Assessments the binding affinity of the corresponding ligands of tumor specific antigen of prostate cancer, opportunity for immunotoxin development

Prostate cancer is the third major cause of death in men worldwide after lung cancer, cardiovascular disease and is known in two decades. Since 1987, the first treatment for prostate cancer was initiated in the wake of the global health So far safer and effective methods to treat this life threatening condition is better. During the past two decades scientists to develop drugs targeted therapies in cancer research priorities were. These therapies primarily based on a specific antigen in tumor tissues will be deployed. Prostate cancer-specific antigens of the most valuable PSMA (Prostate specific membrane antigen) is. In this study, to evaluate the PSMA binding affinity ligands can be connected to evaluate and recommend the best ligand for use in targeted drugs .

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy

Purpose: Epithelial cell adhesion molecule (EpCAM) is a dominant antigen in human colon carcinoma tissue. Topology features of this antigen are different in normal and malignant conditions; for instance, EpCAM is much less accessible to antibodies in normal cells than in cancerous tissues. Hence, EpCAM has been considered as a suitable candidate for cancer target therapy via immunotoxins (ITs) development. In this study, attention was focused on the stability assessment of anti-EpCAM-IT (anti-Ep-IT) to design a novel IT. Methods: The 3D structures of the antibody template and the toxin segment of anti-Ep-IT were retrieved from PDB. Discovery Studio3.0 was used to separate the ligands and water molecules. The antibody (Ab) fragment of anti-Ep-IT was aligned using protein blast (BLAST-p), and SWISS-MODEL database was used for Ab modeling. IT modeling was accomplished using MODELLER 9.15. Also, GROMACS 5.07 was used for molecular dynamic (MD) simulation step. Moreover, ERRAT and RAMPAGE databases were used for quality assessment of the structures. Results: BLAST-p results indicated that antibody moiety of IT has the highest E-value and query coverage scores to the monoclonal antibody (mAb) 4D5MOC-B. Modeling by SWISS-MODEL provided a reasonable template for Ab portion compared to MODELLER. The best modeled full-length IT with the lowest RMSD values was selected. Finally, RMSD plot for MD stage demonstrated constant values from 7000ps to 20000ps. Conclusion: In general, both modeling results and their quality evaluations were satisfactory for designing IT. Moreover, RMSD plot revealed that IT stability was preserved during the simulation. Overall, our findings led to modeling and simulation of the anti-Ep-IT with more structural stability

A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis

Funding Information: This study was supported by grants from the Mashhad University of Medical Sciences (Grant Number 980955). The authors thank the management of advanced computational centre, Khayyam Innovation Ecosystem, Mashhad, Iran for providing the facilities and encouragement to carry out this research work.Peer reviewedPublisher PD

Bioinformatics Analysis of Upstream Region and Protein Structure of Fungal Phytase Gene

Phytase increases the bioavailability of phytate phosphorus in seed-based animal feeds and reduces the phosphorus pollution of animal waste. Since most animal feeds for pellets are heated up to 65-80 °C, the production of a thermostable structure for phytase can be useful. In this study, we sought to perform bioinformatics analysis of the upstream region and protein structure of fungal phytase to improve its expression and thermostability properties. We used bioinformatics methods such as similarity search, multiple alignment, statistical analysis of physicochemical properties of amino acids, pattern recognition, and protein modeling to find out the effective factors in heat resistance of phytase. Change in Gibbs free energy (ΔG) of the best pattern promoter resulting from the interaction between RNA polymerase and the promoter sequences of modified genes of phytase was equal to -9 kcalmol-1, which is lower compared to other interactions. The evaluation of the three-dimensional structure of new phytases showed that amino acid substitutions aimed at improving thermostability did not change the form and structure of the protein. The results of Prochek, Whatcheck, and ERRAT for structural analysis and verification were 84, 72, and 70, respectively, that were satisfactory

Resveratrol-Mediated Gold-Nanoceria Synthesis as Green Nanomedicine for Phytotherapy of Hepatocellular Carcinoma

In the present study, resveratrol was used to prepare complexes of cerium and nanoceria, also coated with gold (CeO2@Au core-shells) to improve the surface interactions in physiological conditions.The CeO2@Au core-shells were characterized using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy (FTIR), transmission electron microscope (TEM) analysis, dynamic light scattering (DLS) and ζ potential.The experiment was led to the successful synthesis of nanosized CeO2@Au core-shells, although agglomeration of particles caused the distribution of the larger particles. The TEM analysis demonstrated the particles sizes ranged from 20 nm to 170 nm. Moreover, the PXRD analysis showed that both nanoceria and gold with the same crystal systems and space groups. To investigate the anticancer activity of the CeO2@Au core-shells, the cytotoxicity of the nanoparticles was investigated against liver cancerous cell lines (HepG2).The results indicated biosynthesized NCs have significant cellular toxicity properties against HepG2 and could be utilized in hepatocarcinoma therapy. Furthe

ECEL1 novel mutation in arthrogryposis type 5D: A molecular dynamic simulation study.

