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1.  Pre-Existing Venous Calcification Prior to Dialysis Vascular Access Surgery 
Seminars in dialysis  2012;25(5):592-595.
Vascular calcification is present in arterial vessels used for dialysis vascular access creation prior to surgical creation. Calcification in the veins used to create a new vascular access has not previously been documented. The objective of this study was to describe the prevalence of venous calcification in samples collected at the time of vascular access creation.
67 vein samples were studied. A von Kossa stain was performed to quantify calcification. A semi-quantitative scoring system from 0–4+ was used to quantify the percentage positive area for calcification as a fraction of total area (0=0; 1+ = 1–10%; 2+ =11–25%; 3+ = 26–50%; 4+ >50% positive).
22/67(33%) samples showed evidence of venous calcification. Histologic examination showed varying degrees of calcification within each cell layer. Among the subset of patients with calcification, 4/22 (18%), 19/22 (86%), 22/22 (100%), and 7/22 (32%) had calcification present within the endothelium, intima, media, and adventitia, respectively. The mean semi-quantitative scores of the 22 samples with calcification were 0.18±0.08, 1.2±0.14, 1.6±0.13, and 0.36±0.12 for the endothelium, intima, media, and adventitia, respectively.
Our results demonstrate that vascular calcification is present within veins used to create new dialysis vascular access, and located predominately within the neointimal and medial layers.
doi:10.1111/j.1525-139X.2012.01063.x
PMCID: PMC3961753  PMID: 22452638
Vascular Calcification; Hemodialysis Vascular Access; Vascular Access Stenosis
2.  Altered Default Mode Network Connectivity in Older Adults with Cognitive Complaints and Amnestic Mild Cognitive Impairment 
Default mode network (DMN) disruption has been reported in Alzheimer’s disease (AD), yet the specific pattern of altered connectivity over the course of prodromal AD remains to be characterized. The aim of this study was to assess DMN connectivity in older adults with informant-verified cognitive complaints (CC) but normal neuropsychological performance compared to individuals with mild cognitive impairment (MCI) and healthy controls (HC). DMN maps were derived from resting-state fMRI using independent component analysis. Group comparisons of DMN connectivity were performed between older adults with MCI (n = 18), CC (n = 23), and HC (n = 16). Both CC and MCI showed decreased DMN connectivity in the right hippocampus compared to HC, with the CC group showing greater connectivity than MCI. These differences survived atrophy correction and correlated with cognitive performance. DMN connectivity appears sensitive to early prodromal neurodegenerative changes associated with AD, notably including pre-MCI individuals with cognitive complaints.
doi:10.3233/JAD-130080
PMCID: PMC3962306  PMID: 23481685
Alzheimer’s disease; cognitive complaints; default mode network; functional connectivity; hippocampus; memory; mild cognitive impairment
3.  Recognition of self and altered self by T cells in autoimmunity and allergy 
Protein & cell  2013;4(1):8-16.
T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.
doi:10.1007/s13238-012-2077-7
PMCID: PMC3951410  PMID: 23307779
altered self; neoantigen; antigen presenting; T cell recognition; autoimmunity; allergy; diabetes; dermatitis; drug hypersensitivity
4.  The mediating role of self-efficacy in the relationship between Big five personality and depressive symptoms among Chinese unemployed population: a cross-sectional study 
BMC Psychiatry  2014;14:61.
Background
Besides the rapid growth of economy, unemployment becomes a severe socio-economic problem in China. The huge population base in China makes the unemployed population a tremendously huge number. However, health status of unemployed population was ignored and few studies were conducted to describe the depressive symptoms of unemployed individuals in China. This study aims to examine the relationship between Big five personality and depressive symptoms and the mediating role of self-efficacy in this relationship.
Methods
This cross-sectional study was performed during the period of July to September 2011. Questionnaires consisting of the Center for Epidemiologic Studies Depression Scale (CES-D), the Big Five Inventory (BFI) and the General Self-efficacy Scale (GSE), as well as demographic factors, were used to collect information of unemployed population. A total of 1,832 individuals (effective response rate: 73.28%) became our subjects. Hierarchical linear regression analyses were performed to explore the mediating role of self-efficacy.
