No abstract

In recent years, the role of PET imaging in the prediction of mild cognitive impairment (MCI) to Alzheimer's disease (AD) conversion has been the subject of many longitudinal studies. The purpose of this study was to perform a meta-analysis to estimate the diagnostic accuracy of (18) F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) and (11) C-Pittsburgh Compound B-positron emission tomography (PIB-PET) for prediction of short-term conversion to AD in patients with MCI. The MEDLINE and EMBASE databases were systematically searched for relevant studies. Methodological quality of the included studies was assessed. Sensitivities and specificities of PET in individual studies were calculated and meta-analysis was undertaken with a random-effects model. A summary receiver operating characteristic (SROC) curve was constructed with the Moses-Shapiro-Littenberg method. Heterogeneity was tested, and the presence of publication bias was assessed. Potential sources for heterogeneity were explored by assessing whether or not certain covariates significantly influenced the relative diagnostic odds ratio (DOR). Pooled estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), DOR and the SROC curve of each PET imaging were determined. A total of 13 research studies (seven FDG-PET and six PIB-PET) met inclusion criteria and had sufficient data for statistical analysis. FDG-PET pooled estimates had 78.7% sensitivity (95% CI, 68.7-86.6%),74.0% specificity (95% CI, 67.0-80.3%), 18.1 LR+(95% CI, 7.3-45.0) and 0.32 LR-(95% CI, 0.16-0.61); and PIB-PET pooled estimates had 93.5% sensitivity (95%CI, 71.3-99.9%), 56.2% specificity (95% CI, 47.2-64.8%), 2.01 LR+ (95% CI, 1.57-2.58) and 0.17 LR-(95% CI, 0.08-0.36). Overall DOR was 17.3 (95% CI, 5.08-59.2) for FDG-PET and 12.8 (95% CI, 5.35-30.54) for PIB-PET. Area under the SROC curve was 0.88 ± 0.05 for FDG-PET and 0.85 ± 0.04 for PIB-PET. The data from FDG-PET research studies had high heterogeneity and funnel plot suggested a publication bias. The diagnostic accuracy determined for both FDG-PET and PIB-PET in this meta-analysis suggests that they are potentially valuable techniques for prediction of progression in patients with MCI. Both have their advantages and their combined use is a promising option for prediction purposes depending on availability and experience.

Bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for cardiovascular disease. However, there is no evidence so far that BMSCs can heal pathological myocardial hypertrophy. In this study, BMSCs were indirectly cocultured with neonatal rat ventricular cardiomyocytes (NRVCs) in vitro or intramyocardially transplanted into hypertrophic hearts in vivo. The results showed that isoproterenol (ISO)-induced typical hypertrophic characteristics of cardiomyocytes were prevented by BMSCs in the coculture model in vitro and after BMSC transplantation in vivo. Furthermore, activation of the Ca 2+ /calcineurin/nuclear factor of activated T cells cytoplasmic 3 (NFATc3) hypertrophic pathway in NRVCs was abrogated in the presence of BMSCs both in vitro and in vivo. Interestingly, inhibition of vascular endothelial growth factor (VEGF) release from BMSCs, but not basic fibroblast growth factor and insulin-like growth factor 1, abolished the protective effects of BMSCs on cardiomyocyte hypertrophy. Consistently, VEGF administration attenuated ISO-induced enlargement of cellular size; the upregulation of atrial natriuretic peptide, brain natriuretic peptide, and b-myosin heavy chain expression; and the activation of Ca 2+

Background/Aims: Doxorubicin is a widely used chemotherapeutic agent, but its clinical use is restricted because of a high risk of cardiotoxicity. Bone marrow-derived mesenchymal stem cells (BMSCs) may repair ischaemically damaged myocardium through transdifferentiation and paracrine action. The aim of this study is to investigate if doxorubicin causes the apoptosis of BMSCs and in turn impairs its healing ability. Methods: BMSCs were exposed to doxorubicin, and cell apoptosis was determined by western blot and stainings. Results: Doxorubicin reduced the survival ratio and caused the apoptosis of BMSCs, with the increase of intracellular ROS level and depolarization of mitochondrial membrane potential. The ROS scavenger NAC abrogated these consequences. Moreover, doxorubicin markedly activated phosphorylated ERK, p38 and JNK proteins in BMSCs. The specific inhibitors for p38 (SB203580) and JNK (SP600125) may abolish doxorubicin-induced apoptosis of BMSCs but the specific ERK inhibitor (PD98059) not, indicating p38 and JNK activation contribute to BMSCs apoptosis. Also, the phosphorylated and total p53 proteins were increased in doxorubicin-treated BMSCs. Proapoptotic cleaved caspases-3 was upregulated and antiapoptotic Bcl-2 protein was reduced in doxorubicin-treated BMSCs. At last, ELISA assay showed that doxorubicin treatment reduced the VEGF and IGF-1 released by BMSCs. Conclusion: Taken together, doxorubicin caused BMSCs apoptosis associated with p38, JNK and p53 pathways.