Publications by authors named "Rezaee S"

167 Publications

A Peptide Construct Mediates Focal Adhesion Pathway Through the Activation of Integrin Receptor.

Curr Pharm Des 2020 ;26(15):1749-1755

Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran.

Background: The integrin family receptors stimulate the cellular proliferation and migration through the focal adhesion pathway by the activation of PTK2, VASP and TSP1 proteins. The purpose of this study was to investigate the integrin-ligated motifs through the activation of focal adhesion pathway.

Methods: A chimeric peptide was predicted from the integrin-mediated ligands by bioinformatics tools. The VSMCs were treated with the chimeric peptide and simvastatin. The PTK2, VASP and TSP1 protein and gene expression levels were measured by RT-qPCR and Western Blotting techniques, respectively. AutoDock Tools were used for the docking technique.

Results: The PTK2, VASP and TSP1 protein expression levels increased significantly in the VSMCs treated with chimeric peptide in conversely with the effects of simvastatin. The docking results suggested two motifs in the chimeric peptide.

Conclusion: In conclusion, the chimeric peptide activated the focal adhesion pathway. The motifs 1 and 2 may be directly involved in the transduction of signal by integrin family receptors.
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http://dx.doi.org/10.2174/1381612826666200311125325DOI Listing
November 2020

Evaluation of the Effects of 1,25 Vitamin D3 on Regulatory T Cells and T Helper 17 Cells in Vitamin D-deficient Women with Unexplained Recurrent Pregnancy Loss.

Curr Mol Pharmacol 2020 ;13(4):306-317

Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad Branch, Mashhad, Iran

Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms that are yet unknown. The aim of this study was to evaluate the effect of 1,25VitD3 on regulatory T cells (Tregs) and T helper17 (Th17) cell populations In vitro in unexplained recurrent pregnancy loss (URPL) patients and healthy women.

Methods: Samples from 20 non-pregnant women with a history of URPL were compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMC) were divided into 3 wells for each subject: in the presence of 1, 25 VitD3 (50 nM, for 16 hours), PHA (positive control) (10μM), and without any treatment (as a baseline or negative control). The percentage of regulatory T cells and Th17 cells was measured by flow cytometry at baseline and then after cell culture experiments.

Results: Our study indicated that the percentage of Tregs in patients with URPL was significantly lower than the control group (2.42 ± 0.27 vs. 3.41 ± 0.29, P= 0.01). The percentage of Th17 cells was significantly greater in URPL patients compared to the control group (2.91 ± 0.33 vs. 1.18± 0.15, P=0.001). 1, 25VitD3 treatment significantly increased the percentage of Tregs from the baseline in the URPL group compared to that in the control group (1.23 ± 0.03 vs. 1.00 ± 0.03, P= 0.01).

Conclusion: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests supplementation of women with Vit D pre-pregnancy may be protective against URPL.
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http://dx.doi.org/10.2174/1874467213666200303130153DOI Listing
January 2020

Evaluating physicochemical properties of crude oil as indicators of low-salinity-induced wettability alteration in carbonate minerals.

Sci Rep 2020 Feb 28;10(1):3762. Epub 2020 Feb 28.

Department of Chemical and Biomolecular Engineering, Rice University, 6100 Main St., MS-362, Houston, TX, 77005, USA.

The injection of low-salinity brine enhances oil recovery by altering the mineral wettability in carbonate reservoirs. However, the reported effectiveness of low-salinity water varies significantly in the literature, and the underlying mechanism of wettability alteration is controversial. In this work, we investigate the relationships between characteristics of crude oils and the oils' response to low-salinity water in a spontaneous imbibition test, aiming (1) to identify suitable indicators of the effectiveness of low-salinity water and (2) to evaluate possible mechanisms of low-salinity-induced wettability alteration, including rock/oil charge repulsion and microdispersion formation. Seven oils are tested by spontaneous imbibition and fully characterized in terms of their acidity, zeta potential, interfacial tension, microdispersion propensity, water-soluble organics content and saturate-aromatic-resin-asphaltene fractionation. For the first time, the effectiveness of low-salinity water is found to positively correlate with the oil interfacial tension in low-salinity water. Oils with higher interfacial activity are found to respond more positively to low-salinity water. Moreover, cryogenic transmission electron microscopy images suggest that microdispersion is essentially macroemulsion, and its formation is an effective indicator - but not the root cause - of wettability alteration. The repulsive zeta potential for the rock and the oil in low-salinity water is found to be an insufficient condition for wettability alteration in carbonate minerals.
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http://dx.doi.org/10.1038/s41598-020-60106-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048854PMC
February 2020

Pichia pastoris: A highly successful expression system for optimal synthesis of heterologous proteins.

J Cell Physiol 2020 09 14;235(9):5867-5881. Epub 2020 Feb 14.

Mashhad University of Medical Sciences, Antimicrobial Resistance Research Center, Mashhad, Iran.

