elham rezaee

It has been found that the second isoform of COX enzyme known as COX-2 plays an important role in inflammation and rheumatoid arthritis and osteoarthritis. Thus, designing COX-2 inhibitors to treat inflammation is among the most important goals of researchers. In this study, the inhibitory effect of 3 new imidazole derivatives on COX-2 was evaluated by in silico approach. Molecular docking was done using Autodock Vina and the best binding mode of inhibitors was used as input of molecular dynamics (MD) simulation. MD was performed using Gromacs software for 120 ns. Then, structural and thermodynamic analyzes (ΔGbinding) and prediction of physicochemical properties were performed. RMSD data showed the compounds reached a good equilibrium and had favorable stability during simulation. Also, the RMSF showed that due to binding of inhibitors, the fluctuations of complexes decreased and the active site residues had the lowest amount. Rg, SASA and DSSP analysis showed that the protein structure did not change significantly. It was also found that Ser530 and Tyr355 residues play a more effective role in hydrogen bond formation. Physicochemical parameters determined the good drug-likeness properties for all compounds. Structural and thermodynamic analyzes (MM-PBSA) and IC50 data indicate the favorable inhibitory effect of compound 5b.

 Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity.

 Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug.

 Twenty-four Wistar and Sprague–Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method.

 Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain.

 Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

 Cerasomes, due to their external siloxane network, demonstrate markedly higher physicochemical stability and, therefore, easier handling and storage than liposomes.

 The main objective of this study was to compare the pharmacokinetics (PK) of cerasome and liposome following intravenous administration. The PK of PEGylated and non-PEGylated cerasomes was also compared to see whether the presence of a hydrophilic siloxane network on the surface of cerasomes can play the role of polyethylene glycol (PEG) in increasing the blood circulation of these vesicles.

 Silver sulfide (Ag2S) quantum dots (Qds)-loaded PEGylated and non-PEGylated cerasomes and PEGylated liposomes were fabricated and thoroughly characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and in vitro stability. For pharmacokinetic evaluation, the free Qds and the selected formulations were intravenously injected into rats, and blood samples were collected for up to 72 hours. Pharmacokinetic parameters were calculated by the non-compartmental method.

 Both cerasomal and liposomal carriers significantly improved the PK of Qds. For example, the elimination half-life (t1/2) and the area under the plasma concentration-time curve from time 0 to time infinity (AUC0-∞) for the free Qds were 4.39 h and 8.01 µg/mL*h and for cerasomal and liposomal formulations were 28.82 versus 26.95 h and 73.25 versus 62.02 µg/mL*h, respectively. However, compared to each other, the plasma concentration-time profiles of PEGylated cerasomes and liposomes displayed similar patterns, and the statistical comparison of their pharmacokinetic parameters did not show any significant difference between the two types of carriers. For PEGylated cerasomes, t1/2 and AUC0-∞ values were respectively 1.6 and 3.3 times greater than the classic cerasome, indicating that despite the presence of a hydrophilic siloxane network, the incorporation of PEG is necessary to reduce the clearance of cerasomes.

 The comparable PK of PEGylated cerasomes and liposomes, along with the higher physicochemical stability of cerasomes, can be considered an important advantage for the clinical application of cerasomes. Additionally, the easy surface functionalizing ability of cerasomes confers a dual advantage over liposomes. The study findings also showed that the presence of a hydrophilic siloxane network on the surface of cerasomes alone is not enough to make them circulate long.

 Malaria is considered one of the most serious life-threatening diseases in Yazd, a central province of Iran, which hosts both domestic and foreign immigrants. This study aimed to investigate the trend of Malaria in Yazd during 2011-2020.

 In this descriptive retrospective study, all episodes of the disease (imported malaria) recorded at Yazd health center in Iran were carefully evaluated and reported. After preparing the peripheral blood smear and fixation with methanol, it was stained with Giemsa and examined with a light microscope by a skilled technician.

Totally, 95 confirmed malaria patients were investigated from 2011 to 2020. Plasmodium falciparum was the predominant species with 81 cases (85.26%). The highest rate of infection was observed in 49 cases (51.6.3%), in the age group of 50 years with 27 cases (42.86%), and in the working class with 69 cases (72.63%). Despite a decrease in Malaria cases through the implementation of the eradication program compared to the last two decades, its imported type is still showing up in the country, especially in the cosmopolitan city of Yazd, where domestic and foreign workers and tourists usually travel; thus it requires to be further monitored and controlled.

