1.YZG-330 regulates the TRPM8 ion channel through the P38 MAPK signaling pathway to reduce body temperature in mice
Zi-yu ZHU ; Yuan-zhi YU ; Yue YUAN ; Jian-jun ZHANG
Acta Pharmaceutica Sinica 2022;57(5):1336-1343
Preliminary research in our laboratory found that compound YZG-330 can reduce mouse body temperature, which could be blocked by adenosine A1 receptor (A1R) antagonist DPCPX. Based on the downstream signaling pathway of the A1R, the mechanism by which YZG-330 lowers body temperature was further studied. The pharmacodynamics of YZG-330 was evaluated by measuring the rectal temperature; expression of the transient receptor potential (TRP) ion channel, the P38 protein and its phosphorylated form in mouse hypothalamic homogenate were detected by Western blotting. A Ca2+ fluorescent probe, Fluo-3AM, was added to cells to detect the effect of YZG-330 on the Ca2+ content of mouse hypothalamic cells. YZG-330 dose-dependently reduced the body temperature in mice, and the selective P38 inhibitor SB-203580 (20 mg·kg-1, i.p.) significantly inhibited the hypothermic effect of YZG-330. A TRPM8 antagonist 2 (0.1 μg per mouse, i.c.v.) markedly attenuated the hypothermic effect of YZG-330 (0.25 or 1 mg·kg-1, i.p.). YZG-330 (2 mg·kg-1, i.p.) significantly increased the phosphorylation of P38, an effect that could be attenuated by the A1R antagonist DPCPX (5 mg·kg-1, i.g.) in mouse hypothalamus. In addition, YZG-330 also prominently enhanced the expression of TRPM8, which could be blocked by SB-203580; YZG-330 (0.1-10 μmol·L-1) increased intracellular Ca2+ concetration in mouse hypothalamic cells in a dose-dependent manner, and was inhibited by the A1R inhibitor DPCPX (0.5 and 1 μmol·L-1) and TRPM8 antagonist 2 (1 μmol·L-1). In conclusion, YZG-330 exerts its hypothermic effect by activating the A1R to promote the phosphorylation of P38 protein and thereby up-regulating the expression and activity of the TRPM8 ion channel, resulting in increased intracellular Ca2+ concentration to stimulate mouse hypothalamus cells to down-regulate body temperature. All animal experiments were approved by the Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences.
2.Osteogenic effects of induced autologous endothelial cells on bone marrow stromal cells of rabbits in co-culture condition
Yuan SUN ; Hong LIN ; Zi-Zheng WU ; Yu CHEN ; Jian DONG ;
Chinese Journal of Orthopaedic Trauma 2004;0(10):-
Objective To study the osteogenic effects of induced endothelial cell(EC)on bone marrow stromal cells(BMSCs)of rabbits in co-culture condition.Methods BMSCs were obtained from rabbits by density gradient centrifugation.The adhesive ceils were preserved to passage in culture.The cultured cells were divided into four groups:group A(BMSCs),group B(BMSCs osteogenic induction),group C(EC induction)and group D (co-culture of induced BMSCs and EC).The cell morphology,immunofluorescence,cell proliferation,alkaline pbosphatase(ALP)activity,osteocalcin synthesis were observed to determine the effects of induced autologous EC on the osteogenic potential and cellular compatibility of BMSCs.Results The immunochemical staining showed that the BMSCs were induced into EC in group C.The cellular compatibility of BMSCs and EC was good.The ALP activity and osteocalcin content were obviously higher in group D than in any other groups(P<0.05).The cell proliferation difference was not obvious between groups(P>0.05).Conclusions The cellular compatibility of induced osteoblasts and induced EC is perfect.The ECs can significantly increase the viability and ALP activity of induced osteoblasts.
