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1.  Primary synovial sarcoma of the prostate metastatic to the liver and lung: a case report 
Primary synovial sarcoma of the prostate is an uncommon malignant tumor. There are few cases reported in the English medical literature to date. Here, we present a case of 22-year-old man with primary synovial sarcoma of the prostate metastatic to the liver and lung. To our knowledge, only six reports of synovial sarcoma involving the prostate have been previously published. We also reviewed the previous treatments and prognoses in previous case reports and evaluate the proper treatment for this disease.
doi:10.1186/1477-7819-12-194
PMCID: PMC4086276  PMID: 24969223
Prostate; Synovial sarcoma; Metastasis
2.  Nrf2 Signaling Contributes to the Neuroprotective Effects of Urate against 6-OHDA Toxicity 
PLoS ONE  2014;9(6):e100286.
Background
Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood.
Results
In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) and heme oxygenase-1 (HO-1), both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment.
Conclusion
Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.
doi:10.1371/journal.pone.0100286
PMCID: PMC4069024  PMID: 24959672
3.  Global Metabolomic Analyses of the Hemolymph and Brain during the Initiation, Maintenance, and Termination of Pupal Diapause in the Cotton Bollworm, Helicoverpa armigera 
PLoS ONE  2014;9(6):e99948.
A strategy known as diapause (developmental arrest) has evolved in insects to increase their survival rate under harsh environmental conditions. Diapause causes a dramatic reduction in the metabolic rate and drastically extends lifespan. However, little is known about the mechanisms underlying the metabolic changes involved. Using gas chromatography-mass spectrometry, we compared the changes in the metabolite levels in the brain and hemolymph of nondiapause- and diapause-destined cotton bollworm, Helicoverpa armigera, during the initiation, maintenance, and termination of pupal diapause. A total of 55 metabolites in the hemolymph and 52 metabolites in the brain were detected. Of these metabolites, 21 and 12 metabolite levels were altered in the diapause pupal hemolymph and brain, respectively. During diapause initiation and maintenance, the number of metabolites with increased levels in the hemolymph of the diapausing pupae is far greater than the number in the nondiapause pupae. These increased metabolites function as an energy source, metabolic intermediates, and cryoprotectants. The number of metabolites with decreased levels in the brain of diapausing pupae is far greater than the number in the nondiapause pupae. Low metabolite levels are likely to directly or indirectly repress the brain metabolic activity. During diapause termination, most of the metabolite levels in the hemolymph of the diapausing pupae rapidly decrease because they function as energy and metabolic sources that promote pupa-adult development. In conclusion, the metabolites with altered levels in the hemolymph and brain serve as energy and metabolic resources and help to maintain a low brain metabolic activity during diapause.
doi:10.1371/journal.pone.0099948
PMCID: PMC4057385  PMID: 24926789
4.  Virus-related liver cirrhosis: Molecular basis and therapeutic options 
Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8+ T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
doi:10.3748/wjg.v20.i21.6457
PMCID: PMC4047331  PMID: 24914367
Liver cirrhosis; Hepatitis B virus; Hepatitis C virus; Evolution; Immune cells; Signaling pathway; Hepatic stellate cells; Antiviral therapy
5.  Effect of NQO1 C609T polymorphism on prostate cancer risk: a meta-analysis 
OncoTargets and therapy  2014;7:907-914.
Background
Some studies have found that the NAD(P)H:quinone oxidoreductase 1 (NQO1) SNP609 is associated with an increased risk for several malignancies. Numerous epidemiological studies have evaluated the association between the NQO1 C609T polymorphism and the risk of prostate cancer. However, the results of these studies have been conflicting. The aim of this study was to provide a more precise estimation of its relationship with prostate cancer using a meta-analysis.
Methods
Electronic searches of several databases were conducted for all publications on the association between the NQO1 C609T polymorphism and prostate cancer before May 2013. The odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis.
