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1.  Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts 
Scientific Reports  2015;5:8077.
L-type voltage-sensitive calcium channels (LTCCs), particularly Cav1.2 LTCCs, play fundamental roles in cellular responses to mechanical stimuli in osteoblasts. Numerous studies have shown that mechanical loading promotes bone formation, whereas the removal of this stimulus under microgravity conditions results in a reduction in bone mass. However, whether microgravity exerts an influence on LTCCs in osteoblasts and whether this influence is a possible mechanism underlying the observed bone loss remain unclear. In the present study, we demonstrated that simulated microgravity substantially inhibited LTCC currents and suppressed Cav1.2 at the protein level in MC3T3-E1 osteoblast-like cells. In addition, reduced Cav1.2 protein levels decreased LTCC currents in MC3T3-E1 cells. Moreover, simulated microgravity increased miR-103 expression. Cav1.2 expression and LTCC current densities both significantly increased in cells that were transfected with a miR-103 inhibitor under mechanical unloading conditions. These results suggest that simulated microgravity substantially inhibits LTCC currents in osteoblasts by suppressing Cav1.2 expression. Furthermore, the down-regulation of Cav1.2 expression and the inhibition of LTCCs caused by mechanical unloading in osteoblasts are partially due to miR-103 up-regulation. Our study provides a novel mechanism for microgravity-induced detrimental effects on osteoblasts, offering a new avenue to further investigate the bone loss induced by microgravity.
doi:10.1038/srep08077
PMCID: PMC4308706  PMID: 25627864
2.  Computational cancer biology: education is a natural key to many locks 
BMC Cancer  2015;15:7.
Background
Oncology is a field that profits tremendously from the genomic data generated by high-throughput technologies, including next-generation sequencing. However, in order to exploit, integrate, visualize and interpret such high-dimensional data efficiently, non-trivial computational and statistical analysis methods are required that need to be developed in a problem-directed manner.
Discussion
For this reason, computational cancer biology aims to fill this gap. Unfortunately, computational cancer biology is not yet fully recognized as a coequal field in oncology, leading to a delay in its maturation and, as an immediate consequence, an under-exploration of high-throughput data for translational research.
Summary
Here we argue that this imbalance, favoring ’wet lab-based activities’, will be naturally rectified over time, if the next generation of scientists receives an academic education that provides a fair and competent introduction to computational biology and its manifold capabilities. Furthermore, we discuss a number of local educational provisions that can be implemented on university level to help in facilitating the process of harmonization.
doi:10.1186/s12885-014-1002-2
PMCID: PMC4298945  PMID: 25588624
Cancer; Computational biology; Genomics data; Computational oncology; Computational genomics; Statistical genomics; Systems medicine
3.  Repeating the Past: Prevention Focus Motivates Repetition, Even For Unethical Decisions 
Psychological science  2013;25(1):179-187.
Prevention-focused individuals are motivated to maintain the status quo. Given this, we predicted that individuals with a strong prevention focus, either as a chronic predisposition or situationally induced, would treat their initial decision of how to behave on a first task as the status quo, and thus be motivated to repeat that decision on a subsequent task—even for decisions that are ethically questionable. Five studies supported this prediction in multiple ethical domains: whether or not to overstate performance (Studies 1, 2a, 2b), to disclose disadvantageous facts (Study 3), and to pledge a donation (Study 4). The prevention-repetition effect was observed when initial and subsequent decisions were in the same domain (Studies 1-3) and in different domains (Study 4). Alternative accounts such as justification for the initial decision and preference for consistency were ruled out (Study 2b).
doi:10.1177/0956797613502363
PMCID: PMC3899102  PMID: 24277774
Motivation; Morality; ethics; regulatory focus; prevention focus; slippery slope
4.  Citrate Synthase Expression Affects Tumor Phenotype and Drug Resistance in Human Ovarian Carcinoma 
PLoS ONE  2014;9(12):e115708.
Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.
doi:10.1371/journal.pone.0115708
PMCID: PMC4278743  PMID: 25545012
5.  Proteome changes underpin improved meat quality and yield of chickens (Gallus gallus) fed the probiotic Enterococcus faecium 
BMC Genomics  2014;15(1):1167.
Background
Supplementation of broiler chicken diets with probiotics may improve carcass characteristics and meat quality. However, the underlying molecular mechanism remains unclear. In the present study, 2D-DIGE-based proteomics was employed to investigate the proteome changes associated with improved carcass traits and meat quality of Arbor Acres broilers (Gallus gallus) fed the probiotic Enterococcus faecium.
Results
The probiotic significantly increased meat colour, water holding capacity and pH of pectoral muscle but decreased abdominal fat content. These meat quality changes were related to the altered abundance of 22 proteins in the pectoral muscle following E. faecium feeding. Of these, 17 proteins have central roles in regulating meat quality due to their biological interaction network. Altered cytoskeletal and chaperon protein expression also contribute to improved water holding capacity and colour of meat, which suggests that upregulation of chaperon proteins maintains cell integrity and prevents moisture loss by enhancing folding and recovery of the membrane and cytoskeletal proteins. The down-regulation of β-enolase and pyruvate kinase muscle isozymes suggests roles in increasing the pH of meat by decreasing the production of lactic acid. The validity of the proteomics results was further confirmed by qPCR.
Conclusions
This study reveals that improved meat quality of broilers fed probiotics is triggered by proteome alterations (especially the glycolytic proteins), and provides a new insight into the mechanism by which probiotics improve poultry production.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1167) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-1167
PMCID: PMC4325948  PMID: 25532559
Broiler chicken (Gallus gallus); Enterococcus faecium; Carcass; Meat quality; Pectoral muscle proteome; Probiotics
6.  microRNA-148a inhibits hepatocellular carcinoma cell invasion by targeting sphingosine-1-phosphate receptor 1 
microRNA (miR)-148a has been shown to act as an important suppressor in numerous human malignancies and is markedly downregulated in hepatocellular carcinoma; however, the role of miR-148a in the regulation of hepatocellular carcinoma cell invasion, as well as the underlying mechanism, has never been studied. In the present study, the expression level of miR-148a was found to be significantly decreased in hepatocellular carcinoma tissues and HepG2 cells when compared with that in the normal adjacent tissues. Furthermore, a novel target of miR-148a was found, sphingosine-1-phosphate receptor 1 (S1PR1), whose expression was negatively regulated by miR-148a at a post-transcriptional level in hepatocellular carcinoma HepG2 cells. Upregulation of miR-148a by transfection with miR-148a mimics notably suppressed HepG2 cell invasion, similar to the effect of the SIPR1 downregulation induced by SIPR1-specific small interfering RNA, while the restoration of S1PR1 expression reversed the inhibitory effect of miR-148a upregulation on HepG2 cell invasion. Accordingly, the current study suggests that miR-148a plays an inhibitory role in the regulation of hepatocellular carcinoma cell invasion by directly targeting S1PR1.
doi:10.3892/etm.2014.2137
PMCID: PMC4280928  PMID: 25574238
hepatocellular carcinoma; microRNA-148a; sphingosine-1-phosphate receptor 1; invasion
7.  Prognostic significance of minichromosome maintenance proteins in breast cancer 
A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients.
