1.Discovery of natural BH3 mimetics and research on related mechanism
Si-Meng GU ; Shuai-Shuai LIU ; Yue ZHANG ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):281-282
In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.
2.Inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism
Shuai-Shuai LIU ; Si-Meng GU ; Jian-Hui DUAN ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):295-296
Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.
3.Simulation study of electrical impedance tomography based on approaching real finite-element model of brain
Wan-Jun SHUAI ; Xiu-Zhen DONG ; Feng FU ; Youfu-Sheng ; Rui-Gang LIU ; Xue-Tao SHI ;
Chinese Medical Equipment Journal 2003;0(11):-
This paper is to build a finite element model of brain with a real brain shapeon which simulation studies of electrical impedance tomography EIT in the brain is based. A curve of a real brain shape is simulated with the curve-fitting methods and EIT in the brain is finished with finite-element methods and Equipotential Lines Back-Projection algorithm.The locationarea and amplitude of the change of the resistivity are reconstructed accurately. But the image quality has to be further improved.This paper provides a basis for clinical applications of EIT in brain.
4.Inhibitory action of Potentilla anserine polysaccharide fraction on H2O2-induced apoptosis of murine splenic lymphocytes.
Xue-Hong SHUAI ; Ting-Jun HU ; Xia ZHANG ; Fu-Sheng CHENG ; Jiong-Ran CHEN
Acta Pharmaceutica Sinica 2009;44(9):987-993
A water-soluble polysaccharide fraction from root of Potentilla anserine was obtained. Gas chromatogram, FT-IR, physical and chemical characteristics of the Potentilla anserine polysaccharide fraction (PAPF) were analyzed. The protective effects of PAPF against the H2O2 induced process of apoptosis of murine splenic lymphocytes were investigated in vitro. Morphological assessment of apoptosis was performed with light microscope and laser scanning confocal microscope. DNA fragmentation was visualized by agarose gel electrophoresis. The amount of apoptotic cells was measured by flow cytometry. The results showed that PAPF is composed of rhamnose, arabinose glucose and galactose. H2O2 (200 micromol x L(-1)) induced apoptosis of murine splenic lymphocytes with the cell volume reduced, cytoplasm and nuclear shrunk and DNA stained non-uniformly. Condensed chromatin and formation of apoptotic body were observed in the apoptotic cells. Apoptotic bodies in the cells treated with PAPF and H2O2 were less than those in H2O2 treatment alone. DNA fragmentation assay showed that PAPF (50, 100, 200, and 400 microg x mL(-1)) obviously reduced H2O2-induced ladder bands. Flow cytometry analysis showed that H2O2 increased the populations of apoptotic sub-G1 cells from 5.60% (control) to 45.40%, and PAPF decreased H2O2-induced apoptosis to 37.80%, 22.70%, 17.70%, and 8.50%, respectively. In conclusion, PAPF reduced H2O2-induced oxidative damage in a dose dependent manner.
Animals
;
Apoptosis
;
drug effects
;
Cells, Cultured
;
DNA Fragmentation
;
Flow Cytometry
;
Hydrogen Peroxide
;
pharmacology
;
Lymphocyte Count
;
Lymphocytes
;
cytology
;
drug effects
;
Mice
;
Polysaccharides
;
pharmacology
;
Potentilla
;
Spleen
;
cytology
5.Formula Optimization in Renshen Jianxin Capsule Based on Uniform Design and Anti-myocardial Ischemia Effect.
Chua-hua YANG ; Yun-lun LI ; Hai-qiang JIANG ; Lei NIE ; Jiang-qing JU ; Shuai LI ; Xue-yi DING ; Shi-jun ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(9):1105-1108
OBJECTIVETo realize quadratic formula optimization of Renshen Jianxin Capsule (RJC) by screening Chinese herbs with major anti-myocardial ischemia effect in RJC and optimize their optimal dosages.
METHODSBy following "uniform design-pharmacodynamic experiment-mathematical modeling-formula optimization", authors employed U10(10(8)) uniform design in the experiment. Eight Chinese herbs contained in RJC were taken as observatory factors. Electrocardiograph (ECG) changes of myocardial ischemia induced by isoproterenol were taken as pharmacodynamic indices. The mathematical model between herbal factors and pharmacodynamic indices was established using stepwise regression analysis to screen Chinese herbs with major anti-myocardial ischemia effect. Their optimal dosages were optimized using the grid algorithm.
