This study aimed to investigate the effects of oral administration of lactic acid bacteria (LAB) on gene expression in murine ileum.
The distinct effects of orally administered Lactobacillus rhamnosus GG and Lactococcus lactis subsp. lactis C59 on gene expression in the murine small intestine.
Specimen part
View SamplesThis study aimed to investigate the effects of oral administration of lactic acid bacteria (LAB) on gene expression in murine ileum.
The distinct effects of orally administered Lactobacillus rhamnosus GG and Lactococcus lactis subsp. lactis C59 on gene expression in the murine small intestine.
Sex, Age, Specimen part, Treatment
View SamplesChronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice.
Sex, Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective -secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC.
The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models.
Specimen part
View SamplesTumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC). Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC. Overall design: Expression of mRNA in a ccRCC cell line OS-RC-2 under the knockdown of Arkadia or ESRP2. Knock-down of ESRP2 was confirmed by RT-PCR because of low expression of ESRP2 which resulted in non-quantitative FPKM value.
The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
No sample metadata fields
View SamplesWe evaluated the role of Arkadia and ESRP2 in HEK293T cells Overall design: Expression of mRNA in HEK293T cells under the knockdown of Arkadia or ESRP2
The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
No sample metadata fields
View SamplesAnalysis of synchronized HCT116 cells at various time points up to 10 hours following treatment with DMSO or Nocodazole.
A signature-based method for indexing cell cycle phase distribution from microarray profiles.
Cell line, Treatment
View SamplesThe aim of this study is to investigate the gene expression profiles during masculinization of neonatal female mice brain by exogenous androgen treatment.
Gene expression profile of the neonatal female mouse brain after administration of testosterone propionate.
Sex, Specimen part, Treatment
View SamplesMAP kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses. In Caenorhabditis elegans, the KGB-1 JNK signaling pathway regulates the response to heavy metal stress. The deletion mutants of this cascade show hypersensitivity to heavy metals like copper or cadmium. However, factors that function downstream of KGB-1 pathway are not well characterized.
The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex.
Age
View SamplesInduced pluripotent stem cells (iPSCs) are a promising source for cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminegic (DA) neurons progressively degenerate. However, long-term analysis of human iPSC-derived DA neurons in primate PD models has never been performed. Here we show that DA progenitor cells derived from iPSCs of both healthy individuals and PD patients survived well in the brains of PD model primates and improved animal behavior. Magnetic resonance and positron emission tomography were useful to monitor the survival and function of the DA neurons. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature DA neurons extended dense neurites into the host striatum. In addition, we never observed tumor formation for two years. Thus, this preclinical study using primate models indicates that human iPSC-derived DA progenitors are clinically applicable to treat PD patients.
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.
Specimen part
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