فصلنامه علوم پزشکی دانشگاه آزاد اسلامی
سال سی‌ام شماره 4 (پیاپی 102، زمستان 1399)

Recent years, allogeneic bone marrow transplantation (BMT) has proved to be the successful cure for patients with thalassemia major, however this is restricted due to limited matched-related donor. Its complications include chronic graft-versus-host disease in 5-8% of patients. So, a molecular approach, such as gene therapy for direct normal beta globin gene transmission, seems quite promising to cure thalassemia. The goal of beta thalassemia gene therapy is to restore normal RBC production capacity in patients by suitable vector and correct inherited anemia. Virus therapy has recently been recognized as a promising new therapeutic approach in medical research. In this regard, the use of viruses as non-replicating gene therapy vectors or as replication viruses (oncolytic viruses) has provided attractive opportunities for viral therapy applications. Currently viral vectors have been used in nearly 70% of the clinical trials. In recent years, many researchers have designed erythroid-specific lentiviral vectors carrying the beta-globin gene that have obtained significant results. Their findings are presented in this study.

Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary. Nanoparticles (NP) prepared with chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner. Current study is focused on preparation several kinds of chitosan formulations and different concentrations of cross linking agents in various conditions and characterization for achievement of most stable and biocompatible nanoparticle which labeled by FITC for in vitro tracking.
Analysis

In order to better investigate, in addition to chitosan, carboxymethyl chitosan was used. Preparation of chitosan nanoparticles is done by Ionotropic gelation method using different concentration of sodium tripolyphosphate (TPP) as cross-linking agent. Moreover, the synthesis of FITC-labeled chitosan at a combination of time, pH, different concentrations of salt and enzyme was investigated to produce stable nanoparticles for intestinal drug delivery. Physical characterization of nanoparticles were estimated by DLS and TEM as well as conjugation and covalent links were confirmed by FITR.

The size of the nanoparticles by transmission electron microscopy (TEM) was about 100±50.Hydrodynamic diameter was measured by DLS around 150±50 nm. In FTIR, covalent conjugation to the chitosan nanoparticles with control samples was confirmed. UV spectroscopy was used to determine the efficiency of conjugation which was over 70%.

All of these findings favor the notion that the FITC conjugated chitosan nanoparticles produced in our work may offer promise for the development of an efficient therapeutic and diagnosis carrier for colon cancer in the future. However, further investigation is required to provide more evidence on different aspects of the targeting activity and stability of this nanoparticle in in vivo.

The purpose of using nano-carriers for drugs delivery, such as nanotubes, is slow release of drug and reducing side effects of drugs. Drugs are very active due to their many functional groups. Therefore, reactivity of drug is reduced by being in nanotube field due to electronic resonance of drug with nanotube and it stays longer in body. As a result, less amount of drug is used and fewer side effects occur.

In present study, boron nitride nanotubes (n = 9, m = 9) with 7 angstroms length and carbon nanotubes (n=9, m=9) with 7 angstroms were used to compare effects of encapsulating anticancer drug Floxuridine with this nanotube. Using density functional theory (DFT) at theoretical level of B3LYP / 6-31G *, structure of drug and BNNT (9, 9-7), CNT (9, 9-7) and nano- drug systems were optimized.

Using optimized structures, spatial parameters such as bond length and bond angels, HOMO-LUMO orbitals, graphs of density of states (DOS), natural bond orbital (NBO), electronic properties, parameters of atoms in molecules (AIM) and molecular electrostatic potential (MEP) were discussed.

Analysis of adsorption energy and thermodynamic functions shows that the process of encapsulation of the drug by both nanotubes is favorable and based on the results of NBO and AIM, BNNT nanotubes are more suitable for encapsulation of fluoxoridine.

Nowadays transdermal drug delivery systems (TDDS), as an appropriate replacement for oral and parenteral dosage forms, are developing. These systems which designed to transport drugs through skin layers into the systemic circulation, have several benefits such as avoiding first-pass metabolism, sustained and controlled drug release, reducing side effects, and ease of use. The aim of this study was to formulate alprazolam transdermal gel, as a short-acting anxiolytic of benzodiazepines class, based on the nanoliposomes.

At the first, different amounts of phospholipid, and cholesterol were used to produce alprazolam-loaded nanoliposomes through solvent injection method. Vesicle size and encapsulation efficiency tests were performed on the samples and statistical models based on response surface methodology (RSM) were developed to find the optimal formulation. Optimal liposomal structure after morphological characterization was used to produce alprazolam 0.5 mg/g transdermal gel. Three formulated gels with different content of carbomer were examined for viscosity, stability and in vitro skin permeation.

