宋晓东
中国医学科学院阜外医院 新大楼启用筹备办
OBJECTIVE:To investigate the effects of Qihong capsule (QH) on HeLa cells infected by coxsackievirus B3 (CVB3) in vitro and its potential antiviral mechanism.METHODS:HeLa cells were infected by CVB3 in vitro. XTT assay and plaque inhibition assay were performed to determine the 50 % effective dose, (ED50), 50 % inhibitory concentration (IC50), and 50% cytotoxicity concentration (CC50) of QH and the control drug, ribavirin. The total therapeutic index (TI) was calculated. Anti-viral time-course experiments were performed to compare the anti-viral effects at different time points. The inhibitory effects of QH on the attachment and penetration of CVB3 were also observed.RESULTS:XTT assay and plaque inhibition assay showed that the ED50 and IC50 were (7.16+/-0.80) mg/L and (2.63+/-0.50) mg/L in QH group and (4.35+/-0.40) mg/L and (1.92+/-0.30) mg/L in ribavirin group, respectively. CC50 was 16-fold higher in QH group than in ribavirin group QH: (1 648+/-219) mg/L vs. Ribavirin: (103+/-14) mg/L. Time-course studies demonstrated that antiviral effect of QH was mainly found 0-4 hours after infection. QH effectively blocked the attachment and penetration of CVB3 into cells.CONCLUSION:By inhibiting the attachment and penetration of CVB3, QH can effectively inhibit the invasion of virus in vitro with low toxicity.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 2010
GDF15 (growth-differentiation factor 15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy. In the present study, we have investigated the relationship between GDF15 gene variants and left ventricular hypertrophy in human essential hypertension. A community-based hypertensive population sample of 1527 individuals (506 men and 1021 women) was genotyped for three GDF15 genetic variants, including one tag variant -3148C>G (rs4808793) and two exonic variants +157A>T (rs1059369) and +2438C>G (rs1058587). The effects of those variants on gene expression were studied by use of luciferase reporter assays and the determination of plasma GDF15 levels. Only the tag variant -3148G was significantly associated with a lower risk of left ventricular hypertrophy [odds ratio=0.75 (95% confidence interval, 0.63-0.89); P=0.0009]. Multiple regression analyses confirmed that -3148G predicted the decrease in left ventricular end-diastolic diameter (beta=-0.10, P=0.0001), end-systolic diameter (beta=-0.09, P=0.0007), mass (beta=-0.11, P<0.0001) and indexed mass (beta=-0.12, P<0.0001). These effects were independent of conventional factors, including gender, age, body surface area, blood pressure, diabetes, cigarette smoking and alcohol consumption. The transcription activity of the -3148G-containing construct was increased 1.45-fold (P=0.015) at baseline and 1.73-fold (P=0.008) after stimulation with phenylephrine when compared with the -3148C construct. The -3148G allele was also associated with a significant increase in the plasma GDF15 level in hypertensive subjects (P=0.04). In conclusion, the results show that a promoter haplotype containing the -3148G variant increases GDF15 transcription activity and is associated with favourable left ventricular remodelling in human essential hypertension.
Clinical science (London, England : 1979) 2009
AIM:The genetic background of orthostatic blood pressure dysregulation remains poorly understood. Since the renin-angiotensin system plays an important role in blood pressure regulation and response to position change, we hypothesized that angiotensin-converting enzyme (ACE) and ACE2 genetic polymorphisms might contribute, at least partially, to orthostatic blood pressure dysregulation in hypertensive patients.METHODS:Two tag single nucleotide polymorphisms (SNPs) of ACE2 and ACE I/D were genotyped in 3630 untreated hypertensive patients and 826 normotensive subjects. Orthostatic hypertension was defined as an increase in systolic blood pressure of 20 mmHg or more and orthostatic hypotension as a drop in blood pressure of 20/10 mmHg or more within three minutes of assumption of upright posture.RESULTS:Female and male patients had similar rates of orthostatic hypertension (16.5% vs 15.3%) and hypotension (22.5% vs 23.8%). No significant differences were detected in the minor allele frequency of ACE2 rs2106809, rs2285666, or ACE I/D in either female or male patients with orthostatic hypertension (15.1%, 22.7%, 19.6%, respectively), hypotension (13.8%, 25%, 16.5%), or normal orthostatic blood pressure response (14.4%, 21.9%, 15.8%) in additive, dominant or recessive models after adjustment for confounders (all P>0.05). The orthostatic changes in systolic and diastolic blood pressure were also comparable among patients carrying different genotypes. Similar results were observed in normotensive subjects.CONCLUSION:These data provide no support for the involvement of ACE or ACE2 in the genetic predisposition to orthostatic hypotension or hypertension.
Acta pharmacologica Sinica 2009
Stroke is a common complex trait and does not follow Mendelian pattern of inheritance. Gene-gene or gene-environment interactions may be responsible for the complex trait. How the interactions contribute to stroke is still under research. This study aimed to explore the association between gene-gene interactions and stroke in Chinese in a large case-control study. Nearly 4,000 participants were recruited from seven clinical centers. Eight variants in five candidate genes were examined for stroke risk. Gene-gene interactions were explored by using Generalized Multifactor Dimensionality Reduction (GMDR). A significant gene-gene interaction was found by GMDR. The best model including MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T scored 10 for Cross-Validation Consistency and 9 for Sign Test (P = 0.0107). The individuals with combination of MTHFR 677TT, ALOX5AP 2354AA and NOTCH3 381TT/TC had a significantly higher risk of thrombotic stroke (OR 3.165, 95% CI 1.461-6.858, P = 0.003). Our results show that combination of these alleles conferred higher risk for stroke than single risk allele. The gene-gene interaction may serve as a novel area for stroke research. The three-locus combination may change the susceptibility of particular subjects to the disease.
