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Niloofar Arsalan, 1,* Elahe Hassan Kashi, 2,* Anwarul Hasan, 3, 4 Mona Edalat Doost, 5 Behnam Rasti, 6 Bilal Ahamad Paray, 7 Mona Zahed Nakhjiri, 1 Soyar Sari, 2 Majid Sharifi, 8 Koorosh Shahpasand, 9 Keivan Akhtari, 10 Setareh Haghighat, 5 Mojtaba Falahati 8 1Department of Biology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University (IAU), Lahijan, Guilan, Iran; 2Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 3Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 4Biomedical Research Centre, Qatar University, Doha 2713, Qatar; 5Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Microbiology, Faculty of Basic Sciences, Islamic Azad University (IAU), Lahijan, Guilan, Iran; 7Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; 8Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 9Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology (RI-SCBT), Tehran, Iran; 10Department of Physics, University of Kurdistan, Sanandaj, Iran*These authors contributed equally to this workCorrespondence: Mojtaba Falahati; Anwarul Hasan Email mojtaba.falahati@alumni.ut.ac.ir; ahasan@qu.edu.qaAim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects.Methods: Herein, the interaction of as-synthesized Co 3O 4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co 3O 4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co 3O 4 NPs against three pathogenic bacteria were disclosed by antibacterial assays.Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co 3O 4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of − 33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co 3O 4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co 3O 4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co 3O 4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria.Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.Keywords: cobalt oxide, nanoparticle, synthesis, spectroscopy, docking, anticancer, antibacterial

Mubashra Zehra,1 Waliya Zubairi,2 Anwarul Hasan,3,4 Hira Butt,1 Amna Ramzan,1 Maryam Azam,2 Azra Mehmood,1 Mojtaba Falahati,5 Aqif Anwar Chaudhry,2 Ihtesham Ur Rehman,6 Muhammad Yar2 1National Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 53700, Pakistan; 2Interdisciplinary Research Centre in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan; 3Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 4Biomedical Research Center, Qatar University, Doha 2713, Qatar; 5Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; 6Engineering Department, Faculty of Science and Technology, Lancaster University, Lancaster LA1 4YW, UKCorrespondence: Anwarul Hasan; Muhammad Yar Tel +974-70569169; +92 42 001007 Ext 828Email ahasan@qu.edu.qa; drmyar@cuilahore.edu.pkIntroduction: Diabetic wounds are challenging to treat due to a wide range of pathophysiological changes. Hypoxia is one of the predominant contributing factors of poor vascularization and chronicity in diabetic wounds. This study was designed to develop polycaprolactone (PCL)-based oxygen-releasing electrospun wound dressings and evaluate their efficacy for improved full thickness wound healing in diabetic rats.Methods: PCL-based oxygen releasing wound dressings were made using electrospinning technology. The developed dressings were characterized in terms of physical as well as biological properties both in vitro and in vivo. E-spun nanofibrous dressings were physically characterized with scanning electron microscopy, Fourier-transform infrared spectroscopy, and Energy-dispersive X-ray spectroscopy. To study the likely impact of the fabricated wound dressings in hypoxic conditions, HIF-1α expression analysis was carried out both at gene and protein levels. Wound dressings were further evaluated for their healing potential for extensive wounds in diabetic rat models.Results: The experimental results showed that the developed dressings were capable of continuously generating oxygen for up to 10 days. Cell studies further confirmed pronounced expression of HIF-1α at gene and protein levels in cells seeded on PCL-sodium percarbonate (SPC) and PCL scaffolds compared with the cells cultured on a tissue culture plate. Chorioallantoic membrane assay revealed the supportive role of oxygen releasing dressings on angiogenesis compared to the control group. Histological assessment of the regenerated skin tissues proved that full thickness wounds covered with SPC loaded PCL dressings had a comparatively better vascularized and compact extracellular matrix with completely covered thick epithelium.Discussion: The developed oxygen generating polymeric nanofibrous wound dressings could potentially be used as an envisioned approach for the efficient recovery of chronic diabetic wounds.Keywords: skin regeneration, diabetic wound healing, oxygenation, polymeric nanofibers, electrospinning