One of the most important branches of genetic engineering is the expression of recombinant proteins using biological expression systems. Nowadays, different expression systems are used for the production of recombinant proteins including bacteria, yeasts, molds, mammals, plants, and insects. Yeast expression systems such as Saccharomyces cerevisiae (S. cerevisiae) and Pichia pastoris (P. pastoris) are more popular. P. pastoris expression system is one of the most popular and standard tools for the production of recombinant protein in molecular biology. Overall, the benefits of protein production by P. pastoris system include appropriate folding (in the endoplasmic reticulum) and secretion (by Kex2 as signal peptidase) of recombinant proteins to the external environment of the cell. Moreover, in the P. pastoris expression system due to its limited production of endogenous secretory proteins, the purification of recombinant protein is easy. It is also considered a unique host for the expression of subunit vaccines which could significantly affect the growing market of medical biotechnology. Although P. pastoris expression systems are impressive and easy to use with well-defined process protocols, some degree of process optimization is required to achieve maximum production of the target proteins. Methanol and sorbitol concentration, Mut forms, temperature and incubation time have to be adjusted to obtain optimal conditions, which might vary among different strains and externally expressed protein. Eventually, optimal conditions for the production of a recombinant protein in P. pastoris expression system differ according to the target protein.
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http://dx.doi.org/10.1002/jcp.29583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228273PMC
September 2020

Micromorphology analysis of TiO thin films by atomic force microscopy images: The influence of postannealing.

Microsc Res Tech 2020 May 8;83(5):457-463. Epub 2020 Jan 8.

School of Physics, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran, Iran.

This work describes an analysis of titanium dioxide (TiO ) thin films prepared on silicon substrates by direct current (DC) planar magnetron sputtering system in O /Ar atmosphere in correlation with three-dimensional (3D) surface characterization using atomic force microscopy (AFM). The samples were grown at temperatures 200, 300, and 400°C on silicon substrate using the same deposition time (30 min) and were distributed into four groups: Group I (as-deposited samples), Group II (samples annealed at 200°C), Group III (samples annealed at 300°C), and Group IV (samples annealed at 400°C). AFM images with a size of 0.95 μm × 0.95 μm were recorded with a scanning resolution of 256 × 256 pixels. Stereometric analysis was carried out on the basis of AFM data, and the surface topography was described according to ISO 25178-2:2012 and American Society of Mechanical Engineers (ASME) B46.1-2009 standards. The maximum and minimum root mean square roughnesses were observed in surfaces of Group II (Sq = 7.96 ± 0.1 nm) and Group IV (Sq = 3.87 ± 0.1 nm), respectively.
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http://dx.doi.org/10.1002/jemt.23433DOI Listing
May 2020

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis.

Retrovirology 2019 12 30;16(1):46. Epub 2019 Dec 30.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP.

Results: High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12).

Conclusions: High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.
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http://dx.doi.org/10.1186/s12977-019-0508-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937958PMC
December 2019

Separation of the Epitopes in a Multi-Epitope Chimera: Helical or Flexible Linkers.

Protein Pept Lett 2020 ;27(7):604-613

Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The engineered chimeric peptides including functional multi-epitope structures fused by various peptide linkers are widely applied in biotechnological research to improve the expression level and biological activity of chimera.

Objective: The aim of our study was to evaluate the effect of helical and flexible linkers on solubility, expression level and folding of multi-epitope chimera containing four epitopes of Human T Lymphotropic Virus Type 1 (HTLV-1).

Methods: For this purpose, the chimera sequences connected by the helical or flexible linker were inserted into different plasmid vectors and expressed in E. coli strains. The expressed products were analyzed using SDS-PAGE and Western blot techniques. Additionally, the molecular modeling study of the chimera with helical or flexible linker was performed using iterative threading assembly refinement (I-TASSER) to attain their three-dimensional structures.

Results: Comparison of the chimera expression indicated that the insertion of a flexible (GGGGS)3 linker among chimera epitopes could significantly enhance the level of expression, whereas, the low-level of chimera expression was observed for chimera containing the contiguous helical (EAAAK)5 linker. According to the results of sequence alignment and plasmid stability test, the structure and function of a consecutive helical linker among chimera epitopes were similar to porins as the outer-membrane pore-forming proteins. The molecular modeling results confirmed our experimental study.

Conclusion: This investigation illustrated the key role of linker design in determining the expression level of multi-epitope chimera and conformational folding.
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http://dx.doi.org/10.2174/0929866526666191112124602DOI Listing
January 2021

Abnormal vitamin D and lipid profile in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Mol Biol Rep 2020 Jan 11;47(1):631-637. Epub 2019 Nov 11.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of host-HTLV-1 interactions. In many virus-associated diseases and multiple sclerosis, the importance of vitamin-D and lipid profile has been demonstrated, thus similarly, their impacts were evaluated in HAM/TSP patients, in this study. Vitamin D and lipid profile were assessed in 120 healthy subjects (HSs), along with a proviral load (PVL) in 91 HAM/TSPs and 169 HTLV-1 carriers (ACs). The mean level of triglyceride and LDL in the HAM/TSPs were higher than HSs (P = 0.008 and 0.008, respectively), but no significant difference has been found between ACs and HSs. However, the level of HDL and vitamin-D in the HAM/TSP subjects were lower than HSs (P = 0.01 and P = 0.006, respectively). In HTLV-1 infected subjects, PVL was statistically associated with cholesterol (R = 0.24, P = 0.038), triglycerides (R = 0.26, P = 0.01) and HDL (R = 0.28, P = 0.001), and in HAM/TSPs there was a strong association between the severity of the disease, as determined by the OMDS and cholesterol (P = 0.01). Furthermore, in the HAM/TSPs, positive correlations between vitamin-D and age (R = 0.23, P = 0.028) and triglycerides (R = 0.38, P = 0.001) were found, also a significant correlation between PVL and LDL (R = 0.21, P = 0.001) and a weak correlation between PVL and OMDS (R = 0.4, P = 0.07) were noted. However, there was no correlation between PVL and urinary disturbance. Furthermore, PVL range of more than 600 copies/10 lymphocytes had a strong correlation with OMDS (P = 0.05), but not with urinary disturbance. It's more likely that HAM/TSP patients have an imbalanced lipid profile and low levels of vitamin D and may represent a potentially useful target for intervention in HTLV-1 associated diseases.
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http://dx.doi.org/10.1007/s11033-019-05171-1DOI Listing
January 2020

