Profile of disposition, tissue distribution and excretion of the novel anti-human immunodeficiency virus (HIV) agent W-1 in rats

Ying-Yuan Lu,Xiao-Wei Wang,Xin Wang,Wen-Bing Dai,Qiang Zhang,Pu Li,Ya-Qing Lou,Chuang Lu,Jun-Yi Liu,Guo-Liang Zhang 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.7

The purpose of this study was to characterize the disposition, distribution, excretion and plasma protein binding of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W- 1) in rats. Concentrations of W-1 within biological samples were determined using a validated high performance liquid chromatography method. The plasma protein binding of W-1 was examined by equilibrium dialysis method. After oral administration of W-1 (50, 100 and 200 mg/kg, respectively) in self-microemulsifying drug delivery system formulation, the pharmacokinetic parameters of W-1 were as follows: the peak plasma concentrations (Cmax) were 0.42, 1.50 and 2.55 μg/mL, the area under the curve (AUC0-t) were 0.89, 2.27 and 3.96 lg/h mL and the plasma half-life (t1/2) were 5.15, 3.77 and 3.77 h, respectively. Moreover, the prototype of W-1 was rapidly and extensively distributed into fifteen tissues, especially higher concentrations were detected in intestine, stomach and liver, respectively. The plasma protein binding of W-1 in rat, beagle dog and human were in the range of 97.96–99.13 %. This study suggested that W-1 has an appropriate pharmacokinetics in rats, such as rapid absorption, moderate clearance, and rapid distribution to multiple tissues. Those properties provide important information for further development W-1 as an anti-HIV-1 drug candidate.

EphB1 and Ephrin-B, New Potential Biomarkers for Squamous Cell/adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder

Yuan, Yuan,Yang, Zhu-Lin,Miao, Xiong-Ying,Liu, Zi-Ru,Li, Dai-Qiang,Zou, Qiong,Li, Jing-He,Liang, Lu-Feng,Zeng, Gui-Xiang,Chen, Sen-Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC ($P_{SC/ASC}$ =0.000) or AC ($P_{AC}$ =0.000 or $P_{AC}$ =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

Interleukin-18 Synergism with Interleukin-2 in Cytotoxicity and NKG2D Expression of Human Natural Killer Cells

Qi, Yuan-Ying,Lu, Chao,Ju, Ying,Wang, Zi-E,Li, Yuan-Tang,Shen, Ya-Juan,Lu, Zhi-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type ginsenosides through Escherichia coli engineered with uridine diphosphate glycosyltransferase genes

Lu Yu,Yuan Chen,Jie Shi,Ru-Feng Wang,Ying-Bo Yang,Li Yang,Shujuan Zhao,Zheng-Tao Wang 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with GT95syn selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3eOH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing p2GT95synK1, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20eOH and C3eOH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

Functional Evaluation of Transplanted Kidneys with Reduced Field-of-View Diffusion-Weighted Imaging at 3T

Yuan Xie,Yanjun Li,Jiqiu Wen,Xue Li,Zhe Zhang,Jianrui Li,Yan’e Zhao,Peng Wang,Jun Zhang,Ying Tian,Long Jiang Zhang,Guang Ming Lu 대한영상의학회 2018 Korean Journal of Radiology Vol.19 No.2

Objective: To determine the feasibility of reduced field-of-view diffusion-weighted imaging (rFOV DWI) with multi-b values to detect functional variability in transplanted kidneys. Materials and Methods: Using a 3T MRI scanner, multi-b rFOV DWI of transplanted kidney or native kidney was performed in 40 renal transplantation recipients and 18 healthy volunteers. The patients were stratified, according to an estimated glomerular filtration rate (eGFR): Group 1, eGFR ≥ 60 mL/min/1.73 m2; Group 2, eGFR ≥ 30 mL/min/1.73 m2 and < 60 mL/min/1.73 m2; Group 3, eGFR < 30 mL/min/1.73 m2. Total apparent diffusion coefficient (ADCT), perfusion-free ADC (ADCD) and perfusion fraction (FP) of kidneys were calculated and compared among the four groups. Correlations between the imaging results and eGFR were assessed. Results: All volunteers had eGFR ≥ 60 mL/min/1.73 m2, while 16, 16, and 8 patients were included in Groups 1, 2, and 3, respectively. In the renal cortex, ADCT was higher in Group 1 ([1.65 ± 0.13] x 10-3 mm2/s) than Group 3 ([1.44 ± 0.11] x 10-3 mm2/s) (p < 0.05), and the inter-group differences of FP values were significant (all p < 0.05) (0.330 ± 0.024, 0.309 ± 0.019, 0.278 ± 0.033, and 0.250 ± 0.028 for control group, Groups 1, 2, and 3, respectively). Renal cortical ADCT, ADCD, FP, and renal medullary ADCT and FP correlated positively with eGFR (r = 0.596, 0.403, 0.711, 0.341, and 0.323, respectively; all p < 0.05). When using 0.278 as the cutoff value, renal cortical FP had a sensitivity of 97.1% and a specificity of 66.7% for predicting decreased renal function. Conclusion: Multi-b rFOV DWI presents transplanted kidneys with high resolution, which is a promising functional tool for non-invasively monitoring function of transplanted kidneys.

