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1.  Self-Rated Health Status and Subjective Health Complaints Associated with Health-Promoting Lifestyles among Urban Chinese Women: A Cross-Sectional Study 
PLoS ONE  2015;10(2):e0117940.
This study aimed to investigate whether self-rated health status (SRH) and subjective health complaints (SHC) of urban Chinese women are associated with their health-promoting lifestyles (HPL).
We conducted a cross-sectional study on 8142 eligible Chinese participants between 2012 and 2013. Demographic and SHC data were collected. Each subject completed the SRH questionnaire and the Chinese version of the Health-Promoting Lifestyle Profile-II (HPLP-II). Correlation and binary regression analyses were performed to examine the associations of SRH and SHC with HPL.
Both SRH and HPL of urban Chinese women were moderate. The most common complaints were fatigue (1972, 24.2%), eye discomfort (1571, 19.3%), and insomnia (1542, 18.9%). Teachers, highly educated subjects and elderly women had lower SRH scores, while college students and married women had better HPL. All items of HPLP-II were positively correlated with SRH (r = 0.127-0.533, P = 0.000) and negatively correlated with SHC to a significant extent (odds ratio [OR] = 1.40-11.37).
Aspects of HPL, particularly stress management and spiritual growth, are associated with higher SRH and lower SHC ratings among urban Chinese women. Physical activity and health responsibility are additionally related to reduced fatigue and nervousness. We believe that these findings will be instrumental in encouraging researchers and urban women to adopt better health-promoting lifestyles with different priorities in their daily lives.
PMCID: PMC4324778  PMID: 25671578
2.  Evidences of grain boundary capacitance effect on the colossal dielectric permittivity in (Nb + In) co-doped TiO2 ceramics 
Scientific Reports  2015;5:8295.
The (Nb + In) co-doped TiO2 ceramics were synthesized by conventional solid-state sintering (CSSS) and spark plasma sintering (SPS) methods. The phases and microstructures were studied by X-ray diffraction, Raman spectra, field-emission scanning electron microscopy and transmission electron microscopy, indicating that both samples were in pure rutile phase while showing significant difference in grain size. The dielectric and I–V behaviors of SPS and CSSS samples were investigated. Though both possess colossal permittivity (CP), the SPS samples exhibited much higher dielectric permittivity/loss factor and lower breakdown electric field when compared to their CSSS counterparts. To further explore the origin of CP in co-doped TiO2 ceramics, the I–V behavior was studied on single grain and grain boundary in CSSS sample. The nearly ohmic I–V behavior was observed in single grain, while GBs showed nonlinear behavior and much higher resistance. The higher dielectric permittivity and lower breakdown electric field in SPS samples, thus, were thought to be associated with the feature of SPS, by which reduced space charges and/or impurity segregation can be achieved at grain boundaries. The present results support that the grain boundary capacitance effect plays an important role in the CP and nonlinear I–V behavior of (Nb + In) co-doped TiO2 ceramics.
PMCID: PMC4319151  PMID: 25656713
3.  Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma 
Molecular Cancer  2015;14(1):10.
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.
Methods and results
We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis.
This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.
PMCID: PMC4320626  PMID: 25622857
Alcohol; Angiogenesis; Human hepatocellular cancer; Metastasis; Reactive oxygen species
4.  Small-Molecule Inhibitors of Urea Transporters 
Sub-cellular biochemistry  2014;73:165-177.
Urea transporter (UT) proteins, which include isoforms of UT-A in kidney tubule epithelia and UT-B in vasa recta endothelia and erythrocytes, facilitate urinary concentrating function. Inhibitors of urea transporter function have potential clinical applications as sodium-sparing diuretics, or ‘urearetics,’ in edema from different etiologies, such as congestive heart failure and cirrhosis, as well as in syndrome of inappropriate antidiuretic hormone (SIADH). High-throughput screening of drug-like small molecules has identified UT-A and UT-B inhibitors with nanomolar potency. Inhibitors have been identified with different UT-A versus UT-B selectivity profiles and putative binding sites on UT proteins. Studies in rodent models support the utility of UT inhibitors in reducing urinary concentration, though testing in clinically relevant animal models of edema has not yet been done.