Results
A total of six studies with 717 cases and 1,794 controls were included. No significant association was found between the NQO1 C609T polymorphism and prostate cancer risk in the total population analysis. In subgroup meta-analysis by ethnicity, a positive association was found in an Asian subgroup (T versus C, OR 1.337, 95% CI 1.014–1.763, P=0.040; TT + CT versus CC, OR 1.419, 95% CI 1.053–1.913, P=0.021). However, no significant association in any genetic models was observed in Caucasians.
Conclusion
This meta-analysis showed that the NQO1 SNP609 T allele might be a risk factor for prostate cancer in Asians. However, this result should be verified by additional population-based studies with large sample sizes.
doi:10.2147/OTT.S62046
PMCID: PMC4051819  PMID: 24940075
NQO1; SNP609; polymorphism; prostate cancer
6.  Surface modification and characterization of carbon spheres by grafting polyelectrolyte brushes 
Nanoscale Research Letters  2014;9(1):283.
Modified carbon spheres (CSPBs) were obtained by grafting poly(diallyl dimethyl ammonium chloride) (p-DMDAAC) on the surface of carbon spheres (CSs). It can be viewed as a kind of cation spherical polyelectrolyte brushes (CSPBs), which consist of carbon spheres as core and polyelectrolytes as shell. The method of synthesizing carbon spheres was hydrothermal reaction. Before the polyelectrolyte brushes were grafted, azo initiator [4,4′-Azobis(4-cyanovaleric acyl chloride)] was attached to the carbon spheres' surface through hydroxyl groups. CSPBs were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), conductivity meter, and system zeta potential. The results showed that compared with carbon spheres, the conductivity and zeta potential on CSPBs increased from 9.98 to 49.24 μS/cm and 11.6 to 42.5 mV, respectively, after the polyelectrolyte brushes were grafted. The colloidal stability in water was enhanced, and at the same time, the average diameter of the CSPBs was found to be 173 nm, and the average molecular weight and grafted density of the grafted polyelectrolyte brushes were 780,138 g/mol and 4.026 × 109/nm2, respectively.
doi:10.1186/1556-276X-9-283
PMCID: PMC4053276  PMID: 24948900
Carbon spheres; Cation spherical polyelectrolyte brushes; Surface modification; Azo initiator; DMDAAC
7.  Association of T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (Tim-3) Polymorphisms with Susceptibility and Disease Progression of HBV Infection 
PLoS ONE  2014;9(5):e98280.
Purpose
T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma.
Methods
A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection.
Results
Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05).
Conclusions
Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.
doi:10.1371/journal.pone.0098280
PMCID: PMC4035322  PMID: 24867713
8.  The Effect of Electroacupuncture on the Extracellular Matrix Synthesis and Degradation in a Rabbit Model of Disc Degeneration 
The present study was aimed at determining if the electroacupuncture (EA) is able to protect degenerated disc in vivo. New Zealand white rabbits (n = 40) were used for the study. The rabbits were randomly assigned to four groups. EA intervention was applied to one of the four groups. Magnetic resonance imaging and Pfirrmann's classification were obtained for each group to evaluate EA treatment on the intervertebral disc degeneration. Discs were analyzed using immunofluorescence for the labeling of collagens 1 and 2, bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-13 (MMP-13), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). For protein expression analysis, western blot was used for biglycan and decorin. Outcomes indicated that EA intervention decreased the grades compared with the compressed disc. Immunofluorescence analysis showed a significant increase of collagens 1 and 2, TIMP-1, and BMP-2 positive cells, in contrast to MMP-13 after EA treatment for 28 days. The protein expression showed a sign of regeneration that decorin and biglycan were upregulated. It was concluded that EA contributed to the extracellular matrix (ECM) anabolic processes and increased the ECM components. MMPs and their inhibitors involved in the mechanism of EA intervention on ECM decreased disc. It kept a dynamic balance between ECM synthesis and degradation.
doi:10.1155/2014/731395
PMCID: PMC4058458  PMID: 24987434
9.  A Population-Based Study Examining Hepatitis B Virus Infection and Immunization Rates in Northwest China 
PLoS ONE  2014;9(5):e97474.
