Stephen Kwok-Wing Tsui

Publications of Stephen Kwok-Wing Tsui

• Interferons induce the expression of IFITM1 and IFITM3 and suppress the proliferation of rat neonatal cardiomyocytes.

  Authors: Samantha Lai-Yee Lau, Man-Leuk Yuen, Cecy Ying-Chuck Kou, Ka-Wing Au, Junwei Zhou, Stephen Kwok-Wing Tsui

  Journal of cellular biochemistry. 03/2012; 113(3):841-7.

  Cardiovascular diseases have been one of the leading killers among the human population worldwide. During the heart development, cardiomyocytes undergo a transition from hyperplastic to hypertrophicCardiovascular diseases have been one of the leading killers among the human population worldwide. During the heart development, cardiomyocytes undergo a transition from hyperplastic to hypertrophic growth with an unclear underlying mechanism. In this study, we aim to investigate how interferons differentially stimulate the interferon-inducible transmembrane (IFITM) family proteins and further be involved in the process of heart development. The expression levels of three IFITM family members, IFITM1, IFITM2, and IFITM3 were investigated during Sprague-Dawley rat myocardial development and differentiation of H9C2 cardiomyocytes. The effects of interferon-α, -β, and -γ on DNA synthesis in H9C2 cells were also characterized. Up-regulation of IFITM1 and IFITM3 were observed during the heart development of Sprague-Dawley rat and the differentiation of H9C2 cells. Moreover, interferon-α and -β induce the expression of IFITM3 while interferon-γ up-regulates IFITM1. Finally, interferon-α and -β were demonstrated to inhibit DNA synthesis during H9C2 cell differentiation. Our results indicated interferons are potentially involved in the differentiation and cell proliferation during heart development.

• F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis.

  Authors: Xiaofan Lu, Li Liu, Xu Zhang, Terrence Chi Kong Lau, Stephen Kwok Wing Tsui, Yuanxi Kang, Purong Zheng, Bojian Zheng, Gang Liu, Zhiwei Chen

  Antimicrobial agents and chemotherapy. 01/2012; 56(1):341-51.

  Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. WeNonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (+)-calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397-1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory-adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses by in vitro serial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI.

• Covariation of major and minor viral capsid proteins in norovirus genogroup II genotype 4 strains.

  Authors: Martin Chi-Wai Chan, Nelson Lee, Wing-Shan Ho, Carmen Oi-Kwan Law, Terrence Chi-Kong Lau, Stephen Kwok-Wing Tsui, Joseph Jao-Yiu Sung

  Journal of virology. 11/2011; 86(2):1227-32.

  We report sequence hypervariability in the viral protein 1 (VP1) interaction domain of VP2 in the norovirus (NoV) genogroup II genotype 4 (GII.4) lineage on 3 levels: (i) the global evolution ofWe report sequence hypervariability in the viral protein 1 (VP1) interaction domain of VP2 in the norovirus (NoV) genogroup II genotype 4 (GII.4) lineage on 3 levels: (i) the global evolution of pandemic/epidemic strains from the mid-1970s through post-2006, (ii) the local emergence of an epidemic strain, and (iii) an immunocompromised patient chronically shedding NoV. When a quantitative yeast two-hybrid assay was used, VP2 was found to interact with VP1 in a time-ordered, strain-dependent manner among 3 NoV GII.4 strains. Our findings suggest that VP1 and VP2 may covary in virus evolution and that sequence hypervariability of VP2 may be functionally driven. Further investigations are warranted.

• Transcriptional profiling of angiogenesis activities of calycosin in zebrafish.

  Authors: Shang Li, Shaoke Lou, Benson U Wang Lei, Ting-Fung Chan, Yiu Wa Kwan, Shun Wan Chan, George Pak Heng Leung, Stephen Kwok-Wing Tsui, Simon Ming Yuen Lee

  Molecular bioSystems. 09/2011; 7(11):3112-21.

  Angiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with the dysregulation of angiogenesis. The commonly used Chinese herbal medicineAngiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with the dysregulation of angiogenesis. The commonly used Chinese herbal medicine Radix Astragali (known as Huang qi in Chinese) is a potential candidate for treating this type of disease. Calycosin, a major isoflavonoid in Radix Astragali, was identified in our earlier study and shown to induce angiogenesis in human umbilical vein endothelial cells (HUVEC) in vitro and in zebrafish embryos in vivo. Using zebrafish as a testing model, we investigated the angiogenic effect of calycosin on the subintestinal vessels (SIVs) in zebrafish embryos. Our findings using transcriptional profiling by deep sequencing, and confirmed by quantitative real-time PCR (qPCR), demonstrate that calycosin modulated vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and ErbB signaling pathways. The inhibitory effects of calycosin-induced phenotypic responses by several pathway-specific inhibitors (VRI, SU5402, MEK1/2 Inhibitor, Wortmannin and LY294002) further identified the potential involvement of VEGF(R) and FGF(R) signaling pathways in the angiogenic activities of calycosin. We present a comprehensive framework of study using fluorescence microscopy, transcriptomics and qPCR to demonstrate the proangiogenic effects of calycosin in vivo. The data have elucidated the connection between morphological observations and genomic evidence, indicating the potential roles of several key signaling pathways in angiogenesis.

• Characterization of human FHL2 transcript variants and gene expression regulation in hepatocellular carcinoma.

  Authors: Chor-Fung Ng, Wayne Jun-Wei Zhou, Patrick Kwok-Shing Ng, Man-Shan Li, Yuen-Keng Ng, Paul Bo-San Lai, Stephen Kwok-Wing Tsui

  Gene. 07/2011; 481(1):41-7.

  The four-and-a-half LIM protein 2 (FHL2) was originally identified to be expressed abundantly in the heart, as well as in a wide range of tissues demonstrated in various studies. The human FHL2 geneThe four-and-a-half LIM protein 2 (FHL2) was originally identified to be expressed abundantly in the heart, as well as in a wide range of tissues demonstrated in various studies. The human FHL2 gene expresses different transcripts which are known to differ only in the 5'UTR region. However, little is known about the functional role of the different variants and the mechanism of gene regulation. In the present study, we characterized the different alternative spliced transcripts of FHL2 by in silico analysis and RT-PCR analysis. A novel transcript variant was identified. The FHL2 gene produces transcripts by different 5' exons, which may be responsible for tissue-specific regulation. To study the mechanism of FHL2 gene regulation, the potential promoter region was investigated. We have identified a functional promoter region upstream of the transcription start site. Deletion mutation analysis of 5' flanking region showed that the fragment from -138 to +292 bp have positive regulatory effect. We identified the binding sites of Pax-5/ZF5 in this region and found that Pax-5 and ZF5 expression in HCC samples had a significant positive correlation with FHL2 expression, suggesting a possible role for these transcription factors in the regulation of FHL2 expression.

• Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model.

  Authors: Kai Heng Lam, Deepa Alex, In Kei Lam, Stephen Kwok Wing Tsui, Zi Feng Yang, Simon Ming Yuen Lee

  Journal of cellular biochemistry. 07/2011; 112(11):3313-21.

  Traditional Chinese medicinal herbs are a rich source of compounds with reported anti-inflammatory and anti-carcinogenic effects. Growing evidence shows the codependence of chronic inflammation andTraditional Chinese medicinal herbs are a rich source of compounds with reported anti-inflammatory and anti-carcinogenic effects. Growing evidence shows the codependence of chronic inflammation and angiogenesis, and the potential benefits of targeting angiogenesis in the treatment of chronic inflammation and targeting inflammation in the treatment of diseases with impaired angiogenesis. We hypothesized that the anti-inflammatory activity of the natural compounds may owe at least some of its efficacy to their anti-angiogenic activity and hence we investigated the anti-angiogenic activity of these compounds in vivo in zebrafish embryos and in vitro in human umbilical vein endothelial cells (HUVECs). Nobiletin, a polymethoxylated flavonoid from citrus fruits, showed anti-angiogenic activity in both assays. Nobiletin inhibited the formation of intersegmental vessels (ISVs) in live transgenic zebrafish embryos expressing green fluorescent protein (GFP) in the vasculature. Cell cycle analysis of dissociated zebrafish embryo cells showed that nobiletin induced G0/G1 phase accumulation in a dose-dependent manner in GFP-positive endothelial cells. Nobiletin also dose-dependently induced VEGF-A mRNA expression. In HUVECs, nobiletin inhibited endothelial cell proliferation and, to a greater extent, tube formation in a dose-dependent manner. As in the in vivo study, nobiletin induced G0/G1 cell cycle arrest in HUVECs. However, this arrest was not accompanied by an increase in apoptosis, indicating a cytostatic effect of nobiletin. This study, for the first time, identifies nobiletin as having potent anti-angiogenic activity and suggests that nobiletin has a great potential for future research and development as a cytostatic anti-proliferative agent.

