1.A review of the expression and activity of drug metabolism enzymes in tumorous cells.
Wenjing XIAO ; Guangji WANG ; Jiye A
Acta Pharmaceutica Sinica 2014;49(10):1377-86
Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviewed the expression and activity features of major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences.
2.Pharmacokinetics and in vitro-in vivo correlation evaluation of self-emulsifying drug delivery system and conventional tablets of aniracetam
Juan LI ; Yan ZHANG ; Guangji WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2007;12(4):434-439
AIM: To evaluate the correlation between in vitro release and in vivo absorption of aniracetam in conventional tablets and self-emulsifying drug delivery system (SEDDS), to investigate pharmacokinetics of aniracetam self-emulsifying drug delivery system and conventional tablets of aniracetam after oral administration to rats. METHODS: Dissolution behavior of these formulations was evaluated in vitro to assess the properties of dosage forms. And a new RP-HPLC method was developed for the in vivo quantitative determination of 4-p-anisamidobutyric acid (PABA), the active metabolite of aniracetam. To approach the in vitro-in vivo correlation, fraction absorbed in vivo (f) was calculated by Wagner-Nelson method, and then compared with in vitro released drug percentages (Q%). RESULTS: Aniracetam was released rapidly from SEDDS with 80%±4% of accumulation dissolution rate compared to that from conventional tablets at 15 min. The recovery of active metabolite of aniracetam was about 90%, and the intra-days and inter-day precision were within 4% and 6%, respectively. The AUC0-∞ value of aniracetam SEDDS was (11 168±2 395) ng·mL-1·h, which was about 3 folds greater than conventional tablets. The parameter MRT0-∞ of aniracetam SEDDS and conventional tablets were (2.7±0.6) h and (1.7±0.6) h, respectively, and the difference was statistically significant(P<0.05). The linear equation of in vitro-in vivo correlation for conventional tablets was obtained by regression as well. Whereas nonlinear correlation was obtained for aniracetam SEDDS, which fitted the quadric model very well and the correlation coefficient was 0.972. CONCLUSION: Aniracetam can be released faster from SEDDS than that from conventional tablets, and SEDDS improved the bioavailability of aniracetam significantly. The SEDDS composed by oil and compound surfactants which could enhance the absorption showed the expressing rate of dissolution, and those formed the o/w microemulsion with gastrointestinal liquid could absorb through lymphatic transport route.
3.Illustrate Six Merdians Theory with the Images of Bagua
Hong CHANG ; Dong WANG ; Guangji ZHANG
Journal of Zhejiang Chinese Medical University 2014;(11):1266-1268
Objective] The explanations of the six meridians theory in the book Shanghan Lun were always divergent, most of them explained it with medical theory of later ages.However, il ustrating it from the philosophic perspective was not commonly seen. Yi Jing, the book of changes, was the origin of traditional Chinese philosophy, and the six meridian system, which included three yin and three yang, was just derived from the four xiang(a traditional Chinese concept which refers to taiyang, shaoyin, shaoyang, taiyin). [Method] Through the eight trigrams and the images were analyzed with the Treatise on Six Classicsstate gasification combined with analysis Zhongjing Six Classics theoretical system and the principle of prescription. [Result] Found that eight trigrams can be good images of the corresponding six by the system, the difficult provisions in Tretise on Febrile Diseases were wel explained. [Conclusion]Through combining the images of Bagua(eight trigrams) in Yi Jing with six meridians in Shanghan Lun,il ustrating six meridians from philosophic aspect, and explaining the six meridians theory with philosophical ideas before Zhongjing ’s(the writer of Shanghan Lun) age, in order to provide new ways of thinking in comprehending the six meridians system.
