Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities

<div><p>Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.</p></div

Speech Timing Deficit of Stuttering: Evidence from Contingent Negative Variations

<div><p>The aim of the present study was to investigate the speech preparation processes of adults who stutter (AWS). Fifteen AWS and fifteen adults with fluent speech (AFS) participated in the experiment. The event-related potentials (ERPs) were recorded in a foreperiod paradigm. The warning signal (S1) was a color square, and the following imperative stimulus (S2) was either a white square (the Go signal that required participants to name the color of S1) or a white dot (the NoGo signal that prevents participants from speaking). Three differences were found between AWS and AFS. First, the mean amplitude of the ERP component parietal positivity elicited by S1 (S1-P3) was smaller in AWS than in AFS, which implies that AWS may have deficits in investing working memory on phonological programming. Second, the topographic shift from the early phase to the late phase of contingent negative variation occurred earlier for AWS than for AFS, thus suggesting that the motor preparation process is promoted in AWS. Third, the NoGo effect in the ERP component parietal positivity elicited by S2 (S2-P3) was larger for AFS than for AWS, indicating that AWS have difficulties in inhibiting a planned speech response. These results provide a full picture of the speech preparation and response inhibition processes of AWS. The relationship among these three findings is discussed. However, as stuttering was not manipulated in this study, it is still unclear whether the effects are the causes or the results of stuttering. Further studies are suggested to explore the relationship between stuttering and the effects found in the present study.</p></div

Phase Behavior of a Hydrogen-Bonded Polymer with Lamella-to-Cylinder Transition: Complex of Poly(4-vinylpyridine) and Small Dendritic Benzoic Acid Derivative

Phase behavior of a supramolecular system based on poly­(4-vinylpyridine) (P4VP) and 3,4,5-tris­(dodecyloxy)­benzoic acid (TDBA) [P4VP­(TDBA)_<i>x</i>, where <i>x</i> is the molar ratio of TDBA to P4VP repeating unit] was investigated by means of FTIR, differential scanning calorimetry, polarized optical microscopy, and X-ray scattering method. The intermolecular hydrogen-bonding interaction between P4VP and TDBA is confirmed by FTIR. While almost all of the added TDBA molecules are hydrogen bonded to the P4VP chains at <i>x</i> < ∼0.60, the hydrogen-bonding interaction becomes incomplete at <i>x</i> > 0.60 and saturates at <i>x</i> > 0.90. The phase structure of P4VP­(TDBA)_<i>x</i> is composition dependent. At <i>x</i> < ∼0.30, the complex is homogeneous. With ∼0.30 < <i>x</i> < ∼0.60, P4VP­(TDBA)_<i>x</i> forms a lamella phase, of which the long period is proportional to 1/<i>x</i>. Further adding TDBA causes a lamella-to-cylinder transition. At <i>x</i> > ∼0.60, the lattice parameter of the cylinder or hexagonal columnar (Φ_H) phase decreases with increasing <i>x</i>. Considering the microphase separation between the polar part and the nonpolar part of alkyl tails, the lamella-to-cylinder transition can be understood using a volumetric argument. We consider that the large nonpolar part of TDBA enhances the microphase separation of P4VP­(TDBA)_<i>x</i>, and moreover, the fan-like shape of TDBA facilitates the formation of Φ_H phase. We also roughly estimated the domain size of the P4VP chains in the microphase-separated mesophase. For both the lamellar and Φ_H phase, increasing <i>x</i> results in stronger confinement on the P4VP chains. During the lamella-to-cylinder transition the confinement imposed by the TDBA molecules may be partially released, which favors the Φ_H phase formation

Peak amplitudes for AWS and AFS.

<p>The mean peak amplitudes and the standard deviations of S2-N2 and S2-P3 elicited by the Go and the NoGo signals are shown for AWS and AFS.</p

The mean slope values and standard deviations at the nine electrodes for AFS and AWS.

<p>The mean slope values and standard deviations at the nine electrodes for AFS and AWS.</p

Peak amplitudes for AWS and AFS.

<p>The mean peak amplitudes and the standard deviations of S1-N2 and S1-P3 elicited by S1 are shown for AWS and AFS.</p

Flumethrin transmits an inhibitory (punishing) component in PER conditioning.

<p>The figure shows the conditioned responses in the second phase of the experiment. Age/+ continued to receive sucrose as a reward, Age/− received no sucrose reward anymore (extinction), and Age+Flu/− received Age then followed by Flu, without sucrose reward. Number of animals in each group (n = 90).</p

The Sagittal main effects and the <i>Sagittal</i> × <i>Group</i> interactions for each CNV interval.

<p>The Sagittal main effects and the <i>Sagittal</i> × <i>Group</i> interactions for each CNV interval.</p

The S2-evoked ERPs.

<p>The mean amplitudes of ERPs at different electrodes are presented for AWS (red solid line) and AFS (black solid line) under the Go condition and for AWS (red dashed line) and AFS (black dashed line) under the NoGo condition. The mean RTs (speech onset time) are indicated in vertical dashed lines. An example of S2-N2 is shown at Fz, and an example of S2-P3 is shown at Pz.</p

Topographic shifts of the CNV.

<p>The top panel presents the scalp voltage distribution of AFS and AWS, and the lower panel displays the mean amplitudes of ERPs at the FZ (blue line), the FCZ (red line) and the CZ (green line).</p