Protein nanoparticle: A unique system as drug delivery vehicles

Over the past three decades, there has been a considerable research interest in the area of developing drug delivery using nanoparticles (NPs) as carriers for small and large molecules. Targeting delivery ofdrugs to the diseased lesions is one of the most important aspects of drug delivery system. They have been used in vivo to protect the drug entity in the systemic circulation, restrict access of the drug to thechosen sites and to deliver the drug at a controlled and sustained rate to the site of action. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. This review presents the most outstandingcontributions in the field of protein nanoparticles used as drug delivery systems. Methods of preparation of protein nanoparticles, characterization, drug loading, release and their applications in delivery of drug molecules and therapeutic genes are considered

Genetic variability of Taenia saginata inferred from mitochondrial DNA sequences

Taenia saginata is an important tapeworm, infecting humans in many parts of the world. The present study was undertaken to identify inter- and intraspecific variation of T. saginata isolated from cattle in different parts of Iran using two mitochondrial CO1 and 12S rRNA genes. Up to 105 bovine specimens of T. saginata were collected from 20 slaughterhouses in three provinces of Iran. DNA were extracted from the metacestode Cysticercus bovis. After PCR amplification, sequencing of CO1 and 12S rRNA genes were carried out and two phylogenetic analyses of the sequence data were generated by Bayesian inference on CO1 and 12S rRNA sequences. Sequence analyses of CO1 and 12S rRNA genes showed 11 and 29 representative profiles respectively. The level of pairwise nucleotide variation between individual haplotypes of CO1 gene was 0.3–2.4 % while the overall nucleotide variation among all 11 haplotypes was 4.6 %. For 12S rRNA sequence data, level of pairwise nucleotide variation was 0.2–2.5 % and the overall nucleotide variation was determined as 5.8 % among 29 haplotypes of 12S rRNA gene. Considerable genetic diversity was found in both mitochondrial genes particularly in 12S rRNA gene. © 2015, Springer-Verlag Berlin Heidelberg

Molecular Identification and Sequencing of Mannose Binding Protein (MBP) Gene of Acanthamoeba palestinensis

"nBackground: Acanthamoeba keratitis develops by pathogenic Acanthamoeba such as A. pal­es­tinen­sis. Indeed this species is one of the known causative agents of amoebic keratitis in Iran. Mannose Binding Protein (MBP) is the main pathogenicity factors for developing this sight threatening disease. We aimed to characterize MBP gene in pathogenic Acanthamoeba isolates such as A. palestinensis."nMethods: This experimental research was performed in the School of Public Health, Tehran University of Medical Sciences, Tehran, Iran during 2007-2008.  A. palestinensis was grown on 2% non-nutrient agar overlaid with Escherichia coli. DNA extraction was performed using phenol-chloroform method. PCR reaction and amplification were done using specific primer pairs of MBP. The amplified fragment were purified and sequenced. Finally, the obtained fragment was deposited in the gene data bank."nResults: A 900 bp PCR-product was recovered after PCR reaction. Sequence analysis of the purified PCR product revealed a gene with 943 nucleotides. Homology analysis of the ob­tained sequence showed 81% similarity with the available MBP gene in the gene data bank. The fragment was deposited in the gene data bank under accession number EU678895"nConclusion: MBP is known as the most important factor in Acanthamoeba pathogenesis cas­cade. Therefore, characterization of this gene can aid in developing better therapeutic agents and even immunization of high-risk people

Effect of ethanolic extract of beet roots and leaves on motor coordination in male Wistar rats

زمینه و هدف: عدم تعادل حرکتی در اثر عوامل مختلفی از جمله ضایعات مغزی عصبی، مشکلات عضلانی، کم خونی و مصرف داروها رخ می دهد. گیاه چغندر با نام علمی Beta vulgaris L. دارای اثرات متنوع از جمله اثرات ضد التهابی، آنتی اکسیدانی، ضد استیل کولین استرازی و کاهش قند خون می باشد که در این مطالعه اثر عصاره اتانولی برگ و ریشه این گیاه بر تعادل حرکتی بررسی شده است. روش بررسی: در این مطالعه تجربی عصاره اتانولی ریشه و برگ گیاه چغندر به روش ماسراسیون تهیه شد. موش های صحرایی نر بالغ به طور تصادفی در 7 گروه 8 تایی تقسیم شدند و به مدت 25 روز آب مقطر، دوزهای مختلف عصاره ریشه (250،500 و mg/kg1000) و برگ چغندر (50 و mg/kg100) را به صورت داخل صفاقی دریافت کردند. روز 26، نیم ساعت بعد از آخرین تزریق قدرت حفظ تعادل حرکتی موش ها به وسیله روتارود اندازه گیری شد. یافته ها: عصاره ریشه چغندر در دوزهای 500 و mg/kg1000 سبب افزایش معنی دار در تعادل حرکتی شد (p0.05). نتیجه گیری: عصاره های ریشه و برگ گیاه چغندر باعث بهبود فعالیت حرکتی در موش های صحرایی نر بالغ می شود

