Jie-Yao Li

Enteral nutrition within 48 hours of admission improves clinical outcomes of acute pancreatitis by reducing complications: a meta-analysis.

Background Enteral nutrition is increasingly advocated in the treatment of acute pancreatitis, but its timing is still controversial. The aim of this meta-analysis was to find out the feasibility of early enteral nutrition within 48 hours of admission and its possible advantages. Methods and Findings We searched PubMed, EMBASE Databases, Web of Science, the Cochrane library, and scholar.google.com for all the relevant articles about the effect of enteral nutrition initiated within 48 hours of admission on the clinical outcomes of acute pancreatitis from inception to December 2012. Eleven studies containing 775 patients with acute pancreatitis were analyzed. Results from a pooled analysis of all the studies demonstrated that early enteral nutrition was associated with significant reductions in all the infections as a whole (OR 0.38; 95%CI 0.21–0.68, P<0.05), in catheter-related septic complications (OR 0.26; 95%CI 0.11–0.58, P<0.05), in pancreatic infection (OR 0.49; 95%CI 0.31–0.78, P<0.05), in hyperglycemia (OR 0.24; 95%CI 0.11–0.52, P<0.05), in the length of hospitalization (mean difference −2.18; 95%CI −3.48−(−0.87); P<0.05), and in mortality (OR 0.31; 95%CI 0.14–0.71, P<0.05), but no difference was found in pulmonary complications (P>0.05). The stratified analysis based on the severity of disease revealed that, even in predicted severe or severe acute pancreatitis patients, early enteral nutrition still showed a protective power against all the infection complications as a whole, catheter-related septic complications, pancreatic infection complications, and organ failure that was only reported in the severe attack of the disease (all P<0.05). Conclusion Enteral nutrition within 48 hours of admission is feasible and improves the clinical outcomes in acute pancreatitis as well as in predicted severe or severe acute pancreatitis by reducing complications.

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

Diabetes mellitus increases the risk of colorectal neoplasia: An updated meta-analysis

OBJECTIVE Recent studies proved that patients with diabetes were at significantly higher risk of developing colorectal cancer. However, the association between diabetes mellitus and the risk of colorectal adenoma remains undefined. Thus we conducted an updated meta-analysis to identify the association between diabetes mellitus and the risk of colorectal neoplasia including adenoma and cancer. METHODS We conducted a search in databases including Pubmed, Web of Science, EMBASE Databases, Cochrane CENTRAL, Wanfang Data, and CNKI database. Case-control and cohort studies were included. All articles were published before January 2015 and the quality of each study was evaluated by the Newcastle-Ottawa Scale. Odds ratios (ORs) or relative risks (RRs) and its corresponding 95% confidence intervals (CIs) for each study were calculated and summary relative risk estimates with corresponding 95% CIs were generated using the random-effects model. Heterogeneity and publication bias were assessed. RESULTS Twenty-nine articles including ten case-control studies and nineteen cohort studies were included in this meta-analysis. In a pooled analysis of all studies, diabetes mellitus was associated with increased risk of colorectal neoplasia (RR=1.35, 95% CI=1.28-1.42). The risk increased significantly for both colorectal cancer (RR=1.37, 95% CI=1.30-1.45) and adenoma (RR=1.26, 95% CI=1.11-1.44). Subgroup analyses on study design, gender, geographical region, and type of diabetes mellitus further evidenced these findings. CONCLUSIONS Diabetes mellitus was associated with an increased risk of colorectal neoplasia. Not only the increased risk of colorectal cancer but also the higher risk of adenoma was identified in patients with diabetes mellitus.

miRNA‐30e regulates abnormal differentiation of small intestinal epithelial cells in diabetic mice by downregulating Dll4 expression

Depression of the Notch/Hes1 pathway has been reported to play a role in abnormal differentiation of intestinal epithelial cells (IECs) in diabetes mellitus (DM). However, the mechanism by which this pathway influences IEC differentiation has remained unclear. In this study, we have investigated the role of microRNAs (miRNAs) in regulating the Notch/Hes1 pathway in IECs of DM mice.

