Publications by authors named "Mohammad Javad Hajipour"

24 Publications

  • Page 1 of 1

A nationwide study of metabolic syndrome prevalence in Iran; a comparative analysis of six definitions.

PLoS One 2021 3;16(3):e0241926. Epub 2021 Mar 3.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: To integrate and execute a proper preventive plan and reduce the risk of non-communicable diseases (NCDs), policy makers need to have access to both reliable data and a unique definition of metabolic syndrome (MetS). This study was conducted on the data collected by cross-sectional studies of WHO's STEPwise approach to surveillance of NCD risk factors (STEPs) to estimate the national and sub-national prevalence rates of MetS in Iran in 2016.

Materials And Methods: The prevalence of MetS was estimated among 18,414 individuals aged ≥25 years living in urban and rural areas of Iran using various definition criteria; National Cholesterol Education Program Adult Treatment Panel III 2004 (ATP III), International Diabetes Federation (IDF), American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), Joint Interim Statement (JIS). Regional IDF (RIDF) and JIS (RJIS) were defined using ethnicity-specific values of waist circumference for the country.

Results: National prevalence rate of MetS based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS criteria were 38.3% (95% CI 37.4-39.1), 43.5% (42.7-44.4), 40.9% (40.1-41.8), 47.6% (46.8-48.5), 32.0% (31.2-32.9), and 40.8% (40.0-41.7), respectively. The prevalence was higher among females, in urban residents, and those aged 65-69 years. MetS was expected to affect about 18.7, 21.3, 20.0, 23.3, 15.7, and 20.0 million Iranians, respectively, based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS. The two most common components noted in this population were reduced high-density lipoprotein cholesterol (HDL-C) levels and central obesity.

Conclusion: High prevalence rate of MetS among Iranian adults is alarming, especially among females, urban residents, and the elderly. The JIS definition criteria is more appropriate to determine higher number of Iranians at risk of NCDs. Proper management and prevention of MetS is required to adopt multiple national plans including lifestyle modifications, medical interventions, and public education on NCDs risk factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241926PLOS
March 2021

Distribution of Dietary Risk Factors in Iran: National and Sub-National Burden of Disease.

Arch Iran Med 2021 01 1;24(1):48-57. Epub 2021 Jan 1.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Non-communicable diseases (NCDs) are one of the greatest threats to public health, and have been related to poor quality dietary patterns. This study was conducted to determine the distribution of dietary risk factors in Iran.

Methods: Cross-sectional data was gathered between April and November 2016 from 30,541 eligible adults (out of 31 050 individuals who were selected through systematic proportional to size cluster random sampling) living in urban and rural areas, using the WHO-based STEPs risk factor questionnaire. Low intakes of fruits, vegetables, dairy products, and fish, and high intakes of salty processed food (SPF), as well as daily intake of hydrogenated fat (HF) were considered as nutritional risk factors.

Results: At the national level, 82.8% (95% CI: 82.4-83.2), 57.8% (95% CI: 57.2-58.4), 80.6% (95% CI: 80.1-81) and 90.3% (95% CI: 90-90.6) of participants of all age groups had sub-optimal intakes of fruits, vegetables, dairy products and fish, respectively. Furthermore, 12.8% (95% CI: 12.4-13.1), and 29.4% (95% CI: 28.9-29.9) of respondents had high SPF intakes and HF use, respectively. At the sub-national level, the highest distribution of suboptimal intake of fruits (97.2%; 95% CI:96-98.3), vegetables (79.2%; 95% CI: 76.3-82.1) and dairy products (92.9%; 95% CI: 91-94.7) was observed in Sistan and Baluchistan. Except for Boushehr and Hormozgan, the majority of the population of other provinces consumed fish less than twice a week. Similarly, the high intake of SPF was found mostly in the population of Yazd (23.7; 95% CI: 20.2-27.2). HF consumption was the highest in North Khorasan (64.2%; 95% CI: 60.3-68.1).

Conclusion: These findings highlight the widespread distribution of dietary risk factors in Iran, which should be a priority for the people and the politicians in order to prevent NCDs.
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http://dx.doi.org/10.34172/aim.2021.08DOI Listing
January 2021

Iranian population exposures to heavy metals, PAHs, and pesticides and their intake routes: a study protocol of a national population health survey.

