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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) comprises around 20-30% of all BC subtypes and is correlated with poor prognosis. For many years, trastuzumab, a monoclonal antibody, has been used to inhibit the HER2 activity. Though, the main resistance to trastuzumab has challenged the use of this drug in the management of HER2-positive BC. Therefore, the determination of resistance mechanisms and the incorporation of new agents may lead to the development of a better blockade of the HER family receptor signaling. During the last few years, some therapeutic drugs have been developed for treating patients with trastuzumab-resistant HER2-positive BC that have more effective influences in the management of this condition. In this regard, the present study aimed at reviewing the mechanisms of trastuzumab resistance and the innovative therapies that have been investigated in trastuzumab-resistant HER2-positive BC subjects., (© 2019 Wiley Periodicals, Inc.)

Advances in biomanufacturing techniques have opened the doors to recapitulate human sensory organs such as the nose and ear in vitro with adequate levels of functionality. Such advancements have enabled simultaneous targeting of two challenges in engineered sensory organs, especially the nose: i) mechanically robust reconstruction of the nasal cartilage with high precision and ii) replication of the nose functionality: odor perception. Hybrid nasal organs can be equipped with remarkable capabilities such as augmented olfactory perception. Herein, a proof-of-concept for an odor-perceptive nose-like hybrid, which is composed of a mechanically robust cartilage-like construct and a biocompatible biosensing platform, is proposed. Specifically, 3D cartilage-like tissue constructs are created by multi-material 3D bioprinting using mechanically tunable chondrocyte-laden bioinks. In addition, by optimizing the composition of stiff and soft bioinks in macro-scale printed constructs, the competence of this system in providing improved viability and recapitulation of chondrocyte cell behavior in mechanically robust 3D constructs is demonstrated. Furthermore, the engineered cartilage-like tissue construct is integrated with an electrochemical biosensing system to bring functional olfactory sensations toward multiple specific airway disease biomarkers, explosives, and toxins under biocompatible conditions. Proposed hybrid constructs can lay the groundwork for functional bionic interfaces and humanoid cyborgs., Competing Interests: The authors declare no conflict of interest., (© 2020 Brigham and Women's Hospital/Harvard Medical School. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction : Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases. Area covered : Herein, the authors discuss different aspects of leukodystrophies. The authors used MEDLINE, EMBASE, and GOOGLE SCHOLAR to provide an extensive update about epidemiology, classifications, pathology, clinical findings, diagnostic tools, and treatments of leukodystrophies. Comprehensive evaluation of clinical findings, brain magnetic resonance imaging, and genetic studies play the key roles in the early diagnosis of individuals with leukodystrophies. No cure is available for most heritable white matter disorders but symptomatic treatments can significantly decrease the burden of events. New genetic methods and stem cell transplantation are also under investigation to further increase the quality and duration of life in affected population. Expert opinion : The improvements in molecular diagnostic tools allow us to identify the meticulous underlying etiology of leukodystrophies and result in higher diagnostic rates, new classifications of leukodystrophies based on genetic information, and replacement of symptomatic managements with more specific targeted therapies. Abbreviations: 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive.

Background: Toxoplasma gondii is the agent of a zoonotic protozoan infection with worldwide distribution. The rates of infection in different areas are depending on climatic conditions and also social and cultural habits of the people. This cross-sectional study aimed to find out the seroprevalence of toxoplasmosis in nomadic people in Boyer-Ahmad County, in the southwest of Iran., Methods: Blood samples (5 mL) were collected from 1005 individuals of nomadic tribes of Boyer-Ahmad County in Kohgiluyeh and Boyer-Ahmad Province in 2016. A predesigned questionnaire, containing basic epidemiological information was filled out for each subject during the sampling. Sera were evaluated for anti-T. gondii antibodies (both IgG and IgM), using a commercial ELISA kit. Collected data were analyzed by SPSS, using descriptive statistics and Chi-square test., Results: Out of the 1005 studied subjects, 227 (22.6%) were male and 778 (77.4%) were female. The mean age of participants was 41 years (SD: ±17). The most represented (24.4%) age class was 21-30 years and the least (1.9%) 1-10 years. Anti-T. gondii antibodies were detected in 174 (17.3%) of the cases. No statistically significant associations were found between seropositivity to T. gondii and area of residence, age, gender and educational levels of the participants., Conclusions: Findings of this study show that the seroprevalence of toxoplasmosis among the nomads of Kohgiluyeh and Boyer-Ahmad province is alike to other communities in our country. Further study is required to elucidate the genotype of T. gondii in this community.

Background: Kinesin-related gene diversity among strains and species of Leishmania may impact the sensitivity and specificity of serodiagnostic tests for visceral leishmaniasis (VL)., Methods: In this study, we report on the recombinant expression of this novel Iranian Leishmania infantum (MCAN14/47) homologue of rK39 (Li-rK39), in L. tarentolae. The diagnostic potential of the Li-rK39 antigen was evaluated in an ELISA, using sera from 100 VL patients, 190 healthy endemic controls, 46 non-endemic healthy controls and 47 patients with other infections., Results: The results showed a sensitivity of 96% and a specificity of 93.8%. A commercial rK39 immunochromatographic test (ICT) was 90% sensitive and 100% specific on the same cohort., Conclusions: Here, we show that the K39 gene from an Iranian L. infantum isolate is heterozygous as compared to the sequence of the Brazilian L. infantum (former L. chagasi), whose antigen is incorporated in most rK39-based immunochromatographic tests. Therefore, Li-rK39 has the potential to be used as an alternative for VL diagnosis in Iran.

