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1.  Angiotensin II Reduces Cardiac AdipoR1 Expression through AT1 Receptor/ROS/ERK1/2/c-Myc Pathway 
PLoS ONE  2013;8(1):e49915.
Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2) mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII) on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1) receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS) scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.
PMCID: PMC3551944  PMID: 23349663
3.  The Expression Levels of Transcription Factors T-bet, GATA-3, RORγt and FOXP3 in Peripheral Blood Lymphocyte (PBL) of Patients with Liver Cancer and their Significance 
Objectives: To investigate the expression of transcriptional factors (TFs) T-bet, GATA-3, RORγt and FOXP in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to evaluate the correlation between the imbalances of Th1/Th2, Th17/Treg at the expression levels and liver cancer
Methods: The peripheral venous blood was drawn from 20 HCC-patients (HCC-group) and 20 health participants (C-group). The expression levels of Th1, Th2 and Th17 and the major Treg-specific TFs T-bet, GATA-3, RORγt and FOXP3 in the PBMC were measured with quantitative real-time PCR(RT-qPCR).
Results: The mRNA level of Th1-specific TF T-bet in HCC-group was significantly lower than that of C-group (52.34±34.07 VS 104.01±56.00, P<0.01); the mRNA level of Th2-specifc TF, GATA-3, in HCC group was significantly higher than that in C-group (1.38±1.15 VS 0.58±0.65, P<0.05) and T-bet mRNA/GATA-3 mRNA ratio was significantly lower in HCC-group than in C-group (86.01±116.71 VS 461.88±708.81, P<0.05). The mRNA level of Th17-specific TF RORγt in HCC-group was significantly higher than that of C-group (72.32±32.82 VS 33.07±22.86, P<0.01). Treg-specific TF FOXP3 mRNA level was significant higher in HCC-group than in C-group (3.17±1.59 VS 1.39±1.13, P<0.01)
Conclusion: T-bet mRNA level was reduced whereas GATA-3 mRNA level was increased and T-bet/GATA-3 ratio was significantly reduced in PBMC, indicating that Th1/Th2 ratio was of imbalance at TF levels in PBMC of HCC, displaying Th2 thrift phenomena. The mRNA levels of RORγt and FOXP3 in PBMC of HCC were significantly increased, indicating the existence of a predominant phenomenon of Th17- and Treg-expressing PBMC in HCC.
PMCID: PMC4278870  PMID: 25552913
RORγt; Th1; Th2; Th17; Treg; Hepatocellular carcinoma (HCC).
4.  Psychiatric Correlates of Snuff and Chewing Tobacco Use 
PLoS ONE  2014;9(12):e113196.
Compared to the association between cigarette smoking and psychiatric disorders, relatively little is known about the relationship between smokeless tobacco use and psychiatric disorders. To identify the psychiatric correlates of smokeless tobacco use, the analysis used a national representative sample from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) wave 1. Smokeless tobacco use was classified as exclusive snuff use, exclusive chewing tobacco, and dual use of both snuff and chewing tobacco at some time in the smokeless tobacco user's life. Lifetime psychiatric disorders were obtained via structured diagnostic interviews. The results show that the prevalence of lifetime exclusive snuff use, exclusive chewing tobacco, and dual use of both snuff and chewing tobacco was 2.16%, 2.52%, and 2.79%, respectively. After controlling for sociodemographic variables and cigarette smoking, the odds of exclusive chewing tobacco in persons with panic disorder and specific phobia were 1.53 and 1.41 times the odds in persons without those disorders, respectively. The odds of exclusive snuff use, exclusive chewing tobacco, and dual use of both products for individuals with alcohol use disorder were 1.97, 2.01, and 2.99 times the odds for those without alcohol use disorder, respectively. Respondents with cannabis use disorder were 1.44 times more likely to use snuff exclusively than those without cannabis use disorder. Respondents with inhalant/solvent use disorder were associated with 3.33 times the odds of exclusive chewing tobacco. In conclusion, this study highlights the specific links of anxiety disorder, alcohol, cannabis, and inhalant/solvent use disorders with different types of smokeless tobacco use.
