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1.
Chinese Pharmacological Bulletin ; (12): 209-214, 2022.
Article in Chinese | WPRIM | ID: wpr-1014196

ABSTRACT

Aim To study the effect of tetrandrine derivative HL-49 on the conformation and biological ac-tivity of Bloom helicase ( BLM ) , and to explore its antitumor mechanism.Methods The effect of HL-49 on the conformation of BLM helicase was studied by ultra- violet spectroscopy.The effects of HL-49 on DNA binding activity, DNA chain dissociation activity and ATPase activity of HL-49 on BLM DNA helicase were analyzed by fluorescence polarization and malachite green-ammonium phosphomolybdate colorimetric method.Results HL-49, a tetrandrine derivative, indirectly inhibited the ATPase activity of BLM DNA heli- case and DNA unwinding activity by reversible binding with DNA.The results of fluorescence polarization experiments showed that HL-49 could not affect the bind ing activity of BLM DNA helicase to DNA (dsDNA/ss- DNA) , but could bind to DNA in a concentration-de- pendent manner (P < 0.01).With the increase of HL- 49 concentration, the DNA unwinding ability of BLM DNA helicase decreased, and the Kobs value decreased gradually.The results of malachite green-ammonium phosphomolybdate colorimetry showed that HL-49 could significantly inhibit the ATPase activity of BLM DNA helicase.Conclusions HL49 can inhibit the ATPase activity and DNA unwinding activity of BLM DNA helicase by the reversible binding with DNA.

2.
Chinese Pharmacological Bulletin ; (12): 934-939, 2018.
Article in Chinese | WPRIM | ID: wpr-705155

ABSTRACT

Aim To investigate the effects of bisbenzyl-isoquinoline alkaloid tetrandrine derivative HL-27 on the biological properties of the BLM642-1290 helicase. Methods Fluorescence polarization technique was used to investigate the effects of bisbenzylisoquinoline alkaloid tetrandrine derivative HL-27 on the DNA bind-ing activity and unwinding activity of the BLM642-1290 helicase. Malachite green-phosphate ammonium molyb-date colorimetry was used to investigate the effects of HL-27 on the ATPase activity of the BLM642-1290 heli-case. Ultraviolet spectral scanning was used to investi-gate the effects of HL-27 on the conformation of the BLM642-1290 helicase. Results When the concentra-tion of HL-27 reached 33.34 μmol·L-1, the inhibi-tion ratio of dsDNA and ssDNA binding activity of the BLM642-1290 helicase was 41.35% and 59.54% , re-spectively. When the concentration of HL-27 reached 50 μmol·L-1, the inhibition ratio of DNA unwinding activity of the BLM642-1290 helicase was 78.68% . When the concentration of HL-27 reached 100 μmol· L-1, the inhibition ratio of ATPase activity of the BLM642-1290 helicase was 43.8% . Conclusion The DNA binding activity, ATPase activity and unwinding activity of the BLM642-1290 helicase can be inhibited by bisbenzylisoquinoline alkaloid tetrandrine derivative HL-27.

3.
Chinese Journal of Cardiology ; (12): 709-713, 2013.
Article in Chinese | WPRIM | ID: wpr-261502

ABSTRACT

<p><b>OBJECTIVE</b>To systematically investigate the possible associations between G1165C and A145G polymorphism of β1-adrenoceptor (ADRB1) and resting heart rate (HRrest) in Northern Han Chinese.</p><p><b>METHODS</b>HRrest of 700 healthy Northern Han Chinese were measured in the sitting position.SNPs were genotyped by the TaqMan assay.Genotypes were differentiated by analyzing the fluorescence levels of PCR products using an ABI Prism 7900HT Sequence Detector.</p><p><b>RESULTS</b>HRrest was significantly lower in A145G AA carriers than in AG and GG carriers (all P < 0.01) . Multiple linear regression analysis showed that age, smoking habits, systolic blood pressure, triglyceride, serum creatinine and A145G polymorphism were associated with HRrest (P < 0.01) . A145G was significantly related with HRrest independent of other possible confounding variables, and the partial regression coefficient was 2.148 (P < 0.05) . After adjusting for other confounding factors, significant association between A145G and HRrest was only found in male subjects (P < 0.05) but not in female subjects (P > 0.05) .</p><p><b>CONCLUSION</b>The A145G polymorphism of ADRB1 gene is associated with HRrest in Northern male Han Chinese.</p>


Subject(s)
Female , Humans , Male , Middle Aged , Asian People , Genetics , Genotype , Heart Rate , Genetics , Polymorphism, Single Nucleotide , Receptors, Adrenergic, beta-1 , Genetics
4.
Article in Chinese | WPRIM | ID: wpr-323888