In this work, biological synthesis of MgO/perlite nanocomposites (NCs) besides their effects on morphology and secondary metabolite profiles of Melissa officinalis plant organ cultures were evaluated. MgO NPs were immobilized on the surface of nanoperlite using M. officinalis extract as a capping agent. The as-synthesized MgO/perlite NCs were characterized by using FTIR, XRD, SEM, EDS and DLS. The average particle size of nanoperlite and MgO/perlite NCs was about 10 and 30 nm, respectively. Morphological observations showed that nanoperlite and MgO/perlite NCs had no effect on root number, as well as root and shoot length. None of the applied concentrations of perlite and MgO/perlite NCs could significantly increase the growth parameters in comparison to the control, except for 150 mg/L of nanoperlite which caused an increase in the shoot number. Although, the contents of chlorophyll and carotenoids were not affected, the maximum content of volatile compounds obtained at 100 of MgO/perlite NCs. Rosmarinic acid was detected in shoots, which treated with 25-100 mg/L of perlite and 25, 50 and 150 mg/L of MgO/perlite NCs. Our results provided the evidence that nanoperlite and MgO/perlite NCs at specific levels may act as a novel elicitor for in vitro biosynthesis of valuable secondary metabolites., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Visceral leishmaniasis (VL) can lead to death in more than 95% of cases if left untreated. Accurate and early diagnosis has an important role in reducing mortality rate of this disease., Objective: To express recombinant H2B antigen from an Iranian isolate of Leishmania Infantum and evaluate its efficacy in the diagnosis of VL., Methods: The recombinant H2B antigen was produced in a prokaryotic system, and its efficacy for VL diagnosis was evaluated by ELISA. The serum samples from 80 VL patients, 100 individuals from endemic and non-endemic regions of VL, and 58 non-VL patients were collected. VL cases were confirmed based on the clinical sign, positive IFAT (>64), real time PCR, and response to treatment., Results: The H2B gene sequence of the Iranian L. infantum isolate had about 4% diversity in comparison with the H2B gene of the L. infantum counterpart. ELISA, using the produced H2B recombinant antigen, showed sensitivity of 71.25% (95% CI: 60.05%-80.82%) and specificity of 69.62% (95% CI: 61.81%-76.68%) regarding VL diagnosis., Conclusion: Recombinant H2B antigen expressed in the prokaryotic system had suboptimal performance for the serological diagnosis of VL. It seems that the production and expression of recombinant H2B antigen in a eukaryotic system may enhance the performance of this antigen in the diagnosis of VL in Iran.

Background: The presence of cruciate ligaments is very important for normal knee kinematics. Knee arthroplasty prostheses, in which these ligaments are maintained, have better kinematics. The aim of the present study was to investigate the association between femoral intercondylar notch (FIN) narrowing in radiography and clinical and histopathologic integrity of anterior cruciate ligament (ACL) in patients undergoing knee replacement surgery., Methods: FIN index was measured in tunnel view radiography of the knees of 102 candidates of knee replacement surgery. The anatomical status of ACL was also examined during total knee arthroplasty (TKA). ACL was removed and sent for histopathologic examination to assess its degeneration rate. The association between the FIN index and the clinical and histopathological health of ACL was investigated., Results: Among 102 patients with mean age of 69.73 ± 7.81 years , 39 patients (38.32%) had no or torn ACL, 31 patients (30.39%) had weak ACL, and 32 (31.37%) had normal ACL. There was a significant association between age and clinical status of ACL during surgery ( P=0.017 ). There was a significant difference in FIN and ACL health status during surgery between the two groups with an index of more and less than 0.252 ( P=0.019 and P=0.019 , respectively). There was no significant difference in the mean total degeneration score (TDS) of ACL between the two groups with FIN more and less than 0.252 ( P=0.816 )., Conclusion: There was a significant difference between the age and FIN narrowing (less than 0.252) as well as ACL clinical status during surgery. FIN narrowing had no significant effect on the severity of ACL degeneration and there was no significant difference in the severity of degenerative histopathologic changes between healthy and attenuated ACLs. This indicates that if ACL exists, although apparently attenuated, it has the histologic characteristic of a healthy ligament., (2019 © BY THE ARCHIVES OF BONE AND JOINT SURGERY.)

The acetylcholine receptor (AChR) is a member of the superfamily of transmitter-gated ion channels having a critical role in controlling electrical signals between nerves and muscle cells. Disruptive mutations in genes encoding different subunits of AChR result in multiple pterygium syndrome (MPS), which can be associated with a severe prenatally lethal presentation. This study aimed to investigate the etiology of lethal MPS (LMPS) in two consanguineous families with a history of miscarriages. DNA was extracted from a tissue sample of two aborted fetuses (probands) from two different families with a history of spontaneous miscarriages. Parental peripheral blood samples were collected for confirmatory analysis and follow-up testing. Whole-exome sequencing (WES) was performed on DNA from the probands. The results were confirmed and segregated by Sanger sequencing. Moreover, protein structure evaluations were accomplished. We identified a homozygous frameshift mutation of c.753_754delCT (p.V253fs*44) and a homozygous missense mutation of c.715C>T (p.Arg239Cys) in the CHRNG gene. Both aborted fetuses had pterygium, severe arthrogryposis, and fetal hydrops with cystic hygroma, being compatible with LMPS. The heterozygous state was confirmed in parents for both CHRNG variants. Likewise, CHRNG mutation was predicted to display the damaging effects by lowering the number of helixes and modifying the surface electrostatic potential. The present study identified rare sequence variants in the CHRNG gene in aborted fetuses from consanguineous couples with recurrent miscarriage history. WES is a comprehensive and cost-effective approach to study heterogeneous diseases including MPS. Such findings can improve our knowledge of MPS databases, particularly for genetic counseling of high-risk families and preimplantation genetic diagnosis.

The current study aimed to determine the seroprevalence of Toxoplasma gondii infection and associated risk factors in children in a rural community in Fars province in southern Iran. Blood samples were collected from 671 children living in three rural areas, and sera and buffy coats were isolated from each sample. Anti-T. gondii antibodies were detected by ELISA, using a commercial kit. Also, buffy coats of seropositive children were examined by a PCR method, targeting a 529 bp gene of T. gondii. Of 671 children participating in the study, 319 (51.7%) were boys and 298 (48.3%) were girls. The mean age of the children was 9.7 (±10.7) years. Anti-Toxoplasma antibodies were detected in sera of 23 out of 671 children, corresponding to a seroprevalence rate of 3.8%. Gender and level of education had no significant influence on the risk of Toxoplasma infection (p>0.05). Toxoplasma DNA was not detected in buffy coats of any of the seropositive cases. Geographic location, as well as the low age of the participants, may contribute to the low rate of Toxoplasma infection in children of rural areas in southern Iran.

Structure activity correlation revealed that the quinoxaline ring is a satisfactory backbone for anticancer activity and a specific functional group at position 1 and 2 can improve the activity. In this basis, besides quinoxaline, imidazoles as potential anticancer agents were used as a supplementary agents for cancer treatment. In this paper, a new series of N-alkyl-2, 4-diphenylimidazo [1, 2-a] quinoxalin-1-amine derivatives were synthesized in a simple and efficient step. The products are fully characterized by 1H NMR, 13 C NMR, FT-IR, HRMS, and CHN elemental analysis. Several starting materials with different functionalities have been used for the synthesis of the final products with high isolated yields. The biological activities of the synthesized compounds were evaluated in kinase inhibition and cytotoxic activity in several cancerous cell lines. All compounds (6) were evaluated for inhibition of the cell proliferation using 4 cancerous cell lines. Five of the more active compounds were studied for determination of IC50 %. Compounds 6(32-34) showed good activity on some of cancerous cell lines. The results showed that compound 6-32 has the highest biological activity (IC 50 % 9.77 for K562 cell line). An IC 50 % value of 15.84 µM was observed for 6-34. Furthermore 6-34 exhibited inhibition of ABL1 and c-Src kinases with an IC50% value of 5.25 µM and 3.94 µM respectively. Docking simulation was performed to position active synthesized compounds 6-32, 6-33, and 6-34 over the ABL1 active site in two different wild-type (DFG-in and DFG-out motif conformer) and T315I mutant to determine the probable binding orientation, conformation and mode of interaction. According to docking study, the docked location in wild type forms is similar and can be found near the P-loop region while in the case of T315I mutant form, the compounds have a distinct docked location which is close to the αC helix and activation loop. Also, it concluded the role of R 1 substituent on phenyl ring produced higher interaction energy. Additionally, the detailed inter-molecular energy and types of non-bonding interaction of these compounds over the wild-type and mutant form of ABL1., (Copyright © 2019. Published by Elsevier Inc.)