Background and Aim
Current baseline data regarding the prevalence of hepatitis B virus (HBV) infections and the immune status in hyperendemic areas is necessary in evaluating the effectiveness of ongoing HBV prevention and control programs in northwest China. This study aims to determine the prevalence of chronic HBV infections, past exposure rates, and immune response profiles in Wuwei City, northwest China in 2010.
Methods
Cross-sectional household survey representative of the Wuwei City population. 28,579 participants were interviewed in the seroepidemiological survey ≥1 year of age. House to house screening was conducted using a standard questionnaire. All serum samples were screened by enzyme-linked immunoassays for the presence of hepatitis B surface antigen, antibodies against HBV surface antigen, and antibodies to the hepatitis B core antigen.
Results
Among individuals ≥1 year of age, 7.2% (95%CI: 6.3–8.1%) had chronic HBV infections, 43.9% (CI: 40.4–47.4%) had been exposed to HBV, and 23.49% (CI: 21.6–25.3%) had vaccine-induced immunity. Multi-factor weighted logistic regression analysis showed that having household contact with HBV carriers (OR = 2.6, 95%CI: 2.3–3.0) and beauty treatments in public places (OR = 1.2, 95%CI: 1.1–1.3) were the risk factors of HBV infection in whole population. Having household contact with HBV carriers (OR = 3.8, 95% CI: 2.2–6.5) and lack of hepatitis vaccination (OR = 2.0, 95% CI: 1.4–3.3) were the risk factors for HBV infection in children aged 1–14 years.
Conclusions
Hepatitis B infection remains a serious public health problem in northwest China. Having household contact with HBV carriers and beauty treatments in public places represented HBV infection risk factors. Hepatitis B vaccine immunization strategies need further improvement, particularly by targeting the immunization of rural migrant workers.
doi:10.1371/journal.pone.0097474
PMCID: PMC4022626  PMID: 24832483
10.  Feedforward-Feedback Hybrid Control for Magnetic Shape Memory Alloy Actuators Based on the Krasnosel'skii-Pokrovskii Model 
PLoS ONE  2014;9(5):e97086.
As a new type of smart material, magnetic shape memory alloy has the advantages of a fast response frequency and outstanding strain capability in the field of microdrive and microposition actuators. The hysteresis nonlinearity in magnetic shape memory alloy actuators, however, limits system performance and further application. Here we propose a feedforward-feedback hybrid control method to improve control precision and mitigate the effects of the hysteresis nonlinearity of magnetic shape memory alloy actuators. First, hysteresis nonlinearity compensation for the magnetic shape memory alloy actuator is implemented by establishing a feedforward controller which is an inverse hysteresis model based on Krasnosel'skii-Pokrovskii operator. Secondly, the paper employs the classical Proportion Integration Differentiation feedback control with feedforward control to comprise the hybrid control system, and for further enhancing the adaptive performance of the system and improving the control accuracy, the Radial Basis Function neural network self-tuning Proportion Integration Differentiation feedback control replaces the classical Proportion Integration Differentiation feedback control. Utilizing self-learning ability of the Radial Basis Function neural network obtains Jacobian information of magnetic shape memory alloy actuator for the on-line adjustment of parameters in Proportion Integration Differentiation controller. Finally, simulation results show that the hybrid control method proposed in this paper can greatly improve the control precision of magnetic shape memory alloy actuator and the maximum tracking error is reduced from 1.1% in the open-loop system to 0.43% in the hybrid control system.
doi:10.1371/journal.pone.0097086
PMCID: PMC4020807  PMID: 24828010
11.  A Functional Variant of PTPN22 Confers Risk for Vogt-Koyanagi-Harada Syndrome but Not for Ankylosing Spondylitis 
PLoS ONE  2014;9(5):e96943.
Background
Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS).
Methods
A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry.
Results
The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10−7, OR = 1.54; Pc = 3.83×10−8, OR = 1.40; Pc = 6.35×10−4, OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype.
