Publications by authors named "Long Wong"

8 Publications

  • Page 1 of 1

Two Blends of Refined Rice Bran, Flaxseed, and Sesame Seed Oils Affect the Blood Lipid Profile of Chinese Adults with Borderline Hypercholesterolemia to a Similar Extent as Refined Olive Oil.

J Nutr 2020 12;150(12):3141-3151

Clinical Nutrition Research Centre (CNRC), Singapore Institute of Food and Biotechnology Innovations (SIFBI), Agency for Science Technology and Research (A*STAR), Singapore.

Background: Individual vegetable oils have a characteristic fatty acids (FA) composition and unique phytonutrient profiles, enabling formulation of oil blends that may have health-promoting effects.

Objective: The primary objective of this study was to investigate effects of 2 oil blends made with refined rice bran, flaxseed, and sesame oils, with distinct monounsaturated to saturated FA, polyunsaturated to saturated FA, and omega-3 (n-3) to omega-6 FA ratios and different phytonutrient concentrations on blood lipid profile, compared with refined olive oil as a control. The secondary outcomes were other markers of cardiometabolic health.

Methods: A parallel-design, randomized controlled trial compared consumption of 30 g of allocated intervention oil per day for a period of 8 wk. The study recruited 143 borderline hypercholesterolemic (LDL cholesterol: 3.06-4.51 mmol/L) Chinese volunteers between 50 and 70 y old and with a BMI (kg/m2) ≤27.5. All outcomes were measured every 2 wk, and the time × treatment interactions and the main effects of treatment and time were analyzed using an intention-to-treat approach.

Results: Compared with baseline (week 0), there were significant reductions during the post-intervention time points in serum total cholesterol (-3.47%; P < 0.0001), LDL cholesterol (-4.16%; P < 0.0001), triglycerides (-10.3%; P < 0.0001), apoB (-3.93%; P < 0.0001), total to HDL-cholesterol (-3.44%; P < 0.0001) and apoB to apoA1 (-3.99%; P < 0.0001) ratios, systolic and diastolic blood pressures (-3.32% and -3.16%, respectively; both P < 0.0001), and serum glucose (-1.51%; P < 0.05) and a small but significant increase in body weight (+0.7%; P < 0.001) for all 3 intervention oils but no effects of intervention on HDL-cholesterol or apoA1 concentration. No significant effects of treatment or time × treatment interactions were found.

Conclusions: Using blended vegetable oils that are extensively consumed in Asia, this study found that specific oil blends can improve blood lipid profile and other cardiometabolic parameters, to a similar extent as refined olive oil, in Chinese adults with borderline hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03964857.
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http://dx.doi.org/10.1093/jn/nxaa274DOI Listing
December 2020

Amorphous ternary nanoparticle complex of curcumin-chitosan-hypromellose exhibiting built-in solubility enhancement and physical stability of curcumin.

Colloids Surf B Biointerfaces 2018 Jul 27;167:483-491. Epub 2018 Apr 27.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore. Electronic address:

The low aqueous solubility of curcumin (CUR) had greatly limited the clinical efficacy of CUR therapy despite its well-known potent therapeutic activities. Previously, we developed amorphous nanoparticle complex (nanoplex) of CUR and chitosan (CHI) as a solubility enhancement strategy of CUR by electrostatically-driven drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, (1) lacked a built-in ability to produce prolonged high apparent solubility of CUR in the absence of crystallization-inhibiting agents, and (2) exhibited poor physical stability during long-term storage. For this reason, herein we developed amorphous ternary nanoplex of CUR, CHI, and hypromellose (HPMC) where HPMC functioned as the crystallization inhibitor. The effects of incorporating HPMC on the (1) physical characteristics and (2) preparation efficiency of the CUR-CHI-HPMC nanoplex produced were investigated. Compared to the CUR-CHI nanoplex, the HPMC inclusion led to larger nanoplex (≈300-500 nm) having lower zeta potential (≈1-15 mV) and lower CUR payload (≈40-80%), albeit with higher CUR utilization rates (≈100%) attributed to the CUR interactions with both CHI and HPMC. The CUR-CHI-HPMC nanoplex's physical characteristics could be controlled by varying the HPMC to CHI ratio in the feed. Subsequently, the CUR-CHI-HPMC and CUR-CHI nanoplexes were examined in terms of their (1) storage stability, (2) dissolution characteristics in simulated gastrointestinal fluids, and (3) in vitro solubility enhancement. The results showed that the CUR-CHI-HPMC nanoplex exhibited superior (i) amorphous state stability after twelve-month storage, (ii) dissolution characteristics, and (iii) solubility enhancement in simulated gastrointestinal fluids, with minimal cytotoxicity towards human gastric epithelial cells.
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http://dx.doi.org/10.1016/j.colsurfb.2018.04.049DOI Listing
July 2018

Effects of sulfonylurea as initial treatment on testosterone of middle-aged men with type 2 diabetes: A 16-week, pilot study.

J Diabetes Investig 2015 Jul 16;6(4):454-9. Epub 2015 Jan 16.

Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou, Guangdong, China.

Aims/introduction: To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes.

Materials And Methods: As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study. After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks. Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group.

Results: Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index. Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values. Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline.

Conclusions: It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.
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http://dx.doi.org/10.1111/jdi.12324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511305PMC
July 2015

Spatially resolved microrheology of heterogeneous biopolymer hydrogels using covalently bound microspheres.

Biomech Model Mechanobiol 2014 Aug 26;13(4):839-49. Epub 2013 Oct 26.

Chemical and Pharmaceutical Engineering, Singapore-MIT Alliance, National University of Singapore, Singapore, 117576, Singapore.