Background: Accurate and accessible diagnosis is key for the control of visceral leishmaniasis (VL). Yet, current diagnostic tests for VL have severe limitations: they are invasive or not suitable as point of care (POC) test or their performance is suboptimal in East Africa. We analysed the antigens in the VL serodiagnostics development pipeline to identify shortcomings and to propose strategies in the development of an alternative POC test for VL in East Africa., Objectives: The objective of this study was to identify and to analyse all antigens for VL serodiagnosis that have been published before 2018 in order to identify candidates and gaps in the pipeline for a new POC test in East Africa., Methods: A systematic literature search was performed on PubMed for original research articles on Leishmania-specific antigens for antibody detection of VL in humans. From each article, the following information was extracted: the antigen name, test format and characteristics, its reported sensitivity and specificity and study cohort specifications., Results: One hundred and seven articles containing information about 96 tests based on 89 different antigens were included in this study. Eighty six of these tests, comprising 80 antigens, were evaluated in phase I and II studies only. Only 20 antigens, all of which are native, contain a carbohydrate and/or lipid moiety. Twenty-four antigens, of which 7 are non-native, are composed of antigen mixtures. Nineteen tests, comprising 18 antigens, have been evaluated on East African specimens, of which only 2 (rK28 based immunochromatographic test and intact promastigote based indirect fluorescent antibody technique) consistently showed sensitivities above 94 and specificities above 97% in a phase III study and one in a phase II study (dot blot with SLA). Only rK28 is a non-native mixture of antigens which we consider suitable for further evaluation and implementation., Conclusions: The development pipeline for an alternative serodiagnostic test for VL is almost empty. Most antigens are not sufficiently evaluated. Non-protein antigens and antigen mixtures are being neglected. We propose to expand the evaluation of existing antigen candidates and to investigate the diagnostic potential of defined non-native carbohydrate and lipid antigens for VL serodiagnosis in East Africa., Competing Interests: The authors have declared that no competing interests exist.

The transcription factor T-cell factor 3 (TCF3), one component of the Wnt pathway, is known as a cell-intrinsic inhibitor of many pluripotency genes in embryonic stem cells (ESCs) that influences the balance between pluripotency and differentiation. In this study, the effects of inhibition of TCF3 transcription factor on the stemness of mouse ESCs (mESCs) were investigated using the decoy oligodeoxynucleotides (ODNs) strategy. The TCF3 decoy and its scramble ODNs were designed and synthesized. The interaction specificity of the TCF3 decoy with the TCF3 transcription factor was evaluated by the electrophoretic mobility shift assay. Subcellular localization was carried out using fluorescence and confocal microscopy. Self-renewal and pluripotency of mESCs were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), cell cycle and apoptosis, alkaline phosphatase (ALP), embryoid body (EB) formation, and real-time assays. All experiments were performed in triplicate. The results showed that knockdown of TCF3 by decoy ODNs transfection in mESCs led to an increase in the cell proliferation, ALP enzyme activity, and master regulatory stemness genes and a decrease in the number and diameter of EBs. These results supported TCF3 as a potential target to maintain the pluripotency and self-renewal capacity of mESCs. Knockdown of the TCF3 transcription factor using decoy ODNs can be a promising method to maintain the stemness of stem cells in regenerative medicine and cell therapy researches., (© 2019 International Federation for Cell Biology.)

Recently, the usage of electrospinning technology for the fabrication of fine fibers with a good deal of variation in morphology and structure has drawn the attention of many researchers around the world. These fibers have found their way in the many fields of science including medical diagnosis, tissue engineering, drug delivery, replica molding, solar cells, catalysts, energy conversion and storage, physical and chemical sensors and other applications. Among all applications, biosensing with the aim of rapid and sensitive biomarker detection is an area that warrants attention. Electrospun nanofibrous membranes enjoy numerous factors which benefit them to be used as potential candidates in biosensing platforms. Some of these factors include a high surface to volume ratio, analogous scale compared to bioactive molecules and relatively defect-free properties of nanofibers (NFs). In this review, we focused on the recent advances in electrospun nanofibrous membrane-based micro-analytical devices with an application as diagnostic systems. Hence, a study on the electrospun nanofiber usage in lab-on-a-chip and paper-based point-of-care devices, with an opening introduction to biosensors, nanofibers, the electrospinning method, and microfluidics as the principles of the intended subject, is provided. It is anticipated that the given examples in this paper will provide sufficient evidence for the potential of electrospun NFs for being used as a substrate in the commercial fabrication of highly sensitive and selective biosensors.

Cancer therapies using defects in homologous recombination (HR) DNA repair pathway of tumor cells are not yet approved to be applicable in patients with malignancies other than BRCA1/2-mutated tumors. This study was designed to determine the efficacy of combination therapy of a histone deacetylase inhibitor, valproic acid (VPA) and a novel PARP inhibitor AZD2461 in both PC-3 (PTEN-mutated) and DU145 (PTEN-unmutated) prostate cancer cell lines. The Trypan blue dye exclusion assay and the tetrazolium-based colorimetric (MTT) assay were performed to measure the cytotoxicity while combination effects were assessed based on Chou-Talalay's principles. Flow-cytometric assay determined the type of cell death. The real-time PCR analysis was used to evaluate the alterations in mRNA levels of HR-related genes while their protein levels were measured using the ELISA method. γ-H2AX levels were determined as a marker of DNA damage. We observed a synergistic relationship between VPA and AZD2461 in all affected fractions of PC-3 cells (CI<0.9), but not in DU145 cells (CI>1.1). Annexin-V staining analysis revealed a significant induction of apoptosis when PC-3 cells were treated with VPA+AZD2461 ( p<0.05 ). Both mRNA and protein levels of Rad51 and Mre11 were significantly decreased in PC-3 cells co-treated with VPA+AZD2461 while enhanced H2AX phosphorylation was found in PC-3 cells after 12 and 24 hours of co-treatment ( p<0.05 ). Our findings established a preclinical rationale for selective targeting of HR repair pathways by a combination of VPA and AZD2461 as a mechanism for reducing the HR pathway sufficiency in PTEN -mutated prostate cancer cells.