Conclusions
The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.
doi:10.1371/journal.pone.0096943
PMCID: PMC4016172  PMID: 24816862
12.  Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival 
Background
Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation.
Methods
Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated.
Results
Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival.
Conclusions
Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.
doi:10.1186/1749-8090-9-82
PMCID: PMC4026832  PMID: 24886081
Odor; Tokishakuyaku-san; Heart transplantation; Regulatory cells; Mouse
13.  Fabrication of nanochannels with ladder nanostructure at the bottom using AFM nanoscratching method 
Nanoscale Research Letters  2014;9(1):212.
This letter presents a novel atomic force microscopy (AFM)-based nanomanufacturing method combining the tip scanning with the high-precision stage movement to fabricate nanochannels with ladder nanostructure at the bottom by continuous scanning with a fixed scan size. Different structures can be obtained according to the matching relation of the tip feeding velocity and the precision stage moving velocity. This relationship was first studied in detail to achieve nanochannels with different ladder nanostructures at the bottom. Machining experiments were then performed to fabricate nanochannels on an aluminum alloy surface to demonstrate the capability of this AFM-based fabrication method presented in this study. Results show that the feed value and the tip orientation in the removing action play important roles in this method which has a significant effect on the machined surfaces. Finally, the capacity of this method to fabricate a large-scale nanochannel was also demonstrated. This method has the potential to advance the existing AFM tip-based nanomanufacturing technique of the formation these complex structures by increasing the removal speed, simplifying the processing procedure and achieving the large-scale nanofabrication.
doi:10.1186/1556-276X-9-212
PMCID: PMC4039066  PMID: 24940171
Atomic force microscopy; Nanochannel; Ladder nanostructure
14.  HLA-DP Polymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections, Possibly through Interacting with Viral Mutations 
Journal of Virology  2013;87(22):12176-12186.
Genetic polymorphisms of HLA-DP have been associated with hepatitis B virus (HBV) persistence. We aimed to determine the effect of HLA-DP polymorphisms on the generation of HBV mutations and their interactions on the outcomes of HBV infection. rs3077, rs3135021, rs9277535, and rs2281388 were genotyped in 1,342 healthy controls, 327 HBV clearance subjects, and 2,736 HBV-positive subjects, including 1,108 hepatocellular carcinoma (HCC) patients, using quantitative PCR. HBV mutations were determined by sequencing. Multiplicative interactions of HLA-DP polymorphisms and viral mutations were assessed by multivariate logistic regression. rs3077 (from subjects with genotype CT combined with those from subjects with genotype TT [CT+TT] versus CC), rs3135021 (GA+AA versus GG), rs9277535 (GA+AA versus GG), and rs2281388 (CC versus CT+TT) significantly decreased HBV persistence. This effect was found only in genotype B HBV-infected subjects compared to HBV clearance subjects. HLA-DP polymorphisms promoting HBV clearance were associated with a lower prevalence of mutations increasing HCC risk (C1653T, T1674C/G, A1846T, G1896A and pre-S2 mutations and pre-S deletion in genotype C) and a higher prevalence of mutations decreasing HCC risk (G1652A, T1673C, T1674C, G1719T, G1730C, and G1799C in genotype B and A1727T in genotype C). Significant effects of viral mutations on cirrhosis and HCC were selectively evident in those with HLA-DP polymorphisms promoting HBV persistence. The interactions of C1653T, T1674C/G, and G1896A mutations with HLA-DP polymorphisms promoting HBV clearance significantly decreased cirrhosis risk. The interaction of rs9277535 AA with the T1674C/G or G1719T mutation in genotype C significantly decreased HCC risk. In conclusion, HLA-DP polymorphisms affect genotype B HBV clearance, regulate immune selection of viral mutations, and influence cirrhosis and HCC risks contributed by HBV mutations.
doi:10.1128/JVI.02073-13
PMCID: PMC3807892  PMID: 24006435
15.  Glycation of Apoprotein A-I Is Associated With Coronary Artery Plaque Progression in Type 2 Diabetic Patients 
Diabetes Care  2013;36(5):1312-1320.
