[Show abstract][Hide abstract] ABSTRACT: Human bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated.
[Show abstract][Hide abstract] ABSTRACT: A simple technique for the identification of common genotypes of the hepatitis B virus (HBV) remains to be identified. The present study was conducted to establish such a methodology. Four plasmids of genotypes A‑D and 123 clinical serum specimens of HBV‑infected patients were genotyped. HBV genotypes would be detected successfully when the HBV genotype reached a viral load of 1 x 103 copies/ml or the BC genotype mixed samples reached a 5% level. The lower limit of detection of HBV DNA in serum specimens was determined to be 2.14x102 IU/ml. The assay sensitivity and specificity were 100% and the consistency was demonstrated to reach as high as 90.24 and 100% compared with that of the DNA sequencing and cloning. The frequencies of the genotypes B, C, BC, BD and BCD were found to be 65.0, 23.6, 7.3, 3.3 and 0.8%, respectively. The accuracy of detection of the mixed infections was also higher using the rapid and simple SNaPshot method compared with that achieved with the DNA sequencing methods. The results of the present study indicated that the SNaPshot technique accurately distinguishes the HBV genotypes A‑D and is able to be readily applied as a monitoring tool in HBV prognosis and treatment.
Molecular Medicine Reports 07/2014; · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: RAB GTPase 5A (RAB5A), a member of the Rab subfamily of small GTPases, acts as an oncogene and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Recently, it has been reported that the Rab5a gene is involved in the progression of cancer. Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers, and it is usually associated with persistent hepatitis B virus (HBV) infections. Emerging evidence suggests that HBV alters microRNA (miRNA) expression profiles, but the mechanisms underlying this process have not yet been fully elucidated. Here, we examine how HBV affects the production of miR-101-1, which has been shown to be downregulated in HCC. We found that HBV could repress miR-101-3p by inhibiting its promoter activity. Downregulation of miR-101-3p promoted cancer cell growth and migration, and a specific miR-101-3p inhibitor was able to enhance proliferation and migration. Moreover, we identified Rab5a was one of the target genes of miR-101-3p in HBV-related HCC. Forced expression of miR-101-3p in liver cell lines resulted in a marked reduction of the expression of Rab5a at both the mRNA and protein level by directly targeting the 3'untranslated region of Rab5a. Overexpression of Rab5a resulted in a reversal of the suppression of proliferation and migration of SMMC-7721 cells mediated by miR-101-3p. Taken together, our data show that HBV can downregulate miR-101-3p expression by inhibiting its promoter activity and that downregulation of miR-101-3p promotes HCC cell proliferation and migration by targeting Rab5a. This provides new insights into the mechanisms of HBV-related HCC pathogenesis.
Archives of Virology 05/2014; · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis B virus (HBV) infection is a worldwide problem and HBV reactivation following anticancer chemotherapy has become an emerging clinical challenge. However, the mechanisms of HBV reactivation following chemotherapy remain unclear. Epirubicin is an anthracycline drug used in chemotherapy to treat numerous types of malignancy, including breast cancer, acute leukemia, malignant lymphoma, lung cancer, ovarian cancer and stomach cancer. Epirubicin acts by intercalating DNA strands and inhibiting DNA and RNA synthesis. In this study, it was demonstrated that epirubicin directly upregulated the levels of in vitro HBV replication in a concentration‑dependent manner. Exposure to epirubicin for 24 h induced >11- and 6-fold increases in the levels of intracellular and secreted HBV DNA, respectively. In concordance with the elevated levels of HBV DNA, the expression levels of HBV pregenomic RNA, intracellular HBV surface and HBV core antigens, and secreted HBV e antigen were significantly increased by treatment with 0.5 µM epirubicin. Notably, epirubicin promoted cellular excretion of HBV nucleocapsids, which are closely associated with the pathological effects of HBV, including acute liver failure. In conclusion, epirubicin exhibited a direct stimulatory effect on HBV replication and this may be a novel mechanism of HBV reactivation following cytotoxic anticancer chemotherapy.
