Publications by authors named "Leila Sadeghi"

32 Publications

Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network.

Sci Rep 2021 Apr 15;11(1):8252. Epub 2021 Apr 15.

Department of Medical Physiology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments.
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http://dx.doi.org/10.1038/s41598-021-87555-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050094PMC
April 2021

Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3.

Intervirology 2021 Mar 31:1-5. Epub 2021 Mar 31.

Iranian Institute for Reduction of High-Risk Behaviors, Iranian Research Center For HIV/AIDS, Tehran, Iran.

Objectives: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis.

Methods: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD).

Results: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02).

Conclusions: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.
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http://dx.doi.org/10.1159/000514385DOI Listing
March 2021

Structural and kinetic insights into HIV-1 reverse transcriptase inhibition by farnesiferol C.

Int J Biol Macromol 2021 Mar 29;174:309-318. Epub 2021 Jan 29.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is the key enzyme for the virus gene replication and the most important target for antiviral therapy. Toxicity, drug resistance and side effects have led to search for new antiviral agents. Farnesiferol C (FC) is a well-known biologically active sesquiterpene coumarin derivative from genus Ferula. The current study was designed to examine the impacts of FC on the structure and function of HIV-1 RT, using some theoretical and experimental methods. FC inhibited HIV-1RT activity via mixed inhibition mechanism (IC = 30 μM). Spectroscopic data showed some conformational changes in the secondary as well as tertiary structure of HIV-1RT following the interaction with FC. Results showed that FC could quench the intrinsic fluorescence emission of HIV-1RT through static quenching mechanism. Thermodynamic parameters revealed that hydrogen bondings and van der Waals forces are the major forces in the binding reaction and the low equilibrium constants (K) value obtained from surface plasmon resonance data, confirmed the high affinity of FC for HIV-1RT. Molecular docking studies indicated that FC interacts with enzyme through hydrophobic pocket. Taken together, the outcomes of this research revealed that, sesquiterpene coumarines can be used to design natural remedies as anti-HIV agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.173DOI Listing
March 2021

The inhibitory effects of bile acids on catalytic and non‑catalytic functions of acetylcholinesterase as a therapeutic target in Alzheimer's disease.

Acta Neurobiol Exp (Wars) 2020 ;80(2):108-116

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Acetylcholine is a fast-acting neurotransmitter in synapses and neuromuscular junctions that is decreased in Alzheimer's disease (AD) by hyper‑activation of acetylcholinesterase (AChE), which leads to progressive loss of memory and neurobehavioral abnormalities. Therefore, AChE inhibitors have therapeutic potential in AD that could include natural compounds such as bile acids. Bile acids, as potent molecules, could improve some types of neurodegenerative diseases via antioxidant effects and other unknown mechanisms. The aim of this study was to investigate beneficial effects of bile acids on AChE catalytic and non‑catalytic functions, amyloid plaque deposit and memory in a rat model of AD. The effects of sodium deoxycholate and cholic acid on AChE activity were assessed by in vitro assay. Then, the bile acids' potential therapeutic effects were investigated on nucleus basalis of Meynert lesioned rats using behavioral evaluation, biochemical tests and histological methods. Molecular docking simulation was also implemented to investigate the possible interaction between bile acids and AChE. According to the in vitro and in vivo results, sodium deoxycholate could efficiently inhibit the catalytic function of the enzyme by interacting with the catalytic site, while cholic acid interacted with the peripheral anionic site and inhibited chaperone activity of the enzyme that led to the reduced amyloid plaque deposition. The co‑administration of cholic acid and sodium deoxycholate showed these compounds are able to simultaneously inhibit the catalytic and non‑catalytic functions of the enzyme. This study clarifies the roles of natural bile acids in the nervous system and in AChE function through multiple experimental and simulation methods.
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January 2020

Cumulative effects of ciprofloxacin and pilocarpine on cytotoxicity and G0 phase arrest in hepatoma-derived Hep G2 cell line.

J Pharm Pharmacol 2020 Oct 21;72(10):1383-1393. Epub 2020 Jun 21.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

Objectives: Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma-derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca homoeostasis as major hub in unchecked proliferation.

Methods: Cells were treated by CPF and/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated.

Key Findings: MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF-exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P-Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction.

Conclusions: Ciprofloxacin imposed mitochondrial-independent apoptosis while PILO + CPF caused mitochondrial-dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms.
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http://dx.doi.org/10.1111/jphp.13318DOI Listing
October 2020

The inefficacy of donepezil on glycated-AChE inhibition: Binding affinity, complex stability and mechanism.

