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1.  Common SNP in hsa-miR-196a-2 increases hsa-miR-196a-5p expression and predisposes to idiopathic male infertility in Chinese Han population 
Scientific Reports  2016;6:19825.
MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913, and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR-196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC-2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P < 0.05). Additionally, apoptosis levels were significantly increased in hsa-miR-196a-5p mimic treated GC-2 cells, while decreased in hsa-miR-196a-5p inhibitor treated GC-2 cells. Our data revealed a significant relationship between hsa-miR-196a-2 polymorphism and idiopathic male infertility.
doi:10.1038/srep19825
PMCID: PMC4726409  PMID: 26805933
2.  A conserved pattern in plant‐mediated interactions between herbivores 
Ecology and Evolution  2016;10.1002/ece3.1922.
Abstract
Plant‐mediated interactions between herbivores are important determinants of community structure and plant performance in natural and agricultural systems. Current research suggests that the outcome of the interactions is determined by herbivore and plant identity, which may result in stochastic patterns that impede adaptive evolution and agricultural exploitation. However, few studies have systemically investigated specificity versus general patterns in a given plant system by varying the identity of all involved players. We investigated the influence of herbivore identity and plant genotype on the interaction between leaf‐chewing and root‐feeding herbivores in maize using a partial factorial design. We assessed the influence of leaf induction by oral secretions of six different chewing herbivores on the response of nine different maize genotypes and three different root feeders. Contrary to our expectations, we found a highly conserved pattern across all three dimensions of specificity: The majority of leaf herbivores elicited a negative behavioral response from the different root feeders in the large majority of tested plant genotypes. No facilitation was observed in any of the treatment combinations. However, the oral secretions of one leaf feeder and the responses of two maize genotypes did not elicit a response from a root‐feeding herbivore. Together, these results suggest that plant‐mediated interactions in the investigated system follow a general pattern, but that a degree of specificity is nevertheless present. Our study shows that within a given plant species, plant‐mediated interactions between herbivores of the same feeding guild can be stable. This stability opens up the possibility of adaptations by associated organisms and suggests that plant‐mediated interactions may contribute more strongly to evolutionary dynamics in terrestrial (agro)ecosystems than previously assumed.
doi:10.1002/ece3.1922
PMCID: PMC4720690  PMID: 26811746
Genetic variation; herbivory; indirect interactions; induced defense; plant resistance
3.  Comparison of Two Botulinum Neurotoxin A Injection Patterns with or without the Medial Lower Eyelid in the Treatment of Blepharospasm 
Journal of Ophthalmology  2016;2016:5957812.
The aim of this study was to evaluate the efficacy of two botulinum toxin A (BoNT-A) injection patterns with or without the medial lower eyelid (MLE) in treating benign essential blepharospasm (BEB) and influencing lacrimal drainage. Two different injection patterns of BoNT-A were randomly applied to 98 eyes of 49 BEB patients: MLE Group received a full injection pattern of 5 sites and non-MLE Group received a MLE waived injection pattern of 4 sites. Tear breakup time (BUT), Schirmer I test, lagophthalmos height, and lower lid tear meniscus height (TMH) were measured and Jankovic Rating Scale (JRS) was surveyed before injection and at 1 week, 1 month, and 3 months after injection. The symptom of BEB was relieved in both groups as suggested by JRS scores at all time points after injection, and MLE Group came up with a better JRS score at 3 months. The increases of Schirmer I test value and TMH in MLE Group were higher than those in non-MLE Group at 1 week after injection. This study shows that the MLE-involved full injection pattern is a better choice for patients with BEB. It has longer-lasting effects in relieving BEB symptoms and better efficacy in reducing lacrimal drainage. Clinical Trials registration number is NCT02327728.
doi:10.1155/2016/5957812
PMCID: PMC4738946  PMID: 26885381
4.  Remote Ischemic Postconditioning Ameliorates the Mesenchymal Stem Cells Engraftment in Reperfused Myocardium 
PLoS ONE  2016;11(1):e0146074.
Objectives
Remote Ischemic postconditioning (RIPoC) is a cardioprotective strategy for alleviating the reperfusion injury. We hypothesized that RIPoC or ischemic postconditioning (IPoC) could protect the engrafted mesenchymal stem cells (MSCs) in reperfusion myocardium.