PMCID: PMC4300722  PMID: 25628920
Minichromosome maintenance complex; breast cancer; survival; prognosis
8.  Concerns of and coping strategies by parents of pediatric liver transplant recipients: a qualitative study from China 
Parents of liver transplant recipient children have to face complicated health issues of their children. Coping strategies of parents as major care providers not only impacts on their handling of stresses on themselves but also on the recipients’ quality of life. In this study, we sought to investigate the coping strategies of parents of Chinese pediatric liver transplant recipients at a single tertiary care institution in China. Twenty-five parents of liver transplant recipients were selected by the purposive sampling method and data was collected using qualitative semi-structured interview. Interviews were conducted until thematic saturation was achieved. We extracted 5 major themes: 1) guilt and self-blame for not giving a happy life to the sick child; 2) seeking social support for helping to treat the sick child; 3) standing firm by not giving up on treating the sick child; 4) cautious caretaking; 5) compromise: a helpless acceptance of truth. In summary, parents of transplant recipients present 5 major coping strategies. Proper assessment of stresses on parents of liver transplant recipient children and their coping strategies may help the medical staff and social services to provide more targeted support, and help and promote the balance of the family function.
PMCID: PMC4307545  PMID: 25664098
Liver transplant; children; parents; coping; qualitative study
9.  Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation 
BMC Molecular Biology  2014;15(1):27.
Background
Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure.
Results
Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope.
Conclusions
Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.
doi:10.1186/s12867-014-0027-z
PMCID: PMC4266902  PMID: 25495845
Progeria; Nuclear envelope; Aging
10.  Detection of JAK2 V617F mutation increases the diagnosis of myeloproliferative neoplasms 
Oncology Letters  2014;9(2):735-738.
The Janus kinase (JAK)2 gene, which is located on chromosome 9p24, is involved in the signaling transduction pathways of the hematopoietic and immune system. Mutations in the JAK2 gene have served as disease markers for myeloproliferative neoplasms (MPNs). The aim of the present study was to investigate the occurrence of the JAK2 gene mutation in 140 clinical samples, and to evaluate its clinical significance in MPNs and other hematological diseases. Genomic DNA was extracted from the peripheral blood leukocytes or bone marrow karyocytes of 140 clinical samples, which included 130 patients with various types of hematological disease and 10 control patients. In addition, exons 12 and 14 of the JAK2 gene were analyzed by direct sequencing and the mutation rates of various MPN subtypes were evaluated. Of the 140 samples, exons 12 and 14 were tested in 74 samples, however, exon 14 only was tested in 66 samples. No mutations were identified in exon 12. The V617F mutation rate in polycythemia vera was 82.1% (23/28), and the mutation rates in essential thrombocythemia histiocytosis, primary myelofibrosis and other MPNs were 53.1% (17/32), 40.0% (4/10) and 60.0% (6/10), respectively. Therefore, the total mutation rate of the JAK2 gene in MPN was 62.5% (50/80). For non-MPN hematological diseases, four V617F mutations were detected in samples of leukocytosis of unknown origin (4/12), however, no JAK2 V617F mutations were identified in the 10 controls. Therefore, JAK2 V617F mutations may present a novel marker for diagnosis of MPNs. Furthermore, the direct sequencing method appeared to be satisfactory for the clinical gene testing of hematological samples.
doi:10.3892/ol.2014.2801
PMCID: PMC4301535  PMID: 25624900
Janus kinase 2 gene; V617F; gene test; direct sequencing; myeloproliferative neoplasms
11.  Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1α pathway in human ovarian cancer in vitro 
Background
Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Numerous evidences demonstrate that cancer cells undergo metabolic abnormality during tumorigenesis in tumor microenvironment and further facilitate tumor progression. Succinate dehydrogenase (SDH or Complex II) is one of the important enzymes in the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been recognized as a tumor suppressor. However the role of SDHB in ovarian cancer is still unclear.
Methods
Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer was investigated in vitro, using proliferation, migration and invasion assays. To explore the mechanism, proliferation and migration related proteins such as Bcl-2, cleaved caspase 3, p-ERK, MMP-2, and p-FAK were examined by western blot. P-P38, p-AMPKα, and HIF-1α were also examined by western blot. CoCl2 was used to induce HIF-1α expression in SKOV3 and A2780 cells.