Int J Biol Macromol 2020 Oct 23;160:35-46. Epub 2020 May 23.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.. Electronic address:

Donepezil (DPZ) is a well-known drug for Alzheimer's disease that inhibits acetylcholinesterase activity (AChE). In the present study, the inhibitory effect of DPZ on non-enzymatic glycated-AChE (GLY-AChE) was studied by different experimental and simulation techniques. The initial investigation revealed that glycation process could reduce AChE activity approximately 60% in the pure enzyme and 38% in the extracted crude AChE from neural cells cultured in the presence of high glucose (HG) concentration. It is suggested that glycation of lysine residues on the structure of AChE could change the conformation of the active site (Trp-86 and His-447) in a way that the orientation of acetylcholine interrupted. The further studies indicated that DPZ is although a strong inhibitor for the native enzyme, it is not able to affect the GLY-AChE activity. The K values of AChE-DPZ and GLY-AChE-DPZ complexes were estimated to be 1.88 × 10 and 2.10 × 10, respectively. The stability assessment showed that AChE-DPZ complex is more stable than the glycated complex. Our results indicate that, glycation process could impact on the conformation of the residues involved in the DPZ binding cavity on α-helix domain. Therefore, DPZ is not able to bind its specific cavity to induce its inhibitory effects on GLY-AChE.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.177DOI Listing
October 2020

Effects of Delphinidin on Pathophysiological Signs of Nucleus Basalis of Meynert Lesioned Rats as Animal Model of Alzheimer Disease.

Neurochem Res 2020 Jul 15;45(7):1636-1646. Epub 2020 Apr 15.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, P.O. Box 5166616471, Tabriz, Iran.

Alzheimer's disease (AD) is an advanced neurodegenerative disorder greatly accompanied by cognitive deficits, oxidative stress, inflammation, amyloid plaques deposition, and acetylcholinesterase (AChE) hyper-activation. Growing evidence suggests natural compounds with antioxidant and anti-inflammatory features improve pathophysiological signs of AD. The present study was designed to investigate the effects of Delphinidin (25, 50 mg/kg) as an anthocyanidin on spatial memory impairment and AD hallmarks such as hippocampal AChE activity, amyloid plaques deposition, oxidative stress and expression of amyloid precursor protein (APP), AChE, and amyloid beta (Aβ) proteins in nucleus basalis of Meynert (NBM) lesioned rats as the most prevalent animal model of AD. Interestingly, Delphinidin-treated animals showed a significant decrease in escape latency and distance moved. Furthermore, in probe test, NBM lesioned rats treated with both doses of Delphinidin spent more time in the target quadrant zone in Morris water maze task. It could also interact with catalytic site of AChE enzyme and inhibits acetylcholine hydrolysis in in vitro and in vivo conditions. In addition, Delphinidin could scavenge additional produced reactive oxygen molecules dose dependently. Our immunoblotting analysis confirmed high dose of Delphinidin reduced AChE, APP and Aβ contents in AD model. Staining of hippocampus tissue revealed that Delphinidin treatment decreased amyloid plaques formation in NBM lesion rats. It seems that Delphinidin is a plate-like molecule intercalated between β-plated sheets related to Aβ molecules and inhibited amyloid fibril formation. Altogether, Delphinidin and Delphinidin-rich fruits could be suggested as a therapeutic adjuvant in AD and other related cognitive disorders.
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http://dx.doi.org/10.1007/s11064-020-03027-wDOI Listing
July 2020

Surface plasmon resonance, fluorescence, and molecular docking studies of bovine serum albumin interactions with natural coumarin diversin.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Apr 11;230:118063. Epub 2020 Jan 11.

Departments of Ophthalmology and Visual Sciences, Cell and Regenerative Biology, and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

In the present study the binding of diversin (DIV), a prenylated coumarin isolated from Ferula diversivittata, to bovine serum albumin (BSA) was investigated using surface plasmon resonance (SPR), spectrofluorimetry, and molecular docking approaches. Following the activation of carboxylic groups, via NHS/EDC, BSA was immobilized on the carboxymethyl dextran (CMD) hydrogel coated Au sensor, and was used for real-time monitoring of the interactions between DIV and BSA. K value of DIV binding to BSA increased with increasing temperature, confirmed that the affinity between BSA and DIV decreases with rising temperature. In addition, the fluorescence and synchronous fluorescence spectroscopic data revealed that the intrinsic emission intensity of BSA was quenched via a dynamic mechanism. In addition, the micro-region around BSA tyrosine residue was changed upon interaction with DIV. The thermodynamic parameter findings suggested that the hydrophobic interactions were dominant in the binding and formation of the BSA and DIV complex. The molecular docking outputs indicated that there is only one binding site on BSA for DIV, in agreement with experimental data, and DIV bind BSA in subdomain IB.
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http://dx.doi.org/10.1016/j.saa.2020.118063DOI Listing
April 2020

Prognostic Value of Cardiac Biomarkers Assessment in Combination with Myocardial 2D Strain Echocardiography for Early Detection of Anthracycline-Related Cardiac Toxicity.

Cardiovasc Hematol Disord Drug Targets 2020 ;20(1):74-83

Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Anthracyclines, a widely used chemotherapy agent with a definite survival improvement, can result in cardiac toxicity presenting with HF (heart failure).

Objective: We aim to assess the predictive value of cardiac biomarkers assessment in combination with myocardial two-dimensional strain echocardiography for early detection of cardiac toxicity in patients who underwent Anthracycline-based chemotherapy.