Molecular Medicine Reports 04/2014; 9(4):1345-50. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MicroRNA-101(miR-101) has been shown to be down-regulated in hepatocellular carcinoma (HCC). The hepatitis B virus (HBV) is a major risk factor in the development and progression of HCC. However, the correlation between HBV and miR-101 has not yet been fully elucidated. In this study, we reported that HBV could repress miR-101-3p by inhibiting its promoter activity and identified the potential effects of miR-101-3p on some important biological properties of HCC cells by targeting Rap1b. Dual-luciferase reporter assays showed that HBV down-regulated miR-101-3p by inhibiting its promoter activity. Down-regulation of miR-101-3p promoted cell proliferation, migration, and reduced apoptosis, and resulted in up-regulation of Rap1b, while overexpression of miR-101-3p inhibited these processes. Moreover, overexpression of Rap1b was able to reverse the suppressed cell proliferation and migration mediated by miR-101-3p. Our data showed that HBV down-regulated miR-101-3p expression by inhibiting its promoter activity, which resulted in up-regulation of Rap1b, and down-regulation of miR-101-3p or up-regulation of Rap1b promoted proliferation and migration of HCC cells. This provides a new understanding of the mechanism of HBV-related HCC pathogenesis and the potential application of miR-101-3p in cancer therapy.
Biochemistry and Cell Biology 04/2014; 92(2):152-62. · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence showed that microRNAs are involved in development and progression of multiple tumors. Recent studies have found that miR-181a were dysregulated in several types of cancers, however, the function of miR-181a in hepatocellular carcinoma (HCC) remains unclear. In this study we assessed the potential association between miR-181a, HBV and HCC.
The expression of miR-181a in HBV-expressing cells was determined by using qRT-PCR. Dual-Luciferase reporter Assay, qRT-PCR and western blot were performed to investigate the target genes of miR-181a. The effects of miR-181a on HCC proliferation were analyzed by MTS and colony formation assay. Tumor growth assay was used to analyze the effect of miR-181a on tumor formation.
HBV up-regulated miR-181a expression by enhancing its promoter activity. Overexpression of miR-181a in hepatoma cells promoted cell growth in vitro and tumor formation in vivo. Conversely, inhibition of miR-181a suppressed the proliferation of HBV-expressing cells. Mechanism investigation revealed that miR-181a inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3[prime]UTR. Moreover, E2F5 inhibition induced cell growth and rescued the suppressive effect of miR-181a inhibitor on the proliferation of SMMC-7721 cells. Interestingly, we also discovered that HBV could down-regulate E2F5 expression.
Those results strongly suggested that HBV down-regulated E2F5 expression, in part, by up-regulating the expression of miR-181a. Up-regulation of miR-181a by HBV in hepatoma cells may contribute to the progression of HCC possibly by targeting E2F5, suggesting miR-181a plays important role in HCC development.
BMC Cancer 02/2014; 14(1):97. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China.
A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors.
Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP.
Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.
PLoS ONE 01/2014; 9(1):e86200. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nearly ten randomized controlled trials (RCTs) of pre-exposure prophylaxis (PrEP) have been completed or are ongoing worldwide to evaluate the effectiveness of PrEP in HIV transmission among HIV-uninfected high risk populations. The purpose of this study was to evaluate the role of PrEP to prevent HIV transmission through a Mata-analysis.
A comprehensive computerized literature search was carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wan Fang, CNKI and related websites to collect relevant articles (from their establishment date to August 30, 2013). The search terms were "pre-exposure prophylaxis", "high risk population", "HIV infection", "reduction", "relative risk" and "efficacy". We included any RCT assessing PrEP for the prevention of HIV infection in high risk populations. Interventions of the studies were continuously daily or intermittent doses of single or compound antiretrovirals (ARVs) before HIV exposure or during HIV exposure. A meta-analysis was conducted using Stata 10.0. A random-effects method was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI) for all studies included.
