However, the presence of statistical differences between the two groups in both cerebral and peripheral vascular AbMole Ellipticine function reinforces our hypothesis that diabetes causes subclinical vascular complications also in the presence of optimal metabolic control and relatively short duration of the disease. This slight still significant alteration is likely to be due to initial endothelial dysfunction, and not to altered autonomic control of vessel smooth muscle cell tone. Endothelium independent vasodilation was not evaluated in the present study, due to our hospital policy. This measure could have helped us to more accurately assess vascular smooth muscle function. Another limitation of our study is the presence of a difference in the number of smokers between diabetic subjects and controls. However, this difference was not statistically significant, and, also after correcting for this variable, our results were confirmed. A further limitation of this study is that neuroimaging was not available for the majority of our subjects. Therefore, we can exclude only clinically relevant vascular episodes, while silent cerebrovascular events cannot be ruled out. In conclusion, the observation of impaired cerebral hemodynamics and systemic endothelial function 
in T2DM patients with well-controlled disease and preserved autonomic balance, but with clinical features of metabolic syndrome strongly suggests that factors other than chronic hyperglycemia play a role in vascular dysfunction even in the absence of marked metabolic derangement. The observation of an impaired cerebrovascular reactivity in patients with T2DM is of particular interest, since it could be responsible for the increased risk of stroke and silent cerebral ischemia observed in patients with diabetes mellitus. Long-term prospective studies should be performed in order to evaluate the clinical AbMole Corosolic-acid course of cerebrovascular impairment and endothelial dysfunction in the natural history of diabetic disease. Polycystic ovary syndrome is the most common cause of female infertility, affecting 5 to 10% of women during their reproductive age. It is characterized by ovarian hyperandrogenism, insulin resistance and dysregulation of paracine factors, all of which can perturb the intrafollicular environment. The ovary of individuals with PCOS experiences abnormal apoptotic activity and folliculogenesis, making it a clinical pathological model for studying oocyte maturation and development. Currently, the cause and pathophysiological mechanism of PCOS is unclear; however, evidence indicates there is an imbalance between pro-apoptotic and anti-apoptotic factors within the ovary. Heat shock protein 27, a member of the small heat shock protein family, is an apoptotic regulator which can inhibit apoptosis. As a molecular chaperone protein, Hsp27 is involved in cellular protection in response to a variety of stresses, such as heat shock, toxicants, injury, and oxidative stress. Emerging evidence indicates that Hsp27 has strong anti-apoptotic properties, mediated by a direct interaction with the caspase activation components in apoptotic pathways, consequently exerting protective effects in apoptosis-related injuries. For example, Hsp27 has been shown to protect cells against apoptosis by binding with cytochrome C, inhibiting the activation of Caspase 9 and blocking the extrinsic Fas- and TNF-mediated apoptotic pathways. Interestingly, we previously found that Hsp27 was mainly expressed in human oocytes, and was downregulated in ovarian tissue isolated from women with PCOS. We also found that downregulation of Hsp27 improves oocyte maturation in mice, while increasing early stage apoptosis in oocytes by inducing the activation of the extrinsic, caspase 8mediated, apoptotic pathway.