Klotho inhibits growth and promotes apoptosis in human lung cancer cell line A549

<p>Abstract</p> <p>Background</p> <p>Klotho, as a new anti-aging gene, can shed into circulation and act as a multi-functional humoral factor that influences multiple biological processes. Recently, published studies suggest that klotho can also serve as a potential tumor suppressor. The aim of this study is to investigate the effects and possible mechanisms of action of klotho in human lung cancer cell line A549.</p> <p>Methods</p> <p>In this study, plasmids encoding klotho or klotho specific shRNAs were constructed to overexpress or knockdown klotho in vitro. A549 cells were respectively treated with pCMV6-MYC-KL or klotho specific shRNAs. The MTT assay was used to evaluate the cytotoxic effects of klotho and flow cytometry was utilized to observe and detect the apoptosis of A549 cells induced by klotho. The activation of IGF-1/insulin signal pathways in A549 cells treated by pCMV6-MYC-KL or shRNAs were evaluated by western blotting. The expression levels of bcl-2 and bax transcripts were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).</p> <p>Results</p> <p>Overexpression of klotho reduced the proliferation of lung cancer A549 cells, whereas klotho silencing in A549 cells enhanced proliferation. Klotho did not show any effects on HEK-293 cells. Klotho overexpression in A549 cells was associated with reduced IGF-1/insulin-induced phosphorylation of IGF-1R (IGF-1 receptor)/IR (insulin receptor) (<it>P </it>< 0.01). Overexpression of klotho can promote the apoptosis of A549 cells (<it>P </it>< 0.01). Overexpression of klotho, a bcl family gene bax, was found up-regulated and bcl-2, an anti-apoptosis gene, was found down-regulated (<it>P </it>< 0.01). In contrast, bax and bcl-2 were found down-regulated (<it>P </it>< 0.05) and up-regulated (<it>P </it>< 0.01), respectively when silencing klotho using shRNAs.</p> <p>Conclusions</p> <p>Klotho can inhibit proliferation and increase apoptosis of A549 cells, this may be partly due to the inhibition of IGF-1/insulin pathways and involving regulating the expression of the apoptosis-related genes bax/bcl-2. Thus, klotho can serve as a potential tumor suppressor in A549 cells.</p

A computational model for functional mapping of genes that regulate intra-cellular circadian rhythms

BACKGROUND: Genes that control circadian rhythms in organisms have been recognized, but have been difficult to detect because circadian behavior comprises periodically dynamic traits and is sensitive to environmental changes. METHOD: We present a statistical model for mapping and characterizing specific genes or quantitative trait loci (QTL) that affect variations in rhythmic responses. This model integrates a system of differential equations into the framework for functional mapping, allowing hypotheses about the interplay between genetic actions and periodic rhythms to be tested. A simulation approach based on sustained circadian oscillations of the clock proteins and their mRNAs has been designed to test the statistical properties of the model. CONCLUSION: The model has significant implications for probing the molecular genetic mechanism of rhythmic oscillations through the detection of the clock QTL throughout the genome

Finding the spectral radius of a nonnegative irreducible symmetric tensor via DC programming

The Perron-Frobenius theorem says that the spectral radius of an irreducible nonnegative tensor is the unique positive eigenvalue corresponding to a positive eigenvector. With this in mind, the purpose of this paper is to find the spectral radius and its corresponding positive eigenvector of an irreducible nonnegative symmetric tensor. By transferring the eigenvalue problem into an equivalent problem of minimizing a concave function on a closed convex set, which is typically a DC (difference of convex functions) programming, we derive a simpler and cheaper iterative method. The proposed method is well-defined. Furthermore, we show that both sequences of the eigenvalue estimates and the eigenvector evaluations generated by the method $Q$-linearly converge to the spectral radius and its corresponding eigenvector, respectively. To accelerate the method, we introduce a line search technique. The improved method retains the same convergence property as the original version. Preliminary numerical results show that the improved method performs quite well

High-efficiency Algorithm for the Most Unfavourable Load Case Combinations of Multilayered Frame-Type Wharf Structure

The wharf, which was built in the Three Gorges Reservoir of China, is constructed as a layered frame-type structure for adapting to large water level fluctuations that exceed 30 m. These large fluctuations cause the frame-type structure to exhibit a considerably higher number of load case combinations than traditional marine high-piled wharfs. To estimate the most adverse combined internal force and the corresponding unfavourable load case combinations of significant components for multilayered frame-type wharf structures in the Three Gorges Reservoir of China, a high-efficiency algorithm is developed in this study. This algorithm can skilfully transform the computational mode of load case combinations into a matrix operations process by computer programming. By applying the proposed algorithm, the number of load case combinations for eight significant components of frame-type wharf, including piles, columns, beams, braces and berthing components, are resolved to a total of 21 from the original quantity of more than six billion. This high-efficiency algorithm can provide powerful technical support for evaluating the bearing capability of multilayered frame-type wharfs in the Three Gorges Reservoir of China