Profiling Gene Expression During Gland Morphogenesis of a Glanded and a Glandless Upland Cotton

Ying-Fan Cai,Min Chen,Quan Sun,Yong-Fang Xie,Sheng-Wei Li,Jian-Chuan Mo,Ming-Feng Jiang,You-Lu Yuan,Yu-Zhen Shi,Huai-Zhong Jiang,Zheng Pan,Yun-Ling Gao,Peng-Sheng Ye,Hua-Lan Zeng 한국식물학회 2009 Journal of Plant Biology Vol.52 No.6

The pigment gland is an important character of the Gossypium plant. With the aim of identifying genes involved in pigment gland morphogenesis in cotton, gene expression during pigment gland morphogenesis in Chuan 2802, which is glanded both in seed and plant, and a glandless line N5 was profiled using Affymetrix Cotton microarray. The results showed that there were 564 differentially expressed genes greater than twofold during gland morphogenesis. About 60.2% of these genes shares similarity with known genes on GenBank and about 39.8% with no functional description in the database. These described genes may play roles in defense response, response to oxidative stress, peroxidase activity, and the other metabolic pathways. The KEGG Orthology-Based Annotation System indicated that these above twofold expressed genes involved seven biochemical pathways on KEGG. These findings suggest that a complicated regulation is associated with pigment gland morphogenesis and the associated defense response including gossypol biosynthesis in cotton.

ENHANCEMENT OF LIPID EXTRACTION BY MIXTRURE OF ETHYL ACETATE AND EHANOL FROM MICROALGAE VIA DEEP EUTECTIC SOLVENTS PRETREATMENT

Weidong LU,Zhongming WANG,Ying PAN,Zhenhong Yuan 한국신재생에너지학회 2015 AFORE Vol.2015 No.11

The Influence of Resilience on the Coping Strategies in Patients with Primary Brain Tumors

Shu-Yuan Liang,Hui-Chun Liu,Yu-Ying Lu,Shu-Fang Wu,Ching-Hui Chien,Shiow-Luan Tsay 한국간호과학회 2020 Asian Nursing Research Vol.14 No.1

Purpose: The purpose of this study was to assess the amount of variance in the coping strategies of patients with brain tumors that could be accounted for by resilience. Methods: This cross-sectional survey involved 95 patients who had experienced surgical, chemotherapy, or radiotherapy therapies for their brain tumors at least 1 month before data collection. The investigator collected data using the scales of the Ways of Coping Checklist-Revised and Resilience Scale. Data were analyzed using descriptive statistics, t tests, analysis of variance, Pearson product–moment correlation, and hierarchical multiple regression. Results: The results revealed that resilience was significantly positively associated with patients' problem-focused coping (r = .65, p < .001) and total coping (r = .49, p < .001). In addition, resilience accounted for 27% (R2inc = .27, p < .001) and 16% (R2inc = .16, p < .001) of the distinct variances in predicting patients’ problem-focused coping and total coping. Conclusion: The current results provide evidence to support the importance of resilience in shaping the coping strategies of relevant patients. As resilience shows a crucial element in patient coping with brain tumors, health team members should develop and employ appropriate strategies to improve the resilience of patients with brain tumors.

Dong Hai Bridge Sea-Crossing Project in Shanghai, China : General Concept, Design, Construction and Durability 설계, 시공, 내구성 및 일반사항

Lin, Yuan-Pei,Zhang, Zeng-huan,Tang, Wei,Lu, Yong-Cheng,Ding, Jian-Kang,Zhang, Jian-Ying Korean Group of IABSE;Korea wind Engineering Resea 2006 Proceedings of the International Symposium on Sea- Vol.2006 No.-

Dong Hai Bridge in Shanghai is the longest in world and the first sea-crossing project in china, the total length of which is 32.5km and the width of the bridge is 31.5m. In this paper the general concepts of design, construction and durability are introduced. 상하이의 동해대교는 전장 32.5km 폭 31.5m 의 세계 최장 교량이며, 중국에서는 최초의 해상 횡단 프로젝트이다. 이논문에서는 동해대교의 설계, 건설, 그리고 내구성에 대한 기본 개념을 소개한다.

Clinical Significance of BCR-ABL Fusion Gene Subtypes in Chronic Myelogenous and Acute Lymphoblastic Leukemias

Ye, Yuan-Xin,Zhou, Juan,Zhou, Yan-Hong,Zhou, Yi,Song, Xing-Bo,Wang, Jun,Lin, Li,Ying, Bin-Wu,Lu, Xiao-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.