Results
The prevalence of depressive symptoms was 67.7% among Chinese unemployed individuals. After adjusting for demographic characteristics, extraversion, agreeableness and conscientiousness were all negatively associated with depressive symptoms whereas neuroticism was positively associated with depressive symptoms. The proportion of mediating effect of self-efficacy in the relationship between extraversion/agreeableness/conscientiousness/neuroticism and depressive symptoms was 25.42%, 10.91%, 32.21% and 36.44%, respectively. Self-efficacy is a mediator in the relationship between extraversion/agreeableness/conscientiousness/neuroticism and depressive symptoms.
Conclusion
Self-efficacy partially mediated the relationship between Big five personality and depressive symptoms among Chinese unemployed individuals. Interventions that focus on both individuals’ personality and self-efficacy may be most successful to reduce depressive symptoms of unemployed individuals.
doi:10.1186/1471-244X-14-61
PMCID: PMC3976156  PMID: 24581332
Depressive symptoms; Big five personality; Self-efficacy; Unemployed
5.  Biochemical properties, expression profiles, and tissue localization of orthologous acetylcholinesterase-2 in the mosquito, Anopheles gambiae 
Acetylcholinesterases (AChEs) catalyze the hydrolysis of acetylcholine, a neurotransmitter for cholinergic neurotransmission in animals. Most insects studied so far possess two AChE genes: ace-1 paralogous and ace-2 orthologous to Drosophila melanogaster ace. We characterized the catalytic domain of Anopheles gambiae AChE1 in a previous study (Jiang et al., 2009) and report here biochemical properties of A. gambiae AChE2 expressed in Sf9 cells. An unknown protease in the expression system cleaved the recombinant AChE2 next to Arg110, yielding two non-covalently associated polypeptides. A mixture of the intact and cleaved AChE2 had a specific activity of 72.3 U/mg, much lower than that of A. gambiae AChE1 (523 U/mg). The order of Vmax/KM values for the model substrates was acetylthiocholine > propionylthiocholine ≈ acetyl-(β-methyl)thiocholine > butyrylthiocholine. The IC50’s for eserine, carbaryl, BW284C51, paraoxon and malaoxon were 1.32, 13.6, 26.8, 192 and 294 nM, respectively. A. gambiae AChE2 bound eserine and carbaryl stronger than paraoxon and malaoxon, whereas eserine and malaoxon modified the active site Ser232 faster than carbaryl or paraoxon did. Consequently, the ki’s were 1.173, 0.245, 0.029 and 0.018 μM−1min−1 for eserine, carbaryl, paraoxon and malaoxon, respectively. Quantitative polymerase chain reactions showed a similar pattern of ace-1 and ace-2 expression. Their mRNAs were abundant in early embryos, greatly decreased in late embryos, larvae, pupae, and pharate adult, and became abundant again in adults. Both transcripts were higher in head and abdomen than thorax of adults and higher in male than female mosquitos. Transcript levels of ace-1 were 1.9- to 361.8-fold higher than those of ace-2, depending on developmental stages and body parts. Cross-reacting polyclonal antibodies detected AChEs in adult brains, thoracic ganglia, and genital/rectal area. Activity assays, immunoblotting, and tandem mass spectrometric analysis indicated that A. gambiae AChE1 is responsible for most of acetylthiocholine hydrolysis in the head extracts. Taken together, these data indicate that A. gambiae AChE2 may play a less significant role than AChE1 does in the mosquito nervous system.
doi:10.1016/j.ibmb.2012.12.005
PMCID: PMC3578101  PMID: 23267863
cholinergic synapse; organophosphate; carbamate; insecticide resistance
6.  Autophagy regulates inflammation following oxidative injury in diabetes 
Autophagy  2013;9(3):272-277.
