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1.  Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis 
Disease markers  2013;34(6):379-386.
BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas.
METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed.
RESULTS: A total of 16 studies dealing with various carcinomas were included for this meta-analysis. For overall survival, higher miR-155 expression could significantly predict worse outcome with the pooled HR of 2.057 (95% CI: 1.392–3.039). For relapse or progress-free survival, elevated miR-155 was also a significant predictor, with a combined HR of 1.918 (95% CI: 1.311–2.806,). In addition, subgroup analysis showed that higher expression of miR-155 had the trends to predict worse outcome in lung cancer. However, the HRs did not reach the statistical significance.
CONCLUSION: Our findings suggest that miR-155 detection has a prognostic value in cancer patients. Regularly measuring miR-155 expression may be useful in clinical practice.
doi:10.3233/DMA-130984
PMCID: PMC3810250  PMID: 23481631
miR-155; cancer; prognosis; clinical
2.  The Epithelial–Mesenchymal Transition Promotes Transdifferentiation of Subcutaneously Implanted Hepatic Oval Cells Into Mesenchymal Tumor Tissue 
Stem Cells and Development  2009;18(9):1293-1298.
Hepatic oval cells are thought to represent facultative hepatic epithelial stem cells in liver in which damage inhibits hepatocyte proliferation and liver regeneration. The LE/6 hepatic stem cell line was derived from the liver of male Sprague-Dawley rats fed a choline-deficient diet containing 0.1% ethionine. They are histochemically characterized by their expression of hepatocytic (hepPar1), cholangiocytic cytokeratin (CK19), hepatic progenitor cell (OV-6), and hematopoietic stem cell (c-kit) markers. In this study, we transplanted LE/6 cells by subcutaneous injection into adult female nude mice, and examined their engraftment and differentiation potential in the subcutaneous microenvironment in vivo. Our results demonstrated that following subcutaneous transplantation, differentiation of LE/6 cells into mesenchymal tumor tissue (MTT) was associated with reduced E-cadherin expression, upregulation of E-cadherin repressor molecules (Snail proteins), and increased expression of vimentin and N-cadherin, all of these events are characteristic of the epithelial–mesenchymal transition (EMT).
doi:10.1089/scd.2008.0321
PMCID: PMC3156617  PMID: 19226223
3.  Major complications after radiofrequency ablation for liver tumors: Analysis of 255 patients 
AIM: To investigate the major complications after radiofrequency ablation (RFA) for the treatment of liver tumors and analyze possible risk factors that precipitate these complications.
METHODS: From March 2001 to April 2008, 255 patients with liver tumors (205 male, 50 female; age range, 18-89 years; mean age, 56.0 years) who received RFA were enrolled in this study. Of these patients, 212 had hepatocellular carcinoma, 39 had metastatic liver tumors and four had cholangiocellular carcinoma. One hundred and forty eight patients had a single tumor, and 107 had multiple tumors. Maximum diameter of the tumors ranged 1.3-20 cm (mean, 5.1 cm). All patients were treated with a cooled-tip perfusion electrode attached to a radiofrequency generator (Radionics, Burlington, MA, USA). RFA was performed via the percutaneous approach (n = 257), laparoscopy (n = 7), or open surgical treatment (n = 86). The major complications related to RFA were recorded. The resultant data were analyzed to determine risk factors associated these complications.
RESULTS: Among the 255 patients, 425 liver tumors were treated and 350 RFA sessions were performed. Thirty-seven (10%) major complications were observed which included 13 cases of liver failure, 10 cases of hydrothorax requiring drainage, three cases of tumor seeding, one case of upper gastrointestinal bleeding, one case of intrahepatic abscess, one case of bile duct injury, one case of cardiac arrest, and five cases of hyperglycemia. Seven patients had more than two complications. Liver failure was the most severe complication and was associated with the highest mortality. Eleven patients died due to worsening liver decompensation. Child-Pugh classification (P = 0.001) and choice of approach (P = 0.045) were related to post-treatment liver failure, whereas patient age, tumor size and number were not significant factors precipitating this complication.
CONCLUSION: RFA can be accepted as a relatively safe procedure for the treatment of liver tumors. However, attention should be paid to possible complications even though the incidences of these complications are rare. Careful patient selection and the best approach choice (percutaneous, laparoscopy, or laparotomy) will help to minimize the incidence and morbidity rate of complications which occur after RFA.
doi:10.3748/wjg.15.2651
PMCID: PMC2691498  PMID: 19496197
Complication; Hepatocellular carcinoma; Metastatic liver tumor; Radiofrequency ablation; Liver failure
4.  Validation of a Novel Clinical Prediction Score for Severe Coronary Artery Diseases before Elective Coronary Angiography 
PLoS ONE  2014;9(4):e94493.
