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.

Characteristics and Health Risks of Particulate Polycyclic Aromatic Hydrocarbons and Nitro-polycyclic Aromatic Hydrocarbons at Urban and Suburban Elementary Schools in Shanghai, China

Lulu Zhang,Takahiro Tokuda,Lu Yang,Quanyu Zhou,Xuan Zhang,Wanli Xing,Qing Wu,Zhijun Zhou,Renjie Chen,Takayuki Kameda,Akira Toriba,Kazuichi Hayakawa,Ning Tang 한국대기환경학회 2019 Asian Journal of Atmospheric Environment (AJAE) Vol.13 No.4

PM2.1 was collected at urban and suburban elementary schools in Shanghai during two sampling periods in cold and warm seasons in 2007. Nine polycyclic aromatic hydrocarbons (PAHs) and ten nitro-polycyclic aromatic hydrocarbons (NPAHs) in PM2.1 were determined. During both seasons, the concentrations of PAHs and NPAHs at urban and suburban schools were not significantly different (p>0.05) and were higher in the cold period than in the warm period. According to the diagnostic ratios, PAHs and NPAHs at both schools were subject to the mixed effects of vehicle emission and coal combustion during both periods. Moreover, the results of the backward trajectory showed that PAHs and NPAHs were more susceptible to external polluted air masses in the cold period. At both urban and suburban schools, the inhalation cancer risk of PAHs and NPAHs in PM2.1 for children during elementary period was dozens of times of the acceptable risk level regulated by the U.S.EPA, highlighting the adverse impact of exposure to PAHs and NPAHs on the healthy development of children.

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.

Partially Mode-dependent Asynchronous Filtering of T-S Fuzzy MSRSNSs with Parameter Uncertainty

Xia Zhou,Lulu Chen,Jun Cheng,Kaibo Shi 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.1

The issue of fuzzy filtering for Markov switching repeat scalar nonlinear systems (MSRSNSs) with parameter uncertainty is explored. With consideration of uncertainty, a more general class of MSRSNSs is inferred. By resorting to a hidden Markov model technique, the asynchronous partially mode-dependent filter is established, in which the filter modes operate asynchronously with the target plant ones. By constructing the diagonally dominanttype Lyapunov functional, sufficient conditions are derived to ensure that the filtering error MSRSNS is stochastically stable with a desired H∞ performance index. Two simulation examples are given to validate the correctness and applicability of the presented theoretical results.

Omp16, a conserved peptidoglycan-associated lipoprotein, is involved in Brucella virulence in vitro

Feijie Zhi,Dong Zhou,Junmei Li,Lulu Tian,Guangdong Zhang,Yaping Jin,Aihua Wang 한국미생물학회 2020 The journal of microbiology Vol.58 No.9

Brucella, the bacterial agent of common zoonotic brucellosis, primarily infects specific animal species. The Brucella outer membrane proteins (Omps) are particularly attractive for developing vaccine and improving diagnostic tests and are associated with the virulence of smooth Brucella strains. Omp16 is a homologue to peptidoglycan-associated lipoproteins (Pals), and an omp16 mutant has not been generated in any Brucella strain until now. Very little is known about the functions and pathogenic mechanisms of Omp16 in Brucella. Here, we confirmed that Omp16 has a conserved Pal domain and is highly conserved in Brucella. We attempted to delete omp16 in Brucella suis vaccine strain 2 (B. suis S2) without success, which shows that Omp16 is vital for Brucella survival. We acquired a B. suis S2 Omp16 mutant via conditional complementation. Omp16 deficiency impaired Brucella outer membrane integrity and activity in vitro. Moreover, inactivation of Omp16 decreased bacterial intracellular survival in macrophage RAW 264.7 cells. B. suis S2 and its derivatives induced marked expression of IL-1β, IL-6, and TNF-α mRNA in Raw 264.7 cells. Whereas inactivation of Omp16 in Brucella enhanced IL-1β and IL-6 expression in Raw 264.7 cells. Altogether, these findings show that the Brucella Omp16 mutant was obtained via conditional complementation and confirmed that Omp16 can maintain outer membrane integrity and be involved in bacterial virulence in Brucella in vitro and in vivo. These results will be important in uncovering the pathogenic mechanisms of Brucella.

