The aim of our study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC) and to investigate miRNA profiles in regard to clinicopathological characteristics. Tissue and plasma samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were downregulated in EEC plasma samples. Endometrial cancer is the fourth most often diagnosed malignancy in the female population of the developed countries and the most common cancer of the female reproductive tract. In 2008, 82,530 endometrial cancer cases were recorded in Europe.1 Estimated number of new cases diagnosed in 2011 in the United States was 46,470 and was higher than in 2010.2 Data deposited in the Polish Cancer Registry indicated a progressive increase in endometrial cancer incidence over the period between 1999 and 2008.3 Similar trend has been observed in Great Britain. 4 Endometrial cancer is a heterogeneous malignancy comprising many histological types, which differ significantly in terms of pathogenesis, clinical presentation and prognosis. Such heterogeneity impedes development of screening and treatment strategies. Despite a great improvement in endometrial cancer treatment and diagnosis, advanced stages of the disease are still difficult to manage with the 5-year survival rate of $10-29%.5 Increase in the incidence of endometrial cancer and the lack of powerful yet nontoxic treatment strategies indicate the need of developing novel diagnostic, prognostic and treatment strategies for this malignancy.

Amyloid precursor protein cleavage through β- and γ-secretases produces β-amyloid peptide, which is believed to be responsible for death of neurons and dementia in Alzheimer’s disease. Levels of β- and γ-secretase are increased in sensitive areas of the Alzheimer’s disease brain, but the mechanism of this process is unknown. In this review, we prove that brain ischemia generates expression and activity of both β- and γ-secretases. These secretases are induced in association with oxidative stress following brain ischemia. Data suggest that ischemia promotes overproduction and aggregation of β-amyloid peptide in brain, which is toxic for ischemic neuronal cells. In our review, we demonstrated the role of brain ischemia as a molecular link between the β- and the γ-secretase activities and provided a molecular explanation of the possible neuropathogenesis of sporadic Alzheimer’s disease.

BackgroundAlterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility.MethodsWe investigated expression of mTOR kinase transcripts in 46 fresh tissue samples. Expression of miR-99a, miR-100 and miR-199b was investigated in the same group of fresh samples, and in additional 58 FFPE sections as well as in 48 plasma samples using qPCR. Relative quantification was performed using experimentally validated endogenous controls.ResultsmTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. Down-regulation of the investigated miRNAs was discovered in plasma of EEC patients and miRNA signatures classified EEC tissues (miR-99a/miR-100/miR-199b) and plasma (miR-99a/miR-199b) samples with higher accuracy in comparison to single miRNAs. We also revealed that miR-100 was an independent prognostic marker of overall survival.ConclusionsWe conclude that increased expression of mTOR kinase coexists with down-regulation of its targeting miRNAs, which could suggest a new mechanism of mTOR pathway alterations in EEC. In addition, our findings implicate that miRNA signatures can be considered promising biomarkers for early detection and prognosis of endometrioid endometrial carcinoma.

The study of sporadic Alzheimer's disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer's disease, the basis of this entity is not yet clear. At present, the bestestablished and accepted "culprit" in Alzheimer's disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may lead to pathological accumulation of amyloid in brain according to the "amyloid hypothesis." We will critically review these observations and highlight inconsistencies between the predictions of the "amyloid hypothesis" and the published data. There is still controversy over the role of amyloid in the pathological process. A question arises whether amyloid is responsible for the neurodegeneration or if it accumulates because of the neurodegeneration. Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer's disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia. Nowadays, a handful

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Trace elements play a crucial role in many biochemical processes, mainly as components of vitamins and enzymes. Although small amounts of metal ions have protective properties, excess metal levels result in oxidative injury, which is why metal ion homeostasis is crucial for the proper functioning of the brain. The changes of their level in the brain have been proven to be a risk factor for Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis. Therefore, it is currently an important application of various analytical methods. This review covers the most important of them: inductively coupled ground mass spectrometry (ICP-MS), flame-induced atomic absorption spectrometry (FAAS), electrothermal atomic absorption spectrometry (GFAAS), optical emission spectrometry with excitation in inductively coupled plasma (ICP-OES), X-ray fluorescence spectrometry (XRF), and neutron activation analysis (NAA). Additionally, we present a summary of concentration values found by different research groups.

In conclusion, we suggest that average expression of those snoRNAs could be used as a reliable endogenous control in microRNA qPCR studies in endometrioid endometrial cancer. In addition to identifying suitable endogenous controls in EEC, our study presents an appropriate strategy for validation of candidate reference genes for any microRNA qPCR study.