1.Pharmacokinetics of ginsenosides Rg1 and its metabolites in rats
Liang FENG ; Changjiang HU ; Lingying YU
Acta Pharmaceutica Sinica 2010;45(5):636-40
To study the pharmacokinetics of ginsenosides Rg1 and its metabolites after iv and oral administration in Wistar rats, the LC-MS/MS method was selected to determine ginsenosides Rg1 and its metabolites in plasma and their pharmacokinetic parameters were calculated. After oral administration of ginsenosides Rg1 to rats, ginsenosides Rg1, Rh1, F1 and protopanaxatriol (Ppt) could be detected in plasma. Their Tmax were 0.92, 3.64, 5.17, and 7.30 h, respectively; MRT were 2.68, 5.06, 6.65, and 5.33 h, respectively; AUC(o-t), were 2 363.5, 4 185.5, 3 774.3, and 396.2 ng x mL(-1) x h, respectively. After iv administration of ginsenosides Rg1 to rats, ginsenosides Rg1, Rh1 and FI could be detected in plasma. Their T1/2betaS were 3.12, 5.87, and 6.87 h, respectively; MRTs were 1.92, 5.99, and 7.13 h, respectively; AUCo-tS were 1 454.7, 597.5, and 805.6 ng x mL(-1) x h, respectively. So, it can be concluded that after oral administration, the amounts of metabolites were higher than the prototype in vivo, and the distribution and elimination of the metabolites were relatively slow. After iv administration, the amount of prototype were higher than that of the metabolites in vivo, and the distribution and elimination of the metabolites were relatively slow.
2.Effects of adiponectin on atherosclerotic plaque evaluated by intravascular ultrasound in rabbits
Changjiang LI ; Mei ZHANG ; Yun ZHANG ; Huiwen SUN ; Liang CHEN ; Yuanyuan RONG ; Rong WANG
Chinese Journal of Ultrasonography 2008;17(8):716-719
Objective To investigate the effects of adiponectin on the development of atherosclerosis.Methods The in vivo role of adiponectin on the development of atherosclerosis in rabbits was investigated mainly using adiponectin-producing adenovirus(Ad-APN)and intravascular ultrasound(IVUS).On day 14 after Ad-APN local transfer to the intima of abdominal aortas,abdominal IVUS images were recorded and then rabbits were sacrificed.Abdominal aortas were collected and performed histochemical analysis.Results Ultrasonography revealed a significantly reduced atherosclerotic area,in abdominal aortas of rabbits infected through intima with Ad-APN,by 36.39% compared with the area in adenovirus expressing β galactosidase gene(Ad-βgal)treated rabbits(P<0.01),and by 37.50% compared with that before treatment(P<0.01).The lumen area stenosis was also reduced by 23.37%(P<0.05)and 33.15%(P<0.01),respectively.In rabbits with Ad-APN infection,the atherosclerotic plaque area as seen on Oil Red O staining was reduced significantly,by 30.70%(P<0.05)and the greatest thickness of plaque was reduced,by 20.83%(P<0.05)as compared with those in Ad-βgal-treated rabbits,respectively.Conclusions Intravascular ultrasound analysis is a valuable method in the in vivo study about the effects of adiponectin on the development of atherosclerosis.