Epigenetics evaluation of the oncogenic mechanisms of two closely related bovine and human deltaretroviruses: A system biology study.

Microb Pathog 2020 Feb 4;139:103845. Epub 2019 Nov 4.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Human T-cell lymphotropic virus (HTLV-1) and bovine leukemia virus (BLV) are oncogenic deltaretroviruses, which are the cause of adult T cell leukemia/lymphoma (ATLL) and enzootic bovine leukosis (EBL), respectively. In this study, to evaluate the virus-host interactions in the manifestation of the associated malignancy, four pooled RNA samples of each host (three RNAs in each sample) were applied to RNA-seq. Differential expression analyses were conducted separately between ATLL and EBL groups, in comparison with the healthy group, to identify functional Gene Ontology (GO) terms and hub genes, using DAVID database and MCODE plugin in Cytoscape software, respectively. A broad range of effective genes, involved in the ATLL and EBL, was up- and downregulated. In the virus side, in both malignancy, Tax was expressed very low, but the HTLV-1-HBZ and BVL-As2 transcripts were highly expressed. Some upregulated hub genes, IL2, TOP2A, MKI67, TP73, MYC, and downregulated FOS gene family (FOS, FOSB, and FOSL2), are similarly activated in both human and bovine hosts, in related cell cycle and growth factors. Taken together, it seems that in preventing the infections and cell transformations, Tax must be targeted as a viral factor, and shared peptide in virological and immunological synapses as host factors. Therefore, in the malignant stages, HBZ and As2 transcripts along with growth factors, particularly IL-2R-γ and T-bet or TOP2A, and MKI67 should be targeted in both hosts. Additional studies at the protein level are necessary to elucidate the more useful targets for the therapy of these life-threatening diseases.
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http://dx.doi.org/10.1016/j.micpath.2019.103845DOI Listing
February 2020

Direct conversion of inorganic complexes to platinum/thin oxide nanoparticles decorated on MOF-derived chromium oxide/nanoporous carbon composite as an efficient electrocatalyst for ethanol oxidation reaction.

J Colloid Interface Sci 2019 Nov 6;555:655-666. Epub 2019 Aug 6.

Department of Chemistry, Shahid Beheshti University, Tehran 19839-63113, Iran. Electronic address:

In this work, we present the design and fabrication of a novel nanocomposite based on noble metal and metal oxide nanoparticles dispersed on highly porous carbon obtained via the pyrolysis of an inorganic complex and metal-organic frameworks. This nanocomposite is prepared by a two-step procedure: first, the composite support of nanoporous carbon (NPC) is obtained by the direct carbonization of the Cr-benzene dicarboxylic ligand (BDC) MOF in an Argon atmosphere at 500 °C (CrO-NPC). A mixture containing CrO-NPC and [PtCl(SnCl)(SMe)] is then prepared, and underflow of Argon is heated to 380 °C. Finally, Pt-SnO nanoparticles are loaded on the CrO-NPC support, and the obtained nanocomposite was denoted as Pt-SnO/CrO-NPC. The morphology and crystalline structure of the prepared nanocomposites were characterized using XRD, SEM, EDX, FT-IR, and XPS. In addition, the prepared nanocomposite was examined as a novel electrocatalyst for the ethanol electro-oxidation reaction (EOR). The obtained results demonstrated that, compared with Pt/CrO-NPC, Pt-SnO/CrO-NPC showed higher electrocatalytic activity, lower onset potential, and a higher level of poisoning tolerance toward of ethanol oxidation in acidic media. The overall results corroborate the predominant role of SnO as an excellent catalytic-enhancing agent thorough facilitating the charge transfer process and increasing the CO poisoning oxidation by the spillover of OH to the Pt surface. Thus, the prepared Pt-SnO/CrO-NPC catalyst could be considered a promising anode catalyst for direct ethanol fuel cells.
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http://dx.doi.org/10.1016/j.jcis.2019.08.018DOI Listing
November 2019

Immunoregulatory and anti-inflammatory properties of (Saffron) and its main active constituents: A review.