Amitis Naskhi,1,* Sanaz Jabbari,1,* Goran Qader Othman,2 Falah Mohammad Aziz,3 Abbas Salihi,3,4 Majid Sharifi,5 Soyar Sari,1 Keivan Akhtari,6 Shang Ziyad Abdulqadir,3 Asaad AB Alasady,7 Osama K Abou-Zied,8 Anwarul Hasan,9,10 Mojtaba Falahati5 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Medical Laboratory, Health Technical College, Erbil Polytechnique University, Erbil, Iraq; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 5Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Physics, University of Kurdistan, Sanandaj, Iran; 7Anatomy, Histology, and Embryology Unit, College of Medicine, University of Duhok, Kurdistan Region, Iraq; 8Department of Chemistry, Faculty of Science, Sultan Qaboos University, Muscat, Sultanate of Oman; 9Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 10Biomedical Research Center, Qatar University, Doha 2713, Qatar*These authors contributed equally to this workCorrespondence: Mojtaba FalahatiDepartment of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, IranEmail mojtaba.falahati@alumni.ut.ac.irAnwarul HasanDepartment of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, QatarEmail hasan.anwarul.mit@gmail.comAims: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays.Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays.Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1.Conclusion: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.Keywords: α- Syn, single-walled carbon nanotube, aggregation, vitamin K1, cytotoxicity

Zahra Zand,1,* Pegah Afarinesh Khaki,2,* Abbas Salihi,3,4 Majid Sharifi,5,6 Nadir Mustafa Qadir Nanakali,7,8 Asaad AB Alasady,9 Falah Mohammad Aziz,3 Koorosh Shahpasand,10 Anwarul Hasan,11,12 Mojtaba Falahati51Department of Biochemistry and Biophysics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Molecular Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 5Department of Nanomedicine, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Animal Science, Faculty of Agriculture, University of Tabriz, Tabriz, Iran; 7Department of Biology, College of Science, Cihan University-Erbil, Kurdistan Region, Iraq; 8Department of Biology, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq; 9Anatomy, Biology and Histology Unit, College of Medicine, University of Duhok, Kurdistan Region, Iraq; 10Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 11Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 12Biomedical Research Center, Qatar University, Doha 2713, QatarCorrespondence: Mojtaba FalahatiDepartment of Nanomedicine, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, IranEmail mojtaba.falahati@alumni.ut.ac.irAnwarul HasanDepartment of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, QatarEmail hasan.anwarul.mit@gmail.com*These authors contributed equally to this workAim: Among therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation.Methods: In this paper, the inhibitory effect of cerium oxide (CeO2) NPs against α-synuclein (α-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of α-syn amyloid either alone or with CeO2 NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays.Results: ThT and ANS fluorescence assays indicated that CeO2 NPs inhibit the formation of aggregated species and hydrophobic patches of α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and β-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of α-syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of α-syn is disaggregated in the presence of CeO2 NPs. Moreover, cellular assays depicted that CeO2 NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with α-syn amyloids.Conclusion: It may be concluded that CeO2 NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.Keywords: cerium oxide, nanoparticle, amyloid, cytotoxicity, spectroscopy, cellular assay, inhibition