PMCID: PMC4306426  PMID: 25298345
Urea transporters; Diuretic; Kidney; High-throughput screening
5.  Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients 
BioMed Research International  2015;2015:740301.
The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD) patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years) and 32 unstable CAD (72.03 ± 4.3 years) and 20 healthy subjects (71.7 ± 5.2 years), matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC) of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.
PMCID: PMC4312568  PMID: 25664324
6.  Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells 
Mediators of Inflammation  2015;2015:362126.
Cannabinoid Δ9-tetrahydrocannabinol (THC) is effective in treating osteoarthritis (OA), and the mechanism, however, is still elusive. Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown. Cofilin-1 is a cytoskeleton protein, participating in the inflammation of OA. In this study, MG-63 cells, an osteosarcoma cell-line, were exposed to lipopolysaccharide (LPS) to mimic the inflammation of OA. We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1. We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin- (IL-) 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB) expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells. However, administration of CB2 receptor antagonist or the CB2-siRNA, not CB1 antagonist AM251, partially abolished the THC-induced anti-inflammatory effects above. In addition, overexpression of cofilin-1 significantly reversed the THC-induced anti-inflammatory effects in MG-63 cells. These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.
PMCID: PMC4310496  PMID: 25653478
7.  Quercetin Inhibits Radiation-Induced Skin Fibrosis 
Radiation research  2013;180(2):205-215.
Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.
PMCID: PMC4281888  PMID: 23819596
8.  Prediction of piRNAs using transposon interaction and a support vector machine 
BMC Bioinformatics  2014;15(1):419.
Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNA primarily expressed in germ cells that can silence transposons at the post-transcriptional level. Accurate prediction of piRNAs remains a significant challenge.
We developed a program for piRNA annotation (Piano) using piRNA-transposon interaction information. We downloaded 13,848 Drosophila piRNAs and 261,500 Drosophila transposons. The piRNAs were aligned to transposons with a maximum of three mismatches. Then, piRNA-transposon interactions were predicted by RNAplex. Triplet elements combining structure and sequence information were extracted from piRNA-transposon matching/pairing duplexes. A support vector machine (SVM) was used on these triplet elements to classify real and pseudo piRNAs, achieving 95.3 ± 0.33% accuracy and 96.0 ± 0.5% sensitivity. The SVM classifier can be used to correctly predict human, mouse and rat piRNAs, with overall accuracy of 90.6%. We used Piano to predict piRNAs for the rice stem borer, Chilo suppressalis, an important rice insect pest that causes huge yield loss. As a result, 82,639 piRNAs were predicted in C. suppressalis.
Piano demonstrates excellent piRNA prediction performance by using both structure and sequence features of transposon-piRNAs interactions. Piano is freely available to the academic community at
Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0419-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4308892  PMID: 25547961
piRNAs; piRNA prediction; Support vector machine (SVM); Chilo suppressalis; Drosophila melanogaster; Homo sapiens; Mus musculus; Rattus norvegicus
9.  Optimal contouring of seminal vesicle for definitive radiotherapy of localized prostate cancer: comparison between EORTC prostate cancer radiotherapy guideline, RTOG0815 protocol and actual anatomy 
Intermediate- to-high-risk prostate cancer can locally invade seminal vesicle (SV). It is recommended that anatomic proximal 1-cm to 2-cm SV be included in the clinical target volume (CTV) for definitive radiotherapy based on pathology studies. However, it remains unclear whether the pathology indicated SV extent is included into the CTV defined by current guidelines. The purpose of this study is to compare the volume of proximal SV included in CTV defined by EORTC prostate cancer radiotherapy guideline and RTOG0815 protocol with the actual anatomic volume.
