2.Adeno-associated vector mediated intracellular biological activity of human Kallistatin.
Xun-Wei DUAN ; Si-Yi CHEN ; Feng WANG ; Zhi-Yun CHENG ; Ming-Qing TANG ; Rui-An XU
Acta Pharmaceutica Sinica 2014;49(7):993-999
Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis
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Cell Proliferation
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Dependovirus
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Genetic Vectors
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Human Umbilical Vein Endothelial Cells
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metabolism
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Humans
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Lung Neoplasms
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metabolism
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Serpins
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metabolism
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Signal Transduction
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Transfection
3.Analysis of the facet joint morphology for degenerative lumbar spondylolisthesis
Wenzhi ZHANG ; Yingsheng DING ; Liqun DUAN ; Xu LI ; Rui HE ; Feng ZHANG
Chinese Journal of Orthopaedics 2015;(8):865-870
Objective To investigate the etiologic effect of the lumbar facet joint morphology on the occurrence of degener?ative lumbar spondylolisthesis (DLS). Methods From January 2007 to July 2013, 115 patients with DLS treated in our hospi?tal were randomly selected. There were 28 males and 87 females with an average age of 57.3 years (range, 41-76 years). 115 age? and sex? matched people including 31 males and 84 females with an average age of 56.4 years (range, 45-77 years) free from DLS and back or leg pain were selected randomly as control group from a group coming for routine physical examination in our hospital. Both groups received lumbar anteroposterior and lateral X?ray films、CT scanning and multiplanar reformation, the degree of spondylolisthesis (Taillard index) was measured in DLS group on lateral radiographs; at L3,4 and L4,5 level of both groups the facet joint angles on CT scan images were measured and facet tropism was evaluated, the pedicle?facet angle (the P?F angle) was measured in the sagittal plane on multiplanar reformation CT images, and then all angles of corresponding level were compared and analyzed; L4,5 facet joint degeneration in both groups was evaluated and compared in bone window, the de?gree of spondylolisthesis (Taillard index) in DLS group at different degenerative grade of facet joints were analyzed. The corre?lation between L4,5 facet joint angle、P?F angle and degrees of spondylolisthesis were analyzed. Results All L4,5 spondylolisthe?sis in DLS group were grade I, the facet joint angles were more sagittal in DLS group than those in the control group at L 3,4 and L4,5 levels, and the P?F angles were more horizontal in DLS group compared with control group;the facet tropism in DLS group at L 4,5 level were significantly different as compared to the control group, but there was no significant difference at L 3,4 level between the two groups. Significant difference was found in L4,5 facet joint degeneration grade between two groups,but there was no significant difference in degree of spondylolisthesis during different degeneration grades in DLS group. There was no significant correlation between the facet joint angle and the P?F angle and degree of spondylolisthesis at L4,5 level in DLS group. Conclusion The facet joint morphology abnormality (smaller facet joint angle, horizontal P?F angle, the facet tropism) has an important etiologic meaning in the occurrence of degenerative lumbar spondylolisthesis, however its role cannot be excessively exaggerated. The facet joint de?generation is a secondary change with aging,while the development of DLS aggravates the degeneration.
4.Genome-wide association study of high altitude pulmonary edema.
Rui-Feng DUAN ; Wei LIU ; Chao-Liang LONG ; Yan-Fang ZHANG ; Wen-Yu CUI ; Yin-Hu WANG ; Hai WANG
Chinese Journal of Applied Physiology 2014;30(2):101-105
OBJECTIVEHigh altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.
METHODSWe performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.
RESULTSThirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.
CONCLUSIONIt suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.
Adult ; Altitude Sickness ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Hypertension, Pulmonary ; genetics ; Polymorphism, Single Nucleotide ; Young Adult
5.Protective effects of histone deacetylase inhibitor on stress-induced myocardial injury in rats.
Lei WU ; Xiao-hua LIU ; Tian-hui WANG ; Rui-feng DUAN ; Xue-si ZHOU ; Hong-tao LIU ; Zhi-qing ZHANG
Chinese Journal of Applied Physiology 2015;31(3):193-196
OBJECTIVETo observe the protective effects of histone deacetylase inhibitor on stress-induced myocardial injury.