Results
SDHB silencing promoted cell proliferation, invasion, and migration, but inhibited apoptosis of SKOV3 and A2780 cells. In contrast, overexpression of SDHB inhibited cell proliferation, invasion, migration, and promoted apoptosis in SKOV3 cells. It was observed that up-regulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK, and p-FAK, inhibition of cleaved caspase 3 in SDHB-silenced cells. Meanwhile, decreased Bcl-2 and MMP-2, inhibition of p-P38, p-ERK, and p-FAK, activation of cleaved caspase 3 were shown in SDHB-overexpressed SKOV3 cells. HIF-1α, an essential factor in tumor progression, was up-regulated in SDHB-silenced cells with the activation of p-AMPKα and down-regulated in SDHB-overexpressed cancer cells with the decreased p-AMPKα. And SDHB was proved to be decreased due to upregulation of HIF-1α expression in CoCl2-treated cancer cells.
Conclusions
Our results firstly revealed that SDHB played a key role in cell proliferation, invasion, migration, and apoptosis of human ovarian carcinoma via AMPK-HIF-1α pathway. SDHB-overexpression might be a new approach to inhibit tumor progression in human ovarian carcinoma.
Electronic supplementary material
The online version of this article (doi:10.1186/s13048-014-0115-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s13048-014-0115-1
PMCID: PMC4279696  PMID: 25491408
Succinate dehydrogenase subunit B; HIF-1α; AMPK; Gene silence; Gene overexpression; Ovarian carcinoma
12.  Identification and Characterization of Non-Tuberculous Mycobacteria Isolated from Tuberculosis Suspects in Southern-Central China 
PLoS ONE  2014;9(12):e114353.
The incidence of non-tuberculous mycobacteria (NTM)-related death has increased globally recently. To obtain information of the species and characterization of pathogens involved in NTM pulmonary infection in Southern-central China, we identified 160 non-tuberculous infection cases from 3995 acid-fast bacilli (AFB)-positive tuberculous suspects. We then randomly selected 101 non-tuberculous patients, isolated bacteria from their sputa and genotyped the pathogens using the 16S rRNA gene and 16S-23S rRNA internal transcribed spacer sequences. M. intracellulare (32.67%, 33/101), M. abscessus (32.67%, 33/101) and M. fortuitum (7.92%, 8/101) are identified in these isolates. Surprisingly, non-mycobacteria including Gordonia (8.91%, 9/101), Nocardia (5.94%, 6/101) and Tsukamurella (0.99%, 1/101) are also discovered, and the case of Tsukamurella pulmonis infection is first discovered in Southern-central China. Moreover, species of M. mucogenicum group, M. chubuense, M. kansasii, M. gastri, M. avium, M. porcinum and M. smegmatis are identified. In addition, nine immune compromised cases (8.91%, 9/101), including type two diabetes mellitus and HIV/AIDS are found to be infected with non-tuberculous bacteria. This study revealed the distribution and characteristics of non-tuberculous AFB pathogen infection occurred in Southern-central China, and suggested that physicians should be alert of the emerging of NTM and non-mycobacteria infection in AFB positive cases and take caution when choosing chemotherapy for tuberculosis-like pulmonary infections. Generally, this study may help with the development of new strategy for the diagnosis and treatment of mycobacterial infection.
doi:10.1371/journal.pone.0114353
PMCID: PMC4252139  PMID: 25463697
14.  Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues 
Oncotarget  2014;5(23):12398-12409.
Lysosomal associated membrane protein 3 (LAMP3) is a newly identified tumor-specific protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical and breast cancers. However, little is known of LAMP3 protein expression in gastrointestinal cancer and its prognostic value. We determined protein expression of LAMP3 and TP53 in both gastric (n=750) and colorectal (n=479) tissues by immunohistochemistry analysis on tissue microarray (TMA), their expression was correlated with patients' clinical parameters. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. In both gastric and colorectal cancers, high LAMP3 protein expression (LAMP3+) was significantly associated with tumor stage (P=0.014 and P<0.001). No correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 expression but not high TP53 expression had a poor overall survival (for gastric cancer P<0.001, CI: 1.762-4.567; for colorectal cancer P=0.036, CI: 1.062-5.980). Our data suggest that epithelial LAMP3 expression is an independent prognostic marker for gastrointestinal cancer.