 Toxoplasmosis is a common parasitic infection that can endanger mother's and neonates' health during pregnancy. The disease is also prevalent in Iran. This study intended to evaluate the seroepidemiology of toxoplasmosis in neonates and postpartum mothers referred to health centers of Yazd in Iran in 2020.

 Totally, 184 postpartum mothers and 184 neonatal umbilical cords in health centers of Yazd were evaluated for Toxoplasma infection through a specific IgM and IgG antibodies kit. The obtained data were analyzed by SPSS18.

Out of 184 samples of postpartum mothers, 8 cases (4.35%) were seropositive, and 176 (95.65%) were seronegative for IgG antibody; moreover, 7 cases (3.80%) were seropositive, and 177 (96.20%) seronegative for IgM antibody. Also, 184 neonatal umbilical cords were IgM negative, and no toxoplasmosis infection was reported. No significant correlation was found between seroprevalence of Toxoplasma infection and caring for pets, consumption of raw meat, level of education, blood type, job, living area and type of delivery (P>0.05). However, a significant correlation was identified between the number of deliveries and the prevalence of toxoplasmosis (P=0.014). This study also illustrated a low prevalence of Toxoplasma infection in postpartum mothers and no congenital transmission of the disease in diverse health centers of the province. However, there was no statistically significant relationship between risk factors and the prevalence of Toxoplasma.

Leishmaniasis, a cosmopolitan parasitic infection, is a sandfly-borne parasitic disease caused by different species of Leishmania. Many attempts have been made to discover effective and safe vaccines against leishmaniasis, but most of them are not accompanied by promising results. During the last decade, the characterization of new antigens for potential vaccine candidates based on classical and molecular protocols has been a hot research topic in immunological science. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis. Here, molecular approaches to leishmaniasis vaccine development are described. Also, implications and restrictions are discussed.

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world’s most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 µM and an EC50 of 8.4 µM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 µM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents.

 Developing a potent and safe scaffold is challenging in anti-cancer drug discovery.

 The study focused on developing novel series of compounds based on the inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) as one of the most promising compounds in cancer therapy.

 In this study, a novel series of quinazoline-2,4,6-triamine derivatives were designed and synthesized through intramolecular C-H activation reaction of para-nitro aniline, trichloroacetonitrile, and isocyanides employing a one-pot reaction.

 The in-vitro antitumor activities of the compounds which showed acceptable inhibitory effects were investigated against breast (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines by employing MTT assay. All compounds had the most negligible cytotoxicity toward normal fibroblast human cell lines. Based on structural and thermodynamics analysis results, it was found that Met 769 is a key residue in interaction with all inhibitors through the formation of hydrogen bonds with high occupancies with the amine group on the quinazoline ring of inhibitors. Also, there was a good consistency between calculated ΔG binding and experimental IC50 values of compounds 10d, 10e, and erlotinib.

 Compound 10e had an extensive range of antitumor activity on three diverse cell lines comparable with erlotinib and doxorubicin reference drugs. Also, compound 10d showed selective cytotoxicity against cancerous lung cells (A-549). On the other side, computational studies confirmed that Met 769 is a crucial residue in interaction with all inhibitors.

Impaired cell cycle regulation and disturbance in signal transduction pathway are twomajor causes of a condition defined as cancer, one of the significant reasons formortality worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been commonly used as anticancer agents, and the majority of this medications possess quinazoline moiety as a heteroaromatic core. In this study, two novel series of EGFR-TKIs containing quinazolinone core were designed and synthesized. Most compounds showed reasonable inhibitory activity against EGFR-TK compared to that of erlotinib, a reversible inhibitor of this enzyme. Compound 8b, 2-((2-chlorobenzyl)amino)-6-phenoxyquinazolin-4(1H)-one, with an IC50 value of 1.37 nM exhibited the highest potency. Molecular docking study of compound 8b showed that it had the same direction of erlotinib and formed proper hydrogen bonds and hydrophobic interactions with the important amino acid residues of the active site. Based on in-silico calculations of ADME properties, our novel compounds have the potential to be orally active agents.