Molecular and morphological characterization of the tapeworm Taenia hydatigena (Pallas, 1766) in sheep from Iran

Although Taenia hydatigena is one of the most prevalent taeniid species of livestock, very little molecular genetic information exists for this parasite. Up to 100 sheep isolates of T. hydatigena were collected from 19 abattoirs located in the provinces of Tehran, Alborz and Kerman. A calibrated microscope was used to measure the larval rostellar hook lengths. Following DNA extraction, fragments of cytochrome c oxidase 1 (CO1) and 12S rRNA genes were amplified by the polymerase chain reaction method and the amplicons were subjected to sequencing. The mean total length of large and small hooks was 203.4 μm and 135.9 μm, respectively. Forty CO1 and 39 12S rRNA sequence haplotypes were obtained in the study. The levels of pairwise nucleotide variation between individual haplotypes of CO1 and 12S rRNA genes were determined to be between 0.3-3.4% and 0.2-2.1%, respectively. The overall nucleotide variation among all the CO1 haplotypes was 9.7%, and for all the 12S rRNA haplotypes it was 10.1%. A significant difference was observed between rostellar hook morphometry and both CO1 and 12S rRNA sequence variability. A significantly high level of genetic variation was observed in the present study. The results showed that the 12S rRNA gene is more variable than CO1. © 2013 Cambridge University Press

A study of the time of hospital discharge of differentiated thyroid cancer patients after receiving iodine-131 for thyroid remnant ablation treatment

The aim of this study was to measure the radiation exposure rate from differentiated thyroid carcinoma (DTC) patients who had received iodine-131 (131I) treatment, and to evaluate hospital discharge planning in relation to three different sets of regulations. We studied 100 patients, 78 females and 22 males, aged 13 to 79 years (mean 44.40±15.83 years) with DTC, in three Groups who were treated with 3.7, 5.5 or 7.4GBq of 131I, respectively. The external whole-body dose rates following oral administration of 131I were measured after each one of the first three hospitalization days. A multivariant linear analysis was performed, considering exposure rates as dependent variables to the administered dose for treatment, age, gender, regional and/or distant metastases, thyroglobulin (Tg), antibodies to Tg and thyroid remnant in the three dose groups. We found that the exposure rates after each of the three first days of hospitalization were 30, 50 and 70μSvh-1 at 1m. All our DTC patients had an acceptable dose rate on days 2 and 3 that allowed their hospital discharge. After only 1 day of hospitalization, just 3/11 cases showed not permissible exposure rates above 70μSvh-1. In conclusion, it is the opinion of the authors that after measuring the exposure rates, most treated, DTC patients could be discharged after only one day of hospitalization, even some of those treated with high doses of 131I (7.4GBq). Patients, who received the higher doses of 131I, should not be released before their individual exposure rate is measured

CRISPR/Cas9-based editing of a sensitive transcriptional regulatory element to achieve cell type-specific knockdown of the NEMO scaffold protein

The use of alternative promoters for the cell type-specific expression of a given mRNA/protein is a common cell strategy. NEMO is a scaffold protein required for canonical NF-κB signaling. Transcription of the NEMO gene is primarily controlled by two promoters: one (promoter B) drives NEMO transcription in most cell types and the second (promoter D) is largely responsible for NEMO transcription in liver cells. Herein, we have used a CRISPR/Cas9-based approach to disrupt a core sequence element of promoter B, and this genetic editing essentially eliminates expression of NEMO mRNA and protein in 293T human kidney cells. By cell subcloning, we have isolated targeted 293T cell lines that express no detectable NEMO protein, have defined genomic alterations at promoter B, and do not support activation of canonical NF-κB signaling in response to treatment with tumor necrosis factor. Nevertheless, noncanonical NF-κB signaling is intact in these NEMO-deficient cells. Expression of ectopic wildtype NEMO, but not certain human NEMO disease mutants, in the edited cells restores downstream NF-κB signaling in response to tumor necrosis factor. Targeting of the promoter B element does not substantially reduce NEMO expression (from promoter D) in the human SNU423 liver cancer cell line. Thus, we have created a strategy for selectively eliminating cell typespecific expression from an alternative promoter and have generated 293T cell lines with a functional knockout of NEMO. The implications of these findings for further studies and for therapeutic approaches to target canonical NF-κB signaling are discussed.Published versio

