1.Role of p53-mediated mitochondrial apoptotic pathway in arsenic liver injury caused by coal-burning
Chinese Journal of Pharmacology and Toxicology 2014;(2):210-215
OBJECTIVE To investigate the apoptosis of hepatocytes in arsenic poisoning rats caused by coal-burning and explore the effects of p53-induced mitochondrial apoptotic pathway on arsenic liver injury.METHODS Wistar rats were fed with 164.74 pp m arsenic conta minated grain at the levels of 15%,30% and 60% (arsenic contents were 25,50 and 100 mg·kg -1 ,respectively)for 90 d. The arsenic contents of urine and hair,apoptosis of hepatocytes and mRNA expression of p53,Bax and Bcl2 in peripheral blood and hepatocytes were evaluated.At the sa me ti me,protein expression of p53, Bax and Bcl2 in hepatocytes were analyzed.RESULTS The arsenic contents of urine and hair increased with the elevation of arsenic dose.The apoptotic rate of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 16.49 ±2.06 and 15.83 ±1 .28,respectively which were significantly higher than the control group and arsenic 25 mg·kg -1 group (9.00 ±0.59 and 9.27 ±0.36,respectively,P <0.05).p53 mRNA expression of peripheral blood in arsenic 100 mg·kg -1 group was 2.69 ±1 .84 while p53 mRNA expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .63 ±0.28, 1 .91 ±0.38 and 1 .71 ±0.18,respectively which were significantly higher than the control group (0.86 ± 0.15 and 1 .22 ±0.12,respectively,P<0.05).Bax mRNA expression of peripheral blood in arsenic 50 and 100 mg·kg -1 group were 1 .36 ±0.30 and 1 .94 ±0.65 while Bax mRNA expression of hepatocytes in arsenic 100 mg·kg -1 group was 1 .34 ±0.23 which were significantly higher than the control group (0.77 ±0.15 and 0.84 ±0.34,respectively,P<0.05).Bcl2 mRNA expression of hepatocytes in arse-nic 100 mg·kg -1 group was 0.98 ±0.50 which was significantly lower than the control group (2.14 ± 1 .15,P<0.05).p53 protein expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .06 ±0.56,1 .15 ±0.77 and 0.74 ±0.27,respectively while Bax protein expression of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 0.74 ±0.43 and 0.69 ±0.37 which were significantly higher than the control group (0.36 ±0.1 9 and 0.25 ±0.09,respectively,P<0.05).CONCLUSION Arsenic can induce hepatocytes apoptosis and p53-mediated mitochondrial apoptotic pathway may be involved in the develop ment of rat liver injury in arsenic poisoning rats caused by coal-burning.
2.Protective effect and mechanism of exenatide on HRMCs injured by fluctuating hyperglycemia
Jianshuang ZHANG ; Tingting GUO ; Yun XIE
Tianjin Medical Journal 2017;45(7):682-685
Objective To observe the effect of exenatide on endoplasmic reticulum stress (ERS) in human renal mesangial cells (HRMCs) injured by fluctuating hyperglycemia culture,and to explore the mechanism.Methods HRMCs were randomly divided into three groups:control group (group N,cells were cultured in 5.6 mmol/L glucose for 24 h),fluctuating hyperglycemia group (group F,cells were cultured in 30 mmol/L glucose for 3 h,5.6 mmol/L glucose for 2 h,repeated three times in one day,then 5.6 mmoll/L glucose overnight),fluctuating hyperglycemia and exenatide group (group F+G,HRMCs were cultured in fluctuating hyperglycemia and 100 nmol/L exenatide).MTT assay was used to measure the viability in each group.The apoptosis rates were detected by flow cytometry in three groups.The relative expression of glucose regulated protein78 (GRP78) and CCAAT/enhancerbinding protein homologous protein (CHOP) were tested by Western blot assay.Results Compared with the group N,the cell proliferation level decreased,the cell apoptosis rate increased,and the expression levels of GRP78 and CHOP increased in F group (P < 0.05).After treatment with exenatide,the cell proliferation rate increased,cell apoptosis rate decreased (P < 0.05),and the expression levels of GRP78 and CHOP decreased in F+G group,compared with those of the group F (P < 0.05).Conclusion Exenatide can reduce the damage of fluctuating hyperglycemia on HRMCs by down-regulating the stress levels of the endoplasmic reticulum stress.
3.Study on Bactericidal Activity of Thymopentin Peptide and Its Derived Peptides
Ting XIE ; Tingting TAO ; Ningsheng LIANG
China Pharmacy 2015;(28):3918-3919,3920
OBJECTIVE:To study the bactericidal activity of thymopentin and its derived peptides. METHODS:Agar plate count was adopted to determine the bactericidal activity of thymopentin [arginine(R)-lysine(K)-aspartic acid(D)-valine(V)-tyro-sine(Y),RKDVY],its derived peptide 1 [RKN(agedoite,N)VY] and derived peptide 2(RKKVY)to Gram negative bacterial (Proteusbacillus vulgaris,Escherichia coli) and Gram positive bacterial (Staphylococcus aureus,Enterococcus faecium). There were 15.625-1 000 μg/ml for peptides,102 CFU for bacteria. RESULTS:Three pentapeptides possessed bactericidal activity against Gram negative bacteria. The activities of RKKVY and RKNVY were stronger than RKDVY(P<0.01),there was no significant dif-ference between RKKVY and RKNVY(P>0.05). They also possessed bactericidal activity against Gram positive bacteria,and the activity from strong to weak was RKKVY>RKNVY>RKDVY(P<0.01). CONCLUSIONS:Thymopentin and its derived peptides possess bactericidal activity against Gram negative and positive bacteria,with dose-effect relationship.
