فهرست مطالب razieh jalal

Leishmaniasis is taken into account as a parasitic disease caused by the Leishmania genus. A major challenge of the leishmaniasis is associated with the occurrence of treatment failure after drug treatment. Target identification is a significant factor to reach a drug development. Hence, protein kinases play an important role in drug designing (e.g, LmxMPK and CRK3). This study is developed to predict and assess the three-dimensional structure for E9BJT5 protein in Leishmania and its binding affinity for different calcium channel blockers.

The three-dimensional structure was predicted and assessed for the protein by the I-TASSER and Procheck servers, respectively. In the molecular docking method, interactions between different calcium channel blockers and the predicted model of E9BJT5 were investigated using the Autodock vina in PyRx 0.8 software. Thereafter, the interaction results were analyzed by Chimera software, and thus the stronger potential interactions were identified.

Docking results showed that the lidoflazine and lercanidipine (the values were -8.3 and -7.6 kcal/mol, respectively) were obtained as the top-ranked drugs in the binding to the active site of the protein.

In this study, using in silico approach, the E9BJT5 protein could be a viable target for designing the novel drugs against the Leishmania parasite. The docking results demonstrated that two drugs (i.e., lidoplasin and lercantipine) may be considered as anti-leishmanial drugs. Further studies are recommended to evaluate the interactions between these drugs and the target.

This study aimed to investigate the interaction between 5-(2-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-1,3thiazolidine-2,4-dione (oxindole A) and DNA with and without ultrasound treatment. Absorption studies have indicated that oxindole A could bind to CT-DNA with the binding constant of 30,000 and 26,666 M-1 with and without ultrasound treatment, respectively. In the competitive fluorescence method, the displacement of 4′,6-diamidino-2-phenylindole (DAPI) as a probe bound to the groove, from the DNA groove occurred by oxindole A. Using the Stern-Volmer plot, quenching constant was calculated to be 1,411 and 2,753 M-1 with and without ultrasound, respectively. Viscometric experiments have confirmed the groove binding of oxindole A to the DNA, which is consistent with the molecular dynamic simulation. The analysis of Pi, as a measure of affinity for ligand binding, has also revealed that the DA3, DG4, DC5, DT7, DC8, and DG9 of DNA have the highest affinity toward oxindole A. In addition, the results of the cell viability assay of the DU145 cell line have demonstrated that oxindole A has cytotoxic effects.

Hypothesis: In the past decades, the increasing resistance to antibiotics among some nosocomial infection pathogens has been one of the largest challenges of human health. One of the ways to reduce antibiotic resistance in bacteria is the combination use of cationic polymers with antibiotics. Poly(styrene-alt-maleic-anhydride) (PSMA) is an alternative biodegradable copolymer which can react with bioactive agents such as alkyl amines through a ring-opening reaction. In this study, for the first time, the antibacterial activity of poly(styrene-alt-maleic-anhydride) (PSMA) conjugated with spermine (Spm-PSMA) and its influence on resistance of Enterococcus faecalis to ceftazidime and ciprofloxacin antibiotics have been investigated.
Spm-PSMA was synthesized by reaction of PSMA with spermine in the presence of triethylamine catalyst under argon atmosphere at room temperature and characterized by FTIR and DSC. The antibacterial activity of Spm-PSMA was evaluated against two nosocomial infective bacteria, Enterococcus faecalis (E. faecalis) and Acinetobacter baumannii (A. baumannii) by two-fold microdilution method. Its ability to reduce the resistance of E. faecalis to the ciprofloxacin (CP) and ceftazidime (CAZ) antibiotics, active oxygen species (ROS) levels and morphological changes in acidic conditions was evaluated.
Findings: The glass transition temperature of Spm-PSMA (197°C) is higher than that of PSMA (164°C) due to intermolecular hydrogen bonding. Spm-PSMA reduces the growth of Gram-positive E. faecalis in a dose-independent manner, whereas it has no significant antibacterial activity against Gram-negative A. baumannii in acidic condition. E. faecalis susceptibility to ceftazidime and ciprofloxacin antibiotics is increased in the presence of Spm-PSMA at pH 5.5. The SEM results show that Spm-PSMA alone and in combination with antibiotics causes the transformation of E. faecalis cells from coccoid to coccobacilli shape. The results of this study show that Spm-PSMA is a biocompatible polymer with antibacterial activity and antibiotic sensitivity against E. faecalis bacteria.

