Synthesis and Characterization of a Novel Gene Delivery Cargo Based on Magnetic Nanoparticle Functionalized with Poly-vinylimidazolium

Introduction: The gene delivery vectors are generally classified into two types: viral and non-viral. The chemical vectors have several advantages such as convenient synthesis or chemical modification, unlimited DNA carrying capacity, and low immunogenicity. Recently, Ionic Liquids (ILs) have attracted more and more interest for gene delivery. Magnetic nanoparticles (MNPs) act as effective carriers for DNA, the surface of the particles is better to be modified to enable attachment of the target molecules. Here, we design a particular carrier including the MNPs and ILs to transfer GFP gene to cells. Methods: First, imidazolium-type ILs-modified magnetite nanoparticle was synthesized. By this mean, Magnetic nanoparticles were modified with acryloyl amide according to reported procedure. Then, vinyl imidazole was copolymerized by free radical polymerization. Poly(vinylimidazole)-grafted silica-MNP was treated with methyl iodide to form a quaternary salt of poly(vinylimidazole). The chemical structure characterization was carried out by FT-IR and the organic content was determined by CHN analysis. The topography was studied by SEM, TEM, AFM. On the next step, The Green Florescent Protein (GFP) gene was attached to synthesized polymer by electrostatic interactions. The complex of polymer-DNA was added to cell line (HepG2) and the expression of GFP was evaluated. Results and Discussion: The result of chemical structure characterization was in line with our expectations. Imidazolium-type ILs-modified magnetite nanoparticle was characterized. This novel functionalized nanoparticle was a potential vehicle for gene delivery. Conclusion: In summary, we have reported the synthesis of poly-(vinylimidazolium)-modified iron oxide nanoparticles and estimated their potential gene delivery application. The Polyvinylimidazolium provided an efficient cationic group to increase binding capacity for biomolecules such as DNA

Analysis of Genetic Relationship Among 11 Iranian Ethnic Groups with Bayesian Multidimensional Scaling Using HLA Class II Data

Background: The key feature of Bayesian methods is their lack of dependence on defaults necessary for classical statistics. Because of the high volume of simulation, Bayesian methods have a high degree of accuracy. They are efficient in data mining and analyzing large volumes of data, and can be upgraded by entering new data. Objective: We used Bayesian multidimensional scaling (MDS) to analyze the genetic relationships among 11 Iranian ethnic groups based on HLA class II data. Method: Allele frequencies of three HLA loci from 816 unrelated individuals belonging to 11 Iranian ethnic groups were analyzed by Bayesian MDS using R and WinBUGS software. Results: like the results of correspondence analysis as a prototype of classical MDS analysis, the results of Bayesian MDS also showed Arabs from Famur, Balochis, Zoroastrians and Jews to be separate from other Iranian ethnic groups. Decreases stress in Bayesian MDS method compared to classical method revealed the accuracy of Bayesian MDS for HLA data analyses. Conclusion: This study reports the first application of Bayesian multidimensional scaling to HLA data analysis with Nei's DA genetic distances. Stress reduction in Bayesian MDS compared to classical MDS showed that the Bayesian approach can improve the accuracy of genetic data analysis

Mechanistic Assessment of Functionalized Mesoporous Silica-Mediated Insulin Fibrillation

Insulin, which is a small protein hormone consisting of 51 amino acids, rapidly fibrillates under stressogenic conditions. This biotechnological/ medical problematic reaction quickly accelerates in the presence of some particles, while there are several other particles that slow down the kinetic process. To address the unexplored demand of the particles that modulate protein fibrillation, we have synthesized two amino-based particles and a chitosan-coated mesoporous silica particle (MS-NH2, MS-3NH2, and MS-chitosan) to investigate insulin fibrillation. While these particles were fairly similar in size, they are differ in their net positive charge and surface hydrophobicity. To monitor the exact role of the hydrophobic interaction between the protein and MS-chitosan during the fibrillation, we have also co- and preincubated insulin with cholesterol and the particles under stressogenic conditions. The results indicate that MS-NH2 and MS-3NH2, due to their high positive charges and lack of surface hydrophobicity, repel the positively charged unfolded insulins at pH 2.0. Moreover, MS-chitosan with 25% surface hydrophobicity stacks partially unfolded insulins to its surface and induces some α-helix to β-sheet structural transitions to the protein. Consequently, both amino- and chitosan-based particles slow down the kinetics of the fibrillation. We also showed that cholesterol can structurally participate in insulin fibril architecture as a hydrophobic bridge, and extraction of this molecule from the preformed fibrils may disrupt the fibril structure