• FHL2 exhibits anti-proliferative and anti-apoptotic activities in liver cancer cells.

  Authors: Chor-Fung Ng, Patrick Kwok-Shing Ng, Vivian Wai-Yan Lui, Jialiang Li, Judy Yuet-Wa Chan, Kwok-Pui Fung, Yuen-Keng Ng, Paul Bo-San Lai, Stephen Kwok Wing Tsui

  Cancer letters. 03/2011; 304(2):97-106.

  FHL2 displays tumor promoting or tumor suppressing activities depending on the types of tumor cells. In this study, we demonstrated that FHL2 overexpression inhibits the proliferation of human HCCFHL2 displays tumor promoting or tumor suppressing activities depending on the types of tumor cells. In this study, we demonstrated that FHL2 overexpression inhibits the proliferation of human HCC cells Hep3B through cell cycle regulation by decreasing cyclin D1 expression while increasing the expressions of p21 and p27. FHL2 overexpression also inhibits migration and invasion of Hep3B cells through the regulation of epithelial-mesenchymal transition. Surprisingly, we also demonstrated an antiapoptotic function for FHL2 overexpression with increased resistance to doxorubicin-induced apoptosis, which indicates the separation of anti-proliferative and anti-apoptotic role of FHL2. Taken together, our results indicate FHL2 could exert anti-apoptotic effect independent of tumor growth suppression.

• Combined in vivo imaging and omics approaches reveal metabolism of icaritin and its glycosides in zebrafish larvae.

  Authors: Zhen Hua Li, Deepa Alex, Shiu On Siu, Ivan Keung Chu, Joerg Renn, Christoph Winkler, Shaoke Lou, Stephen Kwok-Wing Tsui, Hai Yu Zhao, Wendy Ru Yan, Gail B Mahady, Guo Hui Li, Yiu Wa Kwan, Yi Tao Wang, Simon Ming-Yuen Lee

  Molecular bioSystems. 03/2011; 7(7):2128-38.

  Flavonoids isolated from Herba Epimedii such as icaritin, icariin and epimedin C have been suggested as potential bone anabolic compounds. However, the "specific localized effects" of theseFlavonoids isolated from Herba Epimedii such as icaritin, icariin and epimedin C have been suggested as potential bone anabolic compounds. However, the "specific localized effects" of these flavonoids in bone, in vivo, and the metabolism of these flavonoids in zebrafish larvae have never been demonstrated. In this study, we used multiple methods including in vivo imaging, drug metabolites profiling, transcriptomic and proteomic approaches to determine the mechanisms involved in the distribution and metabolism of the flavonoids in zebrafish larvae by measuring the fluorescence emission, in vivo, of icaritin and its glycoside derivatives. The fluorescence emission mechanism of icaritin in vitro was identified by spectrophotometric analysis, and the fluorescent property of icaritin was used as a probe to visualize the metabolism and distribution of icaritin and its glycoside derivatives in zebrafish larvae. Phase I and phase II metabolism of icaritin and its derivatives were identified in zebrafish by mass spectrometry. The combined transcriptomics and proteomics demonstrate a high degree of conservation of phase I and phase II drug metabolic enzymes between zebrafish larvae and mammals. Icaritin and its glycoside derivatives were demonstrated using combined approaches of in vivo imaging, drug metabolites identification, and transcriptomic and proteomic profiling to illustrate phase I and phase II metabolism of the flavonoids and their distribution in bone of zebrafish larvae. This study provides a new methodological model for use of the zebrafish larvae to examine drug metabolism.