Mina Mousavi,1,* Saman Hakimian,1,* Twana Ahmed Mustafa,2 Falah Mohammad Aziz,3 Abbas Salihi,3,4 Mahsa Ale-Ebrahim5,* Mirsasan Mirpour,6 Behnam Rasti,6 Keivan Akhtari,7 Koorosh Shahpasand,8 Osama K Abou-Zied,9 Mojtaba Falahati101Department of Biochemistry and Biophysics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Kurdistan Region, Iraq; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 5Department of Physiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University (IAU), Lahijan, Guilan, Iran; 7Department of Physics, University of Kurdistan, Sanandaj, Iran; 8Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology (RI-SCBT), Tehran, Iran; 9Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box 36, Postal Code 123 Muscat, Oman; 10Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran*These authors contributed equally to this workAim: Nanoparticles (NPs) have been receiving potential interests in protein delivery and cell therapy. As a matter of fact, NPs may be used as great candidates in promoting cell therapy by catalase (CAT) delivery into high oxidative stress tissues. However, for using NPs like SiO2 as carriers, the interaction of NPs with proteins and mesenchymal stem cells (MSCs) should be explored in advance.Methods: In the present study, the interaction of SiO2 NPs with CAT and human MSCs (hMSCs) was explored by various spectroscopic methods (fluorescence, circular dichroism (CD), UV-visible), molecular docking and dynamics studies, and cellular (MTT, cellular morphology, cellular uptake, lactate dehydrogenase, ROS, caspase-3, flow cytometry) assays.Results: Fluorescence study displayed that both dynamic and static quenching mechanisms and hydrophobic interactions are involved in the spontaneous interaction of SiO2 NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO2 NPs. UV-visible study also revealed that the kinetic parameters of CAT such as Km, Vmax, Kcat, and enzyme efficiency were not changed after the addition of SiO2 NPs. Molecular docking and dynamics studies showed that Si and SiO2 clusters interact with hydrophobic residues of CAT and SiO2 cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO2 NPs induce significant cell mortality, change in cellular morphology, cellular internalization, ROS elevation, and apoptosis in hMSCs at higher concentration than 100 μg/mL (170 μM).Conclusion: The current results suggest that low concentrations of SiO2 NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC.Keywords: silica nanoparticles, catalase, mesenchymal stem cells, interaction, spectroscopy, docking, molecular dynamics, cellular assays

Seyedeh Sahar Tahaei Gilan,1,* Dorsa Yahya Rayat,1,* Twana Ahmed Mustafa,2 Falah Mohammad Aziz,3 Koorosh Shahpasand,4 Keivan Akhtari,5 Abbas Salihi,3,6 Osama K Abou-Zied,7 Mojtaba Falahati81Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Kurdistan Region, Iraq; 3Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq; 4Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 5Department of Physics, University of Kurdistan, Sanandaj, Iran; 6Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq; 7Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box 36, Postal Code 123 Muscat, Oman; 8Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran*These authors contributed equally to this workAim: It has been indicated that NPs may change the amyloidogenic steps of proteins and relevant cytotoxicity. Therefore, this report assigned to explore the impact of ZVFe NPs on the amyloidogenicity and cytotoxicity of α-synuclein as one of the many known amyloid proteins.Methods: The characterization of α-synuclein at amyloidogenic condition either alone or with ZVFe NPs was carried out by fluorescence, CD, UV-visible spectroscopic methods, TEM study, docking, and molecular modeling. The cytotoxicity assay of α-synuclein amyloid in the absence and presence of ZVFe NPs was also done by MTT, LDH, and flow cytometry analysis.Results: ThT fluorescence spectroscopy revealed that ZVFe NPs shorten the lag phase and accelerate the fibrillation rate of α-synuclein. Nile red and intrinsic fluorescence spectroscopy, CD, Congo red adsorption, and TEM studies indicated that ZVFe NP increased the propensity of α-synuclein into the amyloid fibrillation. Molecular docking study revealed that hydrophilic residues, such as Ser-9 and Lys-12 provide proper sites for hydrogen bonding and electrostatic interactions with adsorbed water molecules on ZVFe NPs, respectively. Molecular dynamics study determined that the interacted protein shifted from a natively discorded conformation toward a more packed structure. Cellular assay displayed that the cytotoxicity of α-synuclein amyloid against SH-SY5Y cells in the presence of ZVFe NPs is greater than the results obtained without ZVFe NPs.Conclusion: In conclusion, the existence of ZVFe NPs promotes α-synuclein fibrillation at amyloidogenic conditions by forming a potential template for nucleation, the growth of α-synuclein fibrillation and induced cytotoxicity.Keywords: α-synuclein, ZVFe NP, amyloid, cytotoxicity, spectroscopy