Iran J Basic Med Sci 2019 Apr;22(4):334-344

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

The medicinal uses of saffron, the dried stigmas of L., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases. is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on thimmune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. This review summarizes the protective roles of and its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions.
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http://dx.doi.org/10.22038/ijbms.2019.34365.8158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535192PMC
April 2019

Reliability and Concurrent Validity of a Culturally Adapted Persian Version of the Brace Questionnaire in Adolescents With Idiopathic Scoliosis.

Spine Deform 2019 07;7(4):553-558

Rehabilitation Research Center, School of Rehabilitation Sciences, Iran University of Medical Sciences, Madadkaran Avenue, Shahnazari St., Madar square, Mirdamad Blvd., Tehran, Iran.

Study Design: Cross-sectional.

Objectives: To determine the validity and reliability of culturally adapted Persian version of the Brace Questionnaire (P-BrQ).

Summary Of Background Data: The BrQ has proved to be a reliable and valid instrument for evaluating the quality of life of adolescents with idiopathic scoliosis and has been translated to different languages. But, lack of a Persian translated version makes its use impractical in the Persian speaking scoliotic patients.

Methods: Forward and backward translation of P-BrQ was conducted according to the International Quality of Life Assessment guidelines. The final version of the P-BrQ was administered to 51 adolescents (1 boy and 50 girls) with idiopathic scoliosis. The mean age of the participants was 13.88 ± 2.14 years. The questionnaire's internal consistency was determined using Cronbach's alpha. A subgroup of 38 participants were randomly selected to complete the BrQ for a second time one week later. The test-retest reliability was then analyzed using the intraclass correlation coefficient, while the concurrent validity was assessed by comparing the BrQ with the Scoliosis Research Society-22 questionnaire.

Results: The total Cronbach's alpha coefficient of the P-BrQ was 0.96, and the overall intraclass correlation coefficient of the questionnaire was also 0.96. The intraclass correlation coefficients for the corresponding domains were as follows: general health perception, 0.96; physical functioning, 0.96; emotional functioning, 0.98; self-esteem, 0.80; vitality, 0.97; school activity, 0.98; pain, 0.97; and social functioning, 0.98.

Conclusions: The culturally adapted Persian version of the BrQ can be used to assess the quality of life of adolescents with idiopathic scoliosis who wear a brace.

Level Of Evidence: II.
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http://dx.doi.org/10.1016/j.jspd.2018.10.001DOI Listing
July 2019

HTLV-1-host interactions facilitate the manifestations of cardiovascular disease.

Microb Pathog 2019 Sep 6;134:103578. Epub 2019 Jun 6.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery diseaseHTLV-1 (CADHTLV-1), 8 CADHTLV-1, and 17 CADHTLV-1 patients and 11 healthy subjects (CADHTLV-1) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CADHTLV-1 group was higher than CADHTLV-1 (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CADHTLV-1 was higher in comparison with CADHTLV-1group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CADHTLV-1 subjects was higher than CADHTLV-1 and CADHTLV-1 (P = 0.001, P = 0.005, respectively). In CADHTLV-1 subjects, CCR2 was higher than CADHTLV-1 (P = 0.03). The mean PVL in CADHTLV-1 group is more than CADHTLV-1 (P = 0.041). In HTLV-1 patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CADHTLV-1. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.
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http://dx.doi.org/10.1016/j.micpath.2019.103578DOI Listing
September 2019

Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):2123-2133

d Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences , Hamadan , Iran.

Indinavir (IDV) is a potent HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV). IDV is a weak base with limited aqueous solubility in its unprotonated form; therefore, solubility of IDV in the gastrointestinal tract fluids is the rate-limiting step of its absorption and onset of action. However, in many cases, drugs are not absorbed well in the gastrointestinal tract; polymer nanoparticles were recognized as an effective carrier system for drug encapsulation and are now studied as a vehicle for oral delivery of insoluble compounds. Preparation of methoxy poly (ethylene glycol)-poly (e-caprolactone) (mPEG-PCL) nanoparticles is among the strategies to overcome low bioavailability of drugs with poor aqueous solubility. The structure of the copolymers was characterized using H NMR, FTIR, DSC and GPC techniques. IDV loaded mPEG- PCL nanoparticles prepared by emulsification solvent evaporation method were optimized using D-optimal experimental design and were characterized by various techniques such as DLS, DSC, XRD, AFM and SEM. Using Caco-2 cells as a cellular model, we studied the cellular uptake and transport. pharmacokinetic studies were performed in rats. The plasma AUC (0-), and of IDV-mPEG-PCL NPs were increased by 5.30, 5.57 and 1.37 fold compared to the IDV solution, respectively. The results of this study are promising for the use of biodegradable polymeric nanoparticles to improve oral drug delivery.
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http://dx.doi.org/10.1080/21691401.2019.1616553DOI Listing
December 2019

Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.

Infect Genet Evol 2019 09 16;73:460-469. Epub 2019 May 16.

