A Genetic Variant in miR-196a2 Increased Digestive System Cancer Risks: A Meta-Analysis of 15 Case-Control Studies

<div><h3>Background</h3><p>MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies.</p> <h3>Methodology/Principal Findings</h3><p>An updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07–1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13–1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10–1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01–1.30; C vs. T, OR = 1.15, 95% CI = 1.05–1.26). We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC) (CT vs. TT, OR = 1.23, 95% CI = 1.04–1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08–1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07–1.46; C vs. T, OR = 1.15, 95% CI = 1.05–1.28), while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98–1.38) showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC) was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed.</p> <h3>Conclusion/Significance</h3><p>Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.</p> </div

A Lightweight Privacy-Preserving Fair Meeting Location Determination Scheme

Equipped with mobile devices, people relied on location-based services can expediently and reasonably organize their activities. But location information may disclose people\u27s sensitive information, such as interests, health status. Besides, the limited resources of mobile devices restrict the further development of location-based services. In this paper, aiming at the fair meeting position determination service, we design a lightweight privacy-preserving solution. In our scheme, mobile users only need to submit service requests. A cloud server and a location services provider are responsible for service response, where the cloud server achieves most of the calculation, and the location services provider determines the fair meeting location based on the computational results of the cloud server and broadcasts it to mobile users. The proposed scheme adopts homomorphic encryptions and random permutation methods to preserve the location privacy of mobile users. The security analyses show that the proposed scheme is privacy-preserving under our defined threat models. Besides, the presented solution only needs to calculate n Euclidean distances, and hence, our scheme has linear computation and communication complexity

Cost-effective secure e-health cloud system using identity based cryptographic techniques

Nowadays E-health cloud systems are more and more widely employed. However the security of these systems needs more consideration for the sensitive health information of patients. Some protocols on how to secure the e-health cloud system have been proposed, but many of them use the traditional PKI infrastructure to implement cryptographic mechanisms, which is cumbersome for they require every user having and remembering its own public/private keys. Identity based encryption (View the MathML sourceIBE) is a cryptographic primitive which uses the identity information of the user (e.g., email address) as the public key. Hence the public key is implicitly authenticated and the certificate management is simplified. Proxy re-encryption is another cryptographic primitive which aims at transforming a ciphertext under the delegator AA into another ciphertext which can be decrypted by the delegatee BB. In this paper, we describe several identity related cryptographic techniques for securing E-health system, which include new View the MathML sourceIBE schemes, new identity based proxy re-encryption (View the MathML sourceIBPRE) schemes. We also prove these schemes’ security and give the performance analysis, the results show our View the MathML sourceIBPRE scheme is especially highly efficient for re-encryption, which can be used to achieve cost-effective cloud usage.Peer ReviewedPostprint (author's final draft

Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy

Mengen Zhang1,2, Rui Guo2, Yin Wang2, Xueyan Cao2, Mingwu Shen2, Xiangyang Shi1-31State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People&amp;rsquo;s Republic of China; 3Centro de Qu&amp;iacute;mica da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, PortugalBackground: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics.Methods: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors.Results: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 &amp;micro;g/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors.Conclusion: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.Keywords: PAMAM dendrimers, combretastatin A4, inclusion complexes, targeted cancer therap

Dendrimer-entrapped gold nanoparticles as potential CT contrast agents for blood pool imaging

The purpose of this study was to evaluate dendrimer-entrapped gold nanoparticles [Au DENPs] as a molecular imaging [MI] probe for computed tomography [CT]. Au DENPs were prepared by complexing AuCl4- ions with amine-terminated generation 5 poly(amidoamine) [G5.NH2] dendrimers. Resulting particles were sized using transmission electron microscopy. Serial dilutions (0.001 to 0.1 M) of either Au DENPs or iohexol were scanned by CT in vitro. Based on these results, Au DENPs were injected into mice, either subcutaneously (10 μL, 0.007 to 0.02 M) or intravenously (300 μL, 0.2 M), after which the mice were imaged by micro-CT or a standard mammography unit. Au DENPs prepared using G5.NH2 dendrimers as templates are quite uniform and have a size range of 2 to 4 nm. At Au concentrations above 0.01 M, the CT value of Au DENPs was higher than that of iohexol. A 10-μL subcutaneous dose of Au DENPs with [Au] ≥ 0.009 M could be detected by micro-CT. The vascular system could be imaged 5 and 20 min after injection of Au DENPs into the tail vein, and the urinary system could be imaged after 60 min. At comparable time points, the vascular system could not be imaged using iohexol, and the urinary system was imaged only indistinctly. Findings from this study suggested that Au DENPs prepared using G5.NH2 dendrimers as templates have good X-ray attenuation and a substantial circulation time. As their abundant surface amine groups have the ability to bind to a range of biological molecules, Au DENPs have the potential to be a useful MI probe for CT

Risk Evaluation of Debris Flow Hazard Based on Asymmetric Connection Cloud Model

Risk assessment of debris flow is a complex problem involving various uncertainty factors. Herein, a novel asymmetric cloud model coupled with connection number was described here to take into account the fuzziness and conversion situation of classification boundary and interval nature of evaluation indicators for risk assessment of debris flow hazard. In the model, according to the classification standard, the interval lengths of each indicator were first specified to determine the digital characteristic of connection cloud at different levels. Then the asymmetric connection clouds in finite intervals were simulated to analyze the certainty degree of measured indicator to each evaluation standard. Next, the integrated certainty degree to each grade was calculated with corresponding indicator weight, and the risk grade of debris flow was determined by the maximum integrated certainty degree. Finally, a case study and comparison with other methods were conducted to confirm the reliability and validity of the proposed model. The result shows that this model overcomes the defect of the conventional cloud model and also converts the infinite interval of indicators distribution into finite interval, which makes the evaluation result more reasonable