Aida Fardanesh,1,* Sedigheh Zibaie,1,* Behdad Shariati,1 Farnoosh Attar,2 Fatemeh Rouhollah,1 Keivan Akhtari,3 Koroosh Shahpasand,4 Ali Akbar Saboury,5 Mojtaba Falahati6 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran; 3Department of Physics, University of Kurdistan, Sanandaj, Iran; 4Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 5Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 6Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran *These authors contributed equally to this work Background: Nanoparticles (NPs) when injected into the body can reach target tissues like nervous system and interact with tau proteins and neurons. This can trigger conformational changes of tau and may affect NP toxicity. Methods: In this study, we used several biophysical techniques (extrinsic and intrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy, ultraviolet (UV)-visible spectroscopy), transmission electron microscopy (TEM) investigations, molecular docking and molecular dynamics studies, and cellular assays [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry) to reveal how structural changes of tau protein can change the cytotoxicity of titanium dioxide (TiO2) NPs against neuron-like cells (SH-SY5Y) cells. Results: It was shown that TiO2 NPs result in hydrophilic interactions, secondary and tertiary structural changes, and the formation of amorphous tau aggregates. Conformational changes of tau increased the induced cytotoxicity by TiO2 NPs. These data revealed that the denatured adsorbed protein on the NP surface may enhance NP cytotoxicity. Conclusion: Therefore, this study provides useful insights on the NP–protein interactions and discusses how the protein corona can increase cytotoxicity to determine the efficacy of targeted delivery of nanosystems. Keywords: titanium oxide nanoparticle, tau, amorphous aggregation, cytotoxicity, neuron-like cells

Elham Behzadi,1,* Rozhin Sarsharzadeh,1,* Mina Nouri,1 Farnoosh Attar,2 Keivan Akhtari,3 Koorosh Shahpasand,4 Mojtaba Falahati5 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran; 3Department of Physics, University of Kurdistan, Sanandaj, Iran; 4Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 5Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran *These authors contributed equally to this work Background: Recently, nanomaterials have moved into biological and medicinal implementations like cancer therapy. Therefore, before clinical trials, their binding to plasma proteins like human serum albumin (HSA) and their cytotoxic effects against normal and cancer cell lines should be addressed. Methods: Herein, the interaction of magnesium oxide nanoparticles (MgO NPs) with HSA was studied by means of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and docking studies. Afterwards, the cytotoxic impacts of MgO NPs on human leukemia cell line (K562) and peripheral blood mononucleated cells (PBMCs) were evaluated by MTT and flow cytometry assays to quantify reactive oxygen species (ROS) generation and apoptosis. Results: It was demonstrated that MgO NPs spontaneously form a static complex with HSA molecules through hydrophobic interactions. Docking study based on the size of NPs demonstrated that different linkages can be established between MgO NPs and HSA. The CD investigation explored that MgO NPs did not alter the secondary structure of HSA. Cellular studies revealed that MgO NPs induced cytotoxicity against K562 cell lines, whereas no adverse effects were detected on PBMCs up to optimum applied concentration of MgO NPs. It was exhibited that ROS production mediated by IC50 concentrations of MgO NPs caused apoptosis-associated cell death. The pre-incubation of K562 with ROS scavenger (curcumin) inhibited the impact of MgO NPs -based apoptosis on cell fate, revealing the upstream effect of ROS in our system. Conclusion: In summary, MgO NPs may exhibit strong plasma distribution and mediate apoptosis by ROS induction in the cancer cell lines. These data demonstrate a safe aspect of MgO NPs on the proteins and normal cells and their application as a distinctive therapeutic approach in the cancer treatment. Keywords: spectroscopy, anticancer, magnesium oxide, nanoparticles, albumin, K562 cells