PMCID: PMC4275177  PMID: 25535739
5.  Inhibitory effects of dobutamine on human gastric adenocarcinoma 
World Journal of Gastroenterology : WJG  2014;20(45):17092-17099.
AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells.
METHODS: Dobutamine was used to treat gastric adenocarcinoma cells (SGC-7901) and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of dobutamine combined with cisplatin on cell viability were also analyzed. Cell migration was studied using the wound healing assay, and cell proliferation was analyzed using the colony formation assay. A cell invasion assay was carried out using Transwell cell culture chambers. The cell cycle and cell apoptosis were analyzed by flow cytometry. Western blot and immunocytochemistry were performed to determine the expression of Yes-associated protein (YAP) in treated cells.
RESULTS: Dobutamine significantly inhibited cell growth, migration, cell colony formation, and cell invasion into Matrigel. Dobutamine also arrested the cell cycle at G1/S phase, and increased the rate of apoptosis of gastric adenocarcinoma cells. The expression of YAP was detected mainly in the nucleus in the absence of dobutamine. However, reduced expression of phosphorylated YAP was mainly found in the cytosol following treatment with dobutamine.
CONCLUSION: Dobutamine has significant inhibitory effects on gastric adenocarcinoma cells and may be used in neoadjuvant therapy not only for gastric cancer, but also for other tumors.
PMCID: PMC4258577  PMID: 25493021
Dobutamine; Gastric adenocarcinoma cells; Yes-associated protein; Hippo pathway; Human gastric adenocarcinoma cell line SGC-7901; Therapy
6.  Illicit and nonmedical drug use among Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race individuals 
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.06.008.
The racial/ethnic composition of the United States is shifting rapidly, with non-Hispanic Asian-Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals the fastest growing segments of the population. We determined new drug use estimates for these rising groups. Prevalences among Whites were included as a comparison.
Data were from the 2005–2011 National Surveys on Drug Use and Health. Substance use among respondents aged ≥12 years was assessed by computer-assisted self-interviewing methods. Respondents’ self-reported race/ethnicity, age, gender, household income, government assistance, county type, residential stability, major depressive episode, history of being arrested, tobacco use, and alcohol use were examined as correlates. We stratified the analysis by race/ethnicity and used logistic regression to estimate odds of drug use.
Prevalence of past-year marijuana use among Whites increased from 10.7% in 2005 to 11.6–11.8% in 2009–2011 (P<0.05). There were no significant yearly changes in drug use prevalences among Asian-Americans, NHs/PIs, and mixed-race people; but use of any drug, especially marijuana, was prevalent among NHs/PIs and mixed-race people (21.2% and 23.3%, respectively, in 2011). Compared with Asian-Americans, NHs/PIs had higher odds of marijuana use, and mixed-race individuals had higher odds of using marijuana, cocaine, hallucinogens, stimulants, sedatives, and tranquilizers. Compared with Whites, mixed-race individuals had greater odds of any drug use, mainly marijuana, and NHs/PIs resembled Whites in odds of any drug use.
Findings reveal alarmingly prevalent drug use among NHs/PIs and mixed-race people. Research on drug use is needed in these rising populations to inform prevention and treatment efforts.
PMCID: PMC3818295  PMID: 23890491
Asian Americans; drug use; marijuana use; mixed race; multiple race; Native Hawaiians; nonmedical opioid use; Pacific Islanders
8.  Comorbid substance use disorders with other Axis I and II mental disorders among treatment-seeking Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race people 
Journal of psychiatric research  2013;47(12):10.1016/j.jpsychires.2013.08.022.