• Discovering approximate-associated sequence patterns for protein-DNA interactions.

  Authors: Tak-Ming Chan, Ka-Chun Wong, Kin-Hong Lee, Man-Hon Wong, Chi-Kong Lau, Stephen Kwok-Wing Tsui, Kwong-Sak Leung

  Bioinformatics (Oxford, England). 02/2011; 27(4):471-8.

  MOTIVATION: The bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental protein-DNA interactions in transcriptional regulation. Extensive effortsMOTIVATION: The bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental protein-DNA interactions in transcriptional regulation. Extensive efforts have been made to better understand the protein-DNA interactions. Recent mining on exact TF-TFBS-associated sequence patterns (rules) has shown great potentials and achieved very promising results. However, exact rules cannot handle variations in real data, resulting in limited informative rules. In this article, we generalize the exact rules to approximate ones for both TFs and TFBSs, which are essential for biological variations. RESULTS: A progressive approach is proposed to address the approximation to alleviate the computational requirements. Firstly, similar TFBSs are grouped from the available TF-TFBS data (TRANSFAC database). Secondly, approximate and highly conserved binding cores are discovered from TF sequences corresponding to each TFBS group. A customized algorithm is developed for the specific objective. We discover the approximate TF-TFBS rules by associating the grouped TFBS consensuses and TF cores. The rules discovered are evaluated by matching (verifying with) the actual protein-DNA binding pairs from Protein Data Bank (PDB) 3D structures. The approximate results exhibit many more verified rules and up to 300% better verification ratios than the exact ones. The customized algorithm achieves over 73% better verification ratios than traditional methods. Approximate rules (64-79%) are shown statistically significant. Detailed variation analysis and conservation verification on NCBI records demonstrate that the approximate rules reveal both the flexible and specific protein-DNA interactions accurately. The approximate TF-TFBS rules discovered show great generalized capability of exploring more informative binding rules.

• ABMapper: a suffix array-based tool for multi-location searching and splice-junction mapping.

  Authors: Shao-Ke Lou, Bing Ni, Leung-Yau Lo, Stephen Kwok-Wing Tsui, Ting-Fung Chan, Kwong-Sak Leung

  Bioinformatics (Oxford, England). 02/2011; 27(3):421-2.

  Sequencing reads generated by RNA-sequencing (RNA-seq) must first be mapped back to the genome through alignment before they can be further analyzed. Current fast and memory-saving short-read mappersSequencing reads generated by RNA-sequencing (RNA-seq) must first be mapped back to the genome through alignment before they can be further analyzed. Current fast and memory-saving short-read mappers could give us a quick view of the transcriptome. However, they are neither designed for reads that span across splice junctions nor for repetitive reads, which can be mapped to multiple locations in the genome (multi-reads). Here, we describe a new software package: ABMapper, which is specifically designed for exploring all putative locations of reads that are mapped to splice junctions or repetitive in nature. AVAILABILITY AND IMPLEMENTATION: The software is freely available at: http://abmapper.sourceforge.net/. The software is written in C++ and PERL. It runs on all major platforms and operating systems including Windows, Mac OS X and LINUX.

• Data Mining on DNA Sequences of Hepatitis B Virus.

  Authors: Kwong-Sak Leung, Kin-Hong Lee, Jin Feng Wang, Eddie Y. T. Ng, Henry L. Y. Chan, Stephen Kwok-Wing Tsui, Tony Shu Kam Mok, Pete Chi-Hang Tse, Joseph J. Y. Sung

  IEEE/ACM Trans. Comput. Biology Bioinform. 01/2011; 8:428-440.

• The G1613A mutation in the HBV genome affects HBeAg expression and viral replication through altered core promoter activity.

  Authors: Man-Shan Li, Terrence Chi-Kong Lau, Sophie Ka-Ping Chan, Chi-Hang Wong, Patrick Kwok-Shing Ng, Joseph Jao-Yiu Sung, Henry Lik-Yuen Chan, Stephen Kwok-Wing Tsui

  PloS one. 01/2011; 6(7):e21856.

  Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstratedInfection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC.