Environ Sci Pollut Res Int 2021 Jan 4. Epub 2021 Jan 4.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Cancer is the second leading cause of death in the world and the third leading cause of death in Iran. It has been proven that numerous cancer cases are caused by exposure to environmental pollutants. There is a public health concern regarding an increase in exposure to carcinogens across Iran through different sources (air, food, and water) and a lack of research to address this issue. This study aims to gather data on exposure to heavy metals, polycyclic aromatic hydrocarbons (PAHs), and pesticides and their intake routes during the implementation of a national population health survey. This is a cross-sectional study of environmental pollutants in Iran, with a stratified multi-stage random sampling method, which led to 660 nationally representative samples in 132 clusters in three sequential parts. The first will be questionnaires to obtain demographics, assets, food records, air quality, and food frequency. The second will be physical measurements, including anthropometric and body composition. The third will be lab assessments that measure 26 types of environmental pollutants (7 heavy metals, 16 PAHs, and 3 pesticides) in urine, inhaled air, and consumed food and water of the population under study using ICP-MS and GS-MS devices. The results of this study will inform policymakers and the general population regarding the level of threat and will provide evidence for the development of interventional and observatory plans on the reduction of exposures to these pollutants. It could also be used to develop local standards to control contaminants through the three exposure routes. This study protocol will obtain data needed for policymakers to set surveillance systems for these pollutants at the national and provincial level to address the public concerns regarding the contamination of food, air, and water.
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http://dx.doi.org/10.1007/s11356-020-12004-3DOI Listing
January 2021

Nanomedicine in Healing Chronic Wounds: Opportunities and Challenges.

Mol Pharm 2021 02 10;18(2):550-575. Epub 2020 Jun 10.

Department of Radiology and Precision Health Program, Michigan State University, East Lansing, Michigan 48824, United States.

The poor healing associated with chronic wounds affects millions of people worldwide through high mortality rates and associated costs. Chronic wounds present three main problems: First, the absence of a suitable environment to facilitate cell migration, proliferation, and angiogenesis; second, bacterial infection; and third, unbalanced and prolonged inflammation. Unfortunately, current therapeutic approaches have not been able to overcome these main issues and, therefore, have limited clinical success. Over the past decade, incorporating the unique advantages of nanomedicine into wound healing approaches has yielded promising outcomes. Nanomedicine is capable of stimulating various cellular and molecular mechanisms involved in the wound microenvironment via antibacterial, anti-inflammatory, and angiogenetic effects, potentially reversing the wound microenvironment from nonhealing to healing. This review briefly discusses wound healing mechanisms and pathophysiology and then highlights recent findings regarding the opportunities and challenges of using nanomedicine in chronic wound management.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00346DOI Listing
February 2021

Is salt intake reduction a universal intervention for both normotensive and hypertensive people: a case from Iran STEPS survey 2016.

Eur J Nutr 2020 Oct 4;59(7):3149-3161. Epub 2019 Dec 4.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: There is a direct association between salt intake and blood pressure (BP), one of the main risk factors for CVDs. However, yet there has been a debate that how strong is this association in people with and without hypertension. This study was conducted to evaluate the magnitude of the association between salt intake and BP in hypertensive and normotensive population among a nationally representative population.

Methods: The study was conducted on a nationally representative sample of 18,635 Iranian adults aged 25 years and older who participated in the STEPS survey 2016 and provided urine sample. Salt intake was estimated through spot urine sample and Tanaka equation. Multiple linear regression model in survey data analysis was used to assess the independent effect of salt intake on BP.

Results: After adjusting for covariates, there was a significant association between salt intake and SBP in hypertensive (p < 0.001) and normotensive people (p < 0.001). In hypertensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.37 mmHg and 0.07 mmHg, respectively. Whereas in normotensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.26 mmHg and 0.05 mmHg, respectively. Moreover, there was a significant trend toward an increase of SBP across salt intake quartiles in both hypertensive (p < 0.001) and normotensive people (p = 0.002), though the slope was steeper in hypertensive than in normotensive people.

Conclusions: The present study demonstrated that salt intake significantly increased SBP in both hypertensive and normotensive people, though the magnitude of this increase was greater in hypertensive people as compared with normotensive people.
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http://dx.doi.org/10.1007/s00394-019-02153-8DOI Listing
October 2020

Supramolecular Insights into Domino Effects of Ag@ZnO-Induced Oxidative Stress in Melanoma Cancer Cells.

