Physicochemical characterization and cytotoxicity of chitosanmodified single walled carbon nanotubes as drug carriers

Qing‑Ri Cao,Xiao‑Xue Zhang,Hao‑Yan Huang,Li‑Qing Chen,Hehua Jin,Beom‑Jin Lee,Jing‑Hao Cui 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.1

The application of single-walled carbon nanotubes (SWCNTs) as drug carriers is limited by their poor dispersal in aqueous medium. This study aimed to prepare chitosan (CS)-modified SWCNTs (CS-SWCNTs) and to evaluate their physicochemical properties and cytotoxicity. Oxidized SWCNTs (O-SWCNTs) were prepared with the use of strong acid, and the effects of acidizing conditions on the oxidation degree of the O-SWCNTs were investigated. CS was then non-covalently modified on the surfaces of O-SWCNTs. O-SWCNTs and CS-SWCNTs were characterized through ultraviolet spectroscopy, Fourier transform-infrared spectroscopy, Raman spectroscopy, and transmission electron microscopy. The cytotoxic effects of the functionalized SWCNTs were determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. O-SWCNTs with relatively complete structure were successfully synthesized through 5 h of treatment with 5 M acid. The amine group of the CS and the carboxyl group of O-SWCNTs interacted in CS-SWCNTs. The functionalized SWCNTs did not aggregate or precipitate in water and exerted no cytotoxic effects on A549 and MCF-7 tumor cells. The CS-SWCNTs possess the advantages of a simple preparation process, excellent water dispersibility, and biocompatibility for drug loading.

Synthesis and characterization of cholic acid-containing biodegradable hydrogels by photoinduced copolymerization

Hao, Jin-Qing,Li, Hong,Woo, Hee-Gweon Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of applied polymer science Vol.112 No.5

<P>A cholic acid (CA)-containing biodegradable hydrogel (PLA-PEG-PLA-co-MACAH) was synthesized from the photoinduced copolymerization of a CA-modified methacrylate monomer (MACAH), bearing a spacer of hexane-1,6-diol spacer between the methacryloyl and the cholanoate moieties, and a macromonomer (PLA-PEG-PLA-DA), bearing two acryloyl end groups derived from a poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) triblock copolymer. The structure of MACAH was confirmed by FTIR, <SUP>1</SUP>H-NMR, and MS. The hydrogel PLA-PEG-PLA-co-MACAH was characterized by scanning electron microscopy and X-ray diffraction. The experiment results showed that the swelling ratios of the hydrogels decreased with the increase of the CA fraction. The investigation on the in vitro degradation of the hydrogel showed that the CA-containing hydrogels degraded much slower than the hydrogels without CA component. The bioactivity of the synthesized hydrogels was assessed by the simulated body fluid method. The observed formation of hydroxyapatite on the scaffold of the hydrogels indicated that the hydrogels possess good bioactivity. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009</P>

RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells

Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

Anticancer Effects of the Hsp90 Inhibitor 17-Demethoxy-Reblastatin in Human Breast Cancer MDA-MB-231 Cells

( Qing Zhao ),( Cheng Zhu Wu ),( Jae Kyoung Lee ),( Su Rong Zhao ),( Hong Mei Li ),( Qiang Huo ),( Tao Ma ),( Jin Zhang ),( Young Soo Hong ),( Hao Liu ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.7

Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel nonbenzoquinone- type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

Effect of Solvents on Physical Properties and Release Characteristics of Monolithic Hydroxypropylmethylcellulose Matrix Granules and Tablets

Qing-Ri Cao,최연웅,Jing-Hao Cui,Beom-Jin Lee 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.4

Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and coating. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/ water showed dual release with about 50% drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.

Effect of Solvents on Physical Properties and Release Characteristics of Monolithic Hydroxypropylmethylcellulose Matrix Granules and Tablets

Cao Qing-Ri,Choi Yun-Woong,Cui Jing-Hao,Lee Beom-Jin The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.4

Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and coating. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/water showed dual release with about $50\%$ drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.

Down-regulation of miRNA-452 is Associated with Adriamycin-resistance in Breast Cancer Cells

Hu, Qing,Gong, Jian-Ping,Li, Jian,Zhong, Shan-Liang,Chen, Wei-Xian,Zhang, Jun-Ying,Ma, Teng-Fei,Ji, Hao,Lv, Meng-Meng,Zhao, Jian-Hua,Tang, Jin-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

ORiginal Article : PNPLA3 rs738409 Polymorphism Associated with Hepatic Steatosis and Advanced Fibrosis in Patients with Chronic Hepatitis C Virus: A Meta-Analysis

( Jia Hao Fan ),( Ming Que Xiang ),( Qing Ling Li ),( Hong Tao Shi ),( Jin Jun Guo ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: The recognition of a correlation between patatin-like phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not reached a consensus. This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis and advanced fibrosis in CHC patients. Methods: We performed a comprehensive literature search from the PubMed, Embase, Web of Science, and Google Scholar databases up to December 31, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using Stata 12.0 software. Results: The meta-analysis revealed the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians (versus CC+CG: OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity analysis indicated the results of this meta-analysis were stable and no publication bias was detected. Conclusions: PNPLA3 rs738409 (C>G) was associated with the risk of both advanced liver fibrosis and steatosis in patients with CHC, especially among Caucasian populations. (Gut Liver 2016;10:456-463)

Bioconversion of ginsenoside Rc into Rd by a novel α-L-arabinofuranosidase, Abf22-3 from Leuconostoc sp. 22-3: cloning, expression, and enzyme characterization.