Reconceptualizar el constructo de oportunidad: una respuesta a un dilema teórico a través de una revisión sistemática de la literatura

After Shane’s seminal work in 2000 which highlighted the importance of entrepreneurial opportunities, the number of studies focusing on entrepreneurial opportunity increased rapidly. Different definitions of this concept were provided in the field, ranging from subjective to objective ones, which gave rise to a lack of consensus among researchers and this, in turn, was an obstacle that slowed down theorizing in entrepreneurship. Taking into account the past trends in management sciences, it seems to be the right moment to re-conceptualize the core construct of opportunity. The major critique of existing definitions is their operationalization. To provide a better operationalization, the present study aimed to offer a more accurate conceptual definition. To this end, the study first examined current debates on opportunity, which revealed the major problem causing the debates. Then, through a systematic literature review, from among more than seven thousand documents in the Scopus database containing opportunity keywords, 74 papers were selected following different phases of filtration. The papers were analyzed in detail to extract different constructs. Then, using the framework of Hansen et al, they were classified along six dimensions. The concepts under each dimension were examined to finally provide a bigger picture of the construct of opportunity and offer a re-conceptualization. The results of this study highlight the gaps for future research and pave the ground for other systematic literature reviews in the field.Después de que el influyente trabajo de Shane en 2000 destacó la importancia de las oportunidades empresariales, el número de estudios centrados en las oportunidades empresariales aumentó rápidamente. En el campo se aportaron distintas definiciones de este concepto, que van desde las subjetivas hasta las objetivas, lo que generó una falta de consenso entre los investigadores y esto, a su vez, fue un obstáculo que frenó la teorización en el emprendimiento. Teniendo en cuenta las tendencias pasadas en las ciencias de la administración, parece ser el momento adecuado para reconceptualizar el constructo central de la oportunidad. La principal crítica de las definiciones existentes es su operacionalización. Para brindar una mejor operacionalización, el presente estudio tuvo como objetivo ofrecer una definición conceptual más precisa. Con este fin, el estudio examinó en primer lugar los debates actuales sobre las oportunidades que revelaron el principal problema que suscitan los debates. Luego, mediante una revisión sistemática de la literatura, de entre más de siete mil documentos en la base de datos Scopus que contienen palabras clave de oportunidad, se seleccionaron 74 artículos siguiendo diferentes fases de filtración. Los artículos se analizaron en detalle para extraer diferentes constructos. Luego, utilizando el marco de Hansen et al, se clasificaron en seis dimensiones. Se examinaron los conceptos de cada dimensión para finalmente proporcionar una imagen más amplia del constructo de oportunidad y ofrecer una reconceptualización. Los resultados de este estudio destacan las brechas para futuras investigaciones y preparan el terreno para otras revisiones sistemáticas de la literatura en este campo

Synthesis and Characterization of Simvastatin-N-succinyl chitosan-citicoline Conjugated Form Intended for Improving Alzheimer’s Disease in Long Term Use of Simvastatin

Introduction: Simvastatin is a semisynthesis statin. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme of cholesterol synthesis, in AMPK (AMP-activated protein kinase) signaling pathway. Simvastatin is able to cross blood brain barrier more than the other statins, due to its lipophilic nature. There is controversy about the effect of simvastatin on Alzheimer’s disease (AD). For example, simvastatin can induce AD through insulin signaling pathway but can ameliorate AD via MAPK (Mitogen-Activated Protein Kinase) signaling pathway.  In this study, we report the synthesis of a conjugated form of simvastatin with citicoline, to block negative effect of simvastatin on insulin signaling pathway and increase positive effect of simvastatin on MAPK signaling pathway and chitosan as a linker between these two drugs.   Methods and Results: for simvastatin-n-succinyl chitosan-citicoline synthesis, chitosan reacted with succinic acid to form n-succinyl chitosan. Then simvastatin connected to n-succinyl chitosan via acetylation reaction. After 24 hours citicoline was added to reaction media. H-NMR and FT-IR were done to examine whether the conjugation reaction has been done or not. Characterization and morphology tests have been done on reaction result. H-NMRresults approved the synthesis of drug-polymer. FT-IR results showed both amide and ester peaks.  Maximum absorptions (λmax) of all primary chemicals were seen in UV visible spectroscopy results of conjugated form.SEM result showed that the conjugated form has nanoparticulate structure in size range of 100-300 nanometers. X-RD result showed a peak under 25 theta. Another characterization test wasRBC hemolysis with six different concentrations, in which normal saline was negative control and Triton was positive control. Conclusions: Conjugation of lipophilic simvastatin with hydrophilic citicoline to improve AD can be done with helping of a polymer which is rich in carboxylic acid

