Bariatric surgery is the most effective therapy of severe human obesity. It is associated with improvements in metabolic and non metabolic co-morbidities which are thought to be mediated by a decrease of adipose tissue inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. We analyzed expression profiles in subcutaneous adipose tissue from 22 obese women before and 3 months after surgery using the RNA-seq technology. Of 15,972 detected genes, 1214 were differentially expressed after surgery. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, we identified 26 modules of coexpressed genes. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue, including a general signature of innate immune cells, an adaptive immune response elicited by T lymphocytes, a neutrophil-mediated inflammatory signature and an interferon-signaling pathway, respectively. After surgery, a few crucial molecules involved in chemotaxis and activation of immune cells were disconnected from their respective networks. These molecules may represent therapeutic targets against adipose inflammation. Overall design: mRNA sequencing of subcutaneous adipose tissue (SAT) samples from 22 obese women before and 3 months after bariatric surgery
Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study.
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View SamplesObesity is a major risk factor for metabolic disorders like insulin resistance and diabetes. We previously identified GPS2 as a clinical relavant repressor of metaflammation. No animal KO models were used to study its physiological function in vivo. The role of GPS2 in macrophage activation and inflammation is also largely unknown.
Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
Sex
View SamplesIxodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
Early immunologic events at the tick-host interface.
Specimen part, Time
View SamplesTo determine whether the intestine-restricted transcription factor (TF) CDX2 functionally interacts with the endoderm-wide TF HNF4A, we crossed tissue-specific conditional Cdx2 and Hnf4a knockout mice to generate compound mutant mice. We used RNA-sequencing to profile gene expression changes in compound mutant mice compared to control mice. The compound mutant mice had a significantly worse phenotype than either single mutant, and gene expression was significantly perturbed in compound mutants compared to control mice. Overall design: Total RNA isolated from control and compound mutant (Hnf4a-del;Cdx2-del) jejunal mouse intestinal epithelium was prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75-base-pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype.
Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.
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View SamplesPURPOSE: Previous mouse studies using corn oil (-6) as the dietary fat source suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. However, other studies, in which the diet was composed around saturated fat, showed no difference in outcomes between high-fat and low-fat diets. The relative effects of other fats, such as fish oil and olive oil, also remain unexplored. To our knowledge, no trial has yet compared the effect of various fats on prostate cancer progression. Therefore, we sought to systematically study the effect of fish oil, olive oil, corn oil, and saturated fat on prostate cancer progression. METHODS: A total of 96 male SCID mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were singly-housed and randomized to either a fish oil, olive oil, corn oil, or saturated fat based diet. Animals were euthanized when tumors reached 1,000 mm3. Serum was collected at sacrifice and assayed for PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Tumors were also assayed for PGE-2, and COX-2 levels, and gene array analysis was performed. RESULTS: Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish-oil consumption was associated with improved survival, relative to all other dietary groups (Log-rank, all p<0.05). We did not detect any significant difference in serum PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Glucose at the time of sacrifice was statistically different between groups, with the fish-oil fed mice having the highest levels of serum glucose (Kruskal-Wallis, p=0.03).
Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression.
Specimen part
View SamplesCD133-positive colorectal cancer cells exhibit enhanced tumorigenicity over CD133-negative cells. The CD133+ cells are more interactive with and responsive to their stromal microenvironment because they also express the cognate receptors, such as CXCR4, for ligands produced by their neighboring carcinoma-associated fibroblasts, such as SDF-1 (stromal-derived growth factor).
CD133+ colon cancer cells are more interactive with the tumor microenvironment than CD133- cells.
Specimen part, Disease, Disease stage
View Samples-myosin heavy chain promoter controlled MerCreMer expression enables conditional, cardiomyocyte specific and tamoxifen dependent gene inactivation of floxed genes. Administration of tamoxifen has been linked to development of acute and transient cardiomyopathy. The mechanism for this is unknown.
Cre-loxP DNA recombination is possible with only minimal unspecific transcriptional changes and without cardiomyopathy in Tg(alphaMHC-MerCreMer) mice.
Sex, Specimen part, Time
View SamplesGATA6 is a transcription factor involved in the differentiation of intestinal epithelial cells into differentiated absorptive epithelial cells.
GATA factors regulate proliferation, differentiation, and gene expression in small intestine of mature mice.
Specimen part, Treatment
View SamplesH929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours.
The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway.
Specimen part, Cell line, Treatment
View SamplesCardiomyopathy in type 1 diabetic patients is characterized by early onset diastolic and late onset systolic dysfunction. The mechanism underlying development of diastolic and systolic dysfunction in diabetes remains unknown.
Activation of a novel long-chain free fatty acid generation and export system in mitochondria of diabetic rat hearts.
Age
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