The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes, and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine, and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133+ cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer.
Acquiring a whole mouse brain at the micrometer scale is a complex, continuous and time-consuming process. Because of defects caused by sample preparation and microscopy, the acquired image data sets suffer from various macroscopic density artefacts that worsen the image quality. We have to develop the available preprocessing methods to improve image quality by removing the artefacts that effect cell segmentation, vascular tracing and visualization. In this study, a set of automatic artefact removal methods is proposed for images obtained by tissue staining and optical microscopy. These methods significantly improve the complicated images that contain various structures, including cells and blood vessels. The whole mouse brain data set with Nissl staining was tested, and the intensity of the processed images was uniformly distributed throughout different brain areas. Furthermore, the processed image data set with its uniform brightness and high quality is now a fundamental atlas for image analysis, including cell segmentation, vascular tracing and visualization.
Long non-coding RNAs are associated with a spectrum of biological processes such as gene regulation on transcriptional and post-transcriptional levels. Increasing evidence indicates that SPRY4-IT1 plays an important role in carcinogenesis, and the mechanisms whereby SPRY4-IT1 induces colorectal carcinoma progression remain largely unknown. The aim of this study is to evaluate the expression and function of SPRY4-IT1 in colorectal carcinoma. In this study, we analyzed SPRY4-IT1 expression levels in a series of colorectal carcinoma patients by quantitative reverse transcription polymerase chain reaction. Knockdown of SPRY4-IT1 by RNA interference was performed to explore its roles in cell proliferation, migration, and invasion. Our results found that SPRY4-IT1 was upregulated in human primary colorectal carcinoma tissues. Knockdown of SPRY4-IT1 inhibited colorectal carcinoma cell proliferation, migration, and invasion. Moreover, we confirmed that the expression of epithelial-mesenchymal transition-related genes was modulated through alteration of SPRY4-IT1 expression. SPRY4-IT1 could negatively regulate the expression of miR-101-3p in colorectal carcinoma cells. The bioinformatics prediction revealed putative miR-101-3p binding sites within SPRY4-IT1 transcripts. Above all, knockdown of SPRY4-IT1 could represent a rational therapeutic strategy for colorectal carcinoma.
Psychological disturbances, including anxiety and depression, are common during human pregnancy. Our objective was to determine whether these maternal disturbances influence cardiovascular responses of the offspring. The psychological status of 231 pregnant women was determined. Offspring (216) of these women were subsequently exposed to a video challenge stress when aged 7-9 years. Heart rate (HR) and blood pressure (BP) of the children were determined at rest, in response to video stress and during subsequent recovery. Children's resting and stress-induced increases in HR (bpm), systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) BP were all greater in children whose mothers reported anxiety during pregnancy. Values (mean±s.d.) for resting HR, SBP and DBP were 75.15±5.87, 95.37±2.72 and 66.39±4.74 for children whose mothers reported no anxiety and an average of 81.62±6.71, 97.26±2.90 and 68.86±2.82 for children whose mothers reported anxiety at any level. Respective values for stress-induced increments in HR, SBP and DBP were 14.83.±2.14, 16.41±1.97 and 12.72±2.69 for children whose mothers reported no anxiety and 17.95±3.46, 18.74±2.46 and 14.86±2.02 for children whose mothers reported any level of anxiety. Effects of maternal depression were less consistent. The effects of maternal anxiety remained in multivariate analyses, which also included children's birth weight. The results indicate a long-term influence of maternal psychological status during pregnancy on the cardiovascular responses to stress among offspring. These effects may contribute to prenatal influences on subsequent health of the offspring.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.