Improving Translation of Organization Names Combining Translation Model and Web Mining

Bin Li,Yin Zhou,Ning Ma,Wuqi Liang,Lulu Dong 보안공학연구지원센터 2016 International Journal of Database Theory and Appli Vol.9 No.1

Named entity (NE) translation is a fundamental task in machine translation (MT) and cross-language information retrieval (CLIR). Furthermore, Organization name (ON) translation is the most complex among all the NEs. A novel system for translating ONs from Chinese to English, with a translation model and web resources, is proposed. Firstly, we built a translation model with Chunk. Then query expansion was adopted with the translation model and term-subject co-occurrence. Thirdly, we extracted the Chinese Organization names with English sentences using the method of frequency shifting and adjacency information to find English fragments as translation candidates. Finally, we found the best translation by computing the trustworthiness of all candidates. The experimental results showed that the approach returned a better performance than machine translation-based systems.

Cloning of porcine chemerin, ChemR23 and GPR1 and their involvement in regulation of Lipogenesis

( Jianfeng Huang ),( Jian Zhang ),( Ting Lei ),( Xiaodong Chen ),( Yan Zhang ),( Lulu Zhou ),( An Yu ),( Zhilong Chen ),( Ronghua Zhou ),( Zaiqing Yang ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.7

Chemerin is a novel adipokine which is abundant in adipose tissue to promote adipocyte differentiation and with significant relativity to BMI and insulin sensitivity. We report here the molecular characterization of porcine chemerin and its receptors ChemR23 and GPR1, as well as their transcriptional regulation during lipogenesis. Chemerin was mainly expressed in liver, intestine, kidney and adipose tissue, consistent with the expression pattern of GPR1, but not ChemR23, which was predominantly present in spleen and temperately in adipose tissue. We further investigated the lipogenesis-related transcriptional activation of PPARγ and KLF15 on chemerin and its receptors. The data showed that KLF15, but not PPARγ, can up-regulate the mRNA level of chemerin, ChemR23 and GPR1, which was consistent with the results of luciferase assay that confirmed the effect of KLF15 on ChemR23 promoter. Taken together, our data provide basic molecular information for the further investigation on the function of chemerin in lipogenesis. [BMB reports 2010; 43(7): 491-498]

Endophytic Fungi from Dalbergia odorifera T. Chen Producing Naringenin Inhibit the Growth of Staphylococcus aureus by Interfering with Cell Membrane, DNA, and Protein

Yuan Gao,Yubin Ji,Wenlan Li,Fuling Wang,Fuling Wang,Xiaomeng Zhang,Zhihui Niu,Lulu Zhou,Lijun Yan 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.2

This study focused on the antibacterial effects of the endophytic fungi producing naringenin from Dalbergia odorifera T. Chen against Staphylococcus aureus. The antibacterial activity was measured by the inhibition diameters, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The time-killing curve was also used to evaluate its antibacterial efficacy. The results of antibacterial activity determinations showed that endophytic fungi secondary metabolites can inhibit the growth of five pathogenic bacteria (S. aureus, Escherichia coli, Salmonella enteritidis, Pseudomonas aeruginosa, and Bacillus subtilis) and the most sensitive strain was S. aureus that had the MIC and MBC values of 0.13 and 0.50 mg/mL, respectively. The membrane permeability study was measured by a DNA leakage assay and electrical conductivity assay. Furthermore, the whole-cell protein lysates and DNA fragmentation assay was evaluated. The morphology of S. aureus treated with the endophytic fungi products was observed by scanning electron microscopy (SEM). The probable antibacterial mechanism of endophytic fungi secondary metabolites was the increased membrane permeability that leads to leaks of nucleic acids and proteins. SEM results further confirmed that the extracts can interfere with the integrity of S. aureus cell membrane and further inhibit the growth of bacteria, resulting in the death of bacteria. This study provides a new perspective for the antibacterial functions of endophytic fungi secondary metabolites for biomedical applications.