Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.</p>

A novel hot-spot mutation S236G in the cardiac myosin binding protein C gene in Chinese patient with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify the disease-causing gene mutations and to reveal the relationship between the genotype and the phenotype in Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>One hundred unrelated patients with HCM and 120 controls were enrolled in this study. The full encoding exons and flanking sequences of the cardiac myosin binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>A novel missense mutation c.706T > C was identified in exon 6 of MYBPC3 gene in three HCM patients, which resulted a Serine (S) to Glycine (G) exchange at amino acid residue 236 (S236G). The clinical phenotypes of the three patients were different (2 obstructive HCM, 1 non-obstructive HCM). The 120 controls were normal in the genetic test.</p><p><b>CONCLUSIONS</b>The novel S236G mutation in MYBPC3 gene was a hot-spot mutation in Chinese patients with HCM.</p>

The genotype-phenotype correlation of MYH7 gene G15391A mutation and MYBPC3 gene G12101A mutation in familial hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To reveal genotype-phenotype correlation of disease-causing gene mutations in Chinese hypertrophic cardiomyopathy (HCM) pedigree.</p><p><b>METHODS</b>Peripheral venous blood samples were collected from two Chinese HCM families and 120 healthy subjects were recruited as normal control. The full encoding exons and flanking sequences of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7) and myosin binding protein C gene (MYBPC3) were amplified with the polymerase chain reaction method, DNA sequencing was used to detect the mutation.</p><p><b>RESULTS</b>In ZZJ family, mutation G12101A was identified in exon 21 of MYBPC3 gene in 4 family members [the arginine (R) converted to histidine (H)]. In this pedigree, three out of eight family members were diagnosed as HCM and with a penetrance of 75%. In FHL family, mutation G15391A was identified in exon 23 of MYH7 gene in 3 family members [the glutamic acid (E) converted to lysine (K)]. In this pedigree, three out of six family members were diagnosed as HCM and with a penetrance of 100%. Echocardiography showed obstruction of left ventricular outflow tract in two out of the three HCM patients.</p><p><b>CONCLUSIONS</b>Our results showed that the G12101A mutation of MYBPC3 gene is the causal mutation of familial HCM with mild phenotype. The G15391A mutation of MYH7 gene is the causal mutation of familial HCM with malignant phenotype and a penetrance of 100%. Screening mutations in the MYH7 gene should be viewed as a reasonable procedure in obstructive HCM patients.</p>

Determination of metanephrine and normetanephrine by high-performance liquid chromatography with electrochemical detector and its diagnostic application for pheochromocytoma / 中华检验医学杂志

Objective To establish high-performance liquid chromatography with electrochemical detector(HPLC-ECD) method for the determination for metanephrine and normetanephrine in 24 h urine, and provide a superior test for the diagnostic of pheochromocytomas over plasma/urine catecholamine.Methods MCX solid-phase cartridge was used for extraction of metanephrine and normetanephrine,HPLC-ECD was used for their measurements.The intra-assay CVs,interassay CVs and recoveries of metanephrine and normetanephrine were also calculated.104 hypertensive patients without pheochromocytomas and 5 pheochromocytomas patients were selected in this study.The concentrations of metanephrine and normetanephrine were compared with the plasma and 24h urinary catecholamines concentrations.Results The intra-assay CV,inter-assay CV and recovery of metanephrine were 5.9%, 7.5%,91.1% respectively;the intra-assay CV,inter-assay CV and recovery of normetanephrine were 6.3%,6.6%,88.5%,respectively.The MN,NMN,plasma CA and urine CA of all pheochromocytomas patients were positive.MN and NMN were negative in controls,while plasma CA and urine CA are false positive in 15 patients and 14 patients in controls,respectively.Conclusions The study establish a fast and accurate method for quantification of metanephrine and normetanephrine in 24 h urine by HPLC-ECD.These findings also prove that it is the best biochemical assays for pheochromocytomas at present.