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Solubilization and formulation of chrysosplenol C in solid dispersion with hydrophilic carriers
Ng, C.L.,Lee, S.E.,Lee, J.K.,Kim, T.H.,Jang, W.S.,Choi, J.S.,Kim, Y.H.,Kim, J.K.,Park, J.S. Elsevier/North Holland 2016 International journal of pharmaceutics Vol.512 No.1
We investigated how to overcome problems associated with the solubility, dissolution, and oral bioavailability of the poorly water-soluble drug compound, chrysosplenol C (CRSP), as well as the effects of single and binary hydrophilic polymers (PVP K-25 and/or PEG 6000) on the solubility and dissolution parameters of CRSP. Then an optimized formulation was further developed with a surfactant. To select a surfactant suitable for a CRSP-loaded solid dispersion (SD), the solubility of CRSP in distilled water containing 1% surfactant was compared with the solubilities in other surfactants. Sodium lauryl sulfate (SLS) showed the highest drug solubility. Overall, a formulation containing CRSP, binary hydrophilic polymers (PVP and PEG 6000), and SLS at a ratio of 2.0/0.2/1.1/0.7 showed the optimum in vitro release profile. This optimized formulation had better safety properties than pure CRSP in cell viability examinations. SD formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy. Our optimized SD formulation is expected to improve the bioavailability of CRPS because it improves the solubility and dissolution rate of CRSP.
Ng, Maggie C.Y.,Park, Kyong Soo,Oh, Bermseok,Tam, Claudia H.T.,Cho, Young Min,Shin, Hyoung Doo,Lam, Vincent K.L.,Ma, Ronald C.W.,So, Wing Yee,Cho, Yoon Shin,Kim, Hyung-Lae,Lee, Hong Kyu,Chan, Juliana American Diabetes Association 2008 Diabetes Vol.57 No.8
<P><B>OBJECTIVE—</B> Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed <I>TCF7L2</I> as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear.</P><P><B>RESEARCH DESIGN AND METHODS—</B> We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea.</P><P><B>RESULTS—</B> We confirmed the associations of <I>TCF7L2</I>, <I>SLC30A8</I>, <I>HHEX</I>, <I>CDKAL1</I>, <I>CDKN2A</I>/<I>CDKN2B</I>, <I>IGF2BP2</I>, and <I>FTO</I> with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 × 10<SUP>−12</SUP> < <I>P</I><SUB>unadjusted</SUB> < 0.016). In addition, the A allele of rs8050136 at <I>FTO</I> was associated with increased BMI in the control subjects (<I>P</I><SUB>unadjusted</SUB> = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations.</P><P><B>CONCLUSIONS—</B> Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.</P>
E.L.H. Ng,K.K. Lau,W.J. Lau,Faizan Ahmad 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.104 No.-
Hollow fiber membrane contactor (HFMC) has been widely studied for gas separation process due to itsprocess intensification capability of combining conventional contactors with membrane technology. Inthe area of modeling and simulation of HFMC, the development of mathematical model for non-ideal conditions,that is incorporated into process design is key to accurately reflect actual industrial gas separationprocess. This article aims to review the modelling and simulation techniques, the capabilities and thelimitations of different mathematical models in predicting gas separation performance in HFMC for bothlaboratory analysis and industrial applications. The approach of incorporating the HFMC models into gasseparation system and the current progress of process simulation works to develop industrial scale gasseparation process will be highlighted. Future works and challenges towards developing comprehensivemodel in HFMC for industrial gas separation process would also be presented to portray the potential ofmodelling and simulation in designing and optimizing the HFMC system.
Crack analysis of reinforced concrete members with and without crack queuing algorithm
P.L. Ng,F.J. Ma,A.K.H. Kwan 국제구조공학회 2019 Structural Engineering and Mechanics, An Int'l Jou Vol.70 No.1
Due to various numerical problems, crack analysis of reinforced concrete members using the finite element method is confronting with substantial difficulties, rendering the prediction of crack patterns and crack widths a formidable task. The root cause is that the conventional analysis methods are not capable of tracking the crack sequence and accounting for the stress relief and re-distribution during cracking. To address this deficiency, the crack queuing algorithm has been proposed. Basically, at each load increment, iterations are carried out and within each iteration step, only the most critical concrete element is allowed to crack and the stress re-distribution is captured in subsequent iteration by re-formulating the cracked concrete element and re-analysing the whole concrete structure. To demonstrate the effectiveness of the crack queuing algorithm, crack analysis of concrete members tested in the literature is performed with and without the crack queuing algorithm incorporated.
이공훈(Ko ng H oon Lee),김욱중(Oo k Joo ng K im),하수석(Su seok H a),강새별(Sae By ul Kan g),이준식(Joon Sik L ee) 대한기계학회 2003 대한기계학회 춘추학술대회 Vol.2003 No.11
Analysis has been carried out to investigate the temperature variation and the uniformity of the<br/> temperature distribution of the glass panel by infrared radiant heating. Halogen lamps are used to heat<br/> the panel and located near the top and bottom of the rectangular chamber. The thermal energy is<br/> transfered only by radiation and the radiation exchange occurs only on the solid surfaces and is<br/> considered by using the view factor. The results show that the uniformity of the temperature<br/> distribution of the panel is improved but the time for heating increases as the wall reflectivity is large.<br/> The temperature difference reaches a maximum in the early stage of the heating process and then<br/> decreases until it reaches the uniform steady-state value.
Mammalian Systems Biotechnology Reveals Global Cellular Adaptations in a Recombinant CHO Cell Line
Yusufi, F.N.K.,Lakshmanan, M.,Ho, Y.S.,Loo, B.L.W.,Ariyaratne, P.,Yang, Y.,Ng, S.K.,Tan, T.R.M.,Yeo, H.C.,Lim, H.L.,Ng, S.W.,Hiu, A.P.,Chow, C.P.,Wan, C.,Chen, S.,Teo, G.,Song, G.,Chin, J.X.,Ruan, X. Cell Press 2017 Cell systems Vol.4 No.5
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipid species, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner.
( Y. Y. Wang ),( Z. B. Fu ),( K. L. Ng ),( C. C. Lam ),( A. K. N. Chan ),( K. F. Sze ),( W. K. R. Wong ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.6
Production of recombinant proteins by excretory expression has many advantages over intracellular expression in Escherichia coli. Hyperexpression of a secretory exoglucanase, Exg, of Cellulomonas fimi was previously shown to saturate the SecYEG pathway and result in dramatic cell death of E. coli. In this study, we demonstrated that overexpression of the PspA in the JM101(pM1VegGcexL-pspA) strain enhanced excretion of Exg to 1.65 U/ml using shake-flask cultivation, which was 80% higher than the highest yield previously obtained from the optimized JM101(pM1VegGcexL) strain. A much higher excreted Exg activity of 4.5 U/ml was further achieved with high cell density cultivation using rich media. Furthermore, we showed that the PspA overexpression strain enjoyed an elevated critical value (CV), which was defined as the largest quotient between the intracellular unprocessed precursor and its secreted mature counterpart that was still tolerable by the host cells prior to the onset of cell death, improving from the previously determined CV of 20/80 to the currently achieved CV of 45/55 for Exg. The results suggested that the PspA overexpression strain might tolerate a higher level of precursor Exg making use of the SecYEG pathway for secretion. The reduced lethal effect might be attributable to the overexpressed PspA, which was postulated to be able to reduce membrane depolarization and damage. Our findings introduce a novel strategy of the combined application of metabolic engineering and construct optimization to the attainment of the best possible E. coli producers for secretory/excretory production of recombinant proteins, using Exg as the model protein.