Tabassom Sedaghat Anbouhi,1,* Elnaz Mokhtari Esfidvajani,2,* Fahimeh Nemati,1 Setareh Haghighat,3 Soyar Sari,2 Farnoosh Attar,4 Arezoo Pakaghideh,5 Mohammad Javad Sohrabi,6 Seyyedeh Elaheh Mousavi,6 Mojtaba Falahati7 1Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 3Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 4Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran; 5Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, Iran; 6Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran *These authors contributed equally to this work Background: Nanoparticles (NPs) have been emerging as potential players in modern medicine with clinical applications ranging from therapeutic purposes to antimicrobial agents. However, before applications in medical agents, some in vitro studies should be done to explore their biological responses.Aim: In this study, protein binding, anticancer and antibacterial activates of zero valent iron (ZVFe) were explored. Materials and methods: ZVFe nanoparticles were synthesized and fully characterized by X-ray diffraction, field-emission scanning electron microscope, and dynamic light scattering analyses. Afterward, the interaction of ZVFe NPs with human serum albumin (HSA) was examined using a range of techniques including intrinsic fluorescence, circular dichroism, and UV–visible spectroscopic methods. Molecular docking study was run to determine the kind of interaction between ZVFe NPs and HSA. The anticancer influence of ZVFe NPs on SH-SY5Y was examined by MTT and flow cytometry analysis, whereas human white blood cells were used as the control cell. Also, the antibacterial effect of ZVFe NPs was examined on Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), and Staphylococcus aureus (ATCC 25923). Results: X-ray diffraction, transmission electron microscope, and dynamic light scattering analyses verified the synthesis of ZVFe NPs in a nano-sized diameter. Fluorescence spectroscopy analysis showed that ZVFe NPs spontaneously formed a complex with HSA through hydrogen bonds and van der Waals interactions. Also, circular dichroism spectroscopy study revealed that ZVFe NPs did not change the secondary structure of HSA. Moreover, UV–visible data presented that melting temperature (Tm) of HSA in the absence and presence of ZVFe NPs was almost identical. Molecular dynamic study also showed that ZVFe NP came into contact with polar residues on the surface of HSA molecule. Cellular assays showed that ZVFe NPs can induce cell mortality in a dose-dependent manner against SH-SY5Y cells, whereas these NPs did not trigger significant cell mortality against normal white bloods in the concentration range studied (1–100 µg/mL). Antibacterial assays showed a noteworthy inhibition on both bacterial strains. Conclusion: In conclusion, it was revealed that ZVFe NPs did not induce a substantial influence on the structure of protein and cytotoxicity against normal cell, whereas they derived significant anticancer and antibacterial effects. Keywords: zero valent iron, nanoparticle, spectroscopy, docking, anticancer, antibacterial activity

Mohammad Mahdi Nejadi Babadaei,1,* Mina Feli Moghaddam,1,* Sara Solhvand,1 Ehsan Alizadehmollayaghoob,1 Farnoosh Attar,2 Elham Rajabbeigi,3 Keivan Akhtari,4 Soyar Sari,1 Mojtaba Falahati5 1Department of Cellular and Molecular Biology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran; 2Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran; 3Department of Biochemistry, Faculty of Advance Science and Technology, Medical Sciences Branch, Islamic Azad University, Tehran, Iran; 4Department of Physics, University of Kurdistan, Sanandaj, Iran; 5Department of Nanotechnology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran *These authors contributed equally to this work Background: Implementations of nanoparticles have been receiving great interest in medicine and technology due to their unique characteristics. However, their toxic impacts on the biological system are not well explored.Aim: This study aims to investigate the influence of fabricated nano graphene oxide (NGO) sheets on the secondary and quaternary structural alterations of human hemoglobin (Hb) and cytotoxicity against lymphocyte cells.Materials and methods: Different spectroscopic methods, such as extrinsic and synchronous fluorescence spectroscopy and far circular dichroism (CD) spectroscopy, molecular docking investigation, cellular assays (trypan blue exclusion, cellular uptake, ROS, cell cycle, and apoptosis), and molecular assay (fold changes in anti/proapoptotic genes [B-cell lymphoma-2 {BCL2}/BAX] expression levels) were used in this study.Results: Transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and zeta potential investigations revealed the nano-sized nature of NGOs with good colloidal stability. Extrinsic fluorescence spectroscopy by using 8-anilinonaphthalene-1-sulfonic acid and synchronous fluorescence spectroscopy showed that NGOs can unfold the quaternary structure of Hb in the vicinity of Tyr residues. The CD investigation demonstrated that the α-helicity of Hb experienced substantial alteration upon interaction with increasing concentrations of NGOs. The molecular docking study showed that NGOs interacted with polar residues of Hb. Cellular and molecular assays revealed that NGOs lead to ROS formation, cell cycle arrest, and apoptosis through the BAX and BCL2 pathway.Conclusion: These data reveal that NGOs can induce some protein structural changes and stimulate cytotoxicity against normal cell targets. Therefore, their applications in healthy systems should be limited. Keywords: nano graphene oxide, human hemoglobin, lymphocyte cell, fluorescence spectroscopy, circular dichroism spectroscopy, docking, cytotoxicity, ROS, cell cycle, flow cytometry

