The advance anticancer role of polymeric core-shell ZnO nanoparticles containing oxaliplatin in colorectal cancer

We evaluated the activity of core-shell ZnO nanoparticles (ZnO-NPs@polymer shell) containing Oxaliplatin via polymerization through in vitro studies and in vivo mouse models of colorectal cancer. ZnO NPs were synthesized in situ when the polymerization step was completed by co-precipitation. Gadolinium coordinated-ZnONPs@polymer shell (ZnO-Gd NPs@polymer shell) was synthesized by exploiting Gd's oxophilicity (III). The biophysical properties of the NPs were studied using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy, Ultraviolet-visible spectroscopy (UV-Vis), field emission electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy, dynamic light scattering, and z-potential. (3-(4,5-Dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) (MTT) was used to determine the antiproliferative activity of ZnO-Gd-OXA. Moreover, a xenograft mouse model of colon cancer was exerted to survey its antitumor activity and effect on tumor growth. In the following, the model was also evaluated by histological staining (H-E; Hematoxylin & Eosin and trichrome staining) and gene expression analyses through the application of RT-PCR/ELISA, which included biochemical evaluation (MDA, thiols, SOD, CAT). The formation of ZnO NPs, which contained a crystallite size of 16.8 nm, was confirmed by the outcomes of the PXRD analysis. The Plate-like morphology and presence of Pt were obtained in EDX outcomes. TEM analysis displayed the attained ZnO NPs in a spherical shape and a diameter of 33 ± 8.5 nm, while the hydrodynamic sizes indicated that the particles were highly aggregated. The biological results demonstrated that ZnO-Gd-OXA inhibited tumor growth by inducing reactive oxygen species and inhibiting fibrosis, warranting further research on this novel colorectal cancer treatment agent.     

Knowledge-based computational mutagenesis for predicting the disease potential of human non-synonymous single nucleotide polymorphisms

Certain genetic variations in the human population are associated with heritable diseases, and single nucleotide polymorphisms (SNPs) represent the most common form of such differences in DNA sequence. In particular, substantial interest exists in determining whether a non-synonymous SNP (nsSNP), leading to a single residue replacement in the translated protein product, is neutral or disease-related. The nature of protein structure-function relationships suggests that nsSNP effects, either benign or leading to aberrant protein function possibly associated with disease, are dependent on relative structural changes introduced upon mutation. In this study, we characterize a representative sampling of 1790 documented neutral and disease-related human nsSNPs mapped to 243 diverse human protein structures, by quantifying environmental perturbations in the associated proteins with the use of a computational mutagenesis methodology that relies on a four-body, knowledge-based, statistical contact potential. These structural change data are used as attributes to generate a vector representation for each nsSNP, in combination with additional features reflecting sequence and structure of the corresponding protein. A trained model based on the random forest supervised classification algorithm achieves 76% cross-validation accuracy. Our classifier performs at least as well as other methods that use significantly larger datasets of nsSNPs for model training, and the novelty of our attributes differentiates the model as an orthogonal approach that can be utilized in conjunction with other techniques. A dedicated server for obtaining predictions, as well as supporting datasets and documentation, is available at http://proteins.gmu.edu/automute.     

Papaver bracteatum,potential commercial source of codeine

Papaver bracteatum, native to Iran and southern Russia, has been grown successfully in many countries. Research in the northwest United States has confirmed the potential for its commercial production as a source of the alkaloid thebaine. Potential for the chemical conversion of thebaine into codeine, one of man’s most widely used alkaloidal medicinal agents, is reviewed. Economic and social advantages of growing this species over opium poppy (Papaver somniferum) are discussed. The value of the seed oil for cooking and industrial use is considered.     

Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances

The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.     

Immunogenicity and protective efficacy of recombinant M2e.Hsp70c(Hsp70_(359–610)) fusion protein against influenza virus infection in mice

New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.     

Metal-doped graphene layers composed with boron nitride–graphene as an insulator: a nano-capacitor

A new family of energetic azacubane N-oxides were designed by introducing N-oxides into azacubanes and investigated by using density functional theory. Introducing the N-oxides into the azacubanes could improve their detonation performance significantly due to the increase of the OB and ρ but would also increase the sensitivity to some extent. These effects would be further enhanced as the numbers of N-oxides increase. Among all the designed azacubane N-oxides, D6-4 (1,3,5,7-tetraazacubane-1,3,5,7-tetraoxides) has higher detonation performance than one famous high explosive HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) and lower sensitivity than one very insensitive explosive TNT (1-methyl-2,4,6-trinitrobenzene), suggesting that its overall performance is outstanding and may be considered as the potential candidate of insensitive high explosives. The internal small cage C-N skeleton of D6-4 is surrounded by the external big cage hydrogen bonds and this special double cage structure may be an important reason why it has low sensitivity.