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region. The genome size of HTLV-1-MhD (Mashhad) was found to be 9036 bp and sequence analysis of the LTR region showed that it belongs to cosmopolitan subtype A. Comparing the sequences with isolates from another endemic area (HTLV-1ATK) revealed variations in the U3 region (~3.4%), while there was 99.1% and 97.0% similarity in R and U5 regions, respectively. The nucleotide sequences of HTLV-1 gag, pro and pol genes had a difference of 1.1% compared with HTLV-1 ATK with 16 nucleotides replaced in the gag and 27 in the pol regions. There was no variability in the amino acid sequences in the p24, however three residues were different in the p19 and one in the p15. The nucleotide sequence of env showed a divergence of 1.5% compared to ATK with 22-nucleotide variation. The HTLV-1-MhD Tax, p13, p30, and p12 had 99.1, 100, 98.8, and 98%, respectively similarity with the prototype strain. Four amino acid changes were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. The nucleotide identity between the isolates of Mashhad and those isolated from France, Germany, China, Canada and Brazil was 99.1%, 99.2%, 97.9%, 99% and 99.3%, respectively. Four amino acid changes compared with HTLV-1ATK from Japan were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. This data could provide information regarding the evolutionary history, phylogeny, origin of the virus and vaccine design.
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http://dx.doi.org/10.1016/j.meegid.2019.05.012DOI Listing
September 2019

Magnetic brain targeting of naproxen-loaded polymeric micelles: pharmacokinetics and biodistribution study.

Mater Sci Eng C Mater Biol Appl 2019 Jul 3;100:771-780. Epub 2019 Mar 3.

Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

The blood brain barrier is a major obstacle to the entry of the majority of CNS-active agents. In the present research, the potential of magnetic polymeric micelles (MPMs) for brain-targeting of naproxen was evaluated. The MPMs were made of methoxy poly(ethyleneglycol)-poly (caprolactone) copolymer and super paramagnetic iron oxide nanoparticles (SPIONs). To investigate the impact of particle size on the in vivo biofate of nanoparticles, MPMs with two different sizes were prepared. The prepared magnetic polymeric micelles had diameters of 137 ± 3.5 nm (MPM137) and 242 ± 6.2 nm (MPM242) and their surface charges were about -6.5 and - 4.5 mV, respectively. Pharmacokinetic and biodistribution of nanoparticles were characterized in rats using an external magnet of 0.4 Tesla field strength located on the skull of anesthetized animals. Significant differences in volumes of central as well as peripheral compartments were observed between both MPM formulations and free naproxen solution. After 8 h of administration, the brain concentration of naproxen was shown to be higher in the case of MPM137 in comparison with MPM242 and free drug. The findings revealed that the polymeric magnetic micelles with diameters smaller than 150 nm could be initially considered as a promising carrier to improve therapeutic agent accumulation in the brain for the treatment of CNS diseases.
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http://dx.doi.org/10.1016/j.msec.2019.03.004DOI Listing
July 2019

Mycobacterium tuberculosis Ag85b:hfcγ1 recombinant fusion protein as a selective receptor-dependent delivery system for antigen presentation.

Microb Pathog 2019 Apr 31;129:68-73. Epub 2019 Jan 31.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Introducing an effective vaccine for tuberculosis (TB) is an urgent need. Mycobacterium tuberculosis (Mtb) Ag85 complex is suggested for making protective immunodominant antigens for design and development of novel TB vaccine. In the present study, a pDR2EF1-Fcγ1 vector has been used to make Ag85B:hFcγ1 recombinant fusion protein. Briefly, specific XbaI and NotI site incorporated primers were used to amplify Mtb-fbpB gene by PCR, TA-cloned and amplified in E.coli DH5α. The resulting vector then subcloned into the pDR2EF1.Fcγ1 vector and transferred to Chinese hamster ovary (CHO) cell line. DNA sequencing was performed to confirm that Ag85B:hFcγ1 construct is precise and in-frame. Then, Ag85B:hFcγ1 protein was produced by CHO expression system and recombinant protein was purified using HiTrap rProtein A Sepharose Fast Flow column. The presence of recombinant fusion protein confirmed by immunofluorescence (IFA) and Western blotting (WB). This fusion protein containing Fc fragment of human IgG1, apart from stability and adjuvanticity potential, could bind to FcRγI (CD64) on the surface of antigen-presenting cells (APCs) and induce cross-presentation in favour of host immune response and can be used as a potential candidate along with other subunit vaccines against Mtb.
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http://dx.doi.org/10.1016/j.micpath.2019.01.045DOI Listing
April 2019

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement.

Drug Dev Ind Pharm 2019 May 4;45(5):736-744. Epub 2019 Feb 4.

a Department of Pharmaceutical Nanotechnology, School of Pharmacy , Zanjan University of Medical Sciences , Zanjan , Iran.

Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood-brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain.

Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.

Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112 ± 3.5 nm, 0.20 ± 0.02, and -33.2 ± 2.6 mV, respectively. From in vivo studies in animal model of rats, the AUC of brain concentration-time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug.

Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.
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http://dx.doi.org/10.1080/03639045.2019.1569039DOI Listing
May 2019

Current approaches for detection of human T-lymphotropic virus Type 1: A systematic review.

J Cell Physiol 2019 08 11;234(8):12433-12441. Epub 2019 Jan 11.

Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex, UK.

Background: Human T-lymphotropic virus Type 1 (HTLV-1) is a retrovirus that is endemic in some regions of the world. It is known to cause several diseases like adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Serology and molecular methods have been used to detect this virus. Of these, enzyme-linked immunosorbent assay (ELISA) is used as a primary screening method and this is usually followed by western blotting (WB) and polymerase chain reaction (PCR) methods as confirmatory tests. We conducted a systematic review of the different techniques used in the diagnosis of HTLV-1 infection.