3.The study of anterior sclera thickness and associated ocular parameters
Mei, LI ; Yu, CAI ; Ying-zi, PAN ; Rong-hua, QIAO ; Yuan, FANG ; Jie, WANG
Chinese Journal of Experimental Ophthalmology 2013;(1):81-85
Background The condition of the sclera is associated with many ocular diseases.The measurement of human scleral thickness in vivo is helpful for us to understand the features of the sclera and related diseases.Objective The present study was to measure the anterior sclera thickness(AST) in patients with senile cataract and to analyze the relationship among AST and other associated ocular parameters.Methods This study was approved by the Ethic Commission of First Hospital of Peking University.Written informed consent was obtained from each individual prior to examination.One hundred and five senile cataract patients were recruited in this study.Central corneal thickness (CCT),corneal curvature (CCV) and axial length were measured using ultrasonic pachymeter,keratometer,and A-scan unit,respectively.The AST was measured at 2 mm posterior to the scleral spur in the temporal meridian using ultrasound biomicroscope (UBM).The differences of CCT,CCV,ocular axial length and AST between bilateral eyes and the different sexes were compared by the Paired test and independent sample t test.The correlations among various parameters were assessed by the Pearson linear correlation analysis.The differences of CCT and AST among different axial length groups were evaluated by one-way ANOVA.Results No significant differences were found in the CCT,CCV,axial length and AST between bilateral eyes (t =0.584,P =0.561 ; t =1.161,P =0.248 ; t =0.140,P =0.889 ; t =0.342,P =0.773).Temporal AST at 2 mm posterior to the sclera spur was (0.589 ±0.051)mm in the right eyes.An insignificant decline in CCT was found in the male group compared with the female group (right eyes:t =0.469,P =0.641 ; left eyes:t =0.465,P =0.643).However,compared with the female group,the increase of axial length,reduction of the mean CCV value and enhancement of the mean AST were observed(right eyes:all P<0.01 ;left eyes:all P<0.01).CCV showed a negative correlation with ocular axial length (r =-0.50,P<0.01),but no significant correlation was found among age,CCT,ocular axial length and AST(P>0.05).No remarkable differences were found in CCT and AST among the various axial length groups (CCT:F =0.998,P=0.372;AST:F=1.919,P=0.383).Conclusions In senile cataract patients,correlation is not found between AST and CCT;the increase of axial length is not associated with the thinning of the eyeball wall to a certain extent.Differences exist in some ocular parameters between different sexes.
4.Measurement of anterior scleral thickness and its correlation with central corneal thickness and axial length in different types of glaucoma patients
Mei, LI ; Rong-hua, QIAO ; Ying-zi, PAN ; Yu, CAI ; Yuan, FANG ; Jie, WANG
Chinese Journal of Experimental Ophthalmology 2013;(3):249-253
Background A close relation between sclera thickness and glaucoma has been determined.Clinical features vary in different types of glaucoma patients,which hints that the scleral thickness might be distinct among these patients.Objective The aim of this study was to investigate the differences of central corneal thickness(CCT),anterior scleral thickness(AST) and axial length in glaucomatous patients.Methods This study was approved by the Ethic Commission of First Hospital of Peking University.Written informed consent was obtained from each individual prior to the examination.A retrospective descriptive study was designed.One hundred and sixty consecutive patients were recruited from March,2009 to November,2010 in First Hospital of Peking University,including 35 eyes with primary angle closure glaucoma(PACG) (35 cases),34 eyes with primary open-angle glaucoma POAG) (34 cases),37 eyes with normal tension glaucoma(NTG) (37 cases)and 17 eyes of ocular hypertension OHT) (17 cases).Thirty-seven eyes of 37 subjects with incipient cataract served as the control group.CCT and ocular axial length were measured with ultrasonic pachymeter and A-scan unit,respectively,and AST at the temporal quadrant 2 mm posterior to the scleral spur was measured by ultrasonic biomicroscopy (UBM).The measuring parameters among different groups were compared by analysis of covariance,and the correlations of AST,CCT with ocular axial length were analyzed using Pearson linear correlation and linear regression.The differences and correlation of CCT,AST and