1.Immunotoxin BAC5-CT treated nasopharyngeal carcinoma
Huiling YANG ; Changzheng LIU ; Yongshen ZHAO
Chinese Journal of Pathophysiology 2001;17(8):729-
In this study, immunotoxin (IT) was prepared by conjugating BAC5 and CT with SPDP. The effects of IT on NPC and its mechanisms were explored using double labeled with radioactive nuclides, immunography and electron microscope technique in vivo and in vitro. The specific concentration of BAC5 in the tumor area showed. The radioactivity rate of tumor/nontumor (T/NT) was up to 10.26. IT had cytotoxic effects both on the cultured CNE-2 cell line and tumor multicell spheroides. In vivo, the preliminary result indicated that IT also had a inhibitory action on the nude mice models bearing human NPC (Reported in another article). Under electron microscope, the necrosis and apoptosis of tumor cells were found. The membranes of most tumor cells were found intacted not or corrosined, some of them had the character of apoptosis, including reduce of tumor cells membrane villi, condensation of cytoplasm and pyknosis or cleavage of nuclear. There were many of apoptosis bodies, which were occasionally phagocytosed by tumor cells. The infiltration of immunocytoes in tumor tissue could be seen. The results indicated that BAC5 can specifically combine with NPC cells and BAC5-CT has the inhibitory effect on NPC in vitro and in vivo, mechanism of which may be related to the effects that ‘warhead' CT dissolute the membrane of tumor cells directly, or/and IT promote the infiltration of immunocytoes so as to induce the apoptosis of tumor cell.
2.Different Effects of Mahuang Decoction and Maxing Shigan Decoction on Animal Temperature Tropism and Correlation to Differences of Cold and Hot Nature of Chinese Materia Medica
Jiabo WANG ; Yanling ZHAO ; Xueru ZHANG ; Canping ZHOU ; Tasi LIU ; Haiping ZHAO ; Yongshen REN ; Xiaohe XIAO
Chinese Herbal Medicines 2010;02(3):211-215
Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica(CMM)through the different effects of Mahuang decoction(MHD)and Maxing Shigan decoction(MSD)on animal temperature tropism.Methods The equipment with cold/hot pads was used to investigate the variety ofthe temperature tropism between two groups of mice treated by MHD and MSD,respectively.Meanwhile,the activities ofadenosine triphosphatase(ATPase),superoxide dismutase,succinate dehydrogenase,and malondialdehyde were measured.Results After treated by MHD,the macroscopic behavioral index of remaining rate on warm pad(40 ℃)of mice decreasedsignificantly(P < 0.05),suggesting the enhancement of cold tropism,meanwhile,the internal indices of ATPase activity and oxygen consuming volume increased significantly(P < 0.05),suggesting the enhancement of energy metabolism.On theother hand,the above-mentioned indices in MSD group changed on the inverse way.Conclusion The relative drug natureof MHD and MSD revealed in this study is consistent with the theoretical prognostication or definition.It indicates that theinternal cold and hot nature of CMM could be reflected in ethological way on the changes of animal temperature tropismwhich might be internally regulated by body energy metabolism.
3.Compatibility evaluation of Chinese medicines injections based on isothermal titration calorimetry.
Xue FENG ; Dan YAN ; Yan YAN ; Yongshen REN ; Ping ZHANG ; Yumei HAN ; Kuijun ZHAO ; Xiaohe XIAO
Acta Pharmaceutica Sinica 2011;46(3):322-8
The paper is to report the establishment of a method for quickly evaluating compatibility of Chinese medicines injections. Isothermal titration calorimetry (ITC) was used to evaluate compatibility of Yiqifumai (YQFM) and vitamin C injection (Vc)/5% glucose injection (5% GS). The diversification of Gibbs free energy (deltaG), enthalpy (deltaH) and entropy (deltaS) were used to decide reaction types of colliquefaction procedures of different injections. The reactive profiles were used to determine signs and quantity of heat. And high performance liquid chromatography (HPLC) was used as a supportive method for ITC. Then, feasible binding sites were analyzed based on the information of spatial structures of major compositions. During the colliquefaction procedure of YQFM and Vc, [deltaH] > T[deltaS], so, the reaction is enthalpy-driving. And the reactive profile showed that a big deal of heat was given out during the procedure. Obviously, chemical reactions happened and the major compositions changed. On the other side, the reaction of YQFM mixed with 5% GS was entropy-driving, because [deltaH] < T[deltaS]. The reactive profile showed there was a little heat gave out. So, non-chemical reactions happened, and the major compositions did not change. The conformity existed between the results of ITC and HPLC. ITC could be used to evaluate the compatibility of Chinese medicines injections because of the advantages of ITC, such as real time, fast, sensitive and having more parameters.
