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Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation
Lee HY, Jeong YI, Choi KC
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S26458
Abstract: ir dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation Original Research (3575) Total Article Views Authors: Lee HY, Jeong YI, Choi KC Published Date November 2011 Volume 2011:6 Pages 2879 - 2888 DOI: http://dx.doi.org/10.2147/IJN.S26458 Hye-Young Lee1,*, Young-IL Jeong2,*, Ki-Choon Choi3 1Anyang Science University, Anyang, Gyeonggi, South Korea; 2Chonnam National University Hwasun Hospital, Jeonnam, South Korea; 3Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration, Chungnam, South Korea *These authors contributed equally to this work. Background: p-Phenylenediamine (PDA) or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair dyes such as PDA are known to have potent contact allergy reactions in humans, and severe allergic reactions are problematic. Methods: PDA-incorporated nanoparticles were prepared based on ion-complex formation between the cationic groups of PDA and the anionic groups of poly(γ-glutamic acid) (PGA). To reinforce PDA/PGA ion complexes, glycol chitosan (GC) was added. PDA-incorporated nanoparticles were characterized using field-emission scanning electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering, and powder X-ray diffractometry (XRD). Results: Nanoparticles were formed by ion-complex formation between the amine groups of PDA and the carboxyl groups of PGA. PDA-incorporated nanoparticles are small in size (<100 nm), and morphological observations showed spherical shapes. FT-IR spectra results showed that the carboxylic acid peak of PGA decreased with increasing PDA content, indicating that the ion complexes were formed between the carboxyl groups of PGA and the amine groups of PDA. Furthermore, the intrinsic peak of the carboxyl groups of PGA was also decreased by the addition of GC. Intrinsic crystalline peaks of PDA were observed by XRD. This crystalline peak of PDA was completely nonexistent when nanoparticles were formed by ion complex between PDA, PGA, and GC, indicating that PDA was complexed with PGA and no free drug existed in the formulation. During the drug-release experiment, an initial burst release of PDA was observed, and then PDA was continuously released over 1 week. Cytotoxicity testing against HaCaT human skin keratinocyte cells showed PDA-incorporated nanoparticles had lower toxicity than PDA itself. Furthermore, PDA-incorporated nanoparticles showed reduced apoptosis and necrosis reaction at HaCaT cells. Conclusion: The authors suggest that these microparticles are ideal candidates for a vehicle for decreasing side effects of hair dye.
Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation
Lee HY,Jeong YI,Choi KC
International Journal of Nanomedicine , 2011,
Abstract: Hye-Young Lee1,*, Young-IL Jeong2,*, Ki-Choon Choi31Anyang Science University, Anyang, Gyeonggi, South Korea; 2Chonnam National University Hwasun Hospital, Jeonnam, South Korea; 3Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration, Chungnam, South Korea*These authors contributed equally to this work.Background: p-Phenylenediamine (PDA) or its related chemicals are used more extensively than oxidative hair dyes. However, permanent hair dyes such as PDA are known to have potent contact allergy reactions in humans, and severe allergic reactions are problematic.Methods: PDA-incorporated nanoparticles were prepared based on ion-complex formation between the cationic groups of PDA and the anionic groups of poly(γ-glutamic acid) (PGA). To reinforce PDA/PGA ion complexes, glycol chitosan (GC) was added. PDA-incorporated nanoparticles were characterized using field-emission scanning electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering, and powder X-ray diffractometry (XRD).Results: Nanoparticles were formed by ion-complex formation between the amine groups of PDA and the carboxyl groups of PGA. PDA-incorporated nanoparticles are small in size (<100 nm), and morphological observations showed spherical shapes. FT-IR spectra results showed that the carboxylic acid peak of PGA decreased with increasing PDA content, indicating that the ion complexes were formed between the carboxyl groups of PGA and the amine groups of PDA. Furthermore, the intrinsic peak of the carboxyl groups of PGA was also decreased by the addition of GC. Intrinsic crystalline peaks of PDA were observed by XRD. This crystalline peak of PDA was completely nonexistent when nanoparticles were formed by ion complex between PDA, PGA, and GC, indicating that PDA was complexed with PGA and no free drug existed in the formulation. During the drug-release experiment, an initial burst release of PDA was observed, and then PDA was continuously released over 1 week. Cytotoxicity testing against HaCaT human skin keratinocyte cells showed PDA-incorporated nanoparticles had lower toxicity than PDA itself. Furthermore, PDA-incorporated nanoparticles showed reduced apoptosis and necrosis reaction at HaCaT cells.Conclusion: The authors suggest that these microparticles are ideal candidates for a vehicle for decreasing side effects of hair dye.Keywords: p-phenylenediamine, keratinocyte, PDA, PGA
Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups
Hong SC,Lee JH,Lee J,Kim HY
International Journal of Nanomedicine , 2011,
Abstract: Seong Cheol Hong1,*, Jong Ho Lee1,*, Jaewook Lee1, Hyeon Yong Kim1, Jung Youn Park2, Johann Cho3, Jaebeom Lee1, Dong-Wook Han11Department of Nanomedical Engineering, BK21 Nano Fusion Technology Division, College of Nanoscience and Nanotechnology, Pusan National University, 2Department of Biotechnology Research, National Fisheries Research and Development Institute, Busan, 3Electronic Materials Lab, Samsung Corning Precision Materials Co, Ltd, Gumi City, Gyeongsangbukdo, Korea*These authors contributed equally to this workAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with –O-groups, so-called bare SPIONs. Following this, they were modified with three different functional groups – hydroxyl (–OH), carboxylic (–COOH), and amine (–NH2) groups – by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2',7'-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation
Cost–utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model
Lee HY,Yang BM,Hong JM,Lee TJ
ClinicoEconomics and Outcomes Research , 2013,
Abstract: Hwa-young Lee,1 Bong-Min Yang,1 Ji-min Hong,1 Tae-Jin Lee,1 Byoung-Gie Kim,2 Jae-Weon Kim,3 Young-Tae Kim,4 Yong-Man Kim,5 Sokbom Kang61Graduate School of Public Health, Seoul National University, Seoul, South Korea; 2Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Seoul National University, Seoul, South Korea; 4Department of Obstetrics and Gynecology, Yonsei University, Seoul, South Korea; 5Department of Obstetrics and Gynecology, University of Ulsan, Ulsan, South Korea; 6Department of Obstetrics and Gynecology, National Cancer Center, Kyeonggi-do, South KoreaObjective: We performed a cost–utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer.Methods: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC) before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC). These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were transportation expenses. Utilities were also derived from the literature. Costs and utilities were discounted at an annual rate of 5% per cycle.Results: PLD/carboplatin combination as the second line in the sequence is more effective and costly than paclitaxel/carboplatin combination, showing an additional US$21,658 per quality-adjusted life years. This result was robust in a deterministic sensitivity analysis except when median time to progression of second-line therapies and administration cost of PLD/carboplatin per administration cycle were varied. The probability of cost-effectiveness for PLD/carboplatin combina
Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups
Hong SC, Lee JH, Lee J, Kim HY, Park JY, Cho J, Lee J, Han DW
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S26355
Abstract: btle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups Original Research (4218) Total Article Views Authors: Hong SC, Lee JH, Lee J, Kim HY, Park JY, Cho J, Lee J, Han DW Published Date December 2011 Volume 2011:6 Pages 3219 - 3231 DOI: http://dx.doi.org/10.2147/IJN.S26355 Seong Cheol Hong1,*, Jong Ho Lee1,*, Jaewook Lee1, Hyeon Yong Kim1, Jung Youn Park2, Johann Cho3, Jaebeom Lee1, Dong-Wook Han1 1Department of Nanomedical Engineering, BK21 Nano Fusion Technology Division, College of Nanoscience and Nanotechnology, Pusan National University, 2Department of Biotechnology Research, National Fisheries Research and Development Institute, Busan, 3Electronic Materials Lab, Samsung Corning Precision Materials Co, Ltd, Gumi City, Gyeongsangbukdo, Korea *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with –O-groups, so-called bare SPIONs. Following this, they were modified with three different functional groups – hydroxyl (–OH), carboxylic (–COOH), and amine (–NH2) groups – by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2',7'-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell cu
Spectrum of EGFR Gene Copy Number Changes and KRAS Gene Mutation Status in Korean Triple Negative Breast Cancer Patients
Yoonjung Kim, Juwon Kim, Hy-De Lee, Joon Jeong, Woochang Lee, Kyung-A Lee
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079014
Abstract: Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D), 1.0% (exon 19 del) and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.
Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells
Davy CW Lee, Chris KP Mok, Anna HY Law, Malik Peiris, Allan SY Lau
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-71
Abstract: Genetic characterization and phylogenetic analysis revealed that there are multiple lineages of H9N2 viruses isolated from various types of poultry including chickens, ducks, quail and pigeons. The H9N2 virus lineages found to be the most prevalent in poultry in southern China include the H9N2/G1-like lineage represented by A/Quail/Hong Kong/G1/97 (H9N2/G1) and the H9N2/Y280-like lineage represented by A/Duck/Hong Kong/Y280/97 (H9N2/Y280) and A/Chicken/Hong Kong/G9/97 (H9N2/G9) since 1997 [1]. These H9N2 lineages continued to disseminate in domestic poultry with the development of multiple reassortant subtypes from East Asia to the Middle East [2]. Additionally, avian-to-mammalian transmissions of H9N2 viruses were reported in Southeastern China [3].H9N2 viruses have repeatedly infected humans albeit causing a mild disease [3-5]. The low pathogenic H9N2 virus is widespread in poultry across Asia and Europe with ample opportunities for interaction with humans. It has caused infection in pigs (a putative mixing vessel for pandemic emergence) and causes severe disease in experimentally infected mice without prior adaptation [6]. The virus has an affinity for binding sialic acid receptors found on the human upper respiratory tract [7]. As past pandemics were not caused by highly pathogenic avian influenza viruses, the endemic of H9N2 viruses in poultry as well as their tropism for humans are at least as likely to cause the potential pandemic as the H5N1 virus, which is still the focus of attention [8]. Additionally, the H9N2/G1 viruses share six viral genes (viz. PB2, PB1, PA, NP, M and NS) with the lethal H5N1 viruses causing human disease in 1997 [1]. Furthermore, an H9N2 avian-human reassortant virus has been shown to have enhanced replication and efficient transmission in ferrets [9]. Thus H9N2 virus group is regarded by the World Health Organization as a potential pandemic candidate. Therefore we examined the replication characteristics of H9N2 virus lineages in th
In vitro suppression of oral squamous cell carcinoma growth by ultrasound-mediated delivery of curcumin microemulsions
Lin HY, Thomas JL, Chen HW, Shen CM, Yang WJ, Lee MH
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S28510
Abstract: vitro suppression of oral squamous cell carcinoma growth by ultrasound-mediated delivery of curcumin microemulsions Original Research (2984) Total Article Views Authors: Lin HY, Thomas JL, Chen HW, Shen CM, Yang WJ, Lee MH Published Date February 2012 Volume 2012:7 Pages 941 - 951 DOI: http://dx.doi.org/10.2147/IJN.S28510 Received: 23 November 2011 Accepted: 12 January 2012 Published: 21 February 2012 Hung-Yin Lin1,2, James L Thomas3, Huan-Wen Chen1, Chih-Min Shen4, Wen-Jen Yang2, Mei-Hwa Lee4 1Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung, Taiwan; 2Institute of Biotechnology, National University of Kaohsiung, Kaohsiung, Taiwan; 3Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM; 4Department of Materials Science and Engineering, I-Shou University, Kaohsiung, Taiwan Abstract: There is increasing interest in using natural products as anticancer agents, as many have antioxidative properties that may help to prevent cellular damage that can lead to cancer. In addition, there is the expectation that many natural products will have low toxicity and few side effects. However, most anticancer and antioxidative agents are hydrophobic, reducing their bioavailability in vivo and making them problematic to deliver. Curcumin provides a good model system for study. In low doses it shows both anticancer and antioxidation effects, whereas in high doses and delivered locally it could be cytotoxic for cancer cells. In this paper, curcumin microemulsions were formed with food-grade chemicals, including soybean lecithin, soybean oil, and Tween 80, a Food and Drug Administration-approved surfactant. The optimized composition formed curcumin microemulsions with a mean size of 40–50 nm, carrying a concentration of curcumin as high as 15 μM. The stability of curcumin microemulsions refrigerated at 5°C over at least 968 days was assessed by size distribution and zeta potential. The effects of low-frequency ultrasound on two oral squamous cell carcinoma cell lines (OSCC-4 and OSCC-25), and the synergy between treatment with curcumin microemulsions and low-frequency sonic stimulation, were tested. Finally, microscopic imaging of the cells confirmed the toxic effects of the curcumin microemulsions, showing damaged and ruptured cells after treatment. Brief exposure to the curcumin-containing microemulsions did have cytotoxic effects, but the addition of ultrasound strongly enhanced those effects, especially on OSCC-25 cells.