Methods
Female Sprague-Dawley rats were subject to 30 minutes of occlusion of left anterior descending (LAD). Ischemia reperfusion (IR) received reperfusion without interruption after ischemia. RIPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the limb at the onset of reperfusion. IPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the LAD at the same time. Male MSCs were intramyocardially administered after ischemia.
Results
Compared with that in IR group, ischemic myocardium in RIPoC+IPoC group, RIPoC group and IPoC group were found to have higher anti-oxidative stress and mitochondrial function level, lower lipid peroxidation and inflammational injury level, higher level of stromal cell derived factor-1 alpha and vascular endothelium growth factor gene expression at 3 days later. By immunohistochemical examination and quantitative polymerase chain reaction, more engrafted MSCs, better cardiac function and less cardiac fibrosis in RIPoC+IPoC group, RIPoC group and IPoC group were detected at 3 weeks after delivery. There were no significant differences between RIPoC and RIPoC+IPoC group.
Conclusions
Combination therapy using intramyocardial MSCs transplantation with RIPoC enhanced transplantation efficiency and cardiac function, and reduced cardiac fibrosis. These beneficial effects were mainly attributed to hospitable milieu for engrafted cells. IPoC could not render additional effect on MSCs engraftment elicited by RIPoC.
doi:10.1371/journal.pone.0146074
PMCID: PMC4712013  PMID: 26760781
5.  CXCL14 as an emerging immune and inflammatory modulator 
CXCL14, a relatively novel chemokine, is a non-ELR (glutamic acid-leucine-arginine) chemokine with a broad spectrum of biological activities. CXCL14 mainly contributes to the regulation of immune cell migration, also executes antimicrobial immunity. The identity of the receptor for CXCL14 still remains obscure and therefore the intracellular signaling pathway is not entirely delineated. The present review summarizes the contribution of CXCL14 in these two aspects and discusses the biological mechanisms regulating CXCL14 expression and potential CXCL14 mediated functional implications in a variety of cells.
doi:10.1186/s12950-015-0109-9
PMCID: PMC4700668  PMID: 26733763
CXCL14; Migration; Antimicrobial activity; Infection; Inflammation
6.  Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cell 
Developmental cell  2014;31(6):707-721.
Summary
Acquisition and maintenance of vascular smooth muscle fate is essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMC) can result in structural alterations associated with aneurysms and vascular wall calcification. Here we report that maturation of sclerotome-derived vSMC depends on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time, Notch/Jag1-mediated repression of sclerotome transcription factors Pax1, Scx and Sox9 is necessary to fully enable vSMC maturation. Specifically, Notch signaling in vSMC antagonizes sclerotome and cartilage transcription factors, and promotes upregulation of contractile genes. In the absence of the Notch ligand Jag1, vSMC acquire a chondrocytic transcriptional repertoire that can lead to ossification. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming and promote vascular wall integrity.
doi:10.1016/j.devcel.2014.11.023
PMCID: PMC4311887  PMID: 25535917
7.  Effects of Maillard reaction conditions on the functional properties of WPI chitosan oligosaccharide conjugates 
Journal of Food Science and Technology  2013;51(12):3794-3802.
Whey proteins are widely used as food material, but their functional properties are affected by processing conditions, in which Maillard reaction commonly occurs. The objective of this study was to investigate the effects of reaction conditions (saccharide rate (SR), setting time and setting temperature) on the functional properties of conjugates of whey protein isolates (WPI) - chitosan oligosaccharide (COS), which were produced by Maillard reaction. Response surface methodology (RSM) was used in this study, models for solubility, heat stability (HS), emulsifying activity (EA) and emulsifying stability (ES) of WPI-COS were established. Results indicated that the solubility of WPI-COS was 98.8 % at 29.8 % SR, 17.4 h, 46.7 °C; the heat stability of WPI-COS was 92.95 % at 27.2 % SR, 18.1 h, 48.7 °C; the EA of WPI-COS was 1.87 at 25.3 % SR, 20.0 h, 46.1 °C; the ES of WPI-COS was 13.28 min at 32.5 % SR, 12.0 h, 35.0 °C and setting temperature was the major factor affecting EA and ES while SR was the major factor affecting solubility and heat stability. Conditions were optimized for the preparation of WPI-COS to obtain improved functional properties.
doi:10.1007/s13197-013-0946-6
PMCID: PMC4252465  PMID: 25477646
Whey protein isolate; Chitosan oligosaccharide; Solubility; Heat stability; Emulsifying property
8.  Long-term upregulation of cortical glutamatergic AMPA receptors in a mouse model of chronic visceral pain 
Molecular Brain  2015;8:76.