AL among five groups were analyzed.Results The CCT values in PACG group,POAG group,NTG group,OHT group and control group were (535.54 ± 5.20),(550.47 ± 5.28),(521.61 ± 5.07),(575.75 ± 7.76) and (535.06± 5.06) μm,respectively,showing a significant difference among them (F =9.560,P =0.000),and the CCT value of OHT group was increased in comparison with POAG group,PACG group,NTG group and control group(all P =0.000).The CCT of the POAG group was thicker than that in the PACG group,NTG group and control group(P=0.046,0.000,0.040).No significant difference was found in CCT among NTG group,PACG group and control group(P=0.950,0.060).The AST values of PACG group,POAG group,NTG group,OHT group and control group were(0.593±0.050),(0.600±0.050),(0.592-±0.060),(0.610-±0.060) and(0.604±0.060) mm,respectively,showing a insignificant difference among them (F =0.700,P =0.590).The axial length in the patients with PACG was shorter than that of the POAG group,NTG group,OHT group and control group (all P =0.000).The Pearson correlation analysis showed significantly positive correlation between CCT and AST in POAG group and NTG group(r=0.445,P=0.008;r=0.400,P=0.014).Conclusions This study confirms that there is dissimilarity in CCT but not in AST among different types of glaucomatous patients.The changes of CCT and AST are consistent in POAG and NTG patients.
5.Correlation between aortic elasticity and coronary artery calcification evaluated by CT
Yanhua LI ; Yuan ZI ; Fengling GONG ; Peng YU ; Weibin CHEN ; Huiying ZHANG ; Chunmei MA ; Yongping XU
Chinese Journal of Medical Imaging Technology 2017;33(6):880-883
Objective To discuss the correlation between aortic elasticity and coronary artery calcification by CT.Methods Totally 111 patients who were diagnosed of coronary artery disease underwent coronary artery CTA.The images were qualified for aortic elasticity measurement.All patients were divided into calcification negative group (n=43) and calcification positive group (n =68).The calcification positive group was further divided into light,medium,and serious groups according to their calcification scores.The ascending aortic images were reconstructed every 5 % R-R intervals.The cross-sectional areas and diameters of aortic in each R-R interval were measured automatically,then diameter variation rate (% A0),aortic distensibility (A0D),aortic compliance (A0C) and aortic stiffness (A0SI) were calculated to evaluate aortic elasticity.Correlation between aortic elasticity and coronary artery calcification were analyzed.Results % A0,A0 D,A0C were lower and A0SI was higher in calcification positive group than those in calcification negative group (all P<0.05).There was no significant differences in the four reference indexes of aortic elasticity among light,medium,and serious groups in calcification positive group (all P>0.05).Correlation analysis demonstrated negative correlations between % A0,A0 D,A0 C and calcification scores,and a positive correlation between A0SI and calcification scores.Conclusion Aortic elasticity is correlated with coronary artery calcification,and the combination of them will be beneficial for the early diagnosis of coronary heart disease.
6.The current research status and thinking on the history of stomatology in modern China.
Chinese Journal of Stomatology 2022;57(8):861-866
The research on the history of stomatology in modern China began in the middle of 20th century. The history of stomatology is a branch of medical history and stomatology education research. Most of researches on it were general historical researches, but problems on its medical knowledge dissemination and system, development process and social relations, etc. had not been drawn wider attentions at the moment. In order to innovate the research methods of stomatology history, and to promote the study of stomatology history from the perspective of empirical and cultural mutual corroboration, this article classifies and summarizes the research status, characteristics and trends of the stomatology history in modern China.
China
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History, 20th Century
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Oral Medicine/history*
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Research Design
7.Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells HepG2.
Ding YU ; Zi-hui WANG ; Li-yuan ZHU
Chinese Journal of Oncology 2003;25(2):120-123
OBJECTIVETo investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML).
