http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Chang-Keun Cho,Pureum Kang,Hye-Jung Park,Eunvin Ko,Chou Yen Mu,Yun Jeong Lee,Chang-Ik Choi,Hyung Sik Kim,Choon-Gon Jang,Jung-Woo Bae,Seok-Yong Lee 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.5
Piroxicam is a non-steroidal anti-inflammatorydrug used to alleviate symptoms of osteoarthritis andrheumatoid arthritis. CYP2C9 genetic polymorphism significantly infl uences the pharmacokinetics of piroxicam. The objective of this study was to develop and validate thepiroxicam physiologically based pharmacokinetic (PBPK)model related to CYP2C9 genetic polymorphism. PK-Sim ®version 10.0 was used for the PBPK modeling. The PBPKmodel was evaluated by predicted and observed plasma concentration–time profi les, fold errors of predicted to observedpharmacokinetic parameters, and a goodness-of-fi t plot. Theturnover number (k cat ) of CYP2C9 was adjusted to capturethe pharmacokinetics of piroxicam in diff erent CYP2C9genotypes. The population PBPK model overall accuratelydescribed and predicted the plasma concentration–timeprofi les in diff erent CYP2C9 genotypes. In our simulations,predicted AUC inf in CYP2C9*1/*2 , CYP2C9*1/*3 , andCYP2C9*3/*3 genotypes were 1.83-, 2.07-, and 6.43-foldhigher than CYP2C9*1/*1 genotype, respectively. All fold error values for AUC, C max , and t 1/2 were included in theacceptance criterion with the ranges of 0.57–1.59, 0.63–1.39, and 0.65–1.51, respectively. The range of fold errorvalues for predicted versus observed plasma concentrationswas 0.11–3.13. 93.9% of fold error values were within thetwo-fold range. Average fold error, absolute average folderror, and root mean square error were 0.93, 1.27, and 0.72,respectively. Our model accurately captured the pharmacokineticalterations of piroxicam according to CYP2C9 geneticpolymorphism.
Yen N. Diep,Hee Jung Park,Joon‑Ho Kwon,Minh Tran,Hae Young Ko,조한희,Jisu Kim,Jee‑In Chung,김태영,Dongwoo Kim,Jong Hee Chang,You Jung Kang,C. Justin Lee,윤미진,Hansang Cho 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Background Glial scar formation is a reactive glial response confining injured regions in a central nervous system. However, it remains challenging to identify key factors formulating glial scar in response to glioblastoma (GBM) due to complex glia-GBM crosstalk. Methods Here, we constructed an astrocytic scar enclosing GBM in a human assembloid and a mouse xenograft model. GBM spheroids were preformed and then co-cultured with microglia and astrocytes in 3D Matrigel. For the xenograft model, U87-MG cells were subcutaneously injected to the Balb/C nude female mice. Results Additional glutamate was released from GBM-microglia assembloid by 3.2-folds compared to GBM alone. The glutamate upregulated astrocytic monoamine oxidase-B (MAO-B) activity and chondroitin sulfate proteoglycans (CSPGs) deposition, forming the astrocytic scar and restricting GBM growth. Attenuating scar formation by the glutamate– MAO-B inhibition increased drug penetration into GBM assembloid, while reducing GBM confinement. Conclusions Taken together, our study suggests that astrocytic scar could be a critical modulator in GBM therapeutics.
Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening
Chang, Chih-Chun,Liou, Ching-Biau,Su, Ming-Jang,Lee, Yi-Chen,Liang, Chai-Ting,Ho, Jung-Li,Tsai, Huang-Wen,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15
Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.
Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects
Chang-Keun Cho,Ji-Young Byeon,Pureum Kang,Hye-Jung Park,Eunvin Ko,Chou Yen Mu,Choon-Gon Jang,Seok-Yong Lee,Yun Jeong Lee 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.2
Tolperisone hydrochloride is a centrally-acting muscle relaxant used for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. It is metabolized to the inactive metabolite mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. In our previous study, the pharmacokinetics of tolperisone was significantly affected by the genetic polymorphism of CYP2D6, but the wide interindividual variation of tolperisone pharmacokinetics was not explained by genetic polymorphism of CYP2D6 alone. Thus, we studied the effects of CYP2C19 genetic polymorphism on tolperisone pharmacokinetics. Eighty-one subjects with different CYP2C19 genotypes received a single oral dose of 150 mg tolperisone with 240 mL of water, and blood samples were collected up to 12 h after dosing. The plasma concentration of tolperisone was measured by a liquid chromatography-tandem mass spectrometry system. The CYP2C19PM group had significantly higher Cmax and lower CL/F values than the CYP2C19EM and CYP2C19IM groups. The AUCinf of the CYP2C19PM group was 2.86-fold and 3.00-fold higher than the CYP2C19EM and CYP2C19IM groups, respectively. In conclusion, the genetic polymorphism of CYP2C19 significantly affected tolperisone pharmacokinetics.
Chang, Yung-Shan,Choi, Mingi,Baek, Minki,Hsieh, Ping-Yen,Yong, Kijung,Hsu, Yung-Jung Elsevier 2018 Applied Catalysis B Vol.225 No.-
<P><B>Abstract</B></P> <P>In this study, we have synthesized CdS/CdSe co-sensitized brookite TiO<SUB>2</SUB> nanostructures with hydrogen doping (H:TiO<SUB>2</SUB>/CdS/CdSe) in a facile solution reaction and studied their PEC performances. Compared to undoped brookite TiO<SUB>2</SUB>, the H:TiO<SUB>2</SUB>/CdS/CdSe composites exhibit much enhanced photocurrent generation, which originates from the improved charge transfer kinetics endowed by hydrogen doping and sensitization. Time-resolved photoluminescence (PL) and electrochemical impendence spectroscopy (EIS) are employed to explore the charge transfer dynamics between sensitizers and TiO<SUB>2</SUB> and charge carrier kinetics at the semiconductor/electrolyte interface. According to the analytical results, sensitizations of TiO<SUB>2</SUB> are found to enhance the charge separation efficiency. Besides, the hydrogen doping into TiO<SUB>2</SUB> generates oxygen vacancy states, providing additional charge transfer pathway and prohibiting charge recombination, beneficial for enhancing the PEC performances as well. Based on the charge dynamics data, we further develop charge transfer models for TiO<SUB>2</SUB>/CdS/CdSe and H:TiO<SUB>2</SUB>/CdS/CdSe. The findings from this work can help understanding the charge transfer dynamics in brookite TiO<SUB>2</SUB>-based composite systems as well as designing versatile photoelectrodes for solar energy conversion.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CdS/CdSe co-sensitized brookite H:TiO<SUB>2</SUB> exhibit much enhanced photoactivity. </LI> <LI> Superiority of H:TiO<SUB>2</SUB>/CdS/CdSe results from the improved charge transfer. </LI> <LI> Practical use for photoelectrochemical hydrogen production was demonstrated. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>