Radiotherapy planning CT images from 114 patients with intermediate- (36.8%) or high-risk (63.2%) prostate cancer were reconstructed with 1-mm-thick sections. The starting and ending points of SV and the cross sections of SV at 1-cm and 2-cm from the starting point were determined using 3D-view. Maximum (D1H, D2H) and minimum (D1L, D2L) vertical distance from these cross sections to the starting point were measured. Then, CTV of proximal SV defined by actual anatomy, EORTC guideline and RTOG0815 protocol were contoured and compared (paired t test).
Median length of D1H, D1L, D2H and D2L was 10.8 mm, 2.1 mm, 17.6 mm and 8.8 mm (95th percentile: 13.5mm, 5.0mm, 21.5mm and 13.5mm, respectively). For intermediate-risk patients, the proximal 1-cm SV CTV defined by EORTC guideline and RTOG0815 protocol inadequately included the anatomic proximal 1-cm SV in 62.3% (71/114) and 71.0% (81/114) cases, respectively. While for high-risk patients, the proximal 2-cm SV CTV defined by EORTC guideline inadequately included the anatomic proximal 2-cm SV in 17.5% (20/114) cases.
SV involvement indicated by pathology studies was not completely included in the CTV defined by current guidelines. Delineation of proximal 1.4 cm and 2.2 cm SV in axial plane may be adequate to include the anatomic proximal 1-cm and 2-cm SV. However, part of SV may be over-contoured.
PMCID: PMC4299806  PMID: 25526901
Prostate cancer; Radiotherapy; Seminal vesicle; Target delineation; CT reconstruction
10.  Efficacy of local delivery of ardipusilloside I using biodegradable implants against cerebral tumor growth 
Ardipusilloside I (ADS-I) is a natural compound that can be isolated from the Chinese medicinal herb Ardisiapusilla A.DC, and has been reported to inhibit the growth of glioblastoma cells in cultures. This study was designed to test its efficacy by the delivery using biodegradable implants against glioblastoma in vivo. ADS-I was incorporated into polymer microspheres, which were prepared by a mixture of poly (D, L-lactic acid) and poly (D, L-lactic-co-glycolic acid) polymers and then fabricated into wafers. The anti-glioma activities of ADS-I-loaded wafers were examined by methylthiazol tetrazolium (MTT) assay in cultured rat C6 glioma cells, and by magnetic resonance imaging (MRI) and survival monitoring in C6 glioma-bearing rats. Here, we showed that ADS-I-loaded wafers sustained ADS-I release in vitro for 36 days in Higuchi model of kinetics, and had the same cytotoxic activity as ADS-I in the solution against the growth of C6 glioma cells in cultures. In C6 glioma-bearing rats, ADS-I wafer implants inhibited tumor growth in a dose-dependent matter, and were more effective than the same dosage of ADS-I in the solution. The tumor suppression efficacies of ADS-I wafer implants were positively correlated with an increase in tumor cell apoptosis and prolonged animal survival, and were associated with a decrease in vascular endothelial growth factor, C-reactive protein, tumor necrosis factor-α and interleukin-6, and an increase in interleukin-2 expression. In conclusion, this study demonstrates significant efficacy of local delivery of ADS-I using polymer implants against glioma tumor growth in vivo, suggesting the potential of ADS-I-loaded wafers for glioma treatment.
PMCID: PMC4300708  PMID: 25628934
Ardipusilloside I; glioblastoma; interstitial therapy; implant wafer; anti-tumor activities
11.  Associations between breakfast eating habits and health-promoting lifestyle, suboptimal health status in Southern China: a population based, cross sectional study 
Suboptimal health status (SHS) is the intermediate health state between health and disease, refers to medically undiagnosed or functional somatic syndromes, and has been a major global public health challenge. However, both the etiology and mechanisms associated with SHS are still unclear. Breakfast eating behavior is a dietary pattern marker and previous studies have presented evidence of associations between failure to consume breakfast and increased diseases. Accordingly, in view of the significance of breakfast eating behaviors with respect to health status, the associations between breakfast eating habits and healthy lifestyle, SHS require further elucidation.
