Impact of NR1I2, adenosine triphosphate-binding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers

Zhou, Luping,Chen, Lulu,Wang, Yaqin,Huang, Jie,Yang, Guoping,Tan, Zhirong,Wang, Yicheng,Liao, Jianwei,Zhou, Gan,Hu, Kai,Li, Zhenyu,Ouyang, Dongsheng The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.3

Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

Impact of NR1I2, adenosine triphosphateebinding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers

Luping Zhou,Lulu Chen,Yaqin Wang,Jie Huang,Guo Ping Yang,Zhi-Rong Tang,Yicheng Wang,Jianwei Liao,Gan Zhou,Kai-hua Wei,Zhenyu Li,Dongsheng Ouyang 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.3

Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. Thisstudy examined the impact of polymorphisms in NR1I2, adenosine triphosphateebinding cassette (ABC)transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using SequenomMassARRAY system to investigate their association with major pharmacokinetic parameters of CK and itsmetabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using theAutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK anddecreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowestmaximum concentration (Cmax) of CK. The area under the curve from zero to the time of the lastquantifiable concentration (AUClast) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygouscarriers, while Cmax was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, andNR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrugresistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interactionof CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, thesehereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

Characterization of SiC/C Nanocomposite Powders Synthesized by Arc-Discharge

Zhou, Lei,Yu, Jie Yi,Gao, Jian,Wang, Dong Xing,Gan, Xiao Rong,Xue, Fang Hong,Huang, Hao,Dong, Xing Long Korean Society of Microscopy 2015 Applied microscopy Vol.45 No.4

In this paper, three carbon sources, i.e., solid graphite, gaseous CH4 and liquid ethanol, and one solid silicon source were employed to synthesize SiC/C nanocomposite powders by arc-discharge plasma. The processing conditions such as the component ratios of raw materials, atmospheric gases, etc. were adjusted for controllable synthesis of the nanopowders. It is indicated that both of solid graphite and silicon can be co-evaporated and reacted to form nanophases of cubic ${\beta}$-SiC with ~50 nm in mean size and a little free graphite; the carbon atoms decomposed from gaseous $CH_4$ favor to combine with the evaporated silicon atoms to form the dominant SiC nanophase; liquid carbon source of ethanol can also be used to harvest the main ${\beta}$-SiC and minor 6H-SiC phases in the assembly of nanoparticles. The as-prepared SiC/C nanocomposite powders were further purified by a heat-treatment in air and their photocatalytic performances were then greatly improved.

Synthesis of Azole-containing Piperazine Derivatives and Evaluation of their Antibacterial, Antifungal and Cytotoxic Activities

Gan, Lin-Ling,Fang, Bo,Zhou, Cheng-He Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.12

A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to $25\;{\mu}g/mL$, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: $25\;{\mu}g/mL$, $50\;{\mu}g/mL$ and $100\;{\mu}g/mL$ in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis

Gan Junqing,Liu Shan,Zhang Yu,He Liangzi,Bai Lu,Liao Ran,Zhao Juan,Guo Madi,Jiang Wei,Li Jiade,Li Qi,Mu Guannan,Wu Yangjiazi,Wang Xinling,Zhang Xingli,Zhou Dan,Lv Huimin,Wang Zhengfeng,Zhang Yanqiao,Q 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.

HESnW: History Encounters-Based Spray-and-Wait Routing Protocol for Delay Tolerant Networks

Gan, Shunyi,Zhou, Jipeng,Wei, Kaimin Korea Information Processing Society 2017 Journal of information processing systems Vol.13 No.3

Mobile nodes can't always connect each other in DTNs (delay tolerant networks). Many DTN routing protocols that favor the "multi-hop forwarding" are proposed to solve these network problems. But they also lead to intolerant delivery cost so that designing a overhead-efficient routing protocol which is able to perform well in delivery ratio with lower delivery cost at the same time is valuable. Therefore, we utilize the small-world property and propose a new delivery metric called multi-probability to design our relay node selection principles that nodes with lower delivery predictability can also be selected to be the relay nodes if one of their history nodes has higher delivery predictability. So, we can find more potential relay nodes to reduce the forwarding overhead of successfully delivered messages through our proposed algorithm called HESnW. We also apply our new messages copies allocation scheme to optimize the routing performance. Comparing to existing routing algorithms, simulation results show that HESnW can reduce the delivery cost while it can also obtain a rather high delivery ratio.

HESnW: History Encounters-Based Spray-and-Wait Routing Protocol for Delay Tolerant Networks

( Shunyi Gan ),( Jipeng Zhou ),( Kaimin Wei ) 한국정보처리학회 2017 Journal of information processing systems Vol.13 No.3

Mobile nodes can`t always connect each other in DTNs (delay tolerant networks). Many DTN routing protocols that favor the “multi-hop forwarding” are proposed to solve these network problems. But they also lead to intolerant delivery cost so that designing a overhead-efficient routing protocol which is able to perform well in delivery ratio with lower delivery cost at the same time is valuable. Therefore, we utilize the small-world property and propose a new delivery metric called multi-probability to design our relay node selection principles that nodes with lower delivery predictability can also be selected to be the relay nodes if one of their history nodes has higher delivery predictability. So, we can find more potential relay nodes to reduce the forwarding overhead of successfully delivered messages through our proposed algorithm called HESnW. We also apply our new messages copies allocation scheme to optimize the routing performance. Comparing to existing routing algorithms, simulation results show that HESnW can reduce the delivery cost while it can also obtain a rather high delivery ratio.

Feature Extraction based on Local Directional Pattern with SVM Decision-level Fusion for Facial Expression Recognition

Juxiang Zhou,Tianwei Xu,Jianhou Gan 보안공학연구지원센터 2013 International Journal of Bio-Science and Bio-Techn Vol.5 No.2

Synthesis of Azole-containing Piperazine Derivatives and Evaluation of their Antibacterial, Antifungal and Cytotoxic Activities

Lin-Ling Gan,Bo Fang,Cheng-He Zhou 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.12

A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to 25 μg/mL, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: 25 μM, 50 μΜ and 100 μM in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

An adaptive deviation-resistant neutron spectrum unfolding method based on transfer learning

Cao, Chenglong,Gan, Quan,Song, Jing,Yang, Qi,Hu, Liqin,Wang, Fang,Zhou, Tao Korean Nuclear Society 2020 Nuclear Engineering and Technology Vol.52 No.11

Neutron spectrum is essential to the safe operation of reactors. Traditional online neutron spectrum measurement methods still have room to improve accuracy for the application cases of wide energy range. From the application of artificial neural network (ANN) algorithm in spectrum unfolding, its accuracy is difficult to be improved for lacking of enough effective training data. In this paper, an adaptive deviation-resistant neutron spectrum unfolding method based on transfer learning was developed. The model of ANN was trained with thousands of neutron spectra generated with Monte Carlo transport calculation to construct a coarse-grained unfolded spectrum. In order to improve the accuracy of the unfolded spectrum, results of the previous ANN model combined with some specific eigenvalues of the current system were put into the dataset for training the deeper ANN model, and fine-grained unfolded spectrum could be achieved through the deeper ANN model. The method could realize accurate spectrum unfolding while maintaining universality, combined with detectors covering wide energy range, it could improve the accuracy of spectrum measurement methods for wide energy range. This method was verified with a fast neutron reactor BN-600. The mean square error (MSE), average relative deviation (ARD) and spectrum quality (Qs) were selected to evaluate the final results and they all demonstrated that the developed method was much more precise than traditional spectrum unfolding methods.