1.Quantitative cardiotoxicity assessment of gambogic acid using multiple cellular phenotype analysis
Chinese Journal of Pharmacology and Toxicology 2017;31(1):73-79
OBJECTIVE To evaluate the cardiotoxicity of a widen-spectrum antineoplastic drug, gambogic acid, through quantitative multiple cellular phenotypic characterization. METHODS H9c2 cell line was used as a model with doxorubicin (Dox) and amiodarone (Ami) as positive controls, hypaconi?tine as negative control and 0.1% DMSO as normal control. An optimized protocol was established to identify the morphology and function of cell nuclei. The effect of drugs on cell viability, nuclear area (Hoechst33342), mitochondria mass (MitoTracker Deep Red) and cytoplasmic calcium ion mobilization (Rhod2 AM)was studied. EC50 and Z′values were calculated to evaluate the degree of toxicology and to estimate the precision and false-positive rate, respectively. RESULTS Dose-response analysis indicated that EC50 of Dox on cell viability, nuclear area, mitochondrial mass was 0.72, 0.014 and 1.21μmol · L-1, respectively. On the other hand, EC50 of Ami on the parameters of cell viability, nuclear area and mitochon?drial mass was 14.83, 6.72 and 4.54μmol·L-1, respectively with Z′value above 0.5. Hypaconitine decreased the SER ridge of mitochondria. Gambogic acid caused significant mortality of H9c2 cells and induced nuclear shrinkage as Ami did. The EC50 values of cell viability and nuclear area were 0.24 and 1.16 μmol · L- 1. Meanwhile,gambogic acid disturbed the mitochondrial function as indicated by the increased mitochondrial area (EC50=0.44 μmol · L-1), abnormal SER Ridge(EC50=0.99 μmol · L-1) and decreased mitochondrial mass(EC50=1.21 μmol · L- 1). Cellular calcium mobilization was lower than normal (EC50=0.41 μmol · L-1). CONCLUSION The EC50 values of positive controls calculated from our assessment are similar those reported in literature. A multi-parameter and simultaneous evaluation enables a comprehensive analysis of the morphology of nuclei and mitochondria of cardiomyocytes and a preliminary assessment of the mechanisms of toxicity.
2.Etiology of recurrent diabetes ketoacidosis in children with type 1 diabetes
jie, YAN ; chun-xiu, GONG ; yan-mei, SANG ; chen, ZHU
Journal of Applied Clinical Pediatrics 1994;0(04):-
Objective To analyze the etiology of diabetes ketoacidosis(DKA) in children with type 1 diabetes.Methods Totally 850 person-time of type 1 diabetes children in recent 20 years in our hospital were selected as studied subjects. Two hundred and twenty-five person-time of them were hospitalized because of DKA.Fifty-six cases (131 person-time) were due to recurrent DKA.These patients were classified into 2 groups according to onset time: group 1(diagnosed from 1982 to 1991) and group 2(diagnosed from 1992 to 2001).Results The analysis of recurrent DKA suggested that 71.8 % of them was due to infection, 20.4 % of them did not obey diabetic diet and 9.2 % of them discontinued insulin injection. The etiology of DKA showed no difference in two groups. The number of recurrent DKA in two groups was significantly different (P
3.Effects of hepatocyte growth factors on contractile function of disused gastrocnemius atrophy in rats
Yan HUANG ; Bin YU ; Dang WANG ; Jie ZHU ;
Chinese Journal of Orthopaedic Trauma 2004;0(06):-
Objective To explore the possible effects of hepatocyte growth factors (HGF) on prevention and therapy of disused gastrocnemius atrophy in rats by observing their effects on the wet weight and contractile function of the gastrocnemius of fixed hind limbs. Methods Twenty-four Wister male rats were randomly divided into a blank group, a contrast group and an experimental group. Their right hind limbs were fixed for four weeks with plastic piaster from metatarsus to 1 cm up the knee. Their knee joint was fixed in 100?flexion and their ankle joint in 60?plantar flexion. Rats in the contrast group were injected with 0. 2 mL of normal saline, and rats in the ex- perimental group were injected with HGF (10 mg/kg, 10 mg/mL). Their whole gastrocnemius of the right hind limb was dissected four weeks later to measure its contractile function and wet weight. Results Compared with the blank group, single maximal contraction, maximal tetanus, and wet weight of the gastrocnemius in the contrast and experimental groups decreased significantly (P<0. 05), and fields of electric stimulation also decreased signifi- cantly (P<0. 05). Compared with the contrast group, single maximal contraction, maximal tetanus, and wet weight of the gastrocnemius in the experimental group were significantly superior (P<0.05), and fields of electric stimulation significantly increased. Conclusion Since after a local injection of HGF, the contractile function and wet weight can be significantly increased, HGF may have a preventive effect on disused atrophy.
