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Infant botulism is caused by ingesting Clostridium botulinum spores and characterized by symmetric descending paralysis, which can progress to respiratory failure in severe cases (1). Specific therapies include intravenous administration [...]

Objective: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. Methods: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation profiling of gene promoters to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen MM8 CpG plus Promoter Microarray. We further integrated epigenomics data with gene expression profiling to identify promoters exhibiting an association between methylation status and the expression of downstream genes. Results: A total of 24 hypermethylated promoters and 42 hypomethylated promoters in epididymal fat were selected as methylation markers, which were associated with downregulated and upregulated gene expression, respectively. The promoter methylation and differential gene expression of three markers (Mmp2, Foxj3 and Ube2q2) in the fat were validated by sequencing bisulfite-modified DNA and real-time reverse transcriptase PCR. The genes with these differentially methylated promoters and the associated transcriptional expression in the fat were primarily involved in biological activities in lipid metabolism and storage, cellular differentiation, immunity and the pathogenesis of obesity-related complications. Conclusions: This study represents the first effort to determine methylation markers in obese mice that may regulate gene transcription in obesity. Our approach has potential relevance for clinical applications by identifying markers useful in elucidating the mechanisms of obesity pathogenesis and its complications.

Abstract Background The expression of leptin is increased in obesity and inhibited by n-3 polyunsaturated fatty acids (n-3 PUFAs), but the underlying molecular mechanisms have not been firmly established. Methods In this study, we investigated the effects of dietary n-3 PUFAs on the methylation of CpG islands in the promoter regions of the leptin, leptin-R and POMC genes, as well as the effects of n-3 PUFA status in early life on the modification of the promoters of these three genes. Male C57 BL/6J mice were fed a high-fat diet with one of four different fat types: sunflower oil (n-3 PUFA deficient), soy oil, fish oil, or a mixture of soy and fish oil (soy:fish oil = 1:1). Two low-fat diets with sunflower oil or soy oil served as controls. Female mice were fed two breeding diets, sunflower oil or a mixture of soy and fish oil (soy:fish oil = 1:1), during pregnancy and lactation to breed new pups. Results Compared to mice fed the control diets, the expression of leptin in fat tissue and leptin-R and POMC in the hypothalamus was higher in the diet-induced obesity (DIO) mice, and the n-3 PUFAs in the diets reversed these elevated expression levels. The mean methylation levels of CpG sites in the promoter regions of the leptin and POMC genes showed no difference between the DIO and the control diet groups nor between the n-3 PUFA-containing and -deficient diet groups. For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups. Feeding mice with the n-3 PUFA diet during pregnancy and lactation did not affect CpG methylation in the leptin or POMC promoters. Conclusions Our findings indicate that promoter DNA methylation may not be related to the expression of leptin, leptin-R or its related hypothalamic satiety regulator POMC.

Pediatric acute respiratory distress syndrome (PARDS) is a relatively common critical illness in the pediatric intensive care unit with an incidence of about 3%. It has a high mortality rate; although this number has decreased in the last de-cades, it is still as high as 18%; in some developing countries, it even reached 40%-50% in the last 2-3 years. Optimized mechanical ventilation strategy contributes to an improved prognosis. To this end, this article reviews the current status of research on mechanical ventilation strategies in PARDS.