Background
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and it causes long-lasting visceral pain and discomfort. AMPA receptor mediated long-term potentiation (LTP) has been shown to play a critical role in animal models of neuropathic and inflammatory pain. No report is available for central changes in the ACC of mice with chronic visceral pain.
Results
In this study, we used integrative methods to investigate potential central plastic changes in the anterior cingulate cortex (ACC) of a visceral pain mouse model induced by intracolonic injection of zymosan. We found that visceral pain induced an increased expression of AMPA receptors (at the post synapses) in the ACC via an enhanced trafficking of the AMPA receptors to the membrane. Both GluA1 and GluA2/3 subunits were significantly increased. Supporting biochemical changes, excitatory synaptic transmission in the ACC were also significantly enhanced. Microinjection of AMPA receptor inhibitor IEM1460 into the ACC inhibited visceral and spontaneous pain behaviors. Furthermore, we found that the phosphorylation of GluA1 at the Ser845 site was increased, suggesting that GluA1 phosphorylation may contribute to AMPA receptor trafficking. Using genetically knockout mice lacking calcium-calmodulin stimulated adenylyl cyclase subtype 1 (AC1), we found that AMPA receptor phosphorylation and its membrane trafficking induced by zymosan injection were completely blocked.
Conclusions
Our results provide direct evidence for cortical AMPA receptors to contribute to zymosan-induced visceral and spontaneous pain and inhibition of AC1 activity may help to reduce chronic visceral pain.
doi:10.1186/s13041-015-0169-z
PMCID: PMC4653882  PMID: 26585043
AMPA; Anterior cingulate cortex; Irritable bowel syndrome; AC1
9.  Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress 
Background
Apoptosis is mediated by the endoplasmic reticulum (ER) stress pathway, mitochondrial pathway, and death receptor. Data herein suggested an inhibitory effect of marchantin M on tumor formation in nude mice as well as the impact on CHOP and GRP78 expression.
Material/Methods
The role of marchantin M on proliferation and apoptosis of DU145 cells were measured by MTT and flow cytometry, respectively. Western blot was applied to detect the expression of GRP78 and CHOP. The mice received abdominal injection at 1 time/2 d and 2 ml/time. Tumor volume was measured every 6 days. The mice were euthanatized 30 days after marchantin injection and tumor weight was measured. Cell apoptosis was determined by TUNEL. The expressions of CHOP and GRP78 were detected by immunohistochemistry.
Results
Tumor size and weight in marchantin groups were significantly lower than in the control group (A, B) (P<0.05), and the inhibitory rate presented a dose-dependent increase. Compared with controls, the levels of CHOP and GRP78 expression elevated obviously following the treatment with marchantin (P<0.05). It showed statistically significant difference among groups C, D, E, with different levels of apoptosis indexes incremented in groups of marchantin H, M, L, compared with groups A and B (P<0.05).
Conclusions
Overall, this study shows that marchantin M circumvents the growth of prostate cancer PC-3 tumor and up-regulates expressions of CHOP and GRP78. Our data also indicate that marchantin M limits the proliferation and favors apoptosis of DU145 cells in a time- and dose-dependent manner.
doi:10.12659/MSM.894476
PMCID: PMC4657764  PMID: 26581488
Aspergillosis, Allergic Bronchopulmonary; Calcitonin Gene-Related Peptide; Prostatic Neoplasms
10.  The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis 
BioMed Research International  2015;2015:856704.