Neda Eskandari,1,* Mohammad Mahdi Nejadi Babadaei,1,* Sanaz Nikpur,2 Ghazal Ghasrahmad,2 Farnoosh Attar,3 Masoumeh Heshmati,1 Keivan Akhtari,4 Seyed Mahdi Rezayat Sorkhabadi,5 Seyyedeh Elaheh Mousavi,5 Mojtaba Falahati6 1Department of Cellular and Molecular Biology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran; 2Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, Iran; 3Department of Biology, Faculty of Food Industry & Agriculture, Standard Research Institute (SRI), Karaj, Iran; 4Department of Physics, University of Kurdistan, Sanandaj, Iran; 5Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Nanotechnology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran *These authors contributed equally to this work Introduction: The application of nanoparticles (NPs) in medicine and biology has received great interest due to their novel features. However, their adverse effects on the biological system are not well understood. Materials and methods: This study aims to evaluate the effect of cerium oxide nanoparticles (CNPs) on conformational changes of human hemoglobin (HHb) and lymphocytes by different spectroscopic (intrinsic and synchronous fluorescence spectroscopy and far and near circular dichroism [CD] spectroscopy), docking and cellular (MTT and flow cytometry) investigations.Results and discussion: Transmission electron microscopy (TEM) showed that CNP diameter is ~30 nm. The infrared spectrum demonstrated a strong band around 783 cm−1 corresponding to the CNP stretching bond. Fluorescence data revealed that the CNP is able to quench the intrinsic fluorescence of HHb through both dynamic and static quenching mechanisms. The binding constant (Kb), number of binding sites (n), and thermodynamic parameters over three different temperatures indicated that hydrophobic interactions might play a considerable role in the interaction of CNPs with HHb. Synchronous fluorescence spectroscopy indicated that microenvironmental changes around Trp and Tyr residues remain almost unchanged. CD studies displayed that the regular secondary structure of HHb had no significant changes; however, the quaternary structure of protein is subjected to marginal structural changes. Docking studies showed the larger CNP cluster is more oriented toward experimental data, compared with smaller counterparts. Cellular assays revealed that CNP, at high concentrations (>50 µg/mL), initiated an antiproliferative response through apoptosis induction on lymphocytes. Conclusion: The findings may exhibit that, although CNPs did not significantly perturb the native conformation of HHb, they can stimulate some cellular adverse effects at high concentrations that may limit the medicinal and biological application of CNPs. In other words, CNP application in biological systems should be done at low concentrations. Keywords: cerium oxide nanoparticles, human hemoglobin, fluorescence spectroscopy, thermodynamic, circular dichroism spectroscopy, docking, flow cytometry

Background and Objectives: Peganum Harmala L. (Zygophylaceae) has been used in a variety of practical applications in medical science. The aim of this study was to determine antifungal activity of seed extract of Peganum Harmala against fungal strains.Methods: In vitro antifungal activities of Alkaloid extract of Peganum Harmalawere tested against Aspergillusniger, Microsporumgypseum, Candida albicans and Saccharomyces cerevisiae. Minimal inhibitory concentration (MIC) was determined using broth microdilution method. After that, the effects of extract were compared with those of miconazole.Results: Peganum Harmala alkaloid extract had antifungal activity against all the fungi species tested with MIC values ranging from 1 to 3.2 mg/ml.Conclusion: The results indicate that alkaloid extract of P. Harmala has antifungal activity and might be promising, at least, in treatment of fungal-associated diseases from mentioned fungi.

