ABSTRACT
To investigate the protective effect of spermine (Sp) on diabetic cardiomyopathy (DCM) and high glucose-induced cardiac fibroblasts (CFs), and to explore its mechanism. ①Animal experiments: 24 male Wistar rats were randomly divided into control group, type 1 diabetes group (TID) and spermine group (TID+Sp, each group n=8). TID rats were induced by streptozocin (STZ, 60 mg/kg), and TID+Sp rat were pretreated with spermine (Sp, 5 mg/(kg·d)) for 2 weeks before STZ injection. After 12 weeks of modeling, blood glucose, insulin levels, ejection fraction (EF) and shortening fraction (FS) were measured, and Masson staining and Sirius red staining were performed in the rat cardiac tissues. ②Cell experiments: primary CFs were extracted from newborn (1-3 d) Wistar rat hearts, and were randomly divided into control group, high-glucose group (HG) and HG+Sp group (n=6 per group). HG group was treated with 40 mmol/L glucose, and the HG+Sp group was pretreated with 5 μmol/L Sp for 30 min before HG treatment. The cell viability of CFs was detected by CCK8, the content of collagen in culture medium was analyzed by ELISA, and protein expressions of cell cycle related proteins (PCNA, CyclinD1 and P27) were detected by Western blot. Compared with control group, the blood glucose and collagen content were increased, and the insulin level and heart function were decreased in the T1D group. Meanwhile, HG induced an increasing of the cell viability, the collagen content in the medium and the expressions of PCNA and CyclinD1, while the expression of P27 was down-regulated. Spermine could reduce the above changes, manifested as improving the cardiac function, regulating the expression of cyclin and reducing the level of myocardial fibrosis. Spermine can alleviate myocardial fibrosis in diabetic cardiomyopathy, which mechanism is related to the regulation of cell cycle.
ABSTRACT
To observe the protective effects of exogenous spermine on renal fibrosis induced by diabetic nephropathy (DN) and to explore its mechanism. Twenty-four male C57 mice were randomly divided into control group, type 1 diabetes group (TID) and spermine pretreatment group (TID+Sp, n=8 in each group). TID mice were induced by STZ (60 mg/kg), and TID+Sp mice were pretreated with spermine (5 mg/(kg·d)) for 2 weeks before STZ injection. The mice were killed at the 12th week. The renal function was determined by serum creatinine and urea nitrogen. HE, PAS and Masson staining were used to evaluate renal tissue injury and fibrosis. The expressions of matrix metalloproteinase (MMP-2, MMP-9) and collagen IV (Coll-IV) in the kidney of mice were detected by Western blot. Compared with the control group, the blood glucose (5.67±0.22 vs 28.40±0.57 mmol/L), creatinine (14.33±1.22 vs 30.67±4.73 μmol/L) and urea nitrogen (6.93±4.94 vs 22.00±1.04 mmol/L) in the T1D group were increased significantly (P＜0.05), the glomerular basement membrane was thickened, the collagen was significantly increased, the expressions of MMP-2, MMP-9 and Coll-IV protein were increased (0.57±0.07 vs 1.06±0.20, 47.00±0.04 vs 1.29±0.09 and 0.42±0.16 vs 0.95±0.18,P＜0.05). Exogenous spermine significantly alleviates the above-mentioned changes. Exogenous spermine pretreatment could significantly alleviate renal fibrosis in diabetic mice by regulating the balance between MMPs and collagen.
ABSTRACT
Objective To evaluate vitamin D nutritional status and its relationship with ultrasonic bone mineral density among children in Wenzhou City.Methods Overnight fasting venous blood samples of 546 children were collected to measure the concentration of serum 25 -hydroxyvitamin D (25 (OH)D),and bone mineral density was measured.Results The average concentration of serum 25 (OH)D was 25. 42 ±0. 590 ng/mL,25. 09% of participants were found with sufficient vitamin D,the rate of severe deficiency,deficiency and insufficiency were 1. 47%,32. 60% and 40. 84%respectively.The concentration of 25 (OH)D in different age groups was statistically significantly different (P<0. 01 ). Vitamin D nutritional status of the older groups was poor than that of the younger ones.In the group of children aged 7 to 1 1 and 11 to 14,the levels of 25(OH)D of boy was significantly higher than that of girl.Compared to those with sufficient vitamin D,children with vitamin D deficiency or insufficiency had lower bone mineral density(BMD)(P<0. 05 ).The level of 25(OH)D was correlated with BMD (r=0. 197,P<0. 01).After adjusted age and BMI,there was still a positive correlation between 25(OH)D level and BMD (r=0. 115,P<0. 01).Conclusions The vitamin D level of children in Wenzhou area is low.The level of serum 25 (OH)D may be related to BMD .More attention should be paid to the supplementation of vitamin D.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding xenogeneic alpha-fetoprotein (AFP) on breaking the immune tolerance and induction of immunity against hepatocellular carcinomas.</p><p><b>METHODS</b>Human and mouse alpha-fetoprotein full-length cDNA were cloned from human HepG2 and mouse Hepa 1 - 6 hepatoma cell lines, respectively, using RT-PCR, and then inserted into adenoviral shuttle vectors to construct Ad hAFP and Ad mAFP. Mice were immunized with Ad hAFP-infected DC and in vitro CTL activity against Hepa 1 - 6 cells was examined by standard (51)Cr release assay. Survival was studied of the immunized mice, with or without depletion of CD8+ or CD4+ T cells, inoculated with Hepa 1 - 6 mouse hepatoma cells.</p><p><b>RESULTS</b>The lytic activity of CTL elicited by the Ad hAFP-infected DCs were much stronger than that by Ad mAFP-infected DCs. 80% of the Ad hAFP/DCs-immunized mice of the inoculated with 5 x 10(6) Hepa 1 - 6 hepatoma cells were still alive two months after inoculation. However, the Ad mAFP/DCs-immunized mice inoculated with 1 x 10(6) Hepa 1 - 6 cells were just 20% surviving two months later. Depletion of CD8+ or CD4+ T cells abolished such an antigen-specific immunity elicited by the DCs infected with Ad hAFP.</p><p><b>CONCLUSION</b>Adenovirus vector-mediated xenogeneic AFP-infected DCs can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce strong antigen-specific T cell response, which are dependent on CD8+ and CD4+ T cells.</p>