Seven RCTs involving 14,804 individuals in high risk populations were eligible for this study. The number of subjects in the experimental groups was 8,195, with HIV infection rate of 2.03%. The number of subjects in the control groups was 6,609, with HIV infection rate of 4.07%. The pooled RR was 0.53 (95% CI = 0.40∼0.71, P<0.001). The re-analyzed pooled RR were 0.61 (95% CI = 0.48∼0.77, P<0.001), 0.49 (95% CI = 0.38∼0.63, P<0.001), respectively, by excluding the largest study or two studies without statistical significance. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 1,022.
These results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.
PLoS ONE 01/2014; 9(2):e87674. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and children under five years of age. The novel genotype ON1 has a 72-nucleotide duplication, which is the largest duplicated genome portion of RSV. Whether the ON1 genotype will follow the pattern of the BA genotype, which has a 60-nucleotide duplication, and become the predominant RSV-A strain is a global concern. To obtain information regarding the prevalence of the ON1 genotype in Chongqing in Southwestern China, we examined the circulation pattern of RSV-A identified over four consecutive years (June 2009 to August 2013). In this study, 312 (12%) RSV-A strains were isolated from 2601 nasopharyngeal aspirates, and partial G gene was sequenced successfully in 250 isolates. Of the sequenced Chongqing RSV-A isolates, 237 (94.8%) strains were the NA1 genotype, 4 (1.6%) strains were the NA3 genotype, 4 (1.6%) strains were the NA4 genotype, 1 (0.4%) strain was the GA1 genotype, and 4 (1.6%) strains were identified as the ON1 genotype. Analysis of the distribution, phylogeny, and evolution of the ON1 strains that were collected globally until December 2013 revealed that the ON1 genotype has rapidly disseminated across the world under positive selection pressures. Future studies will determine whether this new genotype will continue to spread and become the dominant strain of RSV-A worldwide. These findings may contribute to the understanding of RSV evolution and to the potential development of a vaccine against RSV.
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) causes respiratory tract infection, particularly acute lower respiratory tract infection (ALRTI), in early childhood. The RSV fusion protein (F protein) is an important surface protein, and it is the target of both cytotoxic T lymphocytes (CTL) and neutralizing antibodies; thus, it may be useful as a candidate for vaccine research. This study investigated the genetic diversity of the RSV F protein. To this end, a total of 1800 nasopharyngeal aspirates from hospitalized children with ALRTI were collected for virus isolation between June 2009 and March 2012. There were 333 RSV-positive cases (277 cases of RSV A, 55 of RSV B, and 1 with both RSV A and RSV B), accounting for 18.5 % of the total cases. Next, 130 clinical strains (107 of RSV A, 23 of RSV B) were selected for F gene sequencing. Phylogenetic analysis revealed that the F gene sequence is highly conserved, with significant amino acid changes at residues 16, 25, 45, 102, 122, 124, 209, and 447. Mutations in human histocompatibility leukocyte antigen (HLA)-restricted CTL epitopes were also observed. Variations in RSV A F protein at the palivizumab binding site 276 (N→S) increased between 2009 and 2012 and became predominant. Western blot analysis and microneutralization data showed a substitution at residue 276 (N→S) in RSV A that did not cause resistance to palivizumab. In conclusion, the RSV F gene is geographically and temporally conserved, but limited genetic variations were still observed. These data could be helpful for the development of vaccines against RSV infection.
Archives of Virology 12/2013; · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The risk of cardiovascular disease is increased by up to 33 to 50× in chronic inflammatory states and convention doses of statins may not provide the same cardiovascular protection as in noninflamed patients. This study investigated whether the increase in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-R)-mediated cholesterol synthesis observed under inflammatory stress was resistant to the action of statins and if so, whether this was because of interference with the sterol regulatory element binding protein cleavage-activating protein pathway.
