Dioscin ameliorates inflammatory bowel disease by up-regulating miR-125a-5p to regulate macrophage polarization.

PURPOSE: Dioscin has been proven to have anti-cancer, anti-inflammatory, and anti-infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study. METHODS: The colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR-125a-5p level were detected by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), FITC-dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin-4 (IL-4), were treated with Dioscin and miR-125a-5p inhibitor, miR-125a-5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT-PCR and MTT assay. RESULTS: Dioscin (20, 40, or 80 mg/kg) relieved DSS-triggered colitis and restrained the serum and colon of pro-inflammatory cytokines expression. Meanwhile, different concentrations' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR-125a-5p level in colitic mice. Moreover, miR-125a-5p inhibitor reversed the modulation of Dioscin on miR-125a-5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase-1) expressions in vitro, which was reversed by miR-125a-5p inhibitor. CONCLUSION: Dioscin modulated macrophage polarization by increasing miR-125a-5p, thereby improving the intestinal epithelial barrier function and reducing IBD.

Prediction of severe acute pancreatitis using classification and regression tree analysis.

BACKGROUND: The available prognostic scoring systems for acute pancreatitis have limitations that restrict their clinical value. AIMS: To develop a decision model based on classification and regression tree (CART) analysis for the prediction of severe acute pancreatitis (SAP). METHODS: A total of 420 patients with acute pancreatitis were enrolled. Study participants were randomly assigned to the training sample and test sample in a 2:1 ratio. First, univariate analysis and logistic regression analysis were used to identify predictors associated with SAP in the training sample. Then, CART analysis was carried out to develop a simple tree model for the prediction of SAP. A receiver operating characteristic (ROC) curve was constructed in order to assess the performance of the model. The prediction model was then applied to the test sample. RESULTS: Four variables (systemic inflammatory response syndrome [SIRS], pleural effusion, serum calcium, and blood urea nitrogen [BUN]) were identified as important predictors of SAP by logistic regression analysis. A tree model (which consisted of pleural effusion, serum calcium, and BUN) that was developed by CART analysis was able to early identify among cohorts at high (79.03%) and low (7.80%) risk of developing SAP. The area under the ROC curve of the tree model was higher than that of the APACHE II score (0.84 vs. 0.68; P < 0.001). The predicted accuracy of the tree model was validated in the test sample with an area under the ROC curve of 0.86. CONCLUSIONS: A decision tree model that consists of pleural effusion, serum calcium, and BUN may be useful for the prediction of SAP.

Cell division cycle protein 42 regulates the inflammatory response in mice bearing inflammatory bowel disease.

This study aimed to explore the effect of cell division cycle protein 42 (CDC42) on inflammatory response and immune response in mice bearing inflammatory bowel disease (IBD). Trinitrobenzene sulfonic acid was injected into the colon of mice to establish IBD model. The mice were divided into four groups (n = 4): control, model, Ad5, and Ad5-CDC42. After establishing IBD model, mice which were treated with AD5 empty vector and AD5-CDC42 expression vector served as the Ad5 group and Ad5-CDC42 group, respectively. The mRNA and protein levels of interleukin 10 (IL-10), interferon-γ (IFN-γ), IL-4, and tumor necrosis factor-α (TNF-α) in the colon tissues were evaluated by RT-PCR and western blot, respectively. Their levels in the serum and colon tissues were examined by ELISA assay and immunohistochemical analysis, respectively. Their changes in the mRNA and protein levels were consistent and similar changes in the colon tissues and the serum were found among various groups. The levels of IL-10, IFN-γ, IL-4, and TNF-α were lowest in the control group. Their levels in the model group and the Ad5 group were similar (p > .05) and significantly higher than those in the control group (p < .05). In comparison with the model group and the Ad5 group, their levels were significantly reduced in the Ad5-CDC42 group (p < .05). In conclusion, the levels of inflammatory cytokines were elevated in the colon tissues and serum of IBD mice, which could be reduced by the CDC42 treatment. CDC42 regulated the inflammatory response and the innate immune response in IBD mice.