4.Study on Four Seasons’Influence on the Six Meridians Theory in Shanghan Lun and the Pulse System
Hong CHANG ; Dong WANG ; Guangji ZHANG
Journal of Zhejiang Chinese Medical University 2015;(6):433-435
Objective]To study the correspondence between human and universe theory in Shanghan Lun starting with Zhongjing ’s doctrine of treatment based on four seasons,analyse the influence of the changing seasons on giving names to the six meridians by Zhongjing ,research on the influence of pulse theory based on four seasons in Huangdi Neijing on the pulse system includes the six meridians system ,summarize the rules of the four seasons’ influence on the six meridians system in Shanghan Lun,and return to Zhongjing’s original viewpoint of four seasons and their yin and yang condition. [Method]By studying the Treatise on Four Seasons treatment Dafa Six Classics and veins in the school system, restore Treatise on Heavencorresponding way of thinking. [Result] It finds that seasons law is the core of six distinguished by its Zhongjing school system clock. [Conclusion] Studying the Four Seasonslaw andseasons therapy Dafa can know Treatise on Six by the corresponding season and six by the significance and reflects theTreatise onlearning system from four seasons pulse method.
5.PROLIFERATION/APOPTOSIS INDEX——A NEW TOOL IN EVALUATING THE MALIGNANT DEGREE OF GLIOMAS
Jianqi WANG ; Guangji ZHANG ; Yanhua HAN
Medical Journal of Chinese People's Liberation Army 2001;0(09):-
To establish the proliferation and apoptosis index(P/AI), and to explore its relationship to the malignant degree of gliomas. Specimens of normal brain tissues obtained from 8 patients undergoing decompression operation for head injury, and 69 paraffin-embedded specimens and 26 fresh specimens of the glioma were studied. Immunohistochemical staining of proliferation cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase mediated dUTP DIG nick end labeling(TUNEL) were used to determine the proliferation and apoptosis rates of the glioma. Grading was defined by the ratio between PCNA positive rate and TUNEL positive rate (P/AI). An increase in P/AI denoted an increase in malignancy. It was found that P/AI of normal brain tissue was 0.2-1.5. In 85.1% of grades Ⅰ and Ⅱ gliomas, P/AI was lower than 2.5 and while in 91.7% of grades Ⅲ and Ⅳ gliomas P/AI was 2.5. There were significant differences between normal group, grades Ⅰ and Ⅱ and grades Ⅲ and Ⅳ over gliomas (P
6.Clinical significance of segmental somatosensory evoked potential in diagnosing the lumbar spinal stenosis
Guangji WANG ; Ningjiang SHEN ; Jian CHEN
Orthopedic Journal of China 2006;0(05):-
[Objective]To investigate the effect of dermatomal somatosensory evoked potential(DSEP) in diagnosing the damage of nerve root in lumbar spinal stenosis. [Method]Diagnostic test was deployed in this reseach.All experiment objects were divided into the case group and the control group.There were 47 cases in the case group.There were 14 males and 33 females with the mean age of 52.6 and the mean stature was 1.64 m.In the control group,there were 50 cases which include 26 males and 24 females with the mean age of 50.4 and the mean stature of 1.65 m.The DSEP P40 latency and P1-N1 amplitude of cutis plate in L4、5 and S1 segment were determined.The data of the case group were compared with those of control group and analyzed statistically.[Result]In the case group,the P40 latency of 91 segments prolonged obviously and P40 wave of 103 segments disappeared.Comparing the P40 latency and P1-N1 amplitude of 3 segments(L3、4、L4、5and L5S1) in two groups,the change was remarkable(P
7.THE ROLE OF TELOMERASE OLIGODEOXYNUCLEOTIDE IN THE INHIBITION OF GROWTH OF MALIGNANT GLIOMA CELLS
Jianqi WANG ; Guangji ZHANG ; Yanhu HAN
Medical Journal of Chinese People's Liberation Army 1981;0(06):-
To evaluate the curative effect of antisense telomerase ODN on malignant glioma cells. The activity of telomerase in 16 fresh malignant gliomas was detected positive by PCR ELISA method. After covered with lipofectin, the 5?mol/L telomerase ODN was incubated with cultured gliomas cells. PCNA, TUNEL positive rate and the phase of cell cycle were detected by FcM per 24h. The results showed: Anti sense ODN inhibited telomerase activity after being applied for 48 hours, and inhibition was complete at 72 hours, The ODN inhibited proliferation of malignant gliomas and promoted their apoptosis markedly at 72 hours. After 96 hours, most transfected glioma cells were stopped to grow at G 2/M phase, and the number of apoptosis cells increased as time went on. The results suggested that anti sense telomerase ODN could inhibit the telomerase activity, and in turn promote aptoptosis of glioma cells and inhibit the growth of the tumor.