Little is known about behavioral healthcare needs of Asian Americans (AAs), Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race people (MRs)—the fastest growing segments of the U.S. population. We examined substance use disorder (SUD) prevalences and comorbidities among AAs, NHs/PIs, and MRs (N=4572) in a behavioral health electronic health record database. DSM-IV diagnoses among patients aged 1–90 years who accessed behavioral healthcare from 11 sites were systematically captured: SUD, anxiety, mood, personality, adjustment, childhood-onset, cognitive/dementia, dissociative, eating, factitious, impulse-control, psychotic/schizophrenic, sleep, and somatoform diagnoses. Of all patients, 15.0% had a SUD. Mood (60%), anxiety (31.2%), adjustment (30.9%), and disruptive (attention deficit-hyperactivity, conduct, oppositional defiant, disruptive behavior diagnosis, 22.7%) diagnoses were more common than others (psychotic 14.2%, personality 13.3%, other childhood-onset 11.4%, impulse-control 6.6%, cognitive 2.8%, eating 2.2%, somatoform 2.1%). Less than 1% of children aged <12 years had SUD. Cannabis diagnosis was the primary SUD affecting adolescents aged 12–17. MRs aged 35–49 years had the highest prevalence of cocaine diagnosis. Controlling for age at first visit, sex, treatment setting, length of treatment, and number of comorbid diagnoses, NHs/PIs and MRs were about two times more likely than AAs to have ≥2 SUDs. Regardless of race/ethnicity, personality diagnosis was comorbid with SUD. NHs/PIs with a mood diagnosis had elevated odds of having SUD. Findings present the most comprehensive patterns of mental diagnoses available for treatment-seeking AAs, NHs/PIs, and MRs in the real-world medical setting. In-depth research is needed to elucidate intraracial and interracial differences in treatment needs.
PMCID: PMC3846388  PMID: 24060266
Asian Americans; comorbidity; mixed race; Native Hawaiians; Pacific Islanders; substance use disorder
9.  Stanniocalcin-1 protects bovine intestinal epithelial cells from oxidative stress-induced damage 
Journal of Veterinary Science  2014;15(4):475-483.
Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 µM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over-expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
PMCID: PMC4269589  PMID: 24962416
Bcl-2; chronic enteritis; oxidative damage; stanniocalcin-1
10.  Chlorogenic acid suppresses interleukin-1β-induced inflammatory mediators in human chondrocytes 
We investigated the anti-inflammatory properties of chlorogenic acid (CGA) in interleukin-1β-induced chondrocytes. The nitric oxide (NO) and prostaglandin E2 (PGE2) were detected by Griess and Enzyme-linked immunosorbent assay (ELISA) respectively. Quantitative real-time PCR and western blot were performed to measure the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Our results indicate that CGA inhibited the production of NO and PGE2 as well as the expression of iNOS and COX-2 in chondrocytes. Our data suggest that CGA possess potential value in the treatment of OA.
PMCID: PMC4314010
Chlorogenic acid; inducible NO synthase; cyclooxygenase; chondrocyte
11.  Ambient air pollution and birth defects in Haikou city, Hainan province 
BMC Pediatrics  2014;14(1):283.
Evidence shows exposure to ambient air pollution during pregnancy was associated with an increased risk of adverse birth outcomes, such as preterm birth, low birth weight and intrauterine growth retardation, but the results for birth defects have been inconsistent.
The data on birth defects was collected from the Birth Defects Monitoring Network of Haikou city. Air pollution data for PM10, SO2 and NO2 were obtained from Haikou Environmental Monitoring Center. Logistic regression analysis was used to evaluate these associations.
The risk of birth defects was related to PM10 levels (adjusted OR = 1.039; 95% CI = 1.016-1.063) and SO2 levels (adjusted OR = 0.843; 95% CI = 0.733-0.969) for the second month of pregnancy. In the third month of pregnancy, the risk of birth defects was also related to PM10 levels (adjusted OR = 1.066; 95% CI = 1.043-1.090) and SO2 levels (adjusted OR = 0.740; 95% CI = 0.645-0.850).