OBJECTIVE
To investigate whether glycation level of apoprotein (apo)A-I is associated with coronary artery disease (CAD) and plaque progression in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS
Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment.
RESULTS
Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients.
CONCLUSIONS
ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients.
doi:10.2337/dc12-1411
PMCID: PMC3631856  PMID: 23230102
16.  Expression of Hippo Pathway in Colorectal Cancer 
Background/Aims:
Hippo pathway plays a crucial role in cell proliferation, apoptosis, and tumorigenesis. This study aimed to investigate the expression of Hippo pathway components in the progression and metastasis of colorectal cancer (CRC).
Materials and Methods:
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the mRNA expression levels of MST1, LATS2, YAP, TAZ, TEAD1, CDX2, and OCT4, and western blot (WB) was used to examine the protein expression levels of MST1, YAP, TEAD1, and CDX2 in 30 specimens of human colorectal adenomas, 50 pairs of human CRC tissues, and adjacent nontumorous tissues from CRC patients. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the housekeeping gene in qRT-PCR.
Results:
The mRNA expression levels of MST1 and LATS2 showed an increasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). Conversely, the mRNA expression levels of YAP, TAZ, TEAD, and OCT4 showed a decreasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). MST1 protein was downregulated and YAP and TEAD1 proteins were upregulated in CRC (all P < 0.001). The mRNA and protein expression levels of CDX2 in CRC were significantly lower than those in colorectal adenomas and adjacent nontumorous tissues (P < 0.001), but there was no significant difference between the latter two groups (qRT-PCR, P = 0.113; WB, P = 0.151). Furthermore, statistical analysis showed that the expression levels of Hippo signal pathway components were associated with tumor differentiation, lymph node metastasis, and TNM stage.
Conclusion:
Hippo pathway is suppressed in the progression from colorectal adenomas to CRC and is associated with CRC progression and metastasis. This study suggests the components of Hippo pathway might be prognostic indicators for CRC patients.
doi:10.4103/1319-3767.133025
PMCID: PMC4067916  PMID: 24976283
Colorectal adenomas; colorectal cancer; Hippo pathway; tumorigenesis
17.  Histone acetylation associated up-regulation of the cell wall related genes is involved in salt stress induced maize root swelling 
BMC Plant Biology  2014;14:105.
Background
Salt stress usually causes crop growth inhibition and yield decrease. Epigenetic regulation is involved in plant responses to environmental stimuli. The epigenetic regulation of the cell wall related genes associated with the salt-induced cellular response is still little known. This study aimed to analyze cell morphological alterations in maize roots as a consequence of excess salinity in relation to the transcriptional and epigenetic regulation of the cell wall related protein genes.
Results
In this study, maize seedling roots got shorter and displayed swelling after exposure to 200 mM NaCl for 48 h and 96 h. Cytological observation showed that the growth inhibition of maize roots was due to the reduction in meristematic zone cell division activity and elongation zone cell production. The enlargement of the stele tissue and cortex cells contributed to root swelling in the elongation zone. The cell wall is thought to be the major control point for cell enlargement. Cell wall related proteins include xyloglucan endotransglucosylase (XET), expansins (EXP), and the plasma membrane proton pump (MHA). RT-PCR results displayed an up-regulation of cell wall related ZmEXPA1, ZmEXPA3, ZmEXPA5, ZmEXPB1, ZmEXPB2 and ZmXET1 genes and the down-regulation of cell wall related ZmEXPB4 and ZmMHA genes as the duration of exposure was increased. Histone acetylation is regulated by HATs, which are often correlated with gene activation. The expression of histone acetyltransferase genes ZmHATB and ZmGCN5 was increased after 200 mM NaCl treatment, accompanied by an increase in the global acetylation levels of histones H3K9 and H4K5. ChIP experiment showed that the up-regulation of the ZmEXPB2 and ZmXET1 genes was associated with the elevated H3K9 acetylation levels on the promoter regions and coding regions of these two genes.