microRNAs (miRNAs) are a novel class of single-stranded RNAs with a key role in the regulation of gene expression. miRNA main mechanism of action involves interaction with the mRNA transcribed from the genes, leading to the target mRNA silencing and degradation. Indeed, it is easy to conceive that a defective miRNA-based mRNA regulation may compromise normal cell function and cause genetic diseases. A wide spectrum of studies has focused on the identification and introduction of regulatory diseases-specific miRNAs for the past decade. Overexpression or downregulation of several miRNAs can potentially stimulate or inhibit pathways related to the pathogenesis of celiac disease (CD). CD is a chronic inflammatory disease characterized by small intestinal mucosal injury and nutrient malabsorption in genetically susceptible individuals after the dietary ingestion of gluten. The disease is characterized by villous atrophy, intraepithelial lymphocyte infiltration, and chronic inflammation and activation of lamina propria T cells. The common genetic background in CD is the presence of heterodimeric human leukocyte antigen class II molecules DQ2 or DQ8 that account for ∼40% of the genetic predisposition in this disease. In fact, by minute identification of these miRNAs and related targets and mechanisms, specific therapeutics can be developed to suppress these pathophysiological pathways through the enhancement or inhibition of miRNAs. This development can open a new prospect for personalized medicine.

A new series of coumarin-3-carboxamide-N-morpholine hybrids 5a-5l was designed and synthesized as cholinesterases inhibitors. The synthetic approach for title compounds was started from the reaction between 2-hydroxybenzaldehyde derivatives and Meldrum's acid to afford corresponding coumarin-3-carboxylic acids. Then, amidation of the latter compounds with 2-morpholinoethylamine or N-(3-aminopropyl)morpholine led to the formation of the compounds 5a-5l. The in vitro inhibition screen against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) revealed that most of the synthesized compounds had potent AChE inhibitory while their BuChE inhibitions are moderate to weak. Among them, propylmorpholine derivative 5g (N-[3-(morpholin-4-yl)propyl]-2-oxo-2H-chromene-3-carboxamide) bearing an unsubstituted coumarin moiety and ethylmorpholine derivative 5d (6-bromo-N-[2-(morpholin-4-yl)ethyl]-2-oxo-2H-chromene-3-carboxamide) bearing a 6-bromocoumarin moiety showed the most activity against AChE and BuChE, respectively. The inhibitory activity of compound 5g against AChE was 1.78 times more than that of rivastigmine and anti-BuChE activity of compound 5d is approximately same as rivastigmine. Kinetic and docking studies confirmed the dual binding site ability of compound 5g to inhibit AChE., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-β were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-β and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-β production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.

Leukodystrophies are heterogeneous group of genetic white matter disorders with a wide range of neurologic and systemic manifestations. Defects in genes encoding aminoacyl tRNA (transfer ribonucleic acid) synthetase enzymes (aaRSs) are recently identified as the etiology of some leukodystrophies. Herein, we described two unrelated children referred to Children's Medical Center, Tehran, Iran, with developmental delay, nystagmus, seizures, psuedo-bulbar palsy and dystonia. Whole exome sequencing (WES) in both patients identified a homozygous (c.2T > C) variant in exon one of RARS gene, encoding cytoplasmic arginyl-tRNA synthetase. Our finding was confirmed by segregation analysis. In silico analyses of the c.2T > C variant showed its possible pathogenic role due to the absence of the start codon. Severe hypomyelination was the common neuroimaging finding of both cases. Spinal cord involvement was found in one of our patients which was not previously reported in studies. We, therefore, showed that RARS -related hypomyelination might affect spinal cord., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Resistance to trastuzumab has become a limiting factor for therapeutic efficacy of human epidermal growth factor 2 (HER2)-positive breast cancer. Different expression levels of miRNAs in cancer cells have been associated with poor prognosis and response to chemotherapy. The aim of this study was to evaluate miRNAs that were thought to be associated with HER2-positive breast cancer chemoresistance. In this study, the relative expression of candidate miRNAs to U6 RNA was evaluated in trastuzumab-resistant and trastuzumab-sensitive cells using relative real-time PCR. Our results demonstrated that miR-23b-3p, miR-195-5p, miR-656-5p, and miR-340-5p were significantly dysregulated. For the first time in this study, these miRNAs were identified to be involved in trastuzumab resistance. TargetScan and miRDB were then used for predicting the potential targets of the candidate miRNAs. Our results also revealed that the predicted potential targets of these miRNAs were strongly associated with drug resistance pathways. As a relative expression of candidate miRNAs was statistically different in trastuzumab-resistant and trastuzumab-sensitive cells, their potential targets were involved in drug resistance pathways. We strongly hypothesized the dysregulation of miRNAs as a possible mechanism of trastuzumab resistance. We also assumed that the strategic manipulation of these regulatory networks might be a possible therapeutic strategy to improve the results of chemotherapy for this resistance. However, more research is needed to evaluate the role of these miRNAs in the acquisition of trastuzumab resistance.

Background: Intestinal parasitic infections are the one of the most common health problems in developing countries., Objective: A number of patients die annually due to complications caused by these parasites.Therefore, the aim of this study was to investigate the rate and type of parasitic infections, determine the factors affecting them in Ilam city and also provide strategies to prevent them.In this descriptive cross-sectional study conducted in one of the Ilam labs in 2016, 417 stool specimens were randomly collected. All specimens were examined using direct and ethanol formaldehyde.Suspect specimens were examined using Trichrom staining. Demographic information was also recorded in a questionnaire, and finally the results were analyzed using statistical software SPSS 20.The data were then compared with Chi-square test., Results: Out of the 417 patients examined, 59 (14.1%) were infected with intestinal parasites. The type of parasitic infection in 9.4% was Blastocystis hominis, 3.6% Entamoeba coli, 0.5% Entamoeba histolytica, 0.5% Giardia and 0.2% Trichomonas hominis., Conclusion: Despite the improvement of public health, parasitic infections are still considered as one of the health problems in the city of Ilam. Therefore, proper planning, public health education, raising the level of health in the area and the provision of safe drinking water are some of the ways to reduce parasitic infections in the region., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The current study aimed at the seroepidemiological survey of human cystic echinococcosis (CE) in nomadic people in Boyer-Ahmad District in the southwest of Iran. One thousand and five nomads were selected by cross-sectional sample collection in nomadic tribes of Boyer-Ahmad District in the southwest of Iran. Blood samples were taken from each individual, and the sera were tested for detection of anti-hydatid cyst antibodies using antigen B-ELISA. A predesigned questionnaire which contained basic epidemiological and individual information related to hydatid cyst was filled for each subject during sample collecting. Subjects of the study were 227 males (22.6%) and 778 (77.4%) females. The mean age of the participants was 40.4 years old (±16.6). Anti-hydatid cyst antibodies were detected in 81 (8.1%) of the subjects. Seroprevalence rate for CE in females (9%) was more than males (4.8%). Multivariate logistic regression revealed significant associations between CE seropositivity and sex (odds ratio [OR] = 1.88; 95% confidence interval [CI] = 0.93-3.80) and dog ownership (OR = 8.3; 95% CI = 3.94-16.37). The rate of infection with CE in nomadic people in southwest of Iran is considerable. Treatment of dogs and increasing the level of people awareness may contribute a substantial advancement in the control of the disease in the area.