3.Bone marrow mesenchymal stem cell treatment for myocardial ischemia/reperfusion injury: mechanisms of exosomes and factors
Changjiang ZHANG ; Guiyou LIANG
Chinese Journal of Tissue Engineering Research 2019;23(12):1455-1460
BACKGROUND: Myocardial ischemia/reperfusion injury is one of the most common complications in ischemic cardiomyopathy and open heart surgery. The development of bone marrow mesenchymal stem cells provides a new method for clinical prevention and treatment of myocardial ischemia/reperfusion injury. OBJECTIVE: To review the therapeutic effect and potential mechanisms of bone marrow mesenchymal stem cells in the treatment of myocardial ischemia/reperfusion injury, in order to provide a theoretical basis for the clinical application of bone marrow mesenchymal stem cells. METHODS: Chinese Journal Full-text Database (CNKI) , WanFang, and PubMed were retrieved for articles related to the use of bone marrow mesenchymal stem cells for myocardial ischemia-reperfusion injury published from January 2000 to October 2018. The search terms were "bone marrow mesenchymal stem cells; myocardial ischaemia/reperfusion; research process" in Chinese and "bone marrow mesenchymal stem cells; myocardial ischaemia/reperfusion; cell therapy; clinical trial studies" in English. Old and repetitive viewpoints were excluded, the searched literatures were sorted out, and finally 56 articles were included for further analysis and discussion. RESULTS AND CONCLUSION: (1) In this paper, we summarize paracrine factors, exosomes miRNA and their effects in the treatment of myocardial ischemia/reperfusion injury with bone marrow mesenchymal stem cells, such as anti-inflammation, anti-apoptosis, anti-fibrosis, repair of myocardium and neovascularization. (2) We also summarize the possible molecular mechanisms of bone marrow mesenchymal stem cells involved in the treatment of myocardial ischemia/reperfusion injury, such as the role of mitochondrial fusion protein 2, regulation of myocardial autophagy, and regulation of AMPK/mTOR signaling pathway. Overall, we attempt to provide a theoretical basis for the clinical application of bone marrow mesenchymal stem cells in the treatment of myocardial ischemia/reperfusion injury.
4.Application of artificial intelligence-assisted diagnosis for cervical liquid-based thin-layer cytology
Xiaohui ZHU ; Xiaoming LI ; Wenli ZHANG ; Minmin LIAO ; Yu LI ; Feifei WANG ; Bin SHANG ; Linggan PENG ; Yongjian SU ; Zejun YOU ; Jianyuan SHI ; Wenlong ZHONG ; Xinrong LIANG ; Changjiang LIANG ; Li LIANG ; Wenting LIAO ; Yanqing DING
Chinese Journal of Pathology 2021;50(4):333-338
Objective:To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening.Methods:A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao′an People′s Hospital(Group) and Changsha Yuan′an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared.Results:The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual.Conclusions:Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.
5.Effects of Adiponectin on the Expression of Myocardial AMPK in Myocardial Insulin Resistance Model Dogs during Cardio- pulmonary Bypass
Dengshen ZHANG ; Guiyou LIANG ; Daxing LIU ; Feng WANG ; Sisi PAN ; Changjiang ZHANG
China Pharmacy 2019;30(7):878-882
OBJECTIVE: To investigate the effects of adiponectin (APN) on the expression of myocardial AMPK in myocardial insulin resistance (IR) model dogs during cardiopulmonary bypass (CPB). METHODS: Totally 24 dogs were randomly divided into control group, model group, APN group (36 μg/kg), AMPK inhibition group (APN 36 μg/kg+AMPK inhibitor compound C 0.5 mg/kg), with 6 dogs in each group. All dogs underwent CPB; except for control group without medicine, CPB myocardial IR model were established in other groups, and perfused with St.Thomas cardiac cardioplegia lipid no medicine or containing relevant drugs after main artery block. Coronary sinus blood and carotid artery blood samples were collected before bypass and after 15, 90 min reperfusion following 60 min myocardial ischemia. Left ventricular apical tissue was taken, and the uptake rate of myocardial glucose and insulin resistance index (IRI) were determined and calculated; the changes of myocardial injury indexes (cTnT concentration) and cardiac function indexes (LVSP, +dp/dtmax) were monitored. The level of p-AMPK was detected. RESULTS: There was no statistical significance in above indexes of dogs before bypass (P>0.05). Compared with control group, the rate of myocardial glucose uptake, the levels of LVSP, +dp/dtmax and p-AMPK in model group were decreased significantly after 15, 90 min reperfusion (P<0.05), and the concentrations of IRI and cTnT were increased significantly (P<0.05). Compared with model group, the rate of myocardial glucose uptake, LVSP, +dp/dtmax and p-AMPK were increased significantly in APN group and AMPK inhibitor group (P<0.05), while the concentrations of IRI and cTnT were decreased significantly (P<0.05); moreover, the effect of APN group was better than that of AMPK inhibitor group (P<0.05). CONCLUSIONS: APN can promote myocardial glucose uptake and metabolism, and contribute the recovery of cardiac function, the mechanism of which may be associated with increasing the activity of AMPK.
