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Search Results: 1 - 10 of 7646 matches for " Kwong-Man Ng "
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Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells
Kwong-Man Ng,Yee-Ki Lee,Wing-Hon Lai,Yau-Chi Chan,Man-Lung Fung,Hung-Fat Tse,Chung-Wah Siu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019787
Abstract: The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway.
Origin of Secretin Receptor Precedes the Advent of Tetrapoda: Evidence on the Separated Origins of Secretin and Orexin
Janice K. V. Tam,Kwan-Wa Lau,Leo T. O. Lee,Jessica Y. S. Chu,Kwong-Man Ng,Alain Fournier,Hubert Vaudry,Billy K. C. Chow
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019384
Abstract: At present, secretin and its receptor have only been identified in mammals, and the origin of this ligand-receptor pair in early vertebrates is unclear. In addition, the elusive similarities of secretin and orexin in terms of both structures and functions suggest a common ancestral origin early in the vertebrate lineage. In this article, with the cloning and functional characterization of secretin receptors from lungfish and X. laevis as well as frog (X. laevis and Rana rugulosa) secretins, we provide evidence that the secretin ligand-receptor pair has already diverged and become highly specific by the emergence of tetrapods. The secretin receptor-like sequence cloned from lungfish indicates that the secretin receptor was descended from a VPAC-like receptor prior the advent of sarcopterygians. To clarify the controversial relationship of secretin and orexin, orexin type-2 receptor was cloned from X. laevis. We demonstrated that, in frog, secretin and orexin could activate their mutual receptors, indicating their coordinated complementary role in mediating physiological processes in non-mammalian vertebrates. However, among the peptides in the secretin/glucagon superfamily, secretin was found to be the only peptide that could activate the orexin receptor. We therefore hypothesize that secretin and orexin are of different ancestral origins early in the vertebrate lineage.
Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2
Annie Po-yee Yim,Hiu-yan Yeung,Guangquan Sun,Kwong-man Lee,Tzi-bun Ng,Tsz-ping Lam,Bobby Kin-wah Ng,Yong Qiu,Alain Moreau,Jack Chun-yiu Cheng
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms14036345
Abstract: The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate whether the abnormal MT2 expression in AIS is quantitative or qualitative. Cultured osteoblasts were obtained from 41 AIS girls and nine normal controls. Semi-quantification of protein expression by Western blot and mRNA expression by TaqMan real-time PCR for both MT1 and MT2 were performed. Anthropometric parameters were also compared and correlated with the protein expression and mRNA expression of the receptors. The results showed significantly lower protein and mRNA expression of MT2 in AIS girls compared with that in normal controls ( p = 0.02 and p = 0.019, respectively). No differences were found in the expression of MT1. When dichotomizing the AIS girls according to their MT2 expression, the group with low expression was found to have a significantly longer arm span ( p = 0.036). The results of this study showed for the first time a quantitative change of MT2 in AIS that was also correlated with abnormal arm span as part of abnormal systemic skeletal growth.
Relative shortening and functional tethering of spinal cord in adolescent scoliosis – Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE
Winnie CW Chu, Wynnie MW Lam, Bobby KW Ng, Lam Tze-ping, Kwong-man Lee, Xia Guo, Jack CY Cheng, R Geoffrey Burwell, Peter H Dangerfield, Tim Jaspan
Scoliosis , 2008, DOI: 10.1186/1748-7161-3-8
Abstract: In the absence of any accepted scientific theory for the etiology of idiopathic scoliosis treatment remains pragmatic with a very incomplete scientific basis. The International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. The Statement written by Dr WCW Chu and colleagues is based on important spinal imaging research, neurological findings and anthropometric data already published [1-3], Moderator see [4]. The research is part of a series of studies [5-11] to evaluate the hypothesis that in AIS there is a systemic disturbance of growth [12-15] manifest in each of the appendicular skeleton, vertebral column and skull that points to a problem of axial skeletal growth control [7]. In addition to skeletal findings, neurological features are also addressed including clinical neurological examination, cerebellar tonsillar level at the foramen magnum and somatosensory evoked potentials (SSEPs). They address the pathogenesis and pathomechanisms of AIS, not its etiology.Dr Chu applied the new method of multiplanar reformat magnetic resonance imaging to the spine of 28 AIS girls and 14 matched normal girls [1]. In severe AIS compared with normal subjects, the thoracic vertebral column is significantly longer without detectable change in spinal cord length evaluated as cord-to-vertebral length ratios (Figure 1). They speculate that the initiation and progression of AIS result from vertebral column overgrowth through a lordoscoliotic maladaptation of the spine to the subclinical tether of a relatively short spinal cord. This interpretation accommodates both the lordotic [18-21] and the dorsal shear force [22] concepts for the pathogenesis of AIS.Their research confirms and extends the speculation of Roth [23-25] and Porter [26-30] that disproportion of vertebro-neural growth [23-25] and uncoupled neuro-osseous growth [28] explains the pathogenesis of progressive AIS. The
Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid-Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets
Ge Zhang, Xin-Luan Wang, Hui Sheng, Xin-Hui Xie, Yi-Xin He, Xin-Sheng Yao, Zi-Rong Li, Kwong-Man Lee, Wei He, Kwok-Sui Leung, Ling Qin
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006419
Abstract: Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.
PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance
Mian Cao equal contributor,Zhuo Mao equal contributor,Chuen Kam,Nan Xiao,Xiaoxing Cao,Chong Shen,Kenneth K. Y. Cheng,Aimin Xu,Kwong-Man Lee,Liwen Jiang,Jun Xia
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001541
Abstract: Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which blocks vesicle budding from the Golgi, increased the amount of PICK1 and ICA69 at TGN. On the other hand, mature secretory granules were associated with PICK1 only, not ICA69. PICK1 deficiency in mice caused the complete loss of ICA69 and led to increased food and water intake but lower body weight. Glucose tolerance tests demonstrated that these mutant mice had high blood glucose, a consequence of insufficient insulin. Importantly, while the total insulin level was reduced in PICK1-deficient beta cells, proinsulin was increased. Lastly, ICA69 knockout mice also displayed similar phenotype as the mice deficient in PICK1. Together, our results indicate that PICK1 and ICA69 are key regulators of the formation and maturation of insulin granules. Author Summary Insulin is a key regulator of blood glucose and insufficient insulin leads to diabetes. Insulin is synthesized as proinsulin, processed in endoplasmic reticulum and Golgi, and eventually packaged into insulin granules, a type of dense core vesicles. Despite its importance, the molecular mechanisms governing the biogenesis and maturation of insulin granules are not fully understood. In this study, we identified two cytosolic proteins, PICK1 and ICA69, as important regulators of insulin granule biogenesis and maturation. Both PICK1 and ICA69 have the banana-shaped BAR domain that can bend the lipid membrane and help the formation of dense core vesicles. We show that without PICK1 or ICA69, insulin granules cannot be properly formed and, as a result, proinsulin cannot be effectively processed into mature insulin. Mice lacking functional PICK1 or ICA69 genes have reduced insulin but increased proinsulin. Consequently, these mice have high levels of glucose, a prominent feature found in diabetes patients. These results add to previous findings that PICK1 is important for the generation
A Review of Pinealectomy-Induced Melatonin-Deficient Animal Models for the Study of Etiopathogenesis of Adolescent Idiopathic Scoliosis
Man Gene Chi Wai,Wang William Wei Jun,Yim Annie Po Yee,Wong Jack Ho,Ng Tzi Bun,Lam Tsz Ping,Lee Simon Kwong Man,Ng Bobby Kin Wah,Wang Chi Chiu,Qiu Yong,Cheng Jack Chun Yiu
International Journal of Molecular Sciences , 2014, DOI: 10.3390/ijms150916484
Abstract: Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.
Correction: Wai, M.G.C., et al. A Review of Pinealectomy-Induced Melatonin-Deficient Animal Models for the Study of Etiopathogenesis of Adolescent Idiopathic Scoliosis. Int. J. Mol. Sci. 2014, 15, 16484–16499
Gene Chi Wai Man,William Wei Jun Wang,Annie Po Yee Yim,Jack Ho Wong,Tzi Bun Ng,Tsz Ping Lam,Simon Kwong Man Lee,Bobby Kin Wah Ng,Chi Chiu Wang,Yong Qiu,Jack Chun Yiu Cheng
International Journal of Molecular Sciences , 2015, DOI: 10.3390/ijms16023017
Abstract: The authors wish to make the following corrections to this paper [1]: The first name and surname of the authors were reversed. It should be corrected in the following format (with the surname in bold text):[...]
Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast and Gastric Cancer Patients
Enders K. O. Ng, Candy P. H. Leung, Vivian Y. Shin, Chris L. P. Wong, Edmond S. K. Ma, Hong Chuan Jin, Kent-Man Chu, Ava Kwong
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022233
Abstract: Background Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma. Methodology/Principal Findings SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%. Conclusions These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis.
An Improved Heaviside Approach to Partial Fraction Expansion and its Applications
Yiu-Kwong Man
Lecture Notes in Engineering and Computer Science , 2008,
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