Latex agglutination test (KAtex) has been used in the last two decades for the diagnosis of visceral leishmaniasis (VL) in different VL-endemic areas. Here, we present a meta-analysis of studies which evaluated the KAtex for the diagnosis of VL to find out its overall diagnostic performance. A database search was performed on PubMed, Scopus, ISI Web of Science, Iranmedex and Google Scholar. The search of databases found 57 papers, of which 17 articles fulfilled our eligibility criteria. Meta-analysis of diagnostic accuracy (MADA) and Hierarchical Summary Receiver Operating Curve (HSROC) packages were used to do the meta-analysis and to obtain pooled estimates of sensitivity and specificity. Fixed effect bivariate analysis was conducted, using Mantel-Haenszel estimator, to measure the performance and diagnosis odds ratio (DOR) of the test. Heterogeneity of the test results was assessed by Chi-squared test. The sensitivity of individual studies ranged from 39.8 to 100%, and the specificity ranged from 64 to100%. The combined sensitivity and specificity estimates of KAtex were 77% (95% CI, 70-83%), and 97% (95% CI, 93-97%), respectively. Comparing the performance of the test by region suggests a significant difference where the lowest and highest sensitivities are reported from Nepal/Tunisia and Europe/Middle East respectively (p < 0.05). On the other hand, the lowest and highest rates of specificity were reported from Sudan and America/Middle East respectively. The overall specificity of KAtex is satisfactory. However, KAtex suffers from low sensitivity and this shortcoming should be improved. The test provides a rapid and simple diagnosis of VL and improvement of its sensitivity deserve further studies., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2018 Bahador Sarkari, Mohammad Fararouei, Samaneh Abdolahi Khabisi, Zahra Rezaei.)

The current study was performed to find out the seroprevalence of Toxocara infection in children living in a rural community in Fars province, southern Iran. Venous blood was taken from 617 children and evaluated for anti-Toxocara antibodies, using an ELISA system. Of the 617 studied children, 318 (51.5%) were boys and 299 (48.5%) were girls. Mean age of the participants was 9.2 (±10.7) years. Most cases of the recruited subjects (37.4%) were in the age group of 0-5 years. Anti-Toxocara antibodies were detected in sera of 39 (6.3%) of children. From these, 23 (62.2%) were boys and 14 (37.8%) were girls. The infection rate was almost the same in different age groups. No statistically significant differences were seen between seropositivity to Toxocara infection and gender or age of the participants. Dogs or cats ownership was not associated with Toxocara seropositivity. The adjusted associations of the study variables suggested that the visceral leishmaniasis (VL) seropositivity is significantly associated with the seroprevalence of Toxocara infection (P < 0.001). Findings of the current study revealed that Toxocara infection is a common infection among children in the studied rural community in Iran. Preventive measurements are necessary to minimize the rate of Toxocara infection in children in such communities., (© 2018 John Wiley & Sons Ltd.)

A novel series of ciprofloxacin-dithiocarbamate hybrids 7a - 7l were designed, synthesized, and evaluated against Gram-positive and Gram-negative bacteria. A significant part of the title compounds showed considerable antibacterial activity against Gram-positive species. The most potent compound against Gram-positive bacteria was 2-chloro derivative 7h and the most potent derivative against Gram-negative bacteria was 3-chloro compound 7i. In vitro antibacterial evaluation of compound 7h against clinically isolated bacteria methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) showed that this compound acted better than ciprofloxacin against the latter bacteria. Docking study of compound 7h in the active site of S. aureus DNA gyrase revealed that this ciprofloxacin-dithiocarbamate derivative interacted with the main components of the active site of the enzyme., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Nanoparticles are tiny materials with nanosized components less than 100 nm in at least one dimension with physicochemical properties, which make them very attractive for medical application. These compounds have been evaluated as potential medicines for several decades. Nanotechnology has provided advances in the various fields of health sciences such as diagnosis, prevention and treatment by application of the agents named nanomedicines, including proteins, polymers, micelles, dendrimers, liposomes, emulsions, nanocapsules and nanoparticles. These materials can act as a scaffold, gene/drug delivery, tumor suppressor, conjugated with surgical implant, etc. They can also use as a nanocomposite, artificial tooth and dental caries preventing agent in the dentistry science. This current review tries to summarize recent applications of nanomedicine in the medical and dental fields., (© 2018 APMIS. Published by John Wiley & Sons Ltd.)

Background: Chlamydia trachomatis and Neisseria gonorrhoeae are the two common transmissible pathogens from pregnant women to their neonates. Given the lack of routine screening and treatment of pregnant women in some areas, the possibility of transmission rises. This study seeks to determine the prevalence of C. trachomatis and N. gonorrhoeae in the pregnant women with no clinical symptoms and the vertical transmission rate to their neonates., Methods: The study was conducted on endocervical and eye swab samples of 239 pregnant women and their neonates. Identification was based on PCR method., Results: The prevalence rates of C.trachomatis in women and neonates were 37/239 (15.5%) and 28/239 (11.7%), and for N. gonorrhoeae 3/239 (1.3%), 1/239 (0.4%), respectively. The vertical transmission rates to the neonates were 28/37(75.6%) for C. trachomatis and 1/3 for N. gonorrhoeae., Conclusions: In the areas with a high prevalence of chlamydial or gonococcal infections, and in the absence of screening and treatment of the pregnant women, ocular prophylaxis with antibiotics is suggested as a part of routine neonatal care program for the prevention of chlamydial and gonococcal ophthalmia.