ACS Appl Mater Interfaces 2019 Dec 4;11(50):46408-46418. Epub 2019 Dec 4.

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM) , Tehran University of Medical Sciences , 1417755469 Tehran , Iran.

Recent studies suggest that cancer cell death accompanied by organelle dysfunction might be a promising approach for cancer therapy. The Golgi apparatus has a key role in cell function and may initiate signaling pathways to mitigate stress and, if irreparable, start apoptosis. It has been shown that Golgi disassembly and fragmentation under oxidative stress act as indicators for stress-mediated cell death pathways through cell cycle arrest in the G2/M phase. The present study shows that UV-induced reactive oxygen species (ROS) generation by Ag@ZnO nanoparticles (NPs) transform the Golgi structures from compressed perinuclear ribbons into detached vesicle-like structures distributed in the entire cytoplasm of melanoma cells. This study also demonstrates that Ag@ZnO NP-induced Golgi fragmentation cooccurs with G2 block of cell cycle progression, preventing cells from entering the mitosis phase. Additionally, the increased intracellular ROS production triggered by Ag@ZnO NPs upon UV exposure promoted autophagy. Taken together, Ag@ZnO NPs induce stress-related Golgi fragmentation and autophagy, finally leading to melanoma cell apoptosis. Intracellular oxidative stress generated by Ag@ZnO NPs upon UV irradiation may thus represent a targeted approach to induce cancer cell death through organelle destruction in melanoma cells, while fibroblast cells remained largely unaffected.
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http://dx.doi.org/10.1021/acsami.9b13420DOI Listing
December 2019

Nanoscale Technologies for Prevention and Treatment of Heart Failure: Challenges and Opportunities.

Chem Rev 2019 11 6;119(21):11352-11390. Epub 2019 Sep 6.

Precision Health Program , Michigan State University , East Lansing , Michigan 48824 , United States.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.
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http://dx.doi.org/10.1021/acs.chemrev.8b00323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003249PMC
November 2019

Impact of Gold Nanoparticles on Amyloid β-Induced Alzheimer's Disease in a Rat Animal Model: Involvement of STIM Proteins.

ACS Chem Neurosci 2019 05 1;10(5):2299-2309. Epub 2019 Apr 1.

Department of Toxicology & Pharmacology, Faculty of Pharmacy; Toxicology and Poisoning Research Centre , Tehran University of Medical Sciences , Tehran 1416753955 , Iran.

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aβ) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aβ fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. In this study, acquisition and retention of spatial learning and memory are studied in a rat animal model of AD after intrahippocampal (IH) and intraperitoneal (IP) injections of a model NP, i.e., gold NPs (AuNPs). The outcomes revealed that the AuNPs could improve the acquisition and retention of spatial learning and memory in Aβ treated rats as indicated by decreased time (Aβ: 39.60 ± 3.23 s vs Aβ+AuNPs: 25.78 ± 2.80 s) and distance (Aβ: 917.98 ± 50.81 cm vs Aβ+AuNPs: 589.09 ± 65.96 cm) of finding the hidden platform during training days and by increased time spent in the target quadrant (Aβ: 19.40 ± 0.98 s vs Aβ+AuNPs: 29.36 ± 1.14 s) in the probe test in Morris water maze (MWM). Expression of brain-derived neurotrophic factor, BDNF, cAMP response element binding protein, CREB, and stromal interaction molecules, e.g., STIM1 and STIM2 was also increased, supporting improved neural survival. Our outcomes may pave a way for mechanistic insights toward the role of NPs on retrieval of the deteriorated behavioral functions in brain tissue after AD outbreak.
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http://dx.doi.org/10.1021/acschemneuro.8b00622DOI Listing
May 2019

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein.

ACS Nano 2019 03 27;13(3):3243-3256. Epub 2019 Feb 27.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute , Tehran University of Medical Sciences , Tehran 1411713137 , Iran.

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.
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http://dx.doi.org/10.1021/acsnano.8b08983DOI Listing
March 2019

Molecular interaction of fibrinogen with zeolite nanoparticles.

Sci Rep 2019 02 7;9(1):1558. Epub 2019 Feb 7.

Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States.

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ), located in D-domain, showed the highest level of exposure compared to other sequences/residues.
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http://dx.doi.org/10.1038/s41598-018-37621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367512PMC
February 2019

Nanoparticles affect bacterial colonies' optical diffraction patterns.