• LIM domain protein FHL1B interacts with PP2A catalytic β subunit--a novel cell cycle regulatory pathway.

  Authors: Chi-Hang Wong, Yin-Wan Wendy Fung, Enders Kai-On Ng, Simon Ming-Yuen Lee, Mary Miu-Yee Waye, Stephen Kwok-Wing Tsui

  FEBS letters. 10/2010; 584(22):4511-6.

  Four-and-a-half LIM domain protein 1B (FHL1B) is an alternatively-spliced isoform of FHL1. In this study, FHL1B was demonstrated to interact with the β catalytic subunit (Cβ) of a type 2A proteinFour-and-a-half LIM domain protein 1B (FHL1B) is an alternatively-spliced isoform of FHL1. In this study, FHL1B was demonstrated to interact with the β catalytic subunit (Cβ) of a type 2A protein phosphatase (PP2A) by yeast two-hybrid screening. Domain studies using a small-scale yeast two-hybrid interaction assay revealed the mediation of protein-protein interaction by FHL1B's C-terminus. Interaction between FHL1B and PP2A was further verified by co-immunoprecipitation. FHL1B was also shown to shuttle between nucleus and cytoplasm at different phases of the cell cycle. These data suggest that the FHL1B/PP2A(Cβ) interaction may illustrate a novel cell-cycle regulatory pathway.

• Epigenetic regulation of neonatal cardiomyocytes differentiation.

  Authors: Cecy Ying-Chuck Kou, Samantha Lai-Yee Lau, Ka-Wing Au, Pui-Yin Leung, Stephen Siu-Chung Chim, Kwok-Pui Fung, Mary Miu-Yee Waye, Stephen Kwok-Wing Tsui

  Biochemical and biophysical research communications. 09/2010; 400(2):278-83.

  The relationship between DNA methylation, histone modifications and terminal differentiation in cardiomyocytes was investigated in this study. The upregulation of methylation-related proteins,The relationship between DNA methylation, histone modifications and terminal differentiation in cardiomyocytes was investigated in this study. The upregulation of methylation-related proteins, including DNA methyltransferase (DNMT) 1, methyl-CpG binding domain proteins 1, 2 and 3, and the increase in global methylation during rat neonatal heart development were observed. Moreover, an increase in DNA synthesis and a delay in differentiation were found in 5-azacytidine (5-azaC)-treated cardiomyocytes. Increase in acetylation of H3-K9, H4-K5, H4-K8 and methylation of H3-K4 suggested a more accessible chromatin structure in 5-azaC-treated cells. Furthermore, methyl-CpG-binding protein 2 was found to be upregulated in differentiated cardiomyocytes. Overexpression of this protein resulted in an increase of global methylation levels. Therefore, we suggest that a hypermethylated genome and a more compact chromatin structure are formed during terminal differentiation of cardiomyocytes.

• High genetic diversity of HIV-1 viruses in Macao, China.

  Authors: Yi Tan, Desmond Chan, Denise Chan, Peng Kei Ip, Chong Lam, Nga Yin Fong, Stephen Kwok-Wing Tsui, Shui Shan Lee

  The Journal of infection. 07/2010; 61(2):164-72.

  To investigate the molecular epidemiology of recently diagnosed HIV-1 infection in Macao for better understanding the epidemiology in this Chinese city, in context of its relationship with otherTo investigate the molecular epidemiology of recently diagnosed HIV-1 infection in Macao for better understanding the epidemiology in this Chinese city, in context of its relationship with other countries in Asia and the rest of the world. Serum samples of HIV positive cases reported between 2005 and 2007 were collected from the Macao Public Health Laboratory. HIV genotype was determined by phylogenetic analysis of sequences from gag, RT, and env regions. A total of 30 HIV positive samples were genotyped. The HIV-1 viruses circulating in Macao were characterized by their relatively high genetic diversity. CRF01_AE was predominant (56%), followed by subtype B (13%), CRF12_BF (10%), G/CRF12_BF, A1/CRF10_AD and CRF07_BC, of which CRF12_BF and G/CRF12_BF were first reported in Southeast Asia. Phylogenetic analysis showed that there was no clear clustering of CRF01_AE strains but a distinct CRF12_BF cluster associated with injection drug use could be delineated. The results suggested that there were multiple introductions of HIV strains in Macao that have been circulating for an extended period of time, superimposed by an outbreak in injection drug users.