Methods: Fifty-two consecutive adult patients scheduled to undergo the first course of Anthracycline-based chemotherapy were subjected to the study. All the patients underwent highly sensitive 2D echocardiographic evaluation before the treatment, 4 and 12 weeks after completion of first-course chemotherapy. Longitudinal and segmental strains were measured. Serum levels of High-sensitive cardiac troponin I (hscTn-I) and N-terminal-pro-BNP (NT-proBNP) were also assessed before the initiation and 3 weeks after completion of first-course chemotherapy.

Results: Fifteen patients (28.8%) revealed a decrease in LVEF (Left Ventricular Ejection Fraction) throughout the evaluations, while just 5 patients met the criteria of cardiac toxicity (9.6%). AUC for Global Longitudinal Strain (GLS) ROC curve at 4 weeks of follow-up was calculated to be 0.968. Inferoseptal Systolic Longitudinal Strain (SLS) had the highest AUC value (AUC: 0.934) among different wall SLS. LVESD (Left Ventricular End-Systolic Diameter) at first and second evaluation could predict the risk of cardiac toxicity among LVESD, LVEDD (Left Ventricular End Diastolic Diameter) and LVEDV (Left Ventricular End-Diastolic Volume). Among cardiac biomarkers, hscTnI had higher sensitivity, while NT-proBNP had higher specificity for cardiac toxicity.

Conclusion: This study has shown that hs-cTnI with good sensitivity can predict cardiac toxicity in Anthracycline-based chemotherapy receiver. The use of strain with speckle echocardiography method has a prognostic value; however, both longitudinal and segmental strain should be assessed. Lateral and inferoseptal SLS (Segmental Longitudinal Strain) are specific markers of cardiac toxicity in the course of anthracycline-related cardiac toxicity.
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http://dx.doi.org/10.2174/1871529X19666190912150942DOI Listing
March 2021

Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016.

Intervirology 2018 12;61(6):292-300. Epub 2019 Mar 12.

Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

Aims: The aim of this study was to evaluate drug resistance patterns among Iranian people living with HIV who have taken antiretroviral therapy for 9-15 months.

Methods: A cross-sectional study was conducted between December 2015 and May 2016. Two hundred fifty-two blood samples were collected from all eligible HIV-infected patients at fourteen healthcare settings, located in major provinces in Iran. The samples were examined for presence of drug resistance strains and viral load level. Moreover, a phylogenetic tree, using neighbor joining, was constructed and HIV subtypes were determined.

Results: The most common subtypes were CRF35-AD (47.6%) and A1 (42.8%), followed by 45_CPX (4.8%) and C (4.8%). The resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors was reported as 19.2, 19.2, and 10.3%, respectively. M184I/V mutation was the most frequent (31.6%) mutation among NRTI-based regimens. Moreover, K103E/N was the most frequent (34.2%) NNRTI mutation.

Conclusions: This is the first study to illuminate the emergence of the CPX genotype among Iranian patients. The drug resistance rate of NNRTIs was similar to that of NRTIs. By assessing drug resistance, it is possible to evaluate the efficacy of treatment and patient adherence to treatment.
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http://dx.doi.org/10.1159/000497036DOI Listing
September 2019

The impact of water molecules on binding affinity of the anti-diabetic thiazolidinediones for catalase: Kinetic and mechanistic approaches.

Arch Biochem Biophys 2019 03 7;664:110-116. Epub 2019 Feb 7.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran.

Water molecules play a vital role in efficient drug binding to its target. Thiazolidinediones (TZDs), a class of anti-diabetic drugs, are widely used for treatment of type 2 diabetes mellitus. In the present study, the possible contribution of water molecules to the binding of TZDs to catalase, a potential target in the liver, was investigated by different experimental and theoretical methods. These studies indicated that TZDs could significantly improve the catalase catalytic function with a significant contribution from water molecules. As a probe for the differential number of released water molecules during the catalase transition from E to E* states, the activity of TZDs-catalase complexes was demonstrated to be mainly dependent on water activity. However, free catalase decomposed the substrate more independently. In addition, the spectrofluorimetry studies showed that the binding of TZDs to catalase needed the release of water molecules from the enzyme's binding pocket. The thermodynamic studies indicated that the binding enthalpy and entropy of TZDs for catalase were decreased with lower water activity. The favorable process contributes to release of water molecules from the binding pocket through the formation of hydrophobic interactions between catalase and TZDs in an enthalpic manner. Molecular docking simulations confirmed that the depletion of water molecules from the binding cavity is essential for effective interactions between TZDs and catalase.
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http://dx.doi.org/10.1016/j.abb.2019.02.002DOI Listing
March 2019

Physiological and Biochemical Effects of Echium Amoenum Extract on Mn-Imposed Parkinson Like Disorder in Rats.

Adv Pharm Bull 2018 Nov 29;8(4):705-713. Epub 2018 Nov 29.

Department of Physiology, Payam Noor University of Iran, Iran.