PMCID: PMC4322976  PMID: 25362357
LAMP3; TP53; Prognosis; Gastrointestinal cancer
15.  MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer 
Oncotarget  2014;5(23):12291-12303.
Metastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial–mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC.
PMCID: PMC4323008  PMID: 25460499
ovarian cancer; miR-373; Rab22a; invasion; metastasis
16.  Chronic vagus nerve stimulation improves left ventricular function in a canine model of chronic mitral regurgitation 
Background
Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). We hypothesized that chronic vagus nerve stimulation (VNS) could prevent left ventricular (LV) remodeling and dysfunction in a canine HF model induced by chronic mitral regurgitation (MR).
Methods and results
After the MR inducing procedure, 12 survived canines were randomly divided into the control (n = 6) and the VNS (n = 6) groups. At month 2, a VNS stimulator system was implanted in all canines. From month 3 to month 6, VNS therapy was applied in the VNS group but not in the control group. At month 6, compared with the control group, the canines in VNS group had significantly higher cardiac output (2.3 ± 0.3 versus 2.9 ± 0.4 L/min, P < 0.05, LV forward stroke volume (20.1 ± 3.7 versus 24.8 ± 3.9 ml, P < 0.05), and end-systolic stiffness constant (2.2 ± 0.3 versus 2.7 ± 0.3, P < 0.05). NT-proBNP and C-reactive protein were decreased significantly in the VNS group. However, no statistical difference was found in LV ejection fraction, LV end-diastolic dimension, LV end-diastolic volume, myocyte cross-sectional area, or collagen volume fraction between two groups.
Conclusions
Chronic VNS therapy may ameliorate MR-induced LV contractile dysfunction and improve the expression of biomarkers, but has less effect in improving LV chamber remodeling.
doi:10.1186/s12967-014-0302-2
PMCID: PMC4228179  PMID: 25366939
Autonomic nervous system; Vagus nerve stimulation; Mitral valve insufficiency; Heart failure
17.  Interferon regulatory factor 9 is critical for neointima formation following vascular injury 
Nature Communications  2014;5:5160.
Interferon regulatory factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized ‘IRF9–SIRT1 axis’ in vasculoproliferative pathology modulation.
Blood vessels respond to injury by thickening the supportive smooth muscle layer in a process known as neointima formation. Here the authors describe a novel regulatory pathway of neointima formation that involves a transcription factor, Interferon Regulating Factor 9, and its downstream target, the deacetylase SIRT1.
doi:10.1038/ncomms6160
PMCID: PMC4218966  PMID: 25319116
18.  Genetic Diversity Analysis Reveals that Geographical Environment Plays a More Important Role than Rice Cultivar in Villosiclava virens Population Selection 
Rice false smut caused by Villosiclava virens is an economically important disease of grains worldwide. The genetic diversity of 153 isolates from six fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY), Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were phylogenetically analyzed to evaluate the influence of environments and rice cultivars on the V. virens populations. Isolates (43) from Wuhan were from two rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with different genetic backgrounds. Genetic diversity of isolates was analyzed using random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms (SNP). The isolates from the same cultivars in Wuhan tended to group together, indicating that the cultivars had an important impact on the fungal population. The 110 isolates from individual fields tended to cluster according to geographical origin. The values of Nei's gene diversity (H) and Shannon's information index (I) showed that the genetic diversity among isolates was higher between than within geographical populations. Furthermore, mean genetic distance between groups (0.006) was higher than mean genetic distance within groups (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST) values also showed significant genetic differentiation between most populations. Higher genetic similarity of isolates from individual fields but different rice cultivars suggested that the geographical factor played a more important role in the selection of V. virens isolates than rice cultivars. This information could be used to improve the management strategy for rice false smut by adjusting the cultivation measures, such as controlling fertilizer, water, and planting density, in the rice field to change the microenvironment.
doi:10.1128/AEM.03936-13
PMCID: PMC3993286  PMID: 24584249
19.  Comparative Transcriptome Analysis of a Toxin-Producing Dinoflagellate Alexandrium catenella and Its Non-Toxic Mutant 
Marine Drugs  2014;12(11):5698-5718.