Benzodiazepines (BZD) are among the main classes of tranquilizing drugs, bearing much less toxicity compared to other drugs acting on the CNS. Considering the pharmacophore model of BZD binding to GABA-A receptor, novel diphenyl 1,3,4-oxadiazole compounds as BZD ligands were designed. The compounds were synthesized and structurally confirmed using LCMS, IR and NMR techniques. We investigated the affinity of the compounds to BZD receptors using radioligand [3H]-flumazenil by in-vitro studies. In addition, sedative-hypnotic, anxiety, anticonvulsant, muscle relaxant, memory impairment, and motor coordination activities of the synthesized compounds were evaluated using in-vivo studies. Based on in-vitro studies, compounds 7i and 7j were the most potent with IC50 values of 1.54 and 1.66 nM respectively. In-vivo studies showed that compound 7i has the highest impact on increased sedation, muscle relaxation, and decreased anxiety and these observations were antagonized by flumazenil. Compounds 7e and 7i were the most potent anticonvulsant agents among synthesized compounds in both MES and PTZ induced seizure tests. All synthesized compounds significantly decreased latency to fall in the Rotarod test but none of them had a significant impact on the memory impairment test.

The increasing number of pregnant women being diagnosed as having gestational diabetes mellitus (GDM) and  lead health care providers to develop reliable screening protocols and know the exact worldwide epidemiology of the disease. This study seeks to obtain data that will help to improve the epidemiologic knowledge about this disease.

This cross-sectional study was performed on 953 pregnant women seeking routine prenatal screening tests. Participants participate with using Carpenter-Coustan criteria in the study. Statistical analysis was performed using SPSS software.

Results and Conclusions:

Among 953 pregnant women , 38 participants (4%) were detected to have GDM . Fifty percent of patients in the study were overweight .The data showed a significant difference in the mean age between the diabetic and non-diabetic groups. The high prevalence of GDM in young Iranian pregnant women may emphasize the need for early diagnosis and treatment to avoid adverse outcomes associated with GDM.

The endocannabinoid system plays an important neuromodulatory role in the periphery and central nervous system, which can regulate several physiological processes. The inhibition of enzymatic activities responsible for hydrolysis anandamide and other endogenous fatty acid amides, enhances cannabinoid receptors activity indirectly that may prove to be useful drugs for the treatment of range of ailments including pain, anxiety, and other central nervous system disorders. In this study, we designed, synthesized, and evaluated novel fatty acid amide hydrolase (FAAH) inhibitors based on 4-aminobenzohydrazide derivatives. Most of the synthesized compounds exhibited a proper affinity for the catalytic triad of FAAH in docking studies and had a considerable in-vitro FAAH inhibitory activity in comparison with JZL-195, a potent inhibitor of FAAH. Compound 2-(2-(4-(2-carboxybenzamido)benzoyl)hydrazine-1-carbonyl)benzoic acid, 12, was found to be the most potent inhibitor with IC50 value of 1.62 nM targeting FAAH enzyme.

Vulvovaginal candidiasis (VVC) is an infection caused by Candida species that affects millions of women every year. Due to increased drug resistance, selection of appropriate drugs has an effective role in controlling and improving the infection. The present study aimed to determine the frequency and drug susceptibility pattern in Candida species isolated from VVC in Gerash city.

This cross-sectional study was performed on vaginal samples of 268 patients referred to Amir-al-momenin Ali hospital in Gerash city, for six months from September 2018 to September 2019. All samples were examined direct microscopic and cultured on Sabouraud dextrose agar medium with chloramphenicol (50mg/L). Candida species were identified using standard phenotypic tests and sugar assimilation tests (API20C). The drug susceptibility pattern was investigated by the Kirby-Bauer method. The Chi-square test was used for data analysis.

Out of 268 vaginal samples, 79 cases (29.47%) were positive for Candida species, among them 48 candida albicans strains (60.75%) and 31 Non-albicans candida species (24.39%) were isolated. Itching (51.89%) was the most common clinical symptom. The most and the least drug resistance in candida species was observed to Fluconazole (64.55%) and Amphotericin B (6.32%), respectively.

The VVC caused by Candida albicans is more common in comparison with Non-albicans candida species. For the initial treatment of Vulvovaginal candidiasis, the use of Amphotericin B and Caspofungin drugs is recommended.

Urinary tract infections are one of the most common human infections seen in all age groups and both sexes. Inappropriate use of antibiotics to treat urinary tract infection causes the resistance of the pathogens to the drug. The present study aimed to determine the frequency of gram-negative and gram-positive bacteria and antibiotic resistance patterns in patients with urinary tract infection.

