Acute-On-Chronic Liver Failure ; blood ; pathology ; Case-Control Studies ; Cytochrome Reductases ; metabolism ; Humans ; Prospective Studies ; alpha-Fetoproteins ; metabolism

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 ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

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.

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 ; Humans ; Hypoxia ; drug therapy ; Polycythemia ; drug therapy ; Stilbenes ; pharmacology

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

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

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

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

OBJECTIVETo construct an apparatus for the oxygen uptake measurement of rats exposed to hypobaric hypoxia at different simulated altitude.

METHODSThe capacity of this apparatus was about 0.01 m3. It included animal experimental cabin, reference cabin, altimeter, altitude vertical velocity indicator, pressure difference inductor and oxygen compensator, low scale manometer, soda lime and calcium chloride, small fan, thermometer, circulating water system and vacuum pump. The oxygen uptake of the rats at 6 000 m, 4 000 m and 1 000 m simulated altitude was measured using this apparatus.

RESULTSThe oxygen uptake of the rats at 50 m, 4 000 m and 6 000 m simulated altitude was (24.4 +/- 2.1), (10.8 +/- 2.0) and (8.8 +/- 1.6) ml O2/(kg x min) respectively (average +/- s, n = 10). The oxygen uptake decreased as altitude increased.

CONCLUSIONThis apparatus can be used to measure the oxygen uptake of the rats at different simulated altitude.

Altitude ; Altitude Sickness ; physiopathology ; Animals ; Computer Simulation ; Equipment and Supplies ; Hypoxia ; physiopathology ; Male ; Oxygen ; metabolism ; Oxygen Consumption ; physiology ; Rats ; Rats, Sprague-Dawley

Adolescent ; Altitude ; Brain ; drug effects ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Tablets