[Show abstract][Hide abstract] ABSTRACT: Colorectal liver metastases (CLM) occur frequently and postoperative intestinal infection is a common complication. Our previous study showed that probiotics could decrease the rate of infectious complications after colectomy for colorectal cancer. To determine the effects of the perioperative administration of probiotics on serum zonulin levels which is a marker of intestinal permeability and the subsequent impact on postoperative infectious complications in patients with CLM.
150 patients with CLM were randomly divided into control group (n = 68) and probiotics group (n = 66). Probiotics and placebo were given orally for 6 days preoperatively and 10 days postoperatively to control group and probiotics group respectively. We used the local resection for metastatic tumor ,while for large tumor, the segmental hepatectomy. Postoperative outcome were recorded. Furthermore, complications in patients with normal intestinal barrier function and the relation with serum zonulin were analyzed to evaluate the impact on the liver barrier dysfunction.
The incidence of infectious complications in the probiotics group was lower than control group. Analysis of CLM patients with normal postoperative intestinal barrier function paralleled with the serum zonulin level. And probiotics could also reduce the concentration of serum zonulin (P = 0.004) and plasma endotoxin (P < 0.001).
Perioperative probiotics treatment could reduce the serum zonulin level, the rate of postoperative septicemia and maintain the liver barrier in patients undergoing CLM surgery. we propose a new model about the regulation of probiotics to liver barrier via clinical regulatory pathway. We recommend the preoperative oral intake of probiotics combined with postoperative continued probiotics treatment in patients who undergo CLM surgery.
ChiCTR-TRC- 12002841 . 2012/12/21.
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to develop an in situ immune marker model to predict postoperative oncological outcomes in patients with colorectal cancer (CRC).
Immunohistochemistry for 13 immune cell markers was performed on tumor tissue microarrays from 300 CRC patients who underwent curative resection from January 2000 to January 2006. Genetic algorithm was applied for the construction of an in situ immune marker model.
The infiltration of CD3+ cells, CD45RO+ cells, and FOXP3+ cells, but not the infiltration of Tryptase+ cells, in the tumor was significantly associated with better clinical outcome in overall survival (OS) and disease-free survival (DFS) of CRC patients, as assessed by univariate analysis (P < 0.05). Based on the genetic algorithms, a total of 6 markers, including CD3, CD45RO, IL17, CD15, Tryptase, and FOXP3, were selected to construct an immune marker model. Our model was identified to have an independent predictive capability for both OS and DFS in Cox multivariable model (P < 0.001). This was further confirmed by the ROC analysis (area under curve: OS, 0.669; DFS, 0.684).
The in situ immune marker model constructed in this study provides a novel approach to identify CRC patients who were at an increased risk for poor oncological outcomes.
Annals of Surgical Oncology 11/2015; DOI:10.1245/s10434-015-4889-1 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The majority of biosynthetic secretory proteins initiate their journey through the endomembrane system from specific subdomains of the endoplasmic reticulum (ER). At these locations, coated transport carriers are generated, with the Sar1 GTPase playing a critical role in membrane bending, recruitment of coat components, and nascent vesicle formation. How these events are appropriately coordinated remains poorly understood. Here, we demonstrate that Sar1 acts as the curvature sensing component of the COPII coat complex and highlight the ability of Sar1 to bind more avidly to membranes of high curvature. Additionally, using an atomic force microscopy-based approach, we further show that the intrinsic GTPase activity of Sar1 is necessary for remodeling lipid bilayers. Consistent with this idea, Sar1-mediated membrane remodeling is dramatically accelerated in the presence of its guanine nucleotide activating protein (GAP), Sec23-Sec24, and blocked upon addition of GMP-PNP, a poorly hydrolysable analog of GTP. Our results also indicate that Sar1 GTPase activity is stimulated by membranes that exhibit elevated curvature, potentially enabling Sar1 membrane scission activity to be spatially restricted to highly bent membranes that are characteristic of a bud neck. Taken together, our data support a stepwise model in which the amino-terminal amphipathic helix of GTP-bound Sar1 stably penetrates the ER membrane, promoting local membrane deformation. As membrane bending increases, Sar1 membrane binding is elevated, ultimately culminating in GTP hydrolysis, which may destabilize the bilayer sufficiently to facilitate membrane fission.