Objectives
Coronary artery disease (CAD) severity is associated with patient prognosis. However, few efficient scoring systems have been developed to screen severe CAD in patients with stable angina and suspected CAD before coronary angiography. Here, we present a novel scoring system for CAD severity before elective coronary angiography.
Methods
Five hundred fifty-one patients with stable angina who were admitted for coronary angiography were enrolled in this study. Patients were divided into training (n = 347) and validation (n = 204) cohorts. Severe CAD was defined as having a Gensini score of 20 or more. All patients underwent echocardiography (ECG) to detect ejection fraction and aortic valve calcification (AVC). Multivariable analysis was applied to determine independent risk factors and develop the scoring system.
Results
In the training cohort, age, male sex, AVC, abnormal ECG, diabetes, hyperlipidemia, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were identified as independent factors for severe CAD by multivariable analysis, and the Severe Prediction Scoring (SPS) system was developed. C-indices of receiver operating characteristic (ROC) curves for severe CAD were 0.744 and 0.710 in the training and validation groups, respectively. The SPS system also performed well during calibration, as demonstrated by Hosmer-Lemeshow analysis in the validation group. Compared with the Diamond-Forrester score, the SPS system performed better for severe CAD prediction before elective coronary angiography.
Conclusions
Severe CAD prediction was achieved by analyzing age, sex, AVC, ECG, diabetes status, and lipid levels. Angina patients who achieve high scores using this predicting system should undergo early coronary angiography.
doi:10.1371/journal.pone.0094493
PMCID: PMC3979855  PMID: 24714416
5.  Raman Spectroscopy Analysis of the Biochemical Characteristics of Molecules Associated with the Malignant Transformation of Gastric Mucosa 
PLoS ONE  2014;9(4):e93906.
Objective
The purpose of this study was to comparatively analyze the signature Raman spectra of genomic DNA, nuclei, and tissue of normal gastric mucosa and gastric cancer and to investigate the biochemical transformation of molecules associated with gastric mucosa malignancy.
Method
Genomic DNA, nuclei, and tissue from normal gastric mucosa and gastric cancer were analyzed by Raman spectroscopy.
Results
1) The Raman spectrum of gastric cancer genomic DNA showed that two peaks appeared, one at approximately 1090 cm-1 with a higher intensity than the peak at 1050 cm-1 in the spectrum. Characteristic peaks appeared at 950 cm-1, 1010 cm-1, and 1100-1600 cm-1. 2) Using a hematoxylin and eosin (H&E)-stained section, the intensity of the characteristic peak of nucleic acids at 1085 cm-1 was increased and shifted to 1088 cm-1 in cancer cells. The relative intensity of the characteristic peaks of nucleoproteins at 755 cm-1 and 1607 cm-1 was significantly increased in cancer cells compared with normal cells. 3) Compared with normal tissues, the peak representing PO2- symmetric stretching vibration shifted from 1088 cm-1 to 1083 cm-1 in cancer tissue, and the characteristic peak for collagen at 938 cm-1 shifted to 944 cm-1. In addition, an extra characteristic peak indicating C = C stretching vibration appeared at 1379 cm-1 in the lipid spectrum in cancer tissue.
Conclusions
The position, intensity, and shape of peaks in the Raman spectra of DNA, nuclei, and tissue from gastric cancer were significantly different compared with those of normal cells. These results indicate that the DNA phosphate backbone becomes unstable in cancer cells and might be broken; the relative content of histones is increased and stable; the relative collagen content is reduced, facilitating cancer cell metastasis; and the relative content of unsaturated fatty acids is increased, increasing the mobility of the plasma membrane of cancer cells.
doi:10.1371/journal.pone.0093906
PMCID: PMC3977959  PMID: 24710050
6.  Zinc, Iron, Manganese and Copper Uptake Requirement in Response to Nitrogen Supply and the Increased Grain Yield of Summer Maize 
PLoS ONE  2014;9(4):e93895.