Nanoscale 2019 Feb;11(6):2594-2601

Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

It is increasingly being accepted that bacteria are able to alter their shape/colony pattern in response to adverse environmental conditions. Morphological adaptation of bacteria is known as one of their defence mechanisms against environmental stress/variations. As nanoparticles (NPs) have a unique capacity to induce a wide range of stresses to bacteria, we hypothesized that such NPs can affect the bacterial colony pattern. To test this hypothesis, we incubated a series of superparamagnetic iron oxide nanoparticles (SPIONs) with different physicochemical properties with bacterial colonies and probed the colonies' diffraction patterns by laser. The diffraction patterns of Escherichia coli, Lactobacillus rhamnosus, and Staphylococcus aureus colonies were recorded using a laser. Our results revealed the formation of distinct bacterial diffraction patterns in response to SPIONs with various concentrations and surface chemistries. Our results may pave the way toward the development of new optical approaches for the high-throughput screening of bacterial-NPs/drugs interactions.
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http://dx.doi.org/10.1039/c8nr09332fDOI Listing
February 2019

cis pT231-Tau Drives Neurodegeneration in Bipolar Disorder.

ACS Chem Neurosci 2019 03 23;10(3):1214-1221. Epub 2019 Jan 23.

Department of Brain and Cognitive Sciences, Cell Science Research Center , Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran , Iran.

Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation results in neurodegeneration upon the disease. Recent studies have demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which cis pT231-tau is highly neurotoxic and acts as an early driver of tauopathy in several neurodegenerative diseases. We herein employed an in vitro model, which resembles some aspects of bipolar disorder, to study the cis p-tau mediatory role. We established GSK3β overexpressing SH-SY5Y cells and examined cell viability, cis p-tau formation, and lithium effects by immunofluorescence and flow cytometry. We found an increase in cis p-tau levels as well as viability decrease in the cell model. Furthermore, we discovered that lithium treatment inhibits cis p-tau formation, resulting in diminished cell death. We also examined BD and healthy human brain samples and detected cis p-tau in the patients' brains. Our results show that tauopathy, observed in bipolar disorder, is being mediated through cis p-tau and that a conformer could be the cause of neurodegeneration upon the disease. Our findings would suggest novel therapeutic target to fight the devastating disorder.
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http://dx.doi.org/10.1021/acschemneuro.8b00629DOI Listing
March 2019

The prevalence, awareness, and treatment of lipid abnormalities in Iranian adults: Surveillance of risk factors of noncommunicable diseases in Iran 2016.

J Clin Lipidol 2018 Nov - Dec;12(6):1471-1481.e4. Epub 2018 Aug 10.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Hypercholesterolemia is one of the modifiable risk factors for atherosclerosis and cardiovascular diseases. Prevention and treatment of hypercholesterolemia and other lipid abnormalities require reliable data regarding the current prevalence of these abnormalities in the country.

Objective: This study aims to determine the current prevalence, awareness, and treatment of lipid abnormalities in Iran.

Methods: We planned to recruit 31,050 individuals who are 18 years old and above and take blood samples from individuals who are 25 years and above as representative sample at national and provincial levels in 2016. In practice, we recruited 21,293 Iranian adult aged more than 25 years through a systematic random sampling from 30 provinces of Iran. Sociodemographic, anthropometric, and lifestyle data and history of cardiometabolic diseases were gathered. Serum total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglyceride, low-density lipoprotein-cholesterol (LDL-C), and non-HDL-C were investigated. The prevalence of lipid abnormalities, awareness, treatment, and achievement to non-HDL-C and LDL-C goals were determined based on National Cholesterol Education Program Adult Treatment Panel III criteria.

Results: In this representative Iranian adult population, 80.0% had at least one lipid abnormality, 69.2% had low HDL-C, 39.5% had high non-HDL-C, 28.0% had hypertriglyceridemia, and 26.7% hypercholesterolemia. Of those with hypercholesterolemia, 74.2% were aware of their lipid abnormality. Only 22.0% and 36.5% of the study population met the desired level of non-HDL-C and LDL-C, respectively.

Conclusion: Low HDL-C is the main lipid abnormality in adult Iranian population. The majority of the population did not meet the desired level of non-HDL-C and LDL-C. Public health preventive policies should be made and implemented to better manage dyslipidemia.
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http://dx.doi.org/10.1016/j.jacl.2018.08.001DOI Listing
October 2019

Detection and Discrimination of Bacterial Colonies with Mueller Matrix Imaging.