The dinoflagellates and cyanobacteria are two major kingdoms of life producing paralytic shellfish toxins (PSTs), a large group of neurotoxic alkaloids causing paralytic shellfish poisonings around the world. In contrast to the well elucidated PST biosynthetic genes in cyanobacteria, little is known about the dinoflagellates. This study compared transcriptome profiles of a toxin-producing dinoflagellate, Alexandrium catenella (ACHK-T), and its non-toxic mutant form (ACHK-NT) using RNA-seq. All clean reads were assembled de novo into a total of 113,674 unigenes, and 66,812 unigenes were annotated in the known databases. Out of them, 35 genes were found to express differentially between the two strains. The up-regulated genes in ACHK-NT were involved in photosynthesis, carbon fixation and amino acid metabolism processes, indicating that more carbon and energy were utilized for cell growth. Among the down-regulated genes, expression of a unigene assigned to the long isoform of sxtA, the initiator of toxin biosynthesis in cyanobacteria, was significantly depressed, suggesting that this long transcript of sxtA might be directly involved in toxin biosynthesis and its depression resulted in the loss of the ability to synthesize PSTs in ACHK-NT. In addition, 101 putative homologs of 12 cyanobacterial sxt genes were identified, and the sxtO and sxtZ genes were identified in dinoflagellates for the first time. The findings of this study should shed light on the biosynthesis of PSTs in the dinoflagellates.
doi:10.3390/md12115698
PMCID: PMC4245552  PMID: 25421324
marine dinoflagellates; Alexandrium catenella; paralytic shellfish toxins; mutant; toxin biosynthesis; transcriptome; RNA-seq
20.  Long Non-Coding RNAs: Critical Players in Hepatocellular Carcinoma 
Hepatocellular carcinoma (HCC) is a complex disease with multiple underlying pathogenic mechanisms caused by a variety of etiologic factors. Emerging evidence showed that long non-coding RNAs (lncRNAs), with size larger than 200 nucleotides (nt), play important roles in various types of cancer development and progression. In recent years, some dysregulated lncRNAs in HCC have been revealed and roles for several of them in HCC have been characterized. All these findings point to the potential of lncRNAs as prospective novel therapeutic targets in HCC. In this review, we summarize known dysregulated lncRNAs in HCC, and review potential biological roles and underlying molecular mechanisms of lncRNAs in HCC. Additionally, we discussed prospects of lncRNAs as potential biomarker and therapeutic target for HCC. In conclusion, this paper will help us gain better understanding of molecular mechanisms by which lncRNAs perform their function in HCC and also provide general strategies and directions for future research.
