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  • Öğe
    Fluorescence anisotropy cytosensing of folate receptor positive tumor cells using 3D polyurethane-GO-foams modified with folic acid: molecular dynamics and in vitro studies
    (NLM (Medline), 2023) Esmaeili, Yasaman; Mohammadi, Zahra; Khavani, Mohammad; Sanati, Alireza; Shariati, Laleh; Seyedhosseini Ghaheh, Hooria; Bidram, Elham; Zarrabi, Ali
    Integrated polyurethane (PU)-based foams modified with PEGylated graphene oxide and folic acid (PU@GO-PEG-FA) were developed with the goal of capturing and detecting tumor cells with precision. The detection of the modified PU@GO-PEG surface through FA against folate receptor-overexpressed tumor cells is the basis for tumor cell capture. Molecular dynamics (MD) simulations were applied to study the strength of FA interactions with the folate receptor. Based on the obtained results, the folate receptor has intense interactions with FA, which leads to the reduction in the FA interactions with PEG, and so decreases the fluorescence intensity of the biosensor. The synergistic interactions offer the FA-modified foams a high efficiency for capturing the tumor cell. Using a turn-off fluorescence technique based on the complicated interaction of FA-folate receptor generated by target recognition, the enhanced capture tumor cells could be directly read out at excitation-emission wavelengths of 380-450 nm. The working range is between 1×10 2 to 2×10 4 cells mL -1 with a detection limit of 25 cells mL -1 and good reproducibility with relative standard deviation of 2.35%. Overall, findings demonstrate that the fluorescence-based biosensor has a significant advantage for early tumor cell diagnosis. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
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    Superparamagnetic iron oxide nanoparticles and curcumin equally promote neuronal branching morphogenesis in the absence of nerve growth factor in PC12 cells
    (MDPI, 2022) Zarei, Mahshid; Esmaeili, Abolghasem; Zarrabi, Ali; Zarepour, Atefeh
    Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize the combination of curcumin, as a neurogenesis agent, with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate their effects on PC12 cells? neuronal branching morphogenesis in the absence of nerve growth factor. Therefore, the effects of each component alone and in combination form on the cytotoxicity, neurogenesis, and neural branching morphogenesis were evaluated using MTT assay, immunofluorescence staining, and inverted microscopy, respectively. Results confirmed the effectiveness of the biocompatible iron oxide nanoparticles (with a size of about 100 nm) in improving the percentage of neural branching (p < 0.01) in PC12 cells. In addition, the combination use of these nanoparticles with curcumin could enhance the effect of curcumin on neurogenesis (p < 0.01). These results suggest that SPIONs in combination with curcumin could act as an inducing factor on PC12 neurogenesis in the absence of nerve growth factor and could offer a novel therapeutic approach to the treatment of neurodegenerative diseases. © 2022 by the authors.
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    N-doped carbon nanospheres as selective fluorescent probes for mercury detection in contaminated aqueous media: chemistry, fluorescence probing, cell line patterning, and liver tissue interaction
    (Springer Science and Business Media Deutschland GmbH, 2023) Sojdeh, Soheil; Banitalebi Dehkordi, Ali; Zarrabi, Ali; Badiei, Alireza; Makvandi, Pooyan
    A precise nano-scale biosensor was developed here to detect Hg2+ in aqueous media. Nitrogen-doped carbon nanospheres (NCS) created from the pyrolysis of melamine–formaldehyde resin were characterized by FESEM, XRD, Raman spectra, EDS, PL, UV–vis spectra, and N2 adsorption–desorption, and were used as a highly selective and sensitive probe for detecting Hg2+ in aqueous media. The sensitivity of NCS to Hg2+ was evaluated by photoluminescence intensity fluctuations under fluorescence emission in the vicinity of 390 nm with a ?exc of 350 nm. The fluorescence intensity of the NCS probe weakened in the presence of Hg2+ owing to the effective fluorescence quenching by that, which is not corresponding to the special covalent liking between the ligand and the metal. The effects of the fluorescence nanoprobe concentration, pH, and sensing time were monitored to acquire the best conditions for determining Hg2+. Surprisingly, NCS revealed excellent selectivity and sensitivity towards Hg2+ in the samples containing Co2+, Na+, K+, Fe2+, Mn2+, Al3+, Pb2+, Ni2+, Ca2+, Cu2+, Mg2+, Cd2+, Cr3+, Li+, Cs+, and Ba2+. The fluorescence response was linearly proportional to Hg2+ concentration in 0.013–0.046 µM with a limit of detection of 9.58 nM. The in vitro and in vivo toxicological analyses confirmed the completely safe and biocompatible features of NCS, which provides promise for use for water, fruit, vegetable, and/or other forms of natural-connected materials exposed to Hg2+, with no significant toxicity noticed toward different cells/organs/tissues. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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    Immunotherapeutic approaches in hepatocellular carcinoma: building blocks of hope in near future