4.Quality standard of Zhike Pingchuan Capsules
Ping CHEN ; Ying-Long ZHU ; Qiang WEI ; Bian-Jie YAN ;
Chinese Traditional Patent Medicine 1992;0(03):-
AIM: To establish the quality standard for Zhike Pingchuan Capsule (Radix Panacis Quinquefolii, Semen Pruni Armeniacae, Radix Scutellariae, Radix Glycyrrhizae, Bulbus Fritillariae Cirrhosae, etc.). METHODS: Radix Panacis Quinquefolii, Radix Glycyrrhizae, Bulbus Fritillariae Cirrhosae in Zhike Pingchuan Capsule were identified by TLC and ginsenoside Rb_1 was determined by HPLC. The analysis was carried out on C_~18 column by HPLC. The mobile phase was CH_3CN-H_2O(34∶66). The flow rate was 1.2 mL?min~-1 and the detection wavelength was at 203 nm. The column temperature was at 40.0 ℃ and sensitivity was 0.02 AUFS. RESULTS:The average recovery was 97.20% and RSD was 2.25% and the linear range of ginsenoside Rb_1 was in 0.612-~6.120 ?g. CONCLUSION:This method is simple, rapid with a good reproducibility. This method can be used for the quality control of Zhike Pingchuan Capsule.
5.Necessity and assumption of hospital scientific research fund management platform
Yan WANG ; Zhiyun LIU ; Yun ZHANG ; Jie WU ; Lin ZHU
Chinese Journal of Medical Science Research Management 2017;30(2):116-117,121
Objective Build the hospital scientific research management platform.Methods According to expenditure process and the management standard requirements,the establishment of a fund management system platform to achieve budget、accounted for,spending and audit feedback function.Results Scientific research funds management platform is mainly composed of project application,project establishment and review,the report query and remittance receipt of financial department.Full consideration of the personnel,project,financial and other related system interface.In the construction of data using the standards of the state and the university scientific research information.Conclusions Through building the hospital scientific research management platform,improving the working efficiency,reducing the labor intensity of the management and financial personnel,realizing the accuracy and effectiveness of management.
6.Neuroprotective effect of erythropoietin on intracerebral hemorrhage
Da CHEN ; Yingjie LI ; Yan LIU ; Jie ZHU
Chinese Journal of Emergency Medicine 2009;18(12):1257-1261
Objective To study the neuroprotective effects of erythropoietin on intracerebral hemorrhage (ICH). Method The rat models of 1CH were produced by injecting autologous blood into caudate necleus by using stereotatic techique. One hundred ten male wistar rats were randomly divided into 4 groups, namely normal group,sham operation group, 1CU group, and EPO treatment group. The immunohistochemistry and TUNEL were used to detect expressions of Bc 1-2 and Bax,and apoptosis cells. LSD- t and Pearson correlation were used to analyzing data. Results The positive cells of TUNEL Bcl-2 and Bax in ICH group and EPO group obviously increased over 6 hours,and reached peak 72 hours later,and decreased over 120 hours,and the positive cells in different intervals significantly decreased in ICH group and EPO group compared with those in sham operation group (P < 0.01). The positive cells of TUNEL and Bax in EPO group in different intervals significantly decreased compared with those in ICH group (P < 0.01). The Bcl-2 positive cells in EPO group in different intervals significantly increased compared with those in ICH group (P < 0.01). The Bax protein expression, Bax/Bcl-2 and apoptosis presented positive correlation (P < 0.01). Conclusions Apoptosis may induce some brain injury after ICH,and EPO can decrease the number of apoptotic cells after ICH by up-regulating Bcl-2 and down-regulating Bax.
7.Analysis of correlation between dry eye and diabetic retinopathy in type 2 diabetic patients
Jian-Feng, YU ; Yu, SONG ; Yan, ZHU ; Jun-Jie, LI
International Eye Science 2016;16(6):1187-1189
?AIM:To investigate the correlation between dry eye and different degrees of diabetic retinopathy ( DR ) in type 2 diabetic patients.?METHODS: In the cross-sectional study, 340 patients (340 eyes) with type 2 diabetes were enrolled. Tear film function tests including tear meniscus height, tear film breakup time ( BUT ) , fluorescein staining, Schirmer Ⅰtest were performed followed by surveying questionnaires about dry eye. Retinal status was evaluated by retinal color photography and indirect ophthalmoscopy exam with dilated pupils to evaluate DR and whether companied by macular edema.?RESULTS:The prevalence of dry eye was 49. 41%. The mean duration of diabetes in patients with dry eye was 11.15±7.07a, while 6.92±5.45a without dry eye(P<0.01). Dry eye had the positive correlation to the development of DR. The incidence of dry eye in people with mild nonproliferative diabetic retinopathy ( NPDR ) , moderate NPDR, severe NPDR and proliferative diabetic retinopathy (PDR) was 1. 097 times, 1. 724 times, 2. 86 times and 5. 43 times respectively, compared with people without DR. The occurrence of dry eye in people with macular edema increased by 3. 697 times compared with people without macular edema.?CONCLUSION: Dry eye was more prevalent in people with type 2 diabetes. The incidence of dry eye increased gradually with the occurrence and development of diabetic retinopathy.