High resolution melting technique for molecular epidemiological studies of cystic echinococcosis: Differentiating G1, G3, and G6 genotypes of Echinococcus granulosus sensu lato

Reliable and rapid genotyping of large number of Echinococcus granulosus sensu lato isolates is crucial for understanding the epidemiology and transmission of cystic echinococcosis. We have developed a method for distinguishing and discriminating common genotypes of E. granulosus s.l. (G1, G3, and G6) in Iran. This method is based on polymerase chain reaction coupled with high resolution melting curve (HRM), ramping from 70 to 86 C with fluorescence data acquisition set at 0.1 C increments and continuous fluorescence monitoring. Consistency of this technique was assessed by inter- and intra-assays. Assessment of intra- and inter-assay variability showed low and acceptable coefficient of variations ranging from 0.09 to 0.17 %. Two hundred and eighty E. granulosus s.l. isolates from sheep, cattle, and camel were used to evaluate the applicability and accuracy of the method. The isolates were categorized as G1 (93, 94, and 25 %), G3 (7, 4, and 4 %), and G6 (0, 2, and 71 %) for sheep, cattle, and camel, respectively. HRM results were completely compatible with those obtained from sequencing and rostellar hook measurement. This method proved to be a valuable screening tool for large-scale molecular epidemiological studies. © 2013 Springer-Verlag Berlin Heidelberg

Genetic characterization of Echinococcus granulosus from a large number of formalin-fixed, paraffin-embedded tissue samples of human isolates in Iran

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, presents an important medical and veterinary problem globally, including that in Iran. Different genotypes of E. granulosus have been reported from human isolates worldwide. This study identifies the genotype of the parasite responsible for human hydatidosis in three provinces of Iran using formalin-fixed paraffin-embedded tissue samples. In this study, 200 formalin-fixed paraffin-embedded tissue samples from human CE cases were collected from Alborz, Tehran, and Kerman provinces. Polymerase chain reaction amplification and sequencing of the partial mitochondrial cytochrome c oxidase subunit 1 gene were performed for genetic characterization of the samples. Phylogenetic analysis of the isolates from this study and reference sequences of different genotypes was done using a maximum likelihood method. In total, 54.4%, 0.8%, 1%, and 40.8% of the samples were identified as the G1, G2, G3, and G6 genotypes, respectively. The findings of the current study confirm the G1 genotype (sheep strain) to be the most prevalent genotype involved in human CE cases in Iran and indicates the high prevalence of the G6 genotype with a high infectivity for humans. Furthermore, this study illustrates the first documented human CE case in Iran infected with the G2 genotype. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene

Effect of enhanced external counterpulsation and cardiac rehabilitation on quality of life, plasma nitric oxide, endothelin 1 and high sensitive CRP in patients with coronary artery disease: A pilot study

Objective To investigate the effect of enhanced external counterpulsation (EECP) on plasma nitric oxide (NO), Endothelin 1 (ET1), high sensitive C-reactive protein (HSCRP) and quality of life (QoL) in patients with coronary artery disease (CAD).Methods We conducted a pilot randomized clinical trial in order to evaluate plasma NO, ET1, HSCRP and QoL before and after twenty sessions of EECP (group A) and cardiac rehabilitation (CR, group B) in 42 patients with CAD (21 in each group).Results Forty-two patients (33 male and 9 female) were included in the study. The mean age was 58.2±10 years. The mean HSCRP was 1.52±0.7 in the EECP group and it was reduced to 1.27±0.4 after intervention. The reduction in HSCRP was not statistically significant in EECP and CR groups with p=0.33 and p=0.27, respectively. There was not significant improvement of NO, ET1, and QoL in the EECP and CR groups shortly after therapy (p>0.05).Conclusion Although the short-term EECP treatment in CAD patients improved HSCRP, NO, ET1, and QoL compared with the baseline those improvements are not statistically significant. Further studies are necessary with large study groups and more sessions. © 2015 by Korean Academy of Rehabilitation Medicine