RESULTSThe regression equation was y =1. 7889 -0. 3247 Ginseng xSalvia Miltiorrhiza -0. 0663 Astragalus membranaceus xOriental Waterplantain tuber. Forecasting factors included were Ginseng, Salvia Miltiorrhiza, Astragalus membranaceus, and Oriental Waterplantain tuber. The optimal formula dosage calculated by the grid algorithm was Ginseng 1. 62 g, Astragalus membranaceus 4. 62 g, Salvia Miltiorrhiza 2. 43 g, and Oriental Waterplantain tuber 1. 66 g.
CONCLUSIONUniform design combined with stepwise regression analysis and grid algorithm were able to realize quadratic formula optimization of RJC.
Astragalus membranaceus ; Chemistry, Pharmaceutical ; standards ; Coronary Artery Disease ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Electrocardiography ; Humans ; Isoproterenol ; Myocardial Ischemia ; drug therapy ; Panax ; Salvia miltiorrhiza
6.Correlations between levels of plasma D-dimer and CT images as well as prognosis in patients with acute head injuries
Jie ZHU ; Xiao-Xiong CHEN ; Cong-Shui YE ; Xue-Jun SHUAI
Chinese Journal of Neuromedicine 2008;7(8):812-814
Objective To study the correlations between levels of plasma D-dimer (DD) and CT images as well as prognosis of acute head injury. Methods The levels of plasma DD were quantitatively dynamically measured and CT images were taken in 87 patients with head injuries. The relationships of the concentration of DD with Glasgow coma score (GCS), Glasgow outcome score(GOS) and CT images were studied. Results The level of plasma DD in patients with bead injuries was significantly higher than that of control group (P<0.05). The concentration of DD was positively correlated with CT alterations, and negative correlated with GCS and GOS. Conclusion The level of plasma DD is correlated with change of CT images, which may be useful for judging the severity and prognosis in the early stage of head injury.
7.Rehabilitation by hollow obturator prosthesis immediately after total maxillectomy for malignant tumor
Xiao-Ye LI ; Ai-Hui YAN ; Shuai HAO ; Wei LI ; Xue-Jun JIANG ; Li LU ; Xing-Jun QIN ; Hai-Xin YAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2011;46(5):362-367
Objective The feasibility and clinical effects of hollow obturator prosthesis for the repair of maxillofacial defect immediately after maxillectomy for cancer were assessed. Methods Thirteen patients with T3-4aN0M0 maxillary neoplasm were treated by the prostheses immediately after maxillectomy. According to the 3D-CT reconstruction of nasal sinus, the 3D stereoscopic prototype was constructed before the surgery. Simulating surgery with Surgicare 5. 0 software and then the prosthesis 3D stereoscopic model was shaped. The prosthesis was made quickly and precisely with methacrylate resins according to the model and the print mold before surgery, with supplementary tooth at the bottom of prosthesis. In the surgery, the prosthesis was installed instantly after maxillectomy. The patients were followed up at 1 , 3 and 6 month after the surgery, respectively. The facial features and the pronunciation clarity were examined and the questionnaires were carried out in the patients, with compareation by paired t-test. The hollow obturator prosthesis would be replaced by permanent prosthesis made of methacrylate resins at 6 month after the surgery. ResultsThe hollow obturator prostheses were installed accurately and maxillofacial defects were repaired immediately after maxillectomy in the 13 patients. Postoperative follow-up showed there were significant differences in eyeball sagging (t = 4. 67, P <0. 05 ) , mid-facial region collapse ( t = 5. 67, P < 0.05) , and pronunciation clarity (t = 16. 38, P <0. 05) between patients with and without prostheses. Questionnaires showed that all the patients were satisfied with the retention of prostheses, the improvement of appearance, the improvement of the symptom of water choking and speech definition. Six months after the surgery, the hollow obturator prostheses were replaced smoothly by permanent prostheses in 11 of the 13patients. Conclusion The precise and instant repair of maxillofacial defect by prosthesis after maxillectomy can improve survival quality of patient.
8.Investigation of the health management status and health needs in the physical examination population
Xuan-Qin ZUO ; Li LI ; Li WANG ; Xue-Jun SHUAI ; Fu-Jun CAI ; Wen-Wen LI
Chinese Journal of Modern Nursing 2013;48(36):4441-4444
Objective Investigating the health management status and health needs in the physical examination population in order to explore the suitable health management service mode for special population . Methods Sixty-two persons with hospitalized physical examination were surveyed by the questionnaire on thehealth management service needs according to the descriptive research design .Results The sixty-tworespondents had the strong health consciousness , 64.5% of respondents carried out the physical examinationevery six months or once a year, and 71% of respondents had the positive attitude or didn ’t reject to take thehealth management.But the respondents had more prominent health problems , 47% of respondents did notregularly have the breakfast, and 66% of respondents occasionally or never did exercise .In terms of specificneeds, 91.4% of respondents wanted to have fixed staff to provide health services , 62.3% of respondents hopedto regular physical examination on admission , 57.4% of respondents hoped somebody would provide healthadvice, and 42.6% of respondents hoped to establish the hospital green channel .Conclusions In order to meetthe demand of health management service for special population , the health management services should take thechronic diseases and health /sub-health population as the key and apply the patient -centered humanized service.