• CCAAT/enhancer binding protein beta is up-regulated in giant cell tumor of bone and regulates RANKL expression.

  Authors: Patrick Kwok-Shing Ng, Stephen Kwok-Wing Tsui, Carol Po-Ying Lau, Chi-Hang Wong, Winnie Hiu-Ting Wong, Lin Huang, Shekhar-Madhukar Kumta

  Journal of cellular biochemistry. 03/2010; 110(2):438-46.

  Giant cell tumor (GCT) of bone is an aggressive non-cancerous tumor, which consists of multi-nucleated osteoclast-like giant cells, stromal cells, and monocytes. It is believed that stromal cells areGiant cell tumor (GCT) of bone is an aggressive non-cancerous tumor, which consists of multi-nucleated osteoclast-like giant cells, stromal cells, and monocytes. It is believed that stromal cells are the neoplastic component of this tumor. Expression of the receptor activator of nuclear factor kappa B ligand (RANKL) in the stromal cells stimulates the monocytes to form giant multi-nucleated osteoclast-like cells, causing bone over-resorption at the tumor site. Previously, our group has reported the up-regulation of RANKL in GCT of bone stromal cells, but the mechanism is unknown. Using stromal cell culture of GCT obtained from patients, we demonstrated the up-regulation of the transcriptional activator CCAAT/enhancer binding protein beta (C/EBPbeta). RANKL promoter studies revealed that C/EBPbeta over-expression induced RANKL promoter activity in a dose-dependent manner and a CCAAT-box within the region nt -357/-1 contributed to the basal transcription activity, with a possible C/EBPbeta binding element in the region nt -460/-358 leading to further induction. Furthermore, we also showed that C/EBPbeta bound to the RANKL promoter in GCT stromal cells in vivo by chromatin immunoprecipitation. To conclude, our study has shown that C/EBPbeta is a RANKL promoter activator in stromal cells of GCT of bone and we have proposed a model in which C/EBPbeta plays an important role in the osteolytic characteristics and pathological causes of GCT of bone.

• Detection of splicing events and multiread locations from RNA-seq data based on a geometric-tail (GT) distribution of intron length.

  Authors: Shao-Ke Lou, Jing-Woei Li, Hao Qin, Aldrin Kay-Yuen Yim, Leung-Yau Lo, Bing Ni, Kwong-Sak Leung, Stephen Kwok-Wing Tsui, Ting-Fung Chan

  2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010, Hong Kong, China, 18 - 21 December 2010, Proceedings; 01/2010

• An integrated web medicinal materials DNA database: MMDBD (Medicinal Materials DNA Barcode Database).

  Authors: Shao-Ke Lou, Ka-Lok Wong, Ming Li, Paul Pui-Hay But, Stephen Kwok-Wing Tsui, Pang-Chui Shaw

  BMC genomics. 01/2010; 11:402.

  Thousands of plants and animals possess pharmacological properties and there is an increased interest in using these materials for therapy and health maintenance. Efficacies of the application isThousands of plants and animals possess pharmacological properties and there is an increased interest in using these materials for therapy and health maintenance. Efficacies of the application is critically dependent on the use of genuine materials. For time to time, life-threatening poisoning is found because toxic adulterant or substitute is administered. DNA barcoding provides a definitive means of authentication and for conducting molecular systematics studies. Owing to the reduced cost in DNA authentication, the volume of the DNA barcodes produced for medicinal materials is on the rise and necessitates the development of an integrated DNA database. We have developed an integrated DNA barcode multimedia information platform- Medicinal Materials DNA Barcode Database (MMDBD) for data retrieval and similarity search. MMDBD contains over 1000 species of medicinal materials listed in the Chinese Pharmacopoeia and American Herbal Pharmacopoeia. MMDBD also contains useful information of the medicinal material, including resources, adulterant information, medical parts, photographs, primers used for obtaining the barcodes and key references. MMDBD can be accessed at http://www.cuhk.edu.hk/icm/mmdbd.htm. This work provides a centralized medicinal materials DNA barcode database and bioinformatics tools for data storage, analysis and exchange for promoting the identification of medicinal materials. MMDBD has the largest collection of DNA barcodes of medicinal materials and is a useful resource for researchers in conservation, systematic study, forensic and herbal industry.