ABSTRACT

<p><b>OBJECTIVE</b>To compare the plasma proteome among male normotensive, prehypertensive, and hypertensive subjects.</p><p><b>METHODS</b>Plasma proteome was analyzed by two-dimensional electrophoresis combined with MALDI-TOF mass spectrometry in this case-control study among well matched male normotensive, prehypertensive and hypertensive subjects (n = 26 each).</p><p><b>RESULTS</b>The results showed that there were 22 differentially expressed protein spots among the protein samples derived from the 3 groups which corresponded to 18 proteins associated with inflammation and immunity, lipid metabolism, transport, coagulation and fibrinolysis, cell proliferation and apoptosis, and antioxidation.</p><p><b>CONCLUSION</b>Proteins were differentially expressed in male subjects with various blood pressure levels.</p>


Subject(s)
Adult , Humans , Male , Middle Aged , Blood Pressure , Case-Control Studies , Hypertension , Genetics , Prehypertension , Genetics , Proteomics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
5.
Chinese Journal of Cardiology ; (12): 916-920, 2008.
Article in Chinese | WPRIM | ID: wpr-355865

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate pericardial endothelin (ET) secretion by the human pericardial mesothelial cells.</p><p><b>METHODS</b>Plasma, pericardial fluid and pericardial tissue were obtained in 51 patients receiving open heart surgery (coronary artery bypass grafting, elective heart valvuloplasty or valve replacement). ET concentrations in the plasma, pericardial fluid and pericardial tissues were measured by radioimmunoassay (RIA). ET mRNA expression in the human pericardium was detected by in situ hybridization.</p><p><b>RESULTS</b>(1) The levels of ET in human pericardial fluid was significantly higher than that in the plasma [(128.8 +/- 44.0) ng/L vs. (93.7 +/- 28.6) ng/L, P < 0.001]; (2) ET concentration in the pericardial tissue was (510.3 +/- 156.7) ng/kg; (3) In situ hybridization technique evidenced the abundant ET mRNA expression in human pericardial mesothelial cells.</p><p><b>CONCLUSION</b>The study indicated that pericardium secreted ET into the pericardial space.</p>


Subject(s)
Humans , Coronary Artery Bypass , Endothelin-1 , Metabolism , Endothelins , Pericardial Effusion , Pericardium
6.
Chinese Journal of Cardiology ; (12): 719-722, 2007.
Article in Chinese | WPRIM | ID: wpr-307213

ABSTRACT

<p><b>OBJECTIVE</b>This study investigates the plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients.</p><p><b>METHODS</b>Patients were scruited according to JNC-7 and divided into three groups: 74 normotensive subjects (NT group, 38 males, mean age 47.15 +/- 7.77 years old); 51 prehypertensive patients (PH group, 29 males, mean age 47.82 +/- 5.16 years old) and 71 essential hypertensive patients (EH group, 37 males, mean age 48.25 +/- 7.97 years old). Serum lipids and plasma angiotensin II (Ang II), endothelin (ET), vasopressin (AVP), calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GPX) by radioimmunoassay and enzyme linked immunosorbent assay.</p><p><b>RESULTS</b>Serum Lipids (TG, CHO and LDL) were significantly higher in the PH and EH groups compared to NT group (all P < 0.05). Ang II, AVP and ET were significantly increased while CGRP decreased in the EH group than that in NT group (all P < 0.05). SOD was significantly lower while GPX significantly higher. Further more, in the PH and EH groups than those in the NT group (all P < 0.05).</p><p><b>CONCLUSION</b>SOD was reduced and GPX increased in prehypertensive patients.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Angiotensin II , Blood , Antioxidants , Blood Pressure , Physiology , Calcitonin Gene-Related Peptide , Blood , Case-Control Studies , Endothelins , Blood , Glutathione Peroxidase , Blood , Hypertension , Blood , Nitric Oxide Synthase , Blood , Plasma , Metabolism , Superoxide Dismutase , Blood , Vasopressins , Blood
7.
Chinese Journal of Cardiology ; (12): 914-918, 2007.
Article in Chinese | WPRIM | ID: wpr-299559

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the novel hyperplasia suppressor gene (HSG) expression in vascular smooth muscle cells derived from normotensive and hypertensive patients underwent bypass surgery.</p><p><b>METHODS</b>Coronary heart disease patients underwent coronary artery bypass graft (CABG) operation in BEIJING ANZHEN hospital from 4 - 9, 2006 were enrolled in this study and divided into hypertensive group (n = 28) and normotensive group (n = 26). The preoperative venous blood samples were taken for serum biochemical and vasoactive peptides measurements. Total RNA was extracted from WBC, explanted-vessels and cultured VSMCs using TRIZOL and HSG expression was determined by Semi-Quantitative RT-PCR.</p><p><b>RESULTS</b>Body mass index (BMI) was significantly higher in hypertensive group compared to normotensive group (P < 0.01) while other biochemic parameters and vasoactive peptides were similar between the groups. BMI and GLU, BMI and SBP, BMI and DBP, GLU and TG, SBP and DBP were positively correlated (all P < 0.05). HSG expression in WBC, VSMCs and vessel tissue were significantly lower in hypertensive group than those in normotensive group (all P < 0.05). HSG expression in tissue was negatively correlated to BMI, SBP and DBP (all P < 0.05).</p><p><b>CONCLUSIONS</b>Reduced HSG expression and the negative correlation on vascular tissue HSG expression to BMI, SBP and DBP suggested a possible inhibitory role of HSG on VSMC proliferation and blood pressure.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Body Mass Index , Gene Expression , Genes, Suppressor , Hyperplasia , Genetics , Hypertension , Genetics , Pathology , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Metabolism
8.
Chinese Medical Journal ; (24): 1331-1335, 2007.
Article in English | WPRIM | ID: wpr-280438