Knockdown of linc-POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer

Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). Here, we investigated the association of linc-POU3F3 and prognosis in CRC. We demonstrated that linc-POU3F3 was overexpressed in CRC tissues and positively correlated with tumor grade and N stage. Inhibition of linc-POU3F3 resulted in inhibition of cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, p18, Rb, and phosphorylated Rb. Inhibition of linc-POU3F3 induced apoptosis, and suppressed migration and invasion in LOVO and SW480 cell lines. This inhibition also increased the expressions of epithelial markers and decreased the expressions of mesenchymal markers, thus inhibiting the cancer epithelial-mesenchymal transition. The decreased migration and invasion following linc-POU3F3 knockdown were mediated by an increased BMP signal. Furthermore, autophagy was enhanced by linc-POU3F3 knockdown, suggesting the involvement of autophagy in the induced apoptosis. Collectively, linc-POU3F3 might be crucial in pro-proliferation, anti-apoptosis, and metastasis in LOVO and SW480 cells by regulating the cell cycle, intrinsic apoptosis, BMP signaling and autophagy. Thus, linc-POU3F3 is a potential therapeutic target and novel molecular biomarker for CRC.

Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation

AIMS β-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear. METHODS Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n=6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence. RESULTS Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p<0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient=0.55; p<0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p<0.01). CONCLUSIONS Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.

Overexpression of miR-429 impairs intestinal barrier function in diabetic mice by down-regulating occludin expression

Diabetes mellitus (DM) is a group of metabolic diseases characterised by insulin deficiency/resistance and hyperglycaemia. We previously reported the presence of an impaired tight junction and decreased expression of occludin (Ocln) and zonula occludens-1 (ZO-1) in the intestinal epithelial cells (IECs) of type 1 DM mice, but the exact mechanism remains unclear. In this study, we investigated the role of microRNAs (miRNAs) in impairing the tight junction in IECs of DM mice. Using an integrated comparative miRNA microarray, miR-429 was found to be up-regulated in IECs of type 1 DM mice. Then, miR-429 was confirmed to directly target the 3’-UTR of Ocln, although it did not target ZO-1. Moreover, miR-429 down-regulated the Ocln expression in IEC-6 cells in vitro. Finally, exogenous agomiRNA-429 was shown to down-regulate Ocln and induce intestinal barrier dysfunction in normal mice, while exogenous antagomiRNA-429 up-regulated Ocln in vivo and improved intestinal barrier function in DM mice. In conclusion, increased miR-429 could down-regulate the expression of Ocln by targeting the Ocln 3′-UTR, which impaired intestinal barrier function in DM mice.

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

Background The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. Methods BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. Results COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Conclusion Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

Helicobacter pylori Infection Is Associated with Type 2 Diabetes, Not Type 1 Diabetes: An Updated Meta-Analysis

Background Extragastric manifestations of Helicobacter pylori (H. pylori) infection have been reported in many diseases. However, there are still controversies about whether H. pylori infection is associated with diabetes mellitus (DM). This study was aimed at answering the question. Methods A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reporting H. pylori infection in both DM and non-DM individuals were recruited. Results 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence of H. pylori infection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69, P < 0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77–1.96, P = 0.38). Conclusion Our meta-analysis suggested that there is significantly higher prevalence of H. pylori infection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.

Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state

BackgroundDistinctive structures called crypts harbor intestinal epithelial stem cells (IESCs) which generate progenitor and terminally differentiated cells in the intestinal epithelium. Mammalian IESCs and their daughter cells require the participation of DNA methylation and the transcription factor Sox9 for proliferation and differentiation. However, the association between Sox9 and DNA methylation in this process remains elusive.MethodsThe DNA methylation of small intestinal epithelial crypts in db/db mice was detected via combining methylated DNA immunoprecipitation with microarray hybridization. DNA methylation of Sox9 promoter in crypts and IESCs was validated using bisulfite sequence analysis. The target sequence of the transcription factor Sox9 in IESCs was investigated via chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq).ResultsIncreased Sox9 expression is accompanied by the loss of methylation in its promoter in IESCs. Sox9 targets the enhancers of the Wnt signaling pathway-related genes. Sox9 predominantly acts as a transcriptional activator at proximal enhancers of Wnt4, Tab2, Sox4, and Fzd8, but also functions as a potential transcriptional inhibitor at a distant enhancer of Cdk1. Lack of Sox9 transcriptional activation in specific repressors of the Wnt signaling pathway leads to the loss of intrinsic inhibitory action and ultimately produces overactivation of this pathway in db/db mice.ConclusionsOur study sheds light on the connections among DNA methylation, transcription factor modulation, and Wnt signaling in IESCs in the diabetic state. Hypomethylation in the Sox9 promoter is correlated to increased Sox9 expression in db/db IESCs. Although there is increased expression of Sox9 in db/db IESCs, the loss of Sox9 transcriptional activation in specific repressors of the Wnt signaling pathway might result in abnormalities in this pathway.