Sci Rep 2018 Jul 17;8(1):10815. Epub 2018 Jul 17.

Department of Medical Physics and Biomedical Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The polarization imaging technique is a powerful approach to probe microstructural and optical information of biological structures (e.g., tissue samples). Here, we have studied the polarization properties of different bacterial colonies in order to evaluate the possibility of bacterial detection and discrimination. In this regard, we have taken the backscattering Mueller matrix images of four different bacteria colonies (i.e., Escherichia coli, Lactobacillus rhamnosus, Rhodococcus erythropolis, and Staphylococcus aureus). Although the images have the potential to distinguish qualitatively different bacterial colonies, we explored more accurate and quantitative parameters criteria for discrimination of bacterial samples; more specifically, we have exploited the Mueller matrix polar decomposition (MMPD),frequency distribution histogram (FDH), and central moment analysis method. The outcomes demonstrated a superior capacity of Mueller matrix imaging, MMPD, and FDH in bacterial colonies identification and discrimination. This approach might pave the way for a reliable, efficient, and cheap way of identification of infectious diseases.
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http://dx.doi.org/10.1038/s41598-018-29059-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050273PMC
July 2018

Biomolecular Corona Dictates Aβ Fibrillation Process.

ACS Chem Neurosci 2018 07 30;9(7):1725-1734. Epub 2018 Apr 30.

Pharmacutical Sciences Research Center , Kermanshah University of Medical Sciences , Kermanshah 67145-67346 , Iran.

Amyloid beta (Aβ), which forms toxic oligomers and fibrils in brain tissues of patients with Alzheimer's disease, is broadly used as a model protein to probe the effect of nanoparticles (NPs) on oligomerization and fibrillation processes. However, the majority of the reports in the field have ignored the effect of the biomolecular corona on the fibrillogenesis of the Aβ proteins. The biomolecular corona, which is a layer composed of various types of biomolecules that covers the surface of NPs upon their interaction with biological fluids, determines the biological fates of NPs. Therefore, during in vivo interaction of NPs with Aβ protein, what the Aβ actually "sees" is the human plasma and/or cerebrospinal fluid (CSF) biomolecular-coated NPs rather than the pristine surface of NPs. Here, to mimic the in vivo effects of therapeutic NPs as antifibrillation agents, we probed the effects of a biomolecular corona derived from human CSF and/or plasma on Aβ fibrillation. The results demonstrated that the type of biomolecular corona can dictate the inhibitory or acceleratory effect of NPs on Aβ and Aβ fibrillation processes. More specifically, we found that the plasma biomolecular-corona-coated gold NPs, with sphere and rod shapes, has less inhibitory effect on Aβ fibrillation kinetics compared with CSF biomolecular-corona-coated and pristine NPs. Opposite results were obtained for Aβ peptide, where the pristine NPs accelerated the Aβ fibrillation process, whereas corona-coated ones demonstrated an inhibitory effect. In addition, the CSF biomolecular corona had less inhibitory effect than those obtained from plasma.
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http://dx.doi.org/10.1021/acschemneuro.8b00076DOI Listing
July 2018

Probing fibronectin conformation on a protein corona layer around nanoparticles.

Nanoscale 2018 Jan;10(3):1228-1233

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.

Protein unfolding induced by nanoparticles (NPs) can lead to exposure of cryptic epitopes that might dictate biological identity and affect NP biological fate (e.g., blood circulation time, biodistribution, and tumor accumulation). Here, we monitor the conformation of fluorescence resonance energy transfer (FRET)-labelled fibronectin (FN) on corona-coated gold NPs. We found that the labelled FN proteins, which directly accessed the gold NP surface, underwent more pronounced conformational changes than those associated with the protein corona via protein-protein interactions. FRET and liquid chromatography-mass spectrometry analyses demonstrated that NP size/concentration, pH change, and the level of surface coverage by the corona can tune the accessibility of labelled FN to the gold NP surface. Although some subsequently adsorbing proteins accessed the NP surface thanks to incomplete surface coverage and protein exchange (the Vroman effect), most outer-layer proteins could not directly bind to the NP surface, blocked by pre-adsorbed corona layers. This finding was also partially confirmed by isothermal titration calorimetry (ITC) analysis. These results suggest the proof-of-concept that outermost-layer proteins with modestly changed conformation rather than unfolded proteins at the gold NP surface effectively create the NPs' biological identity, which might have important implications on biological fates of gold NPs.
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http://dx.doi.org/10.1039/c7nr06970gDOI Listing
January 2018

Protocol Design for Large-Scale Cross-Sectional Studies of Surveillance of Risk Factors of Non-Communicable Diseases in Iran: STEPs 2016.