Samples were cultured on Blood Agar and Eosin Methylene Blue. Colonieschr('39') growth was identified by biochemical tests and standard microbiological and antibiotic sensitivity tests, which were performed with the disc diffusion method according to the Clinical and Laboratory Standards Institute 2016 Standard.
Results and

The isolated bacteria showed the highest susceptibility to imipenem (89.66%) and meropenem (87.21%) and the highest resistance to sulfamethoxazole (50.00%) and nalidixic acid (44.09%). So, using imipenem is recommended as the most effective antibiotic for the treatment of infection.

Pediculosis is one of the most common parasitic diseases that affect a wide range of age groups. The prevention of head lice infections promotes the physical and mental health of people in the community. Thus, the aim of this study was to investigate the prevalence of head lice infections and the factors affecting them in those who referred to health centers in Gerash County from 2011 to 2018. This descriptive cross-sectional study was conducted on patients suspected with head lice infections in health centers in Gerash. These infections were diagnosed by observing adult lice, nymphs, or nits on the head with the help of a magnifying glass. The collected data were then analyzed using SPSS software, version 22 and P ˂ 0.05 was considered as the significance level. In general, 66 410 patients suspected with head lice were examined, of whom 2,547 cases (3.83%) were reported with confirmed infections including 2395 female (94.03%) and 152 male (5.97%) cases. The highest levels of infections were reported in the age group of 6-10 years while the lowest levels of infections were found in children less than 6 years of age. A significant statistical relationship was observed between head lice and gender, age, season, and the place of residence, and year of infection (P < 0.05). Due to the increasing trend of head lice infections in recent years, pediculosis is still considered a health problem. Therefore, training on personal hygiene, adequate access to health services, and early diagnosis and treatment can play an important role in the prevention and elimination of head lice.

Soluble epoxide hydrolase enzyme is a promising therapeutic target for hypertension, vascular inflammation, pain and some other risk factors of cardiovascular diseases. The most potent sEH inhibitors reported in the literature are urea-based ones which often have poor bioavailability. In this study, in a quest for finding potent inhibitors of soluble epoxide hydrolase, some 4,6-disubstituted pyridin-2(1H)-one derivatives were designed and synthesized. The designed compounds fit properly in the active site pocket of this enzyme in docking studies and have appropriate distances for effective hydrogen binding to important amino acids Tyr383, Tyr466, and Asp335. The results of biological evaluation of these compounds against soluble epoxide hydrolase enzyme indicate most compounds have acceptable inhibitory activity and compound 9c is the most potent inhibitor with inhibitory activity of 86%.

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the same direction of the sulfonamide group of Celecoxib,a known selective cyclooxygenase-2 inhibitor. Therefore effective hydrogen binding withArg513 is established. Also, additional hydrogen binding could form between NH ofanilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activityagainst cyclooxygenase-2 in micromolar concentrations comparable with the reference,Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC50 of 0.71 μM againstcyclooxygenase-2 was the most potent one.

Tumor necrosis factor alpha (TNF-α) expression amplifies to excess amounts in several disorders such as rheumatoid arthritis and psoriasis. Although, Anti-TNF biologics have revolutionized the treatment of these autoimmune diseases, formation of anti-drug antibodies (ADA) has dramatically affected their use. The next generation antibodies (e.g. Fab, scFv) have not only reduced resulted immunogenicity, but also proved several benefits including better tumor penetration and more rapid blood clearance. Using affinity selection procedures in this study, a scFv antibody clone was isolated from naïve Tomlinson I phage display library that specifically recognizes and binds to TNF-α. The TNF-α recombinant protein was expressed in genetically engineered Escherichia coli SHuffle® T7 Express, for the first time, which is able to express disulfide-bonded recombinant proteins into their correctly folded states. ELISA-based affinity characterization results indicated that the isolated novel 29.2 kDa scFv binds TNF-α with suitable affinity. In-silico homology modeling study using ‘ModWeb’ as well as molecular docking study using Hex program confirmed the scFv and TNF-α interactions with a scFv-TNF- α binding energy of around -593 kj/mol which is well in agreement with our ELSIA results. The cloned scFv antibody may be potentially useful for research and therapeutic applications in the future.