The International Staging System (ISS) is the most important prognostic system for multiple myeloma (MM). It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS) of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p < 0.001), and the median progression-free survival (PFS) was 30/29.5/25 months (p = 0.072), respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.
doi:10.1155/2015/856704
PMCID: PMC4658402  PMID: 26640799
11.  Sequence Variation in HSP40 Gene among 16 Toxoplasma gondii Isolates from Different Hosts and Geographical Locations 
BioMed Research International  2015;2015:209792.
Toxoplasma gondii with worldwide distribution has received substantial medical and scientific attentions as it causes serious clinical and veterinary problems especially for pregnant women and immunocompromised patients. Heat shock protein 40 (HSP40) plays a variety of essential roles in the pathogenesis of this protozoan parasite. In order to detail the genetic diversity of HSP40 gene, 16 T. gondii strains from different hosts and geographical locations were used in this study. Our results showed that HSP40 sequence of the examined strains was between 6621 bp and 6644 bp in length, and their A+T content was from 48.54% to 48.80%. Furthermore, sequence analysis presented 195 nucleotide mutation positions (0.12%–1.14%) including 29 positions in CDS (0.02%–0.12%) compared with T. gondii ME49 strain (ToxoDB: TGME49_265310). Phylogenetic assay revealed that T. gondii strains representing three classical genotypes (Types I, II, and III) were completely separated into different clusters by maximum parsimony (MP) method, but Type II and ToxoDB#9 strains were grouped into the same cluster. These results suggested that HSP40 gene is not a suitable marker for T. gondii population genetic research, though three classical genotypes of T. gondii could be differentiated by restriction enzymes MscI and EarI existing in amplicon C.
doi:10.1155/2015/209792
PMCID: PMC4647022  PMID: 26613080
12.  Separation of Berberine Hydrochloride and Tetrahydropalmatine and Their Quantitative Analysis with Thin Layer Chromatography Involved with Ionic Liquids 
[BMIM]OH was used in mobile and stationary phase of thin layer chromatography (TLC) to analyze berberine hydrochloride and tetrahydropalmatine for the first time. Supported imidazole ionic liquid with hydroxide ion on silica gel (SiO2·Im+·OH−) was synthesized through simple procedure and characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and scanning electron microscope (SEM). Moreover, on the plates prepared by SiO2·Im+·OH−, the contents of the above alkaloids in the Chinese patent medicine (CPM) of “Stomacheasy” capsule were successfully determined by TLC scanner. The key conditions and chromatographic behaviors were also investigated in detail. According to similar ways, ionic liquids (ILs) also can be used in other planar chromatographies in two modes. This study is expected to be helpful in expanding the application of IL and its bonded silica gel in TLC separation field.
doi:10.1155/2015/642401
PMCID: PMC4644556  PMID: 26609463
13.  Effect of Bisphenol A on invasion ability of human trophoblastic cell line BeWo 
Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic cell line BeWo and its possible mechanism were investigated. BeWo cells were exposed to BPA and co-cultured with human endometrial cells to mimic embryo implantation in transwell model. The proliferation and invasion capability of BeWo cells were detected. The expression of E-cadherin, DNMT1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were also analyzed. The results showed that the invasion capability of BeWo was reduced after daily exposure to BPA. BPA had biphasic effect on E-cadherin expression level in BeWo cells and expression level of DNMT1 was decreased when treated with BPA. Moreover, BPA treatment also changed the balance of MMPs/TIMPs in BeWo cells by down-regulating MMP-2, MMP-9 and up-regulating TIMP-1, TIMP-2 with increasing BPA concentration. Taken together, these results showed that BPA treatment could reduce the invasion ability of BeWo cells and alter the expression level of E-cadherin, DNMT1, TIMP-1, TIMP-2, MMP-2, and MMP-9. Our study would help us to understand the possible mechanism of BPA effect on invasion ability of human trophoblastic cell line BeWo.
PMCID: PMC4713537  PMID: 26823751
Bisphenol A; BeWo cells; cell invasion; E-cadherin; DNMT1; MMPs/TIMPs
14.  Anti-inflammatory effects of potato extract on a rat model of cigarette smoke–induced chronic obstructive pulmonary disease 
Food & Nutrition Research  2015;59:10.3402/fnr.v59.28879.
Highlights:
(1) Potato extract (PE) exhibits non-toxic effects on mice.
