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The epithelial tight junctions of intestine were impaired in murine model of type 2 diabetes mellitus (T2DM). The aim of this work was to investigate the alteration of intestinal barrier in T2DM patients.90 patients with T2DM and 28 healthy controls were recruited. Serum lipopolysaccharide (LPS), Zonulin, and intestinal fatty acid binding protein (IFABP) were measured by ELISA, based on which a derived permeability risk score (PRS) was calculated. Subgroup analyses were conducted based on the glycemic control (HbA1c 7%, or HbA1c ≥ 7%), the amount of chronic diabetic complications, and the use of aspirin at the time.Serum LPS, Zonulin, and IFABP, and PRS of T2DM group were significantly higher than those of the control group (p 0.05 for all). Serum LPS and PRS was higher in T2DM patients with poor glycemic control (both p 0.05). Patients with more chronic complications of diabetes had higher serum LPS and IFABP, and PRS (all p 0.05). No differences were found in these serum markers between T2DM patients being treated with aspirin or not.Intestinal barrier function was impaired in T2DM patients. Poor glycemic control and more chronic complications of diabetes were associated with worse intestinal barrier function. Treatment with aspirin did not aggravate the impairment of intestinal barrier in T2DM patients.

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.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.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 p0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient=0.55; p0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p0.01).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.

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P

Colon cancer is one of the most common cancers in the world. Multidrug resistance is related to poor prognosis of advanced colon cancer. The side population plays an important role in multiple drug resistance (MDR) of colon cancer. MicroRNA biomarkers of the side population of colon cancer is still unknown. In the present study, we aimed to explore miRNA markers of side population (SP) cells of colon cancer. The side population was sorted by flow cytometry. Cell viability was measured using an MTT assay. MicroRNA profiling analysis was performed to compare microRNA expression levels in the SP cells of colon cancer with levels in the non-SP cells of colon cancer. RT-PCR was applied to verify the result obtained from the microRNA profiling analysis. miR-5000-3p, miR-5009-3P and miR-552 were all found to be upregulated in SP cells of the colon cancer cell lines HCT-15, HT-29 and LoVo. RT-PCR confirmed the result from the microRNA profiling analysis. This implied that miR-5000-3p, miR-5009-3P and miR-552 may be potential microRNA biomarkers of the side population in colon cancer, which may provide new specific targets of the side population for the reversal of MDR of colon cancer.

National Natural Science Foundation of China [40476040, 41076049]; Marine Public Welfare Project of China [200805064]

National Natural Science Foundation of China [40476040]; New Century Excellent Talents in University (NCET

Several indigenous groups in northwestern North America used native copper prior to EuroAmerican contact. The Arctic, Subarctic, and Northwest Coast culture areas all have archaeological finds and geological sources of native copper. The copper-rich region of south-central Alaska and southwestern Yukon has often been credited as the source of archaeological native copper found on the Northwest Coast despite the presence of native copper sources further south. This paper presents the results of a pilot study using INAA, ICP-MS, and LA-MC-ICP-MS to assess the potential for native copper provenance research in Alaska and the Yukon Territory. Discrete native copper sources could be distinguished from one another intra-regionally. Difficulties associated with future native copper provenance research in northwestern North America are discussed.

The feeding ecology of Sesarma plicata (Grapsidae: Sesarminae), the most abundant crab species in a mangrove forest dominated by Kandelia candel at Jiulongjiang Estuary, China, was investigated through field and laboratory experiments. Feeding preference and consumption rates were determined on mature, senescent and decomposed leaves of Kandelia candel, Bruguiera gymnorrhiza and Aegiceras corniculatum. In the laboratory, S. plicata preferred leaves of K. candel over those of B. gymnorrhiza and A. corniculatum, and consumed significantly more decomposed leaves than mature and senescent ones, irrespective of crab size. Field experiments with limited power failed to reveal detectable species preferences despite more consumption of K. candel, but decomposed leaves of each species were again preferred. Leaf characteristics associated with preference changed with plant species and leaf state. Low tannins and high water content characterized the preference for decomposed state of leaves. Species preference was significantly and negatively related to crude fibers and C:N ratios for mature leaves, and crude fiber for senescent leaves, but significantly and positively related to water content for decomposed leaves. Leaf consumption rates averaged for all leaf categories from laboratory no-choice feeding experiments were 0.101, 0.055 and 0.017 gDW ind−1 d−1 for large, medium and small crabs, respectively. In this forest, mean density of S. plicata was 20.5 ind m−2 as assessed by a manual catching method. Leaf litter removal rate during neap tides by sesarmid crabs was about 1.33 gDW m−2 d−1 in April 2006. The leaves removed by crabs were grazed on the sediment surface or taken into crab burrows, shredded and stored before being eaten.

Distribution properties of macro-benthic faunal communities were compared among rehabilitated Kandelia candel forests of different ages in Jiulongjiang Estuary, China. From July 2005 to April 2006, seasonal surveys were conducted within four representative forests—K4, K7, K19 and K43, with ages of 4, 7, 19 and 43 years, respectively. Two non-vegetated flats (NF1 and NF2) were set as the references. Numbers of faunal species in rehabilitated forests were higher than NF1 and NF2, while younger forests (K4 and K7) generally had more macro-benthic fauna species than older ones (K19 and K43). Among the total 24 species recorded, Uca arcuata , Metaplax elegans , Phascolosoma esculenta and Littoraria melanostoma were dominant. Macro-benthic faunal community structures were different among the four rehabilitated K. candel forests. The dominant species in younger forests was M. elegans , while U. arcuata had a higher abundance than M. elegans in non-vegetation flats and older forests. Gastropods were abundant in younger forests. Distribution properties of dominant species differed among rehabilitated K. candel forests. U. arcuata had the largest density in non-vegetated flats, and was infrequent in younger forests. M. elegans had high abundances in younger forests. High abundance of P. esculenta was found in older forests, while L. melanostoma was more abundant in younger forests. Since both macro-benthic faunal community and vegetation were similar in K19 and K43, rehabilitated K. candel mangrove was considered steady 19 years after being planted. That is, in the case of macro-benthic fauna and vegetation, a K. candel mangrove may evolve to a mature state at a stand age of about 20 years.

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.

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P 0.05). The expression of Zo1 and Ocln in the small intestine of diabetic mice were lower, while the markers for absorptive cell (SI) and Paneth cell (Lyz1) were significantly higher than in control mice (P 0.05). The expression of Msi1, Notch1, and Dll1 in small intestine gradually increased throughout the course of hyperglycemia in diabetic mice (P 0.05). However, the expression of NICD, RBP-jκ, Math1, and Hes1 had a reverse trend compared with Msi1 and Notch1. Intestinal absorptive cells and Paneth cells had a high proliferation rate in diabetic mice. However, the intestinal barrier dysfunction associated with the decreased expressions of Zo1 and Ocln was detected throughout hyperglycemia. In conclusion, downregulation of Notch/Hes1 signal pathway caused by depressed Notch/NICD transduction is associated with the abnormal differentiation of IECs and intestinal barrier dysfunction in diabetic mice.

The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years.This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cirrhosis. Of these, 86 patients received lamivudine 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment.The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine.Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawing definitive conclusions.

BackgroundEnteral 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 findingsWe 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, P0.05). 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 PConclusionEnteral 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.

To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis. Relevant book chapters were also reviewed.Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.Specific antiviral agents not only control viral replication, which permits liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant.Although the treatment of end-stage liver disease is still a challenge worldwide, antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.