Hanry Yu
Email Address
phsyuh@nus.edu.sg
Organizational Units
PHYSIOLOGY
dept
YONG LOO LIN SCH OF MEDICINE
faculty
172 results
Publication Search Results
Now showing 1 - 10 of 172
Publication Detection of telomerase activity in gastric lavage fluid: A novel method to detect gastric cancer(2006) Ching-Ho, Wong S.; Yu, H.; So, J.B.Y.; PHYSIOLOGYBackground. Telomerase is a ribonucleoprotein polymerase that is essential for cell immortality. Recent studies have demonstrated that a high percentage of gastric cancer tissue expressed telomerase. This study describes the presence of telomerase activity in gastric lavage fluid in patients with gastric cancer. Methods. Gastric lavage fluid was collected during esophageogastroduodenoscopy in 70 patients: 25 with gastric cancer, 25 with peptic ulcer disease, and 20 with normal stomach. The fluid and biopsy samples were analyzed for telomerase activity by a polymerase chain reaction-based telomerase repeat amplification protocol. The findings were related to the histological results. Results. Telomerase activity was present in 24 of the 25 (96%) gastric cancer tissue and in 7 of the 25 tissue specimens from peptic ulcer or gastritis. In the gastric lavage fluid, telomerase was detected in 20 patients (80%) with gastric cancer, 7 patients (28%) with peptic ulcer, and none in normal subjects (P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of gastric fluid telomerase expression in gastric cancer patients was 80%, 84%, 74%, and 88%, respectively. Conclusions. The presence of telomerase activity is present in gastric lavage fluid of patients with gastric cancer as compared to those without, may represent a novel method for diagnosis of gastric cancer. © 2006 Elsevier Inc. All rights reserved.Publication An estimate of the contribution of spherical aberration and self-shadowing in confocal and multi-photon fluorescent microscopy(2002) Cheng, P.C.; Hibbs, A.R.; Yu, H.; Lin, P.C.; Cheng, W.Y.; NATIONAL UNIVERSITY MEDICAL INSTITUTESPublication Purpose-driven biomaterials research in liver-tissue engineering(2011-03) Ananthanarayanan, A.; Narmada, B.C.; Mo, X.; McMillian, M.; Yu, H.; NATIONAL UNIVERSITY MEDICAL INSTITUTESBottom-up engineering of microscale tissue (" microtissue") constructs to recapitulate partially the complex structure-function relationships of liver parenchyma has been realized through the development of sophisticated biomaterial scaffolds, liver-cell sources, and in vitro culture techniques. With regard to in vivo applications, the long-lived stem/progenitor cell constructs can improve cell engraftment, whereas the short-lived, but highly functional hepatocyte constructs stimulate host liver regeneration. With regard to in vitro applications, microtissue constructs are being adapted or custom-engineered into cell-based assays for testing acute, chronic and idiosyncratic toxicities of drugs or pathogens. Systems-level methods and computational models that represent quantitative relationships between biomaterial scaffolds, cells and microtissue constructs will further enable their rational design for optimal integration into specific biomedical applications. © 2010 Elsevier Ltd.Publication Non-disruptive three-dimensional culture and harvest system for anchorage-dependent cells(2005-06-14) YU, HANRY; LEONG, KAM W.; CHIA, SER-MIEN; PHYSIOLOGY; DIVISION OF BIOENGINEERING; NATIONAL UNIVERSITY OF SINGAPORE (SINGAPORE, SG); AGENCY FOR SCIENCE, TECHNOLOGY & RESEARCHA non-disruptive three-dimensional culture system allows cell growth and proliferation in three dimensions, permitting cell splitting without subjecting cells to disruptive conditions that affect cell structure and functions. An extracellular matrix provides a good environment for culturing or co-culturing anchorage-dependent cells. The cells cultured this manner can be readily used in such applications as cell transplantation, tissue engineering seeding of cells on scaffolds, and other applications that require immediate availability of functioning cells.Publication Computational analysis reveals the coupling between bistability and the sign of a feedback loop in a TGF-?1 activation model(2017) Li, H; Venkatraman, L; Narmada, B.C; White, J.K; Yu, H; Tucker-Kellogg, L.; PHYSIOLOGY; MECHANOBIOLOGY INSTITUTE; DUKE-NUS MEDICAL SCHOOLBackground: Bistable behaviors are prevalent in cell signaling and can be modeled by ordinary differential equations (ODEs) with kinetic parameters. A bistable switch has recently been found to regulate the activation of transforming growth factor-?1 (TGF-?1) in the context of liver fibrosis, and an ordinary differential equation (ODE) model was