Combination anticancer therapy holds promise for improving the therapeutic efficacy of chemotherapy drugs such as doxorubicin (DOX) as well as decreasing their dose-limiting side effects. Overcoming the side effects of doxorubicin (DOX) is a major challenge to the effective treatment of cancer. Zinc oxide nanoparticles (ZnO NPs) are emerging as potent tools for a wide variety of biomedical applications. The aim of this study was to develop a combinatorial approach for enhancing the anticancer efficacy and cellular uptake of DOX.
ZnO NPs were synthesized by the solvothermal method and were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS) and transmission electron microscopy (TEM). ZnO NPs were dispersed in 10% bovine serum albumin (BSA) and the cytotoxic effect of the resulting ZnO nanofluids was evaluated alone and in combination with DOX on DU145 cells. The influence of ZnO nanofluids on the cellular uptake of DOX and DOX-induced catalase mRNA expression were investigated by fluorescence microscopy and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively.
The MTT results revealed that ZnO nanofluids decreased the cell viability of DU145 cells in a timeand dose-dependent manner. Simultaneous combination treatment of DOX and ZnO nanofluid showed a significant increase in anticancer activity and the cellular uptake of DOX compared to DOX alone. Also, a time-dependent reduction of catalase mRNA expression was observed in the cells treated with ZnO nanofluids and DOX, alone and in combination with each other.
These results indicate the role of ZnO nanofluid as a growth-inhibitory agent and a drug delivery system for DOX in DU145 cells. Thus, ZnO nanofluid could be a candidate for combination chemotherapy.

Arginine-rich peptides are an important class of antimicrobial peptides (AMPs) that exert their antibacterial activity via a lytic mechanism. Although the antibacterial activity of arginine-rich peptides has been already evaluated, no reports have so far been evaluated the influence of reaction conditions on their antimicrobial potential. The aim of the present study was to investigate the influence of pH, temperature, and glycine on antibacterial activity of poly-l-arginine (PLA) with a molecular weight of 5-15 kDa against Escherichia coli O157:H7 and Staphylococcus aureus.
The percentage of growth inhibition of PLA against both bacteria was analyzed at various pH, temperatures and sub-inhibitory concentrations of glycine by two-fold broth microdilution method.
The results showed that PLA had antibacterial activity against E. coli O157:H7 and S. aureus and the inhibitory effect increased with increasing PLA concentration. The antimicrobial activity of PLA against both microorganisms was higher in basic media than under acidic or neutral conditions. At 1/2 times the MIC, heat treatment intensified the toxicity of PLA against E. coli O157:H7 whereas the susceptibility to PLA seems to be temperature independent for S. aureus. The MICs of glycine against E. coli O157:H7 and S. aureus were 12.5 and 25 mg ml-1, respectively. The antibacterial activity of PLA against both microorganisms increased, as indicated by the increasing growth inhibition percentage of this peptide with increasing glycine concentration.
The antibacterial activity of PLA against S. aureus and E. coli O157:H7 depends on pH and glycine concentration.

Bacterial resistance to conventional antibiotics has become a widespread public health prob- lem. The aim of this study was to investigate the influence of zinc oxide nanoparticles (ZnO NPs) on the antibacterial activity of several conventional antibiotics against Pseudomonas aeruginosa.
ZnO NPs were prepared by solvothermal method and dispersed in glycerol with the help of ammo- nium citrate as a dispersant. The antibacterial effects of the resulting ZnO nanofluid, ceftazidime, tobramycin, and ciproflox- acin were investigated against two P. aeruginosa strains, including one clinical isolate and P. aeruginosa ATCC 9027 using microdilution method. For the evaluation of the combined effect of ZnO nanofluid and antibiotics, the fractional inhibitory concentration indices were calculated and isobolograms were plotted.
Clinical strain in comparison to standard strain of P. aeruginosa showed more resistance to ZnO nanofluid and the antibiotics. ZnO nanofluid acted synergistically with ceftazidime and tobramycin against both strains. Combination of ZnO nanofluid and ciprofloxacin displayed synergistic and partial synergistic activity against clinical and standard strains of P. aeruginosa, respectively.
The results suggest that bacterial resistance to antimicrobials could be reduced by the synergistic action of ZnO NPs.