The optimal formulation of the liposomal structure included 10 mg/mL of phospholipid and 10% w/w cholesterol, resulted in the production of nanoliposomes with a size of 115 nm and an encapsulation efficiency of 91%. As the carbomer content in the gel increased, the rate of drug permeation into the skin was decreased.

Alprazolam transdermal gel was successfully formulated in this research with acceptable skin permeation, good stability and appropriate physicochemical characteristics.

Increase of protein purity is a serious challenge in the production of recombinant therapeutic proteins. For this purpose, several strategies have been employed to purify the target protein, among which the affinity chromatography-based purification methods and tagged proteins such as Ni-NTA are common and but costly. Therefore column-free purification techniques, such as using elastin-like proteins (ELPs), are being developed as alternative method. In present study, the efficacy of Ni-NTA, ELP, and the combined Ni-NTA/ELP was evaluated for purification of streptokinase as a model protein at lab scale.

Streptokinase gene was amplified by PCR, cloned into pET21-ELP, and transformed into E.coli BL21 Rosetta cell. The expressed protein was then purified using the methods described above. The identity and purity of the protein were evaluated by western blot using Anti-His antibody and SDS-PAGE, respectively. The purification yield was also calculated for each method by micro-Bradford assay.

The purification yield was calculated as 76 ± 16 μg/ml in ELP precipitation, 108 ± 14 μg/ml in Ni-NTA purification and 88 ± 11 μg/ml in Ni-NTA/ELP combined method, respectively. The SDS-PAGE results showed that the purity of streptokinase purified by the combined method was higher than that of each method separately.

The present study showed that the integration of purification methods in one step can increase the purity and yield in purification process of recombinant therapeutic proteins.

Aromatase is an enzyme that plays an important role in the development of estrogen-positive breast cancer. Estrogens are essential in human and mainly in women because of their role in sexual development and reproduction. Adverse effects of some aromatase inhibitors increase the need to discover new inhibitors with higher selectivity, lower toxicity and improved potency. In this study, the binding state of all three generations of aromatase inhibitors to the molecular structure of this protein using molecular docking method has been studied.

In general, the inhibitors based on steroid scaffolds (formestane and exemestane) have higher binding energy than azole scaffolds (fadrozole, anastrozole, letrozole), which may be due to their high structural strength.

Among all the considered structures studied, exemestane had the highest (negative) binding energy as well as the lowest inhibitory constant. The free energy of binding and the inhibitory constants was -8.77 kcal mol-1 and 373.32 nM respectively, which means that aromatase activity will be inhibited at the low concentrations of this anti-cancer drug.

The knowledge gained from this study will have important implications regarding for pharmaceutical design.

Many diseases, including diabetes, are involve in the development of liver disorders through changes in the expression of genes such as Caspase-3. In the present study, the impact of alcoholic extract of Alhagi maurorum on the expression level of liver Caspase-3 gene was investigated in male Wistar rats following the induction of diabetes mellitus by streptozotocin.

In this experimental study, 42 male Wistar rats were divided into 6 groups. The control group was left untreated, the diabetic control group received one dose of 70 mg/kg streptozotocin, the experimental groups 1 and 2 received 250 and 500 mg/kg Alhagi maurorum alcoholic extract peritoneally respectively, and the experimental groups 3 and 4 first received streptozotocin followed by 250 and 500 mg/kg extracts respectively. To investigate the expression level of the Caspase-3 gene, liver samples were obtained from all the groups, and were evaluated using real time PCR.

The expression of Caspase-3 gene, against β actine, increased significantly in experimental groups compared to the control group, while diabetic groups received extract showed reduced gene expression compared to the streptozotocin group.

It appears that Alhagi maurorum extract is effective in reducing hepatic gene expression of Caspase-3, which increases after using streptozotocin. This effect is possibly due to the anti-oxidants contents, such as flavonoids and anthocyanins.

Depression is a common psychological disorder and recent data confirm the increasing prevalence of this disease in the world. So far, antidepressant effects of many plants have been evaluated and some are accepted in the treatment of depression. The aim of the present study was to determine the antidepressant effect of Melissa Officinalis L. compared to fluoxetine.

In the present study, the antidepressant effect of Melissa officinalis L. was studied and compared with fluoxetine in experimental groups of mice using FST (Forced Swimming Test), TST (Tail Suspension Test). Melissa officinalis L. extract with different doses of 600,800, and 1000 mg/kg was prescribed by gavage for 7 days. One way ANOVA was used to analyze data by SPSS software.

Among the different doses, 600 mg/kg Melissa officinalis L. extract and fluoxetine had the same effect in the reduction of depression.

