Suppression of osteopontin inhibits chemically induced hepatic carcinogenesis by induction of apoptosis in mice

Previous clinical reports have found elevated osteopontin (OPN) levels in tumor tissues to be indicative of greater malignancy in human hepatocellular carcinoma (HCC). However, the role of OPN on carcinogenesis and its underlying mechanism remain unclear. In the present study, we investigated the oncogenic role of OPN in diethylnitrosamine (DEN)-induced hepatic carcinogenesis in mice. The overall incidence of hepatic tumors at 36 weeks was significantly lower in OPN knockout (KO) mice than in wild-type (WT) mice. Apoptosis was significantly enhanced in OPN KO mice, and was accompanied by the downregulation of epidermal growth factor receptor (EGFR). In the in vitro study, OPN suppression also led to lower mRNA and protein levels of EGFR associated with the downregulation of c-Jun in Hep3B and Huh7 human HCC cells lines, which resulted in increased apoptotic cell death in both cell lines. Moreover, a positive correlation was clearly identified between the expression of OPN and EGFR in human HCC tissues. These data demonstrate that the OPN deficiency reduced the incidence of chemically induced HCC by suppressing EGFR-mediated antiapoptotic signaling. An important implication of our findings is that OPN positively contributes to hepatic carcinogenesis.OAIID:RECH_ACHV_DSTSH_NO:T201614207RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:F001304CITE_RATE:5.008DEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM:

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Reduction of Electricity Prices Using the Train to Grid (T2G) System in Urban Railway

Smart transportation technologies are being rapidly developed for enhancing the smart grid establishment. Such technologies are mostly focused on electric vehicles. However, the electric railroad has advantages in various aspects such as facility construction and utilization over an electric vehicle. Therefore, in this paper, we introduce the train-to-grid system using the electric railroads for the smart grid, and propose a reduction method for the electricity prices. The proposed method obtains actual data from the currently operating railroad systems. Furthermore, the number of trains for charging and discharging batteries is decided by using the time-of-use price and the number of railroad operations. The electricity prices are then determined by the energy consumption calculated using the number of trains used for charging and discharging and the capacity of the energy storage system in the trains. The proposed method is simulated using real data, and its superiority is verified by comparing its electric prices with the conventional electricity prices

Aberrant Development of Functional Connectivity among Resting State-Related Functional Networks in Medication-Naïve ADHD Children

<div><p>Objective</p><p>The aim of this study was to investigate the compromised developmental trajectory of the functional connectivity among resting-state-related functional networks (RSFNs) in medication-naïve children with attention-deficit/hyperactivity disorder (ADHD).</p><p>Subjects and Methods</p><p>Using both independent component analysis and dual regression, subject-specific time courses of 12 RSFNs were extracted from both 20 medication-naïve children with ADHD, and 20 age and gender-matched control children showing typical development (TDC). Both partial correlation coefficients among the 12 RSFNs and a resting-state resource allocation index (rsRAI) of the salience network (SN) were entered into multiple linear regression analysis to investigate the compromised, age-related change in medication-naïve ADHD children. Finally, correlation analyses were performed between the compromised RSFN connections showing significant group-by-age interaction and rsRAI of SN or clinical variables.</p><p>Results</p><p>Medication-naïve ADHD subjects failed to show age-related increment of functional connectivity in both rsRAI of SN and two RSFN connections, SN-Sensory/motor and posterior default mode/precuneus network (pDMN/prec) – anterior DMN. Lower SN-Sensory/motor connectivity was related with higher scores on the ADHD Rating Scale, and with poor scores on the continuous performance test. The pDMN/prec-aDMN connectivity was positively related with rsRAI of SN.</p><p>Conclusions</p><p>Our results suggest that medication-naïve ADHD subjects may have delayed maturation of the two functional connections, SN-Sensory/Motor and aDMN-pDMN/prec. Interventions that enhance the functional connectivity of these two connections may merit attention as potential therapeutic or preventive options in both ADHD and TDC.</p></div

Summary of the result of regression analysis of resource allocation index in resting state (rsRAIs) showing a significant group-by-age interaction.

<p>SE: standard error, CI: confidence interval estimated with bootstrapping (type = BCa: bias-corrected, accelerated confidence intervals <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083516#pone.0083516-Efron1" target="_blank">[54]</a>);</p><p>Bonferroni corrected P<0.0125; rFP-SN-pDMN/prec: Regression: F = 3.14, df = 5, p = 0.02; Residual: df = 34, SE = 0.38; Multiple R-squared: 0.31, Adjusted R-squared: 0.21; lFP-SN-pDMN/prec: Regression: F = 4.76, df = 5, p = 0.002; Residual: df = 34, SE = 0.37; Multiple R-squared: 0.41, Adjusted R-squared: 0.33.</p

Twelve spatially independent resting-state-related functional networks (RSFNs).

<p>From left-upper to right-lower part: RSFN1: Frontal; RSFN2: Sensory/motor; RSFN3: Salience (SN, Ventral attentional); RSFN4: Right central executive (rCEN); RSFN5: Left central executive network (lCEN); RSFN6: Dorsal attentional (dAtt); RSFN7: V1; RSFN8: V1/V2; RSFN9: Extrastriate; RSFN10: a temporooccipital part of posterior DMN (pDMN/TO); RSFN11: a precuneus part of Posterior default mode (pDMN/prec); RSFN12: Anterior default mode (aDMN). Radiologic orientation (left is right). MNI coordinates of RSFNs were presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083516#pone.0083516.s003" target="_blank">Table S1</a>.</p