The study provides evidence that exposure to PM10 and SO2 during the second and third month of pregnancy may associated with the risk of birth defects.
PMCID: PMC4254194  PMID: 25416166
Air pollution; Birth defects; PM10; SO2; NO2
12.  Dietary Glutamate Supplementation Ameliorates Mycotoxin-Induced Abnormalities in the Intestinal Structure and Expression of Amino Acid Transporters in Young Pigs 
PLoS ONE  2014;9(11):e112357.
The purpose of this study was to investigate the hypothesis that dietary supplementation with glutamic acid has beneficial effects on growth performance, antioxidant system, intestinal morphology, serum amino acid profile and the gene expression of intestinal amino acid transporters in growing swine fed mold-contaminated feed. Fifteen pigs (Landrace×Large White) with a mean body weight (BW) of 55 kg were randomly divided into control group (basal feed), mycotoxin group (contaminated feed) and glutamate group (2% glutamate+contaminated feed). Compared with control group, mold-contaminated feed decreased average daily gain (ADG) and increased feed conversion rate (FCR). Meanwhile, fed mold-contaminated feed impaired anti-oxidative system and intestinal morphology, as well as modified the serum amino acid profile in growing pigs. However, supplementation with glutamate exhibited potential positive effects on growth performance of pigs fed mold-contaminated feed, ameliorated the imbalance antioxidant system and abnormalities of intestinal structure caused by mycotoxins. In addition, dietary glutamate supplementation to some extent restored changed serum amino acid profile caused by mold-contaminated feed. In conclusion, glutamic acid may be act as a nutritional regulating factor to ameliorate the adverse effects induced by mycotoxins.
PMCID: PMC4236086  PMID: 25405987
13.  Do we really need closed-suction drainage in total hip arthroplasty? A meta-analysis 
International Orthopaedics  2013;37(11):2109-2118.
The clinical use of closed-suction drainage, which aims to reduce postoperative wound haematomas and infection, is common. This study was performed to determine whether closed-suction drainage is safe and effective in promoting wound healing and reducing blood loss and other complications compared with no-drainage in total hip arthroplasty.
The literature search was based on PubMed, the Cochrane Library, MEDLINE, and EMBASE. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group, and then analysed using RevMan 5.0. Twenty randomised controlled trials involving 3,186 patients were included in our analysis.
The results of our meta-analysis indicate that closed-suction drainage reduces the requirement for dressing reinforcement, but increases the rate of homologous blood transfusion. No significant difference was observed in the incidence of infection, blood loss, changes in haemoglobin and haematocrit, functional assessment, or other complications when the drainage group was compared with the no-drainage group.
Our results of the comparison between closed-suction drainage and no drainage in THA have indicated that the routine use of closed-suction drainage for elective total hip arthroplasty may be of more harm than benefit.
PMCID: PMC3824906  PMID: 23982636
Closed-suction drainage; Total hip arthroplasty; Blood loss; Transfusion; Meta-analysis
14.  Identification of Cellular Proteins Interacting with the Retroviral Restriction Factor SAMHD1 
Journal of Virology  2014;88(10):5834-5844.