Retinal pigment epithelium is responsible for maintaining the structural integrity of the retina by an efficient defense against free radicals, photo-oxidative exposure and light energy. For this purpose the main RPE line of defense is melanosomes. Melanin content of retinal pigment epithelium cells in adults and neonates reveals remarkable variations. In the current study we compared melanogenic factors gene expression levels in human adult and neonate RPE cells in culture. RPE cells from adult and neonate human eye globes were isolated and then cultured in DMEM: F12 (1:1) containing 10% FBS. Expression of RPE65 and Cytokeratin 8/18 markers in isolated cells was confirmed by immunocytochemistry. To evaluate the responsible factors in the pathway of melanin biosynthesis, gene expression of orthodenticle homeobox 2, microphthalmia-associated transcription factor A and H as prominent transcription factors, tyrosinase and dopachrome tautomerase as effective enzymes in the melanin biosynthetic pathway were examined in human neonate derived RPE cells compared to human adult derived RPE cells in culture. According to the Real-Time RT-PCR data, gene expression of MITF-H, OTX2, TYR and DCT in RPE cells of the neonates showed a significant increase compared to the adults. With increasing passage number, gene expression of MITF-H, OTX2, TYR and DCT showed remarkable decline. According to the role of OTX2 and MITF-H as the main transcription factor effectors on the TYR and DCT, restoration of OTX2 and MITF-H gene expression may be retain melanin content in RPE cells.

The aim of this study was to investigate whether the rs12255372 (TCF7L2) and D76N (PDX-1) polymorphisms are associated with type 2 diabetes mellitus (T2DM) in Mashhad, northeast Iran. A hundred twenty seven patients with T2DM and 71 non-diabetic controls in Mashhad were genotyped by PCR-RFLP and ARMS-PCR methods. Single nucleotide polymorphisms (SNPs) were confirmed by sequencing in some samples and allelic and genotypic frequencies were then analyzed in each group. The T-allele of the SNP rs12255372 of TCF7L2 (OR = 2.70, 95% CI = 1.12–6.49, P = 0.027) and the A-allele of PDX-1 D76N (OR = 3.93, 95% CI = 1.60–7.68, P = 0.002) were significantly associated with an increased risk of T2DM. The rs12255372 SNP of TCF7L2 and D76N of PDX-1 genes may confer susceptibility to T2DM in the population living in Mashhad.

The antibacterial activity of a series of ionic liquids containing short-chained 1-alkyl-3-methylimidazolium cations ([Cnmim]; n = 2, 4, 6 and 8) and bis (trifluoromethylsulfonyl) imide anion ([Tf2N]) against E. coli and B. subtilis was measured, for the first time. All ILs used in this work were synthesized and analyzed by Fourier transform infrared (FT-IR) spectroscopy, NMR, and Karl-Fischer titration. Antimicrobial activity was determined by the tube dilution method. The ILs investigated showed antibacterial activity against E. coli and B. subtilis. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were in the ranges of 0.041-6.39 mM and 0.67-12.78 mM, respectively. The antibacterial activity for ionic liquids with longer alkyl chain (n ≥ 4) increased with increasing alkyl chain length. The highest inhibition against E. coli was found for [C8mim][Tf2N] (MIC = 0.041 mM and MBC = 0.67 mM). The mechanism of action of these ionic liquids was bacteriostatic.

The prevalence of type 2 diabetes mellitus (T2DM) is rising dramatically in the Middle East, especially in the Islamic Republic of Iran, but the genetic basis of type 2 diabetes in Iran is poorly understood. Polymorphisms of hepatocyte nuclear factor-1α (HNF-1α) and glucagon-like peptide-1 receptor (GLP-1R) genes showed association with type 2 diabetes in several ethnic groups. In this study, we evaluated whether these markers confer susceptibility to T2DM in a diabetic population living in Mashhad (northeast of Iran). Genotyping of Ala98Val (HNF-1α) and Thr149Met (GLP-1R) was done by the restriction fragment length polymorphism-PCR (RFLP-PCR) method in the following groups: 1) early-onset diabetes (age at onset ≤ 35 years); 2) late-onset diabetes (age at onset > 35 years); and 3) control. Our results showed that CT (Ala/Val) genotype of HNF-1α was higher in the early-onset type 2 diabetic group compared to the controls but difference was not significant. We did not find the GLP-1R Thr149Met mutation in all participants. The prevalence of the HNF-1α (Ala98Val) and (GLP-1R) Thr149Met mutations has not been previously reported in Iranian participants. We conclude that these mutations are not a common cause of T2DM in our studied population.

