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Wang C.C.,Chinese University of Hong Kong | Wang C.C.,Li Ka Shing Institute of Health science | Billett E.,Nottingham Trent University | Borchert A.,Charite - Medical University of Berlin | And 2 more authors.
Cellular and Molecular Life Sciences | Year: 2013

Monoamine oxidases (MAOs) are flavoproteins of the outer mitochondrial membrane that catalyze the oxidative deamination of biogenic and xenobiotic amines. In mammals there are two isoforms (MAO-A and MAO-B) that can be distinguished on the basis of their substrate specificity and their sensitivity towards specific inhibitors. Both isoforms are expressed in most tissues, but their expression in the central nervous system and their ability to metabolize monoaminergic neurotransmitters have focused MAO research on the functionality of the mature brain. MAO activities have been related to neurodegenerative diseases as well as to neurological and psychiatric disorders. More recently evidence has been accumulating indicating that MAO isoforms are expressed not only in adult mammals, but also before birth, and that defective MAO expression induces developmental abnormalities in particular of the brain. This review is aimed at summarizing and critically evaluating the new findings on the developmental functions of MAO isoforms during embryogenesis. © 2012 Springer Basel AG. Source

Huang B.,The New School | Li G.,Li Ka Shing Institute of Health science | Li G.,Chinese University of Hong Kong | Jiang X.H.,The New School | Jiang X.H.,Chinese University of Hong Kong
Stem Cell Research and Therapy | Year: 2015

Mesenchymal stem cells (MSCs) hold great promise for therapeutic use in regenerative medicine and tissue engineering. A detailed understanding of the molecular processes governing MSC fate determination will be instrumental in the application of MSCs. Much progress has been made in recent years in defining the epigenetic events that control the differentiation of MSCs into different lineages. A complex network of transcription factors and histone modifiers, in concert with specific transcriptional co-activators and co-repressors, activates or represses MSC differentiation. In this review, we summarize recent progress in determining the effects of histone-modifying enzymes on the multilineage differentiation of MSCs. In addition, we propose that the manipulation of histone signatures associated with lineage-specific differentiation by small molecules has immense potential for the advancement of MSC-based regenerative medicine. © 2015 Huang et al.; licensee BioMed Central. Source

Tsang W.P.,Li Ka Shing Institute of Health science | Ng E.K.O.,Institute of Digestive Disease | Ng S.S.M.,Chinese University of Hong Kong | Jin H.,Institute of Digestive Disease | And 3 more authors.
Carcinogenesis | Year: 2010

H19 is an imprinted oncofetal non-coding RNA recently shown to be the precursor of miR-675. The pathophysiological roles of H19 and its mature product miR-675 to carcinogenesis have, however, not been defined. By quantitative reverse transcription-polymerase chain reaction, both H19 and miR-675 were found to be upregulated in human colon cancer cell lines and primary human colorectal cancer (CRC) tissues compared with adjacent noncancerous tissues. Subsequently, the tumor suppressor retinoblastoma (RB) was confirmed to be a direct target of miR-675 as the microRNA suppressed the activity of the luciferase reporter carrying the 3′-untranslated region of RB messenger RNA that contains the miR-675-binding site. Suppression of miR-675 by transfection with anti-miR-675 increased RB expression and at the same time, decreased cell growth and soft agar colony formation in human colon cancer cells. Reciprocally, enhanced miR-675 expression by transfection with miR-675 precursor decreased RB expression, increased tumor cell growth and soft agar colony formation. Moreover, the inverse relationship between the expressions of RB and H19/miR-675 was also revealed in human CRC tissues and colon cancer cell lines. Our findings demonstrate that H19-derived miR-675, through downregulation of its target RB, regulates the CRC development and thus may serve as a potential target for CRC therapy. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. Source

Tsui N.B.Y.,Li Ka Shing Institute of Health science | Tsui N.B.Y.,Chinese University of Hong Kong | Lo Y.M.D.,Li Ka Shing Institute of Health science | Lo Y.M.D.,Chinese University of Hong Kong
Current Opinion in Hematology | Year: 2012

Purpose of Review: Noninvasive prenatal diagnosis can be achieved by analyzing cell-free fetal DNA in maternal plasma. The fact that circulating fetal DNA represents only a minor fraction of the DNA that is present in maternal plasma has presented analytical challenges for a number of applications. In this review, we discuss such challenges and how they have been resolved by recent developments in the field. Recent Findings: Digital molecular counting methods, such as digital PCR and massively parallel sequencing, have enabled high quantitative precision for maternal plasma DNA analysis. Noninvasive prenatal analysis of monogenic disease mutations has been achieved by identifying small quantitative differences between the mutant and wild-type alleles in maternal plasma. By measuring the small increment in the fractional concentrations of DNA derived from potentially aneuploid chromosomes in maternal plasma, fetal chromosomal aneuploidies have been detected with high diagnostic accuracies. Summary: Recently, advances in molecular technologies have enhanced the diagnostic applications of maternal plasma DNA analysis for noninvasive prenatal diagnosis. We foresee that this technology could play an increasingly important role in prenatal investigations. © 2012 Wolters Kluwer Health | Lippincott Williams and Wilkins. Source

Dennis Lo Y.,Li Ka Shing Institute of Health science | Dennis Lo Y.,Chinese University of Hong Kong | Chiu R.W.,Li Ka Shing Institute of Health science | Chiu R.W.,Chinese University of Hong Kong
Journal of Pathology | Year: 2011

Over the past 15 years there has been increasing interest in the biology and diagnostic applications of circulating DNA in the plasma of human subjects. In particular, DNA from a fetus, a tumour, a transplanted organ and injured tissues has been found in the plasma of pregnant women, cancer patients, transplant recipients and patients suffering from multiple pathologies, respectively. The advent of massively parallel sequencing has given us a quantitative and powerful tool for studying circulating DNA on a genome-wide level. Using this approach, fetal chromosomal aneuploidies can be robustly detected using maternal plasma. Furthermore, a genome-wide genetic map of a fetus can also be constructed using this approach. This method has also allowed one to identify tumour-associated chromosomal translocations, which can then be detected in plasma. The direct application of massively parallel sequencing to the serum of cancer patients has also allowed quantitative aberrations that are associated with malignancy to be detected in serum. The use of massively parallel sequencing on the plasma of transplantation recipients has opened up an approach for detecting rejection. The application of circulating DNA sequencing has also opened up a new method for elucidating the quantitative aberration of circulating DNA in many pathological conditions. Such developments would provide new modalities for molecular diagnostics and would improve our understanding of the biology of circulating nucleic acids. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source

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