T1D (type 1 diabetes) is an autoimmune disease characterized by lymphocytic infiltration, or inflammation in pancreatic islets called ‘insulitis.’ Comparatively speaking, T2D (type 2 diabetes) is traditionally characterized by insulin resistance and islet β cell dysfunction; however, a number of studies have clearly demonstrated that chronic tissue inflammation is a key contributing factor to T2D. The NLR (Nod-like receptor) family of innate immune cell sensors such as the NLRP3 inflammasome are implicated in leading to CASP1 activation and subsequent IL1B (interleukin 1, β) and IL18 secretion in T2D. Recent developments reveal a crucial role for the autophagy pathway under conditions of oxidative stress and inflammation. Increasingly, research on autophagy has begun to focus on its role in interacting with inflammatory processes, and thereby how it potentially affects the outcome of disease progression. In this review, we explore the pathophysiological pathways associated with oxidative stress and inflammation in T2D. We also explore how autophagy influences glucose homeostasis by modulating the inflammatory response. We will provide here a perspective on the current research between autophagy, inflammation and T2D.
doi:10.4161/auto.23628
PMCID: PMC3590249  PMID: 23343748
autophagy; diabetes; inflammation; NLRP3 inflammasome; oxidative stress
7.  Broad Activity against Porcine Bacterial Pathogens Displayed by Two Insect Antimicrobial Peptides Moricin and Cecropin B 
Molecules and Cells  2013;35(2):106-114.
In response to infection, insects produce a variety of antimicrobial peptides (AMPs) to kill the invading pathogens. To study their physicochemical properties and bioactivities for clinical and commercial use in the porcine industry, we chemically synthesized the mature peptides Bombyx mori moricin and Hyalophora cecropia cecropin B. In this paper, we described the antimicrobial activity of the two AMPs. Moricin exhibited antimicrobial activity on eight strains tested with minimal inhibitory concentration values (MICs) ranging between 8 and 128 μg/ml, while cecropin B mainly showed antimicrobial activity against the Gramnegative strains with MICs ranging from 0.5 to 16 μg/ml. Compared to the potent antimicrobial activity these two AMPs displayed against most of the bacterial pathogens tested, they exhibited limited hemolytic activity against porcine red blood cells. The activities of moricin and cecropin B against Haemophilus parasuis SH 0165 were studied in further detail. Transmission electron microscopy (TEM) of moricin and cecropin B treated H. parasuis SH 0165 indicated extensive damage to the membranes of the bacteria. Insights into the probable mechanism utilized by moricin and cecropin B to eliminate pathogens are also presented. The observations from this study are important for the future application of AMPs in the porcine industry.
doi:10.1007/s10059-013-2132-0
PMCID: PMC3887904  PMID: 23456332
antimicrobial peptide; cecropin B; Haemophilus parasuis SH 0165; moricin; transmission electron microscopy
8.  Systematic Review and Meta-Analysis of Randomized Controlled Trials of Xingnaojing Treatment for Stroke 
Objective. Xingnaojing injection (XNJ) is a well-known traditional Chinese patent medicine (TCPM) for stroke. The aim of this study is to assess the efficacy of XNJ for stroke including ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods. An extensive search was performed within using eight databases up to November 2013. Randomized controlled trials (RCTs) on XNJ for treatment of stroke were collected. Study selection, data extraction, quality assessment, and meta-analysis were conducted according to the Cochrane standards, and RevMan5.0 was used for meta-analysis. Results. This review included 13 RCTs and a total of 1,514 subjects. The overall methodological quality was poor. The meta-analysis showed that XNJ combined with conventional treatment was more effective for total efficacy, neurological deficit improvement, and reduction of TNF-α levels compared with those of conventional treatment alone. Three trials reported adverse events, of these one trial reported mild impairment of kidney and liver function, whereas the other two studies failed to report specific adverse events. Conclusion. Despite the limitations of this review, we suggest that XNJ in combination with conventional medicines might be beneficial for the treatment of stroke. Currently there are various methodological problems in the studies. Therefore, high-quality, large-scale RCTs are urgently needed.
doi:10.1155/2014/210851
PMCID: PMC3953647
9.  A geometric scaling model for assessing the impact of aneurysm size ratio on hemodynamic characteristics 
Background
The intracranial aneurysm (IA) size has been proved to have impacts on the hemodynamics and can be applied for the prediction of IA rupture risk. Although the relationship between aspect ratio and hemodynamic parameters was investigated using real patients and virtual models, few studies focused on longitudinal experiments of IAs based on patient-specific aneurysm models. We attempted to do longitudinal simulation experiments of IAs by developing a series of scaled models.