doi:10.3390/ijms151120434
PMCID: PMC4264176  PMID: 25387074
long noncoding RNA; hepatocellular carcinoma; dysregulation; biological roles; molecular mechanism
21.  Clinical diagnostic utility of CA 15-3 for the diagnosis of malignant pleural effusion: A meta-analysis 
Malignant pleural effusion (MPE) is one of the most common pleura-associated conditions observed in clinical practice. The development of MPE usually defines advanced cancer with a poor prognosis. Carbohydrate antigen 15-3 (CA 15-3), as an effective pleural fluid biomarker, has been an object of ongoing research in the detection of MPE. The aim of this meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural CA 15-3 for diagnosing MPE. The databases Medline (using PubMed as the search engine), Embase, Ovid, Web of Science and Cochrane database (up to December 2013) were searched to identify relevant studies. No lower date limit was applied. All literature published in English was reviewed. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio (DOR) were pooled using a random-effect model. Summary receiver operating characteristic (SROC) curve analysis was conducted to evaluate the overall diagnostic value. The methodological quality was assessed in line with the Quality Assessment for Studies of Diagnostic Accuracy statement. Twenty-one studies with a total of 2,861 cases were included in present meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and DOR of CA 15-3 in the diagnosis of MPE were 0.58 [95% confidence interval (CI), 0.56–0.61], 0.91 (95% CI, 0.90–0.93), 8.93 (95% CI, 4.45–17.93), 0.46 (95% CI, 0.37–0.56) and 24.89 (95% CI, 10.39–59.63), respectively. In addition, the area under the curve (AUC) was 0.84. In conclusion, due to the significantly high specificity of pleural CA 15-3 in detecting MPE, it may play a pivotal role in screening to identify patients who may benefit from further invasive pathologic examination, particularly in those presenting clinical manifestations of MPE but with negative cytological findings of the pleural fluid. However, ruling out MPE by testing CA15-3 alone is not recommended due to its limited sensitivity, and it is recommended that the results of CA15-3 assays are interpreted in parallel with conventional test results and other clinical findings.
doi:10.3892/etm.2014.2039
PMCID: PMC4247302  PMID: 25452808
CA 15-3; malignant pleural effusion; diagnosis; meta-analysis
22.  Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives 
OncoTargets and therapy  2014;7:1901-1909.
Gene therapy has promised to be a highly effective antitumor treatment by introducing a tumor suppressor gene or the abrogation of an oncogene. Among the potential therapeutic transgenes, the tumor suppressor gene p53 serves as an attractive target. Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary deoxyribonucleic acid copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). Preclinical in vitro and in vivo studies have shown that Adp53 triggers a dramatic tumor regression response in various cancers. These viruses are engineered to lack certain early proteins and are thus replication defective, including Gendicine, SCH-58500, and Advexin. Several types of tumor-specific p53-expressing conditionally replicating adenovirus vectors (known as replication-competent CRAdp53 vectors) have been developed, such as ONYX 015, AdDelta24-p53, SG600-p53, OBP-702, and H101. Various clinical trials have been conducted to investigate the safety and efficiency of these adenoviral vectors. In this review we will talk about the biological mechanisms, clinical utility, and therapeutic potentials of the replication-deficient Adp53-based and replication-competent CRAdp53-based gene therapy.
doi:10.2147/OTT.S50483
PMCID: PMC4211860  PMID: 25364261
adenovirus; Adp53; CRAdp53
23.  Application of Nano-Carbon in Lymph Node Dissection for Thyroid Cancer and Protection of Parathyroid Glands 
Background
The aim of this study was to explore a new method to identify and protect parathyroid glands in neck lymph node dissection for patients with thyroid cancer.
Material/Methods
One hundred patients with thyroid cancer underwent total thyroidectomy combined with central neck lymph node dissection. During the operation, 50 patients receiving nano-carbon suspension were included in the experiment group, and 50 patients without nano-carbon suspension were included in the control group. We compared changes in parathyroid hormone levels before surgery and at 48 h after surgery between the 2 groups and of serum Ca2+ level within 48 h after surgery, as well as postoperative parathyroid pathological and lymph node dissection results.
Results
Eight and 1 parathyroid glands were detected pathologically in the control and experimental group, respectively. Decrease in parathyroid hormone level at 48 h occurred in 7 patients in the control group and 1 patient in the experimental group. Hypocalcemia was found at 48 h after surgery in 10 patients in the control group and 2 patients in the experimental group.