Background: Infantile Sandhoff disease (ISD) is a GM2 gangliosidosis that is classified as a lysosomal storage disorder. The most common symptoms of affected individuals at presentation are neurologic involvement. Here we report clinical course and demographic features in a case series of infantile Sandhoff disease. Enzymatically and some genetically proven cases of ISD were extracted from the Iranian Neurometabolic Registry (INMR) in Children's Medical Center, Iran, Tehran from December 2010 to December 2016., Result: Twenty five cases of infantile SD (13 female, 12 male) were included in this study. The age range of patients was 9-24 months with a mean of 15.8 months. The consanguinity rate of parents affected families was about 80%. The mean age of patients at disease onset was 6.4 months and the mean age at diagnosis was 14 months. Patients were diagnosed with a mean delay of 7.8 months. Eleven of patients died due to aspiration pneumonia and intractable seizure. The most common features at presentation (92%) were developmental delay or regression in speech and cognitive domains. Cherry red spots were detected in 17 patients (68%). Organomegaly was detected only in two patients. Enzyme studies showed marked reductions of both Hexosaminidase A and B in all patients. HEXB gene mutation studies performed in eight patients identified 6 different mutations, which five of them were novel., Conclusion: Infantile SD should be considered for each child presented with neurologic symptoms such as developmental delay and regression and cherry red spots in ophthalmic examination. Organomegaly is not a frequent clinical finding in infantile SD. Additionally; there are a genetic heterogenisity among Iranian patients.

Visceral leishmaniasis (VL) is a major health concern in patients with HIV infection in endemic areas of VL. In these areas, a substantial number of infected individuals are asymptomatic and the risk of acute VL infection in HIV/VL co-infected cases is high. The current study aimed to determine the prevalence of asymptomatic VL infection among HIV-infected patients in Fars province, southern Iran. Subjects of the study were 251 HIV-confirmed patients who all were clinically asymptomatic for leishmaniasis. Blood samples were obtained from each participant. Anti-Leishmania antibodies were detected in the sera using ELISA. DNA was extracted from the buffy coat of each subject and PCR amplified, targeting an ITS-2 gene of Leishmania. PCR products were purified from the gel and were sequenced. Overall, 19 out of 251 (7.6%) HIV-infected patients were found to be infected with Leishmania, using serological or molecular methods. Anti-Leishmania antibodies were detected in 13 (5.2%) patients and leishmanial DNA in 8 (3.2%) of the patients. The sequence analysis of DNA-positive cases revealed the species of the parasite as L. infantum. The high prevalence of VL among the patients with HIV is a serious challenge which demands further attention to improve the prophylaxis and treatment measurements of VL/HIV co-infection and thereby promoting the life expectancy and quality of life of these patients.

Quinazoline is one of the most widespread scaffolds amongst natural and synthetic bioactive compounds. Recently the quinazoline derivatives and in particular the 4-anilinoquinazolines have attracted much attention for their anticancer properties due to their capability to stabilize the kinase activity of epidermal growth factor receptor (EGFR). A series of fifteen previously designed and synthesized 4-anilinoquinazoline analogs (4-18) were evaluated for cytotoxic activity on two breast cancer cell lines (MCF-7 and MDA-MB-468). Ligand efficiency and binding mode studies were also done and evaluated for their potentially EGFR inhibitory effects in comparison with imatinib and erlotinib as reference drugs. Among the tested 4-anilinoquinazolines, compound 11 , which contains diethoxy at phenyl ring and morpholino pendants at positions 5 and 7 of the quinazoline ring, demonstrated the most potent biological activity on both cell lines. Our new quinazoline derivatives with different substituents such as cyclic or linear ethers and flour groups may be a promising cytotoxic lead compounds for further anti-breast cancer research.

Background: It is obvious that hemodialysis is a stressful process, leading to numerous social and psychological problems, and may cause fatigue and helplessness., Objective: This study aimed to explain the experiences of hemodialysis clients regarding the effect of psychological problems on fatigue., Methods: This article was extracted from a qualitative study conducted on clients undergoing hemodialysis in Khorramabad. To this end, a total of 15 participants were purposefully selected using the snowball sampling method and the required data was collected using individual, face to face, detailed and semi-structured interviews. There were 12 client interviewees and one doctor, one nurse and one hemodialysis client's spouse. Content analysis was used to analyze the data., Results: Continuous analysis of data and documents obtained from the interviews on the hemodialysis clients' experiences and comments regarding the main causes of fatigue revealed two main categories: 1) Psychological effects with subcategories of psychological stress and exhaustion; 2) Needs and constraints with subcategories of individual and social needs and constraints., Conclusion: According to the clients' speech and expression analysis, psychological impacts and disease-induced needs and constraints were the most important cause of fatigue and its continuation among these clients.

Background: Diagnosis of Visceral Leishmaniasis (VL) is still challenging. This review highlighted current status and challenges in the serological diagnosis of VL. Furthermore, the drawback of currently available serological tests and the most recent advancement in the designing and application of these assays for the diagnosis of VL are addressed., Methods: All the published literature cited within PubMed, ISI Web of Science, Google Scholar, Scopus, and IranMedex, regarding the immunodiagnosis of VL in human were sought from 2000 till Mar 2017. The search terms were "visceral leishmaniasis", or "kala-azar" subsequently combined with the search terms "diagnosis", "serodiagnosis", "human", "serological", "antigen detection" or "antibody detection". Data were extracted from literature which fulfilled our eligibility criteria., Results: Direct agglutination test (DAT) and rk39 dipstick have made a great improvement in the serological diagnosis of VL. Besides, other kinesin-related protein including K26, K28, and KE16 provided promisingly diagnostic accuracy in the diagnosis of VL. The Latex Agglutination Test for the diagnosis of VL (KAtex), with moderate sensitivity but high specificity, made a substantial contribution to the field. Moreover, a range of protein antigens has recently been detected in the urine of VL patients with encouraging diagnostic value., Conclusion: The suboptimal diagnostic accuracy of the currently available serological assays for the diagnosis of human VL necessitates further research and development in this field. Outcomes of immunodiagnostic tests based on recombinant antigens are favorable. These proteins might be the most appropriate antigens to be further evaluated and utilized for the diagnosis of human VL., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

The current study aimed to evaluate the seroprevalence of visceral leishmaniasis in asymptomatic healthy children in a rural area of Fars province, Southern Iran. Blood samples were taken from 617 asymptomatic healthy children and serum samples along with buffy coat were separated from the blood. The serum samples were assessed for antibodies against Leishmania infantum by an indirect ELISA and the buffy coats were tested for the presence of L. infantum DNA by molecular method. Of the 617 recruited children, 297 (48.1%) were female and 317 (51.4%) were male. Anti- Leishmania antibodies were detected in 17 (2.8%) of the children. From those 17 seropositive cases, 5 (29.4%) were male and 12 (70.6%) cases were female. Children aged 5-8 years had the highest seroprevalence rate; however, no associations were found between seropositivity to Leishmania and gender or age of the children. Moreover, L. infantum DNA was detected in buffy coat of 8 (1.3%) of 617 children. Three of the PCR-positive cases were seropositive whereas 14 of seropositive subjects (82.3%) were PCR-negative. Findings of the current study revealed a considerable subclinical leishmanial infection in children in the studied rural area in the south of Iran. Results of the current study could be used for surveillance, prevention, and control of VL in the area.