METHODSHealthy male Wistar rats were randomly divided into 3 groups( n = 6), and the stress-induced myocardial injury model was established with chronic restraint stress method. The protective effects of histone deacetylase inhibitor on stress-induced myocardial injury were observed with Trichostatin A (TSA) intervention. Histone acetylation levels in myocardium of rats were detected by Western blot method, spectrophotometry method was used to dynamically determine the activity of rat serum lactate dehydrogenase (LDH), serum creatine kinase isoenzyme-MB (CK-MB) and Caspase 3, and nagar Olsen staining were used to observe the early myocardial damage.
RESULTSRestraint stress could significantly reduce the level of histone acetylation of myocardium in rats, and TSA intervention could inhibit the stress-induced reduction of myocardial levels of histone acetylation. Restraint stress could cause the significant increase of serum LDH activity ( P < 0.05), serum CK-MB activity ( P < 0.05), and the Caspase 3 activity of myocardial tissue (P < 0.05), and early myocardial damage also occurred during restraint stress. ISA intervention could significantly reduce the serum LDH activity (P < 0.05), the serum CK-MB activity (P < 0.05), the activity of myocardial tissue caspase 3 induced by restraint stress (P < 0.05), and the stress-induced myocardial injury was also attenuated by TSA intervention.
CONCLUSIONThe histone deacetylase inhibitor TSA can protect stress-induced myocardial injury.
Acetylation ; Animals ; Cardiotonic Agents ; pharmacology ; Caspase 3 ; blood ; Creatine Kinase, MB Form ; blood ; Histone Deacetylase Inhibitors ; pharmacology ; Hydroxamic Acids ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardium ; pathology ; Rats ; Rats, Wistar ; Restraint, Physical ; Stress, Physiological
6.The physiological effects of resveratrol and its potential application in high altitude medicine.
Hui-li ZHU ; Hong-jing NIE ; Pei-bing LI ; Bing-nan DENG ; Rui-feng DUAN ; Hong JIN ; Zhao-li CHEN
Chinese Journal of Applied Physiology 2015;31(6):498-503
Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.
Altitude
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Humans
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Hypoxia
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drug therapy
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Polycythemia
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drug therapy
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Stilbenes
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pharmacology
7.Proteomic identification of human serum biomarkers associated with high altitude pulmonary edema.
Yuan-Yuan ZHANG ; Rui-Feng DUAN ; Wen-Yu CUI ; Zhi-Yuan PAN ; Wei LIU ; Chao-Liang LONG ; Yin-Hu WANG ; Hai WANG
Chinese Journal of Applied Physiology 2013;29(6):501-507
OBJECTIVEHigh altitude pulmonary edema (HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers.
METHODSA complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay (ELISA).
RESULTSEight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(alpha1-AT), Haptoglobin(Hp), apolipoprotein A-1 (apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV (apoA-IV) decreased significantly. The variation of alpha1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis.
CONCLUSIONSIt is well known that Hp, alpha1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, alpha1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.
Altitude ; Biomarkers ; blood ; Blood Proteins ; metabolism ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Peptide Mapping ; Proteome ; Pulmonary Edema ; blood ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
8.The study of plasma proteomic changes in a patient with high-altitude cerebral edema.
Yuan-Yuan ZHANG ; Rui-Feng DUAN ; Hai WANG
Chinese Journal of Applied Physiology 2011;27(2):180-184
OBJECTIVEHigh-altitude cerebral edema (HACE) is one of the most serious acute mountain sickness and its underlying mechanism is still unknown clearly. The aim of this study was to determine the changes of plasma proteins in high altitude cerebral edema patients for discovering essential biomarkers used for the routine prophylaxis, diagnosis and treatment.
METHODSPlasma protein profiling two dimensional gel electrophoresis followed by mass spectrometry was used to explore protein alterations in one patient with high-altitude cerebral edema (HACE). Striking differences in two-dimensional gel proteomes of plasma were observed between high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) and between high-altitude cerebral edema (HACE) and mild acute mountain sickness (mAMS). Furthermore, apolipoprotein E altered in high-altitude cerebral edema was validated by ELISA.
