Comparison of cytotoxic effect of β-cyclodextrin and dextran micelles loaded with doxorubicin in KG-1 cells

زمینه و هدف: آنتراسیکلین ها درمان اصلی لوسمی حاد میلوژنز می باشند، اما استفاده از آن ها به دلیل عوارض جاننی محدود شده است. استفاده از میسل های پلیمری برای دارورسانی هدفمند دوکسوروبیسین توسط گیرنده های فولات برای لوسمی حاد میلوژنز می تواند این عوارض را کاهش دهد. این مطالعه با هدف مقایسه سمیت سلولی میسل های تهیه شده از بتاسیکلودکسترین و دکستران حاوی دوکسوروبیسین بر رده ی سلولی KG-1 انجام شده است. روش بررسی: در این مطالعه تجربی آزمایشگاهی، کونژوگه های رتینوئیک اسید/ سیکلودکسترین/ فولیک اسید و رتینوئیک اسید/ دکستران/ فولیک اسید به روش استریفیکاسیون تهیه شدند. بارگیری دارو در میسل ها به روش انحلال مستقیم انجام شد. نانوذرات میسلی بهینه سازی شده براساس اندازه ذره ای، پتانسیل زتا، اندکس پلی دیسپرسیتی، کارایی بارگیری و کارآیی رهش دوکسوروبیسین انتخاب شدند. جهت مطالعه اثر ممانعت از رشد سلولی بر رده سلولی KG-1 از روش رنگ سنجی MTT استفاده شد. یافته ها: دوکسوروبیسین بارگیری شده در نانو ذرات بهینه تهیه شده از کونژوگه ی رتینوئیک اسید/ سیکلودکسترین/ فولیک اسید در غلظت g/mlµ377/0، دارای اثر ممانعت از رشد سلولی حدود 5/10 برابر دوکسوروبیسین آزاد، 3 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ سیکلودکسترین و 3/8 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ دکستران/ فولیک اسید بود (05/0>P). دوکسوروبیسین بارگیری شده در نانو ذرات بهینه تهیه شده از کونژوگه رتینوئیک اسید/ دکستران/ فولیک اسید در غلظت g/mlµ377/0، دارای اثر ممانعت از رشد سلولی حدود 3/1 برابر دوکسوروبیسین آزاد و 2/1 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ دکستران بود (05/0>P). نتیجه گیری: نانو ذرات تهیه شده از سیکلودکسترین حاوی دوکسوروبیسین اثربخشی بیشتری علیه سلول های سرطانی KG-1 نسبت به نانو ذرات تهیه شده از دکستران حاوی دوکسوروبیسین و داروی آزاد دارد

Retinoic Acid Decorated Albumin-Chitosan Nanoparticles for Targeted Delivery of Doxorubicin Hydrochloride in Hepatocellular Carcinoma

Retinoic acid (R) grafted chitosan (C) copolymers with different degree of substitution of retinoic acid on the chitosan were synthesized. Retinoic acid targeted chitosan-albumin nanoparticles were prepared for targeted delivery of doxorubicin in hepatocellular carcinoma by coacervation method. Physical properties of nanoparticles including particle size, zeta potential, drug loading efficiency, and drug release profiles were studied. TEM micrographs were taken to see the morphology of nanoparticles. The cytotoxicity of doxorubicin-loaded nanoparticles was studied on HepG2 cells using MTT assay and their cellular uptake by fluorescence microscopy. FTIR and 1HNMR spectra confirmed successful production of RC conjugate which was used in production of the targeted RC-albumin nanoparticles. IC50 of drug loaded in these nanoparticles reduced to half and one-third compared to nontargeted nanoparticles and free drug, respectively

The Effects of Deferoxamine on the Up regulation of Chemokine Receptor 2 in Bone Marrow Stromal Stem Cells

Background: Bone marrow stromal stem cells (BMSCs) are non-hematopoietic, stromal cellsthat can differentiate into mesenchymal and other type of tissues. The BMSCs have properties that make them ideal candidates for tissue engineering. The present study aimed to investigate the effect of deferoxamine (DFO) on homing of bone marrow-derived mesenchymal stem cell, and to examine if DFO can increase migration and subsequent homing of mesenchymal stem cells (MSCs) in vitro.Methods: BMSCs were isolated from the long bones of NMARI rats through density gradientcentrifugation and adherent cell culture. Next, they were treated using DFO in Dulbecco’s modified eagle medium (DMEM) for 24 h. The expression of chemokine receptor 2 (CCR2) were assessed using RT-PCR.Results: BMSCs expressed CCR2 on a large proportion of cells. In DFO-treated BMSCs,expression of CCR2 (P<0.005) significantly increased compared to that in control groups. Elevation and up regulation of CCR2 in DFO-treated MSCs were observed.Conclusion: Preconditioning of BMSCs using DFO prior to transplantation could increasehoming of BMSCs through affecting some chemokine receptors as well as proteases involved and thus improve the efficacy of cell therapy