Methods
In this work, a novel scaling approach was proposed to create IA models with different aneurysm size ratios (ASRs) defined as IA height divided by average neck diameter from a patient-specific aneurysm model and the relationship between the ASR and hemodynamics was explored based on a simulated longitudinal experiment. Wall shear stress, flow patterns and vessel wall displacement were computed from these models. Pearson correlation analysis was performed to elucidate the relationship between the ASR and wall shear stress. The correlation of the ASR and flow velocity was also computed and analyzed.
Results
The experiment results showed that there was a significant increase in IA area exposed to low WSS once the ASR > 0.7, and the flow became slower and the blood was more difficult to flow into the aneurysm as the ASR increased. Meanwhile, the results also indicated that average blood flow velocity and WSS had strongly negative correlations with the ASR (r = −0.938 and −0.925, respectively). A narrower impingement region and a more concentrated inflow jet appeared as the ASR increased, and the large local deformation at aneurysm apex could be found as the ASR >1.7 or 0.7 < the ASR <1.0.
Conclusion
Hemodynamic characteristics varied with the ASR. Besides, it is helpful to further explore the relationship between morphologies and hemodynamics based on a longitudinal simulation by building a series of patient-specific aneurysm scaled models applying our proposed IA scaling algorithm.
doi:10.1186/1475-925X-13-17
PMCID: PMC3930299  PMID: 24528952
Intracranial aneurysm; Scaled models; Aneurysm Size Ratio; Hemodynamics
10.  Midazolam induces apoptosis in MA-10 mouse Leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway 
OncoTargets and therapy  2014;7:211-221.
Purpose
The present study aims to investigate how midazolam, a sedative drug for clinical use with cytotoxicity on neuronal and peripheral tissues, induced apoptosis in MA-10 mouse Leydig tumor cells.
Methods
The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods.
Results
Data showed that midazolam induced the accumulation of the MA-10 cell population in the sub-G1 phase and a reduction in the G2/M phase in a time- and dose-dependent manner, suggesting an apoptotic phenomenon. Midazolam could also induce the activation of caspase-8, -9, and -3 and poly (ADP-ribose) polymerase proteins. There were no changes in the levels of Bax and cytochrome-c, whereas Bid was significantly decreased after midazolam treatment. Moreover, midazolam decreased both pAkt and Akt expression. In addition, midazolam stimulated the phosphorylation of p38 and c-Jun NH2-terminal kinase but not extracellular signal-regulated kinase.
Conclusion
Midazolam could induce MA-10 cell apoptosis through the activation of caspase cascade, the inhibition of pAkt pathway, and the induction of p38 and c-Jun NH2-terminal kinase pathways.
doi:10.2147/OTT.S56084
PMCID: PMC3928462  PMID: 24611016
midazolam; apoptosis; MA-10 cell; caspase; Akt; MAPKs
11.  Evaluation of specific fecal protein biochips for the diagnosis of colorectal cancer 
AIM: To develop and initially test a potential fecal protein biochip for the screening of colorectal cancer (CRC).
METHODS: Fecal protein from 20 colorectal cancer patients and 20 healthy controls were extracted from all of the fecal samples and screened for proteomic differences using a Biotin label-based protein array. Candidate proteins were then verified by ELISA. Finally, we will select out the significant protein and a seven-target multiplex fecal protein biochip was generated and tested for 20 fecal samples to determine the effectiveness of the biochip on identifying CRC. And the value of the protein biochip would be discussed.
