) did not significantly shorten the ICU stay (P = 0.0997). No significant increase was observed on in-hospital mortality (OR = 1.03; 95% CI 0.93-1.13) nor 30-day mortality (OR=1.01; 95% CI 0.87-1.14) with BD delay in this population. CONCLUSION: In severe acute cholangitis patients, delay in BD increased in-hospital LOS. BD after 48 hours was associated with longer ICU LOS. Yet, BD within 24 hours did not significantly reduce the mortality nor shortened the ICU LOS.

Assessing Oral Medication Adherence and Identifying Predictors of Low Adherence in Chinese Inflammatory Bowel Disease Patients.

BACKGROUND: Poor medication adherence in inflammatory bowel disease (IBD) had a negative impact on disease outcomes. In this study, we aimed to determine predictors of low adherence in the Chinese IBD populations and also aimed to compare a self-reported scale to a pharmacy refill index in assessing adherence of 5-ASA and azathioprine taken by Chinese IBD patients. PATIENTS AND METHODS: Adult patients with IBD who had been taking 5-ASA or azathioprine for at least 3 months were recruited from hospital outpatient clinics. The MPR was calculated from previous six-month pharmacy refill data and the self-reported Morisky Medication Adherence Scale (MMAS-8) was issued through QR code questionnaires. Intentional and unintentional adherence scores were calculated according to specific items. Non-adherence was defined as MMAS-8 scores <6 or MPR < 0.8. RESULTS: The response rate in the IBD patients was as high as 97%. 5-ASA non-adherence rate assessed by MPR was 30% and 37% by MMAS-8, and azathioprine non-adherence rate assessed was 33% by both MPR and MMAS-8. In a linear regression analysis, MPR value was significantly correlated with MMAS-8 score in 5-ASA group (r=0.4, p=0.003), and significantly correlated with unintentional adherence score (r=0.47, p<0.001). No significant correlation was observed between MPR value and MMAS-8 score in azathioprine group. Multivariate analysis demonstrated that age (OR: 1.08; 95% CI: 1.02-1.13; P=0.0015) and previous abdominal surgery (OR: 3.18; 95% CI: 2.09-4.27; P=0.04) were associated with high medication adherence. While patients who had small intestine lesion (OR: 0.09; 95% CI: 0.01-0.17; P=0.006) were associated with low adherence. CONCLUSION: Predictors of low adherence were young age, lesions on small intestine, whereas previous abdominal surgery was a protective factor. This study also demonstrated that the MMAS-8 scale was a valid instrument for assessing 5-ASA adherence in IBD patients. Unintentional non-adherence was significantly related to the total non-adherence, which would allow to use the tool to seek ways for adherence improvement.

Construction and analysis of lncRNA-associated ceRNA network identified potential prognostic biomarker in gastric cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are defined as non-coding RNA (ncRNA) with transcripts longer than 200 nucleotides with tissue specificity. Recently it has been found participate in cancer tumorigenesis and progression via transcriptional regulation, post-transcriptional regulation and epigenetic gene regulation. Competitive endogenous RNA (ceRNA) hypothesis assume that lncRNAs compete the target RNA by sponging the common miRNA response elements (MREs) to complete the post-transcriptional regulation. To explore the function and mechanisms of lncRNAs as ceRNAs in gastric cancer (GC), this study performed a genome-wide analysis. METHODS: The lncRNAs, mRNAs and microRNAs (miRNAs) profiles of 375 GC samples and 32 normal samples were obtained from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) datasets. The data was standardized with a cross match in the miRBase (a database at http://www.mirbase.org/), which made 365 samples as the analysis objects. We identify differentially expressed RNAs (DERNAs), including differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) by applying edge R package with thresholds of |log2FC| >2 and false discovery rate (FDR) <0.01. The potential RNAs for the gastric ceRNA network were screened out from the DERNAs based on "ceRNA hypothesis". The further construction of the network and analysis of its topological properties were performed by Cytoscape. Gene oncology (GO) function enrichment was analyzed by BINGO plugin of Cytoscape. Survival analysis was estimated according to Kaplan-Meier curve analysis. RESULTS: The constructed gastric ceRNA network involved 61 mRNAs, 44 lncRNAs and 22 miRNAs. Five lncRNAs out of the DElncRNAs, namely MIR100HG, MAGI2-AS3, AC080038.1, AC010478.1 and MEF2C-AS1, were found mostly involved in the network. The lncRNA AL139147 were detected negatively correlated with overall survival (log-rank, P<0.05). CONCLUSIONS: In conclusion, our study identified promising lncRNAs, which might be potential diagnostic biomarker and therapeutic targets and contribute to further understanding of the ceRNA pathogenesis in GC and guide for further investigation.

Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells.

The aim of the present study was to investigate the effect of cantharidin (CTD) on human gastric cancer cells and to explore the underlying mechanisms of these effects. The human gastric cancer SGC-7901 and BGC-823 cell lines were treated with CTD. MTS assays were then employed to examine cellular proliferation, flow cytometry was used to analyze the cell cycle and apoptosis, and western blot analysis was used to determine protein expression levels. It was found that CTD inhibited the proliferation of the human gastric cancer SGC-7901 and BGC-823 cells in a dose- and time-dependent manner in vitro. CTD also induced G2/M phase arrest and cellular apoptosis in a dose-dependent manner. In addition, CTD increased the levels of p21, caspase-7, -8 and -9, activated caspase-3, poly ADP ribose polymerase and Bad, but decreased the levels of cyclin-dependent kinase 1, cyclin A and B, B-cell lymphoma-2 (Bcl-2) and Bid. The present results suggested that CTD may inhibit the proliferation of human gastric cancer SGC-7901 and BGC-823 cells in vitro by inducing G2/M phase arrest and cell apoptosis. CTD may induce cellular G2/M phase arrest by regulating cycle-associated proteins and induce apoptosis by activating a caspase cascade or regulating the Bcl-2 family proteins.

Non-essential amino acids attenuate apoptosis of gastric cancer cells induced by glucose starvation.

Energy and nutrition are essential requirements for all living cells, including cancer cells. In the initiating stage of cancer in organs, cancer cells grow fast and have inadequate supplies of glucose, oxygen and other nutrients due to deficient angiogenesis. Anaerobic conditions cause cancer cells to rely on glycolysis, which produces pyruvate and ATP that can be used by cancer cells to survive. However, glucose starvation may result in apoptosis or necrosis of cancer cells. It has been reported that autophagy is a consequence of glucose starvation and that amino acids are products of autophagy. The present study investigated whether amino acids may represent an alternative energy source for cancer cells undergoing glucose starvation. With non-essential amino acids, growth inhibition and apoptosis of gastric cancer cells induced by glucose starvation were attenuated compared with that of cells undergoing glucose starvation without amino acids, as measured by cell viability, apoptosis rates, membrane potential of mitochondria, and apoptosis-related genes. Meanwhile, both mitochondrial DNA copy number and amino acid transporter genes were increased compared with those in control cells. Non-essential amino acids prevented gastric cancer cells from glucose starvation-induced apoptosis.