Conclusions
These data suggested that the up-regulation of some cell wall related genes mediated cell enlargement to possibly mitigate the salinity-induced ionic toxicity, and different genes had specific function in response to salt stress. Histone modification as a mediator may contribute to rapid regulation of cell wall related gene expression, which reduces the damage of excess salinity to plants.
doi:10.1186/1471-2229-14-105
PMCID: PMC4005470  PMID: 24758373
Zea mays; Cell enlargement; Cell wall related genes; Histone acetylation; Root swelling; Salt stress
18.  Relative Importance of Deterministic and Stochastic Processes in Driving Arbuscular Mycorrhizal Fungal Assemblage during the Spreading of a Toxic Plant 
PLoS ONE  2014;9(4):e95672.
Both deterministic and stochastic processes are expected to drive the assemblages of arbuscular mycorrhizal (AM) fungi, but little is known about the relative importance of these processes during the spreading of toxic plants. Here, the species composition and phylogenetic structure of AM fungal communities colonizing the roots of a toxic plant, Ligularia virgaurea, and its neighborhood plants, were analyzed in patches with different individual densities of L. virgaurea (represents the spreading degree). Community compositions of AM fungi in both root systems were changed significantly by the L. virgaurea spreading, and also these communities fitted the neutral model very well. AM fungal communities in patches with absence and presence of L. virgaurea were phylogenetically random and clustered, respectively, suggesting that the principal ecological process determining AM fungal assemblage shifted from stochastic process to environmental filtering when this toxic plant was present. Our results indicate that deterministic and stochastic processes together determine the assemblage of AM fungi, but the dominant process would be changed by the spreading of toxic plants, and suggest that the spreading of toxic plants in alpine meadow ecosystems might be involving the mycorrhizal symbionts.
doi:10.1371/journal.pone.0095672
PMCID: PMC3991703  PMID: 24748393
19.  Bony destructive injuries of the calcaneus: long-term results of a minimally invasive procedure followed by early functional exercise: a retrospective study 
BMC Surgery  2014;14:19.
Background
Bony destructive injury of the calcaneus (BDIC) represents one of the most severe comminuted fractures of the calcaneus in which soft tissue coverage remains intact. The features of this injury include a collapsed articular surface, significant widening, severe loss of height and an unrecognisable outline of the calcaneus. This study aims to present the long-term outcomes of BDIC treated in a minimally invasive fashion followed by supervised early exercise.
Methods
Twelve patients with unilateral BDICs were treated at our institution. The main surgical procedures included percutaneous traction and leverage reduction and internal compression fixation with anatomic plates and compression bolts. Early functional exercise was encouraged to mould the subtalar joint. The height, length and width of the calcaneus; Böhler’s and Gissane’s angles; reduction of the articular surfaces; and functional recovery of the affected feet were assessed.
Results
The height, length and width of the calcaneus were substantially restored. The mean Böhler’s and Gissane’s angles of the affected calcaneus were 24.5 and 122.8 degrees, respectively. Five patients regained anatomical or nearly anatomical reduction of their posterior facets. Residual articular displacement of more than 3 mm was noted in three patients. Patients were followed for a mean of 93.9 months. The mean American Orthopaedic Foot and Ankle Society score was 83.8. Nine patients showed excellent or good results. Radiographic evidence of post-traumatic subtalar arthritis was observed in four cases. However, no subtalar arthrodesis was required.
Conclusions
BDICs can be treated effectively with percutaneous reduction and internal compression fixation followed by early active exercise. This protocol resulted in satisfactory radiological and functional outcomes.
doi:10.1186/1471-2482-14-19
PMCID: PMC4021046  PMID: 24725606
Calcaneal fracture; Bony destructive injury; Internal compression fixation; Percutaneous leverage; Early exercise
20.  Abnormal promoter methylation of multiple tumor suppressor genes in human bronchial epithelial malignant cells 
Biomedical Reports  2014;2(4):525-528.