A cross-sectional survey was conducted within a clustered sample of 24,159 individuals aged 12–80 years in 2012–13 within the population of Southern China. Breakfast eating habits were categorically defined by consumption frequency (‘scarcely, sometimes or always’). Health-promoting lifestyle was assessed via the health-promoting lifestyle profile (HPLP-II). SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0).
Of the 24,159 participants, the prevalence rates for the ‘health’ , ‘SHS’ , and ‘disease’ were 18.8%, 46.0%, and 35.2%, respectively. Overall, 19.6% of participants reported ‘scarce’ breakfast eating habits, with frequent breakfast eaters scoring higher on both HPLP-II and SHMS V1.0. After demographic adjustment, regression analyses revealed a significant association between breakfast eating habits and healthy lifestyle (p <0.001). There were lower levels of breakfast consumption regularity amongst individuals with SHS than those with disease. Categorically ‘scarce’ breakfast eaters were approximately three times more likely to be assigned SHS (OR: 2.745, 95% CI: 2.468-3.053), while infrequent breakfast eaters (‘sometimes’) were just less than twice as likely to be assessed as being of SHS (OR: 1.731, 95% CI: 1.595-1.879).
Breakfast eating habits are significantly associated with a healthy lifestyle, and appear to be a useful predictor of a healthy lifestyle. Irregular breakfast eating habits are related to an increased risk of SHS; increased breakfast eating frequency may contribute to lowering the prevalence of SHS in Southern China.
Electronic supplementary material
The online version of this article (doi:10.1186/s12967-014-0348-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4269950  PMID: 25496597
Breakfast eating habits; Suboptimal health status(SHS); Healthy lifestyle; Cross sectional study
12.  Preliminary experience of performing a video endoscopic inguinal lymphadenectomy using a hypogastric subcutaneous approach in patients with vulvar cancer 
Oncology Letters  2014;9(2):752-756.
To evaluate the feasibility and surgical outcome of video endoscopic inguinal lymphadenectomy (VEIL) using a hypogastric subcutaneous approach, 21 patients with vulvar cancer who underwent this procedure were included in the present study. Between December 2010 and March 2013, 21 consecutive patients with vulvar cancer underwent radical vulvectomy and VEIL using a hypogastric subcutaneous approach. The intraoperative and post-operative results and follow-up data were retrospectively analyzed. No intraoperative complications occurred. The mean duration of surgery for the endoscopic inguinal lymphadenectomies was 130 min (range, 80–180 min), with a mean estimated blood loss of 103 ml (range, 30–350 ml). The mean lymph node yield was 15 (range, 10–22 lymph nodes). The suction drains were removed after a mean duration of 7 days (range, 5–11 days). No skin-related complications were observed in the groin region and a lymphocele was only observed in 1/21 (4.8%) patients. After a mean follow-up period of 17 months (range, 3–31 months), recurrence was found in only one patient. All the patients were alive at the time of publication. Based on our preliminary experience, performing VEIL using a hypogastric subcutaneous approach is a safe and feasible technique for patients with vulvar cancer. These results indicate that this surgical technique may decrease the post-operative morbidity of lymphadenectomy without compromising the therapeutic efficacy. Future prospective studies with a greater sample size and a longer duration of follow-up are required.
PMCID: PMC4301472  PMID: 25621046
vulvar cancer; endoscopy; inguinal lymphadenectomy
13.  Shotgun Analysis of the Secretome of Fusarium graminearum 
Indian Journal of Microbiology  2013;53(4):400-409.
Fusarium head blight, caused predominately by Fusarium graminearum, is one of the most destructive diseases of wheat (Triticum aestivum L.) worldwide. To characterize the profile of proteins secreted by F. graminearum, the extracellular proteins were collectively obtained from F. graminearum culture supernatants and evaluated using one-dimensional SDS-PAGE and liquid chromatography-tandem mass spectrometry. A total of 87 proteins have been identified, of which 63 were predicted as secretory proteins including those with known functions. Meanwhile, 20 proteins that are not homologous to genomic sequences with known functions have also been detected. Some of the identified proteins are possible virulence factors and may play extracellular roles during F. graminearum infection. This study provides a valuable dataset of F. graminearum extracellular proteins, and a better understanding of the virulence mechanisms of the pathogen.
