Optimization of Epigenetic Modifier Drug Combination for Synergistic Effect against Glioblastoma Multiform Cancer Cell Lines.

Glioblastoma multiforme (GBM), is a frequent class of malignant brain tumors. Epigenetic therapy, especially with synergistic combinations is highly paid attention for aggressive solid tumors like GBM. Here, RSM optimization has been used to increase the efficient arrest of U87 and U251 cell lines due to synergistic effects.

Development of a continuous fermentation process for the production of recombinant uricase enzyme by Pichia pastoris.

Recent studies in the biopharmaceutical industry have shown an increase in the productivity and production efficiency of recombinant proteins by continuous culture. In this research, a new upstream fermentation process was developed for the production of recombinant uricase in the methylotrophic yeast Pichia pastoris. Expression of recombinant protein in this system is under the control of the AOX1 promoter and therefore requires methanol as an inducing agent and carbon/energy source.

QbD-guided pharmaceutical development of Pembrolizumab biosimilar candidate PSG-024 propelled to industry meeting primary requirements of comparability to Keytruda®.

Pharmaceutical development of biosimilars is primarily focused on meeting the regulatory requirements for analytical comparability of the product's critical quality attributes (CQAs), concerning safety and efficacy, to those of the originator drug of interest. To this end, the early adoption of a systematic science-based approach, as guided by quality-by-design (QbD) principles, is crucial due to the blind starting point where the same insights of an originator developer into the challenges of a given biopharmaceutical and its manufacturing process are lacking. In this study, we devised a pharmaceutical QbD-guided approach to undertake the biosimilar development of Pembrolizumab (Keytruda®), the ace of therapeutic monoclonal antibodies (mAbs) in terms of approved indications and market sales, and its manufacturing process development.

Acceleration of antibacterial activity of curcumin loaded biopolymers against methicillin-resistant : Synthesis, optimization, and evaluation.

Curcumin is a polyphenolic molecule with antibacterial, antioxidant, anti-inflammatory, and antimicrobial properties. This study aimed to prepare nanocurcumin by encapsulating in biopolymers to improve its stability, bioavailability, water-solubility, antibacterial efficiency against methicillin-resistant . Three effective variables of curcumin concentration, polymer concentration, and water volume on curcumin-loaded polymer nanoparticles, were optimized.

Neuroprotective Effect of New Nanochelating-Based Nano Complex, ALZc3, Against Aβ -Induced Toxicity in Rat: a Comparison with Memantine.

Purpose: The current drugs for Alzheimer's disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-βeta (Aβ) injection into the brain.

One-step separation of the recombinant protein by using the amine-functionalized magnetic mesoporous silica nanoparticles; an efficient and facile approach.

The separation process is the main stage of recombinant production. With the advancement of nanotechnology and the development of magnetic nanoparticles, these structures are increasingly used in different applications. In the present study, we produced the recombinant human growth hormone from Pichia pastoris and for protein separation provided the surfaces similar to chromatographic columns on the surface of magnetic nanoparticles.

Emergency Ross Procedure for Pediatric Aortic Valve Myxofibrosarcoma.

Primary cardiac tumors in children are uncommon and rarely demand surgical intervention. We report a malignant tumor arising from the aortic root in a 5-year-old boy presenting with left ventricular outflow tract obstruction and tumor embolism, its surgical management using the Ross procedure, and the unique histopathological aspects of the tumor.

Curcumin-loaded polysaccharide nanoparticles: Optimization and anticariogenic activity against Streptococcus mutans.

Curcumin was loaded into different polysaccharide nanoparticles chitosan, alginate and starch, using the desolvation method. Curcumin-loaded nanoparticles exhibited enhanced solubility in aqueous solutions comparing with free curcumin. Effects of formulation parameters such as curcumin concentration and different volumes of ethanolic solution were affected the particle size and loading efficiency.

Enhanced truncated-t-PA (CT-b) expression in high-cell-density fed-batch cultures of Pichia pastoris through optimization of a mixed feeding strategy by response surface methodology.

Recently, Pichia pastoris has been the focal point of interest as an expression system for production of many recombinant proteins. The study and optimization of feeding strategy are of major importance to achieve maximum volumetric productivity in fed-batch cultivations. Among different feeding strategies used in P.