6.Differential expression profiles analysis of DNA methylation between “disease” and “syndrome” in coronary heart disease-induced unstable angina patientswith Qi deficiency and blood stasis syndrome
WU Huaying ; HU Hongchun ; LIU Yufeng ; LI Liang ; LI Jing ; HAN Yuming ; XIAO Changjiang ; PENG Qinghua
Digital Chinese Medicine 2023;6(4):451-466
Objective:
To explore the differential expression profiles of DNA methylation sites/regions and potential molecular mechanisms in the peripheral blood of coronary heart disease (CHD)-induced unstable angina pectoris patients with or without Qi deficiency and blood stasis syndrome, and to provide scientific evidence for the conbination of disease and syndrome.
Methods:
According to the pre-determined inclusion and exclusion criteria, the study subjects were enrolled and divided into two groups namely CHD-induced unstable angina group (G group) and healthy control group (J group) to conduct “disease” analysis, while G group was further divided into Qi deficiency and blood stasis syndrome group (case group) and non-Qi deficiency blood stasis syndrome group (control group) to perform “syndrome” analysis. The general data and clinical information of the study subjects were collected. The peripheral venous blood was extracted on an empty stomach, and the Illumina Infinium MethylationEPIC BeadChip (850K methylation chip) was used to detect the differential expressionprofiles of DNA methylation in each group, ChAMP software (V 2.14.0) was used for the differential methylation data analysis, with a threshold of the adjusted P value (adj.P.val) < 0.01. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) were employed for the functional and pathway enrichment analyses of related mapped genes.
Results:
A total of 263 differentially methylated CpG positions (DMPs) were screened out between G and J groups, including 191 hypermethylated positions such as cg05845204 and cg08906898, and 72 hypomethylated positions such as cg26919182 and cg13149459. These positions were mainly mapped to 148 genes encompassing RNA binding motif protein 39 (RBM39), acetyl-CoA acyltransferase 2 (ACAA2), protein phosphatase 1 regulatory subunit 12B (PPP1R12B), and the dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2). GO functional enrichment analysis revealed that the genes of the DMPs were primarily enriched in protein localization to chromosomes, regulation of cell morphogenesis, negative regulation of calcium-mediated signals, etc. KEGG pathway analysis suggested that the genes were mainly enriched in fatty acid metabolism and endocytosis pathways. In addition, a total of 23 differential methylation regions (DMRs) were identified, with overlapping genes such as transmembrane protein 232 (TMEM232), ribosomal protein large P1 (RPLP1), peroxisomal biogenesis factor 10 (PEX10), and forkhead box N3 (FOXN3) recognized. It was found that GO functions were mainly enriched in the negative regulation of Ras protein signal transduction, small GTPase-mediated signal transduction, negative regulation, etc. A total of 1 703 differential methylation sites were screened out between case and control groups, including 444 increased methylation positions such as cg05573767 and 1 259 decreased methylationpositions such as cg19938535, and cg03893872. These positions were mapped to 1 108 genes such as ribosomal protein S6 kinase A2 (RPS6KA2), leucine rich repeat containing 16A (LRRC16A), and hedgehog acyltransferase (HHAT). According to the GO functional enrichment analysis, the genes relating to the DMPs were mainly enriched in biological functions such as transmembrane receptor protein serine/threonine kinase signaling pathway and axonogenesis. The KEGG pathway enrichment analysis suggested the involvement of Rap1 signaling pathway, adenosine 5’-monophosphate-activated protein kinase (AMPK) signaling pathway, etc. A total of 21 DMRs were identified, including 22 overlapping genes such as mucin 4 (MUC4), three prime repair exonuclease 1 (TREX1), and LIM homeobox 6 (LHX6). GO analysis demonstrated that the genes primarily participated in molecular functions such as positive regulation of transmembrane transport, regulation of fatty acid metabolism, and copper ion binding.
Conclusion
This study reveals the methylation patterns of DMPs and DMRs in patients with Qi deficiency and blood stasis syndrome caused by CHD-induced unstable angina pectoris. Potential epigenetic regulation of fatty acid metabolism, Rap1 signaling, and other molecular functions are involved in the development of CHD between the "disease" and "syndrome".