The relationships between grain yields and whole-plant accumulation of micronutrients such as zinc (Zn), iron (Fe), manganese (Mn) and copper (Cu) in maize (Zea mays L.) were investigated by studying their reciprocal internal efficiencies (RIEs, g of micronutrient requirement in plant dry matter per Mg of grain). Field experiments were conducted from 2008 to 2011 in North China to evaluate RIEs and shoot micronutrient accumulation dynamics during different growth stages under different yield and nitrogen (N) levels. Fe, Mn and Cu RIEs (average 64.4, 18.1and 5.3 g, respectively) were less affected by the yield and N levels. ZnRIE increased by 15% with an increased N supply but decreased from 36.3 to 18.0 g with increasing yield. The effect of cultivars on ZnRIE was similar to that of yield ranges. The substantial decrease in ZnRIE may be attributed to an increased Zn harvest index (from 41% to 60%) and decreased Zn concentrations in straw (a 56% decrease) and grain (decreased from 16.9 to 12.2 mg kg−1) rather than greater shoot Zn accumulation. Shoot Fe, Mn and Cu accumulation at maturity tended to increase but the proportions of pre-silking shoot Fe, Cu and Zn accumulation consistently decreased (from 95% to 59%, 90% to 71% and 91% to 66%, respectively). The decrease indicated the high reproductive-stage demands for Fe, Zn and Cu with the increasing yields. Optimized N supply achieved the highest yield and tended to increase grain concentrations of micronutrients compared to no or lower N supply. Excessive N supply did not result in any increases in yield or micronutrient nutrition for shoot or grain. These results indicate that optimized N management may be an economical method of improving micronutrient concentrations in maize grain with higher grain yield.
doi:10.1371/journal.pone.0093895
PMCID: PMC3976344  PMID: 24705926
7.  A note on statistical method for genotype calling of high-throughput SNP arrays 
Journal of applied statistics  2013;40(6):1372-1381.
We study the genotype calling algorithms for the high-throughput single-nucleotide polymorphism (SNP) arrays. Building upon the novel SNP-RMA preprocessing approach and the state-of-the-art CRLMM approach for genotype calling, we propose a simple modification to better model and combine the information across multiple SNPs with empirical Bayes modeling, which could often significantly improve the genotype calling of CRLMM. Through applications to the HapMap Trio data set and a non-HapMap test set of high quality SNP chips, we illustrate the competitive performance of the proposed method.
doi:10.1080/02664763.2013.785499
PMCID: PMC3647617  PMID: 23667285
SNP arrays; empirical Bayes; genotype calling algorithm; mixture model
8.  Air pollution: a smoking gun for cancer 
Chinese Journal of Cancer  2014;33(4):173-175.
Once considered a taboo topic or stigma, cancer is the number one public health enemy in the world. Once a product of an almost untouchable industry, tobacco is indisputably recognized as a major cause of cancer and a target for anticancer efforts. With the emergence of new economic powers in the world, especially in highly populated countries such as China, air pollution has rapidly emerged as a smoking gun for cancer and has become a hot topic for public health debate because of the complex political, economic, scientific, and technologic issues surrounding the air pollution problem. This editorial and the referred articles published in this special issue of the Chinese Journal of Cancer discuss these fundamental questions. Does air pollution cause a wide spectrum of cancers? Should air pollution be considered a necessary evil accompanying economic transformation in developing countries? Is an explosion of cancer incidence coming to China and how soon will it arrive? What must be done to prevent this possible human catastrophe? Finally, the approaches for air pollution control are also discussed.
doi:10.5732/cjc.014.10034
PMCID: PMC3975182  PMID: 24636233
Air pollution; cancer; public health
9.  A bird's eye view of the air pollution-cancer link in China 
Chinese Journal of Cancer  2014;33(4):176-188.
Air pollution in China comes from multiple sources, including coal consumption, construction and industrial dust, and vehicle exhaust. Coal consumption in particular directly determines the emissions of three major air pollutants: dust, sulfur dioxide (SO2), and nitrogen oxide (NOx). The rapidly increasing number of civilian vehicles is expected to bring NOx emission to a very high level. Contrary to expectations, however, existing data show that the concentrations of major pollutants [particulate matter-10 (PM10), SO2, and nitrogen dioxide (NO2)] in several large Chinese cities have declined during the past decades, though they still exceed the national standards of ambient air quality. Archived data from China does not fully support that the concentrations of pollutants directly depend on local emissions, but this is likely due to inaccurate measurement of pollutants. Analyses on the cancer registry data show that cancer burden related to air pollution is on the rise in China and will likely increase further, but there is a lack of data to accurately predict the cancer burden. Past experience from other countries has sounded alarm of the link between air pollution and cancer. The quantitative association requires dedicated research as well as establishment of needed monitoring infrastructures and cancer registries. The air pollution-cancer link is a serious public health issue that needs urgent investigation.
doi:10.5732/cjc.014.10030
PMCID: PMC3975183  PMID: 24636232
Lung cancer; air pollution; particulate matter; sulfur dioxide; nitrogen oxide
10.  Store-Independent Orai1/3 Channels Activated by Intracrine LeukotrieneC4: Role in Neointimal Hyperplasia 
Circulation research  2013;112(7):1013-1025.