Characterization of the rheological properties of heterogeneous biopolymers is important not only to understand the effect of substrate elasticity on cell behaviors, but also to provide insights into mechanical changes during cellular remodeling of the environment. Conventional particle-tracking microrheology (PTM) techniques are compromised by probe-network slippage and cage-hopping problems, and require a priori knowledge of network mesh size in order to determine a suitable probe size. We demonstrated here the usefulness of covalently bound probes for PTM of biopolymers to overcome the above limitations. We showed that, in a well-defined system like polyacrylamide gels, surface-modified probe particles using a zero-length crosslinker provided more reliable measurements of network mechanics as compared to standard carboxylated probes. We further demonstrated that appropriate surface modification of microspheres for PTM circumvented the requirement of using microspheres larger than the network mesh, an approach typically considered to be ideal. Using the method presented in this study, we found the local network at the leading edge of a typical C6 glioma cell to be stiffer as compared to the side. Our findings established that permanent interaction between the probe and network is crucial to reliably measure the local network mechanics in reconstituted, heterogeneous networks using PTM.
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http://dx.doi.org/10.1007/s10237-013-0538-4DOI Listing
August 2014

Early stiffening and softening of collagen: interplay of deformation mechanisms in biopolymer networks.

Biomacromolecules 2012 Mar 15;13(3):691-8. Epub 2012 Feb 15.

NUS Graduate School for Integrative Sciences and Engineering, Singapore 117456.

Collagen networks, the main structural/mechanical elements in biological tissues, increasingly serve as biomimetic scaffolds for cell behavioral studies, assays, and tissue engineering, and yet their full spectrum of nonlinear behavior remains unclear. Here, with self-assembled type-I collagen as model, we use metrics beyond those in standard single-harmonic analysis of rheological measurements to reveal strain-softening and strain-stiffening of collagen networks both in instantaneous responses and at steady state. The results show how different deformation mechanisms, such as deformation-induced increase in the elastically active fibrils, nonlinear extension of individual fibrils, and slips in the physical cross-links in the network, can lead to the observed complex nonlinearity. We demonstrate how comprehensive rheological analyses can uncover the rich mechanical properties of biopolymer networks, including the above-mentioned softening as well as an early strain-stiffening, which are important for understanding physiological response of biological materials to mechanical loading.
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http://dx.doi.org/10.1021/bm2015812DOI Listing
March 2012

Response to the methylation inhibitor dihydro-5-azacytidine in mesothelioma is not associated with methylation of p16INK4a: results of cancer and leukemia group B 159904.

J Thorac Oncol 2008 Apr;3(4):417-21

Division of Hematology-Oncology-Transplant, The University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.

Introduction: The molecular mechanisms of oncogenesis in mesothelioma involve the loss of negative regulators of cell growth including p16INK4a. Absence of expression of the p16INK4a gene product is exhibited in virtually all mesothelioma tumors and cell lines examined to date. Loss of p16INK4a expression has also been frequently observed in more common neoplasms such as lung cancer as well. In a wide variety of these malignancies, including lung cancer, p16INK4a expression is known to be inactivated by hypermethylation of the first exon. This project (CALGB 159904) intended to test the hypothesis that in mesothelioma loss of p16INK4a via methylation would correlate with response to the cytidine analog and methylation inhibitor dihydro-5-azacytidine (DHAC).

Methods: Using tissue samples from CALGB 8833 and 9031, two clinical studies which used DHAC based therapy in mesothelioma, this study tested the hypothesis that tumors possessing methylation of p16INK4a would have a better response and survival following DHAC treatment than their nonmethylated counterparts.

Results: Methylation of p16INK4a was identified in 4 of the 20 specimens. Although there was a trend towards improved survival the result was not statistically significant.

Conclusions: There was no significant correlation between the presence of p16INK4a methylation and response to DHAC therapy or overall survival.
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http://dx.doi.org/10.1097/JTO.0b013e318168da0aDOI Listing
April 2008

Inactivation of p16INK4a expression in malignant mesothelioma by methylation.

Lung Cancer 2002 Nov;38(2):131-6

Research Service, Minneapolis VA Medical Center, Minneapolis, MN, USA.

The molecular mechanisms of oncogenesis in mesothelioma involve the loss of negative regulators of cell growth including p16(INK4a). Absence of expression of the p16(INK4a) gene product is exhibited in virtually all mesothelioma tumors and cell lines examined to date. Loss of p16(INK4a) expression has also been frequently observed in more common neoplasms such as lung cancer as well. In a wide variety of these malignancies, including lung cancer, p16(INK4a) expression is known to be inactivated by hypermethylation of the first exon. In a survey of ten mesothelioma cell lines, one cell line (NCI-H2596) was identified as possessing loss of p16(INK4a) gene product following gene methylation. This methylation in these mesothelioma cells could be reversed, resulting in re-expression of p16(INK4a) protein, following the treatment of the cells with cytidine analogs, which are known inhibitors of DNA methylation. In previous clinical trials in mesothelioma, the cytidine analog dihydro-5-azacytidine (DHAC) has been found to induce clinical responses in approximately 17% of patients with mesothelioma treated with this drug, including prolonged complete responses. In addition, we identified evidence for methylation of p16(INK4a) in three of 11 resected mesothelioma tumor samples. When both cell lines and tumors are combined, inactivation of p16(INK4a) gene product expression following DNA hypermethylation was found in four of 21 samples (19%). We are further exploring the clinical significance of inhibition of methylation in mesothelioma by cytidine analogs. This may provide a potential treatment target in some mesothelioma tumors by inhibition of methylation.
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http://dx.doi.org/10.1016/s0169-5002(02)00178-2DOI Listing
November 2002
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