The antidepressant effect of Melissa officinalis L. extract is probably induced by the variation of monoamines release in central nervous system.

Caffeinated energy drinks are common drinks among athletes and general population that have benefits such as providing quick energy, reducing fatigue and creating alertness, but can lead to serious complications in patients, especially those who have cancer and mental, cardiovascular, or renal diseases. The aim of this study was to validate the quantitative analysis and determine caffeine in 10 caffeine-containing drink samples from Tehran markets using high efficiency liquid chromatography (HPLC).

In this study, first the HPLC method was validated using the sample standard. Then the amount of caffeine in 10 samples of drinks was evaluated.

The calibration curve of caffeine was linear in the range of 2-200 ppm and its correlation coefficient was 0.997. The limits of detection and quantification (LOQ and LOD) were 44.65 and 13.39 mg/mL respectively. After validating the method, 10 drink samples collected from Tehran were tested for caffeine content. Comparing the results with international standards showed that the caffeine value of these beverages was lower than the standard.

This method has the accuracy and efficiency in measuring the caffeine of beverages. Comparing with international standards, the amount of caffeine in the beverages is lower than the standard. Due to the increased consumption of these drinks in the country, measuring caffeine at different times is essential.

The most important anabolic and catabolic hormones which levels are altered by resistance training are IGF-1 and cortisol, respectively. The purpose of the present study was to investigate the effect of total body resistance training (TRX) on serum levels of IGF-1, cortisol and some health-related physical factors in active women.  

In this study, 20 active women (mean age 27.05 ± 3.11) were randomly divided into experimental (n= 10) and control (n= 10) groups. The experimental group program consisted of TRX training for 6 weeks, 3 sessions per week for 50-60 minutes under the supervision of a TRX trainer. The intensity of the exercises for the first two weeks, using the Borg scale was in the range of 4-5, in the second and the third two weeks, based on the increase in load in the range of 5-6 and 6-7, respectively. Serum levels of IGF-1, cortisol, body fat percentage, upper and lower body strength and endurance were measured before and after exercise.

Six weeks of TRX training increased cortisol and IGF-1 levels in active women, although this increase was not statistically significant (p>0.05). But the results showed that these exercises can significantly decrease body fat percentage and increase the strength and endurance of the upper and lower muscles of active women.

According to the findings of the present study, it seems that performing the TRX training can significantly improve body fat percentage, strength and muscle endurance in active women and could utilize as an alternative resistance training model to improve fitness factors.

Hyperbilirubinemia is a neonatal ubiquitous condition but the role of life style factors and endocrine disrupting chemicals (EDCs) on the incidence of this globally prevalent symptoms remained unclear. This study aimed to determine the role of EDCs and other predisposition factors in this regard.

At first, 120 mothers and infants (60 pairs as control and 60 pairs as cases) were conveniently sampled after delivery and before their discharge. The mothers were interviewed and their case records were reviewed for risk factors for neonatal jaundice using SPSS software 24. We used studentchr('39')s t test for parametric and Chi-square test for non-parametric analysis of variables. Risk factors calculated by Mann-Whitney U test and p- values< 0.05, OR>1 and CI> 1 were considered as significant difference and jaundice risk factors respectively.

Out of different demographical and lifestyle factors including exposure to outdoor and indoor chemicals, extensive exposure to air fresheners (OR=16.319, 95%CI=2.06-129.292, p=0.001) and detergents (OR=4.958, 95%CI=2.074-11.852, p=0.0001) were considered as two major life style predisposing factors of idiopathic hyperbilirubinemia.

According to the results obtained from this study, unhealthy life style and endocrine disrupting chemicals consumption could significantly increase the risk of jaundice but further animal and clinical studies are necessary to find out their direct associations.

Henoch-Schonlein purpura is a common systemic vasculitis in childhood, usually characterized by skin, abdominal, and renal manifestations. Most patients are 4 to 7 years old and are more common in boys. The disease is very rare in adults with multiple symptoms.

A 20-year-old male patient with final diagnosis of Henoch-Schonlein disease with rare complications was admitted in our center. The patient referred to the hospital with acute abdomen and free fluid in the abdominal space and underwent appendectomy. During the hospitalization of the patient, purpura in the lower limb and acute scrotum were developed, which treatment was successfully performed. Disease and treatment approach of this patient has significant points that are listed below.

incidence of multiple symptoms in Henoch-Schonlein purpura is very rare in adults and may cause organ failure. Therefore, its symptoms should always be considered and appropriate diagnostic measures should be taken to prevent unnecessary surgery. Careful attention and frequent examinations by the surgeon in patients with abdominal complications are also essential.