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Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly inhibited the cellular viability and colony growth of human HT-29 colorectal cancer cells. OMEO induced protective autophagy, associated with downregulation of the mTOR/p70S6K pathway, and activated caspase-8 and caspase-9-dependent apoptosis. Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death. Inversely, inhibition of apoptosis with the pan-caspase inhibitor, Z-VAD-FMK, significantly reduced cell death, suggesting that apoptosis represents the main mechanism of OMEO-induced cell death. Mechanistically, we found that OMEO induces protective autophagy and apoptotic cells death via the activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells. Strikingly, we found that OMEO also induces p38 MAPK-mediated caspase-dependent cleavage of p70S6K, a protein reported to be overexpressed in colon cancer and associated with drug resistance. Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage.Quantitative analysis of formaldehyde (HCHO, FA), especially at low levels, in various environmental media is of great importance for assessing related environmental and human health risks. A highly efficient and convenient FA detection method based on surface-enhanced Raman spectroscopy (SERS) technology has been developed. This SERS-based method employs a reusable and soft silver-coated TiO2 nanotube array (TNA) material, such as an SERS substrate, which can be used as both a sensing platform and a degradation platform. The Ag-coated TNA exhibits superior detection sensitivity with high reproducibility and stability compared with other SERS substrates. The detection of FA is achieved using the well-known redox reaction of FA with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (AHMT) at room temperature. The limit of detection (LOD) for FA is 1.21 × 10-7 M. In addition, the stable catalytic performance of the array allows the degradation and cleaning of the AHMT-FA products adsorbed on the array surface under ultraviolet irradiation, making this material recyclable. This SERS platform displays a real-time monitoring platform that combines the detection and degradation of FA.The number of oral cavity carcinoma (OCC) survivors continues to increase due to advances in definitive surgery and radiation therapy (RT), however the risk of ischemic stroke is unclear in long-term survivors. In this study, survivors are defined as those who survived for >5 years after a diagnosis of OCC. They were matched at a 15 ratio with normal controls. Those who received surgery alone versus surgery+RT were also matched at a 11 ratio. From 2000 to 2005, 5172 OCC survivors who received surgery alone (n = 3205) or surgery+RT (n = 1967), and 25,860 matched normal controls were analyzed using stratified Cox regression models. Adjusted HRs (aHR) revealed that the surgery+RT group (aHR = 1.68, p less then 0.001) had an elevated risk of stroke, but this was not seen in the surgery alone group (aHR = 0.99, p = 0.953). Furthermore, the age at stroke onset was at least 10 years earlier in the surgery+RT group than in the controls. In conclusion, radiotherapy increased the risk of ischemic stroke by 68% and also accelerated the onset of stroke in long-term OCC survivors after primary surgery compared with matched normal controls. Secondary prevention should include stroke as a late complication in OCC survivorship programs.In Sri Lanka, dengue is the most serious arboviral disease. Recent increases in dengue cases suggest a higher infection rate and spread of the disease to new areas. The present study explores gene flow patterns of Ae. https://www.selleckchem.com/products/nimbolide.html aegypti, the main vector of dengue disease, among 10 collection sites including major ports and inland cities using variations at 11 microsatellite loci. Discriminant analysis of principal components (DAPC) and k-means clustering estimated eight genetic clusters. Analysis of Molecular Variance (AMOVA) estimated equal variances among cities and among collections in Colombo, Sri Lanka. Significant evidence, although weak, was detected for isolation by distance. Analysis of gene flow rates and directions using MIGRATE-n indicated that populations throughout the island served as a source of immigrants for Colombo with abundant gene flow among major commercial cities in Sri Lanka, which appear to receive migrant mosquitoes from throughout Sri Lanka. The observed patterns probably arise through human movement of Ae. aegypti during commerce from throughout Sri Lanka into Colombo increasing the risk of spread. The patterns uncovered in this study are significant for global health as Sri Lanka is situated along a key international shipping route.Post-translational modifications are known to be widely involved in the regulation of various biological processes, through the extensive diversification of each protein function at the cellular network level. In order to unveil the system-wide function of the protein lysine modification in cancer cell signaling, we performed global acetylation and ubiquitination proteome analyses of human cancer cells, based on high-resolution nanoflow liquid chromatography-tandem mass spectrometry, in combination with the efficient biochemical enrichment of target modified peptides. Our large-scale proteomic analysis enabled us to identify more than 5000 kinds of ubiquitinated sites and 1600 kinds of acetylated sites, from representative human cancer cell lines, leading to the identification of approximately 900 novel lysine modification sites in total. Very interestingly, 236 lysine residues derived from 141 proteins were found to be modified with both ubiquitination and acetylation. As a consequence of the subsequent motif extraction analyses, glutamic acid (E) was found to be highly enriched at the position (-1) for the lysine acetylation sites, whereas the same amino acid was relatively dispersed along the neighboring residues of the lysine ubiquitination sites.
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