published showing that the net activation of TGF-?1 depends on the balance between two antagonistic sub-pathways. Results: Through modeling the effects of perturbations that affect both sub-pathways, we revealed that bistability is coupled with the signs of feedback loops in the model. We extended the model to include calcium and Krüppel-like factor 2 (KLF2), both regulators of Thrombospondin-1 (TSP1) and Plasmin (PLS). Increased levels of extracellular calcium, which alters the TSP1-PLS balance, would cause high levels of TGF-?1, resembling a fibrotic state. KLF2, which suppresses production of TSP1 and plasminogen activator inhibitor-1 (PAI1), would eradicate bistability and preclude the fibrotic steady-state. Finally, the loop PLS - TGF-?1 - PAI1 had previously been reported as negative feedback, but the model suggested a stronger indirect effect of PLS down-regulating PAI1 to produce positive (double-negative) feedback in a fibrotic state. Further simulations showed that activation of KLF2 was able to restore negative feedback in the PLS - TGF-?1 - PAI1 loop. Conclusions: Using the TGF-?1 activation model as a case study, we showed that external factors such as calcium or KLF2 can induce or eradicate bistability, accompanied by a switch in the sign of a feedback loop (PLS - TGF-?1 - PAI1) in the model. The coupling between bistability and positive/negative feedback suggests an alternative way of characterizing a dynamical system and its biological implications. © 2017 The Author(s).Publication Cloning of rat telomerase catalytic subunit functional domains, reconstitution of telomerase activity and enzymatic profile of pig and chicken tissues(2003-10-10) Wong, S.C.H.; Ong, L.L.; Er, C.P.N.; Gao, S.; Yu, H.; So, J.B.Y.; NATIONAL UNIVERSITY MEDICAL INSTITUTESTelomerase is a ribonucleoprotein polymerase which adds TTAGGG repeats to telomeric ends. Recent studies reported the reverse transcription enzyme activity mostly from the catalytic subunit (TERT) of the enzyme complex. Both human telomerase catalytic subunit (hTERT) and mouse telomerase catalytic subunit (mTERT) had been previously cloned but not rat telomerase catalytic subunit rTERT. In this study, the rTERT functional domains were cloned and was found that its function resemble to mouse and human telomerase. In addition, chicken and pig telomerase activity profile were studied and its enzyme activity is related to its proliferation capability of individual tissues. However, its catalytic subunit does not like mouse, rat and human cases that the telomerase activity could not reconstituted by the in-vitro transfection of mTERT and hTERT cloned vectors. Here we demonstrated that rTERT is similar to mTERT and hTERT but not pig and chicken telomerase. Further studies are needed to verify the malignancy characteristics because nowadays artificial organs/tissues from these animals are used for the transplantation to human body. © 2003 Elsevier Inc. All rights reserved.Publication Datasets describing the growth and molecular features of hepatocellular carcinoma patient-derived xenograft cells grown in a three-dimensional macroporous hydrogel(Elsevier Inc., 2018) Fong, E.L.S.; Toh, T.B.; Lin, Q.X.X.; Liu, Z.; Hooi, L.; Rashid, M.B.M.A.; Benoukraf, T.; Chow, E.K.-H.; Huynh, T.H.; Yu, H.; PHARMACOLOGY; BIOMEDICAL ENGINEERING; PHYSIOLOGY; LIFE SCIENCES INSTITUTE; CANCER SCIENCE INSTITUTE OF SINGAPOREThis data article presents datasets associated with the research article entitled “Generation of matched patient-derived xenograft in vitro–in vivo models using 3D macroporous hydrogels for the study of liver cancer” (Fong et al., 2018) [1]. A three-dimensional macroporous sponge system was used to generate in vitro counterparts to various hepatocellular carcinoma patient-derived xenograft (HCC-PDX) lines. This article describes the viability, proliferative capacity and molecular features (genomic and transcriptomic profiles) of the cultured HCC-PDX cells. The sequencing datasets are made publicly available to enable critical or further analyzes. © 2018 The AuthorsPublication Transient inter-cellular polymeric linker(2007) Ong, S.-M.; Arooz, T.; Tang, G.; Yu, H.; He, L.; Tan, C.-H.; Thuy, Linh N.T.; Tee, Y.