Human and mouse SAMHD1 proteins block human immunodeficiency virus type 1 (HIV-1) infection in noncycling human monocytic cells by reducing the intracellular deoxynucleoside triphosphate (dNTP) concentrations. Phosphorylation of human SAMHD1 at threonine 592 (T592) by cyclin-dependent kinase 1 (CDK1) and cyclin A2 impairs its HIV-1 restriction activity, but not the dNTP hydrolase activity, suggesting that dNTP depletion is not the sole mechanism of SAMHD1-mediated HIV-1 restriction. Using coimmunoprecipitation and mass spectrometry, we identified and validated two additional host proteins interacting with human SAMHD1, namely, cyclin-dependent kinase 2 (CDK2) and S-phase kinase-associated protein 2 (SKP2). We observed that mouse SAMHD1 specifically interacted with cyclin A2, cyclin B1, CDK1, and CDK2. Given the role of these SAMHD1-interacting proteins in cell cycle progression, we investigated the regulation of these host proteins by monocyte differentiation and activation of CD4+ T cells and examined their effect on the phosphorylation of human SAMHD1 at T592. Our results indicate that primary monocyte differentiation and CD4+ T-cell activation regulate the expression of these SAMHD1-interacting proteins. Furthermore, our results suggest that, in addition to CDK1 and cyclin A2, CDK2 phosphorylates T592 of human SAMHD1 and thereby regulates its HIV-1 restriction function.
IMPORTANCE SAMHD1 is the first dNTP triphosphohydrolase found in mammalian cells. Human and mouse SAMHD1 proteins block HIV-1 infection in noncycling cells. Previous studies suggested that phosphorylation of human SAMHD1 at threonine 592 by CDK1 and cyclin A2 negatively regulates its HIV-1 restriction activity. However, it is unclear whether human SAMHD1 interacts with other host proteins in the cyclin A2 and CDK1 complex and whether mouse SAMHD1 shares similar cellular interacting partners. Here, we identify five cell cycle-related host proteins that interact with human and mouse SAMHD1, including three previously unknown cellular proteins (CDK2, cyclin B1, and SKP2). Our results demonstrate that several SAMHD1-interacting cellular proteins regulate phosphorylation of SAMHD1 and play an important role in HIV-1 restriction function. Our findings help define the role of these cellular interacting partners of SAMHD1 that regulate its HIV-1 restriction function.
PMCID: PMC4019113  PMID: 24623419
15.  Curcumin could reduce the monomer of TTR with Tyr114Cys mutation via autophagy in cell model of familial amyloid polyneuropathy 
Transthyretin (TTR) familial amyloid polyneuropathy (FAP) is an autosomal dominant inherited neurodegenerative disorder caused by various mutations in the transthyretin gene. We aimed to identify the mechanisms underlying TTR FAP with Tyr114Cys (Y114C) mutation. Our study showed that TTR Y114C mutation led to an increase in monomeric TTR and impaired autophagy. Treatment with curcumin resulted in a significant decrease of monomeric TTR by recovering autophagy. Our research suggests that impairment of autophagy might be involved in the pathogenesis of TTR FAP with Y114C mutation, and curcumin might be a potential therapeutic approach for TTR FAP.
PMCID: PMC4222630  PMID: 25382970
curcumin; familial amyloid polyneuropathy; transthyretin; autophagy
16.  Extracts and compounds with anti-diabetic complications and anti-cancer activity from Castanea mollissina Blume (Chinese chestnut) 
Castanea mollissima Blume (Chinese chestnut), as a food product is known for its various nutrients and functional values to the human health. The present study was carried out to analyze the anti-diabetic complications and anti-cancer activities of the bioactive compounds present in C. mollissima.
The kernels (CK), shells (CS) and involucres (CI) parts of C. Blume were extracted with 90% alcohol. The water suspension of these dried alcohol extracts were extracted using EtOAc and n-BuOH successively. The n-BuOH fraction of CI (CI-B) was isolated by silica gel column, Sephadex LH 20 column and preparative HPLC. The isolated compounds were identified by 1H-NMR, 13C-NMR, HMBC, HMQC and ESI-Q-TOF MS, All the fractions and compounds isolated were evaluated on human recombinant aldose reductase (HR-AR) assay, advanced glycation end products (AGEs) formation assay and human COLO 320 DM colon cancer cells inhibitory assay.