5.Osteogenic induction of human bone marrow mesenchymal stem cells cultured in complex medium
Lili XU ; Xiaojuan SUN ; Xiuxian HAO ; Tingting XIE ; Nailong YANG
Chinese Journal of Tissue Engineering Research 2015;(10):1501-1505
BACKGROUND:Studies have shown that the number of osteoblasts is often decreased after osteoporosis, and osteoblast replacement therapy becomes a new target for the treatment of osteoporosis. OBJECTIVE:To observe the osteogenic differentiation of human bone marrow mesenchymal stem cels cultured in dexamethasone, vitamin C and beta-glycerophosphate. METHODS:Mesenchymal stem cels were isolated and purified from adult bone marrow using human lymphocyte separation medium. The expression of cel surface markers was detected by flow cytometry. Cel ultrastructure was observed by transmission electron microscope. Then, the bone marrow mesenchymal stem cels were cultured in osteogenic induction medium containing dexamethasone, vitamin C andβ-glycerophosphate, and RT-PCR was used to detect the bone morphogenetic protein-2 mRNA expression after osteogenic induction. RESULTS AND CONCLUSION:A large number of adherent cels were visible as fibrous growth at 2 weeks after culture and strongly expressed CD44, CD29, but did not express CD34, CD45. These cels could be induced to differentiate into osteoblasts, and express bone morphogenetic protein-2 mRNA. Alizarin red staining and alkaline phosphatase staining were positive for the cels. These findings suggest that human bone marrow mesenchymal stem cels cultured in dexamethasone, vitamin C and beta-glycerophosphate can differentiate into osteoblasts, and has a potential for the treatment of osteoporosis.
6.Non-congenital heart disease related pulmonary arterial hypertension in 45 children
Yinping LI ; Tingting XIAO ; Min HUANG ; Jie SHEN ; Lijian XIE
Chinese Journal of Applied Clinical Pediatrics 2015;30(1):30-33
Objective To improve the knowledge of paediatric pulmonary arterial hypertension(PAH) and to elevate the level of early diagnosis and treatment.Methods The clinical data of 45 PAH patients admitted in Shanghai Children's Hospital from Jan.2006 to Dec.2012 were reviewed,including clinical manifestation,laboratory examination,diagnosis,treatment and prognosis.Results Of the 45 PAH patients,21 cases (46.7%) were male and 24 cases (53.3 %) were female,with an average age of 2.5 years old.Among them idiopathic PAH was in 24 cases (53.3 %) and secondary PAH was in 21 cases [including interstitial lung disease in 4 cases,upper airway obstruction in 3 cases,systemic lupus erythematosus in 3 cases,hepatic disease in 3 cases,including hepatic hemangioma 1 case,liver cirrhosis portal hypertension 1 case and autoimmune hepatic sarcoidosis 1 case,tachycardia induced cardiomyopathy in 2 cases,extensive pulmonary small artery stenosis in 2 cases,human immunodeficiency virus (HIV) infection in 1 case,hypothyroidism in 1 case,and familial PAH in 2 cases].Main clinical manifestations were anhelation after exercise (71.1%),fatigue (68.9%),cough (48.9%),chest tightness (26.7%),chest pain (33.3%),syncope (8.9%),et al.The most common physical signs were splitting of the second sound in pulmonary valve area (93.3%),followed by tricuspid murmur (77.8%),cyanosis (53.3%),hepatomegaly (42.2%),hydropericardium (28.9%),and oedema (11.1%),et al.Twenty-seven cases did cardiac catheterization,compared with idiopathic PAH and secondary PAH,pulmonary artery systolic pressure,mean pulmonary artery pressure,pulmonary capillary wedge pressure,pulmonary arteriolar resistance index had significant difference(P < 0.05).Thirty-one cases' condition improved after treatment,11 cases without any improvement and 3 cases died during follow-up visit.Conclusions PAH is a rare disease with no specific symptom and can be easily misdiagnosed in children.Ultrasonic cardiogram and cardiac catheterization are helpful in diagnosis.Actively looking for the cause can improve the prognosis.