Human genetics 2009
BACKGROUND:The use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. Reactive oxygen species (ROSs) play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.METHODS:We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst33258 staining and measurement of lactate dehydrogenase (LDH) release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay.RESULTS:The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 microg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.CONCLUSION:Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.
Chinese medical journal 2009
Mitogen-activated protein kinase kinase 7 (MKK7) induces cardiac hypertrophy by activating the c-Juns NH2-terminal kinases (JNK). It has been reported that growth arrest and DNA-damage-inducible beta (GADD45Beta) binds to MKK7 directly and blocks its catalytic activity, mediates the inhibition of JNK signaling. However, the potential role of GADD45Beta on cardiac hypertrophy has not been investigated. In this study, we found co-infection of cardiomyocytes with adenoviral vectors expressing MKK7 and GADD45B could counteract the characteristic hypertropic responses, including an increase in cell size and elevated atrial natriuretic factor (ANP) expression which induced by overexpression of MKK7. Furthermore, siRNA-mediated knockdown of GADD45B could also cause cardiomyocytes hypertrophy. GeneChip data showed that GADD45B mRNA decreased significantly in patients with hypertrophy cardiomyopathy (HCM) compared with healthy subjects. Association study indicated that haplotype (rs2024144-rs3783501) of GADD45B affected the thickness of inter-ventricular septum in patients with HCM. Dual-luciferase assay showed that C-A haplotype displayed significantly increased transcription activity compared to T-G haplotype.
Biochemical and biophysical research communications 2008
BACKGROUND:Sex-specific responses to antihypertensive drugs are not very well understood.OBJECTIVE:To investigate sex-related differences in blood pressure response to antihypertensive drugs in a community-based prospective clinical trial.METHODS:We recruited 3535 untreated hypertensive patients (2326 women), aged 40-75 years, from 7 rural communities in China. Subjects were randomized to 1 of 4 drug groups: atenolol, hydrochlorothiazide (HCTZ), captopril, or sustained-released nifedipine; duration of the study was 8 weeks. Mean blood pressure reduction, blood pressure control rates, and frequency of adverse events were compared between men and women.RESULTS:Women had a better response to HCTZ in relation to diastolic blood pressure (1.8 mm Hg lower) than did men (p < 0.05) and were 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). In the atenolol group, mean systolic blood pressure decreased 3.9 mm Hg more in women than in men (p < 0.05), and women were 65% more likely to reach the control goal of systolic blood pressure and 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). Significant sex-related differences were also found in drug-related adverse events in the nifedipine group (15.8% in women vs 9.8% in men; p = 0.017) and in the captopril group (14.3% in women vs 8.4% in men; p = 0.005), but no differences were seen with HCTZ or atenolol.CONCLUSIONS:Women have better blood pressure responses to HCTZ and atenolol and experience more adverse effects with sustained-release nifedipine and captopril than do men, indicating that sex should be taken into account when selecting antihypertensive drugs.
The Annals of pharmacotherapy 2008
In this study, we determined the role of PDGF-D, a new member of the PDGF family, in a rat model of balloon injured artery made with a 2F catheter in Sprague-Dawley male rats. PDGF-D expression was studied in the injured and control segments of abdominal aorta. The function of PDGF-D was evaluated in rat vascular smooth muscle cells stably transfected with PDGF-D gene. We found that in normal abdominal aorta, PDGF-D was highly expressed in adventia, moderate in endothelia, and unidentified in media. Stable transfection of PDGF-D gene into vascular smooth muscle cells increased the cell migration by 2.2-fold, and the proliferation by 2.3-fold, respectively, and MMP-2 production and activity as well. These results support the fact that PDGF-D is involved in the formation of neointimal hyperplasia induced by balloon catheter injury and may serve as a target in preventing vascular restenosis after coronary angioplasty.
Biochemical and biophysical research communications 2005
OBJECTIVE:To investigate whether the cell apoptosis could be induced by Coxsackie virus B (Cox B) and Qihong capsule (QHC) has the inhibition on the cell apoptosis.METHODS:Cultured cells were divided into 4 groups, the Cox B infected group, the QHC treated and the Cox B infected group, the QHC control group and the normal control group. The cells apoptosis was determined by TUNEL labeled in situ, Hoechst 33258 staining and Annexin-V/PI staining, the apoptotic incidence was assayed by flow cytometry, and the change in expression of apoptotic related cytokines was measured with RT-PCR.RESULTS:The Cox B infected cell nucleus displayed strong blue fluorescence by Hoechst 33258 staining, and typical change of apoptotic cells could be detected. HeLa cell membrane showed strong green fluorescence and nucleus showed strong red fluorescence by Annexin-V/PI staining. Flow cytometric observation on DNA of PI stained cells showed obviously an apoptotic peak in the Cox B infected group. QHC could decrease the apoptosis incidence, while there was no cell apoptosis occurred in the normal control group. Besides, QHC could regulate the expression of apoptotic related cytokines.CONCLUSION:QHC has effect in inhibiting cell apoptosis induced by Cox B.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine 2005