Prevalence and characteristics of colonic adenoma in mainland China.

BACKGROUND AND AIM: To investigate the prevalence and characteristics of colonic adenoma and advanced colonic adenoma in a large group of patients in mainland China. MATERIALS AND METHODS: We conducted a cross-sectional study on patients who had undergone colonoscopy examination in a university hospital in mainland China. Colonic adenomas and advanced adenomas were recorded. RESULTS: The prevalence of polyps, adenoma, and advanced adenoma was 23.9%, 13.3%, and 3.5%, respectively. Age and sex were independent risk factors for the prevalence of adenoma and advanced adenoma. Polyp size was associated with an increased risk of both colonic adenoma (OR 1.50, 95% CI 1.44-1.56) and advanced adenoma (OR 2.78, 95% CI 2.55-3.03) after sex and age adjustment. Proximal colon polyps were a risk factor for adenoma (OR 1.41, 95% CI 1.20-1.66) and also associated with a significant reduction (44%) in risk of advanced adenoma (OR 0.56, 95% CI 0.36-0.86) compared to distal colon adenoma after sex and age adjustment. A screening indication was associated with a statistically significant decrease in the odds of prevalence of adenoma (OR 0.90, 95% CI 0.81-0.99) and advanced adenoma (OR 0.72, 95% CI 0.59-0.88) compared to a no-screening indication. CONCLUSION: The overall prevalence of adenoma was low in mainland China. It exhibited a varied pattern with respect to age and sex. Polyp size was a risk factor for both colonic adenoma and its transition to advanced adenoma. Proximal colon polyps were a risk factor for adenoma, but a protective factor for advanced adenoma compared to distal colon adenoma.

LINC02163 regulates growth and epithelial-to-mesenchymal transition phenotype via miR-593-3p/FOXK1 axis in gastric cancer cells.

Recently, long non-coding RNAs (lncRNAs) were involved in promoting gastric cancer (GC) initiation and progression. In the current study, we revealed that the expression level of LINC02163 was elevated in GC cell lines and tissues. Knockdown of LINC02163 inhibited GC cells growth and invasion both in vitro and in vivo. Mechanismly, LINC02163 exerted as a ceRNA and negatively regulated miR-593-3p expression. In addition, FOXK1 was identified as a down-stream target of miR-593-3p. The miR-593-3p/FOXK1 axis mediated LINC02163's effect on GC. To the best of our knowledge, our findings provided the first evidence that LINC02163 functioned as an oncogene in GC. LINC02163 may be a candidate prognostic biomarker and a target for new therapies in GC patients.

MiR-199a-5p Inhibits the Growth and Metastasis of Colorectal Cancer Cells by Targeting ROCK1.

Mounting evidence indicates that microRNAs play important roles in the development of various cancers. Aberrant expression of microRNA-199a-5p has been frequently reported in cancer studies; however, the mechanistic details of the role of microRNA-199a-5p in colorectal cancer still remain unclear. Our study aimed to explore the role of microRNA-199a-5p in colorectal cancer cells by targeting Rho-associated coiled coil-containing protein kinase 1. Here, we showed that microRNA-199a-5p was significantly downregulated in colorectal cancer cell lines and tissue samples and was associated with a poor prognostic phenotype. MicroRNA-199a-5p suppressed colorectal cancer cell proliferation, migration, and invasion and induced cell apoptosis. Moreover, we identified Rho-associated coiled coil-containing protein kinase 1 as the direct target of microRNA-199a-5p using luciferase and Western blot assays. Importantly, Rho-associated coiled coil-containing protein kinase 1 overexpression rescued the microRNA-199a-5p-induced suppression of proliferation, migration, and invasion of colorectal cancer cells. Furthermore, the overexpression of microRNA-199a-5p inhibited tumor growth and metastasis by inactivating the phosphoinositide 3-kinase/AKT and Janus kinase 1/signal transducing activator of transcription signaling pathways through downregulation of Rho-associated coiled coil-containing protein kinase 1. Altogether, microRNA-199a-5p/Rho-associated coiled coil-containing protein kinase 1 may be a potential therapeutic target for colorectal cancer therapy.

miR-1273g silences MAGEA3/6 to inhibit human colorectal cancer cell growth via activation of AMPK signaling.