Materials And Methods: Our search was limited to original papers in the English language from 2010 to 2018 using several databases including Pubmed, Scopus, Google Scholar, Iranmedex, and Scientific Information Database. A manual search of references provided in the included papers was also performed.

Results: Of 101 electronically searched citations, 43 met the inclusion criteria. ELISA is commonly used for qualitative and screening detection, and WB and PCR techniques are used to confirm infection.

Conclusion: Among all the reported methods for detection of HTLV-1, only serological and molecular tests are used as the most common technical assays for HTLV-1. The ELISA assay, without a confirmatory test, has several limitations and affect the accuracy of the results. Owing to the prevalence of HTLV-1 and limitations of the current detection methods, further evaluation of the accuracy of these methods is needed. There are new opportunities for applying novel technological advances in microfluidics, biosensors, and lab-on-a-chip systems to perform HTLV-1 diagnostics.
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http://dx.doi.org/10.1002/jcp.28087DOI Listing
August 2019

Role of Receptors for Advanced Glycation End Products and High-Mobility Group Box 1 in the Outcome of Human T Cell Lymphotropic Type 1 Infection.

Viral Immunol 2019 03 26;32(2):89-94. Epub 2018 Dec 26.

3 Immunology Research Centre, Inflammation and Inflammatory Diseases Division, Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Human T cell lymphotropic type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic viral neuroinflammatory disease, which leads to damage of the central nervous system. Inflammatory responses and mediators are both involved in the pathogenesis of the disease and in determining its outcome. High-Mobility Group Box 1 (HMGB1) is a chromatin-associated nuclear protein acting as a signaling molecule in cells after binding to its receptors. Receptor for advanced glycation end products (RAGE) is a transmembrane multiligand receptor that binds to HMGB1. HMGB1-RAGE signaling has an important role in inflammatory and infectious diseases. Inhibition of HMGB1 activity reduces the inflammation in immune-associated diseases. In the present study, we examined the gene expressions and plasma levels of HMGB1 and its receptor RAGE in HAM/TSP patients, HTLV-1-infected asymptomatic carriers (ACs), and healthy controls. Peripheral blood mononuclear cells were collected from all the groups and complementary DNA (cDNA) was synthesized. HMGB-1 messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction (PCR) TaqMan method, and plasma levels of HMGB1 and soluble RAGE (sRAGE) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of HMGB1 was the same among the groups (p > 0.05). No significant difference in the plasma levels of HMGB1 was observed between the groups (p > 0.05). The plasma levels of sRAGE were higher in ACs than HAM/TSP patients, and a significant difference was observed between the two groups (p < 0.001). Our results showed that sRAGE could play a potential role in the control of inflammatory response in HTLV-1 carriers through the inhibition of HMGB1 signaling and potentially could be used as an indicator for evaluation of HAM/TSP developing in HTLV-1-infected individuals.
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http://dx.doi.org/10.1089/vim.2018.0048DOI Listing
March 2019

HTLV-1-host interactions on the development of adult T cell leukemia/lymphoma: virus and host gene expressions.

BMC Cancer 2018 Dec 22;18(1):1287. Epub 2018 Dec 22.

Immunology Research center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, Zip code: 9177948564, Iran.

Background: Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder of HTLV-1-host interactions in infected TCD4+ cells. In this study, the HTLV-1 proviral load (PVL) and HBZ as viral elements and AKT1, BAD, FOXP3, RORγt and IFNλ3 as the host factors were investigated.

Methods: The study was conducted in ATLLs, HTLV-1-associated myelopathy/tropical spastic paraparesis patients (HAM/TSPs) and HTLV-1-asympthomatic carriers (ACs). The DNA and mRNA from peripheral blood mononuclear cells were extracted for gene expression assessments via qRT-PCR, TaqMan assay, and then confirmed by western blotting.

Results: As it was expected, the HTLV-1-PVL were higher in ATLLs than ACs (P = 0.002) and HAM/TSP (P = 0.041). The HBZ expression in ATLL (101.76 ± 61.3) was radically higher than in ACs (0.12 ± 0.05) and HAM/TSP (0.01 ± 0.1) (P = 0.001). Furthermore, the AKT1 expression in ATLLs (13.52 ± 4.78) was higher than ACs (1.17 ± 0.27) (P = 0.05) and HAM/TSPs (0.72 ± 0.49) (P = 0.008). However, BAD expression in ATLL was slightly higher than ACs and HAM/TSPs and not significant. The FOXP3 in ATLLs (41.02 ± 24.2) was more than ACs (1.44 ± 1) (P = 0.007) and HAM/TSP (0.45 ± 0.15) (P = 0.01). However, RORγt in ATLLs (27.43 ± 14.8) was higher than ACs (1.05 ± 0.32) (P = 0.02) but not HAM/TSPs. Finally, the IFNλ3 expression between ATLLs (31.92 ± 26.02) and ACs (1.46 ± 0.63) (P = 0.01) and ACs and HAM/TSPs (680.62 ± 674.6) (P = 0.02) were statistically different, but not between ATLLs and HAM/TSPs.