Arch Iran Med 2017 Sep;20(9):608-616

Non-communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: The rise in non-communicable diseases (NCDs) has gained increasing attention. There is a great need for reliable data to address such problems. Here, we describe the development of a comprehensive set of executive and scientific protocols and instructions of STEPs 2016.

Methods/design: This is a large-scale cross-sectional study of Surveillance of Risk Factors of NCDs in Iran. Through systematic proportional to size cluster random sampling, 31,050 participants enrolled in three sequential processes, of completing questionnaires; physical measurements, and lab assessment.

Results: Out of 429 districts, samples were taken from urban and rural areas of 389 districts. After applying sampling weight to the samples, comparing the distribution of population and samples, compared classification was determined in accordance with the age and sex groups. Out of 31,050 expected participants, 30,541 participant completed questionnaires (52.31% female). For physical measurements and lab assessment, the cases included 30,042 (52.38% female) and 19,778 (54.04% female), respectively.

Discussion: There is an urgent need to focus on reviewing trend analyses of NCDs.To the best of our knowledge, the present study is the first comprehensive experience on systematic electronic national survey. The results could be also used for future complementary studies.
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http://dx.doi.org/0172009/AIM.009DOI Listing
September 2017

Sensing of Alzheimer's Disease and Multiple Sclerosis Using Nano-Bio Interfaces.

J Alzheimers Dis 2017 ;59(4):1187-1202

Department of Nanotechnology and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.
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http://dx.doi.org/10.3233/JAD-160206DOI Listing
April 2018

Advances in Alzheimer's Diagnosis and Therapy: The Implications of Nanotechnology.

Trends Biotechnol 2017 10 27;35(10):937-953. Epub 2017 Jun 27.

Neurosciences Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA. Electronic address:

Alzheimer's disease (AD) is a type of dementia that causes major issues for patients' memory, thinking, and behavior. Despite efforts to advance AD diagnostic and therapeutic tools, AD remains incurable due to its complex and multifactorial nature and lack of effective diagnostics/therapeutics. Nanoparticles (NPs) have demonstrated the potential to overcome the challenges and limitations associated with traditional diagnostics/therapeutics. Nanotechnology is now offering new tools and insights to advance our understanding of AD and eventually may offer new hope to AD patients. Here, we review the key roles of nanotechnologies in the recent literature, in both diagnostic and therapeutic aspects of AD, and discuss how these achievements may improve patient prognosis and quality of life.
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http://dx.doi.org/10.1016/j.tibtech.2017.06.002DOI Listing
October 2017

Zeolite Nanoparticles Inhibit Aβ-Fibrinogen Interaction and Formation of a Consequent Abnormal Structural Clot.

ACS Appl Mater Interfaces 2016 Nov 1;8(45):30768-30779. Epub 2016 Nov 1.

Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.

EMT-type zeolite nanoparticles (EMT NPs) with particle size of 10-20 nm and external surface area of 200 m/g have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD). To evaluate this hypothesis, the clot formation and degradation of Aβ-fibrinogen in the presence and absence of the EMT zeolite NPs were assessed. The results clearly showed that the delay in clot dissolution was significantly reduced in the presence of zeolite NPs. By formation of protein corona, the EMT NPs showed a negligible reduction in their inhibitory strength. Docking of small molecules (Aβ-fibrinogen) introduced a novel potential inhibitory candidate. The zeolite NPs showed similar inhibitory effects on binding of fibrinogen to both Aβ(25-35) and/or Aβ(1-42). This indicates that the inhibitory strength of these NPs is independent of Aβ sequence, and it is suggested that the zeolite NPs adsorb fibrinogen and specifically obstruct their Aβ binding sites. Therefore, the zeolite NPs can be the safe and effective inhibitors in preventing Aβ-fibrinogen interaction and consequent cognitive damage.
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http://dx.doi.org/10.1021/acsami.6b10941DOI Listing
November 2016

External magnetic fields affect the biological impacts of superparamagnetic iron nanoparticles.