PMCID: PMC3779302  PMID: 24426143
Fusarium graminearum; Secretome; Triticum aestivum L.; LC-MS/MS; Virulence
14.  MiR-30a upregulates BCL2A1, IER3 and cyclin D2 expression by targeting FOXL2 
Oncology Letters  2014;9(2):967-971.
FOXL2 is a transcription factor that is essential for ovarian development. Somatic mutations of FOXL2 are associated with ovarian granulosa cell tumorigenesis. In the present study, the expression of FOXL2 was suppressed by microRNAs using the Ago2 knockdown method in COV434 cells. Online bioinformatics tools were utilized to predict that FOXL2 expression may be repressed by miR-30 family members, and dual luciferase assay and western blotting were performed to demonstrate that FOXL2 is a target gene of miR-30a, which is relatively abundant in COV434 cells. Furthermore, miR-30a overexpression upregulates BCL2A1, IER3 and cyclin D2 expression by inhibiting FOXL2. miR-30a is known to function as a tumor suppressor in breast cancer, small cell lung cancer and colorectal carcinoma; however, the present study revealed an opposing function of miR-30a as an oncogene.
PMCID: PMC4301489  PMID: 25621074
FOXL2; microRNA; miR-30a; ovarian granulosa cell tumor
15.  iPathCons and iPathDB: an improved insect pathway construction tool and the database 
Insects are one of the most successful animal groups on earth. Some insects, such as the silkworm and honeybee, are beneficial to humans, whereas others are notorious pests of crops. At present, the genomes of 38 insects have been sequenced and made publically available. In addition, the transcriptomes of dozens of insects have been sequenced. As gene data rapidly accumulate, constructing the pathway of molecular interactions becomes increasingly important for entomological research. Here, we developed an improved tool, iPathCons, for knowledge-based construction of pathways from the transcriptomes or the official gene sets of genomes. Considering the high evolution diversity in insects, iPathCons uses a voting system for Kyoto Encyclopedia of Genes and Genomes Orthology assignment. Both stand-alone software and a web server of iPathCons are provided. Using iPathCons, we constructed the pathways of molecular interactions of 52 insects, including 37 genome-sequenced and 15 transcriptome-sequenced ones. These pathways are available in the iPathDB, which provides searches, web server, data downloads, etc. This database will be highly useful for the insect research community.
Database URL:
PMCID: PMC4227299  PMID: 25388589
16.  Benign giant-cell tumor of the common bile duct: A case report 
World Journal of Gastroenterology : WJG  2014;20(41):15448-15453.
Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor’s possible confusion with other malignant tumors.
PMCID: PMC4223279  PMID: 25386094
Giant-cell tumor; Common bile duct; CD163; Surgical resection
17.  Selenium Inhibits Root Elongation by Repressing the Generation of Endogenous Hydrogen Sulfide in Brassica rapa 
PLoS ONE  2014;9(10):e110904.
Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots.
PMCID: PMC4204939  PMID: 25333279
18.  The Endogenous Nitric Oxide Mediates Selenium-Induced Phytotoxicity by Promoting ROS Generation in Brassica rapa 
PLoS ONE  2014;9(10):e110901.
Selenium (Se) is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS) burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO) in the root of Brassica rapa under Se(IV) stress. Se(IV)-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV)-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR)- and nitric oxide synthase (NOS)-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV)-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV)-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV) stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.
PMCID: PMC4204988  PMID: 25333984
19.  Antibacterial activity and mechanism of action of Monarda punctata essential oil and its main components against common bacterial pathogens in respiratory tract 
The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2’, 7’-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results.
PMCID: PMC4270556  PMID: 25550774
Monarda punctata; essential oil; thymol; p-cymene; Streptococcus pyogenes; methicillin-resistant Staphylococcus aureus
20.  miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6 
Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.