Driving Accidents, Driving Violations, Symptoms of Attention-Deficit-Hyperactivity (ADHD) and Attentional Network Tasks

Iran has serious problems with traffic-related injuries and death. A major reason for traffic accidents is cognitive failure due to deficits in attention. In this study, we investigated the associations between traffic violations, traffic accidents, symptoms of attention-deficit/hyperactivity disorder (ADHD), age, and on an attentional network task in a sample of Iranian adults.; A total of 274 participants (mean age: 31.37 years; 80.7% males) completed questionnaires covering demographic information, driving violations, traffic accidents, and symptoms of ADHD. In addition, they underwent an objective attentional network task (ANT), based on Posner's concept of attentional networks.; More frequent traffic violations, correlated with lower age and poorer performance on the attentional network tasks. Higher symptoms of ADHD were associated with more accidents and more traffic violations, but not with the performance of the attentional tasks. Higher ADHD scores, a poorer performance on attentional network tasks, and younger age predicted traffic violations. Only higher symptoms of ADHD predicted more traffic accidents.; In a sample of Iranian drivers, self-rated symptoms of ADHD appeared to be associated with traffic violations and accidents, while symptoms of ADHD were unrelated to objectively assessed performance on an attentional network task. Poor attentional network performance was a significant predictor of traffic violations but not of accidents. To increase traffic safety, both symptoms of ADHD and attentional network performance appear to merit particular attention

The effects of exogenous melatonin on morphological changes in locus ceruleus nucleus Characterized by REM sleep deprivation

Background: Neurodegeneration in the locus coeruleus (LC) has been documented in several central nervous system (CNS) neurodegenerative diseases and sleep deprivation. In this study, we investigated the possible role of melatonin in reversing cognitive dysfunction induced by SD in rats.Methods: The aim of this work was to determine if REM sleep deprivation would induce morphological changes in the brains of rats. The effects of REM sleep deprivation on the nuclear volume of neurons from the locus coeruleus, the main noradrenergic nucleus in the brain.Results: The results obtained showed that REM sleep deprivation significantly decreased the number of neurons in the locus coeruleus.Conclusion: A change in cell nuclear volume suggests a change in its metabolic activity, therefore, our data provide an anatomical basis for further studies of neuron’s morphology in brain structures after REM sleep deprivation

Er:YAG Laser and Cyclosporin A Effect on Cell Cycle Regulation of Human Gingival Fibroblast Cells

Introduction: Periodontitis is a set of inflammatory disorders characterized by periodontal attachment loss and alveolar bone resorption. Because of deficiency in periodontitis mechanical therapy, this study was aimed to explore the molecular influence of the erbium-doped: yttrium aluminum garnet (Er:YAG) laser and cyclosporin A (CsA) on human gingival fibroblasts (HGFs) for improvement in periodontal diseases therapy.Methods: We focused on articles that studied the proteome profiles of HGFs after treatment with laser irradiation and application of CsA. The topological features of differentially expressed proteins were analyzed using Cytoscape Version 3.4.0 followed by module selection from the protein-protein interaction (PPI) network using Cluster ONE plugin. In addition, we performed gene ontology (GO) enrichment analysis for the densely connected region and key proteins in both PPI networks.Results: Analysis of PPI network of Er:YAG laser irradiation on HGFs lead to introducing YWHAZ, VCP, HNRNPU, YWHAE, UBA52, CLTC, FUS and IGHG1 as key proteins while similar analysis revealed that ACAT1, CTSD, ALDOA, ANXA2, PRDX1, LGALS3, ARHGDI and EEF1A1 are the crucial proteins related to the effect of drug. GO enrichment analysis of hub-bottleneck proteins of the 2 networks showed the different significant biological processes and cellular components. The functional enrichments of module of Er:YAG laser network are included as fatty acid transmembrane transport, cytokinesis, regulation of RNA splicing and asymmetric protein localization. There are not any significant clusters in network of HGF treated by CsA.Conclusion: The results indicate that there are 2 separate biomarker panels for the 2 treatment methods

Developing an Educational Parenting Skills Package to Parents Undergoing Substance Abuse Treatment for Preventing Addiction among Adolescents: A Study Protocol Based on Social Marketing Approach