RESULTS: After tested by protein biochip of the fecal protein from 20 colorectal cancer patients and 20 healthy controls and levels of calprotectin, M2-pyruvatekinase, angiopoietin-2, fibroblast growth factor-23 (FGF-23), proteins of the matrix metalloproteinase, thrombopoietin (TPO) and interleukin-13 (IL-13) were significantly different between CRC and healthy controls. The sensitivity of all the seven proteins combined was 0.7, specificity was 0.4, and area under the receiver operating characteristics was 0.729. The most promising combinations of test proteins were FGF-23, TPO, and IL-13, reaching a sensitivity of 0.7 and a specificity of 0.7. The combination of FGF-23 and TPO scored highest with sensitivity of 0.7 and specificity of 0.8. Its mean that the combination of FGF-23 and TPO has the highest value for the diagnosis of CRC in our study.
CONCLUSION: A protein biochip composed of proteins found to be elevated in the feces of colorectal cancer patients has great potential as a noninvasive diagnostic for colorectal cancer. The addition of new protein biomarkers and technologies, as they are discovered, is an excellent avenue of future research.
doi:10.3748/wjg.v20.i5.1332
PMCID: PMC3921516  PMID: 24574808
Protein biochip; Feces; Colorectal cancer; Fibroblast growth factor-23; Thrombopoietin
12.  2PE-STED Microscopy with a Single Ti: Sapphire Laser for Reduced Illumination 
PLoS ONE  2014;9(2):e88464.
We reported a new effective approach to carry out two-photon excitation stimulated emission depletion (2PE-STED) microscopy using a single Ti:sapphire laser system. With an acoustic-optic Bragg cell, the modulated-CW 2PE STED microscope had the benefits of both CW and pulse approaches: lower input power, simple optical scheme and no complicated synchronization. Additionally, it also took advantages of fluorescence yield increasing. The sub-diffraction-limit resolution was demonstrated using ATTO 425-tagged clathrin-coated vesicles.
doi:10.1371/journal.pone.0088464
PMCID: PMC3916425  PMID: 24516661
13.  Effects of Preventive Acupuncture and Moxibustion on Fat Accumulation, Blood Lipid, and Uterus E2 of Menopause Rats 
Objective. To observe the effect of preventive acupuncture and moxibustion on blood lipid of menopause rats. Methods. Seventy 10-month-old SD rats with estrous cycle disorders were divided into three control groups and four treatment groups (n = 10/group) and another ten 3.5-month-old female SD rats were chosen as young control group. Preventive acupuncture and moxibustion were applied at Guanyuan (CV 4). Body weight growth rate has been recorded. Plasma total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels and uterus E2 level were measured. Results. Compared to young control group, plasma TC and LDL increased and uterus E2 reduced significantly in 12-month-old control group. Compared to 12-month-old control group, plasma TC and LDL level and body weight growth rate decreased while HDL level increased remarkably in preventive acupuncture 12-month-old group. Compared to 14-month-old control group, plasma TC level and body weight growth rate decreased remarkably in preventive moxibustion 14-month-old group. Conclusions. Preventive acupuncture and moxibustion can significantly decrease the plasma TG and LDL, increase the plasma HDL, and prevent fat accumulation. Our finding suggests that preventive acupuncture and moxibustion have beneficial effects on blood lipid. Different treatment effects were found between preventive acupuncture and preventive moxibustion.
doi:10.1155/2014/621975
PMCID: PMC3930127  PMID: 24639882
14.  First Report of the Multiresistance Gene cfr in Streptococcus suis 
The multiresistance gene cfr was identified for the first time in streptococci, namely, in porcine Streptococcus suis isolate S10. The cfr gene was detected on the ∼100-kb plasmid pStrcfr, where it was bracketed by two copies of the novel insertion sequence ISEnfa5, located in the same orientation. The detection of a cfr- and ISEnfa5-containing amplicon by inverse PCR suggests that ISEnfa5 may play a role in the dissemination of cfr.
doi:10.1128/AAC.00713-13
PMCID: PMC3719703  PMID: 23733472
15.  Integrated optical gyroscope using active Long-range surface plasmon-polariton waveguide resonator 
Scientific Reports  2014;4:3855.