Carcinoma of the lung is the leading cause of cancer-related mortality worldwide. In order to understand the pathogenesis of radiation-induced lung cancer, we adopted a model of transformed human bronchial epithelial cells (BEP2D) induced by α-particles. Methylation-specific polymerase chain reaction was performed to detect aberrant promoter methylation of multiple tumor suppressor genes, including p14ARF, p16INK4a, O6-methylguanine-DNA methyltransferase, glutathione S-transferase P1 and death-associated protein kinase genes in the BEP2D cell line and its malignant transformant, the BERP35T1 cell line. Our results demonstrated the distinctive methylation pattern for these tumor suppressor genes in radiation-induced malignant cells, as compared to their wild-type counterparts. Our study revealed epigenetic signatures for the characterization of radiation-mediated carcinogenesis and it may facilitate early diagnosis of patients at high risk for lung cancer.
doi:10.3892/br.2014.268
PMCID: PMC4051483  PMID: 24944801
lung cancer; carcinogenesis; DNA methylation; tumor suppressor genes
21.  Electroacupuncture improves recovery after hemorrhagic brain injury by inducing the expression of angiopoietin-1 and -2 in rats 
Background
Angiopoietin (Ang) is one of the major effectors of angiogenesis, playing a critical role in neurovascular remodeling after stroke. Acupuncture has been widely used for treating stroke in China for a long time. Recently, we have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on the expression of Ang-1 and Ang-2 in the brain after ICH.
Methods
ICH was induced by stereotactic injection of collagenase type VII into the right globus pallidus. Adult male Sprague–Dawley rats were randomized into the following four groups: sham-operation (SHAM), stroke-no electroacupuncture (SNE), stroke-EA at the Zusanli acupoint (SEZ), and stroke-EA at a nonacupoint (SEN). EA was applied to the bilateral Zusanli (ST36) acupoint in the SEZ group and a nonacupoint in the SEN group. The expression of Ang-1 and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR).
Results
Some Ang-1 and Ang-2 immunoreactive microvessels with a dilated outline were detected in the perihematomal tissues after ICH, and the vessels extended into the clot from the surrounding area since day 7. The expression of Ang-1 increased notably as long as 2 weeks after ICH, while Ang-2 immunoreactivity declined at about 7 days following a striking upregulation at 3 days. EA at the Zusanli (ST36) acupoint upregulated the expression of Ang-1 and Ang-2 at both the protein and mRNA levels. However, EA at a nonacupoint had little effect on the expression of Ang-1 and Ang-2.
Conclusions
Our data suggest that EA at the Zusanli (ST36) acupoint exerts neuroprotective effects on hemorrhagic stroke by upregulation of Ang-1 and Ang-2.
doi:10.1186/1472-6882-14-127
PMCID: PMC4012070  PMID: 24708627
Electroacupuncture; Zusanli acupoint; Intracerebral hemorrhage; Angiogenesis; Angiopoietin
22.  Repair of Posterior Semicircular Canal Dehiscence From a High Jugular Bulb 
Objective
To describe the clinical evaluation and operative management of posterior semicircular canal dehiscence caused by a high jugular bulb.
Methods
Retrospective case report.
Results
The patient had clinical and audiometric findings consistent with semicircular canal dehiscence and imaging demonstrating erosion of the posterior semicircular canal by a high jugular bulb. Resurfacing of the eroded canal provided resolution of vestibular symptoms without damage to the inner ear.
Conclusions
Dehiscence of the posterior semicircular canal can cause clinical and audiometric findings similar to those of superior semicircular canal dehiscence syndrome. Resurfacing of the area of dehiscence can be performed to successfully relieve the vestibular symptoms. In the case of dehiscence of the posterior canal from a high jugular bulb, resurfacing may offer advantages over canal plugging for definitive management.