• Transcriptional regulation of IER3IP1 gene by tumor necrosis factor-alpha and Sp family proteins.

  Authors: Wai Han Yiu, Tsz Lun Yeung, Jodie Wing Ming Poon, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Mary Miu-Yee Waye

  Cell biochemistry and function. 11/2009;

  Immediate early response 3 interacting protein 1 (IER3IP1) is an endoplasmic reticulum protein with its potential cellular function involved in cell differentiation and cell death processes. In thisImmediate early response 3 interacting protein 1 (IER3IP1) is an endoplasmic reticulum protein with its potential cellular function involved in cell differentiation and cell death processes. In this report, we investigated the molecular mechanism by which the expression of IER3IP1 gene is regulated by cloning the 5' flanking region of the human IER3IP1 gene for various promoter studies. Deletion analysis was used to identify the basal promoter activity retained at -298/-59 region and mutation analysis proved that Sp1 is a transcriptional activator of this gene expression. As an early response gene, IER3IP1 showed an increase in transcription in response to tumor necrosis factor alpha (TNF-alpha) in a time- and dose-dependent manner. This inducible response to TNF-alpha is mediated by the demonstration of nuclear factor kappaB (NF-kappaB) responsive element on IER3IP1 promoter sequence. From our results, we suggest that IER3IP1 gene is involved in TNF-alpha-mediated cellular response to stressful conditions. Copyright (c) 2009 John Wiley & Sons, Ltd.

• Folic Acid Supplementation Modifies {beta}-Adrenoceptor-Mediated in vitro Lipolysis of the Obese/Diabetic (+db/+db) Mice.

  Authors: Tsz Yan Lam, Sai Wang Seto, Alice Lai Shan Au, Christina Chui-Wa Poon, Alan Ho Yeung Lam, Mandy Wing Sze Lau, Shun-Wan Chan, Sai Ming Ngai, George Pak-Heng Leung, Simon Ming-Yuen Lee, Stephen Kwok-Wing Tsui, Yiu Wa Kwan

  Experimental biology and medicine (Maywood, N.J.). 08/2009;

  The effects of folic acid (5.7 and 71 microg/kg), 4 weeks) consumption on the beta-adrenoceptors (beta-ARs)-elicited lipolysis in vitro of the abdominal adipocytes of the lean/control (+m/+db) andThe effects of folic acid (5.7 and 71 microg/kg), 4 weeks) consumption on the beta-adrenoceptors (beta-ARs)-elicited lipolysis in vitro of the abdominal adipocytes of the lean/control (+m/+db) and obese/diabetic (+db/+db) mice (female) were investigated. beta-AR agonists (salbutamol, a beta2-AR agonist; BRL 37344 and CGP 12177, beta3-AR agonists; adrenaline, a beta-AR agonist)-mediated lipolysis, beta2 and beta3-ARs protein expression of the adipose tissues after folic acid consumption were evaluated. Our results demonstrate that a smaller magnitude of the basal (spontaneous) and the beta-AR agonists-triggered lipolysis was observed in +db/+db mice, and folic acid supplementation (71 microg/kg) resulted in an improvement of both the baseline and the beta-ARs-mediated lipolysis. In controls, a lower beta2 and beta3-ARs protein expression of the adipose tissues was detected in +db/+db mice, compared to +m/+db mice. In both strains fed with folic acid (71 microg/kg), a reduction of beta2-AR protein expression was observed compared to the respective controls. In +db/+db mice, folic acid (5.7 and 71 microg/kg) consumption caused a dose-dependent increase of beta3-AR protein expression compared to controls. We demonstrate that lipolysis elicited by beta-AR (beta2- and beta3-ARs) agonists was blunted in +db/+db mice. Folic acid consumption has significant modulatory effects on beta-ARs protein expression and lipolysis.