Inflammatory stress was induced by adding cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and lipopolysaccharides to vascular smooth muscle cells in vitro and by subcutaneous casein injection in apolipoprotein E/scavenger receptors class A/CD36 triple knockout mice in vivo. Inflammatory stress exacerbated cholesterol ester accumulation and was accompanied in vitro and in vivo by increased HMGCoA-R mRNA and protein expression mediated via activation of the sterol regulatory element binding protein cleavage-activating protein/sterol regulatory element binding protein-2 pathway. Atorvastatin reduced HMGCoA-R enzymatic activity and intracellular cholesterol synthesis in vitro. However, inflammatory stress weakened these suppressive effects. Atorvastatin at concentrations of 16 μmol/L inhibited HMGCoA-R activity by 50% in vascular smooth muscle cells, but the same concentration resulted in only 30% of HMGCoA-R activity in vascular smooth muscle cells in the presence of interleukin-1β. Knocking down sterol regulatory element binding protein cleavage-activating protein prevented statin resistance induced by interleukin-1β, and overexpression of sterol regulatory element binding protein cleavage-activating protein induced statin resistance even without inflammatory stress. In vivo, the amount of atorvastatin required to lower serum cholesterol and decrease aortic lipid accumulation rose from 2 to 10 mg/kg per day in the presence of inflammatory stress.
Increased cholesterol synthesis mediated by HMGCoA-R under inflammatory stress may be one of the mechanisms for intracellular lipid accumulation and statin resistance.
Arteriosclerosis Thrombosis and Vascular Biology 11/2013; · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae SPD0280 is a hypothetical protein that has been putatively identified as a transcriptional regulator. However, it has very low sequence identity to other well characterized transcriptional regulators. Determination of the three-dimensional structure may provide information for the characterization of proteins; therefore, it was decided to use X-ray diffraction analysis to learn more about this protein. Here, the expression, purification, crystallization and preliminary crystallographic analysis of SPD0280 from S. pneumoniae are reported. The crystals belonged to space group P212121, with unit-cell parameters a = 45.886, b = 66.785, c = 150.050 Å, and diffracted to a resolution of 2.5 Å. The crystals are likely to contain one molecule in the asymmetric unit, with a VM value of 2.06 Å(3) Da(-1).
Acta Crystallographica Section F Structural Biology and Crystallization Communications 11/2013; 69(Pt 11):1246-8. · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) DNA replication takes place in the viral capsid that consists of 180 or 240 copies of HBV capsid (HBc or core) protein. The monomeric core protein contains an apical loop region that forms the spikes on the surface of viral capsid upon core dimerization and capsid assembly. To investigate the impact on HBV DNA replication through gene engineering at the spike of HBV capsid. plasmids expressing engineered HBc with linker-fused enhanced green fluorescent protein (EGFP) or shortened EGFP insertion at the spike region were constructed by Restriction Digestion and Ligation-independent Cloning (RLIC). The wildtype or mutant HBc construct was cotransfected with HBV1.1c(-), a plasmid containing 1.1 unit-length HBV genome with deficiency in HBc expression, into HEK293 cells, respectively. GFP signal was observed through a fluorescence microscope and HBV DNA replicative intermediates were assayed by Southern blotting to determine the expression and functions of different recombinants. Our results demonstrated that the RLIC method was effective to generate deletion or insertion in the apical loop region of HBc. Both HBc-EGFP recombinants with different linkers produced green fluorescence but with different subcellular distribution pattern. However, HBV DNA replication was not detected with the trans-complementation of these two HBc recombinants. In addition, other recombinants including the one only with the deletion of aa79-80 failed to support HBV replication. Taken together, our results suggest that RLIC is a robust method which can be broadly applied in gene engineering; different peptide linkers may have different influences on the functions of an engineered fusion protein; and HBc aa79-80 play a critical role for HBc to support HBV DNA replication.
Sheng wu gong cheng xue bao = Chinese journal of biotechnology 11/2013; 29(11):1663-71.
