The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.
Background: To explore any association between the timing of the initiation of sexual activity and sexual behaviors and risks among university students in China.
Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells. In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.
BackgroundMen who have sex with men (MSM) have become one of high-risk population for human immunodeficiency virus (HIV) infection, due to their multiple sex partners and unprotected anal intercourse. Promoting HIV testing is an effective strategy for the prevention and control of HIV infection. We assessed the factors associated with a prior HIV testing history, which could provide guidance for implementation of future HIV intervention programs.MethodsA cross-sectional study was conducted in three cities of Zhejiang Province, namely, Hangzhou, Ningbo and Wenzhou, using respondent-driven sampling, between December 2013 and June 2014. A face-to-face questionnaire survey was employed to collect relevant information about HIV testing. Univariate and multivariate logistic regression analyses were used to identify the factors associated with a prior HIV testing history.ResultsThe adjusted rate of prior HIV testing among MSM in Zhejiang Province was 55.9 %. The adjusted rates of HIV and syphilis infections among MSM in Zhejiang Province were 14.0 % and 11.4 %, respectively. A weighted multivariate analysis showed that MSM of older age were more likely to be tested, as were MSM with higher level of education, self-reported homosexuality and a higher frequency of receiving AIDS/sexually transmitted infections educational intervention in the past year. MSM with suicidal inclination and self-perceived lower possibility of HIV infection were less likely to report ever having undergone an HIV test.ConclusionsThe prevalence of prior HIV testing among MSM in Zhejiang Province, China is low. Effective and more frequent interventional measures should be adopted to improve risk awareness and psychosocial support for younger, less educated MSM, and to encourage more MSM to undergo HIV testing.
ObjectiveThe goal of this study was to understand the knowledge about AIDS, identify the correlates and determine the prevalence of HIV infection, syphilis, HCV among migrant workers in Zhejiang, China.MethodsA cross-sectional study using face-to-face anonymous questionnaire interviews was conducted and blood samples were collected for HIV, syphilis and Hepatitis C infection screening.Results17,377 (92.8%) of 18,730 migrant workers approached were interviewed. Among 17,377 participants, the HIV/AIDS knowledge rate was 66.2%. A total of 12,694 (73%) of the participants reported having ever had sexual intercourse, with 30.1% of single participants reporting having had sexual intercourse. Among those respondents with sexual experiences, 7.5% admitted they had two or more sexual partners and 4.9% reported having had sex with casual (unpaid) partners in the previous 12 months, whilst 3.7% had paid for sex. More than half of those who had paid for sex (59.4%) had not used a condom every time in their sexual acts with the sex workers. Multiple logistic regression analysis indicated that high risk sexual behavior (defined as sex with a casual or commercial sex partner without using a condom consistently) was associated with being divorced or widowed (P<0.05 for single); male gender; shorter duration of stay in Zhejiang; working in factory, market or domestic service (P<0.05 for odd job); having a province of origin inside Zhejiang; and drug use. The prevalence of HIV and HCV infections were 0.02% (95% CI: 0.01%–0.06%) and 0.40% (95%CI: 0.31%–0.51%), respectively. The prevalence of syphilis among those who were sexually active was 0.55% (95% CI: 0.43%–0.70%). Risk factors for syphilis included shorter duration of stay in Zhejiang, ethnic minority status, being divorced or widowed and having had multiple sex partners.ConclusionsMuch greater efforts are needed to promote safer sex, and programs for the control of syphilis need to be tailored for migrant workers in China.
BackgroundHighly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART.MethodsThree cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression.Results3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6–28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province.ConclusionsVirologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.
Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.
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