PMCID: PMC3972486  PMID: 23697325
23.  The Marine Fungal Metabolite, Dicitrinone B, Induces A375 Cell Apoptosis through the ROS-Related Caspase Pathway 
Marine Drugs  2014;12(4):1939-1958.
Dicitrinone B, a rare carbon-bridged citrinin dimer, was isolated from the marine-derived fungus, Penicillium citrinum. It was reported to have antitumor effects on tumor cells previously; however, the details of the mechanism remain unclear. In this study, we found that dicitrinone B inhibited the proliferation of multiple tumor types. Among them, the human malignant melanoma cell, A375, was confirmed to be the most sensitive. Morphologic evaluation, cell cycle arrest and apoptosis rate analysis results showed that dicitrinone B significantly induced A375 cell apoptosis. Subsequent observation of reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) reduction revealed that the apoptosis induced by dicitrinone B may be triggered by over-producing ROS. Further studies indicated that the apoptosis was associated with both intrinsic and extrinsic apoptosis pathways under the regulation of Bcl-2 family proteins. Caspase-9, caspase-8 and caspase-3 were activated during the process, leading to PARP cleavage. The pan-caspase inhibitor, Z-VAD-FMK, could reverse dicitrinone B-induced apoptosis, suggesting that it is a caspase-dependent pathway. Our data for the first time showed that dicitrinone B inhibits the proliferation of tumor cells by inducing cell apoptosis. Moreover, compared with the first-line chemotherapy drug, 5-fluorouracil (5-Fu), dicitrinone B showed much more potent anticancer efficacy, suggesting that it might serve as a potential antitumor agent.
doi:10.3390/md12041939
PMCID: PMC4012433  PMID: 24699111
dicitrinone B; marine-derived fungus; human malignant melanoma cell A375; anticancer activity; apoptosis
24.  Flood Disaster Risk Assessment of Rural Housings — A Case Study of Kouqian Town in China 
Floods are a devastating kind of natural disaster. About half of the population in China lives in rural areas. Therefore, it is necessary to assess the flood disaster risk of rural housings. The results are valuable for guiding the rescue and relief goods layout. In this study, we take the severe flood disaster that happened at Kouqian Town in Jilin, China in 2010 as an example to build an risk assessment system for flood disaster on rural housings. Based on the theory of natural disaster risk formation and “3S” technology (remote sensing, geography information systems and global positioning systems), taking the rural housing as the bearing body, we assess the flood disaster risk from three aspects: hazard, exposure and vulnerability. The hazard presented as the flood submerging range and depth. The exposure presented as the values of the housing and the property in it. The vulnerability presented as the relationship between the losses caused by flood and flood depth. We validate the model by the field survey after the flood disaster. The risk assessment results highly coincide with the field survey losses. This model can be used to assess the risk of other flood events in this area.
doi:10.3390/ijerph110403787
PMCID: PMC4024995  PMID: 24705363
flood disaster; risk assessment; rural housings; “3S” technology
25.  Measurement and Analysis of P2P IPTV Program Resource 
The Scientific World Journal  2014;2014:101702.
With the rapid development of P2P technology, P2P IPTV applications have received more and more attention. And program resource distribution is very important to P2P IPTV applications. In order to collect IPTV program resources, a distributed multi-protocol crawler is proposed. And the crawler has collected more than 13 million pieces of information of IPTV programs from 2009 to 2012. In addition, the distribution of IPTV programs is independent and incompact, resulting in chaos of program names, which obstructs searching and organizing programs. Thus, we focus on characteristic analysis of program resources, including the distributions of length of program names, the entropy of the character types, and hierarchy depth of programs. These analyses reveal the disorderly naming conventions of P2P IPTV programs. The analysis results can help to purify and extract useful information from chaotic names for better retrieval and accelerate automatic sorting of program and establishment of IPTV repository. In order to represent popularity of programs and to predict user behavior and popularity of hot programs over a period, we also put forward an analytical model of hot programs.
doi:10.1155/2014/101702
PMCID: PMC3977418  PMID: 24772008

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