Manganism is a cognitive disorder take places in peoples are exposed to environmental manganese pollution. Overexposure to manganese ion (Mn) mainly influences central nervous system and causes symptoms that increase possibility of hippocampal damages. In this study rats were administrated by two different doses of MnCl2 and behavioral and physiological consequences were evaluated. We also investigated effects of E. Amoenum on Mn-imposed toxicity by behavioral, biochemical, immunoblotting and histological studies on hippocampus tissue. Results showed metal overexposure increases oxidative stress mainly by lipid peroxidation and reactive oxygen species overproduction. Histological studies and caspase 3 analyses by immunoblotting revealed Mn induced apoptosis from mitochondrial-dependent pathway in the presence of low metal dose. This study provides evidence that oral administration of E. amoenum extract inhibited manganese neurotoxicity by oxidative stress attenuation and apoptosis reduction that lead to improved depression like behavior. Plant extract also increased catecholamine content in Mn treated hippocampus. As molecular and pathophysiological effects of E. amoenum, it could be considered as a pre-treatment for Parkinson and Parkinson like disorders in high-risk people.
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http://dx.doi.org/10.15171/apb.2018.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311646PMC
November 2018

New mechanisms of phenytoin in calcium homeostasis: competitive inhibition of CD38 in hippocampal cells.

Daru 2018 Dec 6;26(2):191-198. Epub 2018 Nov 6.

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, P.O. Box 5166616471, Tabriz, Iran.

Purpose: Phenytoin is a major anticonvulsant drug that is effective to improve arrhythmia and neuropathic pain. According to early works, phenytoin affected cell membrane depolarization by sodium channel blocking, guanylyl and adenylyl cyclase suppression that cause to intracellular Na and Ca downregulation. This study was aimed to clarify some ambiguities in pathophysiological action of phenytoin by in vitro and molecular docking analyses.

Methods: In this study intracellular free Ca of primary culture of embryonic mouse hippocampus evaluated via Fura 2 as fluorescent probe. The effects of phenytoin on ADP ribosyl cyclase activity was assessed by recently developed fluorometric assay. Molecular docking simulation was also implemented to investigate the possible interaction between phenytoin and CD38.

Results: Our results confirmed phenytoin competitively inhibits cyclase activity of CD38 (IC = 8.1 μM) and reduces cADPR content. cADPR is a Ca-mobilising second messenger which binds to L-type calcium channel and ryanodine receptors in cell and ER membrane and increases cytosolic free Ca. Ca content of cells decreased significantly in the presence of phenytoin in a dose dependent manner (IC = 12.74 µM). Based on molecular docking analysis, phenytoin binds to deeper site of CD38 active site, mainly via hydrophobic interactions and consequently inhibits proper contact of substrate with catalytic residues specially Glu 226, Trp 186, Thr221.

Conclusion: Taken together, one of the anticonvulsant mechanisms of phenytoin is Ca inhibition from CD38 pathway, therefore could be used in disorders that accompanied by CD38 over production or activation such as heart disease, depression, brain sepsis, airway disease, oxidative stress and inflammation. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s40199-018-0224-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279657PMC
December 2018

Improving effects of Echium amoenum aqueous extract on rat model of Alzheimer's disease.

J Integr Neurosci 2018 ;17(3-4):661-669

Matrix Dynamics Group, University of Toronto, Toronto, Canada.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder greatly accompanied by oxidative stress and acetylcholine reduction in synaptic cleft that leads to dementia. Previously approved there is correlation between nucleus basalis of Meynert (NBM) degeneration and loss of memory, learning ability and thought. The aim of this study was to investigate improving effects of Echium amoenum aqueous extract on memory deficient, pathophysiological and oxidative damages imposed by NBM lesion in rats as documented AD model. Results showed NBM destruction causes hash oxidative stress that possibly leads to neurodegeneration in hippocampus tissue. Orally administration of plant extract significantly reduced oxidative stress by reactive molecules scavenging that resulted to decrease lipid peroxidation also. Plant extract treatment inhibited acetylcholine esterase enzyme (more than 5 folds) in hippocampus tissue related to NBM lesioned rats. Histological studies approved NBM lesion causes harsh neurodegeneration in hippocampus tissue possibly by acetylcholine reduction that was compensated by plant extract protective effects. Interestingly improving effects of plant in molecular level causes improved spatial learning ability in Morris water maze test. By considering pathophysiological and molecular similarities between AD and NBM lesion model, E. amoenum could be used as a therapeutic adjuvant in patients suffering from Alzheimer or similar cognitive disorders.
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http://dx.doi.org/10.3233/JIN-180093DOI Listing
December 2018

HIV-1 Drug Resistance Profiles for the HIV Protease and Reverse Transcriptase Gene in Patients Receiving Combination Therapy in Tehran, Iran.

Infect Disord Drug Targets 2018 ;18(3):241-248

Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

Background: Determination of the drug-resistant mutations has a crucial role in the management of HIV-1 infected patients.

Objective: The aim of the current study was to evaluate drug resistance profile of Reverse transcriptase and Proteasegenes, and to find the correlation between drug resistance mutations and ART regimen to intensifyphysicians'options for the most effective therapy which could also influence the establishment of health-related policies at the national level in Iran.

Method: HIV-1 RNA of 34 samples was extracted from plasma and RT Nested- PCR was performed and the final products were sequenced. Stanford HIV drug resistance sequence database was used for interpretation of the data.

