The Human Glioma-Associated Oncogene Homolog 1 (GLI1) Family of Transcription Factors in Gene Regulation and Diseases

Sonic hedgehog (Shh) signaling is critically important for embryogenesis and other cellular processes in which GLI transcription factors mediate the terminal effects of the pathway. GLI1, in particular, plays a significant role in human cancers. Consequently, GLI1 and its upstream positive regulator Smoothened (SMO) are important targets of anti-cancer therapy and several SMO-targeted small molecule inhibitors are being evaluated clinically. Emerging exciting evidence reveals a high level of complexity that lies within the GLI1-mediated pathway. For example, a recent study provided evidence linking the polymorphic GLI1 variants Q1100/E1100 to chronic inflammatory bowel diseases. Two recent reports uncovered the existence of two novel human GLI1 isoforms that differ structurally and functionally from the wild-type GLI1 identified over two decades ago. Interestingly, although both are products of alternative splicing, GLI1∆N and tGLI1 (truncated GLI1) isoforms are predominantly expressed in normal and malignant tissues, respectively. In addition to these important discoveries, gene expression profiling studies have identified a number of novel wild-type GLI1 and tGLI1 target genes, linking wild-type GLI1 to tumor progression and therapeutic resistance, and tGLI1 to tumor invasion and migration. In light of these new insights, this review will provide a comprehensive overview on GLI1 polymorphisms and the three members of the GLI1 family of proteins, and their impacts on human diseases, including, cancers

Optimization of Process Parameters for Molecular Distillation Based on NN and GA

AbstractIn order to obtain the optimum craft parameters and improve the product purity and yield,a new optimization design method based on NN and GA is proposed. The neural network is used to build the model of target function, namely, a mapping relationship from craft parameters to purity and yield is established. Taking many craft parameters(feed rate,vacuum, and temperature) as optimal variables, purity and yield as optimization target,the optimization model is build and advance optimizing quality and decrease the number of times of numerical simulation. In this article, the essential oil of schisandra chinensis was produced according to the technology of molecular distillation. The technological parameters were optimized. The process and result prove that this method is effective

The impact of stock market policy announcement on commodity prices and share prices

It has been an important issue to analyze the possible impact of macroeconomic effects, such as: exchange rate or interest rate, on the commodity prices since 1970s because of the tremendous volatility of commodity prices on the US. Thereafter, there are a lot of literature in agricultural economics relative to the empirical study. But the results of these literature are ambiguous. On the other hand, Blandchard (1981) incorporated the stock market into the traditional IS-LM model and discussed the interaction between stock market and economy. The financial sector plays an important role to affect the time path of commodity prices it cannot be ignored since agricultural industry is just one of sector among the whole economy. The main purpose of this article is to add the stock market into the two-goods economy. One is commodity product and the other is nonagricultural product. According the model including commodity market, nonagricultural product market, monetary market and stock market and under the assumptions of perfect substitutes between stock and bond and perfect foresight expectation, the effect of stock market policies, such as financing interest rate, financing ratio, on dynamics of commodity and share prices will be analyzed. The result shows that in the long run the impact of stock policies on commodity prices depends on the relative magnitudes of price effect of commodity and interest rate effect. While in the short run, whether share price overshooting or not it depends on the length of time between announcement and implement of policies.commodity prices, share prices, financing interest rate, financing ratio, dynamics

Ameliorative effect of Draba nemorosa extract on chronic heart failure in rats

Purpose: To evaluate the effect of Draba nemorosa extract (DNE) on oxidative stress and hemodynamics in rats with chronic congestive heart failure (CHF).Methods: Adriamycin was used to establish CHF in Sprague Dawley (SD) rat model. Six groups of SD rats were used in this study: control group, CHF group, captopril group (0.1 g/kg), as well as high-, medium- and low-dose DNE groups (5.2, 2.6 and 1.3 g/kg, respectively). Treatment for all groups lasted 4 weeks. Blood pressure and heart index were measured. In addition, serum creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) were determined with enzyme-linked immunosorbent assay (ELISA) kits.Results: In the CHF group, arterial systolic pressure (SBP, 84.22 ± 16.23 mmHg); diastolic pressure (DBP, 77.36 ± 20.29 mmHg); mean arterial pressure (MAP, 78.45 ± 10.56 mmHg); heart rate (HR, 357.18 ± 37.34 beats/min) and left ventricular systolic peak (LVSP, 102.34 ± 16.37 mmHg) were significantly decreased (p < 0.05) when compared with the control group. However, left ventricular end diastolic pressure (LVEDP, 23.38 ± 1.78 mmHg); heart index (2.74 ± 0.16 mg/g); serum CK (0.87 ± 0.15 U/mL); MDA (19.34 ± 2.57 nmol/mL), NO (38.43 ± 3.32 umol/L) and NOS (42.65 ± 3.32 U/mL) were increased. Treatment with high-dose DNE significantly ameliorated hemodynamic function, and reduced MDA (9.13 ± 2.12 nmol/mL) and NO (22.37 ± 3.16 umol/L) levels (p < 0.05). High-dose DNE also led to significant decreases in CK (0.53 ± 0.35 U/mL) and NOS (24.27 ± 3.55U/mL) in the CHF rats (p < 0.05).Conclusion: DNE significantly improves hemodynamic function in CHF rats. Thus, it has a potential for development into a new drug for clinical treatment of CHF.Keywords: Draba nemorosa, Adriamycin, Chronic heart failure, Hemodynamic function, Oxidative stres

EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: A potential mechanism of EGFR-driven antagonism of apoptosis

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) plays an essential role in normal development, tumorigenesis and malignant biology of human cancers, and is known to undergo intracellular trafficking to subcellular organelles. Although several studies have shown that EGFR translocates into the mitochondria in cancer cells, it remains unclear whether mitochondrially localized EGFR has an impact on the cells and whether EGFRvIII, a constitutively activated variant of EGFR, undergoes mitochondrial transport similar to EGFR.</p> <p>Results</p> <p>We report that both receptors translocate into the mitochondria of human glioblastoma and breast cancer cells, following treatments with the apoptosis inducers, staurosporine and anisomycin, and with an EGFR kinase inhibitor. Using mutant EGFR/EGFRvIII receptors engineered to undergo enriched intracellular trafficking into the mitochondria, we showed that glioblastoma cells expressing the mitochondrially enriched EGFRvIII were more resistant to staurosporine- and anisomycin-induced growth suppression and apoptosis and were highly resistant to EGFR kinase inhibitor-mediated growth inhibition.</p> <p>Conclusions</p> <p>These findings indicate that apoptosis inducers and EGFR-targeted inhibitors enhance mitochondrial translocalization of both EGFR and EGFRvIII and that mitochondrial accumulation of these receptors contributes to tumor drug resistance. The findings also provide evidence for a potential link between the mitochondrial EGFR pathway and apoptosis.</p