[Show abstract][Hide abstract] ABSTRACT: Lipocalin α1-microglobulin (α1M) is a conserved glycoprotein present in plasma and in the interstitial fluids of all tissues. α1M is linked to a heterogeneous yellow-brown chromophore of unknown structure, and interacts with several target proteins, including α1-inhibitor-3, fibronectin, prothrombin and albumin. To date, there is little knowledge about the interaction sites between α1M and its partners. Here, we report the crystal structure of the human α1M. Due to the crystallization occurring in a low ionic strength solution, the unidentified chromophore with heavy electron density is observed at a hydrophobic inner tube of α1M. In addition, two conserved surface regions of α1M are proposed as putative protein-protein interface sites. Further study is needed to unravel the detailed information about the interaction between α1M and its partners.
Biochemical and Biophysical Research Communications 09/2013; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enteric viruses are a major cause of diarrhea in children, especially those <5 years old. Identifying the viral agents is critical to the development of effective preventive measures. This study aimed to determine the prevalence of common enteric viruses in children <5 years old presented with diarrhea to the Children's Hospital of Chongqing Medical University.
Five hundred fecal samples were collected between August and November 2010 from children <5 years of age who presented with acute diarrhea at the Children's Hospital of Chongqing Medical University. All samples were tested for rotaviruses A, B, and C, noroviruses GI and GII, adenovirus, sapovirus, and astrovirus using enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction (RT-PCR), or PCR. Partial sequences of norovirus, sapovirus, adenovirus, and astrovirus were phylogenetically analyzed to determine the genotype.
Enteric viruses were detected in 302 of the 500 children who presented with acute diarrhea (277/477; 58.07%) and persistent diarrhea (5/23; 21.74%). In 277 samples from children with acute diarrhea in whom at least one viral agent was found, rotavirus A was the most frequent virus identified (132 cases; 27.67%), followed by norovirus GII in 130 cases (27.25%), adenovirus in 30 cases (6.29%), sapovirus in 9 cases (1.89%) and astrovirus in one case (0.21%). Twenty-two of the norovirus GII-positive cases were randomly selected for genotyping. GII/4 was the predominant strain, followed by GII/6, GII/2, GII/3, and GII/7. Sapovirus was classified into four genotypes: GI/1 was predominant, followed by GI/2, GII/1, and GIV. The predominant adenovirus was type 41. Mixed infections were found in 25 cases, all of which presented with acute diarrhea (25/477; 5.24%). Viruses were positive in 5/23 (21.74%) cases with persistent diarrhea. Neither rotavirus B, rotavirus C, nor norovirus GI were found in any of the samples.
Enteric viruses are a major cause of diarrhea in children <5 years old in Chongqing. Rotavirus A is the most common etiological agent, follow by norovirus.
[Show abstract][Hide abstract] ABSTRACT: The available evidence suggests that HBV proteins play an important role in the development of hepatocellular carcinoma (HCC). RhoC, a member of the Rho subfamily of the Ras superfamily of homologous genes, had been implicated in tumorigenesis and tumor progression. In a previous study, we demonstrated that HBx and HBs could up-regulate RhoC expression by enhancing its promoter activity. However, the specific mechanisms remain unclear. Here, we demonstrate that overexpression of Ets-1 results in upregulation of RhoC promoter activity and mRNA and protein levels. Expression of transcription factor Ets-1 was significantly higher in HepG2.2.15 cells than that in HepG2 cells. Meanwhile, infection of HepG2 cells with an HBV-adenovirus recombinant virus led to up-regulation of Ets-1. Of the four HBV proteins, HBx and HBs, could increase expression of Ets-1, which consequently contributed to the upregulation of RhoC. These findings might provide a novel insight into HBV-induced HCC metastasis.
Archives of Virology 03/2013; · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DnaJ, cooperating with DnaK and GrpE, promotes the folding of unfolded hydrophobic polypeptides, dissociates protein complexes and translocates protein across membranes. Additionally, DnaJ from Streptococcus pneumoniae (SpDnaJ) is involved in the infectious disease process and is being developed as a potential vaccine to prevent bacterial infection. Here the expression, purification, crystallization and preliminary crystallographic analysis of SpDnaJ are reported. The crystals belong to space groups I222 or I212121 and the diffraction resolution is 3.0 Å with unit-cell parameters a = 47.68, b = 104.45, c = 234.57 Å. The crystal most likely contains one molecule in the asymmetric unit, with a VM value of 3.24 Å(3) Da(-1) and a solvent content of 62.1%.
