Myocardial infarction (MI) is one of the leading causes of death worldwide and Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is dependent on the age of the donor, yet the underlying mechanism has not been thoroughly investigated. This study was designed to investigate whether this impaired therapeutic potency is caused by an increased susceptivity of MSCs from old donors to reactive oxygen species (ROS). The MSCs were isolated from the subcutaneous inguinal region of young (8–10 weeks) and old (18 months) Sprague–Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of MSCs from old donors was damaged more severely. Specifically, decreased expression of integrin and reduced phosphorylation of focal adhesion kinase Src and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs from old donors. To study the viability and therapeutic potency of MSCs from young and old donors in vivo, these MSCs were transplanted into acute MI model rats. We observed a more rapidly decreased survival rate of the old MSCs in the infarct region, which may be caused by their increased susceptivity to the micro-environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart. Our study may help to understand the mechanism of MSCs-host interaction during MI, as well as shed light on the design of therapeutic strategy in clinic. 相似文献
The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex. 相似文献
ObjectiveTo estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China.MethodsThe Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed.ResultsThe model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust.ConclusionDapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM. 相似文献
Recombinant chimeric α-amylase (AmyP-Cr) was constructed by a catalytic core of α-amylase (AmyP) from a marine metagenomic library and a starch-binding domain (SBDCr) of α-amylase from Cryptococcus sp. S-2. The molecular fusion did not alter optimum pH, optimum temperature, hydrolysis products, and an ability of preferential and rapid degradation towards raw rice starch, but catalytic efficiency and thermostability were remarkably improved compared with those of the wild-type AmyP. AmyP-Cr achieved the final hydrolysis degree of 61.7 ± 1.2% for 10% raw rice starch and 47.3 ± 0.8% for 15% raw rice starch after 4 h at 40 °C with 1.0 U per mg of raw starch. The catalytic efficiency was very high, with 3.6–4.0 times higher than that of AmyP. The enhanced catalytic efficiency was attributed to the better thermostability and the higher adsorption and disruption to raw rice starch caused by SBDCr. The properties of AmyP-Cr open a new way in terms of a new design of raw rice starch processing.
The chromosome number of thirteen species of Tamarix L. in China is reported in this paper. All of them have the same number (2n=24) and most of them
are reported for the first time except T. hispida, whose chromosome number is the same
as previously reported. 相似文献