Listeria monocytogenes can cause circling disease, encephalitis, meningitis, septicemia, and mastitis in dairy cattle. Contamination from the environment can contaminate foods with Listeria spp. Consumption of foods containing L. monocytogenes can lead to listeriosis in susceptible people (adults with a compromised immune system), pregnant women, and infants. The objective of this study was to determine the prevalence of Listeria spp. and L. monocytogenes in various foods in Iran. We searched PubMed, Science direct, Scopus, Google scholar, and Iranian local databases including Iranian scientific information database and Magiran for relevant studies up to May 2015 using related keywords. In our preliminary search, we retrieved 1344 articles. After removing duplicates and reviewing titles/abstracts, 117 articles were considered, out of which, 75 articles had sufficient quality for inclusion in this meta-analysis. The prevalence of Listeria spp. contamination was about 18.3% in poultry, 8.5% in raw meat, 14.6% in ready-to-eat (RTE) foods, 10% in sea foods, 7.3% in traditional dairy, 3.2% in commercial dairy, and 0.1% in eggs. The findings showed that L. monocytogenes was most prevalent in ready to eat (9.2%), seafood (5.1%), poultry (5%), traditional dairy (4%), raw meat (2.6%), commercial dairy (1.4%), and egg (0.2%), respectively. Furthermore, the presence of L. monocytogenes particularly in RTE foods (that are consumed without further heat processing) and under-cooked products could be a potential risk for public health. So, contamination should be controlled at all levels of the food chain., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented., Patients and Methods: Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed., Results: Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants., Conclusions: Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Childhood leukodystrophies are a fast-growing field of pediatric neurology practice. Epidemiologic studies on the incidence of these disorders in children show different results. This is the first report of childhood leukodystrophies incidence from Iran. The enrolled patients were recruited from the neurometabolic bioregistry system that was organized in 2010 in the Children's Medical Center, Tehran, Iran. Herein is reported the incidence rate of leukodystrophies in those patients who were residents of 2 big popular provinces near Iran's capital city Tehran, with an average child population of 2 988 800 children. Ninety cases of leukodystrophies from Tehran and Alborz provinces who were registered between 2010 and 2016 in the bioregistry system were enrolled in this study. The annual incidence of inherited white matter disorders was 3.01/100 000, the highest number compared with those found in other studies using similar methods throughout the world. One of the main cause of this higher incidence could be the higher number of consanguineous marriages in Iran.

In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a - d and 5g , possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi.

Background: Glucose-induced protein glycation has been implicated in the progression of diabetic complications and age-related diseases. The anti-glycation potential of polyphenol-rich plant extracts has been shown previously. Bunium Persicum has been demonstrated to possess a high level of polyphenols. The aim of current in vitro study was to determine the possible inhibitory effect of Bunium Persicum hydroalcoholic extract (BPE) on glucose-induced bovine serum albumin (BSA) glycation, oxidation, and aggregation., Methods: Folin-Ciocalteu assay was used to measure the content of total phenolic compounds of BPE. To test the in vitro effect of BPE on the formation of glycated BSA, thiol group oxidation, and protein aggregation of BSA, various concentrations of BPE were incubated with BSA and glucose at 37 °C for 72 hr. Glycation, thiol group oxidation, and aggregation of BSA were then measured using thiobarbituric acid, 2, 4-dinitrophenylhydrazine, and Congo red colorimetric methods, respectively. Data were analyzed using the SPSS software (version 16.0). One-way ANOVA followed by Tukey's post hoc test was used to compare group means. P<0.05 was accepted as the statistically significant difference between groups., Results: The results demonstrated that the content of total phenolics of BPE was 122.41 mg gallic acid equivalents per gram dried extract. BPE (10, 15, and 30 μg/ml) significantly inhibited the formation of GA in a concentration-dependent manner. BPE also significantly decreased the levels of thiol group oxidation and BSA aggregation., Conclusion: The results showed that BPE has anti-glycation and antioxidant properties and might have therapeutic potentials in the prevention of glycation-mediated diabetic complications.

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the 14 th day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

Dichloroacetate (DCA) is a simple and small anticancer drug that arouses the activity of the enzyme pyruvate dehydrogenase (PDH) through inhibition of the enzyme pyruvate dehydrogenase kinases (PDK1-4). DCA can selectively promote mitochondria-regulated apoptosis, depolarizing the hyperpolarized inner mitochondrial membrane potential to normal levels, inhibit tumor growth and reduce proliferation by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis. In this study, a series of DCA analogues were applied to quantitative structure-activity relationship (QSAR) analysis. A collection of chemometrics methods such as multiple linear regression (MLR), factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR), and partial least squared combined with genetic algorithm for variable selection (GA-PLS) were applied to make relations between structural characteristics and cytotoxic activities of a variety of DCA analogues. The best multiple linear regression equation was obtained from genetic algorithms partial least squares, which predict 90% of variances. Based on the resulted model, an in silico -screening study was also conducted and new potent lead compounds based on new structural patterns were designed. Molecular docking as well as protein ligand interaction fingerprints (PLIF) studies of these compounds were also investigated and encouraging results were acquired. There was a good correlation between QSAR and docking results.

Glioblastoma multiform (GBM) is described as one of the most frequent primary brain tumors. These types of malignancies constitute only 15% of all primary brain tumors. Despite, extensive developments on effective therapeutic methods during the 20th century as well as the first decade of the present century (21st), the median survival rate for patients suffering from GBM is only approximately 15 months, even in response to multi-modal therapy. numerous types of reticuloendothelial system cells such as macrophages and microglial cells occupied within both GBM and also normal surrounding tissues. These immune cells acquire an otherwise activated phenotype with potent tumor-tropic functions that contribute to the glioma growth and invasion. The CC chemokine, CCL2 (previously named MCP-1) is of the most important CC chemokines family member involving in regulation of oriented migration and penetrative infiltration of mainly reticuloendothelial system cells specifically monocyte/macrophage phenotypes. Fundamental parts are played by CCL2 and its related receptor (the CCR2) in brain tumors and obviously in migration of monocytes from the bloodstream through the vascular endothelium. Therefore, CCL2/CCR2 axis is required for the routine immunological surveillance of tissues, in accordance with response to inflammation. Briefly, in this review, we have tried our best to collect the latest, straightened and summarize literature reports exist within data base regarding the interaction between microglia/macrophages and CCL2/CCR2 axis in GBM. We aimed to discuss potential application of this chemokine/receptor interaction axis for the expansion of future anti-glioma therapies as well., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.