AMP-activated protein kinase (AMPK) is a metabolic regulator that acts to limit the growth of cancer cells. AMPK is downregulated by melanoma antigens A3/6 (MAGEA3/6), which are cancer-specific proteins that enhance the activity of specific E3 ubiquitin ligases to ubiquitinate and degrade AMP-activated protein kinase α1 (AMPKα1). Here, using a bioinformatic approach, we identified a microRNA, miR-1273g-3p, that is predicted to target the 3' untranslated region (UTR) of MAGEA3/6. Analyzing miR-1273g-3p expression in human colon cancer tissues, we found a reduction in miR-1273g-3p expression correlating with increased MAGEA3/6 expression and AMPKα1 downregulation. Expression of miR-1273g in HT-29 cells and primary human colon cancer cells down-regulated MAGEA3/6, leading to AMPKα1 upregulation, inhibition of proliferation and cell apoptosis. The anti-CRC activity of miR-1273g was blocked by AMPKα1 knockout. MAGEA3/6 shRNA silencing mimicked and abolished miR-1273g-induced actions in HT-29 cells. In vivo, miR-1273g- or MAGEA3/6 shRNA-expressing HT-29 tumors grew significantly slower than control tumors. We propose a novel miRNA-based mechanism, whereby miR-1273g represses MAGEA3/6 expression in human CRC cells and tissues, which may provide a novel cancer-specific therapeutic.

Colonic diverticulosis is not a risk factor for colonic adenoma.

BACKGROUND AND AIMS: Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. METHODS: We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. RESULTS: A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. CONCLUSION: There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

Sedated gastroscopy improves detection of gastric polyps.

The detection rate of gastric polyps (GPs) is low, improving the detection rate would be good. The present study aimed to evaluate the role of sedated gastroscopy in GP detection. The data of patients who underwent gastroscopic examination from January 2014 to December 2016 at the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) were retrospectively reviewed. Endoscopic records of 6,195 patients diagnosed with GPs were analyzed. The GP detection rate was 3.12 and 5.11% in the unsedated and sedated gastroscopy group, respectively (P<0.05). Also after stratification by sex, the GP detection rate was significantly higher in the sedated gastroscopy group (P<0.05). In addition, patients aged ≥20 years in the sedated gastroscopy group had a higher GP detection rate than those in the unsedated gastroscopy group (P<0.05). The incidence of cardiac, gastric fundus, gastric body and multiple-site GPs was significantly different between the two groups (P<0.05). GPs ≤0.5 and >0.5 cm were more common in the sedated gastroscopy group than in the unsedated gastroscopy group (P<0.05). The common pathologic types of GPs were gastric fundus gland (52.27%) and hyperplastic polyps (34.74%). In conclusion, the GP detection rate may be improved by inhibition of gastric muscle cramping with sedation.

Prevalence of colonic diverticulosis in mainland China from 2004 to 2014.

