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Search Results: 1 - 10 of 11236 matches for " Koon-Ho Chan "
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Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease
Philip WL Ho, Jessica WM Ho, Hui-Fang Liu, Danny HF So, Zero HM Tse, Koon-Ho Chan, David B Ramsden, Shu-Leong Ho
Translational Neurodegeneration , 2012, DOI: 10.1186/2047-9158-1-3
Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder and increasingly a major burden in an aging population. Although its pathogenesis is unknown, there is evidence to implicate common pathogenic processes towards eventual cell death in PD. These processes include mitochondrial dysfunction, oxidative stress, neuroinflammation, excitotoxicity, and ubiquitin proteasome dysfunction [1-4].There is considerable evidence to link mitochondrial dysfunction and PD. Mitochondrial Complex I activity is reduced in substantia nigra in PD [5]. Inhibition of Complex I activity using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone (both toxins used in experimental parkinsonian models) produce nigrostriatal dopaminergic degeneration in animal models [6,7]. Cybrid cell lines with normal nuclear genome but with mitochondrial DNA from PD patients have reduced Complex I activity and mitochondrial energy-dependent activities [8], have abnormal mitochondrial morphology [9], and are more susceptible to MPTP-induced toxicity. The process of aging involves the mitochondria [10]. Furthermore, dopamine metabolism and mitochondrial dysfunction generate oxidative stress. High basal levels of oxidative stress in substantia nigra are found in normal brain, and are increased in PD. Furthermore, antioxidant activity, such as glutathione (GSH), is reduced in substantia nigra of PD patients [11,12]. Based on the hypothesis that various genetic and environmental etiological factors converge on these common pathogenic processes in PD, targeting proteins which modulate mitochondria bioenergetics appears to be a logical approach in preserving neurons against mitochondrial dysfunction in PD.Mitochondria are rod-shaped cellular organelles, which range in size from between 1 and 10 microns in length. They provide cellular energy by converting oxygen and nutrients into adenosine triphosphate (ATP) via oxidative phosphorylation. Human cells have hundreds to thousands of mitochondria
Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with Type 2 Diabetes
Kui-Kai Lau, Yuen-Kwun Wong, Yap-Hang Chan, Kai-Hang Yiu, Kay-Cheong Teo, Leonard Li, Shu-Leong Ho, Koon-Ho Chan, Chung-Wah Siu, Hung-Fat Tse
Cardiovascular Diabetology , 2012, DOI: 10.1186/1475-2840-11-101
Abstract: We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing adverse atherosclerotic events including acute coronary syndrome (ACS) and ischemic stroke [1-3]. Various risk assessment algorithms, for example the Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), aim to predict the likelihood of developing cardiovascular events [4-6]. Some of these scores have also been recalibrated based on the ethnic differences in cardiovascul
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.
Stroke Patients with a Past History of Cancer Are at Increased Risk of Recurrent Stroke and Cardiovascular Mortality
Kui-Kai Lau, Yuen-Kwun Wong, Kay-Cheong Teo, Richard Shek-Kwan Chang, Sonny Fong-Kwong Hon, Koon-Ho Chan, Raymond Tak-Fai Cheung, Leonard Sheung-Wai Li, Hung-Fat Tse, Shu-Leong Ho, Chung-Wah Siu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088283
Abstract: Background and Purpose Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke. Methods This was a single center, observational study of 1,105 consecutive Chinese ischemic stroke patients recruited from a large stroke rehabilitation unit based in Hong Kong. We sought to determine whether patients with cancer are at higher risk of recurrent stroke and cardiovascular mortality. Results Amongst 1,105 patients, 58 patients (5.2%) had cancer, of whom 74% were in remission. After a mean follow-up of 76±18 months, 241 patients developed a recurrent stroke: 22 in patients with cancer (38%, annual incidence 13.94%/year), substantially more than those without cancer (21%, 4.65%/year) (p<0.01). In a Cox regression model, cancer, age and atrial fibrillation were the 3 independent predictors of recurrent stroke with a hazard ratio (HR) of 2.42 (95% confidence interval (CI): 1.54–3.80), 1.01 (1.00–1.03) and 1.35 (1.01–1.82) respectively. Likewise, patients with cancer had a higher cardiovascular mortality compared with those without cancer (4.30%/year vs. 2.35%/year, p = 0.08). In Cox regression analysis, cancer (HR: 2.08, 95% CI: 1.08–4.02), age (HR: 1.04, 95% CI 1.02–1.06), heart failure (HR: 3.06, 95% CI 1.72–5.47) and significant carotid atherosclerosis (HR: 1.55, 95% CI 1.02–2.36) were independent predictors for cardiovascular mortality. Conclusions Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.
Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays
Koon H Chan, Jason SC Kwan, Philip WL Ho, Jessica WM Ho, Andrew CY Chu, David B Ramsden
Journal of Neuroinflammation , 2010, DOI: 10.1186/1742-2094-7-50
Abstract: Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes.In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250), 75% of patients having relapsing myelitis (RM) with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250), and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000); however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69%) were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3), RM with LETM (3), a single attack of LETM (1), relapsing ON (1) and a single ON attack (1). Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17) and seronegative (n = 6) by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups.Cell-based IIFA is slightly more sensitive than tissue-based IIFA in detection of AQP4 autoantibodies, which are highly specific for NMOSD.Neuromyelitis optica (NMO) is a severe central nervous system inflammatory demyelinating disorder (CNS IDD) characterized by monophasic or relapsing optic neuritis (ON) and acute transverse myelitis (ATM) [1-6]. Relapsing NMO is the predominant type, which can mimic relapsing remitting multiple sclerosis (RRMS), the predominant form of classical multiple sclerosis (CMS), on initial presentation [2-8]. Typical relapsing NMO patients
How Dark Energy Affects the MOND Theory in Clusters  [PDF]
Man Ho Chan
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.329147
Abstract: Modified Newtonian Dynamics (MOND) is one of the successful theories to explain the dark matter problem in galaxies. However, the data from clusters and the cosmic microwave background (CMB) indicate some dark matter should exist in larger scales. In addition, recent dynamical studies of clusters show that the effect of dark energy should not be ignored in cluster scale. In this article, I will demonstrate how dark energy affects the cluster mass calculation by using MOND. Also, I will show that the calculated cluster mass is consistent with the total matter to baryonic matter ratio obtained by the CMB data.
RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis
Ho Yin E. Chan
Frontiers in Cellular Neuroscience , 2014, DOI: 10.3389/fncel.2014.00431
Abstract: Gene transcription produces a wide variety of ribonucleic acid (RNA) species in eukaryotes. Individual types of RNA, such as messenger, structural and regulatory RNA, are known to play distinct roles in the cell. Recently, researchers have identified a large number of RNA-mediated toxicity pathways that play significant pathogenic roles in numerous human disorders. In this article, we describe various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, repeat-associated non-ATG translation, RNA foci formation and cellular protein sequestration. We emphasize RNA toxicity mechanisms that involve nucleotide repeat expansion, such as those related to polyglutamine disorders and frontotemporal lobar degeneration-amyotrophic lateral sclerosis.
Reconciliation of MOND and Dark Matter theory
Man Ho Chan
Physics , 2013, DOI: 10.1103/PhysRevD.88.103501
Abstract: I show that Modified Newtonian Dynamics (MOND) is equivalent to assuming an isothermal dark matter density profile, with its density related to the enclosed total baryonic mass. This density profile can be deduced by physical laws if a dark matter core exists and if the baryonic component is spherically-symmetric, isotropic and isothermal. All the usual predictions of MOND, as well as the universal constant $a_0$, can be derived in this model. Since the effects of baryonic matter are larger in galaxies than in galaxy clusters, this result may explain why MOND appears to work well for galaxies but poorly for clusters. As a consequence of the results presented here, MOND can be regarded as a misinterpretation of a particular dark matter density profile.
A hybrid helical structure of hard sphere packing from sequential deposition
Ho-Kei Chan
Physics , 2013, DOI: 10.1080/14786435.2013.801568
Abstract: A hybrid helical structure of equal-sized hard spheres in cylindrical confinement was discovered as a 'by-product' of the recently developed sequential deposition approach [Physical Review E 84, 050302(R) (2011)] for constructing the densest possible packings of such systems. Unlike the conventional triple-helix structure where its three strands of spheres are packed densely to form triads of close-packed, mutually touching spheres, in this novel helical phase only two of its three strands of spheres are packed in this densest arrangement and the overall structure resembles a hybrid of the single and the double helix. This article explains how this previously unknown structure can be constructed via the abovementioned sequential deposition of spheres, which involves manipulating the positions of a few spheres to create a template for the deposition process. The findings show that it is possible to discover new structures through varying only the configuration of few spheres within the template, where this approach relies on a sensitive dependence of the deposition-generated structures on the template.
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