1.Advances in the study of aldehyde oxidases.
Acta Pharmaceutica Sinica 2014;49(5):582-9
Aldehyde oxidase (AOX), a highly conserved molybdoflavoenzyme in mammal cytoplasm, has broad substrate specificity and ability to catalyze the oxidation of aldehydes and nitrogen, oxygen-containing heterocyclic rings. AOX was found to widely distribute with the individual differences in vivo and plays an important role in phase I metabolism of drugs and xenobiotics. The biological characteristics of AOX and its contributions in drug metabolism are introduced briefly in this review.
2.Inhibition Effect of Water-solubility Nipponica Saponin on NF-κB Pathway of Rheumatoid Cellular Model
Yina DUAN ; Mingjuan WANG ; Jiaqi YANG ; Yufeng GAO ; Guangming CHENG ; Shubin MI ; Hongru SONG
World Science and Technology-Modernization of Traditional Chinese Medicine 2014;(6):1396-1400
This study was aimed to observe the influence of water-solubility nipponica saponin on activation of TNF-α+IL-17-induced rat fibroblast-like synovial cell line RSC-364 cellular model nuclear transcription factor NF-κB pathway as well as TNF-α, IL-1, ICAM-1, MMP-2, MMP-3 secretion. IL-17+ TNF-α were used for stimulating RSC-364 to establish rheumatoid arthritis (RA) cellular model. Water-solubility nipponica saponin in different con-centrations was used for intervention. The influence of water-solubility nipponica saponin in different concentrations on cell viability was detected by semi-quantitative RT-PCR method. Changes in the level of TNF-α, IL-1, ICAM-1, MMP-2, and MMP-3 of culture supernatant were detected by ELISA. The results showed that the activation of NF-κB p65 in RSC-364 stimulated by TNF-α+ IL-17 can be inhibited by water-solubility nipponica saponin ac-cording to its concentration. It improved IκB-α expression, and inhibited TNF-α, IL-1, ICAM-1, MMP-2 and MMP-3 secretion. It was concluded that water-solubility nipponica saponin can inhibit the activation of NF-κB pathway, hinder the secretion and activation of multiple downstream genes, which may be its effect in inhibiting syn-ovial inflammation in RA.
3.Detection and Genetic Characterization of Isolates of Hepatitis E Virus from Pigs and Human in Chungnam Region of Korea.
Mi Kyung CHAE ; Ji Young KIM ; Jiaqi CHU ; Duck Hwan KIM ; Han Sang YOO ; Chang Sik PARK ; Myung Cheol KIM ; Moo Hyung JU
Journal of Bacteriology and Virology 2006;36(1):31-39
Swine hepatitis E virus (HEV) has been reported as a new zoonotic agent due to its close genomic resemblance to the human HEV. Recently this virus is indicated as one of the important pathogens in xenotransplantation that uses pig as a donor animal. We carried out to investigate the prevalence of HEV infections among the pigs and human population in Chungnam region using a nested RT-PCR for detection of a part of HEV ORF2 gene. The sequences of the amplified DNA were analyzed and the genetical divergency were characterized. A total of 18 HEV strains, comprising 16 strains from pig and 2 strains from human, were genetically isolated from the fecal and serum samples. Among the isolates, 5 strains (2.5%) were detected from 200 swine sera and 2 strains (2.0%) from 100 human sera. All of the 16 swine strains were isolated from the pigs at 3 month of age, but none of age groups revealed the positive for swine HEV RNA. In comparison of the nucleotide sequence between 16 swine HEV and 2 human HEV isolates, the range of identities was 91.5% to 100%. Two human HEV isolates shared 99.7% homology. In phylogenetic analysis, all of the isolates were classified into genotype III, and the 18 isolates were also closely related to the prototype of swine HEV and human HEV strains isolated in the United States and others recently identified from swine in Japan and Netherland.