Results: In 14 patients out of 15, the following mutations were observed; Nucleoside RT Inhibitor (NRTI)-Resistance Mutations with the prevalence of 11 patients having this mutation at codon 184 (73%) and Non-Nucleoside RT Inhibitor (NNRTI)-Resistance Mutations with the prevalence of 8 patients having NNRTI mutations at codon 103(53%).In 17 patients, major Protease Inhibitor (PI) Resistance Mutations were found out in 2 (12%) of them while the minor PI was found in7 (41%) patients.

Conclusion: An antiretroviral treatment consisting of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor and protease inhibitor, impairs the emergence of a resistant strain and descends its prevalence among the community. Having a high rate mutation in participants of this study raises concerns about treatment failure in HIV infected people in Iran. Observing high mutations rates in participants of this study raises concerns about treatment failure in HIV infected people in Iran.
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http://dx.doi.org/10.2174/1871526518666180416110259DOI Listing
January 2019

Different Degrees of Immune Recovery Using Antiretroviral Regimens with Vonavir or Zidovudine/Lamivudine/Efavirenz in HIVPositive Patients Receiving First Line Treatment in Iran.

Infect Disord Drug Targets 2018 ;18(3):207-213

Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

Background: The initial antiretroviral therapy (ART) regimens recommended by most national treatment guidelines in resource-limited settings consist of two Nucleoside Reverse-Transcriptase Inhibitors (NRTIs) and one Non-Nucleoside Reverse- Transcriptase Inhibitor (NNRTI). The NRTIs are Zidovudine (AZT) or Stavudine (d4T) with Lamivudine (3TC); the NNRTI components are either Nevirapine (NVP) or Efavirenz (EFV). Existing data regarding the effectiveness of Vonavir compared to other first-line ART regimens in increasing CD4+ T cell counts are unsatisfactory.

Methods: Immunological outcomes of 134 individuals who were on initial stage of antiretroviral therapy with Vonavir or a combination of Zidovudine/Lamivudine and Efavirenz were analyzed. The immunological response was then assessed during 28 weeks.

Results: Both groups demonstrated a significant increase in their CD4+ T cell count which was greater in Zidovudine/Lamivudine and Efavirenz treated group. We observed a noticeable increase in CD4+ T cells rates in the first three months of therapy; however, our results indicated a greater increase of cell counts in individuals with baseline CD4 lower than 100 cells/mm3 treated with Vonavir in first 12 weeks of treatment compared to those with higher baseline CD4.

Conclusion: A rapid CD4+ Tcell increase occurred shortly after beginning ART consisting either Vonavir or combination of Zidovudine, Lamivudine and Efavirenz. Late increases in CD4+ T cell counts were more pronounced in therapy using Zidovudine/ Lamivudine and Efavirenz.
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http://dx.doi.org/10.2174/1871526518666180108104031DOI Listing
January 2019

Chrysin as an Anti-Cancer Agent Exerts Selective Toxicity by Directly Inhibiting Mitochondrial Complex II and V in CLL B-lymphocytes.

Cancer Invest 2017 Mar 17;35(3):174-186. Epub 2017 Feb 17.

a Faculty of Pharmacy, Department of Pharmacology and Toxicology , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria. Our findings may provide a potential therapeutic approach for using chrysin to target mitochondria in CLL B-lymphocytes.
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http://dx.doi.org/10.1080/07357907.2016.1276187DOI Listing
March 2017

HIV Drug Resistance and Phylogeny Profile in Naïve and Antiretroviral-Experienced Patients in Tehran, Iran.

Intervirology 2016 15;59(3):131-136. Epub 2016 Dec 15.

Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

Background: Increasing the accessibility of antiretroviral therapy (ART) has caused the emergence of drug resistance in patients receiving ART and in naïve patients. The aim of this study was to evaluate HIV subtype and drug resistance between naïve patients and ART-experienced patients.

Methods: Blood samples were collected from 78 antiretroviral and naïve HIV-1 patients; antiretroviral-resistant mutations and subtyping were then determined by sequencing pol regions.

Results: Phylogenetic analysis revealed that 96.1% of sequences belong to the CRF35-AD subtype. Transmitted drug resistance was determined in 14% of drug-naïve patients and 40% of ART-experienced patients.

Conclusion: The findings of this study illustrated the importance of resistance testing before and during ART treatment. This study can be used to set up a best medicine strategy in Iranian guidelines.
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http://dx.doi.org/10.1159/000452712DOI Listing
March 2017

Hippocampal asymmetry: differences in the left and right hippocampus proteome in the rat model of temporal lobe epilepsy.

J Proteomics 2017 02 5;154:22-29. Epub 2016 Dec 5.

Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran. Electronic address:

The hippocampus is a complex brain structure and undergoes severe sclerosis and gliosis in temporal lobe epilepsy (TLE) as the most common type of epilepsy. The key features of the TLE may be reported in chronic animal models of epilepsy, such as pilocarpine model. Therefore, the current study was conducted in a rat pilocarpine model of acquired epilepsy. Two-dimensional gel electrophoresis based proteomic technique was used to compare the proteome map of the left and right hippocampus in both control and epileptic rats. Generally, 95 differentially expressed spots out of 1300 spots were identified in the hippocampus proteome using MALDI-TOF-TOF/MS. Within identified proteins, some showed asymmetric expression related to the mechanisms underlying TLE imposed by pilocarpine. Assessment of lateralization at the molecular level demonstrated that expression of proteins involved in dopamine synthesis was significantly more in the right hippocampus than the left one. In the epileptic model, reduction in dopamine pathway proteins was accompanied by an increase in the expression of proteins involved in polyamine synthesis, referring to a new regulating mechanism. Our results revealed changes in the laterality of protein expression due to pilocarpine-induced status epilepticus that could present some new proteins as potential candidates for antiepileptic drug design.

Biological Significance: In the current study, two-dimensional gel electrophoresis (2-DE) based proteomic technique was used to profile changes in the left and right hippocampus proteome after pilocarpine induced status epilepticus. Spots of proteome maps for two hemispheres were excised and identified with MALDI-TOF-TOF/MS. Analysis of proteome map of the left and right hippocampus revealed a lateralization at the molecular level, in which the expression of proteins involved in dopamine synthesis and release were significantly more in right hippocampi than the left ones in the normal rats. Also, the expression of proteins involved in polyamine synthesis significantly increased in epileptic hippocampus (considerably higher in right hippocampi), whilst the proteins which included in dopamine pathways were decreased. Our results revealed changes in the laterality of protein expression due to pilocarpine-induced status epilepticus that could present some new proteins as potential candidates for antiepileptic drug design.
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http://dx.doi.org/10.1016/j.jprot.2016.11.023DOI Listing
February 2017

Hand hygiene compliance before and after wearing gloves among intensive care unit nurses in Iran.

Am J Infect Control 2016 11 13;44(11):e279-e281. Epub 2016 Jun 13.

School of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Nosocomial infections are considered a major risk factor in hospital wards, and hand hygiene is the first step in their control. An observational study was conducted in 2015 with 200 nurses working in intensive care units in teaching hospitals of Tabriz, Iran. Data were collected by using the Hand Hygiene Observation Tool questionnaire. The researchers monitored nurses' opportunities for hand hygiene during the 8-week period from February 3-April 4, 2015. A total of 1,067 opportunities occurred for hand hygiene before and after wearing gloves. The results show that hand hygiene compliance before wearing gloves is poor among nurses who work in intensive care units (14.8%). Therefore it is necessary to conduct effective interventions through continuing education programs to improve hand hygiene compliance.
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http://dx.doi.org/10.1016/j.ajic.2016.05.004DOI Listing
November 2016

Selective Anticancer Activity of Acacetin Against Chronic Lymphocytic Leukemia Using Both In Vivo and In Vitro Methods: Key Role of Oxidative Stress and Cancerous Mitochondria.

Nutr Cancer 2016 Nov-Dec;68(8):1404-1416. Epub 2016 Oct 25.

e Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7-dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL B-lymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy B-lymphocytes and their mitochondria. We have found that acacetin (10 μM) can selectively induce apoptosis on CLL B-lymphocyte (25% at 24 h) by directly targeting mitochondria, through increased reactive oxygen species (ROS) formation, MMP collapse, MPT, release of cytochrome c, caspase 3 activation, and finally apoptosis, while sparing normal healthy B-lymphocytes unaffected at similar concentrations. Besides, oral administration of acacetin showed a potent in vivo anticancer activity in CLL xenograft mouse models. Our in vivo findings indicate that acacetin accumulates and kills CLL B-lymphocyte in a rather selective way through targeting cancerous mitochondria and ROS formation, which ends in CLL therapy. Finally, we can recommend acacetin as a promising compound for further drug development assays for the CLL treatment.
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http://dx.doi.org/10.1080/01635581.2016.1235717DOI Listing
December 2017

Antioxidant effects of alfalfa can improve iron oxide nanoparticle damage: Invivo and invitro studies.

Regul Toxicol Pharmacol 2016 Nov 18;81:39-46. Epub 2016 Jul 18.

Department of Physiology, Payam Noor University of Iran, Iran. Electronic address:

Medicago sativa Linn. or alfalfa (Leguminosae) has been used traditionally as an effective cure for CNS, heart and metabolic disorders and digestive aids. Alfalfa is a resistant plant against stress due to small antioxidant molecules and enzymes. Our previous work demonstrated that 100 μg/ml of 50 nm size FeO-NP causes harsh oxidative stress in HepG2 cells and 100 mg/kg of same nanoparticle causes extreme damage in rat's liver. Therefore it can be used as a useful model for invivo and invitro studies of oxidative stress. This study assessed the effects of two concentration of alfalfa on the mentioned invivo and invitro damage. Our results showed alfalfa reduced reactive oxygen species (ROS) production and enhanced reduced glutathione (GSH) that cause reduction of DNA fragmentation and prevent apoptosis pathway so improve viability of the cells. Results also showed alfalfa decreased hepatic enzymes penetrating and lipid peroxidation in rat's liver. Note that FeO-NP potentially has widespread biological application but its usage is limited due to bio incompatibility. A suitable antioxidant compound that reduce nanoparticle side effects can be used as an effective adjuvant with iron oxide nanoparticle (and may be other nanomaterials) in biological applications.
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http://dx.doi.org/10.1016/j.yrtph.2016.07.010DOI Listing
November 2016

Demographic, Clinical and Laboratory Profiles of HIV Infected Patients Admitted into Imam Khomeini Hospital of Tehran, Iran.

