Curcumin is a potent anti-inflammatory compound capable of preventing chemically induced colitis in mice.
Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent.
Treatment
View SamplesNa+/H+ exchanger 3 (NHE3) provides a major route for intestinal Na+ absorption. It has been considered as a target of proinflammatory cytokines and enteropathogenic bacteria and impaired NHE3 expression and/or activity may be responsible for inflammation-associated diarrhea.
Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis.
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View SamplesHepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata
Effects of Boswellia serrata in mouse models of chemically induced colitis.
No sample metadata fields
View SamplesThe two immune cell populations Myeloid-derived suppressor cells (MDSCs), monocytes (MONO) and neutrophils (PMNs) are difficult to differentiate because of shared surface marker expression. Here we utilize the integrin receptor CD11b combined with conventional Ly6G and Ly6C expression to more accurately separate cellular populations via FACS. Then we apply high-throughput RNA Sequencing to Ly6G+Ly6C+CD11bhigh MDSC, Ly6G+Ly6C+CD11blow PMN and Ly6G-Ly6C+ monocyte populations. A total of 6,466 genes were significantly differentially expressed in MDSCs vs. monocytes, whereas only 297 genes were significantly different between MDSCs and PMNs. A number of genes implicated in cell cycle regulation were identified, and in vivo EdU labeling revealed that over 75% of MDSCs proliferated locally at the site of S. aureus biofilm infection. Overall design: RNA-Seq of myeloid-derived suppressor cells (MDSCs), neutrophils (PMNs), and monocytes during S. aureus biofilm infection in mice
Heterogeneity of Ly6G<sup>+</sup> Ly6C<sup>+</sup> Myeloid-Derived Suppressor Cell Infiltrates during Staphylococcus aureus Biofilm Infection.
Specimen part, Cell line, Subject
View SamplesS. aureus biofilms are associated with the organism's ability to cause disease. Biofilm associated bacteria must cope with the host's innate immune system.
Global transcriptome analysis of Staphylococcus aureus biofilms in response to innate immune cells.
No sample metadata fields
View SamplesGene expression profile of cancer cell lines of breast, lung, pancreatic, gasctric, ovarian, hepatocellular, prostate carcinomas and melanomas.
Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations.
No sample metadata fields
View SamplesIn order to understand differentially regulated gene expression after the different treatments, 4 size matched tumors of each group were analyzed by microarrays.
Regulation of myeloid cells by activated T cells determines the efficacy of PD-1 blockade.
Specimen part
View SamplesNeuronal migration disorders such as lissencephaly and subcortical band heterotopia (SBH) are associated with epilepsy and intellectual disability. Doublecortin (DCX), LIS1 and alpha1-tubulin (TUBA1A), are mutated in these disorders, however corresponding mouse mutants do not show heterotopic neurons in the neocortex. On the other hand, the spontaneously arisen HeCo mouse mutant displays this phenotype. The study of this model reveals novel mechanisms of heterotopia formation. While, HeCo neurons migrate at the same speed as WT, abnormally distributed dividing progenitors were found throughout the cortical wall from E13. Through genetic studies we identified Eml1 as the mutant gene in HeCo mice. No full length transcripts of Eml1 were identified due to a retrotransposon insertion in an intron. Re-expression of Eml1, coding for a microtubule-associated protein, rescues the HeCo progenitor phenotype. We further show that EML1 is mutated in giant ribbon-like heterotopia in human. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human.
Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.
Specimen part
View SamplesNOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease. Overall design: RNA-Seq analysis
Common nonmutational <i>NOTCH1</i> activation in chronic lymphocytic leukemia.
Specimen part, Subject
View SamplesTreatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor post-infusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK cell functions following cytokine withdrawal to model post-infusion performance. In contrasts to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided functional advantages. Genome-wide analysis of cytosolic and polysome-associated mRNA revealed cytokine dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced functional advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15 stimulated NK cells was also observed using a clinically applicable protocol for NK cell expansion. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK cell cancer therapy. Overall design: Freshly isolated NK cells from 6 donors were activated with IL-2 or IL-15 for 48 hours, followed by cytokine withdrawal for 24 hours, resulting in four RNA samples per donor. From each sample, both the cytosolic as well as the polysomal fraction were collected. Donor 3 contains activation and post withdrawal data from two different donors due to poor RNA-quality obtained for some samples which did not allow for processing of the complete set of 6 donors (resulting in a total of 40 samples).
IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells.
No sample metadata fields
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