RESULTSDifferent six spots were found in this study from the comparison between HACE and HAPE, and there were different six spots which were detected from the plasma of HACE patient in comparison to mAMS. Apolipoprotein E was identified in the two groups of comparative maps and results of ELISA consisted with the results of 2-DE.
CONCLUSIONIn this study, we used proteomic approach to explore HACE firstly and found different proteins that were probably associated with HACE. This would offer a clue to a better understanding of HACE for precaution, diagnosis and treatment.
Adult ; Altitude ; Altitude Sickness ; complications ; Apolipoproteins E ; blood ; Blood Proteins ; metabolism ; Brain Edema ; blood ; etiology ; Female ; Humans ; Proteomics ; methods
9.The construction and application of a novel apparatus for detecting oxygen consumption of mice under normobaric hypoxia.
Rui-Feng DUAN ; Xiang-Zhi ZENG ; Jia-Li JI ; Zhi-Qing ZHANG ; Yan-Fang ZHANG ; Chao-Liang LONG ; Wei LIU ; Wen-Yu CUI ; Hai WANG
Chinese Journal of Applied Physiology 2014;30(4):382-384
OBJECTIVETo establish a method for real-time recording the oxygen consumption of mice under normobaric hypoxia.
METHODSThe experimental apparatus was made up of animal container, filling water control system, electronic balance, hose, a computer with weight recording software, etc. The working principle was that the oxygen consumed by animal was replaced by water filling which was controlled by the pneumatic and hydraulic actuator. The water was weighted by an electronic balance and the weight signal was recorded into excel file at the same time. The accuracy and precision of the apparatus were detected by a 10 ml syringe. The oxygen consumption characteristics of 6 acute repetitive hypoxia mice and 6 normal mice were observed.
RESULTSThe P value for the paired t test was 1 and the CV value was 4%. The survival time and total oxygen consumption of acute repetitive hypoxia mice were both significantly increased compared to normal mice (P < 0.05), which were (58.8 +/- 6.8) min and (46.0 +/- 8.7) min respectively for the survival time and (85.1 +/- 8.5) ml and (73.6 +/- 5.4) ml respectively for total oxygen consumption.
CONCLUSIONThe hypoxia tolerance of the acute repetitive hypoxia mice can significantly improved by taking more oxygen in the animal cabin. The accuracy and precision of the apparatus are high and it can be used for the determination of oxygen consumption in hypoxia research.
Animals ; Hypoxia ; physiopathology ; Mice ; Monitoring, Physiologic ; instrumentation ; Oxygen Consumption ; physiology
10.Preventive strategies of secondary spinal cord injury caused by subaxial cervical trauma.
Rui-Duan LIU ; Chang-Qing JIA ; Qin FU ; Feng LIANG ; Jie YANG
China Journal of Orthopaedics and Traumatology 2010;23(11):860-863
OBJECTIVETo summarize and analyze preventive strategies of secondary spinal cord injury caused by subaxial cervical trauma.
METHODSFrom April 2004 to April 2009, 67 patients with secondary spinal cord injury caused by subaxial cervical trauma were retrospectively analyzed. There were 40 males and 20 females, with an average age of 40.5 years old ranging from 18 to 69 years. After admission the preventive strategies included using MP and GM-1, early decompression, and high pressure oxygen after operation. The neurological function was classified by Frankel, and the therapeutic effect was evaluated by total recovery rate and useful recovery rate. The total recovery rate was that the level of Frankel raise one or more grade, the useful recovery rate which included Frankel D, E was that the patient can walk by self or crutch, remaining some neurological deficits.
RESULTSAll patients were followed up for 1 to 3 years (averaged 1.5 years), the total recovery rate was 53.7% (36/67), the useful recovery rate was 35.8% (24/67). Seven patients was death, the death rate was 10.4% (7/67), 1 was aggravated, the aggravating rate was 1.5% (1/67).
CONCLUSIONAs possible as using MP, GM-1, early decompression, and high pressure oxygen after operation can be effective strategies for preventing secondary spinal cord injury caused by subaxial cervical trauma.
Adolescent ; Adult ; Aged ; Cervical Vertebrae ; injuries ; Decompression, Surgical ; Female ; Humans ; Hyperbaric Oxygenation ; Male ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries ; prevention & control