Patients who cleared HCV viremia early during therapy tended to show favorable outcomes, whereas patients who needed a longer period to clear HCV had poorer outcomes. We explored the mechanisms of treatment resistance by comparing hepatic gene expression before and during treatment
Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C.
Specimen part, Time
View SamplesIL28B genotype was shown to be associated with treatment outcome of antiviral thearpy for HCV infection. We tried to clarify the molecular feature that was asocciated with IL2B genotype by comparing Hepatic gene expression of HCV related Hepatocellular carcinoma and non-cancerous tissue with Il28B rs8099917 TT genotype and TG/GG genotype.
Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C.
Specimen part
View SamplesThere is a gradient of -catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized -catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of -catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by -catenin activation exhibit activation of Notch signaling and the treatment of -catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.
Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium.
Sex, Specimen part
View SamplesBackground: The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT).
Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
Specimen part
View SamplesFK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Specimen part, Treatment
View SamplesThe liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secreted proteins, termed hepatokines.
A liver-derived secretory protein, selenoprotein P, causes insulin resistance.
Sex, Specimen part, Disease
View SamplesOct3/4, Sox2, Klf4, and c-Myc re-wire somatic cells to achieve induced pluripotency (iPS cells). However, subtle differences in reprogramming methodology may confound comparative studies of reprogramming-induced gene expression changes. We specifically focused on the design of polycistronic reprogramming constructs, which encode all four factors linked with 2A peptides. Notably, publically available cassettes were found to employ one of two Klf4 variants (Klf4S and Klf4L; GenBank Accession Nos: AAC52939.1 and AAC04892.1), differing only by nine N-terminal amino acids. In a polycistronic context, these two variants generated dissimilar protein stoichiometry, where Klf4L vectors produced more Klf4 protein than those encoding Klf4S.
KLF4 N-terminal variance modulates induced reprogramming to pluripotency.
Sex, Specimen part
View SamplesBoron is essential for plants, and boron availability in soil is an important determinant of agricultural production. Boron availability in soil is limited at many regions in the world, including Japan. Under boron deficient conditions, leaf expansion and root elongation, apical dominance, flower development,and fruit and seed sets are inhibited.
The Minimum Open Reading Frame, AUG-Stop, Induces Boron-Dependent Ribosome Stalling and mRNA Degradation.
Age, Specimen part, Treatment
View SamplesAberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33-15.34) and from LINE (OR=2.08; 95% CI=1.03-4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02-0.48) and H3K27me3 (OR=3.28; 95% CI=1.17-9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.
Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.
Cell line
View SamplesThe rate of cell differentiation is tightly controlled and critical for normal development and stem cell differentiation. However, so far it has been difficult to control the rate of ESCs differentiation. Here we report the acceleration of the differentiation rate due to the activation of protein kinase A (PKA) and the associated early loss of embryonic stem cells (ESCs) pluripotency markers and the early appearance of mesodermal and other germ layer cell markers.
Protein kinase A accelerates the rate of early stage differentiation of pluripotent stem cells.
Time
View Samples