(2) Cigarette smoke (CS)–induced COPD rats exhibit significant thickened and disordered lung markings.
(3) PE could improve the histopathological symptoms of lung tissue in COPD.
(4) PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats.
Objective
This study aimed to evaluate the therapeutic effects of potato extract (PE) on cigarette smoke (CS)–induced chronic obstructive pulmonary disease (COPD).
Methods
PE was first prepared by frozen centrifugation, and its amino acid composition was detected. Toxicity of PE was analyzed by changes in morphology, behavior, routine blood indexes, and biochemical criteria of mice. Then, the COPD rat model was established by CS exposure, and PE, doxofylline, and prednisolone acetate were used to treat these rats. After 45 days of treatment, the morphology and behavior of rats were recorded. In addition, the histopathology of lung tissue was evaluated by chest x-ray and hematoxylin and eosin staining. The expression of interleukine-10 (IL-10), tumor necrosis factor-α (TNF-α), and granulocyte colony-stimulating factor (G-CSF) was detected in serum and lung tissue by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively.
Results
Various amino acids were identified in PE, and no toxicity was exhibited in mice. The CS-induced COPD rat model was successfully established, which exhibited significant thickened and disordered lung markings on 90% of the rats. After administering doxofylline and prednisolone acetate, inflammation symptoms were improved. However, side effects such as emaciation, weakness, and loosening of teeth appeared. In the PE group, obviously improved histopathology was observed in lung tissues. Meanwhile, it was revealed that PE could increase the expression of IL-10 and reduce the expression of TNF-α and G-CSF in COPD rats, and doxofylline and prednisolone acetate also elicited similar results.
Conclusion
Our study suggests PE might be effective in the treatment of CS-induced COPD by inhibiting inflammation.
doi:10.3402/fnr.v59.28879
PMCID: PMC4620637  PMID: 26498426
potato extract; cigarette smoke; chronic obstructive pulmonary disease; inflammation
15.  Characteristics of clinical studies of summer acupoint herbal patching: a bibliometric analysis 
Background
Summer acupoint herbal patching (SAHP) has been widely used in China for thousands of years. This bibliometric analysis aims to provide a comprehensive review of the characteristics of clinical studies on SAHP for any condition.
Methods
We included clinical studies such as randomized clinical trials (RCTs), controlled clinical studies (CCTs), case series (CSs), case reports (CRs), and cross-sectional studies on SAHP for any condition. Six databases were searched from date of inception to March 2015. Bibliometric information and study details such as study type, characteristics of participants, details of the intervention and comparison, and outcome were extracted and analyzed.
Results
A total of 937 clinical studies were identified and which were published between 1977 and 2015. This included 404 RCTs, 52 CCTs, 458 CSs, 19 CRs and 4 cross-sectional studies and involved 232,138 participants aged 2 to 90 years from two countries. Almost all studies were from China (936, 99.89 %). The five conditions most commonly treated by SAHP were asthma (401, 42.80 %), chronic bronchitis (146, 15.58 %), allergic rhinitis (117, 12.49 %), chronic obstructive pulmonary disease (73, 7.79 %), and recurrent respiratory tract infection (42, 4.48 %). Among 502 controlled studies, the majority compared SAHP alone with different controls (16 categories, 275 comparisons). The most commonly used controls were western medicine, placebo, traditional Chinese medicine, no treatment and non-pharmaceutical traditional Chinese therapies. Composite outcome measures were the most frequently reported outcome (512, 69.19 %).
Conclusion
A substantial amount of research on SAHP has been published in China and which predominantly focuses on respiratory conditions. The findings from this study can be used to inform further research by highlighting areas of greatest impact for SAHP.
Electronic supplementary material
The online version of this article (doi:10.1186/s12906-015-0905-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12906-015-0905-z
PMCID: PMC4618877  PMID: 26492938
Summer acupoint herbal patching; Sanfutie; Traditional Chinese therapies; Bibliometrics; literature review
16.  Interaction of Wnt pathway related variants with type 2 diabetes in a Chinese Han population 
PeerJ  2015;3:e1304.