PMCID: PMC4221693  PMID: 25277211
21.  Orthologs of Human Disease Associated Genes and RNAi Analysis of Silencing Insulin Receptor Gene in Bombyx mori 
The silkworm, Bombyx mori L., is an important economic insect that has been domesticated for thousands of years to produce silk. It is our great interest to investigate the possibility of developing the B. mori as human disease model. We searched the orthologs of human disease associated genes in the B. mori by bi-directional best hits of BLAST and confirmed by searching the OrthoDB. In total, 5006 genes corresponding to 1612 kinds of human diseases had orthologs in the B. mori, among which, there are 25 genes associated with diabetes mellitus. Of these, we selected the insulin receptor gene of the B. mori (Bm-INSR) to study its expression in different tissues and at different developmental stages and tissues. Quantitative PCR showed that Bm-INSR was highly expressed in the Malpighian tubules but expressed at low levels in the testis. It was highly expressed in the 3rd and 4th instar larvae, and adult. We knocked down Bm-INSR expression using RNA interference. The abundance of Bm-INSR transcripts were dramatically reduced to ~4% of the control level at 6 days after dsRNA injection and the RNAi-treated B. mori individuals showed apparent growth inhibition and malformation such as abnormal body color in black, which is the typical symptom of diabetic patients. Our results demonstrate that B. mori has potential use as an animal model for diabetic mellitus research.
PMCID: PMC4227205  PMID: 25302617
Bombyx mori; human diseases model; diabetes mellitus; INSR; dsRNA
22.  S-1 as Monotherapy or in Combination With Leucovorin as Second-Line Treatment in Gemcitabine-Refractory Advanced Pancreatic Cancer: A Randomized, Open-Label, Multicenter, Phase II Study 
The Oncologist  2014;19(11):1133-1134.
In this study, we compared the efficacy and safety of the oral fluoropyrimidine S-1 as monotherapy or in combination with leucovorin as the second-line treatment for patients with metastatic pancreatic cancer whose disease had progressed on gemcitabine treatment.
The study was a randomized, open-label, controlled study. Patients randomly received S-1 or S-1 in combination with leucovorin (SL arm) in 21-day cycles. The primary endpoint was the 6-month survival rate.
A total of 92 patients were randomized to S-1 (n = 47) and SL (n = 45). No statistically significant differences were observed between the two arms with regard to 6-month survival rates (40% vs. 49%), median overall survival (5.5 vs. 6.3 months), median progression-free survival (1.9 vs. 3.0 months), and overall response rate (4.7% vs. 8.3%). The rate of major grade 3–4 adverse events of digestive toxicity was significantly higher in the SL arm than in the S-1 arm.
Compared with S-1, SL did not improve the survival of patients with metastatic pancreatic cancer who had failed to benefit from prior gemcitabine treatment, but SL had a higher adverse event rate.
PMCID: PMC4221373  PMID: 25273077
23.  Excretion of Urinary Orosomucoid 1 Protein Is Elevated in Patients with Chronic Heart Failure 
PLoS ONE  2014;9(9):e107550.
Easily screening markers for early detection of chronic heart failure (CHF) are lacking. We identified twenty differently expressed proteins including orosomucoid 1(ORM1) in urine between patients with CHF and normal controls by proteomic methods. Bioinformatics analyses suggested ORM1 could be used for further analysis. After verification by western blotting, the urinary levels of ORM1 were quantified with enzyme-linked immunosorbent assay (ELISA) by correcting for creatinine expression. The ORM1-Cr was significantly elevated in CHF patients than normal controls (6498.83±4300.21 versus 2102.26±1069.24 ng/mg). Furthermore, a Spearman analysis indicated that the urinary ORM1 levels had a high positive correlation with the classification of CHF, and the multivariate analysis suggested that the urinary ORM1 content was associated with the plasma amino-terminal pro- brain natriuretic peptide (NT-proBNP) (OR: 2.106, 95% CI: 1.213–3.524, P = 0.002) and the New York Heart Association (NYHA) classification (OR: 3.019, 95% CI: 1.329–4.721, P<0.001). In addition, receiving operating curve (ROC) analyses suggested that an optimum cut-off value of 2484.98 ng/mg with 90.91% sensitivity and 85.48% specificity, respectively, could be used for the diagnosis of CHF. To sum up, our findings indicate that ORM1 could be a potential novel urinary biomarker for the early detection of CHF.
