MicroRNA-21 promotes survival but not functional maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs)

published_or_final_versionThe 16th Medical Resarch Conference (MRC), The University of Hong Kong, Hong Kong, China, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 35, abstract no. 5

MiR-29b negatively regulates cell cycle activity of human embryonic stem cell-derived cardiomyocytes

published_or_final_versionThe 16th Medical Resarch Conference (MRC), The University of Hong Kong, Hong Kong, China, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 50, abstract no. 7

Manipulations of microRNA in human pluripotent stem cells and their derivatives

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells can self-renew while maintaining their pluripotency to differentiate into virtually all cell types. In addition to their potential for regenerative medicine, hESCs and iPSCs can also serve as excellent in vitro models for the study of human organogenesis and disease models, as well as drug toxicity screening. MicroRNAs (miRNAs) are nonencoding RNAs of ∼22 nucleotides that function as negative transcriptional regulators via degradation or inhibition by RNA interference (RNAi). MiRNAs play essential roles in developmental pathways. This chapter provides a description of how miRNAs can be introduced into hESCs/iPSCs or their derivatives for experiments via lentivirus-mediated gene transfer. © 2011 Springer Science+Business Media, LLC.link_to_subscribed_fulltex

MicroRNA and cell cycle of embryonic stem (ES) and induced pluripotent stem (iPS) cells: Insights for eliminating tumorgenicity

Conference Theme: Is Aging a Disease

Functional consequences of overexpressing the gap junction Cx43 in the cardiogenic potential of pluripotent human embryonic stem cells

Gap junctions, encoded by the connexin (Cx) multi-gene family, couple adjacent cells and underlie cell-cell communications. Previous mouse studies suggest that Cxs play an important role in development but their role in human cardiogenesis is undefined. Human embryonic stem cells (hESC) provide a unique model for studying human differentiation. Lentivirus-mediated stable overexpression of Cx43 in hESC (Cx43-hESC) did not affect colony morphology, karyotype and expression of pluripotency genes such as Oct4 but completely suppressed the formation of spontaneously beating, cardiomyocyte-containing clusters in embryoid bodies (EBs). Unlike control hEBs, the transcripts of several mesodermal markers (kallikrein, δ-globin, and CMP), ventricular myosin light chain and cardiac troponin I were absent or delayed. Transcriptomic and pathway analyses showed that 194 genes crucial for movement, growth, differentiation and maintenance were differentially expressed in Cx43-hESC. We conclude that Cx43 mediates the expression of an array of genes involved in human cardiogenesis, in addition to intercellular communication. © 2008 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Distinct roles of microRNA-1 and -499 in ventricular specification and maturation of human embryonic stem cells

Conference Theme: Is Aging a Disease?The 5th International Symposium on Health Aging, Hong Kong, 6-7 March 2010

ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy

Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011. For validation, a group of 20 patients was available. Score selection method using proportional hazard analysis and leave-one-out cross-validation were performed to identify markers associated with outcome. The SNPs rs1799793 and rs13181 were associated with survival and the same SNPs and in addition rs17655 with freedom from loco-regional relapse (ffLRR) in the trainings datasets from all patients. The homozygote major rs1799793 genotype at the ERCC2 gene was associated with better (Hazard ratio (HR): 0.418 (0.234–0.744), p = 0.003) and the homozygote minor rs13181 genotype at ERCC2 with worse survival (HR: 2.074, 95% CI (1.177–3.658), p = 0.017) in comparison to the other genotypes. At the ffLRR endpoint, rs1799793 and rs13181 had comparable prognostic value. The rs1799793 and rs13181 genotypes passed the leave-one-out cross-validation procedure and associated with survival and ffLRR in patients with LadHnSCC treated with definitive radiochemotherapy. While findings were confirmed in a small validation dataset, further validation is underway within a prospective biomarker study of the DKTK

Complexities of Short-Term Mobility for Sex Work and Migration among Sex Workers: Violence and Sexual Risks, Barriers to Care, and Enhanced Social and Economic Opportunities

Despite research on the health and safety of mobile and migrant populations in the formal and informal sectors globally, limited information is available regarding the working conditions, health, and safety of sex workers who engage in short-term mobility and migration. The objective of this study was to longitudinally examine work environment, health, and safety experiences linked to short-term mobility/migration (i.e., worked or lived in another city, province, or country) among sex workers in Vancouver, Canada, over a 2.5-year study period (2010–2012). We examined longitudinal correlates of short-term mobility/migration (i.e., worked or lived in another city, province, or country over the 3-year follow-up period) among 646 street and off-street sex workers in a longitudinal community-based study (AESHA). Of 646 sex workers, 10.84 % (n = 70) worked or lived in another city, province, or country during the study. In a multivariate generalized estimating equations (GEE) model, short-term mobility/migration was independently correlated with older age (adjusted odds ratio (AOR) 0.95, 95 % confidence interval (CI) 0.92–0.98), soliciting clients in indoor (in-call) establishments (AOR 2.25, 95 % CI 1.27–3.96), intimate partner condom refusal (AOR 3.00, 1.02–8.84), and barriers to health care (AOR 1.77, 95 % CI 1.08–2.89). In a second multivariate GEE model, short-term mobility for sex work (i.e., worked in another city, province, or country) was correlated with client physical/sexual violence (AOR 1.92, 95 % CI 1.02–3.61). In this study, mobile/migrant sex workers were more likely to be younger, work in indoor sex work establishments, and earn higher income, suggesting that short-term mobility for sex work and migration increase social and economic opportunities. However, mobility and migration also correlated with reduced control over sexual negotiation with intimate partners and reduced health care access, and mobility for sex work was associated with enhanced workplace sexual/physical violence, suggesting that mobility/migration may confer risks through less control over work environment and isolation from health services. Structural and community-led interventions, including policy support to allow for more formal organizing of sex work collectives and access to workplace safety standards, remain critical to supporting health, safety, and access to care for mobile and migrant sex workers