Acta Crystallographica Section F Structural Biology and Crystallization Communications 03/2013; 69(Pt 3):267-9. · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Pre-exposure prophylaxis (PrEP), as demonstrated in recently published clinical trials, is one promising approach for controlling the emerging epidemic among men who have sex with men (MSM). We evaluated the attitudes towards use of PrEP among MSM in western China. A total of 1402 participants completed a self-administered questionnaire. Overall, 22% of the participants reported that they had heard of PrEP, <1% had ever used medicine to prevent HIV, and 64% reported that they were absolutely willing to use PrEP if it were proven to be safe and effective. The predictors of willingness to use PrEP included lower education, moderate income compared with the lowest income, never or rarely finding sexual partners through the Internet in the past 6 months, sexually transmitted infection (STI) history, more knowledge of AIDS, worrying about HIV as a threat to themselves and their family, having previously heard of PrEP, and believing that PrEP was effective in preventing HIV. This study demonstrates that Chinese MSM have moderate awareness of PrEP and a high interest in using it.
AIDS patient care and STDs 02/2013; · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The yeast silent information regulator 2 (SIR2) is a histone deacetylase that utilizes NAD(+) as a cofactor for its functions. In mammals, SIR2 is represented by seven homologues (SIRT1-7). Sirtuin 1 (SIRT1), the prototypical member of this family, has been implicated in telomere maintenance and the growth of hepatocellular carcinoma (HCC). Nevertheless, the role of other sirtuins in the pathogenesis of HCC remains elusive. RESULTS: We found that Sirtuin 2 (SIRT2), another member of sirtuin family, also contributes to cell motility and invasiveness of HCC. SIRT2 is up-regulated in HCC cell lines and in a subset of human HCC tissues (23/45). Up-regulations of SIRT2 in primary HCC tumors were significantly correlated with the presence of microscopic vascular invasion (p=0.001), a more advanced tumor stage (p=0.004) and shorter overall survival (p=0.0499). Functional studies by shRNA-mediated suppression of SIRT2 expression in HCC cell lines revealed significant inhibition of motility and invasiveness. Depletion of SIRT2 also led to the regression of epithelial-mesenchymal transition (EMT) phenotypes, whereas the ectopic expression of SIRT2 in the immortalized hepatocyte cell line L02 enhanced the expression of EMT markers, and promoted cell motility and invasiveness. Mechanistic studies revealed that SIRT2 regulates the deacetylation and activation of Akt, which subsequently impinges on the GSK-3β/β-catenin signaling pathway to regulate EMT. Concordantly, we showed that there is a positive correlation between the level of SIRT2 and β-catenin in human HCC. CONCLUSIONS: Our findings have uncovered a novel role of SIRT2 in HCC metastasis, and provide a rationale to explore the use of sirtuin inhibitors in HCC therapy. (HEPATOLOGY 2013.).
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP.
Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP.
Only 10 participants (2.8%) reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6%) reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78, <1000 RMB vs. ≥1000 RMB, 95% confidence interval: 1.36-5.69), perceived likelihood of contracting HIV from HIV-positive partner (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12-6.19), and worrying about being discriminated against by others due to oral PrEP use (adjusted odds ratio = 9.43, No vs. Yes, 95% confidence interval: 3.78-23.50).
Our results showed HIV-negative partners in HIV-serodiscordant heterosexual couples in China had low awareness of oral PrEP but high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be taken into consideration in future PrEP prevention strategy. In addition, efforts should be made to reduce stigma attached to oral PrEP use, which may increase its acceptability among potential users.
PLoS ONE 01/2013; 8(7):e67392. · 3.53 Impact Factor