A5066200381- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Autophagy in Disease and Therapy
- Biochemical and Molecular Research
- Growth Hormone and Insulin-like Growth Factors
- Cellular transport and secretion
- Bioactive natural compounds
- Calcium signaling and nucleotide metabolism
- Natural Compounds in Disease Treatment
- Effects of Radiation Exposure
- Radiation Effects and Dosimetry
- Parkinson's Disease Mechanisms and Treatments
- Advanced Radiotherapy Techniques
- Glycosylation and Glycoproteins Research
- Ophthalmology and Eye Disorders
- Radiation Dose and Imaging
- Insect Resistance and Genetics
- Berberine and alkaloids research
- Reproductive System and Pregnancy
- Chromatography in Natural Products
- Sirtuins and Resveratrol in Medicine
- Natural product bioactivities and synthesis
- Ginseng Biological Effects and Applications
- Pituitary Gland Disorders and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
Macau University of Science and Technology
2013-2023
Quality Research
2023
Amicus Therapeutics (United States)
2013-2019
National Institute for Radiological Protection
2015
Chinese Center For Disease Control and Prevention
2015
Amicus Therapeutics (United Kingdom)
2013-2014
Beijing Center for Disease Prevention and Control
2006-2014
Rutgers, The State University of New Jersey
2011
Columbia University
2007
Bristol Royal Infirmary
1995-1998
The eyes of a prospective cohort 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. prevalence strictly age-related cataracts was low, as expected (only 3.9% had nuclear either examination), since 90% the younger than 55 age first examination. However, posterior subcapsular or cortical characteristic radiation exposure present in 25% subjects. data Stage 1 cataracts, specifically revealed significant dose response. When various end...
Abstract Resistance of cancer cells to chemotherapy is a significant problem in oncology and the development sensitising agents or small-molecules with new mechanisms action kill these needed. Autophagy cellular process responsible for turnover misfolded proteins damaged organelles it also recycles nutrients maintain energy levels cell survival. In some apoptosis-resistant cells, autophagy can enhance efficacy anti-cancer drugs through autophagy-mediated death. Because modulation autophagic...
Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances huntingtin and α-synuclein PC-12 cells. Through intensive screening using green fluorescent protein-light chain 3 (GFP-LC3) detection platform, found ethanol extracts Radix Polygalae (Yuan Zhi)...
// Betty Yuen Kwan Law 1 , Simon Wing Fai Mok Wai Kit Chan Su Wei Xu An Guo Wu Xiao Jun Yao Jing Rong Wang Liang Liu Vincent Kam Wong State Key Laboratory of Quality Research in Chinese Medicine, Macau University Science and Technology, Macau, China Correspondence to: Wong, e-mail: bowaiwong@gmail.com Liu, lliu@must.edu.mo Keywords: hernandezine, AMPK activator, autophagy, autophagic cell death, drug-resistant cancer Received: September 13, 2015 Accepted: January 01, 2016 Published: 22,...
Pompe disease is a rare inherited disorder of lysosomal glycogen metabolism due to acid α-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) using alglucosidase alfa, recombinant human GAA (rhGAA), the only approved treatment for disease. Although alfa has provided clinical benefits, its poor targeting key disease-relevant skeletal muscles results in suboptimal efficacy. We are developing an rhGAA, ATB200 (Amicus proprietary rhGAA), with high levels mannose-6-phosphate that...
Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca
Abstract Resistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, identification medicinal compounds against chemoresistant via new mechanism action highly desired. Autophagy important inducing survival therapy. Recently, novel activators isolated from natural products were shown induce autophagic...
Drug resistance in cancer has been classified as innate or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude reverse these mechanisms could be a promising strategy improve chemotherapeutic outcomes. In this study, natural product from Osage Orange, pomiferin, was identified novel autophagy activator that circumvents triggering autophagic cell death via SERCA inhibition activation of the CaMKKβ-AMPK-mTOR...
There is increasing evidence that pituitary ATP receptors may play a novel role in modulating function. This work reports the isolation and expression of receptor gene clone from rat complementary DNA library. The isolated (rpP2U) has 1125-bp coding sequence flanked by 483 bp 5' - 422 3'-untranslated sequences. deduced 374-amino acid product shows structural features common to other G protein-coupled receptors, when stably transfected into glioma cell line lacking endogenous functionally...