Animals
;
Base Sequence
;
Chungcheongnam-do*
;
DNA
;
Genotype
;
Hepatitis E virus*
;
Hepatitis E*
;
Hepatitis*
;
Humans*
;
Japan
;
Korea*
;
Prevalence
;
RNA
;
Swine*
;
Tissue Donors
;
Transplantation, Heterologous
;
United States
4.Detection and Genetic Characterization of Isolates of Hepatitis E Virus from Pigs and Human in Chungnam Region of Korea.
Mi Kyung CHAE ; Ji Young KIM ; Jiaqi CHU ; Duck Hwan KIM ; Han Sang YOO ; Chang Sik PARK ; Myung Cheol KIM ; Moo Hyung JU
Journal of Bacteriology and Virology 2006;36(1):31-39
Swine hepatitis E virus (HEV) has been reported as a new zoonotic agent due to its close genomic resemblance to the human HEV. Recently this virus is indicated as one of the important pathogens in xenotransplantation that uses pig as a donor animal. We carried out to investigate the prevalence of HEV infections among the pigs and human population in Chungnam region using a nested RT-PCR for detection of a part of HEV ORF2 gene. The sequences of the amplified DNA were analyzed and the genetical divergency were characterized. A total of 18 HEV strains, comprising 16 strains from pig and 2 strains from human, were genetically isolated from the fecal and serum samples. Among the isolates, 5 strains (2.5%) were detected from 200 swine sera and 2 strains (2.0%) from 100 human sera. All of the 16 swine strains were isolated from the pigs at 3 month of age, but none of age groups revealed the positive for swine HEV RNA. In comparison of the nucleotide sequence between 16 swine HEV and 2 human HEV isolates, the range of identities was 91.5% to 100%. Two human HEV isolates shared 99.7% homology. In phylogenetic analysis, all of the isolates were classified into genotype III, and the 18 isolates were also closely related to the prototype of swine HEV and human HEV strains isolated in the United States and others recently identified from swine in Japan and Netherland.
Animals
;
Base Sequence
;
Chungcheongnam-do*
;
DNA
;
Genotype
;
Hepatitis E virus*
;
Hepatitis E*
;
Hepatitis*
;
Humans*
;
Japan
;
Korea*
;
Prevalence
;
RNA
;
Swine*
;
Tissue Donors
;
Transplantation, Heterologous
;
United States
5.Effects of isocaloric high-fat diet on energy metabolism and endurance exercise capacity in SD rats
Shuai CHEN ; Xiangyuan DENG ; Hedong LANG ; Ruiliang ZHANG ; Xin RAO ; Jiaqi YUAN ; Jundong ZHU ; Yu QIN ; Mantian MI
Journal of Army Medical University 2024;46(9):940-951
Objective To investigate the effects of a 45%high-fat diet(HFD)with isocaloric intake on energy metabolism and endurance exercise capacity in SD rats.Methods Twenty-four male SD rats were randomly divided into normal chow diet group(CON),HFD group,normal chow diet+exercise training group(CONT),and HFD+exercise training group(HFDT).The CON and CONT groups received normal chow diet,while the HFD and HFDT groups received a 45%high-fat diet with isocaloric intake.The HFDT and CONT groups underwent an endurance training of moderate-intensity running for 6 weeks.Body weight,fat mass,and lean mass were measured weekly.Energy expenditure and basal metabolic rate during rest and exercise states were measured using Pheno Master/Calo Treadmill system.Blood glucose,lipids,and creatine kinase levels were detected after the exhaustion test.Results In 6 weeks after intervention,the endurance exercise capacity was significantly enhanced in the HFDT group than the CONT group(P<0.05).There were no obvious differences in body weight and body composition among the groups under isoenergetic feeding conditions.At rest,no statistical differences were observed in total energy expenditure and basal metabolic rate among the groups.However,prior to the 4th week,the CON group primarily metabolized carbohydrates while the HFD group primarily metabolized fats.But the carbohydrate metabolism was decreased and then increased,and the substrate metabolism rates eventually reached similar levels between the 2 groups on the 5th to 6th week.The HFDT group primarily metabolized fats while the CONT group primarily metabolized carbohydrates,with significant differences persisting after 6 weeks of training(P<0.05).HFD led to elevated levels of serum cholesterol,triglycerides(TG),and high-density lipoprotein cholesterol(HDL-C),but,endurance training resulted in decreased lipid levels in the HFDT group,accompanied by an increase inβ-hydroxybutyrate(βHB)level(P<0.05).Isoenergetic diets had no significant differences in their effects on liver and kidney function or muscle damage indicators.Conclusion An isoenergetic HFD can improve fat utilization ability and extend endurance exercise time in rats without altering body composition or affecting liver and kidney function.