7.Effect of mibefradil on proliferation of human pulmonary artery smooth muscle cells induced by platelet-derived growth factor
Honghong LI ; Tingting XIAO ; Lijian XIE ; Min HUANG ; Jie SHEN
Journal of Clinical Pediatrics 2016;34(6):465-469
Objectives To explore the effect of mibefradil, a kind of novel calcium channel antagonists, on proliferation of human pulmonary artery smooth muscle cells (HPASMCs) induced by platelet-derived growth factor (PDGF). MethodsHPASMCs were culturedin vitro, and randomly divided into control group, PDGF group, Mib group, and PDGF+Mib group. The PDGF group was stimulated by 25 ng/ml of PDGF. Mib group was intervented by 10 μmol/L of Mib. PDGF+Mib group was treated by PDGF and Mib. The reproduction rate in 48 hours and 72 hours were detected by MMT. Cell cycle was detected by lfow cytometry. The expression of proliferating cell nuclear antigen (PCNA) was observed by immunolfuorescence staining (IFS).ResultsThere were statistical differences among four groups in both 48 hours and 72 hours (P all?0.05), especially in 72 hours. PDGF group had the highest level of HPASMC reproduction rate, and there were statistical differences as compared with the other three groups (P all?0.05). However, the HPASMC reproduction rates were similar among PDGF+Mib group, Mib group, and control group (P all?>?0.05). There were statistically differences of G0/G1 phase and S phase among four groups (P?0.05). PDGF group had lowest G0/G1 phase cells and highest S phase cells, and there were statistically differences as compared with the other three groups (P all?0.05). No differences were found among PDGF+Mib group, Mib group, and control group (P all?0.05). There was obviously difference in the expression of PCNA among four groups (P?0.05). PDGF group had the highest expression of PCNA and there were statistically differences as compared with other three groups, (P?0.05). While the expression of PCNA was similar among PDGR+Mib group, Mib group, and control group.Conclusion Mibefradil was able to restrain remarkably the proliferation of HPASMC by inhibit the cell cycle that stimulated by PDGF, and by the expression of PCNA.
8.Relationships between human parvovirus B19 VP1 unique region protein and autoimmune diseases
Xiaojing NIE ; Lei MA ; Li LI ; Tingting XIE ; Lizhu CHEN
Chinese Journal of Microbiology and Immunology 2016;36(7):545-548
Human parvovirus B19, generally referred to as B19 virus, has been closely associated with a variety of different autoimmune diseases due to the features of its capsid protein. B19 virus VP1 unique region protein that has sites of phospholipase A2 and several antigenic determinants is exposed on the outside of the viral capsid protein. As a result of that, B19 virus VP1 unique region protein can stimulate the host to produce autoantibodies, which induces and/or aggravates the autoimmune diseases. The biological characteristics of B19 virus VP1 unique region protein and its relationships with autoimmune diseases are de-scribed in this review based upon the published literatures and the work achieved by our research team. This review will be helpful to the prevention and treatment of B19 virus infection.
9.Three-dimensional finite element simulation and biomechanical analysis of mandible chin blast injury
Tao LEI ; Jiajun ZHENG ; Tingting WANG ; Ying LI ; Liangxian XIE
Chinese Journal of Trauma 2015;31(11):1050-1055
Objective To simulate a finite element model for biomechanical analysis of mandible chin blast injury and analyze the mechanism of maxillofacial blast injury.Methods The three-dimensional element model of human mandible blast injury was established to simulate the dynamic process of injury to the mandible chin.Von Mises stress and effective strain were evaluated in biomechanical study of the simulation results.Results The dynamic damage process of human mandible chin blast injury was simulated successfully.In the condition of 1 000 mg and 3 cm,the Von Mises stress and effective were maximum at condylar neck region (9.1 × 106 Pa,0.62 × 10-3ε),were second at mandibular angle region (6.1 × 106 Pa,0.42 × 10-3ε),and minimum at mental foramen region (6.1 × 106 Pa,0.39 × 10-3ε).Blast distance rather than blast equivalent produced more effect on the mechanical parameters and damage degree.Conclusions Von Mises stress and effective strain can be applied to the evaluation of bone tissue damage.The finite element method is effective in simulating mandible blast injury and can provide a new thought and approach to clinical treatment of oral and maxillofacial blast injury.
10.Establishment and simulation validation of a three-dimensional finite element model of pig mandible impact injury
Tao LEI ; Ying LI ; Jiajun ZHENG ; Tingting WANG ; Liangxian XIE
Chinese Journal of Trauma 2015;31(8):743-747
Objective To develop a three-dimensional element model of pig mandible impact injury and test the simulation results in an attempt to determine the feasibility and reliability of finite element numerical simulation method used in the maxillofacial impact injury.Methods CT data was used to develop a three-dimensional finite element model of pig mandible impact injury,and the dynamic process of impact injury was simulated.The simulation results were compared with the animal experiment and had energy check to validate the reliability and feasibility of the modeling and simulation methods.Results The three-dimensional finite element model was established successfully,containing 61,512 hexahedrons,5,450 tetrahedrons,4,030 trihedrons,and 67,159 nodes.The simulation process was realistic,and the simulation results showed no statistical difference with the animal experiment with regard to strain,acceleration,and other biomechanical properties (P > 0.05).The simulated damage shape had a high similarity with animal specimens,and the result of energy check also complied with energy conservation law.Conclusion Finite element method is effective to simulate the dynamic process of mandible impact which ensures a correct and reliable model and simulation,and thus can be used to analyze the mechanism of maxillofacial impact injury.