Aims. Epistasis from gene set based on the function-related genes may confer to the susceptibility of type 2 diabetes (T2D). The Wnt pathway has been reported to play an important role in the pathogenesis of T2D. Here we applied tag SNPs to explore the association between epistasis among genes from Wnt and T2D in the Han Chinese population.
Methods. Variants of fourteen genes selected from Wnt pathways were performed to analyze epistasis. Gene–gene interactions in case-control samples were identified by generalized multifactor dimensionality reduction (GMDR) method. We performed a case-controlled association analysis on a total of 1,026 individual with T2D and 1,157 controls via tag SNPs in Wnt pathway.
Results. In single-locus analysis, SNPs in four genes were significantly associated with T2D adjusted for multiple testing (rs7903146C in TCF7L2, p = 3.21∗10−3, OR = 1.39, 95% CI [1.31–1.47], rs12904944G in SMAD3, p = 2.51∗10−3, OR = 1.39, 95% CI [1.31–1.47], rs2273368C in WNT2B, p = 4.46∗10−3, OR = 1.23, 95% CI [1.11–1.32], rs6902123C in PPARD, p = 1.14∗10−2, OR = 1.40, 95% CI [1.32–1.48]). The haplotype TGC constructed by TCF7L2 (rs7903146), DKK1 (rs2241529) and BTRC (rs4436485) showed a significant association with T2D (OR = 0.750, 95% CI [0.579–0.972], P = 0.03). For epistasis analysis, the optimized combination was the two locus model of WNT2B rs2273368 and TCF7L2rs7903146, which had the maximum cross-validation consistency. This was 9 out of 10 for the sign test at 0.0107 level. The best combination increased the risk of T2D by 1.47 times (95% CI [1.13–1.91], p = 0.0039).
Conclusions. Epistasis between TCF7L2 and WNT2B is associated with the susceptibility of T2D in a Han Chinese population. Our results were compatible with the idea of the complex nature of T2D that would have been missed using conventional tools.
doi:10.7717/peerj.1304
PMCID: PMC4621788  PMID: 26509107
Epistasis; Wnt pathway; Type 2 diabetes
17.  Clinical and endoscopic-pathological characteristics of colorectal polyps: an analysis of 1,234 cases 
Purpose: To analyze the correlation of clinical symptom and endoscopic-pathological characteristics of colorectal polyps. Methods: A retrospective study was performed on 1,234 continuous colorectal polyp patients. Their clinical, colonoscopic and pathological data were collected and analyzed. Results: In 1,234 patients, 46.0% cases were asymptomatic, and 54.0% cases were symptomatic, and the female to male ratio was 2.23:1 and 1.74:1, respectively (P = 0.048). The mean polyp size in symptomatic group was significantly larger than asymptomatic group [7.6±5.1 mm (95% CI: 7.2, 8.0) vs. 6.3±3.7 mm (95% CI: 6.0, 6.6), P < 0.001]. Tubu-villous polyp and villous polyp occurred more frequently in symptomatic group, compared with asymptomatic group (P = 0.002). In symptomatic group, 37.4% cases complained of abdominal pain and 62.6% cases complained of bowel habit alteration. The polyp number in abdominal pain group was larger than bowel habit alteration group (P = 0.036). Three major symptoms of bowel habit alteration were diarrhea, constipation and hematochezia, with proportion of 54.2% (278/513), 27.7% (142/513) and 18.1% (93/513), respectively. The hematochezia group had larger polyp size than diarrhea group (P = 0.001) and consisted of more villous component than the constipation patients (P = 0.005). Conclusion: Almost half of colorectal polyp patients do not complain of bowel symptoms, especially the male. Colorectal polyp patients have bowel habit alteration more commonly than abdominal pain. Half of patients with bowel habit alteration demonstrate diarrhea. The hematochezia patients are more susceptible to advanced adenomas than the diarrhea and constipation ones.