Rationale
Through largely unknown mechanisms, Ca2+ signaling plays important roles in vascular smooth muscle cell (VSMC) remodeling. Orai1-encoded store-operated Ca2+ entry (SOCE) has recently emerged as an important player in VSMC remodeling. However, the role of the exclusively mammalian Orai3 protein in native VSMC Ca2+ entry pathways, its upregulation during VSMC remodeling and its contribution to neointima formation remain unknown.
Objective
The goal of this study was to determine the agonist-evoked Ca2+ entry pathway contributed by Orai3; Orai3 potential upregulation and role during neointima formation after balloon-injury of rat carotid arteries.
Methods and Results
Ca2+ imaging and patch clamp recordings showed that while the platelet-derived growth factor (PDGF) activates the canonical Ca2+ release-activated Ca2+ (CRAC) channels via store depletion in VSMC, the pathophysiological agonist thrombin activates a distinct Ca2+-selective channel contributed by Orai1, Orai3 and STIM1 in the same cells. Unexpectedly, Ca2+ store depletion is not required for activation of Orai1/3 channel by thrombin. Rather, the signal for Orai1/3 channel activation is cytosolic leukotrieneC4 produced downstream thrombin receptor stimulation through the catalytic activity of leukotrieneC4 synthase. Importantly, Orai3 is upregulated in an animal model of VSMC neointimal remodeling and in vivo Orai3 knockdown inhibits neointima formation.
Conclusions
These results demonstrate that distinct native Ca2+-selective Orai channels are activated by different agonists/pathways and uncover a mechanism whereby leukotrieneC4 acts through hitherto unknown intracrine mode to elicit store-independent Ca2+ signaling that promotes vascular occlusive disease. Orai3 and Orai3-containing channels provide novel targets for control of VSMC remodeling during vascular injury or disease.
doi:10.1161/CIRCRESAHA.111.300220
PMCID: PMC3658112  PMID: 23349245
Calcium signaling; Orai3; Orai1; STIM1; vascular smooth muscle; neointima formation; ion channel
11.  The Common Traits of the ACC and PFC in Anxiety Disorders in the DSM-5: Meta-Analysis of Voxel-Based Morphometry Studies 
PLoS ONE  2014;9(3):e93432.
Background
The core domains of social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder (PD) with and without agoraphobia (GA), and specific phobia (SP) are cognitive and physical symptoms that are related to the experience of fear and anxiety. It remains unclear whether these highly comorbid conditions that constitute the anxiety disorder subgroups of the Diagnostic and Statistical Manual for Mental Disorders – Fifth Edition (DSM-5) represent distinct disorders or alternative presentations of a single underlying pathology.
Methods
A systematic search of voxel-based morphometry (VBM) studies of SAD, GAD, PD, GA, and SP was performed with an effect-size signed differential mapping (ES-SDM) meta-analysis to estimate the clusters of significant gray matter differences between patients and controls.
Results
Twenty-four studies were eligible for inclusion in the meta-analysis. Reductions in the right anterior cingulate gyrus and the left inferior frontal gyrus gray matter volumes (GMVs) were noted in patients with anxiety disorders when potential confounders, such as comorbid major depressive disorder (MDD), age, and antidepressant use were controlled for. We also demonstrated increased GMVs in the right dorsolateral prefrontal cortex (DLPFC) in comorbid depression-anxiety (CDA), drug-naïve and adult patients. Furthermore, we identified a reduced left middle temporal gyrus and right precentral gyrus in anxiety patients without comorbid MDD.
Conclusion
Our findings indicate that a reduced volume of the right ventral anterior cingulate gyrus and left inferior frontal gyrus is common in anxiety disorders and is independent of comorbid depression, medication use, and age. This generic effect supports the notion that the four types of anxiety disorders have a clear degree of overlap that may reflect shared etiological mechanisms. The results are consistent with neuroanatomical DLPFC models of physiological responses, such as worry and fear, and the importance of the ventral anterior cingulate (ACC)/medial prefrontal cortex (mPFC) in mediating anxiety symptoms.
doi:10.1371/journal.pone.0093432
PMCID: PMC3968149  PMID: 24676455
12.  RNA-Seq-Based Analysis of Cold Shock Response in Thermoanaerobacter tengcongensis, a Bacterium Harboring a Single Cold Shock Protein Encoding Gene 
PLoS ONE  2014;9(3):e93289.
