Additional Insertion of gC Gene Triggers Better Immune Efficacy of TK/gI/gE-Deleted Pseudorabies Virus in Mice.

In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 106.0 TCID50 dose after 4 and 6 weeks post-initial immunization (PII) (p < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 105.0 TCID50 dose after 6 weeks PII (p < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 105.0 TCID50, the level of NA was close to that in the triple-gene deletion virus group with 106.0 TCID50 at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 106.0 TCID50. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 105.0 TCID50, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.

Friendship Importance Around the World: Links to Cultural Factors, Health, and Well-Being.

Prioritizing friendship is associated with many health and well-being benefits. However, to date, there have been relatively few studies that have examined cultural moderators of the link between friendship and important outcomes. In other words, is prioritizing friendships more beneficial in some contexts than others? In the current study, we examined how culture- and country-level factors were associated with the importance people place on friendships and the benefits derived from this importance. The sample comprised of 323,200 participants (M = 40.79 years, SD = 16.09 years) from 99 countries from the World Values Survey. Multilevel analyses revealed that women, people with higher levels of education, and people living in countries that are more economically equal and high in indulgence placed more value on friendships. Prioritizing friendships in life was associated with better health and well-being, but these associations depended on many cultural factors. The findings are discussed in the context of the ways in which friendships can enrich health and well-being across different settings.

[Left ventricular systolic synchrony assessed by phase analysis of gated myocardial perfusion imaging in patients with old myocardial infarction].

OBJECTIVE: To assess the left ventricular (LV) systolic synchrony by phase analysis of gated myocardial perfusion imaging (GMPI) with SPECT/CT in patients with old myocardial infarction (OMI) and further to identify independent predictors for LV dyssynchrony. METHODS: Seventy-six OMI patients and seventy-four healthy volunteers (control group) underwent resting GMPI from October 2010 to September 2013 in our hospital were included in this study. The left ventricular systolic synchrony parameters including phase histogram bandwidth (BW) and phase standard deviation (SD) were obtained by Cedars-Sinai quantitative gated SPECT (QGS) phase analysis technique, and LV cardiac function was also measured. The extent of myocardial perfusion defect was analyzed by the Quantitative Perfusion SPECT (QPS) software. The value of BW and SD were compared between OMI and the control groups, between LVEF ≤ 35% and LVEF > 35% groups in OMI patients. Dyssynchrony was defined when the BW exceeded the abnormality threshold derived from a normal control group (threshold = x ± 2s for normal BW). RESULTS: (1) The BW ((91.3 ± 58.6)° vs. (37.2 ± 11.7)°) and SD ((27.3 ± 20.8)° vs. (11.8 ± 5.4)°) were significantly higher and the LVEF was significantly lower in OMI group than in the normal control group (all P < 0.01). In addition, BW ((136.0 ± 52.9)° vs. (51.0 ± 24.0)°) and SD ((38.7 ± 21.3)° vs. (17.1 ± 14.0)°) were significantly higher in patients with LVEF ≤ 35% than in patients with LVEF > 35% (all P < 0.001). (2) Dyssynchrony (BW > 60.6°) prevalence was 57.9% (44/76) in OMI patients. Compared with the synchrony group, LVEF was significantly lower, while the left ventricular end-diastolic volume, end-systolic volume, summed motion score, summed thickening score and extent were significantly higher in dyssynchrony group (all P < 0.001). (3) Additionally, dyssynchrony prevalence was significantly higher in patients with LVEF ≤ 35% compared with patients with LVEF > 35% (91.7% (33/36) vs. 27.5% (11/40), P < 0.001). (4) Pearson correlation analysis showed that LVEF was negatively correlated with BW (r = -0.807, P < 0.001). (5) Multivariate logistic regression analysis revealed that the extent of myocardial perfusion defect was an independent predictor for dyssynchrony in OMI patients (OR = 1.076, 95% CI: 1.015-1.141, P = 0.015). CONCLUSIONS: GMPI phase analysis can reliably reflect left ventricular systolic synchrony. The left ventricular systolic dyssynchrony in OMI patients is significantly increased. Left ventricular dyssynchrony is closely related to LVEF. The extent of myocardial perfusion defect (Extent) is an independent predictor for left ventricular systolic dyssynchrony in OMI patients.

Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner.

Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of insulin in energy metabolism have been well studied, with most of the attention focused on glucose utilization, but the roles of insulin in cell proliferation and differentiation remain unclear. In this study, we observed for the first time that 10 nmol/L insulin treatment induces cell proliferation and cardiac differentiation of P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells. By using real-time polymerase chain reaction (PCR) and Western blotting analysis, we found that the mRNA levels of cyclin D1 and α myosin heavy chain (α-MHC) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100 nmol/L insulin treatment, whereas the mRNA levels of BCL-2-antagonist of cell death (BAD) exists a reverse trend. The similar results were observed in P19CL6 cells expressing GATA-6 or peroxisome proliferator-activated receptor α (PPARα). Our results identified the downstream targets of insulin, cyclin D1, BAD, α-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.

Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals.

PURPOSE: There is significant inter-individual variability in the lipid-lowering effects of atorvastatin and simvastatin. Our goal was to investigate the impact of SLCO1B1 genetic polymorphism on the lipid-lowering effects of atorvastatin and simvastatin. METHODS: We recruited 363 unrelated hyperlipidemic patients with the CYP3A4 1/1, CYP3A5 1/1, and CYP3AP1 1/1 genotypes: 189 of these were treated with atorvastatin and 174 were treated with simvastatin as a single-agent therapy (20 mg day(-1) orally) for 4 weeks. The genotyping of SLCO1B1 c.521T > C (p.V174A, OATP-C5) was performed with allele-specific polymerase chain reaction (AS-PCR), and PCR restriction fragment length polymorphism (RFLP) was performed to detect the carriers of SLCO1B1 c.388A > G (p.N130D, OATP-C1b). Serum triglyceride (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment. RESULTS: The frequencies of the SLCO1B1 521T > C and 388A > G variant alleles in Chinese hyperlipidemic patients were found to be 16.2% and 72.1% respectively. After treatment with 20 mg simvastatin or atorvastatin daily for 4 weeks, TC, TG, and LDL-C concentrations were lower than at baseline, on average, by 18.1 ± 3.7%, 25.8 ± 9.7%, 27.7 ± 5.4% in the simvastatin-treated group, and 17.5 ± 3.7%, 22.6 ± 8.6%, 27.5 ± 5.5% in the atorvastatin-treated group respectively, and the mean relative reduction in serum HDL cholesterol did not reach statistical significance (-1.0 ± 10.9%, 0.5 ± 9.3%). However, no significant differences were observed in the lipid-lowering effects of atorvastatin and simvastatin between subjects with different SLCO1B1 genotypes. CONCLUSION: The SLCO1B1 521T > C and 388A > G variants were found to be relatively common in Chinese patients with essential hyperlipidemia. These frequencies were found to be similar to those observed in healthy Chinese and Japanese individuals, but significantly different from Caucasians and blacks. SLCO1B1 521T > C and 388A > G polymorphisms may not be associated with the lipid-lowering effects of atorvastatin and simvastatin.

Effects of combination therapy with perindopril and losartan on left ventricular remodelling in patients with myocardial infarction.

1. Inhibiting the renin-angiotensin-aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI). 2. The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal peptide (PIIINP) levels in patients with acute MI. 3. Patients with anterior MI were divided into three groups: (i) MI + perindopril; (ii) MI + losartan; and (iii) MI + perindopril + losartan. After successful intervention therapy, perindopril (2-4 mg daily), losartan potassium (25-50 mg daily) or their combination were administered. All patients received aspirin, clopidogrel and statins, and some patients were given beta-blockers, nitrate and a platelet glycoprotein IIb/IIIa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma B-type natriuretic peptide (BNP), serum C-reactive protein (CRP) and PIIINP levels were evaluated using enzyme-linked immunosorbent assay or radioimmunoassay. 4. The baseline characteristics of the three groups were the same. Three months after the initiation of therapy, all patients showed decreased CRP, increased BNP and PIIINP levels and LV dilation and dysfunction. Compared with the two monotherapy groups, patients in the combination group showed significantly lower CRP, BNP and PIIINP levels, less LV dilation and higher LVEF. Serum PIIINP levels were positively correlated with CRP levels (r = 0.597; P < 0.01) and LV end-diastolic volume index (r = 0.543; P < 0.01) and were negatively correlated with LVEF (r = -0.565; P < 0.01). 5. For patients with acute MI, combination treatment with perindopril and losartan significantly inhibited LV remodelling and improved LV function. Inhibition of myocardial interstitial fibrosis may be part of the underlying mechanism.