Etiologic subtype predicts outcome in mild stroke: prospective data from a hospital stroke registry

BACKGROUND: Few studies on whether etiologic subtype can predict outcome in mild stroke are available. The study aim to explore the effect of different etiologic subtype on prognosis of these patients. METHODS: We prospectively registered consecutive cases of acute ischemic stroke from September. 01, 2009 to August. 31, 2011. Patients with National Institute of Health Stroke Scale (NIHSS) ≦3 and within 30 days of symptom onset were included. All cause death or disability (defined as modified Rankin Scale >2) were followed up at 3 months. The multivariate logistical regression model was used to analyse relationship between etiologic subtype and clinical outcomes. RESULTS: We included 680 cases, which accounted for 41.1% (680/1655) of the total registered cases. Mean age were 62.54 ± 13.51 years, and males were 65.4%. The median time of symptoms onset to admission was 72 hours. 3.8% (26/680) of cases admitted within 3 hours and 4.7% (32/680) admitted within 4.5 hours. However, no patient received intravenous thrombolysis. Of included patients, 21.5% large-artery atherosclerosis, 40.6% small-vessel disease, 7.5% cardioembolisms, 2.2% other causes and 28.2% undetermined causes. The rate of case fatality and death/disability was 2.2% and 10.1% respectively at 3 months. After adjustment of potential confounders, such as age, sex, NIHSS on admission and vascular risk factors et al., cardioembolism (RR = 3.395;95%CI 1.257 ~ 9.170) was the predictor of death or disability at 3 months and small vessel occlusion (RR = 0.412;95%CI 0.202 ~ 0.842) was the protective factor of death or disability at 3 months. CONCLUSION: Different etiologic subtype can predict the outcome in patients with mild stroke and it can help to stratify these patients for individual decision-making

IGF-I and IGFBP-3 and the risk of lung cancer: A meta-analysis based on nested case-control studies

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the leading cause of death from cancer worldwide. Conventional studies mainly think that insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may promote and inhibit tumor growth, respectively. However, there are many different results about their function in some recent epidemiological studies. To evaluate the relationship between circulating serum levels of IGF-I, IGFBP-3 and lung cancer, a systematic review and meta-analysis of the published data was performed.</p> <p>Methods</p> <p>Literatures searched on PubMed and Embase databases were enrolled in the Meta-analysis. The Meta-analysis of all eligible studies was applied with Stata 10.0 software, and the pooled odds ratio(OR) and weighted mean difference (WMD) value were obtained. The Q test, Egger's test and Begg's funnel plot were used to evaluate the heterogeneity and publication bias between the studies.</p> <p>Results</p> <p>There are no statistically significant heterogeneity and publication bias between the studies. For IGF- I, the pooled OR and WMD were 0.87(95%CI: 0.60~1.13,) and -3.04(95%CI: -7.10~1.02, P = 0.14), respectively. For IGFBP-3, the pooled OR and WMD were 0.68(95%CI: 0.48~0.88,) and -112.28(95%CI: -165.88~-58.68, P < 0.0001), respectively.</p> <p>Conclusion</p> <p>The association between circulating IGF- I levels and the risk of lung cancer were not statistically significant; IGFBP-3, acts as a tumor suppressor and has a inverse correlation with the risk of lung cancer.</p

Effect of Maize (Zea mays L.) Plant-Type on Yield and Photosynthetic Characters of Sweet Potato (Ipomoea balatas L.) in Intercropping System

Sweet potato/maize relay-cropping mode is considered as the main farming practices of dry land in Southwest China. Although relay-cropping would cause the reduction of fresh tuber yield, it still remained unclear that the reason was shade resulted from maize or genotype of sweet potato. The present work aims at exploring the effects of maize (Zea mays L.) plant-type on photosynthetic physiology and yield of sweet potato (Ipomoea balatas L.) in relay-cropping system. Besides, three plant-types maize cultivars including compact, semi-compact and expanded type were used for relay-cropping with different sweet potato cultivars (‘Yushu-2’, ‘Yushu-6’ and ‘Nanshu-88’) in field. The results showed that the photosynthetically active radiation (PAR) was declined with the increase of expansion of maize plant-type, which decreased by 77.5%, 80.1% and 82.1% respectively. When relay-cropped with extended maize, the yield reduction rate of sweet potato was the highest (67%). The shade-resistance of different genotype of sweet potatoes was different, and the yield reduction rate of ‘Yushu-2’ was the lowest (37.01%). Through conducting correlations analysis, it showed that fresh tuber yield had significant positive correlation with Effective Quantum Yield (Y(II)) and significant negative correlation with Non Photochemical Quenching Coefficient (NPQ). In terms of ‘Yushu-2’, the proportion of heat dissipation was the lowest, and its light quantum efficiency was higher than others. As a result, its reduction rate of yield was lower than the other two. We suggested that compact maize cultivar relay-cropping with strong shade-resistance sweet potato cultivar should be mainly applied in practice of sweet potato