Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma

<p>Abstract</p> <p>Background</p> <p>Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells.</p> <p>Methods</p> <p>By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay.</p> <p>Results</p> <p>The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro) than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects.</p> <p>Conclusion</p> <p>The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.</p

A mixed finite element for interlaminar stress computation

A mixed finite element method (MFEM) aiming at solving the problem of three-dimensional stress analysis of multi-layer composite laminates with a high accuracy is presented. The approach, which is based on the global-local laminate variational model, proposes a mixed use of a hibrid stress element within a high precision stress solution region in the thickness direction of the laminate and a conventional displacement finite element in the remaining. This results in a reduction of the overall computation time while maintaining the solution precision in the area(s) of interest, normally being certain interface(s) within a laminate. A formulation of a 49 stress parameter hybrid stress element in conjunction with a 42 degree of freedom iso-parametric displacement element is given. The quality of the hybrid stress element is assured by a stiffness matrix eigenvalue analysis. Example computations of laminate cylindrical bending and the classical free-edge problem have shown the feasibility of the MFEM approach and the convergence of the specific 49[beta]-42q formulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30305/1/0000707.pd

Intraply crack and delamination interaction in laminate beams under transverse loading

Intraply cracking and delamination are the basic modes of damage in composite laminates and their interaction constitutes an important phase in damage development. Such an interaction is investigated in the present work through a two-dimensional finite element analysis of a three-point bending beam model. This configuration is considered to embody the basic characteristics of lowenergy transverse impact of composite laminates, where damage is a major concern. Interleaves are incorporated in the model to evaluate their role in the damage process. The stacking sequence used is [0/A/90/A/0] (`A' denotes an interleaf), and an intraply crack at 45[deg] to the loading line is assumed in the central 90[deg] ply. The damage process is simulated by specifying the delamination growth at the tips of the intraply crack along the beam axis direction. Stress fields and the strain energy release rates are evaluated at different stages of the delamination growth.The results show that before any delamination takes place, there is a significant transverse normal stress concentration at the tips of the intraply crack. Consequently, there is a strong involvement of mode I component of fracture at this stage. However, with the growth of the delamination, a rapid transition occurs in which the transverse normal stress and its corresponding mode I delamination driving force decrease dramatically relative to their shear counterparts. The entire damage process is therefore summarized as primarily a mode II delamination fracture dominated event preceded by a very limited period of mode I driven fracture at the initiation of the delamination by the intraply crack. The results also indicate that soft interleaves do not alleviate the fracture driving forces at the delamination front. It follows that the interleaf technology relies almost entirely on the toughness of the interleaves.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31914/1/0000867.pd

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective. The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods. Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results. The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion. We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future

Classification of Traditional Chinese Medicine Syndromes in Patients with Chronic Hepatitis B by SELDI-Based ProteinChip Analysis

Traditional Chinese medicine (TCM) syndrome, also called ZHENG, is the basis concept of TCM theory. It plays an important role in TCM practice. There are excess and deficiency syndromes in TCM syndrome. They are the common syndromes in chronic hepatitis B (CHB) patients. Here we aim to explore serum protein profiles and potential biomarkers for classification of TCM syndromes in CHB patients. 24 healthy controls and two cohorts of CHB patients of excess syndrome (n = 25) or deficiency syndrome (n = 19) were involved in this study. Protein profiles were obtained by surface-enhanced laser desorption ionization time-flight mass spectrometry (SELDI-TOF/MS) and multiple analyses were performed. Based on SELDI ProteinChip data, healthy controls and CHB patients or excess and deficiency syndromes in CHB patients were obviously differentiated by orthogonal partial least square (OPLS) analysis. Two significant serum proteins (m/z 4187 and m/z 5032) for classifying excess and deficiency syndromes were found. Moreover, the area under the receiver operating characteristic (ROC) curve was 0.887 for classifying excess and nonexcess syndrome, and 0.700 for classifying deficiency and nondeficiency syndrome, respectively. Therefore, the present study provided the possibility of TCM syndrome classification in CHB patients using a universally acceptable scientific approach

Detecting P2P Botnet in Software Defined Networks

Software Defined Network separates the control plane from network equipment and has great advantage in network management as compared with traditional approaches. With this paradigm, the security issues persist to exist and could become even worse because of the flexibility on handling the packets. In this paper we propose an effective framework by integrating SDN and machine learning to detect and categorize P2P network traffics. This work provides experimental evidence showing that our approach can automatically analyze network traffic and flexibly change flow entries in OpenFlow switches through the SDN controller. This can effectively help the network administrators manage related security problems

Serum cytokine profiling analysis for zheng differentiation in chronic hepatitis B

Approval document of the research protocol by the Medical Ethics Committee of Shuguang Hospital

Divergent and Stereoselective Synthesis of β-Silyl-α-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C−H Bonds

A general and practical Pd^(II)-catalyzed intermolecular silylation of primary and secondary C−H bonds of α-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β-silyl-α-amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late-stage functionalization of biological small molecules, such as (−)-santonin and β-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this β−C(sp^3)-H silylation process