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Search Results: 1 - 10 of 13920 matches for " Philip Wing-Lok Ho "
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Assessment of Cellular Estrogenic Activity Based on Estrogen Receptor-Mediated Reduction of Soluble-Form Catechol-O-Methyltransferase (COMT) Expression in an ELISA-Based System
Philip Wing-Lok Ho, Zero Ho-Man Tse, Hui-Fang Liu, Song Lu, Jessica Wing-Man Ho, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074065
Abstract: Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10-9-10-7M) dose-dependently reduced COMT expression (p<0.05), which was blocked by ICI 182,780. Reduction of COMT expression was readily detectable in cells exposed to picomolar level of E2, comparable to other in vitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different cellular components, a cell-based COMT assay provides useful initial screening to supplement the current assessments of xenoestrogens for potential estrogenic activity.
Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity
Koon-Ho Chan, Karen Siu-Ling Lam, On-Yin Cheng, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Sookja Kim Chung, Jessica Wing-Man Ho, Vivian Yawei Guo, Almin Xu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052354
Abstract: Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 μg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.
Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells
Philip Wing-Lok Ho, Jessica Wing-Man Ho, Ho-Man Tse, Danny Hon-Fai So, David Chi-Wai Yiu, Hui-Fang Liu, Koon-Ho Chan, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032810
Abstract: Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis.
Current Mismatches in Charge Pumps of DLL-Based RF CMOS Oscillators
基于DLL的RF CMOS振荡器中电荷泵电流源失配(英文)

ZHENG Guang-fu,YANG Hong-xing,MAN Cheuk-ho,WONG Wing-lok,An Da-wei,John BURNETT,
李金城
,仇玉林

半导体学报 , 2001,
Abstract: A research on the spurious tones due to the current mismatch in charge pumps of DLL(Delay Locked Loop) based RF CMOS oscillators is performed.An equation for strength evaluation of the spurious tones is derived.Two tables are provided to make it obvious to understand for the characteristics of spurious tones changing with related parameters.Some suggestions are given for the design of a DLL based RF CMOS oscillators.
Herba Epimedii: Anti-Oxidative Properties and Its Medical Implications
Stephen Cho Wing Sze,Yao Tong,Tzi Bun Ng,Chris Lok Yin Cheng,Ho Pan Cheung
Molecules , 2010, DOI: 10.3390/molecules15117861
Abstract: Herba Epimedii is a Chinese herbal medicine with proven efficacy in treating cardiovascular diseases and osteoporosis, and in improving sexual and neurological functions. This efficacy is found to be related to the potent anti-oxidative ability of Herba Epimedii and its flavonoid components, with icarrin as the main effective constituent, along with polysaccharides and vitamin C. These ingredients have been proven to be effective against oxidative-stress related pathologies (cardiovascular diseases, Alzheimer’s disease and inflammation) in animal rodent models and in vitro studies. Their anti-oxidative properties are found to be related to an inductive effect on endogenous free-radical scavenging enzymes such as catalase and glutathione peroxidase and the inherent electron-donating ability of flavonoids.
A Novel Semiconductor CIGS Photovoltaic Material and Thin-Film ED Technology
ZHENG Guang fu,YANG Hong xing,MAN Cheuk ho,WONG Wing lok,AN Da wei,John BURNETT,
A