8.Effect of hepatocyte growth factor on hepatocytes after partial hepatectomy in cirrhotic rats
Hong ZHU ; Yongzhang GUO ; Li LI ; Jie ZHANG ; Zhibin YAN
Chinese Journal of General Surgery 1993;0(01):-
Objective To study the effect of hepatocyte growth factor (HGF) on hepatocytes after partial hepatectomy in chronic liver injury rats.Methods 30% hepatectomy was performed in rats with cirrhosis induced by CCL 4 and alcohol,and subcutaneously injection of cow HGF into intraabdomen was done with different dosages.Results Small dose (0.16mg?100g -1d -1)of HGF did not stimulate liver regeneration or enhance liver function after partial hepatectomy in cirrhotic rats.Large dose (1.3mg?100g -1d -1) of HGF stimulated liver regeneration and enhanced liver function after partial hepatectomy in cirrhotic rats(P
9.Effects of STAT3 aberrant activation on malignant transformation of human umbilical cord mesenchymal stem cells when exposed to human breast cancer microenvironment
Ling WANG ; Jing ZHU ; Jie TIAN ; Bin TAN ; Sha YAN
Basic & Clinical Medicine 2015;(10):1314-1319
Objective_To investigate whether hUCMSCs undergo malignant transformation when exposed to MCF-7B breast cancer microenvironment and whether the abnormal activation and over expression of STAT3 play an impor-tant role in this transformation.Methods_The experiment was divided into three groups:blank group ( hUCMSCs were separately cultured),experimental group(hUCMSCs were indirectly co-cultured with MCF-7B breast cancer cells),positive control group(MCF-7B breast cancer cells were separately cultured).Morphology of cells was detec-ted by invertedmicroscope.Cell cycle was detected by flow cytometry.The mRNA expression of STAT3, c-Myc and Bcl-xL was tested by real-time PCR.The protein expression and location of p-STAT3,c-Myc and Bcl-xL were detected by immunofluorescence.The protein expressions of p-STAT3,STAT3,c-Myc and Bcl-xL were also meas-ured by Western blot.Results_The experimental group cells showed typical morphology of the tumor cells.The cells proportion of experiment group in G1 phase was significantly lower than that of the blank group(P<0.05),but which in S and G2 phase were significantly higher than those of the blank group(P<0.05).The mRNA expression levels of STAT3 ,c-Myc and Bcl-xL in experimental group was significantly higher than those in blank group ( P<0.05).p-STAT3,STAT3,c-Myc and Bcl-xL protein were significantly higher than those of the blank group(P<0.05),and they were mainly located in the nuclei.The protein expression of STATS also showed significant changes in experimental group.Conclusions_hUCMSCs trends to malignant transformations when exposed to MCF-7B breast cancer microenvironment.The abnormal activation and over expression of STAT3 are of important factors leading to the malignant transformation of hUCMSCs.
10.Attenuated store-operated Ca2+ entry in mesenteric artery endothelial cells of aged rat
Xia WANG ; Jie LI ; Yan ZHU ; Juan DU ; Bing SHEN
Chinese Journal of Geriatrics 2015;34(4):434-437
Objective To observe attenuated store-operated Ca2+ entry in superior mesenteric artery endothelial cells of aged rat.Methods The pressure myograph was applied to measure the vasodilation of superior mesenteric artery induced by bradykinin (BK) in aged versus non-elder rats.Primarily cultured MAECs were treated by thapsigargin (TG) and BK to deplete intracellular Ca2+ stores for comparing SOCE.SOCE of MAECs was detected by calcium imaging technology and was compared between aged and non-elder rats.The expression levels of Orai 1 and stromal interaction factor 1 (STIM 1) were observed by immunofluorescence method.Results Compared with the nonelder rats (70.0 ± 4.1 %),BK-induced vasodilation in aged rats (27.0 ± 4.9)% was declined by (60.7±4.3) %.SOCE induced by BK and TG in primarily cultured MAECs was attenuated by 37.6% and 39.2% in aged rats (1.71±0.18 and 1.06±0.03) respectively as compared with non-elder rats (2.72±0.39 and 1.75±0.06).The expressions of SOCE's components Orai 1 and STIM 1 in MAECs were decreased obviously in aged rats than in non elder rats.Conclusions SOCE of MAECs and SOCE-induced vasodilation are significantly attenuated in aged rats.The decreased expression level of Orai 1 and STIM 1 may contribute to this alteration.