Background: We aimed to investigate risky sexual behaviors (RSBs) and condom use barriers in Iranian men with substance use disorders (SUDs)., Methods: Of the total 1800 outpatient drug free (ODF) and methadone maintenance treatment program (MMTP) active centers in Tehran, Iran, six were selected to participate in the current study. Data were collected (n = 300 men) using three questionnaires including a demographic questionnaire, the Risky Sexual Behavior Questionnaire (RSBQ), and the Condom Barriers Scale (CBS). The statistical software R, analysis of variance post hoc and multivariate analysis of variance (MANOVA) logistic regression tests were used in data analysis., Findings: The majority, (n = 194, 64.7%) reported at least one lifetime episode of RSBs. Compared to married participants (23.1%), 88.5% of single and 87.0% of divorced men had a history of RSB. Generally, the lowest and highest subscale scores of the CBS were related to sexual experience (2.60 ± 0.71) and access/availability structure (3.77 ± 0.54), respectively. The results of MANOVA analysis showed that there was a statistically significant difference between the CSB subscales based on the participants' education and marital status (P < 0.001). Only the partner barrier subscale had a significant negative relationship (P = 0.003) with RSB., Conclusion: Sexual dynamic of Iranian men with SUDs is different. Barriers to condom use seem to be socio-culturally determined. Culturally acceptable strategies need to be utilized in Iranian clinical settings reaching beyond simply condom accessibility for this at risk population.

Acute myocardial infarction (AMI) is one of the leading causes of death throughout the world. Usual methods for detecting AMI are expensive, time-consuming and using blood samples as biological samples. Therefore, creating an ultra-fast, sensitive and non-invasive diagnostic test is necessary. Herein, a novel ultra-sensitive, fluorescent, plasmon-exciton coupling hybrid of a gold nanoparticle-quantum dot (PQ)-based aptamer nanobiosensor is presented for the detection of human cardiac troponin I (cTnI), the golden biomarker of AMI, and a preclinical test is performed within saliva. The binding of the cTnI protein to aptamer leads to a fluorescence enhancement of the plexcitonic hybrid system. The response range of this nanobiosensor is 0.4-2500 fM and the limit of detection is 0.3 fM. It seems that this novel design of nanobiosensor in the form of the PQ plexcitonic hybrid system can presents new opportunities for nanobiosensor progress., (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

We study the effect of superdiffusion on the instability in reaction-diffusion systems. It is shown that reaction-superdiffusion systems close to a Turing instability are equivalent to a time-dependent Ginzburg-Landau model and the corresponding free energy is introduced. This generalized free energy which depends on the superdiffusion exponent governs the stability, dynamics, and the fluctuations of reaction-superdiffusion systems near the Turing bifurcation. In addition, we show that for a general n-component reaction-superdiffusion system, a fractional complex Ginzburg-Landau equation emerges as the amplitude equation near a Hopf instability. Numerical simulations of this equation are carried out to illustrate the effect of superdiffusion on spatiotemporal patterns. Finally, the effect of superdiffusion on the instability in the Brusselator model, as a special case of reaction-diffusion systems, is studied. In general, superdiffusion introduces a new parameter that changes the behavior of the system near the instability.

Breastfeeding plays an important role in the growth and development of breastfed infants, especially in the first 6 months of their lives. The present study was conducted to determine the nickel concentrations in breast milk of lactating women in Yazd, Iran. One hundred fifty volunteers were selected among nursing mothers referring to health centers in Yazd. In the first month of lactation, milk samples were collected three times, on days 3 to 5 (first), 16 (Second), and 30 (third) after delivery. Nickel concentration of the samples was measured by atomic absorption spectrophotometer. Demographic variables were collected through a questionnaire which was completed by mothers. The mean age of the study group was 27.40 ± 4.66 years. The mean nickel concentrations in breast milk at the first, second, and third samples were 47.3 ± 7.40, 49.9 ± 8.05, and 54.8 ± 7.38 μg/l, respectively. The concentration of nickel in the breast milk of more than 86 % of mothers was higher than the permissible range for it. There was no significant relationship between the mean value of nickel in breast milk and education, age, and job of mothers. High level of nickel in breast milk may be attributed to consumed food and drinking water containing nickel. Monitoring the nickel level in breast milk regularly is recommended.

Introduction: Sleep hygiene was found as an important predictor for sleep quality. People's sleep hygiene can have a major role in their daily function. The purpose of the study was to determine sleep hygiene patterns and sleep hygiene behaviors and factors affecting them in the general population of Kermanshah, Iran., Material & Methods: In this cross-sectional study, 1829 men and 1262 women were selected randomly from 50 clusters of different parts of the city. The inclusion criteria were age between 12 and 65 years and living in Kermanshah. The exclusion criteria were psychiatric disorder and known general medical conditions that affecting sleep. The data collection instruments were demographic questionnaire and Sleep Hygiene Questionnaire, consisted of 13 items about biological rhythm and bed room environment and behaviors that affecting sleep. Data were analyzed by using SPSS version 16 software., Results: The highest percentage was obtained for irregular woke and went up from day to day or at weekend and holidays (74.8%). Only 213 (6.9%) participants were classified as having good sleep hygiene (score 12-14). The mean age of very poor, poor, moderate, and good sleepers was 34.8 ± 14.4, 33.7 ± 17.4, 36.5 ± 13.8, and 35 ± 13.7years, respectively. There were significant differences between the age of poor and moderate sleepers and also sleep hygiene patterns with respect to sex, education level and job., Conclusion: Poor sleep hygiene were more frequent in Iranian peoples and the major problem in sleep hygiene in our study was inappropriate sleep schedule., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: To determine whether Islamic fasting would change cerebral blood flow during Ramadan., Methods: The study group comprised 20 subjects (16 males and 4 females) on a regimen of 1 month food and water intake restriction, according to Islamic fasting ritual. Subjects were evaluated for cerebral bolo flow through a middle cerebral artery (MCA) by means of transcranial Doppler (TCD), the day before starting Ramadan fasting and the day after the month of Ramadan., Results: Our results showed no statistically significant changes after Ramadan in cerebrovascular hemodynamic, in comparison before Ramadan., Conclusion: Although some studies showed metabolic changes during Ramadan fasting (increasing hematocrite, decreasing amount of hemoglobin, dehydration, platelet aggregation, and lipid profile alternations) the findings suggest that Islamic fasting has no significant effects on cerebral blood flow.