CI-B was found to show a significant inhibitory effect in above biological screenings. Six flavonoids and three polyphenolic acids were obtained from CI-B. They were identified as kaempferol (1), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (2), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-galactopyranoside (3), kaempferol-3-O-[2''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (4), kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-glucopyranoside (5) and kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-galactopyranoside (6), casuariin (7), casuarinin (8) and castalagin (9). Compounds 2–9 were found to show higher activity than quercetin (positive control) in the AR assay. Compounds 3–6, 8, and 9 showed stronger inhibitory effects than amino guanidine (positive control) on AGEs production. Compounds 4–6, 7, and 8 showed much higher cytotoxic activity than 5-fluorouracil (positive control) against the human COLO 320 DM colon cancer cells.
Our results suggest that flavonoids and polyphenolic acids possesses anti-diabetes complications and anti-cancer properties, and they were presumed to be the bioactive components of Castanea mollissima Blume.
Electronic supplementary material
The online version of this article (doi:10.1186/1472-6882-14-422) contains supplementary material, which is available to authorized users.
PMCID: PMC4226895  PMID: 25351676
Anti-diabetic complications; Anti-cancer; Castanea mollissina Blume; Phenolic acids; Flavonoids
17.  Expression of vaspin in the joint and the levels in the serum and synovial fluid of patients with osteoarthritis 
The aim of this study was to determine the expression of vaspin in the joint and investigate the distribution between paired serum and synovial fluid (SF) in osteoarthritis (OA) patients, and serum in healthy controls. The gene expression of vaspin was measured by quantitative real-time polymerase chain reaction (qPCR) in the OA joint tissues. The vaspin protein expression in the cartilage, synovium and osteophyte from OA patients who required total knee replacement (TKR) were detected by immunohistochemistry (IHC). Levels of vaspin in serum and SF were analyzed by enzyme-linked immunosorbent assay (ELISA), including 26 OA patients and 23 healthy controls. All the joint tissues including cartilage, synovium, meniscus, infrapatellar fat pad and osteophyte from OA patients expressed vaspin messenger RNA (mRNA), and the expression of vaspin protein was observed in OA cartilage, synovium and osteophyte. Furthermore, serum vaspin was reduced in OA patients compared to healthy controls, and serum vaspin levels from OA patients exceed those in the paired SF. Serum or SF vaspin were not related to age, gender, or body mass index (BMI). These results suggest that vaspin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA.
PMCID: PMC4238502  PMID: 25419381
Vaspin; osteoarthritis; serum; synovial fluid; joint
18.  Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells 
ACS Medicinal Chemistry Letters  2013;4(10):921-926.
Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignant neoplasm.
PMCID: PMC4027503  PMID: 24900585
Lung cancer; cell cycle; largazole; E2F1; degradation
19.  Relationship between Lung Function and Metabolic Syndrome 
PLoS ONE  2014;9(10):e108989.
Although the link between impaired lung function and cardiovascular events and type 2 diabetes mellitus has been recognized, the association between impaired lung function and metabolic syndrome has not been comprehensively assessed in the United States (U.S.) population. The aim of our study was to explore the association between impaired lung function and metabolic syndrome in a nationally representative sample of men and women. This cross-sectional population-based study included 8602 participants aged 20–65 years in the Third National Health and Nutrition Examination Survey (NHANES III). We examined the relationship between the different features of metabolic syndrome and lung function, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). After adjusting for potential confounders such as age, body mass index, inflammatory factors, medical condition, and smoking status, participants with more components of metabolic syndrome had lower predicted values of FVC and FEV1 (p for trend <0.001 for both). Impaired pulmonary function was also associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, high triglycerides, and low high density lipoprotein (HDL) cholesterol (p<0.05 for all parameters). These results from a nationally representative sample of US adults suggest that a greater number of features of metabolic syndrome is strongly associated with poorer FVC and FEV1. In clinical practice, more comprehensive management strategies to address subjects with metabolic syndrome and impaired lung function need to be developed and investigated.