4.Study on the HPLC Fingerprint of Dry Ginger
Qi GUO ; Xiaohong ZHAO ; Haijian HAN ; Rui SHEN ; Ying YANG ; Hong LEI ; Yongshen LI
China Pharmacist 2015;(3):397-399
Objective:To establish the HPLC fingerprint of dry ginger to provide experimental evidence for the quality control. Methods:An Agilent TC-C18 column (250 mm × 4. 6 mm,5 μm) was used, the flow phase was acetonitrile-water with gradient elu-tion, the flow rate was 1. 0 ml·min-1 , the column temperature was 30℃, and the detection wavelength was 240 nm. The data were e-valuated by the similarity evaluation software for TCM fingerprint. Results:There were 10 common peaks in HPLC chromatogram of 10 batches of dry ginger at 240 nm, and the chemical similar coefficient was 99%. Conclusion: The fingerprint of ginger at 240 nm is highly specific and typical with a rich fund of information, which can provide useful references for the quality control and evaluation of dry ginger.
5.Study toxicity-attenuating effect and dose-toxicity relationship of rhubarb by processing based on correspondence analysis.
Jiabo WANG ; Yonggang MA ; Cheng JIN ; Ping ZHANG ; Xiaohe XIAO ; Yanling ZHAO ; Xiaoyan XING ; Yongshen REN
China Journal of Chinese Materia Medica 2009;34(19):2498-2502
OBJECTIVETo study the toxicity-attenuating effect and the dose-toxicity relationship of rhubarb by processing based on correspondence.
METHODThe effects of different processed materials of rhubarb on the hepatic and renal functions of mice was researched in a way of parallel comparison, as well as the chemical alteration induced by processing was observed. Correspondence analysis, a kind of multivariate statistical analysis, was performed to explore the dose-toxicity relationship of processed materials of rhubarb.
RESULTNo obvious toxic effect was found in mice after single intragastric administration of crude drug of rhubarb at dosage of 76 g x kg(-1), while some lesions to liver and kidney tissues were observed in mice after repeated administration of rhubarb and its processed materials for 14 days at the same dosage. In the correspondence analysis diagram, it could be deduced that there was definite dose-toxicity relationship of processed rhubarb as the distance between trial groups and control group increased along with the dosage and the toxicity. The distance of the processed rhubarb showed as the following consequence: crude drug of rhubarb > vinegar-processed rhubarb > alcohol-processed rhubarb > steamed rhubarb > carbonized rhubarb > Qingning pian. Theerefoer, the toxicity of processed rhubarb was much lower than that of crude drug and the extent of toxicity attenuation was related to the processing intensity. Meanwhile, the toxicity-attenuating effect of processed rhubarb was related to the decline of the contents of both anthraquinone glycosides and tannins, and the former was contributed remarkably to toxicity.
CONCLUSIONThe toxicity-attenuating effect of processed rhubarb was verified in this study and the toxicity of steamed rhubarb attenuated notably while the pharmacological substances degraded little. The correspondence analysis would be useful to assess the pharmacological and toxic effects with multiple indexes of traditional Chinese medicines.
Animals ; Chemistry, Pharmaceutical ; methods ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Female ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mice ; Random Allocation ; Rheum ; chemistry
6.Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways
Shuyi YUAN ; Yanfen LIU ; Yun MU ; Yongshen KUANG ; Shaohong CHEN ; Yun-Tao ZHAO ; You LIU
Journal of Veterinary Science 2024;25(2):e21-
Background:
Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial.
Objectives:
To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication.
Methods:
The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway.
Results:
The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010.
Conclusions
PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.