Conclusions: The present and our previous study demonstrated that HTLV-1-PVL and HBZ and host AKT1 and Rad 51 are novel candidates for molecular targeting therapy of ATLL. However, high level of RORγt may inhibit Th1 response and complicated in ATLL progressions.
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http://dx.doi.org/10.1186/s12885-018-5209-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303995PMC
December 2018

Molecular targeting for treatment of human T-lymphotropic virus type 1 infection.

Biomed Pharmacother 2019 Jan 5;109:770-778. Epub 2018 Nov 5.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases. There are conflicting reports on the efficacy of current enzyme inhibitors, mainly developed against human immunodeficiency virus (HIV), for treatment of HTLV-1 infection. New treatment approaches including monoclonal antibodies show promising results and exert significant cytotoxic effects on ATLL cells. This manuscript reviews the recent developments in molecular targeting for treatment of HTLV-1 infection.
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http://dx.doi.org/10.1016/j.biopha.2018.10.139DOI Listing
January 2019

Long segment detection of HTLV-1 genome based on the fluorescence quenching technique.

Heliyon 2018 Dec 5;4(12):e00996. Epub 2018 Dec 5.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Detecting fluorescence changes due to energy transfer between a quencher and fluorophore is a common method used for the fluorescence-based biosensors. In the present report, a new biosensor for long segment detection of the human T cell-lymphotropic virus 1 genome was constructed based on the fluorescence quenching of graphene oxide by gold nanoparticles. The fluorescence signal of unmodified graphene oxide was measured before and after hybridization of target and probes functionalized with gold nanoparticles. The limit of detection of the biosensor was determined to be around 10 pg/mL. The specific design for long segment of target assures the selectivity of biosensor. Our results proposed that further development may be useful to detect other viruses.
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http://dx.doi.org/10.1016/j.heliyon.2018.e00996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282111PMC
December 2018

Different roles of CXCR1 and CXCR2 in HTLV-1 carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Med Microbiol Immunol 2019 Oct 20;208(5):641-650. Epub 2018 Oct 20.

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

One of the prominent features of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the excessive recruitment of leukocytes to the central nervous system (CNS), which leads to an inflammatory response-with chemokines and their receptors playing the main role in this recruitment. The aim of the study was to examine the relation of CXCR1 and CXCR2, both of which are involved in the trafficking of lymphocytes into the CNS, with the outcome of HTLV-1 infection. The mRNA levels of CXCR1 and CXCR2 were examined in peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls (HCs). Furthermore, the frequency of CD4 and CD8 T cells expressing CXCR1 and CXCR2 was evaluated in the studied groups. The results of the present study showed a substantial increase in the mean mRNA expression of CXCR2 in the HAM/TSP patients compared to the HCs and ACs (p < 0.001). A positive correlation was also found between PVL and CXCR2 mRNA expression in the total population of HTLV-1-infected subjects (R = 0.526, p < 0.001). Moreover, the percentage of CD8 CXCR2-expressing cells was higher in HAM/TSP patients compared to ACs and HCs (p < 0.05, p < 0.01, respectively). Although the percentage of CD4 CXCR2-expressing cells was higher in HAM/TSP patients than in ACs and HCs, a significant difference was only found between HAM/TSP patients and HCs (p < 0.05). No significant difference in the CXCR1 mRNA expression was observed in the studied groups. The frequency of the CD8 CXCR1- and CD4 CXCR1-expressing cells was significantly lower in HAM/TSP patients than in ACs and HCs (p < 0.001 and p < 0.01, respectively). In conclusion, the high frequency of CXCR2 CD8 T cells and the high levels of CXCR2 mRNA expression in HAM/TSP patients are associated with disease pathogenesis, while the high frequencies of CXCR1 T cells in ACs might suggest that these cells act as effector CD8 T cells and are involved in controlling the viral spread and modulation of the immune response.
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http://dx.doi.org/10.1007/s00430-018-0568-8DOI Listing
October 2019

L. Improved Heart Function and Inhibited Myocardial Apoptosis in Isolated Rat Heart Following Ischemia-Reperfusion Injury.

J Pharmacopuncture 2018 Sep 30;21(3):159-167. Epub 2018 Sep 30.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart.

Methods: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with 500 μM of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (±), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples.

Results: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts.

Conclusion: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.
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http://dx.doi.org/10.3831/KPI.2018.21.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168185PMC
September 2018

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

Life Sci 2018 Nov 21;212:9-19. Epub 2018 Sep 21.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenesis-inflammation Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Aims: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice.

Material And Methods: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 10 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues.

Key Findings: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group.

Significance: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.
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http://dx.doi.org/10.1016/j.lfs.2018.09.031DOI Listing
November 2018

Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat.

J Ethnopharmacol 2019 Jan 14;228:142-147. Epub 2018 Sep 14.

Faghihi hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Ethnopharmacological Relevance: Nigella sativa L. seed has been widely used in traditional medicine for the treatment of diabetes. The major reason for vascular complications in diabetic patients is endothelial dysfunction. However, the impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear.

Aim Of The Study: This study was conducted to evaluate the effect of the hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in streptozotocin (STZ)-induced diabetic rat.