Digitoflavone provokes mitochondrial biogenesis in PC12 cells: A protective approach to oxidative stress.

Context: Reactive oxygen species (ROS) are known to be one of the main causes of neurodegenerative disorders, and flavonoids play characteristic roles in a variety of biological activities, and specially are known to be antioxidant reagents.

Objective: In this study, we investigated neuroprotective effects of digitoflavone to suppress H2O2 -induced cell death in neuron-like PC12 cells.

Material And Methods: PC12 cells were pre-treated with digitoflavone for 2 h and then cells were exposed to H2O2 for 18 h.

Homology modeling, docking, molecular dynamics simulation, and structural analyses of coxsakievirus B3 2A protease: an enzyme involved in the pathogenesis of inflammatory myocarditis.

2A protease of the pathogenic coxsackievirus B3 is key to the pathogenesis of inflammatory myocarditis and, therefore, an attractive drug target. However lack of a crystal structure impedes design of inhibitors. Here we predict 3D structure of CVB3 2A(pro) based on sequence comparison and homology modeling with human rhinovirus 2A(pro).

A novel amino acid supplementation strategy based on a stoichiometric model to enhance human IL-2 (interleukin-2) expression in high-cell-density Escherichia coli cultures.

A novel amino acid supplementation strategy was developed for enhancing the production of IL-2 (interleukin-2; as a model protein) by recombinant Escherichia coli BL21 (pET21a-hil2) in fed-batch high-cell-density cultures. The amino acids most needed and their amounts were determined using a stoichiometric model, and full factorial design experiments were conducted to determine the effects of single amino acids and amino acid mixtures on production. One of the most effective amino acid mixtures was found to be leucine, aspartic acid and glycine.

Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology.

Chemical coupling of polyethylene glycol (PEG) to proteins or particles (PEGylation), prolongs their circulation half-life by greater than 50-fold, reduces their immunogenicity, and also promotes their accumulation in tumors due to enhanced permeability and retention effect. Herein, phase separation method was used to prepare bovine serum albumin (BSA) nanoparticles. PEGylation of BSA nanoparticles was performed by SPA activated mPEG through their free amino groups.

Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis.

Neuroinflammation is associated with a number of neurodegenerative diseases. It is known that lipopolysaccharide (LPS) treatment induces neuroinflammation and memory deterioration. Agmatine, the metabolite of arginine by arginine decarboxylase, is suggested to be a neuroprotective agent.

Targeting enteroviral 2A protease by a 16-mer synthetic peptide: inhibition of 2Apro-induced apoptosis in a stable Tet-on HeLa cell line.

Enteroviridae such as coxsackievirus are important infectious agents causing viral heart diseases. Viral protease 2A (2Apro) initiates the virus life cycle, and is an excellent target for developing antiviral drugs. Here, to evaluate the validity of the 2Apro as a proper therapeutic target, and based on the existing information and molecular dynamics, a 16-mer peptide was designed to specifically target the active site of protease 2Apro in order to block the activity of CVB3 2Apro.

5-Fluorouracil-loaded BSA nanoparticles: formulation optimization and in vitro release study.

Over the past few decades, there has been considerable interest in developing protein nanoparticles as drug delivery devices. The underlying rationale is their exceptional characteristics, namely biodegradability and nonantigenicity. Herein, phase separation method was used to prepare 5-fluorouracil-loaded bovine serum albumin (BSA) nanoparticles.

Effect of dextromethorphan on antinociception and tolerance induced by swim-stress in the formalin test.

Background: In the present study, the effect of dextromethorphan on antinociception and tolerance induced by water swim-stress in the formalin test was investigated.

Methods: Swim-stress at 8 masculineC induces antinociception in both phases of the formalin test. Intraperitoneal administration of dextromethorphan (60 mg/kg) also induces antinociception in the second phase of the formalin test.

Effect of lithium on swim stress-induced antinociception in naive mice and mice with subchronic administration of morphine or swim stress in formalin test.

Background: Lithium has been shown to relieve mania and induce antinociception. In the present study, swim stress at 8C induced antinociception in both phases of the formalin test. Intraperitoneal administration of lithium chloride (LiCl) (0.