Background
Although cold shock responses and the roles of cold shock proteins in microorganisms containing multiple cold shock protein genes have been well characterized, related studies on bacteria possessing a single cold shock protein gene have not been reported. Thermoanaerobacter tengcongensis MB4, a thermophile harboring only one known cold shock protein gene (TtescpC), can survive from 50° to 80°C, but has poor natural competence under cold shock at 50°C. We therefore examined cold shock responses and their effect on natural competence in this bacterium.
Results
The transcriptomes of T. tengcongensis before and after cold shock were analyzed by RNA-seq and over 1200 differentially expressed genes were successfully identified. These genes were involved in a wide range of biological processes, including modulation of DNA replication, recombination, and repair; energy metabolism; production of cold shock protein; synthesis of branched amino acids and branched-chain fatty acids; and sporulation. RNA-seq analysis also suggested that T. tengcongensis initiates cell wall and membrane remodeling processes, flagellar assembly, and sporulation in response to low temperature. Expression profiles of TtecspC and failed attempts to produce a TtecspC knockout strain confirmed the essential role of TteCspC in the cold shock response, and also suggested a role of this protein in survival at optimum growth temperature. Repression of genes encoding ComEA and ComEC and low energy metabolism levels in cold-shocked cells are the likely basis of poor natural competence at low temperature.
Conclusion
Our study demonstrated changes in global gene expression under cold shock and identified several candidate genes related to cold shock in T. tengcongensis. At the same time, the relationship between cold shock response and poor natural competence at low temperature was preliminarily elucidated. These findings provide a foundation for future studies on genetic and molecular mechanisms associated with cold shock and acclimation at low temperature.
doi:10.1371/journal.pone.0093289
PMCID: PMC3965559  PMID: 24667527
13.  Chaihuang-Yishen Granule Inhibits Diabetic Kidney Disease in Rats through Blocking TGF-β/Smad3 Signaling 
PLoS ONE  2014;9(3):e90807.
Objective
Increasing evidence shows that TGF-β1 is a key mediator in diabetic nephropathy (DN) and induces renal fibrosis positively by Smad3 but negatively by Smad7. However, treatment of DN by blocking the TGF-β/Smad pathway remains limited. The present study investigated the anti-fibrotic effect of a traditional Chinese medicine, Chaihuang-Yishen granule (CHYS), on DN.
Research Design and Methods
Protective role of CHYS in DN was examined in an accelerated type 1 DN induced by streptozotocin in uninephrectomized Wistar rats. CHYS, at a dose of 0.56 g/kg body weight, was administered by a daily gastric gavage for 20 weeks and the therapeutic effect and potential mechanisms of CHYS on diabetic kidney injury were examined.
Results
Treatment with CHYS attenuated diabetic kidney injury by significantly inhibiting 24-h proteinuria and progressive renal fibrosis including glomerulosclerotic index, tubulointerstitial fibrosis index, and upregulation of extracellular matrix (collagen I, IV, and fibronectin), despite the same levels of blood glucose. Further studies revealed that inhibition of renal fibrosis in CHYS-treated diabetic rats was associated with inhibition of TGF-β1/Smad3 signaling as demonstrated by upregulation of Smad7 but downregulation of TGF-β1, TGF-β receptors, activation of Smad3, and expression of miRNA-21.
Conclusions
CHYS may be a therapeutic agent for DN. CHYS attenuates DN by blocking TGF-β/Smad3-mediated renal fibrosis.
doi:10.1371/journal.pone.0090807
PMCID: PMC3960111  PMID: 24646636
14.  Amphidinolide B: Total Synthesis, Structural Investigation and Biological Evaluation 
The Journal of organic chemistry  2013;78(6):2213-2247.
The total synthesis of amphidinolide B1 and the proposed structure of amphidinolide B2 has been accomplished. Key aspects of this work include the development of a practical, non-transition metal mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent anti-tumor activities with IC50 values ranging from 3.3 nM to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.
doi:10.1021/jo3026077
PMCID: PMC3631602  PMID: 23406192
15.  SOCS3 Promoter Hypermethylation Is a Favorable Prognosticator and a Novel Indicator for G-CIMP-Positive GBM Patients 
PLoS ONE  2014;9(3):e91829.
Background
Hypermethylation of the suppressor of cytokine signaling 3(SOCS3) promoter has been reported to predict a poor prognosis in several cancers including glioblstoma multiforme (GBM). We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP), when a large number of gene loci are simultaneously hypermethylated.