-H.; PHYSIOLOGY; CHEMISTRYThree-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix-poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but transiently with inter-cellular polymeric linker to facilitate cell-cell interaction and aggregation. The linker consists of a non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that can aggregate cells within 30 min by reacting with the aldehyde handles on the chemically modified cell-surface glycoproteins. The cells in the cellular aggregates proliferated; and maintained the cortical actin distribution of the 3D cell morphology while non-aggregated cells died over 7 days of suspension culture. The aggregates lost distinguishable cell-cell boundaries within 3 days; and the ECM fibers became visible around cells from day 3 onwards while the inter-cellular polymeric linker disappeared from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications. © 2007 Elsevier Ltd. All rights reserved.Publication Evaluation of collagen and methylated collagen as gene carriers(2004) Wang, J.; Lee, I.-L.; Lim, W.S.; Leong, K.W.; Mao, H.-Q.; Chia, S.M.; Yu, H.; PHYSIOLOGY; MATERIALS SCIENCEThis study explores the potential of DNA complexes prepared with methylated collagen (MC) and unmodified native collagen (NC) to deliver genes into cells. The physicochemical properties and transfection abilities of these two types of complexes are studied in parallel. MC was prepared by methylation of the carboxyl groups of collagen, rendering the collagen net positively charged at neutral pH. NC/DNA complexes were prepared at pH ∼3, but aggregated rapidly at neutral pH. These complexes did not confer significant protection to DNA due to its poor stability in serum. MC carried a positive charge at neutral pH and formed complexes with DNA in PBS; therefore MC improved DNA binding ability and the stability of the complexes at physiological conditions. MC/DNA complexes were smaller and more stable than NC/DNA complexes in PBS, and sustained released of DNA from MC/DNA complexes was observed for up to 3 weeks in PBS at 37°C. In contrast, NC/DNA complexes released almost all the DNA within 6 h under the same condition. In vitro gene transfection experiments revealed that MC mediated a higher gene expression than NC, although the level of gene expression was still much lower than that achieved with polyethyleneimine/DNA complexes. In contrast to in vitro results, NC/DNA complexes yielded a 3.8-fold higher gene expression than naked DNA and MC/DNA complexes (P < 0.05) at week 2 following intramuscular injection at a DNA dose of 3 μg per muscle and a weight ratio of 1. Higher weight ratios resulted in significant decrease of transfection efficiency, particularly for MC/DNA complexes. The results suggested that gene delivery via the intramuscular route followed a different mechanism that demands a different set of physiochemical properties of the carrier from other parental routes. The potential of these collagen-based gene carriers for other administration routes remain to be further investigated. © 2004 Elsevier B.V. All rights reserved.Publication Hepatic spheroids used as an in vitro model to study malaria relapse(ELSEVIER SCI LTD, 2019-09-01) Chua, Adeline CY; Ananthanarayanan, Abhishek; Ong, Jessica Jie Ying; Wong, Jen Yi; Yip, Andy; Singh, Nisha Hari; Qu, Yinghua; Dembele, Laurent; McMillian, Michael; Ubalee, Ratawan; Davidson, Silas; Tungtaeng, Anchalee; Imerbsin, Rawiwan; Gupta, Kapish; Andolina, Chiara; Lee, Fan; Tan, Kevin S-W; Nosten, Francois; Russell, Bruce; Lange, Amber; Diagana, Thierry T; Renia, Laurent; Yeung, Bryan KS; Yu, Hanry; Bifani, Pablo; Assoc Prof Tan Shyong Wei, Kevin; PHYSIOLOGY; MICROBIOLOGY AND IMMUNOLOGY; MECHANOBIOLOGY INSTITUTE© 2019 The Authors Hypnozoites are the liver stage non-dividing form of the malaria parasite that are responsible for relapse and acts as a natural reservoir for human malaria Plasmodium vivax and P. ovale as well as a phylogenetically related simian malaria P. cynomolgi. Our understanding of hypnozoite biology remains limited due to the technical challenge of requiring the use of primary hepatocytes and the lack of robust and predictive in vitro models. In this study, we developed a malaria liver stage model using 3D spheroid-cultured primary hepatocytes. The infection of primary hepatocytes in suspension led to increased infectivity of both P. cynomolgi and P. vivax infections. We demonstrated that this hepatic spheroid model was capable of maintaining long term viability, hepatocyte specific functions and cell polarity which enhanced permissiveness and thus, permitting for the complete development of both P. cynomolgi and P. vivax liver stage parasites in the infected spheroids. The model described here was able to capture the full liver stage cycle starting with sporozoites and ending in the release of hepatic merozoites capable of invading simian erythrocytes in vitro. Finally, we showed that this system can be used for compound screening to discriminate between causal prophylactic and cidal antimalarials activity in vitro for relapsing malaria.