Journal of Biological Chemistry 11/2015; DOI:10.1074/jbc.M115.672287 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to better understand the effect of amyloid-β plaques on magnetic resonance T2 relaxation time. We investigated these changes associated with age in an APP/PS1 mouse model of AD at 7 Tesla, combined with histology. Ten double-transgenic AD and ten wild type (WT) female mice (aged 12-20 months) were used in a cross-sectional study. Mean T2 values and standard deviations were calculated for each Regions of interest (ROIs) on T2 map. Immunohistochemistry for amyloid plaques and fluorescence staining with thioflavine S were performed of brain sections after imaging. The results showed that mean T2 values of the hippocampus, cortex, corpus callosum, and thalamus of older mice were significantly lower than of the younger. Compared to WT mice, the T2 values of the hippocampus, corpus callosum, and thalamus in younger AD mice were significantly greater, while the T2 values of the hippocampus and cortex in older AD mice were significantly less. Aβ-40 immunohistochemistry and thioflavine S stainging were positive in the matched region both for younger and older AD mice, while neither Aβ-40 nor thioflavine S were observed in WT mice. These findings suggest that regional T2 values of AD mice may decrease with age, and changes in T2 values in AD mice may be influenced by many factors besides amyloid-β plaque accumulation. Furthermore, they support that the standard deviation of the mean T2 value should be considered as well as the mean.
[Show abstract][Hide abstract] ABSTRACT: The ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) is involved in the induction of apoptosis and suppression of tumour formation. We previously showed that it was expressed at lower levels in human glioma tissues compared with normal brain tissues. However, the mechanism underlying this is unclear. Here, we reported that a novel short variant (Nrdp1S), lacking 71 amino acids at the N-terminal, was expressed in normal human brain tissue, but absent from glioma tissues. Similar to Nrdp1, Nrdp1S could be degraded by the proteasomal pathway, but exhibited an even longer half-life than Nrdp1. Nrdp1S was also shown to form a heterodimer with Nrdp1, which increased its stability, thereby augmenting the Nrdp1-mediated ubiquitination and degradation of ErbB3. EdU incorporation, MTT assay and in vitro colony formation demonstrated that Nrdp1S significantly inhibited the cell tumourigenicity. These results together suggest that Nrdp1S is a tumour suppressor that which potentiates the Nrdp1-mediated ubiquitination and degradation of ErbB3. An Nrdp1S deficiency may also be an important factor in the loss of Nrdp1.
Journal of Cellular and Molecular Medicine 11/2015; DOI:10.1111/jcmm.12735 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
B-cell-lymphoma-2 (Bcl-2) is a proto-oncogene that plays an important role in the regulation of apoptosis and cell survival. However, there are much conflicting data in the literature concerning the association between Bcl-2 and prognosis in non-small-cell lung cancer (NSCLC). There is little in the way of meta-analysis focused on Bcl-2 and its effect on NSCLC prognosis. This study was performed to provide an assessment of whether expression levels of Bcl-2 are associated with prognosis in patients with NSCLC.
Materials and methods:
We searched PubMed, the Cochrane Library, and China National Knowledge Infrastructure for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival were evaluated.
Fifty published studies including 6,863 patients with lung cancer were included in this meta-analysis. Overall, Bcl-2 was expressed in 33% of the NSCLC tumors studied. Our analysis indicates that NSCLC patients with Bcl-2-positive expression have a better prognosis than those with Bcl-2-negative expression in both Asian and non-Asian study populations (HR 0.79, 95% CI 0.72-0.87, P<0.00001). However, Bcl-2-positive expression seems to have no significant impact on survival of stage I NSCLC patients.
Our results indicated that Bcl-2 might be a useful prognostic marker for NSCLC generally. Larger clinical trials are needed to confirm the prognostic value of Bcl-2 in stage I NSCLC.
OncoTargets and Therapy 11/2015; 8:3361. DOI:10.2147/OTT.S89275 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single-layered MoS2-based ultrathin membranes with well-controlled thicknesses are prepared by a simple filtration method, and for the first time applied to gas separation. These membranes exhibit superior H2/CO2 separation performance and extremely high H2 permeance. The H2/CO2 separation performance surpasses the state-of-the-art upper-bound of polymeric and inorganic membranes.
[Show abstract][Hide abstract] ABSTRACT: Research on personality and adiposity has focused primarily on Western samples; less is known about the personality correlates of BMI in Asian populations. We examined the association between personality and Body Mass Index (BMI) among community-dwelling Japanese adults (N=380), Chinese adolescents (N=5,882), and a meta-analysis inclusive of a published Korean sample (total N=10,304). In the new samples and meta-analysis, Extraversion and Agreeableness were associated with higher BMI among men. In contrast to what is often found in Western samples, Conscientiousness was mostly unrelated to adiposity. These findings link pro-social tendencies to overweight among Asian men; Conscientiousness may be less relevant for BMI in Eastern societies with a low prevalence of obesity and strong social norms for eating but not thinness.
Journal of Research in Personality 10/2015; 58:137-142. DOI:10.1016/j.jrp.2015.07.006 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods: We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion: All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of human cancers in future studies.