Methods
A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months) and 20 short-term survivors (STS; overall survival ≤ 9 months). The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status.
Results
Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA) and the Chinese Cancer Genome Atlas(CGGA). In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients.
Conclusions
Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.
doi:10.1371/journal.pone.0091829
PMCID: PMC3954800  PMID: 24633048
16.  Diterpenoids and Limonoids from the Leaves and Twigs of Swietenia mahagoni 
Three new compounds, including two diterpenoids, nemoralisins H and I (1 and 2), and a limonoid, 2-methoxy khayseneganin E (3), along with four known constituents (4–7), were isolated from the leaves and twigs of Swietenia mahagoni. Their chemical structures were elucidated by means of spectroscopic analysis. The cytotoxities of these isolated constituents were assayed.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0006-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0006-6
PMCID: PMC3956973  PMID: 24660137
Meliaceae; Swietenia mahagoni; Diterpenoids; Limonoids
17.  Identification of seven Zingiberaceous species based on comparative anatomy of microscopic characteristics of seeds 
Chinese Medicine  2014;9:10.
Background
The fruits and seeds of Alpinia galanga (L.) Willd., Alpinia katsumadai Hayata, Alpinia zerumbet (Pers.) Burtt. & Smith, Amomum kravanh Pierre ex Gagnep., Amomum subulatum Roxb., Amomum tsao-ko Crevost et Lemaire, and Elettaria cardamomum (L.) Maton from Alpinia, Amomum, and Elettaria genera in the Zingiberaceae family are difficult to distinguish between each other. This study aims to identify the seeds of these seven species from Zingiberaceae family based on comparative anatomy of microscopic characteristics.
Methods
We compared the morphological structures of seed coats by observing the microscopic characteristics of seeds in transverse sections. We described the macroscopic characteristics of seeds in detail.
Results
The seeds of these three genera could not be identified to the species level based on their macroscopic features. However, based on the anatomical features of the seed coat observed in transverse sections, a dichotomous key for these seven species was feasible.
Conclusion
Seven species in the Zingiberaceae family could be identified based on comparative anatomy of microscopic characteristics of transverse section of seed.
doi:10.1186/1749-8546-9-10
PMCID: PMC3975278  PMID: 24607026
18.  Enhancement of Antitumor Immunity Using a DNA-Based Replicon Vaccine Derived from Semliki Forest Virus 
PLoS ONE  2014;9(3):e90551.
A DNA-based replicon vaccine derived from Semliki Forest virus, PSVK-shFcG-GM/B7.1 (Fig. 1a) was designed for tumor immunotherapy as previously constructed. The expression of the fusion tumor antigen (survivin and hCGβ-CTP37) and adjuvant molecular protein (Granulocyte-Macrophage Colony-Stimulating Factor/ GM-CSF/B7.1) genes was confirmed by Immunofluorescence assay in vitro, and immunohistochemistry assay in vivo. In this paper, the immunological effect of this vaccine was determined using immunological assays as well as animal models. The results showed that this DNA vaccine induced both humoral and cellular immune responses in C57BL/6 mice after immunization, as evaluated by the ratio of CD4+/CD8+ cells and the release of IFN-γ. Furthermore, the vaccination of C57BL/6 mice with PSVK-shFcG-GM/B7.1 significantly delayed the in vivo growth of tumors in animal models (survivin+ and hCGβ+ murine melanoma, B16) when compared to vaccination with the empty vector or the other control constructs (Fig. 1b). These data indicate that this type of replicative DNA vaccine could be developed as a promising approach for tumor immunotherapy. Meanwhile, these results provide a basis for further study in vaccine pharmacodynamics and pharmacology, and lay a solid foundation for clinical application.
doi:10.1371/journal.pone.0090551
PMCID: PMC3946523  PMID: 24608380
19.  The effects of a tourniquet used in total knee arthroplasty: a meta-analysis 
Background
The purpose of this research is to evaluate the effects of a tourniquet in total knee arthroplasty (TKA).
Methods
The study was done by randomized controlled trials (RCTs) on the effects of a tourniquet in TKA. All related articles which were published up to June 2013 from Medline, Embase, and Cochrane Central Register of Controlled Trails were identified. The methodological quality of the included studies was assessed by the Physiotherapy Evidence Database (PEDro) scale. The meta-analysis was performed using Cochrane RevMan software version 5.1.