PMCID: PMC4694477  PMID: 26770577
Colorectal polyps; bowel symptoms; analysis; advanced adenoma
18.  Elucidation of Echovirus 30's Origin and Transmission during the 2012 Aseptic Meningitis Outbreak in Guangdong, China, through Continuing Environmental Surveillance 
An aseptic meningitis outbreak occurred in Luoding City of Guangdong, China, in 2012, and echovirus type 30 (ECHO30) was identified as the major causative pathogen. Environmental surveillance indicated that ECHO30 was detected in the sewage of a neighboring city, Guangzhou, from 2010 to 2012 and also in Luoding City sewage samples (6/43, 14%) collected after the outbreak. In order to track the potential origin of the outbreak viral strains, we sequenced the VP1 genes of 29 viral strains from clinical patients and environmental samples. Sequence alignments and phylogenetic analyses based on VP1 gene sequences revealed that virus strains isolated from the sewage of Guangzhou and Luoding cities matched well the clinical strains from the outbreak, with high nucleotide sequence similarity (98.5% to 100%) and similar cluster distribution. Five ECHO30 clinical strains were clustered with the Guangdong environmental strains but diverged from strains from other regions, suggesting that this subcluster of viruses most likely originated from the circulating virus in Guangdong rather than having been more recently imported from other regions. These findings underscore the importance of long-term, continuous environmental surveillance and genetic analysis to monitor circulating enteroviruses.
doi:10.1128/AEM.03200-14
PMCID: PMC4357961  PMID: 25616804
19.  Efficacy of Preventive Interventions for Iodinated Contrast-Induced Acute Kidney Injury Evaluated by Intrarenal Oxygenation as an Early Marker 
Investigative radiology  2014;49(10):647-652.
Objective
The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level–dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase–associated lipocalin (NGAL) measurements.
Materials and Methods
Rats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fifty-four Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received.
Blood-oxygen-level–dependent MRI–weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection.
Results
Compared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2* compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2* after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05).
Conclusions
This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2* after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans.
doi:10.1097/RLI.0000000000000065
PMCID: PMC4470575  PMID: 24872003
kidney; oxygenation; BOLD MRI; NGAL; iodinated contrast; acute kidney injury; rats; nitric oxide; furosemide
21.  Recombinant human endostatin enhances the radioresponse in esophageal squamous cell carcinoma by normalizing tumor vasculature and reducing hypoxia 
Scientific Reports  2015;5:14503.
The aim of this study was to investigate the effect of recombinant human endostatin (rh-Endo) in combination with radiation therapy (RT) on esophageal squamous cell carcinoma (ESCC) and explore the potential mechanisms. ECA109-bearing nude mice were administered RT and/or rh-Endo treatment. Tumor volume, survival, hypoxia and vascular parameters were recorded during the treatment schedule and follow-up as measures of treatment response. ESCC cell lines (ECA109 and TE13) and human umbilical vein endothelial cells (HUVECs) were developed to investigate the outcomes and toxicities of rh-Endo and RT in vitro. Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were also evaluated. In vivo studies of ECA109-bearing xenografts showed that rh-Endo improved the radioresponse, with normalization of tumor vasculature and a reduction in hypoxia. In vitro studies showed that rh-Endo did not radiosensitize ESCC cell lines but did affect endothelial cells with a time- and dose-dependent manner. Studies of the molecular mechanism indicated that the improved radioresponse might be due to crosstalk between cancer cells and endothelial cells involving HIF and VEGF expression. Our data suggest that rh-Endo may be a potential anti-angiogenic agent in ESCC especially when combined with RT. The improved radioresponse arises from normalization of tumor vasculature and a reduction in hypoxia.
doi:10.1038/srep14503
PMCID: PMC4585975  PMID: 26412785
22.  JAK/STAT3 signaling pathway mediates endothelial-like differentiation of immature dendritic cells 
Oncology Letters  2015;10(6):3471-3477.