Background: Developing an educational parenting skills package for parents with substance abuse may be effective in preventing the same problem in their adolescents. Social marketing is one of the approaches facilitating the preparation of educational content for this purpose. Social marketing is a regular and planned process focusing on customers and their needs for encouraging a target group to exhibit a particular behavior or adopt a specific idea. This study protocol aims to use the social marketing approach to prepare an educational parenting skills package for the parents undergoing substance abuse treatment to prevent addiction in their adolescents. Methods: An educational parenting skills package will be designed and validated by a combination of qualitative research (descriptive phenomenology), scoping review, and Delphi study based on social marketing approach (4 Ps = product, price, place, promotion). The package will be prepared in four phases including educational need assessment, ranking the identified educational needs, determining the suitable health education constructs, and modeling and developing the educational content based on the identified constructs. The designed educational package will be validated from the perspective of the target group (parents undergoing substance abuse treatment) and experts. Conclusion: Developing educational packages based on a scientific health education approach and mainly the Social Marketing Assessment and Response Tool (SMART) model with an emphasis on market analysis or marketing mix (4 Ps = product, price, place, promotion) can prove effective in attracting the audience and promoting the target activitie

Nanofibrous Chitosan-Polyethylene Oxide Engineered Scaffolds: A Comparative Study between Simulated Structural Characteristics and Cells Viability

3D nanofibrous chitosan-polyethylene oxide (PEO) scaffolds were fabricated by electrospinning at different processing parameters. The structural characteristics, such as pore size, overall porosity, pore interconnectivity, and scaffold percolative efficiency (SPE), were simulated by a robust image analysis. Mouse fibroblast cells (L929) were cultured in RPMI for 2 days in the presence of various samples of nanofibrous chitosan/PEO scaffolds. Cell attachments and corresponding mean viability were enhanced from 50% to 110% compared to that belonging to a control even at packed morphologies of scaffolds constituted from pores with nanoscale diameter. To elucidate the correlation between structural characteristics within the depth of the scaffolds’ profile and cell viability, a comparative analysis was proposed. This analysis revealed that larger fiber diameters and pore sizes can enhance cell viability. On the contrary, increasing the other structural elements such as overall porosity and interconnectivity due to a simultaneous reduction in fiber diameter and pore size through the electrospinning process can reduce the viability of cells. In addition, it was found that manipulation of the processing parameters in electrospinning can compensate for the effects of packed morphologies of nanofibrous scaffolds and can thus potentially improve the infiltration and viability of cells

Comparing four laboratory three-parent techniques to construct human aged non-surrounded nucleolus germinal vesicle oocytes: A case-control study

Background: The three-parent assisted reproductive technique may increase oocyte competence. Objective: In this case-control study, the suitability of germinal vesicle transfer (GVT), synchronous ooplasmic transfer (sOT), asynchronous ooplasmic transfer using cryopreserved MII oocyte (caOT), and asynchronous ooplasmic transfer using waste MII oocyte (waOT) for maturation of the human-aged non-surrounded nucleolus germinal vesicle-stage (NSN-GV) oocyte were investigated. Materials and Methods: NSN-GV oocytes were subjected to four methods: group A (GVT), B (sOT), C (caOT) D (waOT), and E (Control). The fusion rates, MI, MII, ICSI observations and cleavage at 2-cell, 4-cell, and 8-cell stages were compared in the groups. Results: In GVT, none of the oocytes fused. In sOT, all oocytes fused, 20 achieved the MI, 14 progressed to MII, 8 fertilized, 6 cleaved and 5, 4, and 3 achieved the 2- cells, 4-cells and 8-cells, respectively. In caOT, all oocytes fused and achieved the MI, 8 progressed to MII and fertilized, 6 cleaved and 6, 5, and 5 achieved the 2-cells, 4- cells, and 8-cells respectively. In waOT, all oocytes fused, 5 and 3 progressed to MI and MII, respectively, but only one fertilized, cleaved and reached a 4-cells stage. In group E, 6 and 2 oocytes progressed to MI and MII, respectively, and only one fertilized but arrested at the zygote stage. caOT had the highest survival rate when compared to sOT (p = 0.04), waOT (p = 0.002), and control (p = 0.001). Conclusion: The caOT method was beneficial over sOT, waOT, and GVT in supplementing the developmental capacity of human-aged NSN-GV oocytes. Key words: Assisted reproductive techniques, In vitro oocyte maturation techniques, Nuclear transfer techniques, Oocytes, Oocyte donation