Wife fertility by donation sperm or ovum is one of the new methods of laboratory fertility that experts benefit it to treat infertility of one of the spouses. In this technique, by supervision of doctor, wife will be able to fertility by getting donations sperm or ovum.
Infertility treatment of wife by foreign gametes causes some reactions and oppositions from Shia and Sunni scholars, especially this opposition is more precisely considered in relationship with wife fertility by foreign man’s sperm in a way that more scholars treat this prick as adultery and oppose to maintaining chastity. By this citations, it is necessary to study if donation of gametes is unlawful? Or its permission is not out of mind? And by permission assumption, what compliance issues are its provisions? Is administration of this method interference in divine destiny, adultery and violation of caution in frvj? So, in this study, by firm answering to mentioned questions, we prove that benefiting this technique will be conditional lawful.

In this research, impact of different levels of magnetized wastewater were investigated on yield and water use efficiency in maize cv. Maxima and some of soil physical properties. Research was done as factorial experiment with two factors based on complete randomized blocks with 3 replications from June to October 2014 in Research Farm of Zanjan University. Required wastewater was provided from refinery of Zanjan and was distributed in plots in 5 levels included 0% (well water as control), 25, 50, 75 and 100%. Magnetic water was included crossing and no crossing magnetic field. Based on results, leaf area and relative water content of leaf were not significant affect by different levels of wastewater. Maximum value of maize wet mass and water use efficiency for wet mass were in 100% wastewater treatment which were significantly difference with control treatment as 23.9 tone/ha and 7.6 kg/m3 respectively. Difference between maize wet mass and water use efficiency of wet mass for magnetized and no magnetized water were 14.6 tone/ha and 4.7 kg/m3 (respectively) which were statistically significant.
In this study, effect of different levels of wastewater were not significant on soil physical properties in 0-15 and 15-30 cm depths. The effect of magnetic water on soil physical properties was significant in 0-15 cm of soil depth but there was not significant influence in 15-30 cm depth. Results showed, in 0-15 cm of soil depth, magnetic water increased soil bulk density, volume moisture and soil saturate degree and decreased soil porosity compared to no magnetic water as 19%, 3%, 10% and 8% (respectively).

The increasing importance of energy resources in the formation and growth of economic processes as well as the need for utilization of these resources which are based on envirmental consideration and constant development of social and economical ones, to couseing identification subject and study of the factors on energy usage to be emboss. The size and structure of population is also among the factors that are important in issues related to the energy usage and it has been little studied. The electricity may be obtained to those energy which can be used to replace nearby. So this paper uses panel data of 12 provinces of the country, to analyze and compare the effect of the structure of population on the energy consumption of electricity in east (6 provinces) and west (6 provinces separately in a period, and the results show that income variant has a negative effect on electricity consumption in every provinces, however increasing of income in energy eastern provinces decreases the electricity consumption. The effects of variables such as population and urbanization has been positive in both provinces, but positive effects for the population of the eastern provinces on electricity consumption is more because of the high population of east. And the positive effect of urbanization is upper beacause of the existence of installations urban and residents consumption of electricity means.

The present study has examined the effect of export and import of different classifications of technology on the growth of Iranian manufacturing industry during the period 1998-2011 based on two models (a & b). Model a tests the effect of high-tech manufacturing industry on the growth. Then، import of high-tech industry is added to Model b and the effect of export is evaluated in the presence of import. The findings of Model b indicated that in the presence of import، the export of high-tech industry has the positive effect on the growth while the effect of such level of technology import is negative. An important principle to achieve a specific level of development in developing countries is that they should consider import of low-tech goods and export of high techgoods in the early stages of growth. Therefore، since Iran is a developing country، high-tech import could not have a positive effect on growth. Accordingly، the effect of export، with the presence of import،on growth of low-tech industry was tested and insignificant export variable revealed that import plays more important role than export on growth in Iranian low-tech industry.

There are many evidences show that increase in resources and responsibilities of public sector is not match to the degree of accountability in this section. Many factors such as lack of social capital, influence of critical media and decrease or lack of accountability in public institutions has diminished public trust to the government and its organizations. But there are many evidences show that strategic environmental variables such as social trust in society may be effective on current situation too. In this article, we firstly study trust literature and provide a three dimensional model. Then evaluate the effect of public accountability in increase or decrease of public trust to the government and political institutions. We present suggestions to improve current situations too. Thus the purpose of this article is the study and explaining the role of accountability in public trust to governments. We use descriptive method (survey research). Data are gathered with questionnaires and analyzed with SPSS software. Our statistical sample has selected from the research community that formed from educational organizations in Tehran. As regards the role of accountability indicators in public and political trust, this article tries to emphasize this important role and suggests developed model for accountability and public trust to government in Iran. Hence the article can help to improve and complete the knowledge in relevant areas.