The aim of this study was to determine the prevalence of colonic diverticulosis in mainland China. Sixty two thousand and thirty-four colonoscopies performed between Jan 2004 and Dec 2014 were reviewed retrospectively. The overall diverticulosis prevalence was 1.97% and out of this, 85.3% was right-sided. Prevalence does not change, significantly, on trends between the period 2004-2014. The peak of prevalence of diverticulosis was compared between the female group aged >70 years to the male one of 41-50 years. The other peak, otherwise, was compared between the group of 51-60 years with the right-sided diverticulosis to the one of >70 years with left-sided disease. Multivariate analysis suggested that the male gender could be a risk factor for diverticulosis in the group aged ≤70 years, but not for the older patients. In addition, among men was registered an increased risk factor for right-sided diverticulosis and, at the same time, a protective one for left-sided localization. In conclusion, the prevalence of colonic diverticulosis is very low in mainland China and it does not change significantly on trends over the time. Both the prevalence of this condition and its distribution changes according to the age and the genders. These findings may lead the researchers to investigate the mechanisms causing this kind of disease and its distribution in regard of the age and the gender.

Clinical significance of melatonin concentrations in predicting the severity of acute pancreatitis.

AIM: To assess the value of plasma melatonin in predicting acute pancreatitis when combined with the acute physiology and chronic health evaluation II (APACHEII) and bedside index for severity in acute pancreatitis (BISAP) scoring systems. METHODS: APACHEII and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEII and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concentration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEII and BISAP scoring systems, were compared between the two groups. RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEII score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEII scores (≥ 10) between the two groups was not significantly different. CONCLUSION: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.

Prediction of large esophageal varices in cirrhotic patients using classification and regression tree analysis.

OBJECTIVES: Recent guidelines recommend that all cirrhotic patients should undergo endoscopic screening for esophageal varices. That identifying cirrhotic patients with esophageal varices by noninvasive predictors would allow for the restriction of the performance of endoscopy to patients with a high risk of having varices. This study aimed to develop a decision model based on classification and regression tree analysis for the prediction of large esophageal varices in cirrhotic patients. METHODS: 309 cirrhotic patients (training sample, 187 patients; test sample 122 patients) were included. Within the training sample, the classification and regression tree analysis was used to identify predictors and prediction model of large esophageal varices. The prediction model was then further evaluated in the test sample and different Child-Pugh classes. RESULTS: The prevalence of large esophageal varices in cirrhotic patients was 50.8%. A tree model that was consisted of spleen width, portal vein diameter and prothrombin time was developed by classification and regression tree analysis achieved a diagnostic accuracy of 84% for prediction of large esophageal varices. When reconstructed into two groups, the rate of varices was 83.2% for high-risk group and 15.2% for low-risk group. Accuracy of the tree model was maintained in the test sample and different Child-Pugh classes. CONCLUSIONS: A decision tree model that consists of spleen width, portal vein diameter and prothrombin time may be useful for prediction of large esophageal varices in cirrhotic patients.

Prediction of large esophageal varices in cirrhotic patients using classification and regression tree analysis

OBJECTIVES: Recent guidelines recommend that all cirrhotic patients should undergo endoscopic screening for esophageal varices. That identifying cirrhotic patients with esophageal varices by noninvasive predictors would allow for the restriction of the performance of endoscopy to patients with a high risk of having varices. This study aimed to develop a decision model based on classification and regression tree analysis for the prediction of large esophageal varices in cirrhotic patients. METHODS: 309 cirrhotic patients (training sample, 187 patients; test sample 122 patients) were included. Within the training sample, the classification and regression tree analysis was used to identify predictors and prediction model of large esophageal varices. The prediction model was then further evaluated in the test sample and different Child-Pugh classes. RESULTS: The prevalence of large esophageal varices in cirrhotic patients was 50.8 percent. A tree model that was consisted of spleen width, portal vein diameter and prothrombin time was developed by classification and regression tree analysis achieved a diagnostic accuracy of 84 percent for prediction of large esophageal varices. When reconstructed into two groups, the rate of varices was 83.2 percent for high-risk group and 15.2 percent for low-risk group. Accuracy of the tree model was maintained in the test sample and different Child-Pugh classes. CONCLUSIONS: A decision tree model that consists of spleen width, portal vein diameter and prothrombin time may be useful for prediction of large esophageal varices in cirrhotic patients.