ABSTRACT

<p><b>BACKGROUND</b>Current prosthetic, small diameter vascular grafts showing poor long term patency rates have led to the pursuit of other biological materials. Biomaterials that successfully integrate into surrounding tissue should match not only the mechanical properties of tissues, but also topography. Polyglycolic acid (70/30) has been used as synthetic grafts to determine whether human vascular smooth muscle cells and endothelial cells attach, survive and secrete endothelin and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha).</p><p><b>METHODS</b>Endothelial cells and smooth muscle cells were isolated from adult human great saphenous vein. They were seeded on polyglycolic acid scaffold in vitro separately to grow vascular patch (Groups A and B respectively) and cocultured in vitro to grow into vascular patch (Group C). Smooth muscle cells and endothelial cells were identified by immunohistochemical analysis and growth of cells on polyglycolic acid was investigated using scanning electron microscopy. The levels of endothelin and 6-keto-PGF1alpha in the culturing solutions were examined by radioimmunology to measure endothelial function.</p><p><b>RESULTS</b>Seed smooth muscle cells adhered to polyglycolic acid scaffold and over 28 days grew in the interstices to form a uniform cell distribution throughout the scaffold. Then seed endothelial cells formed a complete endothelial layer on the smooth muscle cells. The levels of endothelin and 6-keto-prostaglandin F1 alpha in the culturing solution were (234 +/- 29) pg/ml and (428 +/- 98) pg/ml respectively in Group C and (196 +/- 30) pg/ml and (346 +/- 120) pg/ml in Group B; both significantly higher than in Groups A and D (blank control group, all P < 0.05).</p><p><b>CONCLUSIONS</b>Cells could be grown successfully on polyglycolic acid and retain functions of secretion. Our next step is to use human saphenous vein smooth muscle cells and endothelial cells to grow tubular vascular grafts in vitro.</p>


Subject(s)
Adult , Humans , 6-Ketoprostaglandin F1 alpha , Blood Vessel Prosthesis , Coculture Techniques , Endothelial Cells , Physiology , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Physiology , Polyglycolic Acid , Pharmacology , Saphenous Vein , Cell Biology , Tissue Engineering
9.
Article in Chinese | WPRIM | ID: wpr-299205

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the single nucleotide polymorphism (SNP) of the novel hyperplasia suppressor gene (HSG) to uncover the relationship between HSG SNP and hypertension.</p><p><b>METHODS</b>Totally, 74 normotensive people (38 men and 36 women), 51 patients with essential hypertension (27 men and 24 women) and 20 hypertensive patients with family history of essential hypertension (9 men and 11 women) were chosen, with mean ages of (54 +/- 8) years, (57 +/- 8) years and (38 +/- 22) years, respectively. Peripheral venous blood specimen was collected from each of them and then DNA was extracted. The right primers were designed for DNA amplification with PCR. Each of the PCR-products from different groups was sequenced by ABI PRISM 377-DNA sequencer and their base components and characteristics of the same fragment were compared each other.</p><p><b>RESULTS</b>Blood levels of creatinine (CRE) and urea nitrogen (BUN) were significantly higher in the hypertensives than in the normotensives (P < 0.01). Systolic and diastolic blood pressures were significantly higher in the hypertensives and the hypertensives with family history of essential hypertension than in the normotensives (P < 0.01 and P < 0.05). There existed three kinds of SNP in the HSG 12th intron (1q82139 G/A, 82153C/G and 82273G/-), and there was significant difference in 1q82153C/G and 82273G/- SNP between the hypertensives and normotensives (P < 0.05 and P < 0.01) and between the hypertensives with family history and the normotensives (P < 0.01 and P < 0.01). And, the similar difference in C/G allele and G deletion could be found in different populations. Moreover, the CC genetype of 1q82153 was common in the population (P < 0.01) and G deletion was more common in Chinese Han people with family history of essential hypertension. There was no significant difference existed in 1q82139 G/A mutation among the three groups.</p><p><b>CONCLUSIONS</b>Measurements of renal function indicators (CRE and BUN) could probably reflect earlier advance of hypertension and damage to target organs. There existed three kinds of mutation in the 12th intron of the HSG 1q82139 G/A, 82153 C/G and 82273 G/-. The 1q82139 G/A could be a nonsense mutation and there was significant difference in the 1q82153 C/G and 1q82273 G/- SNP and gene frequencies between different Chinese Han populations, which could be independent risk factors for essential hypertension.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Base Sequence , Genes , Hyperplasia , Metabolism , Hypertension , Blood , Genetics , Molecular Sequence Data , Muscle, Smooth, Vascular , Pathology , Point Mutation , Polymorphism, Single Nucleotide
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