Liu, Qing-Mei,Jung, Hae-Min,Cui, Chang-Hao,Sung, Bong-Hyun,Kim, Jin-Kwang,Kim, Song-Gun,Lee, Sung-Taik,Kim, Sun-Chang,Im, Wan-Taek N.V. Swets en Zeitlinger 2013 Antonie van Leeuwenhoek Vol.103 No.4

<P>A novel α-L-arabinofuranosidase (Abf22-3) that could biotransform ginsenoside Rc into Rd was obtained from the ginsenoside converting Leuconostoc sp. strain 22-3, isolated from the Korean fermented food kimchi. The gene, termed abf22-3, consisting of 1,527 bp and encoding a protein with a predicted molecular mass of 58,486 Da was cloned into the pMAL-c2x (TEV) vector. A BLAST search using the Abf22-3's amino acid sequence revealed significant homology to that of family 51 glycoside hydrolases. The over-expressed recombinant Abf22-3 in Escherichia coli BL21 (DE3) catalyzed the hydrolysis of the arabinofuranoside moiety attached to the C-20 position of ginsenoside Rc under optimal conditions of pH 6.0 and 30 C. This result indicated that Abf22-3 selectively converts ginsenoside Rc into Rd, but did not catalyze the hydrolysis of glucopyranosyl groups from Rc or other ginsenosides such as Rb1 and Rb2. Over-expressed recombinant enzymes were purified by two steps with amylose-affinity and DEAE-cellulose chromatography and then characterized. The kinetic parameters for α-L-arabinofuranosidase showed apparent Km and Vmax values of 0.95 0.02 μM and 1.2 0.1 μmol min(-1) mg of protein(-1) against p-nitrophenyl-α-L-arabinofuranoside, respectively. Using a purified MBP-Abf22-3 (10 μg/ml), 0.1 % of ginsenoside Rc was completely converted to ginsenoside Rd within 20 min.</P>

Identification and Characterization of a <i>Mucilaginibacter</i> sp. Strain QM49 β-Glucosidase and Its Use in the Production of the Pharmaceutically Active Minor Ginsenosides (<i>S</i>)-Rh₁ and (<i>S</i>)-Rg₂

Cui, Chang-Hao,Liu, Qing-Mei,Kim, Jin-Kwang,Sung, Bong-Hyun,Kim, Song-Gun,Kim, Sun-Chang,Im, Wan-Taek American Society for Microbiology 2013 Applied and environmental microbiology Vol.79 No.19

<P>Here, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) from <I>Mucilaginibacter</I> sp. strain QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity, <I>bglQM</I>, consists of 2,346 bp and is predicted to encode 781 amino acid residues. This enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed in <I>Escherichia coli</I> BL21(DE3) using a maltose binding protein (MBP)-fused pMAL-c2x vector system containing the tobacco etch virus (TEV) proteolytic cleavage site. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides Re and Rg<SUB>1</SUB> into (<I>S</I>)-Rg<SUB>2</SUB> and (<I>S</I>)-Rh<SUB>1</SUB>, respectively, by hydrolyzing one glucose moiety attached to the C-20 position at pH 8.0 and 30°C. The <I>K<SUB>m</SUB></I> values for <I>p</I>-nitrophenyl-β-<SMALL>d</SMALL>-glucopyranoside, Re, and Rg<SUB>1</SUB> were 37.0 ± 0.4 μM and 3.22 ± 0.15 and 1.48 ± 0.09 mM, respectively, and the <I>V</I><SUB>max</SUB> values were 33.4 ± 0.6 μmol min<SUP>−1</SUP> mg<SUP>−1</SUP> of protein and 19.2 ± 0.2 and 28.8 ± 0.27 nmol min<SUP>−1</SUP> mg<SUP>−1</SUP> of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM, followed by silica column purification, to produce (<I>S</I>)-Rh<SUB>1</SUB> and (<I>S</I>)-Rg<SUB>2</SUB> at chromatographic purities of 98% ± 0.5% and 97% ± 1.2%, respectively. This is the first report of gram-scale production of (<I>S</I>)-Rh<SUB>1</SUB> and (<I>S</I>)-Rg<SUB>2</SUB> from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3.</P>