PMCID: PMC4162620  PMID: 25215505
24.  Depression in Chinese men undergoing different assisted reproductive technique treatments: prevalence and risk factors 
To explore the prevalence and risk factors for depression in men undergoing different assisted reproductive technique (ART) treatments in Chinese population.
This was a prospective study of 844 men undergoing ART treatments. All men were distributed to four groups, according to they received treatments. The treatments included IUI (intrauterine insemination), IVF(in vitro fertilization), ICSI(intra cytoplasmatic sperm injection) and TESA/PESA (percutaneous epididymal sperm aspiration/testicular sperm aspiration). Their symptoms of depression were measured with use of the Center for Epidemiologic Studies of Depression scale(CES-D). Data were collected about age, BMI, education, duration of marriage, duration of infertility, smoking, type of infertility, infertility causes, history of ejaculation failure, and financial burden of the treatment. We estimated the prevalence of depressive symptom in men undergoing different ART and used logistic regression models to identify risk factors for depression in different groups.
The overall prevalence of depression was 13.3 % for men undergoing ART treatments: 14.5 % of IUI group, 12.4 % of IVF group, 19.2 % of ICSI group and 6.2 % of TESA/PESA group. Prevalence of depression among IUI group, IVF group and ICSI group were not significantly different. For IUI group, the factors were found to increase depression risk were treatment financial burden and duration of marriage, to decrease depression risk was age. For IVF group, the risk factors independently associated with depression were both male and female infertility, unexplained infertility, and history of ejaculation failure.
In a sample of Chinese men undergoing ART treatments, the prevalence of depression was higher than other country. The risk factors for depression varied in different ART treatments groups. when routine screening to identify the sub-group of vulnerable men which need counselling before ART treatments, we should also consider which pattern of ART treatments the man underwent.
PMCID: PMC3800534  PMID: 23907732
Depression; Chinese men; ART; Risk factors; Prevalence
25.  Cheliensisin A Inhibits EGF-induced Cell Transformation with Stabilization of p53 Protein via a Hydrogen Peroxide/Chk1-dependent Axis 
Cheliensisin A (Chel A), a novel styryl-lactone isolated from Goniothalamus cheliensis Hu, has been shown to induce of apoptosis in human promyelocytic leukemia HL-60 cells with Bcl-2 downregulation. Yet the potential chemopreventive effect of Chel A has not been explored. Here we demonstrated that Chel A treatment with various concentrations (0.5, 1.0, 2.0, and 4.0 μM) for 3 weeks could dramatically inhibit EGF-induced cell transformation in Cl41 cells (IC50 approximately 2.0 μM). Also, co-incubation of Cl41 cells with Chel A (2.0 and 4.0 μM) for 48 hours could induce cell apoptosis in a caspase-3-dependent manner. Mechanically, Chel A treatment could result in increased p53 phosphorylation at Ser15 and elevated p53 total protein expression. Moreover, we found that p53 induction by Chel A was regulated at the protein degradation level, but not at either the transcription or the mRNA level. Further studies showed that p53 stabilization by Chel A was mediated via induction of phosphorylation and activation of Chk1 protein at Ser345. This notion was substantiated by the results that transfection of dominant negative mutant of Chk1 (GFP-Chk1 D130A) significantly attenuated the p53 protein expression, cell apoptosis, and inhibition of cell transformation by Chel A. Finally, increased hydrogen peroxide was found to mediate Chk1 phosphorylation at Ser345, p53 protein induction, cell apoptotic induction, and transformation inhibition following Chel A treatment. Taken together, our studies identify Chel A as a chemopreventive agent with the understanding of the molecular mechanisms involved.
PMCID: PMC3769189  PMID: 23852422
Cheliensisin A; apoptosis; anti-cancer; p53; chemoprevetion; cell transformation

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