Infect Disord Drug Targets 2016 ;16(2):113-20

Iranian Research Center for HIV/AIDS (IRCHA), Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The aim of this study was to report the epidemiological, clinical and laboratory profiles of HIV-infected patients who admitted to HIV/AIDS laboratory of Imam Khomeini Hospital in Tehran, Iran.

Methods: HIV positive patients referred to the HIV/AIDS reference laboratory between December 2012 to March 2013 were included in the study. Their demographic characteristics, behavioral and personal history were assessed. Ninety nine patients' files from the medical records at the Voluntary Counseling and Testing Center (VCT) were selected and evaluated. Data was analyzed using SPSS for Windows Version 16. We used Pearson's chi-squared, one-way ANOVA and post hoc tests to examine differences in proportions.

Results: Of 99 participants in the present study, 68.7% were males, the mean age of the patients was 36±1.2 years and about 60% were married and almost half of them were self-employed. The most common transmission route was injection drug use. There was a statistically significant difference in CD4 count among different age groups (P = 0.028). Also, there was significant association between CD4 count and narcotic types (F=3.71, P = 0.012). Patients who used opium, had significantly higher CD4 than who used two or more narcotics (P = 0.005).

Conclusion: Our findings are helpful in understanding the demographic, clinical and laboratory profile of people living with HIV/AIDS. Consideration of useful interventions for high- risk groups and paying more attention to socio demographic background are needed for health care providers.
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http://dx.doi.org/10.2174/1871526516666151230115809DOI Listing
March 2017

The effects of aqueous extract of alfalfa on blood glucose and lipids in alloxan-induced diabetic rats.

Interv Med Appl Sci 2015 Sep 28;7(3):124-8. Epub 2015 Sep 28.

Diabetes is a common metabolic disorder that is specified by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The use of nonpharmacological treatments (herbal agents) is a new approach in the management of diabetes. The aim of this study was to investigate the effect of aqueous extract of alfalfa on blood glucose and serum lipids in alloxan-induced diabetic rats. In this study, 32 female rats (210-250 g) were used which were divided randomly into 4 groups including intact control group, diabetic control group, and 2 diabetic groups which received 250 and 500 mg/kg doses of aqueous extract of alfalfa, respectively. In the diabetic groups, alloxan-monohydrate was injected peritoneally to create diabetic condition. The two last groups orally received aqueous extract of alfalfa for 21 days. At the end of experiment, sugar, cholesterol, triglycerides, high-density and low-density lipoprotein, and aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were measured in the samples. Consumption of aqueous alfalfa extract significantly reduced glucose, cholesterol, triglycerides, and low-density lipoprotein (LDL) levels in the diabetic rats but enhanced high-density lipoprotein (HDL) levels. ALT and AST liver enzyme levels were also reduced in blood. Histological examination showed that the aqueous alfalfa extract caused reconstruction of damaged liver and enhanced Langerhans islets' diameter in pancreas. Therefore, all signs of diabetes were improved by oral administration of alfalfa in defined dose.
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http://dx.doi.org/10.1556/1646.7.2015.3.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609025PMC
September 2015

Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.

Redox Biol 2015 Dec 10;6:461-471. Epub 2015 Sep 10.

Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

To investigate the effects ofellagic acid (EA) on the cytotoxicity, B-lymphocytes isolated from CLL patients and healthy individuals. Flow cytometric assay was used to measure the percentage of apoptosis versus necrosis, intracellular active oxygen radicals (ROS), mitochondrial membrane potential (MMP) and the caspase-3 activity and then mitochondria were isolated from both groups B-lymphocytes and parameters of mitochondrial toxicity was investigated. Based on our results EA decreased the percentage of viable cells and induced apoptosis. EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects. Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients.
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http://dx.doi.org/10.1016/j.redox.2015.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588415PMC
December 2015

Transmitted Drug Resistance Mutations in Antiretroviral-Naïve Injection Drug Users with Chronic HIV-1 Infection in Iran.

PLoS One 2015 11;10(5):e0126955. Epub 2015 May 11.

Department of Pathology and Medical Laboratory Sciences, Faculty of Paramedicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