Materials And Methods: Treated rats received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6 weeks. The fasting blood glucose and lipids were measured and atherogenic index of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity responses of isolated aortic rings were evaluated in the presence of cumulative concentrations of Ach (10-10 M). eNOS, VCAM-1, and LOX-1 genes expression in aortic tissue was assessed by using real time polymerase chain reaction (PCR).

Results: Male diabetic Wistar rats treated with N. sativa seed extract for six weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant responses of aortic rings to Ach were markedly improved. N. sativa seed significantly increased eNOS in mRNA expression level and function, while it decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which assessed only in mRNA level.

Conclusions: The results of this study showed that N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties and improved vasoreactivity, endothelial dysfunction, and vascular inflammation in diabetic rats' aorta.
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http://dx.doi.org/10.1016/j.jep.2018.09.021DOI Listing
January 2019

CO-Switchable-hydrophilicity membrane (CO-SHM) triggered by electric potential: faster switching time along with efficient oil/water separation.

Chem Commun (Camb) 2018 Jul;54(61):8478-8481

Department of Polymer & Materials, Faculty of Chemistry & Oil Sciences, Shahid Behshti University, Evin, P.O. Box 19839-4716, Tehran, Iran.

We report a membrane that can be reversibly switched between a hydrophilic state and a hydrophobic state simply by alternately bubbling CO2 into and passing electric potential (EP) through a solution in contact with the membrane. The prepared membrane could be effectively used for oil/water separation.
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http://dx.doi.org/10.1039/c8cc04266gDOI Listing
July 2018

Interferon Lambda Family along with HTLV-1 Proviral Load, Tax, and HBZ Implicated in the Pathogenesis of Myelopathy/Tropical Spastic Paraparesis.

Neurodegener Dis 2018 10;18(2-3):150-155. Epub 2018 Jul 10.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease related to human T lymphotropic virus type 1 (HTLV-1) infection. Interferon type III (IFN-λ), which includes IL28, IL29, and IL28R, and affects the outcome of viral infections, might be complicated in the progression of HAM/TSP. Here, we investigated the host-virus interactions in the manifestation of HAM/TSP, using IL28B, IL29, IL28R, HTLV-1 Tax, HTLV-1 basic leucine zipper factor (HBZ), and proviral load (PVL). The study groups consisted of 20 patients with HAM/TSP, 20 asymptomatic HTLV-1 carriers (ACs), and 20 healthy controls (HCs). The means of PVL, Tax, and HBZ gene expressions in the HAM/TSP group (p = 0.004, 0.006, and < 0.0001, respectively) were significantly higher than in the AC group. The comparison of IL28B, IL29, and IL28R expression in the HAM/TSP, AC, and HC groups revealed no significant difference between the first 2, but lower concentrations in the HCs (IL28B: p = 0.03, 0.01; IL29: p = 0.07, 0.01; and IL28R: p < 0.0001, respectively). In the HAM/TSP group, correlations were seen between Tax and HBZ (R = 0.61, p = 0.004) and between Tax and IL29 (R = 0.45, p = 0.04). Negative correlations were observed between Tax and IL28B (R = -0.49, p = 0.02) and between HBZ and IL28R (R = -0.43, p = 0.06). In the ACs, an inverse correlation was found between Tax and IL28B (R = -0.42, p = 0.06). These findings suggest that IL29, IL28B, and IL28R interfere in the infection of HAM/TSP, mainly via Tax activation.
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http://dx.doi.org/10.1159/000490058DOI Listing
January 2019

Teucrium polium improves endothelial dysfunction by regulating eNOS and VCAM-1 genes expression and vasoreactivity in diabetic rat aorta.

Biomed Pharmacother 2018 Jul 7;103:1526-1530. Epub 2018 May 7.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.

Endothelial dysfunction is the major cause of vascular complications in diabetes. Teucrium polium L. is traditionally used for the production of antidiabetic herbal medicine. The cardiovascular effects of T. polium, has also been reported. As a result of this, the present study was conducted to evaluate the impacts of T. polium hydroalcoholic extract on the vasoreactivity and endothelial nitric oxide synthase (eNOS) and vascular cell adhesion molecule (VCAM)-1 genes expression as well in streptozotocin (STZ)-induced diabetic rat aorta. Male Wistar rats were randomly divided into six groups: control, diabetic, metformin, and three groups of T. polium (TP 100, TP 200, and TP 400). The control and diabetic groups were given normal saline; metformin group was given 300 mg/kg metformin; and T. polium groups were given 100, 200, and 400 mg/kg T. polium extract, daily by gavage for 6 weeks. T. polium extract was found to significantly reduce serum glucose level. It was also observed that metformin and T. polium extract significantly improved vasorelaxant response of aortic rings to acetylcholine (Ach). Real-time polymerase chain reaction (PCR) analysis showed that T. polium and metformin significantly increased eNOS expression, while it decreased VCAM-1 expressions in aortic tissue of diabetic rats. The results showed that T. polium extract could improve endothelial dysfunction by ameliorating the vasoreactivity and regulating eNOS and VCAM-1 gene expressions as well in STZ-induced diabetic rats' aorta.
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http://dx.doi.org/10.1016/j.biopha.2018.04.158DOI Listing
July 2018
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