Conclusions
Nano-carbon suspension can cause development of the thyroid gland and the central lymph node and a negative development of parathyroid glands. Careful identification and removal of black-stained lymphatic tissues in the process of total thyroidectomy with neck lymph node dissection can ensure a complete lymph node dissection and prevent parathyroid damage, thus effectively reducing the incidence of hypoparathyroidism.
doi:10.12659/MSM.890721
PMCID: PMC4207291  PMID: 25311844
Lymph Node Excision; Nanotubes, Carbon; Parathyroid Glands; Thyroid Neoplasms
24.  Prognostic Value of Rab27B Nuclear Expression in Gastrointestinal Stromal Tumors 
Disease Markers  2014;2014:942181.
Rab proteins of the endocytosis and exocytosis pathways both play critical roles in cancer progression, and Rab27B has a significant relationship with several types of human cancer. However, the association between Rab27B expression and clinical features to determine its clinicopathological significance in gastrointestinal tumor (GIST) has not been investigated. To examine the expression of Rab27B in GIST and investigate the association between its expression and patient prognosis, immunohistochemistry analysis with tissue microarray was used to evaluate expression of Rab27B in 162 patients with GIST. The relationship between Rab27B expression and patient prognosis was analyzed. High nuclear staining of Rab27B was detected in 88 of 162 (54.32%) GIST tissues. Positive staining of Rab27B was significantly associated with tumor size (P = 0.006), mitotic index (P = 0.013), Armed Forces Institute of Pathology Miettinen risk classification (P = 0.002), and tumor grade (P = 0.021). Kaplan-Meier survival curves showed that GIST patients with low Rab27B nuclear expression (P = 0.038) and mitotic index <5 per 50 high-power fields (P = 0.029) had a more favorable prognosis. These findings indicate that Rab27B nuclear expression is correlated with several clinicopathological features of GIST patients, and it may serve as an unfavorable prognostic marker.
doi:10.1155/2014/942181
PMCID: PMC4213986  PMID: 25382899
25.  Cutaneous metastasis from pancreatic cancer: A case report and systematic review of the literature 
Oncology Letters  2014;8(6):2654-2660.
Cutaneous metastasis from pancreatic cancer is uncommon, therefore, the outcome of this progression has rarely been investigated. The aim of the present report was to evaluate the clinical characteristics of patients exhibiting cutaneous metastasis from pancreatic cancer. Thus, the current report presents a rare case of cutaneous metastatic disease from pancreatic cancer and describes a systematic review of the literature. A total of 54 articles comprising 63 cases were included for analysis. The relevant clinical and pathological characteristics, as well as the treatment strategies and survival outcomes of this rare disease presentation were reviewed. The average patient was was aged 63.9 years and males constituted a marginally greater proportion of the cohort (61.9%). The predominant manifestation of the cutaneous metastasis was a nodule or mass (73%) and the most common site of the skin lesion was non-umbilicus rather than umbilicus. The majority (66.7%) of the skin lesions were singular, particularly in patients exhibiting Sister Mary Joseph’s nodule (90%). A wide range of histological subtypes presented, with a predominance of adenocarcinoma (84.1%). Of the cases that specified the tumor differentiation grade, 78.2% were moderately or poorly differentiated. Immunohistochemistry revealed that cytokeratin (CK)20-negative, and CK7-, CK19- and carbohydrate antigen (CA)19-9-positive were specific diagnostic markers for pancreatic cancer. Distal metastases, excluding the skin, were observed in 68.3% of patients and the median survival period was 5 months. Treatment strategies including surgery, radiation, chemotherapy or a combination improved survival time from 3.0 to 8.3 months. Cutaneous metastasis from pancreatic cancer is a rare finding, often providing the only external indication of an internal malignancy and, therefore, should be considered in the differential diagnosis of skin lesions. Metastasis to the skin indicates a widespread, general dissemination and a poor prognosis. A combination of surgery, radiotherapy and chemotherapy appears to result in improved survival rates.
doi:10.3892/ol.2014.2610
PMCID: PMC4214468  PMID: 25364444
pancreatic cancer; cutaneous metastasis

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