Results
Thirteen RCTs that involved a total of 689 patients with 689 knees were included in the meta-analysis, which were divided into two groups. The tourniquet group included 351 knees and the non-tourniquet group included 338 knees. The meta-analysis showed that using a tourniquet in TKA could reduce intraoperative blood loss (weighted mean difference (WMD), -198.21; 95% confidence interval (CI), -279.82 to -116.60; P < 0.01) but did not decrease the calculated blood loss (P = 0.80), which indicates the actual blood loss. Although TKA with a tourniquet could save the operation time for 4.57 min compared to TKA without a tourniquet (WMD, -4.57; 95% CI, -7.59 to -1.56; P < 0.01), it had no clinical significance. Meanwhile, the use of tourniquet could not reduce the possibility of blood transfusion (P > 0.05). Postoperative knee range of motion (ROM) in tourniquet group was 10.41° less than that in the non-tourniquet group in early stage (≤10 days after surgery) (WMD, -10.41; 95% CI, -16.41 to -4.41; P < 0.01). Moreover, the use of a tourniquet increased the risk of either thrombotic events (risk ratio (RR), 5.00; 95% CI, 1.31 to 19.10; P = 0.02) or non-thrombotic complications (RR, 2.03; 95% CI, 1.12 to 3.67; P = 0.02).
Conclusions
TKA without a tourniquet was superior to TKA with a tourniquet in thromboembolic events and the other related complications. There were no significant differences between the two groups in the actual blood loss. TKA with a tourniquet might hinder patients' early postoperative rehabilitation exercises.
doi:10.1186/1749-799X-9-13
PMCID: PMC3973857  PMID: 24602486
Tourniquet; Total knee arthroplasty; Blood loss; Complications
20.  Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions 
Epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET), play important roles in embryogenesis, stem cell biology, and cancer progression. EMT can be regulated by many signaling pathways and regulatory transcriptional networks. Furthermore, post-transcriptional regulatory networks regulate EMT; these networks include the long non-coding RNA (lncRNA) and microRNA (miRNA) families. Specifically, the miR-200 family, miR-101, miR-506, and several lncRNAs have been found to regulate EMT. Recent studies have illustrated that several lncRNAs are overexpressed in various cancers and that they can promote tumor metastasis by inducing EMT. MiRNA controls EMT by regulating EMT transcription factors or other EMT regulators, suggesting that lncRNAs and miRNA are novel therapeutic targets for the treatment of cancer. Further efforts have shown that non-coding-mediated EMT regulation is closely associated with epigenetic regulation through promoter methylation (e.g., miR-200 or miR-506) and protein regulation (e.g., SET8 via miR-502). The formation of gene fusions has also been found to promote EMT in prostate cancer. In this review, we discuss the post-transcriptional regulatory network that is involved in EMT and MET and how targeting EMT and MET may provide effective therapeutics for human disease.
doi:10.1186/1756-8722-7-19
PMCID: PMC3973872  PMID: 24598126
Long non-coding RNA (lncRNA); microRNA (miRNA); Epithelial-to-mesenchymal transition (EMT); Mesenchymal-to-epithelial transition (MET)
21.  A Topic Clustering Approach to Finding Similar Questions from Large Question and Answer Archives 
PLoS ONE  2014;9(3):e71511.
With the blooming of Web 2.0, Community Question Answering (CQA) services such as Yahoo! Answers (http://answers.yahoo.com), WikiAnswer (http://wiki.answers.com), and Baidu Zhidao (http://zhidao.baidu.com), etc., have emerged as alternatives for knowledge and information acquisition. Over time, a large number of question and answer (Q&A) pairs with high quality devoted by human intelligence have been accumulated as a comprehensive knowledge base. Unlike the search engines, which return long lists of results, searching in the CQA services can obtain the correct answers to the question queries by automatically finding similar questions that have already been answered by other users. Hence, it greatly improves the efficiency of the online information retrieval. However, given a question query, finding the similar and well-answered questions is a non-trivial task. The main challenge is the word mismatch between question query (query) and candidate question for retrieval (question). To investigate this problem, in this study, we capture the word semantic similarity between query and question by introducing the topic modeling approach. We then propose an unsupervised machine-learning approach to finding similar questions on CQA Q&A archives. The experimental results show that our proposed approach significantly outperforms the state-of-the-art methods.
doi:10.1371/journal.pone.0071511
PMCID: PMC3942313  PMID: 24595052
22.  Diffusion Tensor Imaging Studies on Chinese Patients with Social Anxiety Disorder 
BioMed Research International  2014;2014:860658.