BACKGROUND: ECEL1 has been presented as a causal gene of an autosomal recessive form distal arthrogryposis (DA) which affects the distal joints. The present study focused on bioinformatic analysis of a novel mutation in ECEL1, c.535A>G (p. Lys179Glu), which was reported in a family with 2 affected boys and fetus through prenatal diagnosis. METHODS: Whole-exome sequencing data analyzed followed by molecular dynamic (MD) simulation of native ECEL1 protein and mutant structures using GROMACS software. One variant c.535A>G, p. Lys179Glu (homozygous) on gene ECEL1 has been detected in proband which was validated in all family members through Sanger sequencing. RESULTS: We demonstrated remarkable constructional differences by MD simulation between wild-type and novel mutant of ECEL1 gene. The reason for the lack of the Zn ion binding in mutation in the ECEL1 protein has been identified by average atomic distance and SMD analysis among the wild-type and mutant. CONCLUSION: Overall, in this study, we present knowledge of the effect of the studied variant on the ECEL1 protein leading to neurodegenerative disorder in humans. This work may hopefully be supplementary to classical molecular dynamics to dissolve the mutational effects of cofactor-dependent protein

Stem cell treatment of degenerative eye disease

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment

Thermostability and functionality evaluation of laccases from Pleurotus ostreatus and Pycnoporus cinnabarinus: An In-silico assay: Biochemical properties of laccases from fungi in silico method

Laccase enzymes are widely used in industrials and therefore achievement to the resources of this enzyme with high thermostability is obligatory. Accordingly, a deeper investigation for understanding the structure and function of PoxA1b from Pleurotus ostreatus, as a fungal enzyme with the possible desired conditions, was accomplished by using in-silico methods. Our study led to modeling a tertiary structure of the enzyme with 72% identity to the laccase from Trametes sp. AH28-2, with high quality. Moreover, structural stability of modeled enzyme compared to laccase from Pycnoporus cinnabarinus (LPC), were proved during 20 ns at 300 and 333K. Interestingly, this data showed that the modeled enzyme is more stable than LPC at 333 K. On the other hand, interaction assay of PoxA1b and LPC with benzo[a]pyrene (BaP), as a Polycyclic aromatic hydrocarbons (PAHs), revealed suitable affinity for both of them with -9.1 and -8.8 of binding energy, respectively. Taken together, these data show that both laccase from Pleurotus ostreatus and Pycnoporus cinnabarinus are stable until 60 °C with suitable affinity to substrate. Bearing in mind, PoxA1b is a favorable candidate for industrial and environmental applications, especially in PAH detoxification

Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum

cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. Materials and Methods: In this experimental study, slow administration of quinolinic acid (QA, 5 μl of 200 μmol, 1 μl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student’s t test. Results: The QA treated group showed marked motor learning deficits on the rotating rod test (p≤0.0001), locomotor asymmetry on the cylinder test (p≤0.0001), dysmetria on the beam balance test (p≤0.0001), abnormalities in neuromuscular strength on the hang wire test (p≤0.0001), spatial memory deficits in the Morris water maze (MWM, p≤0.001) and fear conditioned memory on the passive avoidance test (p≤0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p≤0.001) and granular cell density (p≤0.0001) in the lesioned hemisphere of the cerebellum. Conclusion: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

Among scaffolds used in tissue engineering, natural biomaterials such as plant-based materials show a crucial role in cellular function due to their biocompatibility and chemical indicators. Because of environmentally friendly behavior and safety, green methods are so important in designing scaffolds. A key bioactive flavonoid of the Epimedium plant, Icariin (ICRN), has a broad range of applications in improving scaffolds as a constant and non-immunogenic material, and in stimulating the cell growth, differentiation of chondrocytes as well as differentiation of embryonic stem cells towards cardiomyocytes. Moreover, fusion of ICRN into the hydrogel scaffolds or chemical crosslinking can enhance the secretion of the collagen matrix and proteoglycan in bone and cartilage tissue engineering. To scrutinize, in various types of cancer cells, ICRN plays a decisive role through increasing cytochrome c secretion, Bax/Bcl2 ratio, poly (ADP-ribose) polymerase as well as caspase stimulations. Surprisingly, ICRN can induce apoptosis, reduce viability and inhibit proliferation of cancer cells, and repress tumorigenesis as well as metastasis. Moreover, cancer cells no longer grow by halting the cell cycle at two checkpoints, G0/G1 and G2/M, through the inhibition of NF-κB by ICRN. Besides, improving nephrotoxicity occurring due to cisplatin and inhibiting multidrug resistance are the other applications of this biomaterial