Optical gyroscopes with high sensitivity are important rotation sensors for inertial navigation systems. Here, we present the concept of integrated resonant optical gyroscope constructed by active long-range surface plasmon-polariton (LRSPP) waveguide resonator. In this gyroscope, LRSPP waveguide doped gain medium is pumped to compensate the propagation loss, which has lower pump noise than that of conventional optical waveguide. Peculiar properties of single-polarization of LRSPP waveguide have been found to significantly reduce the polarization error. The metal layer of LRSPP waveguide is electro-optical multiplexed for suppression of reciprocal noises. It shows a limited sensitivity of ~10−4 deg/h, and a maximum zero drift which is 4 orders of magnitude lower than that constructed by conventional single-mode waveguide.
doi:10.1038/srep03855
PMCID: PMC3900930  PMID: 24458281
16.  A New Exhaustive Method and Strategy for Finding Motifs in ChIP-Enriched Regions 
PLoS ONE  2014;9(1):e86044.
ChIP-seq, which combines chromatin immunoprecipitation (ChIP) with next-generation parallel sequencing, allows for the genome-wide identification of protein-DNA interactions. This technology poses new challenges for the development of novel motif-finding algorithms and methods for determining exact protein-DNA binding sites from ChIP-enriched sequencing data. State-of-the-art heuristic, exhaustive search algorithms have limited application for the identification of short (, ) motifs (, ) contained in ChIP-enriched regions. In this work we have developed a more powerful exhaustive method (FMotif) for finding long (, ) motifs in DNA sequences. In conjunction with our method, we have adopted a simple ChIP-enriched sampling strategy for finding these motifs in large-scale ChIP-enriched regions. Empirical studies on synthetic samples and applications using several ChIP data sets including 16 TF (transcription factor) ChIP-seq data sets and five TF ChIP-exo data sets have demonstrated that our proposed method is capable of finding these motifs with high efficiency and accuracy. The source code for FMotif is available at http://211.71.76.45/FMotif/.
doi:10.1371/journal.pone.0086044
PMCID: PMC3901781  PMID: 24475069
17.  A Strategy for Finding the Optimal Scale of Plant Core Collection Based on Monte Carlo Simulation 
The Scientific World Journal  2014;2014:503473.
Core collection is an ideal resource for genome-wide association studies (GWAS). A subcore collection is a subset of a core collection. A strategy was proposed for finding the optimal sampling percentage on plant subcore collection based on Monte Carlo simulation. A cotton germplasm group of 168 accessions with 20 quantitative traits was used to construct subcore collections. Mixed linear model approach was used to eliminate environment effect and GE (genotype × environment) effect. Least distance stepwise sampling (LDSS) method combining 6 commonly used genetic distances and unweighted pair-group average (UPGMA) cluster method was adopted to construct subcore collections. Homogeneous population assessing method was adopted to assess the validity of 7 evaluating parameters of subcore collection. Monte Carlo simulation was conducted on the sampling percentage, the number of traits, and the evaluating parameters. A new method for “distilling free-form natural laws from experimental data” was adopted to find the best formula to determine the optimal sampling percentages. The results showed that coincidence rate of range (CR) was the most valid evaluating parameter and was suitable to serve as a threshold to find the optimal sampling percentage. The principal component analysis showed that subcore collections constructed by the optimal sampling percentages calculated by present strategy were well representative.
doi:10.1155/2014/503473
PMCID: PMC3918405  PMID: 24574893
18.  A Novel Injectable Borate Bioactive Glass Cement as an Antibiotic Delivery Vehicle for Treating Osteomyelitis 
PLoS ONE  2014;9(1):e85472.
Background
A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model.
Materials and Methods
The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin.
Results
The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18±2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects.
Conclusions
These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.
doi:10.1371/journal.pone.0085472
PMCID: PMC3888432  PMID: 24427311
19.  RBP2 Induces Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer 
PLoS ONE  2013;8(12):e84735.
