1.Correlation of brain natriuretic peptide and cardiac function of rabbits with hyperthyroid cardiomyopathy exhibiting different left ventricular geometries
Wenting LUO ; Guangsen LI ; Yuanzheng WANG ; Yan TIAN ; Wen KANG ; Sisi MENG
Chinese Journal of Tissue Engineering Research 2015;(40):6444-6449
BACKGROUND:Toxic effects of excessive thyroid hormone on myocardium can not be ignored with the increased incidence of hyperthyroidism. As a quantitative marker of heart failure, brain natriuretic peptide has a good application prospect to estimate the changes of cardiac function and myocardial damage in hyperthyroid cardiomyopathy. OBJECTIVE:To explore the correlation of brain natriuretic peptide and cardiac function of rabbits with hyperthyroid cardiomyopathy exhibiting different left ventricular geometries. METHODS:Twenty New Zealand purebred rabbits were used in this study. Hyperthyroidism model was established by intraperitoneal injection of levothyroxine (45 μg/kg) for 4 weeks. The success of establishing model is defined upon the appearance of irritation, decreased body weight and increased appetite. Totaly 18 rats were successfuly established. The left ventricular data of hyperthyroidism rabbits were measured by conventional echocardiography. According to the classification of Ganauet al, the 18 hyperthyroidism rabbits were divided into two groups: concentric hypertrophy (n=7) and eccentric hypertrophy (n=11). In addition, ten rats, receiving intraperitoneal injection of 5 mL saline per day, were taken as the control group. RESULTS AND CONCLUSION: Plasma brain natriuretic peptide level of rabbits in the concentric hypertrophy and eccentric hypertrophy groups was obviously higher than that of the control group (alP < 0.01), and the level in the eccentric hypertrophy group was obviously higher than in the concentric hypertrophy group (P< 0.01). Compared with the control group, the average peak diastolic velocity of mitral ring was significantly lower in the concentric hypertrophy and eccentric hypertrophy groups (alP< 0.01), the average peak systolic velocity of mitral ring was also lower in the eccentric hypertrophy group (P < 0.01). The peak systolic and diastolic velocity had a negative correlation with brain natriuretic peptide (alP < 0.01). Experimental findings indicate that brain natriuretic peptide is a sensitive indicator to reflect the cardiac function and myocardial damage in rabbits with hyperthyroid cardiomyopathy, exhibiting different left ventricular geomeies.
2.Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites.
Sisi KANG ; Mei YANG ; Zhongsi HONG ; Liping ZHANG ; Zhaoxia HUANG ; Xiaoxue CHEN ; Suhua HE ; Ziliang ZHOU ; Zhechong ZHOU ; Qiuyue CHEN ; Yan YAN ; Changsheng ZHANG ; Hong SHAN ; Shoudeng CHEN
Acta Pharmaceutica Sinica B 2020;10(7):1228-1238
The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.