Objective: To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods: The rats were divided into 3 groups: Control group, with normal healthy rats (n=15), Spontaneous hypertension (SH) group (n=15), SH rats received intragastric administration of normal saline and Treatment group (n=15), SH rats received intragastric administration of fosinopril 10mg/(kg?d). All animals were treated for 7 weeks. Caudal artery systolic blood pressure (SBP) was measured at each week. blood levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malonaldehyde (MDA) and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine (Ach)/sodium nitroprusside (SNP) induction. Results: From the 1st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P<0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP<0.05; compared with SH group, Treatment group showed elevated SOD activity (P=0.010), while reduced protein levels of MDA (P=0.021) and ROS (P=0.009). Compared with Control group, SH group had the lower content of NO2-/NO3-(P<0.001); both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P<0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP<0.001. Conclusion: Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.

Objective To explore the clinical significance of B7 family homology factor-3 (B7-H3),an expression membrane type of myeloid-derived suppressor cell (MDSC),in patients with acute pancreatitis (AP).Methods A total of 63 patients with AP initially treated in the Emergency Department at the First Affiliated Hospital of Soochow University from January,2014 to December,2015 were selected.Of them,25 suffered from mild AP (MAP),20 had moderate AP (MSAP) and 18 had severe AP (SAP).Another 20 healthy subjects with matching age and gender served as the control group.All patients with AP conformed to the diagnostic criteria of Guidelines or Diagnosis and Treatment of Acute Pancreatitis set in 2013 in China.Patients with other underlying diseases that might influence the clinical outcomes were excluded,including those with tumors,autoimmune diseases,viral infections,trauma and other disorders.A flowcytometer was used to detect the expression rate of MDSC in peripheral venous blood and the expression of B7-H3 on MDSC membrane.The continuous monitoring was carried out for 24 h,48 h and 72 h in patients with AP.Results Compared with healthy subjects,the MDSC cells in patient groups 24 hours after AP onset increased notably (P ＜0.01) especially the highest increase in the SAP group,followed by the MSAP group and the lowest in the MAP group.There were significant differences in pairwise comparisons (P ＜ 0.05).From successive observation of each group,there was no significant difference in MDSC between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,MDSC reached its peak 48 hours after AP onset,but it declined 72 hours after AP onset in the SAP group (P ＜ 0.05).B7-H3 expressed significantly 24 hours after AP onset,but there was no expression of B7-H3 in the healthy group.Meanwhile,B7-H3 was expressed most highly in the SAP group,followed by the MSAP group and lowest in the MAP group.There were significant differences in expression of B7-H3 found in pairwise comparisons (P ＜ 0.05).The successive observation showed that there was no significant difference in B7-H3 expression between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,there was a trend of increase in B7-H3 expression as time prolonged found among 24 hours,48 hours and 72 hours after AP onset in the SAP group (P ＜ 0.05).Conclusions The expressions of MDSC and B7-H3 were high in AP,and there were significant differences in both expressions among MAP,MSAP and SAP groups.These phenomena offer clues in further understanding about the immunological disorders during AP giving better guidelines for clinical practice.

OBJECTIVE: To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism. METHODS: An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg^-1 · min^-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits. RESULTS: The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression. CONCLUSION Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.
Animals ; Mice ; Angiotensin II ; Tumor Suppressor Protein p53 ; Acetylation ; Stroke Volume ; Ventricular Remodeling ; Ventricular Function, Left ; Myocytes, Cardiac

To develop Senecavirus A (SVA) virus-like particles (VLPs), a recombinant prokaryotic expression plasmid pET28a-SVA-VP031 was constructed to co-express SVA structural proteins VP0, VP3 and VP1, according to the genomic sequence of the field isolate CH-FJ-2017 after the recombinant proteins were expressed in E .coli system, and purified by Ni+ ion chromatographic method. The SVA VLPs self-assemble with a high yield in vitro buffer. A typical VLPs with an average diameter of 25-30 nm which is similar to native virions by using TEM detection. Animals immunized by SVA VLPs shown that the VLPs induced high titers neutralizing antibodies in Guinea pigs. This study indicated that the VLPs produced with co-expressing SVA structural proteins VP0, VP3 and VP1 in prokaryotic system is a promising candidate and laid an important foundation for the development of a novel SVA VLPs vaccine.
Animals ; Antibodies, Neutralizing ; Escherichia coli/genetics* ; Genomics ; Guinea Pigs ; Picornaviridae/genetics*