Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.

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Cyclin B1, a key component in the control of cell cycle progression from G(2) to M phase, has been implicated in tumorigenesis and the development of malignancy. However, the underlying mechanism by which cyclin B1 acts as an important oncogenic molecule remains largely unknown. Here we show that ectopic expression of cyclin B1 promotes cell proliferation, enhances cell motility and migration and results in increased ability of cells extravasating through the capillary endothelium. Interestingly, isogenic esophageal squamous cell carcinoma (ESCC) cells overexpressing cyclin B1 reveal strong invasive growth and high potential of metastasis to lung in xenograft mice. Suppression of cyclin B1 expression via small interfering RNA approach in high-metastatic esophagus carcinoma cells specifically inhibits their ability to metastasize from the primary ESCC to lung. Notably, altered expression of epithelial markers and mesenchymal markers were observed in the cells overexpressing cyclin B1, suggesting that cyclin B1 contributes to metastasis probably by promoting an epithelial-mesenchymal transition. These results establish a mechanistic link between cyclin B1 and ESCC metastasis and provide novel insight into understanding of cyclin B1 in the development of ESCC malignancy.

Introduction Aberrant microenvironment and endoplasmic reticulum (ER) stress are associated with solid-tumor progression. Stress proteins, like heat shock proteins and glucose-regulated proteins, are frequently overexpressed in human tumors. It has been reported that derlin-1 is involved in ER stress response. In vitro studies have demonstrated that derlin-1 participates in the retrotranslocation of misfolded proteins from ER into the cytosol. Because the roles of derlin-1 in human cancer have not yet been characterized, we investigated the expression of derlin-1 in human breast carcinoma and whether it protected cancer cells against ER stress-induced apoptosis.

This study suggested that LL-37 may play important role in the pathogenesis of COPD and may be a possible novel therapeutic target in COPD.

Purpose: This study aimed to identify novel biological markers for the prediction of colorectal cancer liver metastasis. Experimental Design: We established two models that mimicked the interactions between colorectal tumor cells and the liver microenvironment. From these models we established subcell lines that had an enhanced ability to metastasize to the liver. Genes that related to hepatic metastasis were screened by microarray. The candidate markers were tested by immunohistochemistry, and their predictive accuracy was assessed by the cross-validation method and an independent test set. Results: Highly metastatic colon cancer cell sublines SW1116p21 and SW1116v3 were established from the tumor cell-microenvironment interaction models. Seven of the upregulated genes in the sublines were selected as candidate markers for predicting metastatic potential. A total of 245 colorectal cancer samples were divided into a training set containing 117 cases and a test set containing 128 cases. In the training set, immunohistochemical analysis showed CCL2 and SNCG expression was higher in the hepatic metastasis group than in the nonmetastasis group, and was correlated with poor survival. Logistic regression analysis revealed that CCL2 and SNCG levels in primary tumors, serum carcinoembryonic antigen level, and lymph node metastasis status were the only significant (P < 0.05) parameters for detecting liver metastasis. In leave-one-out-cross-validation, the two markers, when combined with clinicopathologic features, resulted in 90.5% sensitivity and 90.7% specificity for hepatic metastasis detection. In an independent test set, the combination achieved 87.5% sensitivity and 82% specificity for predicting the future hepatic metastasis of colorectal cancer. Conclusion: Our results suggest that these models are able to mimic the interactions between colorectal cancer cells and the liver microenvironment, and may represent a promising strategy to identify metastasis-related genes. CCL2 and SNCG, combined with clinicopathologic features, may be used as accurate predictors of liver metastasis in colorectal cancer. (Clin Cancer Res 2009;15(17):5485-93) Colorectal carcinoma is one of the major causes of cancer death worldwide (1). Liver is the most common target for metastasis in patients with this disease. It is estimated that approximately 50% of colorectal cancer patients develop liver metastases, with 15% to 25% of synchronous and 20% of heterochronous cases (2). Liver metastasis is the most critical prognostic factor for colorectal cancer. The 5-year overall survival rate of patients with hepatic metastasis is only 25% to 40%

Oxidative stress is one of the main causes of myocardial injury, which is associated with cardiomyocyte death. Mitochondria play a key role in triggering the necrosis and apoptosis pathway of cardiomyocytes under oxidative stress. Although prohibitin (PHB) has been acknowledged as a mitochondrial chaperone, its functions in cardiomyocytes are poorly characterized. The present research was designed to investigate the cardioprotective role of PHB in mitochondria. Oxidative stress can increase the PHB content in mitochondria in a time-dependent manner. Overexpression of PHB in cultured cardiomyocytes by transfection of recombinant adenovirus vector containing PHB sense cDNA resulted in an increase of PHB in mitochondria. Compared with the non-transfection cardiomyocytes, PHB overexpression could protect the mitochondria from oxidative stress-induced injury. The mitochondria-mediated apoptosis pathway was consistently suppressed in PHB-overexpressed cardiomyocytes after hydrogen peroxide (H(2)O(2)) treatment, including a reduced change in mitochondrial membrane permeability transition and an inhibited release of cytochrome c from mitochondria to cytoplasma. As a result, the oxidative stress-induced cardiomyocyte apoptosis was suppressed. These data indicated that PHB protected the cardiomyocytes from oxidative stress-induced damage, and that increasing PHB content in mitochondria constituted a new therapeutic target for myocardium injury.

X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism. © 2016 International Parkinson and Movement Disorder Society.