PMCID: PMC4191965  PMID: 25299452
20.  Smoking and Opioid Detoxification: Behavioral Changes and Response to Treatment 
Nicotine & Tobacco Research  2013;15(10):1705-1713.
The relevance of tobacco use in opioid addiction (OA) has generated a demand for available and more effective interventions. Thus, further analysis of less explored nicotine–opioid clinical interactions is warranted.
A post-hoc analysis of OA participants in a double-blind, randomized very low dose naltrexone (VLNTX) inpatient detoxification trial evaluated measures of opioid withdrawal and tobacco use. Intreatment smokers were compared with nonsmokers, or smokers who were not allowed to smoke.
A total of 141 (81%) of 174 OA participants were smokers, all nicotine-dependent. Inpatient smoking was a predictor of opioid withdrawal discomfort. Intreatment smokers (n = 96) showed significantly higher opioid craving (F = 3.7, p < .001) and lower detoxification completion rate (χ2 = 7.9, p < .02) compared with smokers who were not allowed to smoke (n = 45) or nonsmokers (n = 33). Smoking during treatment was associated with more elevated cigarette craving during detoxification (F = 4.1, p < .001) and a higher number of cigarettes smoked at follow-up (F = 3.6, p < .02). Among intreatment smokers, VLNTX addition to methadone taper was effective in easing opioid withdrawal and craving more than other treatments, whereas the combination VLNTX–clonidine was associated with significantly reduced cigarette craving and smoking during detoxification.
Failure to address tobacco use may negatively affect pharmacologically managed opioid discontinuation. Opioid detoxification may offer a window of opportunity to expand smoking cessation treatment, hence improving OA outcomes. The observed effects support testing of VLNTX–clonidine in smoking cessation trials among individuals with or without substance abuse.
PMCID: PMC3768333  PMID: 23572466
21.  Perceptual Learning Improves Stereoacuity in Amblyopia 
Amblyopia is a developmental disorder that results in both monocular and binocular deficits. Although traditional treatment in clinical practice (i.e., refractive correction, or occlusion by patching and penalization of the fellow eye) is effective in restoring monocular visual acuity, there is little information on how binocular function, especially stereopsis, responds to traditional amblyopia treatment. We aim to evaluate the effects of perceptual learning on stereopsis in observers with amblyopia in the current study.
Eleven observers (21.1 ± 5.1 years, six females) with anisometropic or ametropic amblyopia were trained to judge depth in 10 to 13 sessions. Red–green glasses were used to present three different texture anaglyphs with different disparities but a fixed exposure duration. Stereoacuity was assessed with the Fly Stereo Acuity Test and visual acuity was assessed with the Chinese Tumbling E Chart before and after training.
Averaged across observers, training significantly reduced disparity threshold from 776.7″ to 490.4″ (P < 0.01) and improved stereoacuity from 200.3″ to 81.6″ (P < 0.01). Interestingly, visual acuity also significantly improved from 0.44 to 0.35 logMAR (approximately 0.9 lines, P < 0.05) in the amblyopic eye after training. Moreover, the learning effects in two of the three retested observers were largely retained over a 5-month period.
Perceptual learning is effective in improving stereo vision in observers with amblyopia. These results, together with previous evidence, suggest that structured monocular and binocular training might be necessary to fully recover degraded visual functions in amblyopia.
Chinese Abstract
Traditional treatment cannot fully normalize stereoacuity in amblyopia. This study identifies that perceptual learning is of potential in restoring stereoacuity in adults with anisometropic amblyopia.
PMCID: PMC3989086  PMID: 24508791
perceptual learning; stereoacuity; amblyopia
22.  The National Drug Abuse Treatment Clinical Trials Network Data Share Project: Website Design, Usage, Challenges and Future Directions 
Clinical trials (London, England)  2013;10(6):977-986.