Anxiety symptoms have been reported to be present in many patients with diabetes mellitus. However, little is known about the effects of hyperglycemia in critical periods of the central nervous system development. We assessed locomotive, exploratory, and anxiety behaviors in adult rats that remained from infantile repeated hyperglycemia by the open field and elevated plus maze tests. Our findings showed significant hypo activity, reduced locomotive/exploratory activities, increased fear related behaviors, and anxiety state between hyperglycemic and control adult males and the same differences were observed among females. In addition, no significant behavioral alterations between male and female animals were observed. This study determined that repeated increments in daily blood sugar levels in newborns may affect neuronal functions and provide behavioral abnormalities in adults.

High blood glucose induces molecular, cellular, morphological and behavioral changes in the brain. Metabolic disturbances, contribute to the hippocampus injury and development of partial focal seizures. The aim of this study was to investigate the effects of infantile repeated hyperglycemia on neuronal density of hippocampal CA3 region in newborn Wistar male rats and its effect on chemoconvulsant pentylentetrazol (PTZ) induced generalized seizures in adults.Ten days old male Wistar rats were randomly divided into 2 groups (n=20 for each): hyperglycemic and control. Hyperglycemia was induced by intraperitoneal injections of 2 g/kg dextrose solution, twice a day, for 2 weeks. Control animals received saline solution in the same manner. Blood glucose was regularly measured. After that, the brains of rats from each group (n=10) were removed for histological analysis of the CA3 region of hippocampus by stereological method. Other animals (n=10) were kept to grow older. Afterwards, seizure was induced in hyperglycemic and control adult rats, by an intraperitoneal injection of 45 mg/kg PTZ solution and then latency of convulsions onset and severity of seizures for each group were recorded.Results showed that hippocampal neuronal density decreased significantly and susceptibility to PTZ induced convulsions increased in experimental animals. The result determined that repeated increments in daily blood sugar levels in infantile period may damage neuronal structures of hippocampus and also make adults more susceptible to PTZ induced convulsions in adulthood period.

Diabetes Insulin Resistance Brain IGF-I In insulin-resistance animal models, insulin uptake from the periphery to the brain is impaired. Although brain insulin is not involved in glucose transfer to the neurons, it is required for neuron survival and function, mediated by binding to insulin receptors. Furthermore, an insulin homologue called insulin-like growth factor (IGF-I), which is abundantly expressed in mature neurons and acts in parallel with insulin in the brain, has the ability to bind to the insulin receptor and trigger the signal transduction pathway. Although reduced levels of brain insulin and serum IGF-I have been reported during insulin resistance, no data is available on IGF-I levels in the brain. In this study, we sought to investigate if the expression of IGF-I is also altered in brains of insulin-resistant rats. Wistar rats were given 10% fructose in their drinking water for up to 4 months to induce insulin resistance. The rats were then killed and perfused with PFA 4%; then, there brains were excised, sectioned, and examined for immunoreactivity of IGF-I. Our results showed an increased intensity of IGF-I in most brain areas of the insulin-resistant rats. Altogether, an increased expression of IGF-I in the brain could be a compensatory mechanism and substitute for low levels or lack of insulin in the brains of insulin-resistant animals.

Objective(s)We determined the effect of a high fructose diet either alone or in combination with Iranian shallot or garlic extract on cognitive functions, plasma lipid profile, and the intraperitoneal glucose tolerance test (IPGTT). Materials and MethodsFollowing induction of insulin resistance in fructose-fed rats (Fru-fed), they were randomly assigned to three subgroups. The first subgroup was kept as Fru-fed while the two other subgroups were daily treated by aqueous garlic or shallot extract. ResultsTwelve weeks treatment with shallot or garlic significantly prevented the learning and memory deficits induced by fructose-feeding. Administration of garlic, but not shallot extract could significantly diminish the levels of cholesterol and low-density lipoprotein. Treatment with garlic or shallot extract can significantly improve the IPGTT in the Fru-fed rats.ConclusionThe high fructose diet may contribute to spatial memory deficits. Iranian shallot or garlic extracts appear to improve learning and memory impairments in fructose-fed rats.