Colloids Surf B Biointerfaces 2015 Dec 21;136:1107-12. Epub 2015 Nov 21.

Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the promising nanomaterials for applications in various field of nanomedicine such as targeted imaging/drug delivery, tissue engineering, hyperthermia, and gene therapy. Besides their suitable biocompatibility, SPIONs' unique magnetic properties make them an outstanding candidate for theranostic nanomedicine. Very recent progress in the field revealed that the presence of external magnetic fields may cause considerable amount of SPIONs' agglomeration in their colloidal suspension. As variation of physicochemical properties of colloidal nanoparticles has strong effect on their biological outcomes, one can expect that the SPIONs' agglomeration in the presence of external magnetic fields could change their well-recognized biological impacts. In this case, here, we probed the cellular uptake and toxicity of the SPIONs before and after exposure to external magnetic fields. We found that the external magnetic fields can affect the biological outcome of magnetic nanoparticles.
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http://dx.doi.org/10.1016/j.colsurfb.2015.11.028DOI Listing
December 2015

Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide.

Nanoscale 2015 May;7(19):8978-94

Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the 'personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.
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http://dx.doi.org/10.1039/c5nr00520eDOI Listing
May 2015

Protein corona composition of gold nanoparticles/nanorods affects amyloid beta fibrillation process.

Nanoscale 2015 Mar;7(11):5004-13

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran.

Protein fibrillation process (e.g., from amyloid beta (Aβ) and α-synuclein) is the main cause of several catastrophic neurodegenerative diseases such as Alzheimer's and Parkinson diseases. During the past few decades, nanoparticles (NPs) were recognized as one of the most promising tools for inhibiting the progress of the disease by controlling the fibrillation kinetic process; for instance, gold NPs have a strong capability to inhibit Aβ fibrillations. It is now well understood that a layer of biomolecules would cover the surface of NPs (so called "protein corona") upon the interaction of NPs with protein sources. Due to the fact that the biological species (e.g., cells and amyloidal proteins) "see" the protein corona coated NPs rather than the pristine coated particles, one should monitor the fibrillation process of amyloidal proteins in the presence of corona coated NPs (and not pristine coated ones). Therefore, the previously obtained data on NPs effects on the fibrillation process should be modified to achieve a more reliable and predictable in vivo results. Herein, we probed the effects of various gold NPs (with different sizes and shapes) on the fibrillation process of Aβ in the presence and absence of protein sources (i.e., serum and plasma). We found that the protein corona formed a shell at the surface of gold NPs, regardless of their size and shape, reducing the access of Aβ to the gold inhibitory surface and, therefore, affecting the rate of Aβ fibril formation. More specifically, the anti-fibrillation potencies of various corona coated gold NPs were strongly dependent on the protein source and their concentrations (10% serum/plasma (simulation of an in vitro milieu) and 100% serum/plasma (simulation of an in vivo milieu)).
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http://dx.doi.org/10.1039/c4nr06009aDOI Listing
March 2015

The enhancement of biodesulfurization activity in a novel indigenous engineered Pseudomonas putida.

Iran Biomed J 2009 Oct;13(4):207-13

National Institute of Genetic Engineering and Biotechnology (NIGEB), P.O.Box.14155-6343, Tehran, Iran.

Background: The combustion of sulfur-rich fossil fuels leads to release of sulfur oxide pollution in the environment. In biodesulfurization process, an organism is able to remove sulfur from fossil fuels without decreasing the caloric value of those substrates. The main aim of this research was to design a recombinant microorganism to remove the highest amount of sulfur compounds in fossil fuels.

Methods: Three genes (dszA,B,C) from dsz operon are responsible for the 4S pathway (biodesulfurization pathway) in Rhodococcus erythropolis IGTS8 were inserted into the chromosome of a novel indigenous Pseudomonas putida. The reaction catalyzed by products of dszA,B,C genes require FMNH2 supplied by dszD enzyme. Thus, pVLT31 vector harboring dszD gene was transferred into this recombinant strain.

Results: The results demonstrated a higher biodesulfurization activity when the flavin reductase gene was transferred into recombinant P. putida harboring dszA,B,C. These results were approved by the Gibbs test and HPLC analysis.

Conclusion: These analyses showed that this novel indigenous engineered P. putida could be a promising candidate for an industrial and environmental application for Biodesulfurization process.
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October 2009