RBP2 has been found to actively participate in cancer progression. It inhibits the senescence of cancer cells, mediates cancer cell proliferation and promotes cancer metastasis. It is also essential to drug tolerance. However, the effects of RBP2 on epithelial-mesenchymal transition are still unknown. In this study, we analyzed the effects of RBP2 on epithelial-mesenchymal transition in non-small cell lung cancer. The results showed that RBP2 down-regulated the expression of E-cadherin by inhibiting the promoter activity of E-cadherin and up-regulated the expression of N-cadherin and snail via the activation of Akt signaling, and the overexpression of RBP2 induced epithelial-mesenchymal transition in non-small cell lung cancer cells. Our study further indicated thatRBP2 may be a potential target for anti-lung cancer therapy.
doi:10.1371/journal.pone.0084735
PMCID: PMC3869927  PMID: 24376841
20.  The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat 
Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmax under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside.
doi:10.1155/2013/507832
PMCID: PMC3880758  PMID: 24454984
21.  Marjolin’s ulcer: a preventable malignancy arising from scars 
Background
Marjolin’s ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy.
Methods
A retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU.
Results
An incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = −0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = −0.7, P <0.01).
Conclusions
Patients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.
doi:10.1186/1477-7819-11-313
PMCID: PMC3896958  PMID: 24341890
Marjolin’s ulcer; Squamous cell carcinoma
22.  Enzymatic characterization of a glycoside hydrolase family 5 subfamily 7 (GH5_7) mannanase from Arabidopsis thaliana 
Planta  2013;239:653-665.
Each plant genome contains a repertoire of β-mannanase genes belonging to glycoside hydrolase family 5 subfamily 7 (GH5_7), putatively involved in the degradation and modification of various plant mannan polysaccharides, but very few have been characterized at the gene product level. The current study presents recombinant production and in vitro characterization of AtMan5-1 as a first step towards the exploration of the catalytic capacity of Arabidopsis thaliana β-mannanase. The target enzyme was expressed in both E. coli (AtMan5-1e) and P. pastoris (AtMan5-1p). The main difference between the two forms was a higher observed thermal stability for AtMan5-1p, presumably due to glycosylation of that particular variant. AtMan5-1 displayed optimal activity at pH 5 and 35 °C and hydrolyzed polymeric carob galactomannan, konjac glucomannan, and spruce galactoglucomannan as well as oligomeric mannopentaose and mannohexaose. However, the galactose-rich and highly branched guar gum was not as efficiently degraded. AtMan5-1 activity was enhanced by Co2+ and inhibited by Mn2+. The catalytic efficiency values for carob galactomannan were 426.8 and 368.1 min−1 mg−1 mL for AtMan5-1e and AtMan5-1p, respectively. Product analysis of AtMan5-1p suggested that at least five substrate-binding sites were required for manno-oligosaccharide hydrolysis, and that the enzyme also can act as a transglycosylase.
doi:10.1007/s00425-013-2005-y
PMCID: PMC3928506  PMID: 24327260
GH5_7; β-Mannanase; Glycoside hydrolase; Mannan; Plant cell wall; Carbohydrates
23.  Evaluation of the Potential Effect of Transgenic Rice Expressing Cry1Ab on the Hematology and Enzyme Activity in Organs of Female Swiss Rats 
PLoS ONE  2013;8(11):e80424.
To assess the safety of transgenic rice expressing Cry1Ab protein to vertebrates, the effect of Cry1Ab rice on broad health indicators in blood and various organs of Swiss rats were analyzed. The 30 and 90 day safety studies of Cry1Ab rice on female Swiss rats revealed that Cry1Ab rice had no significant effect on the several elements of blood lymph including hemogram, calcium ion concentration and apoptosis rate of lymphocytes, indicating that Cry1Ab protein could not affect the blood lymph of Swiss rat. Similarly, Cry1Ab rice had no effect on enzyme activities in a variety of organs of Swiss rat. However, Cry1Ab rice did have significant effects on the blood biochemistry indexes including urea, triglyceride (TG), glutamic oxalacetic transaminase (AST) and alkaline phosphatase (ALP) after the rats were fed with Cry1Ab rice for 30 days, but not after 90 days, indicating that Cry1Ab protein may influence blood metabolism for a short duration. Quantitative real-time PCR (qPCR) analysis of the 6 genes encoding enzymes responsible for the major detoxification functions of liver revealed that Cry1Ab rice exerted no influences on the levels of these transcripts in liver of Swiss rat, indicating that significant differences registered in part of the blood biochemical parameters in the 30 day study might result from other untested organs or tissues in response to the stress of exogenous Cry1Ab protein. The results suggest that Cry1Ab protein has no significant long-term (90 day) effects on female Swiss rat.