The are many benefits of data sharing, including the promotion of new research from effective use of existing data, replication of findings through re-analysis of pooled data files, meta-analysis using individual patient data, and reinforcement of open scientific inquiry. A randomized controlled trial is considered as the “gold standard” for establishing treatment effectiveness, but clinical trial research is very costly and sharing data is an opportunity to expand the investment of the clinical trial beyond its original goals at minimal costs.
We describe the goals, developments, and usage of the Data Share website ( for the National Drug Abuse Treatment Clinical Trials Network (CTN) in the US, including lessons learned, limitations and major revisions and considerations for future directions to improve data sharing.
Data management and programming procedures were conducted to produce uniform and Health Insurance Portability and Accountability Act (HIPAA)-compliant de-identified research data files from the completed trials of the CTN for archiving, managing, and sharing on the Data Share website.
Since its inception in 2006 and through October 2012, nearly 1700 downloads from 27 clinical trials have been accessed from the Data Share website, with the use increasing over the years. Individuals from 31 countries have downloaded data from the website, and there have been at least 13 publications derived from analyzing data through the public Data Share website.
Minimal control over data requests and usage has resulted in little information and lack of control regarding how the data from the website are used. Lack of uniformity in data elements collected across CTN trials has limited cross-study analyses.
The Data Share website offers researchers easy access to deidentified data files with the goal to promote additional research and identify new findings from completed CTN studies. To maximize the utility of the website, on-going collaborative efforts are needed to standardize the core measures used for data collection in the CTN studies with the goal to increase their comparability and to facilitate the ability to pool data files for cross-study analyses.
PMCID: PMC3994893  PMID: 24085772
23.  Advances in Opioid Antagonist Treatment for Opioid Addiction 
PMCID: PMC4178977  PMID: 22640757
Addiction treatment; Depot naltrexone; Opioid dependence; Relapse
24.  Study on the effect of BMSCs-EGFP-tk as mediator of HSV1-tk/GCV suicide gene therapy directed against A549 in vitro 
This study aims to observe the expression of HSV1-tk in mouse bone marrow mesenchymal stem cells (BMSCs-EGFP-tk) and detect the inhibition and killing effects of BMSCs as mediator of HSV1-tk/GCV on A549 cells in vitro, which can provide the experimental basis for gene therapy of lung cancer. We constructed the recombinant plasmid Vector pDON-AI-2 Neo-HSV1-tk-IRES2-EGFP with genetic engineering methods. Then we obtained the virus-like particles with infection ability after packaging the virus. The recombinant plasmid was transfected into mouse bone marrow mesenchymal stem cells in vitro. The expressions of EGFP in cells were observed by fluorescence microscopy and HSV1-tk gene was detected with RT-PCR. At last, the A549 cells and BMSCs-EGFP-tk cells were co-cultured with in vitro contact method, and the effect of BMSCs-EGFP-tk/GCV system was determined by MTT. Results indicated that the biological characteristics of BMSCs-EGFP-tk were consistent with those of BMSCs and fluorescent light expression and HSV1-tk gene expression can persist at least 15 days. The A549 cells and BMSCs-EGFP-tk cells were co-cultured and BMSCs-EGFP-tk:A549 = 2:1, adding 1 μg/mL GCV, the theory mortality is 58.44%, but actually the mortality is 90%. There is almost no difference between BMSCs-EGFP-tk and BMSCs cells in biological characteristics. The growth of A549 cells have an obviously inhibition and the bystander effect is outstanding in vitro after co-culture and this experiment lays solid foundation for the future research.
PMCID: PMC4211835  PMID: 25356185
Lung cancer; BMSCs; HSV1-tk; co-culture; bystander effect
25.  Transcriptome Analysis of Indole-3-Butyric Acid-Induced Adventitious Root Formation in Nodal Cuttings of Camellia sinensis (L.) 
PLoS ONE  2014;9(9):e107201.
Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties.
PMCID: PMC4162609  PMID: 25216187

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