International Journal of Nanomedicine 10/2015; 10:6689. DOI:10.2147/IJN.S90587 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 3C-SiC thin films were grown on Si(111) substrates at 1250 °C by horizontal low pressure chemical vapor deposition (LPCVD). We performed an exhaustive study on the effect of H2 flow rate on the crystalline quality, surface morphologies, growth rate, n-type doping of 3C-SiC thin films and the voids at the interface. The films show epitaxial nature with high crystal quality and surface morphology increase obviously with increasing H2 flow rate. The growth rate and n-type doping are also dependent on H2 flow rate. The properties of the voids at the interface are discussed based on the cross-sectional scanning electron microscope characterization. Transformation of voids with increasing H2 flow rate are attributed to higher 3C-SiC film growth rate and H2 etching rate. The mechanism of void formation is discussed based on our model, too. The results demonstrate that H2 flow rate plays a very important role in the heteroepitaxial growth of 3C-SiC films.
[Show abstract][Hide abstract] ABSTRACT: The Legionella pneumophila serogroups O1, O4, O6, O7, O10 and O13 are pathogenic strains associated with pneumonia. The surface O-antigen gene clusters of L. pneumophila serogroups O4, O6, O7, O10 and O13 were sequenced and analyzed, with the function annotated on the basis of homology to that of the genes of L. pneumophila serogroup O1 (L. pneumophila subsp. pneumophila str. Philadelphia 1). The gene locus of the six L. pneumophila serogroups contains genes of yvfE, neuABCD, pseA-like for nucleotide sugar biosynthesis, wecA for sugar transfer, and wzm as well as wzt for O-antigen processing. The detection of O-antigen genes allows the fine differentiation at species and serogroup level without the neccessity of nucleotide sequencing. The O-antigen-processing genes wzm and wzt, which were found to be distinctive for different for different serogroups, have been used as the target genes for the detection and identification of L. pneumophila strains of different O serogroups. In this report, a multiplex PCR assay based on wzm or wzt that diferentiates all the six serogroups by amplicon size was developed with the newly designed specific primer pairs for O1 and O7, and the specific primer pairs for O4, O6, O10, and O13 reported previously. The array was validated by analysis of 34 strains including 15 L. pneumophila O-standard reference strains, eight reference strains of other Legionella non-pneumophila species, six other bacterial species, and five L. pneumophila environmental isolates. The detection sensitivity was one ng genomic DNA. The accurate and sensitive assay is suitable for the identification and detection of strains of these serogroups in environmental and clinical samples.
Antonie van Leeuwenhoek 09/2015; 108(6). DOI:10.1007/s10482-015-0594-0 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The identification and phylogenetic relationships of bacteria within the Bacillus cereus group are controversial. This study aimed at determining the taxonomic affiliations of these strains using the whole-genome sequence-based Genome BLAST Distance Phylogeny (GBDP) approach. The GBDP analysis clearly separated 224 strains into 30 clusters, representing eleven known, partially merged species and accordingly 19-20 putative novel species. Additionally, 16S rRNA gene analysis, a novel variant of multi-locus sequence analysis (nMLSA) and screening of virulence genes were performed. The 16S rRNA gene sequence was not sufficient to differentiate the bacteria within this group due to its high conservation. The nMLSA results were consistent with GBDP. Moreover, a fast typing method was proposed using the pycA gene, and where necessary, the ccpA gene. The pXO plasmids and cry genes were widely distributed, suggesting little correlation with the phylogenetic positions of the host bacteria. This might explain why classifications based on virulence characteristics proved unsatisfactory in the past. In summary, this is the first large-scale and systematic study of the taxonomic status of the bacteria within the B. cereus group using whole-genome sequences, and is likely to contribute to further insights into their pathogenicity, phylogeny and adaptation to diverse environments.
[Show abstract][Hide abstract] ABSTRACT: Polymerase chain reaction (PCR) is widely used in molecular biology and clinical medicine. However, it is inhibited due to its by-product, pyrophosphate, at high temperatures. In this work, we reported a strategy to improve the PCR yield using a conjugate of pyrophosphatase (PPase) with the thermally-responsive polymer poly(N-isopropylacrylamide). The optimum temperature of the conjugates increased to 60 oC. And the thermal stability of the conjugates was greatly improved. Therefore, the conjugates while not the unconjugated PPase stimulated the PCR yield by eliminate pyrophosphate during the reaction. The strategy is expected to be favorable for applications in biotechnology and enzyme engineering.
[Show abstract][Hide abstract] ABSTRACT: Lymph node metastasis is an important factor determining the outcome of colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-α and microRNA (miRNA) have been found to play important roles in lymph node metastasis, the underlying molecular mechanism remains unclear. Here we reported that high expression of microRNA-19a (miR-19a) was associated with lymph node metastasis and played an important role in TNF-α-induced EMT in colorectal cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a was significantly associated with lymph node metastasis. We further analyzed miR-19a lymph node metastasis signature in an external validation cohort of 311 CRC cases of the TCGA. MiR-19a was found to be significantly associated with lymph node metastasis in rectal cancer. In vitro, we showed that overexpression of miR-19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a was up-regulated by TNF-α and miR-19a was required for TNF-α-induced EMT and metastasis in CRC cells. Collectively, miR-19a played an important role in mediating EMT and metastatic behavior in CRC. It may serve as a potential marker of lymph node metastasis.