METHODSHepG2 cells were cultured in MEM medium and treated with different concentrations of As(2)O(3) for either 24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and western blot were performed to observe the expression of PML.
RESULTSTUNEL positive apoptotic cells and DNA ladder could be detected in As(2)O(3) treated groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei almost disappeared after the treatment of 5 micro mol/L As(2)O(3).
CONCLUSIONAs(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration-dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei. The decreased expression of PML is closely correlated with apoptosis. Nuclear matrix associated protein PML could be the target of As(2)O(3) therapy.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Hep G2 Cells ; Hepatoblastoma ; chemistry ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; chemistry ; drug therapy ; pathology ; Nuclear Proteins ; analysis ; Oxides ; pharmacology ; Promyelocytic Leukemia Protein ; Transcription Factors ; analysis ; Tumor Suppressor Proteins ; analysis
8.Investigation of body hair assessment of Chinese women in Shandong region and its preliminary application in polycystic ovary syndrome patients
Jun-Li ZHAO ; Zi-Jiang CHEN ; Yu-Hua SHI ; Ling GENG ; Zeng-Xiang MA ; Yuan LI ; Rong TANG ;
Chinese Journal of Obstetrics and Gynecology 2000;0(09):-
Objective To determine a suitable standard of hirsutism for Chinese polycystic ovary syndrome(PCOS)patients living in Shandong region.Methods A total of 623 unbiased women from the general population in Jinan city,131 PCOS patients and 84 controls from outpatients in Shandong region were studied with questionnaires,physical and pelvic ultrasound examination,body hair on 11 sites were evaluated,and 9(lip,chin,arm,thigh,chest,upperbelly,lowerbelly,upperback,lowback)of them which were called hormone Ferriman-Gallwey(F-G)score and 2(forearm,leg)sites of indifferent hormone score were calculated according to the score system described by Ferriman and Gallwey.Results(1)Both body hair F-G score and indifferent hormone score distribution mode in the≤40 years old population were un-normal and both the 95th percentages of score were 2.(2)The hirsutism was significantly higher in PCOS patients[48.1%(63/131)]than in controls[4.8%(4/84)]by F-G score≥2(X~2=47.68,P
9.Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension
Di CHEN ; Tian-yi YUAN ; Yu-cai CHEN ; Hui-fang ZHANG ; Zi-ran NIU ; Lian-hua FANG ; Guan-hua DU
Acta Pharmaceutica Sinica 2021;56(1):208-216
In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.
10.The effect of Ulinastatin on the delivery of cytokines in patients with septic shock
Long-Yuan JIANG ; Lian-Hong YANG ; Jian-Xing CHANG ; Zhi-Jiang HE ; Tao YU ; Zi-Tong HUANG ;
Chinese Journal of Emergency Medicine 2006;0(12):-
Objective To investigate the effect of Ulinastatin on the delivery of cytokines in patients with septic shock.Methods It was a prospective and controlled clinical study.Seventy-eight patients with septic shock were randomly divided into control group and treatment group and thirty-nine in every group.Patients in treatment group received Ulinastatin 200 000 units intravenous everyday for 3 days,while those in control group received equal volume of normal saline as placebo.At different time points (at 24 th,48 th,72 th hour after start of treatment),the levels of tumor necrosis factor-alpha (TNF-?),interleukin-1 (IL-1),interleukin-6 (IL-6 ),interleukin-8 (IL-8) and superoxide dismutase (SOD) in serum were assayed.Results In comparison with control group,the levels of TNF-?,IL-1,IL-6,IL- 8 of treatment group decreased markedly (P<0.05,P<0.01) at different time points,whereas the level of SOD was higher markedly (P<0.05,P<0.01) at various time points.Conclusion Ulinastatin has protective effect on patients with septic shock through decreasing the levels of TNF-?,IL-1,IL-6,IL-8 and increasing in the level of SOD.