9.Application of nano-sized TiO2 photocatalysis to air purification and sterilization.
Bing-jie LI ; De-hui YANG ; Shuai-qin WU ; Bo-sen LI ; Hao MENG ; Si-peng JIANG ; Guo-jun LIU ; Yue-hui ZHAO ; Hong-bo CUI ; Xue-mei ZHOU ; Zhao-hua ZHONG
Chinese Journal of Preventive Medicine 2008;42(11):831-835
OBJECTIVETo develop and evaluate the efficiency of air purification and sterilization instrument based on nano-sized TiO(2) photocatalytic technique.
METHODSThe nano-sized TiO(2) photocatalytic air purification and sterilization instrument was designed and a sample had been prepared. The sterilization efficiencies for E.coli and Klebsiella by the nano-sized TiO(2) photocatalytic instrument and ultraviolet (UV) were measured in closed labs. The on-site efficiency of the instrument was evaluated, too.
RESULTSThe nano-sized TiO(2) photocatalytic air purification and sterilization instrument was composed of five units: rough filter, nano-sized TiO(2) photocatalytic unit, activated carbon fiber filter, negative ion generator, and programmed control unit. The E.coli killing rates by the nano-sized TiO(2) photocatalytic instrument were 76.0%, 81.8%, 77.5%, and 80.7% at 30, 60, 90, and 120 minutes, respectively. There was no significant difference between the E.coli killing rates of the instrument and UV (P > 0.05), except the 120 minutes timepoint. The Klebsiella killing rates by the instrument were 78.4%, 79.5%, 67.3%, and 58.5% at 30, 60, 90, and 120 minutes, respectively. The Klebsiella killing efficiencies of the instrument at 30 and 60 minutes were better than that of UV (P < 0.01). There was no significant difference between the Klebsiella killing efficiencies of the instrument and UV (P > 0.05).
CONCLUSIONThe air sterilization efficiency of the nano-sized TiO(2) photocatalytic instrument should be equivalent or better as compared with the UV. This instrument might be used for the air purification and sterilization of the public locations.
Air Pollution ; prevention & control ; Decontamination ; methods ; Disinfection ; methods ; Nanostructures ; Photochemistry ; Titanium
10.Cholesteatoma otitis media and supratubal recess.
Xue-jun JIANG ; Hong-quan WEI ; Lian HUI ; Shuai HAO ; Fang ZHANG ; Ning ZHAO ; Li-yang ZHAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2007;42(7):491-493
OBJECTIVETo study the significance of supratubal recess and its aeration pathway to epitympanum in the pathogenesis of cholesteatoma otitis media.
METHODSFifty-two ears of cholesteatoma were selected as study group. Sixteen ears of traumatic facial palsy with pneumatic mastoid, which had no history of chronic otitis media were selected as control group. The status of supratubal recesses of all and their aeration pathways to epitympanum were observed in operations.
RESULTSSixteen ears from control group clearly presented supratubal recesses. Membrane closure was founded in four of them. The aeration pathways of fifty-two ears (100%) from study group were all completely closed. Comparing with control group, the difference was obviously significant (chi2 = 41.7144, P = 0.000). Among these cases, bony closure was observed in thirty-four ears (65.4%), while membrane closure in eighteen ears (34.6%). Their epitympanum space was very narrow and mastoid was sclerotic or poorly developed.
CONCLUSIONSBlockage of the aeration pathway between supratubal recess and epitympanum was possible one of the origins of negative-pressure status of epitympanum and mastoid, which might lead to the formation of aural cholesteatoma. Anatomy variation of the aeration pathway from supratubal recess to epitympanum might be a pathogenesis factor of cholesteatoma otitis media. It suggested that opening the aeration pathway in tympanoplasty with intact canal wall up technique might be helpful to prevent recurrence of aural cholesteatoma.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Cholesteatoma, Middle Ear ; pathology ; Eustachian Tube ; pathology ; Facial Paralysis ; pathology ; Female ; Humans ; Male ; Middle Aged ; Young Adult