8.Advances in molecular mechanisms of organelle interaction and their role in disease developmen
Shuzhen HUANG ; Guangji WANG ; Yuan XIE
Journal of China Pharmaceutical University 2019;50(4):389-396
Organelles have their special functions, they interact with each other and coordinate a series of important physiological functions at the same time. Organelle interaction occurs at membrane contact sites(MCSs), where the membranous organelle endoplasmic reticulum is the core, and specific tethered proteins at the membrane contact site bind to the organelle membrane and various protein complexes work together to perform specific functions, such as lipid transport, Ca2+ transfer, etc. This review studies on the structure and function of membrane contact sites and their key roles in organelle interactions, focusing on the connection between the endoplasmic reticulum and plasma membrane, mitochondria and Golgi, as well as the association between the key proteins at membrane contact sites and the occurrence and development of various diseases.
9.Pharmacokinetics and excretion of phenolicacids from mailuoning injection in rats
Wei WANG ; Guangji WANG ; Haiping HAO ; Nan CUI ; Xuanrong SUN
Chinese Journal of Clinical Pharmacology and Therapeutics 2008;13(7):776-781
AIM: To study the pharmacokinetics of phenolic acids from Mailuoning injection in rats. METHODS: SD rats were given a single i.v. administration dose of Mailuoning injection 10 mL/kg, plasma and urine were collected before and after injection. Phenolic acid components in plasma and urine were measured by LC/MS. Pharmacokinetic parameters were determined from the plasma concentration-time data and urinary excretion-time data with the DAS software package. RESULTS: After i.v. of Mailuoning injection, chlorogenic acid (CGA), 1, 5-dicaffeylquinic acid (1,5-DCQA), 3, 4-dicaffeylquinic acid (3,4-DCQA), 3, 5-dicaffeylquinic acid (3,5-DCQA) and caffeic acid (CA) were quickly excrectioned. The t1/2 of CGA, 1,5-DCQA, 3,4-DCQA, 3,5-DCQA and CA were 0.649, 0.334, 0.479, 0.486 and 0.330 h, respectively. AUC0-∞ were (22.522±2.716), (0.353±0.062), (3.620±1.246), (5.287±1.627) and (2.257±0.360) mg·L-1·h, respectively. After i.v. of Mailuoning injection, CGA, 1,5-DCQA, 3,4-DCQA, 3,5-DCQA and CA can all be detected in the urine. The amounts of CGA, 1,5-DCQA, 3,4-DCQA, 3,5-DCQA and CA excreted from urine during 0-24 h were (122.22±26.49)%, (3.30±1.26)%, (0.24±0.11)%, (1.93±0.77)% and (18.61±4.99)% of dose given in rats, respectively. CONCLUSION: After i.v. of Mailuoning injection, phenolic acids can be excreted quickly. Only a small quantity of 1,5-DCQA, 3,4-DCQA, 3,5-DCQA and CA were excreted from urine. 3,4-DCQA and 3,5-DCQA may be metabolized into CGA in the rat plasma.
10.Studies on pharmacokinetics of guanfu base I,a metabolite of guanfu base A
Xiaotian LI ; Guangji WANG ; Sujun WANG ; Jinghan LIU
Chinese Pharmacological Bulletin 1987;0(03):-
Aim To establish an analytical method for determination of guanfu base I (GFI) concentration in plasma and investigate its pharmacokinetics in rats. Methods Rats were given a 20 mg?kg~-1 dose intravenously. Blood samples were collected at various times after iv administration. The plasma concentration of GFI was determined by LC-MS. Pharmacokinetic parameters were calculated by 3p97 program.Results The method was linear in the 0.05~20 mg?L~-1 concentration range (r=~0.999 4 ). The recovery of guanfu base I was more than 80%.The intraday and interday precision, expressed as the relative standard deviation (RSD), was generally good (