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a progressive neurodegenerative lysosomal storage disorder caused by mutations in TPP1, the gene encoding protease tripeptidyl-peptidase (TPP1). LINCL primarily affects children, fatal and there no effective treatment. Administration of recombinant protein has proved treatment visceral manifestations other disorders but to date, only marginal improvement survival been obtained for neurological diseases. In this study, we have developed...
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In present study, we evaluated effect neferine in terms P-glycoprotein (P-gp) inhibition via vitro cytotoxicity assays, R123 uptake assays drug-resistant cancer cells, silico molecular docking analysis on human P-gp and absorption, distribution, metabolism excretion (ADME), quantitative structure activity...
Abstract Calcium is a second messenger which required for regulation of many cellular processes. However, excessive elevation or prolonged activation calcium signaling would lead to cell death. As such, selectively regulating could be an alternative approach anti-cancer therapy. Recently, we have identified effective analogue resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) elevated the intracellular level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS...
Chumak, V. V., Worgul, B. Kundiyev, Y. I., Sergiyenko, N. M., Vitte, P. Medvedovsky, C., Bakhanova, E. Junk, A. K., Kyrychenko, O. Y., Musijachenko, Sholom, S. Shylo, A., P., Xu, S., Xue, X. and Shore, R. Dosimetry for a Study of Low-Dose Radiation Cataracts among Chernobyl Clean-up Workers. Radiat. Res. 167, 606– 614 (2007).A cohort 8,607 Ukrainian clean-up workers during 1986–1987 was formed to study cataract formation after ionizing radiation exposure. eligibility required the...
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene that encodes α-galactosidase A and characterized pathological accumulation of globotriaosylceramide globotriaosylsphingosine. Earlier, authors demonstrated oral coadministration pharmacological chaperone AT1001 (migalastat HCl; 1-deoxygalactonojirimycin HCl) prior to intravenous administration enzyme replacement therapy improved properties enzyme. In this study, investigated effects coformulating with a...
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure conventional chemotherapy. Innovative therapeutic methods which can overcome non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) central regulator cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that identified natural AMPK activator able to apoptosis-resistant cancer via autophagic cell death. Therefore, an ideal pharmaceutical...
Pompe disease is an inherited lysosomal storage disorder that results from a deficiency in acid α-glucosidase (GAA) activity due to mutations the GAA gene. characterized by accumulation of glycogen primarily heart and skeletal muscles, which leads progressive muscle weakness. We have shown previously small molecule pharmacological chaperone AT2220 (1-deoxynojirimycin hydrochloride, duvoglustat hydrochloride) binds stabilizes wild-type as well multiple mutant forms GAA, can lead higher...
Drug resistance of non-small cell lung cancer (NSCLC) is highly correlated to the mutation epidermal growth factor receptor (EGFR). Although EGFR tyrosine kinase inhibitors (TKIs) are available clinically, molecular complexity NSCLC has made it necessary search for alternative therapeutic approaches overcome drug NSCLC. In present study, we identified a triterpene molecule derived from herbal plant Tripterygium wilfordii, celastrol, as novel autophagy inducer. We demonstrate that celastrol...
Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, the treatment cancers have been extensively investigated over last few decades. Autophagy is now emerging as an important pathway death survival therapy. Recent studies demonstrated variety natural small-molecules could induce autophagic apoptosis-resistant cells, therefore, discovery novel enhancers from products be...
Despite extensive investigation of the insulin-like growth factor (IGF)/IGF-binding protein (IGFBP) system in circulation and body fluids, there is no information on this interstitial fluid. We have compared IGF/IGFBP with that fluid obtained from blisters artificially raised by negative pressure 10 healthy volunteers. IGFBP-1, -2, -3, -4 were all found blister fluid, but concentrations much lower than those matched serum. The IGF-I, IGF-II, IGFBP-3 levels measured RIA 18%, 14%, 16% serum,...
We have recently identified gonadotropes as target cells for ATP action via receptors of the P2U subtype. The present studies used gonadotrope-derived alpha T3-1 to examine possible signaling mechanisms subserving in gonadotropes. Addition produced a biphasic intracellular Ca2+ (Ca2+i) response: transient spike followed by small plateau. Removal extracellular or depolarization with KCl abolished plateau but had no effect on spike. was also blocked cadmium nifedipine not nickel. Pretreatment...
Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease of children caused by mutations in TPP1, the gene encoding lysosomal protease tripeptidyl peptidase 1. LINCL characterized accumulation storage material which only single protein component, subunit c mitochondrial ATP synthase, has been well established to date. Identification other constituents could provide useful insights into pathophysiology and natural substrates for TPP1. We have...