Reproducibility of Corneal Graft Thickness measurements with COLGATE in patients who have undergone DSAEK (Descemet Stripping Automated Endothelial Keratoplasty)
Wong Melissa HY,Chew Annabel,Htoon Hla M,Lee Beng H
BMC Medical Imaging , 2012, DOI: 10.1186/1471-2342-12-25
Abstract: Background The CorneaL GrAft Thickness Evaluation (COLGATE) system was recently developed to facilitate the evaluation of corneal graft thickness from OCT images. Graft thickness measurement can be a surrogate indicator for detecting graft failure or success. The purpose of this study was to determine the reproducibility of the COLGATE system in measuring DSAEK graft area between two observers. Methods This was a prospective case series in which 50 anterior segment OCT images of patients who had undergone DSAEK in either eye were analysed. Two observers (MW, AC) independently obtained the image analysis for the graft area using both semi automated and automated method. One week later, each observer repeated the analysis for the same set of images. Bland-Altman analysis was performed to analyze inter and intra observer agreement. Results There was strong intraobserver correlation between the 2 semi automated readings obtained by both observers. (r = 0.936 and r = 0.962). Intraobserver ICC for observer 1 was 0.936 (95% CI 0.890 to 0.963) and 0.967 (95% CI 0.942 to 0.981) for observer 2. Likewise, there was also strong interobserver correlation (r = 0.913 and r = 0.969). The interobserver ICC for the first measurements was 0.911 (95% CI 0.849 to 0.949) and 0.968 (95% CI 0.945 to 0.982) for the second. There was statistical difference between the automatic and the semi automated readings for both observers (p = 0.006, p = 0.003). The automatic readings gave consistently higher values than the semi automated readings especially in thin grafts. Conclusion The analysis from the COLGATE programme can be reproducible between different observers. Care must be taken when interpreting the automated analysis as they tend to over estimate measurements.
High quality voice conversion using prosodic and high-resolution spectral features
Hy Quy Nguyen,Siu Wa Lee,Xiaohai Tian,Minghui Dong,Eng Siong Chng
Computer Science , 2015, DOI: 10.1007/s11042-015-3039-x
Abstract: Voice conversion methods have advanced rapidly over the last decade. Studies have shown that speaker characteristics are captured by spectral feature as well as various prosodic features. Most existing conversion methods focus on the spectral feature as it directly represents the timbre characteristics, while some conversion methods have focused only on the prosodic feature represented by the fundamental frequency. In this paper, a comprehensive framework using deep neural networks to convert both timbre and prosodic features is proposed. The timbre feature is represented by a high-resolution spectral feature. The prosodic features include F0, intensity and duration. It is well known that DNN is useful as a tool to model high-dimensional features. In this work, we show that DNN initialized by our proposed autoencoder pretraining yields good quality DNN conversion models. This pretraining is tailor-made for voice conversion and leverages on autoencoder to capture the generic spectral shape of source speech. Additionally, our framework uses segmental DNN models to capture the evolution of the prosodic features over time. To reconstruct the converted speech, the spectral feature produced by the DNN model is combined with the three prosodic features produced by the DNN segmental models. Our experimental results show that the application of both prosodic and high-resolution spectral features leads to quality converted speech as measured by objective evaluation and subjective listening tests.
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