Endothelial-like differentiation (ELD) of dendritic cells (DCs) is a poorly understood phenomenon. The present study evaluated the effect on the ELD of DCs by using human esophageal squamous cell carcinoma (ESCC) cells with high or poor differentiation. The results demonstrated that KYSE450 (highly differentiated) and KYSE70 (poorly differentiated) cell supernatants induce the differentiation of immature DCs (iDCs), derived from healthy adult volunteers, away from the DC pathway and towards an endothelial cell (EC) fate. This effect was strongest in the cells treated with the KYSE70 supernatant. During the ELD of iDCs, sustained activation of JAK (janus tyrosine kinase)/STAT3 (signal transducer and activator of transcription 3) signaling was detected. Incubation of iDCs with the JAK inhibitor, AG490 blocked JAK/STAT3 phosphorylation and iDC differentiation. These results suggested that the JAK/STAT3 signaling pathway mediates ELD of iDCs. Furthermore, the poorly differentiated ESCC cells may have a greater effect on the ELD of iDCs than highly differentiated ESCC cells.
doi:10.3892/ol.2015.3752
PMCID: PMC4665379  PMID: 26788152
dendritic cells; esophageal squamous cell carcinoma; endothelial-like differentiation; janus tyrosine kinase; signal transducer and activator of transcription 3
23.  Transcatheter closure of the left atrial appendage: initial experience with the WATCHMAN device 
Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, accounting for approximately one third of hospitalizations for cardiac rhythm disturbance. In patients with non-valvular AF, approximately 90% of thrombi are thought to arise from the left atrial appendage (LAA). Anticoagulation with warfarin has been the mainstay of therapy to reduce stroke risk in these patients; however, it is not without its complications including bleeding and drug interactions. Percutaneous left atrial appendage closure can be an alternative to warfarin treatment in patients with AF at high risk for thromboembolic events and/or bleeding complications. Methods: Patients with atrial fibrillation and CHADSVASc score ≥ 2, not eligible for anticoagulation, were submitted to left atrial appendage closure using the WATCHMAN device. The procedure was performed under general anaesthesia, and was guided by fluoroscopy and transoesophageal echocardiography. Results: Percutaneous LAA closure with the WATCHMAN device was performed in all patients. At 45-day follow-up no recurrent major adverse events and especially no thromboembolic events occurred. Conclusions: Transcatheter closure of the LAA with the WATCHMAN device is generally safe and feasible. Long-term follow-up will further reveal the risk and benefits of this therapy.
PMCID: PMC4658897  PMID: 26629008
Atrial fibrillation; left atrial appendage; WATCHMAN device
24.  Tunable Valley Polarization and Valley Orbital Magnetic Moment Hall Effect in Honeycomb Systems with Broken Inversion Symmetry 
Scientific Reports  2015;5:13906.
In this Letter, a tunable valley polarization is investigated for honeycomb systems with broken inversion symmetry such as transition-metal dichalcogenide MX2 (M = Mo, W; X = S, Se) monolayers through elliptical pumping. Compared to circular pumping, elliptical pumping is a more universal and effective method to create coherent valley polarization. When two valleys of MX2 monolayers are doped or polarized, a novel anomalous Hall effect (called valley orbital magnetic moment Hall effect) is predicted. Valley orbital magnetic moment Hall effect can generate an orbital magnetic moment current without the accompaniment of a charge current, which opens a new avenue for exploration of valleytronics and orbitronics. Valley orbital magnetic moment Hall effect is expected to overshadow spin Hall effect and is tunable under elliptical pumping.
doi:10.1038/srep13906
PMCID: PMC4566088  PMID: 26358835
25.  Eukaryotic elongation factor 2 kinase confers tolerance to stress conditions in cancer cells 
Cell Stress & Chaperones  2014;20(2):217-220.
Eukaryotic elongation factor 2 (eEF2) is a member of the GTP-binding translation elongation factor family that is essential for protein synthesis. eEF2 kinase (eEF2K) is a structurally and functionally unique protein kinase in the calmodulin-mediated signaling pathway. eEF2K phosphorylates eEF2, thereby inhibiting eEF2 function under stressful conditions. eEF2K regulates numerous processes, such as protein synthesis, cell cycle progression, and induction of autophagy and apoptosis in cancer cells. This review will demonstrate the mechanisms underlying eEF2K activity in cancer cells under different stresses, such as nutrient deprivation, hypoxia, and DNA damage via eEF2 regulation. In vivo, in vitro, and clinical studies indicated that eEF2K may be a novel biomarker and therapeutic target for cancer.
doi:10.1007/s12192-014-0545-0
PMCID: PMC4326389  PMID: 25248493
Eukaryotic elongation factor 2 kinase; eEF2K; eEF2; Cancer; Stress

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