Abstract Background and objectives: Candida albicans is a normal flora in skin and mucosa and is not pathogen in normal individuals.The main defence against yeasts ,particulary Candida, is phagocytes, but phagocytesis and opsonization are reduced in thalassemia . the aim of this study was the determination of the frequency of Candida albicans and its species in the oral cavity of patients with major thalassemia and normal individuals. Material and Methods: This descriptive –analytic study was Conducted on 52 patients with major thalassemia and 104 normal individuals in Hamadan,2009. The specimens from oral cavity of the patients and control group were taken by sterile swab and then the direct exam and culture of all specimens were done Results: The Candida species in patients with thalassemia are Candida albicans (32.7%), tropicalis (13.5%) glaberata(10.5%), guilliermondii(10.9%) and Krusei(10.9%). In normal individuals,the frequency is 17.3%for albicans, 3.8% For tropicalis ,1% for glaberata and 1%for kefyr.Fifty-nine percent of the subjects undergone splenctomy and 23% of those with heathy Spleen have Candida in their oral cavity, this differene is statistically meaningful. Conclusion:The results show that suffering from thalassemia and spleenectomy can increase the possibitity of oral infection by Candida species. Key words: Major thalassemia,Candida albicans,Oral Cavity.

Background & Objective: Candidal vulvovaginitis occurs in female genital by the over growth of candida especially candida albicans. This infection may be resistant to therapy and occasionally becomes chronic. In some patients, this form of infection is recurrent. Moreover, discovering new antifungal drugs and the use of these drugs in new methods encourage mycologists to use these techniques. Therefore, according to the above methods, this research investigated effects of several common antifungal drugs with the use of combination methods against candida species isolated from chronic candidal vulvovaginitis. Materials & Methods: This study carried out on 19 strains of candida albicans that were isolated from recurrent vulvovaginitis. The effects of clotrimazole, miconazole, fluconazole were assessed separately and in combination with amphotericin B on candida albicans using micro dilution methods. Results: The mean Minimum Inhibitory Concentration (MIC) of clotrimazole, miconazole, fluconazole, and amphotericin B were 7.05, 10.7,47, and 0.6 μgr/ml, respectively after 48 hours incubating. Then, the azole antifungal drugs were evaluated in combination with amphotericin B. The two combinations of fluconazole + amphotericin and miconazole + amphotericin with the Fungicidal Inhibitory Concentrations (FIC) of 0.6 and 1, respectively, attracted the most attentions. In addition, comparing the antifungal effects, the most effective drug was amphotericin B with the Minimum Fungicidal Concentration (MFC) of 1.18. Conclusion: In this study, amphotericin B with the least MIC had the best antifungal effect. The most and the least synergic effects of combination therapy were for fluconazole + amphotericin B and Miconazole + amphotericin B, respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence and etiological agents of dermatophytoses, and also their distribution according to age, gender, and body site among children in an area south of Tehran. A total of 382 children aged≤16 years suspected to have dermatophytic lesions were examined over a period of 3 years (1999–2001). The incidence rate of dermatophytoses was 6.6 per 100 000 person-years.Trichophyton violaceumwas the most frequent isolate (28.3%) followed byMicrosporum canis(15.1%),Epidermophyton floccosum(15.1%),T. rubrum(13.2%),T. mentagrophytes(11.3%),M. gypseum(7.5%), andT. verrucosum(5.7%). Tinea capitis (39.6%) was the most common type of infection, followed by tinea corporis (30.2%), tinea faciei (18.9%), and tinea manuum (7.5%). [ABSTRACT FROM AUTHOR]

Abstract Aims: In this study, we examined stool specimen from a 3-year-old domesticated dog, which was referred to a veterinary clinic with clinical signs such as nausea or vomiting, dysentery, cachexia and rash in Mashhad city, northeast of Iran. Patient & Methods: A 3-year-old pet dog was referred to veterinary clinic of Mashhad in February 2016 by symptoms including, nausea or vomiting, dysentery, cachexia and rash in Mashhad City, Northeast of Iran. For parasitological examination, formalin-ether concentration technique was used. Fecal smears were made from the sediment, stained with iodine and observed by light microscope. Modified Ziehl Neelsen method was used for the detection of Cryptosporidium spp. Findings: The animal was infected with 10 disease-causing parasites; Taenia spp., Fasciola spp., Dicrocoelium dendriticum, Acanthocephal spp., Trichuris vulpis, Hook worm, Giardia spp., Blastocystis spp., Eimeria spp., and Cystoisospora spp. Conclusion: Domestic and stray dog could be an important sources for distribution of zoonoses disease especially parasitic agents.