The aim of this study was to explore white-matter disruption in social anxiety disorder (SAD) patients by using diffusion tensor imaging (DTI) and to investigate the relationship between cerebral abnormalities and the severity of the symptoms. Eighteen SAD patients and age- and gender-matched healthy controls were recruited. DTI scans were performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC) for each subject. We used voxel-based analysis to determine the differences of FA and ADC values between the two groups with two-sample t-tests. The SAD patient showed significantly decreased FA values in the white matter of the left insula, left inferior frontal gyrus, left middle temporal gyrus, and left inferior parietal gyrus and increased ADC values in the left insula, bilateral inferior frontal gyrus, bilateral middle temporal gyrus, and left inferior parietal gyrus. In SAD patients, we observed a significant negative correlation between FA values in the left insula and the total LSAS scores and a positive correlation between the ADC values in the left inferior frontal gyrus and the total LSAS scores. Above results suggested that white-matter microstructural changes might contribute to the neuropathology of SAD.
doi:10.1155/2014/860658
PMCID: PMC3958773  PMID: 24724105
23.  Clinical Characteristics and Surgical Prognosis of Hepatocellular Carcinoma with Bile Duct Invasion 
Objectives. Bile duct invasion (BDI) is a rare event in hepatocellular carcinoma (HCC). The present study aimed at investigating clinical characteristics and surgical outcome of HCC patients with bile duct invasion. Methods. 413 patients with HCC undergoing curative surgery were divided into two groups with (B+) and without BDI (B−). BDI was further classified as central type (B1) and peripheral type (B2). Survival was compared, and risk factors affecting prognosis were identified. Results. 35 (8.5%) patients were diagnosed BDI. Total bilirubin was significantly higher in B+ group than in B− group (P < 0.001). Multiple lesions and large nodules (>5 cm) were predominantly identified in B+ group (P < 0.01, resp.). Portal vein invasion was more frequently observed in B+ than in B− group (P = 0.003). Univariate and multivariate analyses identified central BDI as a significant factor affecting prognosis of HCC patients (risk 1.3, 95% CI 1.1–2.2, P = 0.015). The gross overall survival of patients in B+ was significantly worse than in B− (P = 0.001), which, however, was not different between B2 and B− (P > 0.05). Conclusions. Central but not peripheral BDI was associated with poorer prognosis of HCC patients. Curative surgical resection of tumors and invaded bile duct supplies the only hope for long-term survival of patients.
doi:10.1155/2014/604971
PMCID: PMC3958710  PMID: 24723944
24.  Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion 
Background
Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery.
Objective
To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model.
Methods
A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3–L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed.
Results
Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05).
Conclusions
The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.
doi:10.1179/2045772312Y.0000000028
PMCID: PMC3595963  PMID: 23809530
Curcumin; Spinal cord; Ischemia/reperfusion injury; Rabbits; Paraplegia; Aneurysm; Abdominal; Aortic; Neuroprotection
25.  Oncogenic Activity of Retinoic Acid Receptor γ Is Exhibited through Activation of the Akt/NF-κB and Wnt/β-Catenin Pathways in Cholangiocarcinoma 
Molecular and Cellular Biology  2013;33(17):3416-3425.
Aberrant expression and function of retinoic acid receptor γ (RARγ) are often involved in the progression of several cancers. However, the role of RARγ in cholangiocarcinoma (CCA), chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In the present study, we found that RARγ was frequently overexpressed in human CCA specimens. Its overexpression was associated with poor differentiation, lymph node metastasis, high serum carbohydrate antigen 19-9 level, and poor prognosis of CCA. Downregulation of RARγ reduced CCA cell proliferation, migration, invasion, and colony formation ability in vitro and tumorigenic potential in nude mice. RARγ knockdown resulted in upregulation of cell cycle inhibitor P21, as well as downregulation of cyclin D1, proliferating cell nuclear antigen, and matrix metallopeptidase 9, in parallel with suppression of the Akt/NF-κB pathway. Furthermore, overexpression of RARγ contributed to the multidrug chemoresistance of CCA cells, at least in part due to upregulation of P glycoprotein via activation of the Wnt/β-catenin pathway. Molecular mechanism studies revealed that RARγ interacted with β-catenin and led to β-catenin nuclear translocation. Taken together, our results suggested that RARγ plays an important role in the proliferation, metastasis, and chemoresistance of CCA through simultaneous activation of the Akt/NF-κB and Wnt/β-catenin pathways, serving as a potential molecular target for CCA treatment.
doi:10.1128/MCB.00384-13
PMCID: PMC3753848  PMID: 23798555

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