Synthesis Of Novel Reducing Agent for Formation of Metronidazole-Capped Silver Nanoparticle and Evaluating Antibacterial Efficiency in Gram-Positive and Gram-Negative Bacteria

In this study, a new type of silver nanoparticles capped with metronidazolium based ionic liquid is synthesized. By this aim, metronidazole is altered to ionic-liquid type structure with citrate counter ion as reducing agent. The produced reducing agent was characterized using 1HNMR and 13CNMR and FT-IR. The capability of metronidazolium-based reducing agent in formation and capping silver nanoparticles was examined in a chemical reaction. More specifically, synthesized silver nanoparticles were synthesized and capped with metronidazolium-citrate based ionic liquid, while the formation of particles in 48 h was monitored by UV-Vis spectroscopy. Fourier transform infrared spectroscopy showed the presence of capping agents around silver nanoparticles. The amount of metronidazolium and citrate as capping agents was determined by thermal gravimetric analysis. The prepared crystalline structure of silver nanoparticles was proved by X-ray diffraction spectroscopy. PSA analysis and TEM was performed to determine the size of particles. The synthesized silver nanoparticle has the potential to be used as an antibacterial agent in preparation of wound dressing with extra capability and efficacy in aerobic and anaerobic bacterium. In this regard, the antibacterial efficacy of discs from different concentration of silver nanoparticles in calcium alginate medium were evaluated in Gram-negative and Gram-positive bacterium

Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU

EDTA-Modified Mesoporous Silica as Supra Absorbent of Copper Ions with Novel Approach as an Antidote Agent in Copper Toxicity

Purpose: Mesoporous silica (MS) have been considered as a biocompatible compound and found to have various pharmaceutical applications. Recently, novel approaches in applications of MS as antidote agents were introduced. In this study, the capacity of ethylenediaminetetraacetic acid modified mesoporous silica (MS-EDTA) was evaluated in in vitro and in vivo adsorption of copper (Cu). Methods: The MS-EDTA was characterized by fourier transform infrared (FT-IR) and X-ray diffraction, while surface area was determined by N2 adsorption–desorption technique. Morphological studies were observed by high resolution-transmission electron microscopy and field emission-scanning electron microscopy and the sizes were determined by dynamic light scattering. The capacity of these particles for copper adsorption was investigated in vitro in both 1.2 and 7.2 pH. In in vivo animal study, the Cu adsorption efficiency of MS-EDTA in Cu-overdosed mice was evaluated. In this case, an animal model of acute copper poisoning was prepared. Results: The MS-EDTA with surface area of 352.35 was synthesized. Scanning electron microscope showed spherical particle formation with less than 500 nm in size. Transmission electron microscope images showed porous and honeycomb structure. FT-IR spectroscopy showed an appropriate formation of functional groups. Particle efficiency was investigated for Cu adsorption. MS-EDTA in both media showed a high adsorption capability for Cu (II) adsorption in pH=1.2 and pH=7.2. In addition, the study of Langmuir, Freundlich, and Redlich–Peterson adsorption models showed that copper adsorption by MS-EDTA followed the Freundlich model with multi-layer adsorption. In vivo evaluation showed that MS-EDTA could alleviate the symptoms of acute copper poisoning by lowering Cu plasma levels. Conclusion: Structural evaluation showed successful formation of MS-EDTA. In vitro analysis demonstrated that supreme Cu adsorption occurs in both pH conditions (7.2 and 1.2), and was especially more favorable in simulated intestinal pH (7.2). The in vivo studies in animal models with acute Cu poisoning showed that MS-EDTA could be a potent antidote agent

Drug-based therapeutic strategies for COVID-19-infected patients and their challenges

Emerging epidemic-prone diseases have introduced numerous health and economic challenges in recent years. Given current knowledge of COVID-19, herd immunity through vaccines alone is unlikely. In addition, vaccination of the global population is an ongoing challenge. Besides, the questions regarding the prevalence and the timing of immunization are still under investigation. Therefore, medical treatment remains essential in the management of COVID-19. Herein, recent advances from beginning observations of COVID-19 outbreak to an understanding of the essential factors contributing to the spread and transmission of COVID-19 and its treatment are reviewed. Furthermore, an in-depth discussion on the epidemiological aspects, clinical symptoms and most efficient medical treatment strategies to mitigate the mortality and spread rates of COVID-19 is presented