The growing incidence and transmission of drug resistant HIV-1 strains due to widespread use of antiretroviral therapy (ART) can jeopardize the success of first-line ART. While there is a known moderate prevalence of transmitted drug resistance (TDR) among newly infected Iranians, no data exist about the rate of these primary resistance mutations among the ART-naïve, chronically infected individuals who are, in fact, the main candidates for ART initiation. To address this issue, we collected blood samples from 40 ART-naïve injection drug-users (IDUs) with chronic HIV-1 infection (seroconversion time ranging from 2 to 9 years) living in Sanandaj, Iran, followed by sequencing of the protease and reverse-transcriptase regions from their HIV-1 genome. Phylogenetic analyses of the sequenced regions revealed that all samples were CRF35_AD. Transmitted resistance mutations were interpreted as surveillance drug-resistant mutations (SDRMs) based on the world health organization (WHO) algorithm. The frequency of SDRMs to any class of antiretroviral drugs was 15%, which included mutations to nucleoside reverse transcriptase inhibitors (NRTIs, 10%), with M41L and M184V as the most common (5%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs, 5%), with K103N as the only detected mutation (5%). Although not in the WHO SDRMs list, several minor protease inhibitor resistant mutations listed in the International Antiviral Society-USA panel were identified, of which M36I, H69K, L89M/V/I (each one 100%) and K20R/T (92.5%) can be considered as polymorphic signatures for CRF35_AD.The relatively high rate of TDR mutations in our study raises concerns about the risk of treatment failure in chronically infected IDUs of Sanandaj city. These results suggest that routine resistance testing should be considered before the therapy initiation in this area. Additional surveillance studies are required to generalize this deduction to other cities of Iran.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427455PMC
February 2016

Identification and DUS Testing of Rice Varieties through Microsatellite Markers.

Int J Plant Genomics 2015 8;2015:965073. Epub 2015 Feb 8.

Seed & Plant Certification and Registration Institute (SPCRI), Collection Avenue, Nabovvat Boulevard, Karaj 31535-1516, Iran.

Identification and registration of new rice varieties are very important to be free from environmental effects and using molecular markers that are more reliable. The objectives of this study were, first, the identification and distinction of 40 rice varieties consisting of local varieties of Iran, improved varieties, and IRRI varieties using PIC, and discriminating power, second, cluster analysis based on Dice similarity coefficient and UPGMA algorithm, and, third, determining the ability of microsatellite markers to separate varieties utilizing the best combination of markers. For this research, 12 microsatellite markers were used. In total, 83 polymorphic alleles (6.91 alleles per locus) were found. In addition, the variation of PIC was calculated from 0.52 to 0.9. The results of cluster analysis showed the complete discrimination of varieties from each other except for IR58025A and IR58025B. Moreover, cluster analysis could detect the most of the improved varieties from local varieties. Based on the best combination of markers analysis, five pair primers together have shown the same results of all markers for detection among all varieties. Considering the results of this research, we can propose that microsatellite markers can be used as a complementary tool for morphological characteristics in DUS tests.
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http://dx.doi.org/10.1155/2015/965073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337753PMC
March 2015

In vitro toxicity of iron oxide nanoparticle: oxidative damages on Hep G2 cells.

Exp Toxicol Pathol 2015 Feb 11;67(2):197-203. Epub 2014 Dec 11.

Department of Physiology, Payam Noor University of Iran, Iran. Electronic address:

During the past years many studies have been done highlighting the great need for a more thorough understanding of cell-iron oxide nanoparticle interactions. To improve our knowledge in this field, there is a great need for standardized protocols that would allow to comparing the cytotoxic potential of any Fe2O3-NP type with previously studied particles. Several approaches are reported that several parameters which are of great importance for Fe2O3 nanoparticle induced toxicity. Nanoparticles because of their very small size can pass through the cell membrane and can make oxidative damage in all parts of the cells such as mitochondria, membrane, DNA due to high surface area. This study focuses on acute cytotoxicity of reactive oxygen species and DNA damaging effects of mentioned nanoparticles. Results showed increase of the oxidative damage leads cells to the apoptosis, therefore reduced cell viability. It is interesting that all of the results are concentration and time dependent.
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http://dx.doi.org/10.1016/j.etp.2014.11.010DOI Listing
February 2015

The toxic effect of manganese on the acetylcholinesterase activity in rat brains.

J Toxicol 2014 26;2014:946372. Epub 2014 Aug 26.

Department of Food Safety and Hygiene, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days.
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http://dx.doi.org/10.1155/2014/946372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160610PMC
September 2014

Extra EF hand unit (DX) mediated stabilization and calcium independency of α-amylase.

Mol Biotechnol 2013 Mar;53(3):270-7

Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.

It is the common feature of α-amylases that calcium ion is required for their structural integrity and thermal stability. All amylases have at least one Ca(2+) per molecule; therefore amino acids involved in calcium binding are specific and conserved. In this study, sequence analysis revealed the presence of EF-hand-like motif in calcium-binding loop of Bacillus megaterium WHO (BMW)-amylase that was previously isolated from BMW. The EF-hand motif and its variants (EF-hand-like motif) are the most common calcium-binding motifs found in a large number of protein families. To investigate the effect of calcium ion on the thermal stability and activity of BMW-amylase, we used site-directed mutagenesis to replace histidine 58 with Asp (D), Ile (I), Tyr (Y), Phe (F), and Arg (R) at the seventh position of EF-hand-like motif. Upon the addition of an extra DX unit to the calcium-binding loop in H58D variant, thermal stability, catalytic activity, and chelating power of the enzyme improved due to higher affinity toward calcium. H58D variant demonstrated calcium independency compared to the wild type and other created mutants. Conformational changes in the presence and absence of Ca(2+) were monitored using fluorescence technique.
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http://dx.doi.org/10.1007/s12033-012-9523-xDOI Listing
March 2013