6.Quercetin improves hepatic lipid accumulation by up-regulating lipolysis and lipophagy pathways
Yan ZHANG ; Yilin YANG ; Jiaqi YUAN ; Mantian MI ; Yu QIN
Journal of Army Medical University 2024;46(20):2301-2312
Objective To investigate the effect and mechanism of quercetin (QUE)in improving lipid accumulation in hepatocytes by regulating lipolysis and lipophagy pathway.Methods The human hepatocyte cell line 5 (HHL-5)was induced by palmitic acid (PA)to establish a steatogenic hepatocyte model.Quercetin at different concentrations (5,10,20 and 40 μmol/L)has been utilized to interfere with HHL-5 cells for 24 h,and the experiment was divided into six groups:control group,PA group,PA+QUE5 group,PA+QUE10 group,PA+QUE20 groupand PA+QUE40 group.In order to determine the influence of lipophagy on QUE effect,3-methyladenine (3-MA)was used to block autophagy,and HHL-5 cells were divided into the control,PA,PA+QUE40,3-MA,PA+3-MA and PA+3-MA+QUE40 groups.The contents of triglyceride (TG),accumulations of lipid droplets,expression of lipolysis and lipophagy related molecules,and degree of co-localization,and expression level of substrate of autophagy P62 were detected in above 2 types of experimental groups.Results Compared with the control group,the TG content and the lipid accumulation were significantly increased,the protein levels,average fluorescence intensities and colocalization degree of lipolysis related molecules adipose triglycerides lipase(ATGL)and comparative gene identification-58(CGI58),and lipophagy related molecules Ras-related protein 7(RAB7)and microtubule-associated protein 1 light chain 3 beta (LC3β)were significantly decreased,while the expression of P62 was enhanced in HHL-5 cells in the PA group (all P<0.05 ).Compared with the PA group,the triglyceride content and the degree of lipid accumulation in the PA+QUE40 group were significantly decreased,and the protein expression level,average fluorescence intensity and co-localization degree of lipolysis and lipophagy related molecules were significantly increased,while P62 was significantly decreased (P<0.05).When 3-MA was added to the steatogenic hepatocytes to inhibit autophagy,the improvement effect of QUE on lipid accumulation and the regulation of lipolysis and liphagy related molecules in steatogenic hepatocytes were neutralized.Conclusion QUE alleviates lipid accumulation in HHL-5 cells by promoting the expression and interaction of molecules related to lipolysis and lipophagy pathways.However,these effects can be weakened by the autophagy inhibitor 3-MA.
7.Pharmacokinetics of H002, a novel S1PRmodulator, and its metabolites in rat blood using liquid chromatography-tandem mass spectrometry.
Jiaqi MI ; Manman ZHAO ; Shu YANG ; Shuang YANG ; Jing JIN ; Xiaojian WANG ; Qiong XIAO ; Jinping HU ; Yan LI
Acta Pharmaceutica Sinica B 2016;6(6):576-583
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2-100 ng/mL for H002 and H002-M, while 0.5-100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from -9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.