doi:10.1371/journal.pone.0080424
PMCID: PMC3842383  PMID: 24312218
24.  Understanding Acupuncture Based on ZHENG Classification from System Perspective 
Acupuncture is an efficient therapy method originated in ancient China, the study of which based on ZHENG classification is a systematic research on understanding its complexity. The system perspective is contributed to understand the essence of phenomena, and, as the coming of the system biology era, broader technology platforms such as omics technologies were established for the objective study of traditional chinese medicine (TCM). Omics technologies could dynamically determine molecular components of various levels, which could achieve a systematic understanding of acupuncture by finding out the relationships of various response parts. After reviewing the literature of acupuncture studied by omics approaches, the following points were found. Firstly, with the help of omics approaches, acupuncture was found to be able to treat diseases by regulating the neuroendocrine immune (NEI) network and the change of which could reflect the global effect of acupuncture. Secondly, the global effect of acupuncture could reflect ZHENG information at certain structure and function levels, which might reveal the mechanism of Meridian and Acupoint Specificity. Furthermore, based on comprehensive ZHENG classification, omics researches could help us understand the action characteristics of acupoints and the molecular mechanisms of their synergistic effect.
doi:10.1155/2013/956967
PMCID: PMC3857847  PMID: 24348731
25.  Association between the Telomerase Reverse Transcriptase (TERT) rs2736098 Polymorphism and Cancer Risk: Evidence from a Case-Control Study of Non-Small-Cell Lung Cancer and a Meta-Analysis 
PLoS ONE  2013;8(11):e76372.
Background
A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. In addition, many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. Nevertheless, the results of related case-control studies remain inconsistent.
Methods
We hypothesized that the genetic risk variant identified in Caucasians may potentially influence the susceptibility to lung cancer in the Chinese population. To test this hypothesis, a case-control study including 539 non-small-cell lung cancer (NSCLC) cases and 627 cancer-free controls was conducted. Furthermore, to investigate the association between rs2736098 and cancer risk, a meta-analysis based on previously published studies and our case-control study was also performed.
Results
Multivariate logistic regression demonstrated that individuals carrying the A allele or the AA genotype exhibited a significantly elevated risk of NSCLC compared with those carrying the G allele or GG genotype (A vs. G: OR = 1.21, 95% CI = 1.02–1.43, P = 0.028; AA vs. GG: OR = 1.48, 95% CI = 1.05–2.09, P = 0.025). Additionally, this association was stronger among adenocarcinoma cases (AA vs. GG: OR = 1.67, 95% CI = 1.12–2.50, P = 0.013; A vs. G: OR = 1.28, 95% CI = 1.05–1.57, P = 0.016). In the meta-analysis, a borderline significant association between the rs2736098 polymorphism and overall cancer risk was observed (AA vs. GG: OR = 1.25, 95% CI = 1.07–1.46; AA vs. AG+GG: OR = 1.22, 95% CI = 1.06–1.41; additive model: OR = 1.10, 95% CI = 1.02–1.18), and further stratifications demonstrated a moderately increased risk for lung and bladder cancer, Asian ethnicity and hospital-based studies.
Conclusions
Our results suggest that the rs2736098 polymorphism may contribute to the risk of lung cancer, especially adenocarcinoma, in the Chinese population. In addition, the current meta-analysis indicates that this genetic variant is only weakly associated with overall cancer risk. However, the rs2736098 polymorphism may affect individual susceptibility to lung and bladder cancer. Further studies are needed to validate our findings.
doi:10.1371/journal.pone.0076372
PMCID: PMC3834105  PMID: 24260099

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