半导体学报 , 2001,
Abstract: In order to achieve low cost high efficiency thin film solar cells,a novel Semiconductor Photovoltaic (PV) active material CuIn 1-x Ga x Se 2 (CIGS) and thin film Electro Deposition (ED) technology is explored.Firstly,the PV materials and technologies is investigated,then the detailed experimental processes of CIGS/Mo/glass structure by using the novel ED technology and the results are reported.These results shows that high quality CIGS polycrystalline thin films can be obtained by the ED method,in which the polycrystalline CIGS is definitely identified by the (112),(204,220) characteristic peaks of the tetragonal structure,the continuous CIGS thin film layers with particle average size of about 2μm of length and around 1 6μm of thickness.The thickness and solar grade quality of CIGS thin films can be produced with good repeatability.Discussion and analysis on the ED technique,CIGS energy band and sodium (Na) impurity properties,were also performed.The alloy CIGS exhibits not only increasing band gap with increasing x ,but also a change in material properties that is relevant to the device operation.The beneficial impurity Na originating from the low cost soda lime glass substrate becomes one prerequisite for high quality CIGS films.These novel material and technology are very useful for low cost high efficiency thin film solar cells and other devices.
Tax Reform for a Fairer, More Vibrant Economy  [PDF]
Lok Sang Ho, Tianle Zhang
Modern Economy (ME) , 2016, DOI: 10.4236/me.2016.78092
Abstract: The paper reviews the recent literature on tax reform, and recommends abolishing the profits tax and treating personal incomes from all sources as taxable, including capital gains and dividends. Abolition of the profits tax will vastly improve the investment environment and eliminate wasteful distortions. We also offer an intermediate “gradualist” approach involving halving the profit tax rate and taxing half of dividends and capital gains. We augmented a model proposed by Chetty and Saez [1] to incorporate the effects of manager effort for investment and showed the strong adverse effect of the profit tax on investment. Given that successive increments in total personal incomes from all sources are typically characterized by increasing intensity in economic rent, a progressive tax structure with high marginal tax rates at the top and wide tax bands is not only more equitable, but can be justified on efficiency grounds.
Silencing BRE Expression in Human Umbilical Cord Perivascular (HUCPV) Progenitor Cells Accelerates Osteogenic and Chondrogenic Differentiation
Elve Chen, Mei Kuen Tang, Yao Yao, Winifred Wing Yiu Yau, Lok Man Lo, Xuesong Yang, Yiu Loon Chui, John Chan, Kenneth Ka Ho Lee
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067896
Abstract: BRE is a multifunctional adapter protein involved in DNA repair, cell survival and stress response. To date, most studies of this protein have been focused in the tumor model. The role of BRE in stem cell biology has never been investigated. Therefore, we have used HUCPV progenitor cells to elucidate the function of BRE. HUCPV cells are multipotent fetal progenitor cells which possess the ability to differentiate into a multitude of mesenchymal cell lineages when chemically induced and can be more easily amplified in culture. In this study, we have established that BRE expression was normally expressed in HUCPV cells but become down-regulated when the cells were induced to differentiate. In addition, silencing BRE expression, using BRE-siRNAs, in HUCPV cells could accelerate induced chondrogenic and osteogenic differentiation. Hence, we postulated that BRE played an important role in maintaining the stemness of HUCPV cells. We used microarray analysis to examine the transcriptome of BRE-silenced cells. BRE-silencing negatively regulated OCT4, FGF5 and FOXO1A. BRE-silencing also altered the expression of epigenetic genes and components of the TGF-β/BMP and FGF signaling pathways which are crucially involved in maintaining stem cell self-renewal. Comparative proteomic profiling also revealed that BRE-silencing resulted in decreased expressions of actin-binding proteins. In sum, we propose that BRE acts like an adaptor protein that promotes stemness and at the same time inhibits the differentiation of HUCPV cells.
The Role of Adjuvant Therapy in Gastrointestinal Stromal Tumor after Operative Treatment
Ka-Ho Lok
Clinical Medicine Insights: Gastroenterology , 2012,
Abstract: The treatment for localized advance gastrointestinal stromal tumor (GIST) is far from ideal. Up to 50% of patient developed post-operative recurrence and died within 5 years. Recently, imatinib was found to significantly improve recurrence-free survival in post-operative patients. The role of adjuvant therapy in high risk GIST patients is discussed.
On Blocking Numbers of Surfaces
Wing Kai Ho
Mathematics , 2008,
Abstract: The blocking number of a manifold is the minimal number of points needed to block out lights between any two given points in the manifold. It has been conjectured that if the blocking number of a manifold is finite, then the manifold must be flat. In this paper we prove that this is true for 2-dimensional manifolds with non-trivial fundamental groups.
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