    (Elsevier, 2023) Minaei, Neda; Ramezankhani, Roya; Tamimi, Atena; Piryaei, Abbas; Zarrabi, Ali; Aref, Amir Reza; Mostafavi, Ebrahim; Vosough, Massoud
    Hepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications. © 2022 The Authors
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    Hyperthermia of magnetically soft-soft core-shell ferrite nanoparticles
    (MDPI, 2022) Narayanaswamy, Venkatesha; Jagal, Jayalakshmi; Khurshid, Hafsa; Al-Omari, Imaddin A. A.; Haider, Mohamed; Kamzin, Alexander S. S.; Obaidat, Ihab M. M.; Issa, Bashar
    Magnetically soft-soft MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized through a seed-mediated method using the organometallic decomposition of metal acetyl acetonates. Two sets of core-shell nanoparticles (S1 and S2) of similar core sizes of 5.0 nm and different shell thicknesses (4.1 nm for S1 and 5.7 nm for S2) were obtained by changing the number of nucleating sites. Magnetic measurements were conducted on the nanoparticles at low and room temperatures to study the shell thickness and temperature dependence of the magnetic properties. Interestingly, both core-shell nanoparticles showed similar saturation magnetization, revealing the ineffective role of the shell thickness. In addition, the coercivity in both samples displayed similar temperature dependencies and magnitudes. Signatures of spin glass (SG) like behavior were observed from the field-cooled temperature-dependent magnetization measurements. It was suggested to be due to interface spin freezing. We observed a slight and non-monotonic temperature-dependent exchange bias in both samples with slightly higher values for S2. The effective magnetic anisotropy constant was calculated to be slightly larger in S2 than that in S1. The magnetothermal efficiency of the chitosan-coated nanoparticles was determined by measuring the specific absorption rate (SAR) under an alternating magnetic field (AMF) at 200-350 G field strengths and frequencies (495.25-167.30 kHz). The S2 nanoparticles displayed larger SAR values than the S1 nanoparticles at all field parameters. A maximum SAR value of 356.5 W/g was obtained for S2 at 495.25 kHz and 350 G for the 1 mg/mL nanoparticle concentration of ferrogel. We attributed this behavior to the larger interface SG regions in S2, which mediated the interaction between the core and shell and thus provided indirect exchange coupling between the core and shell phases. The SAR values of the core-shell nanoparticles roughly agreed with the predictions of the linear response theory. The concentration of the nanoparticles was found to affect heat conversion to a great extent. The in vitro treatment of the MDA-MB-231 human breast cancer cell line and HT-29 human colorectal cancer cell was conducted at selected frequencies and field strengths to evaluate the efficiency of the nanoparticles in killing cancer cells. The cellular cytotoxicity was estimated using flow cytometry and an MTT assay at 0 and 24 h after treatment with the AMF. The cells subjected to a 45 min treatment of the AMF (384.50 kHz and 350 G) showed a remarkable decrease in cell viability. The enhanced SAR values of the core-shell nanoparticles compared to the seeds with the most enhancement in S2 is an indication of the potential for tailoring nanoparticle structures and hence their magnetic properties for effective heat generation.
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    Development of lateral flow assays for rapid detection of troponin ı: a review
    (TAYLOR & FRANCIS INC, 2022) Mohammadinejad, Arash; Nooranian, Samin; Oskuee, Reza Kazemi; Mirzaei, Sepideh; Aleyaghoob, Ghazaleh; Zarrabi, Ali
    Troponin I as a particular and major biomarker of cardiac failure is released to blood demonstrating hurt of myocardial cells. Unfortunately, troponin I detection in the first hours of acute myocardial infarction usually faces with most negligence. Therefore, developments of point of care devices such as lateral flow strips are highly required for timely diagnosis and prognosis. Lateral flow assays are low-cost paper-based detection platforms relying on specific diagnostic agents such as aptamers and antibodies for a rapid, selective, quantitative and semi-quantitative detection of the analyte in a complex mixture. Moreover, lateral flow assay devices are portable, and their simplicity of use eliminates the need for experts or any complicated equipment to operate and interpret the test results. Additionally, by coupling the lateral flow assay technology with nanotechnology, for labeling and signal amplification, many breakthroughs in the field of diagnostics have been achieved. The present study reviews the use of lateral flow assays in early stage, quantitative, and sensitive detection of cardiac troponin I and mainly focuses on the structure of each type of developed lateral flow assays. Finally, this review summarized the improvements, detection time, and limit of detection of each study as well as the advantages and disadvantages.
  • Öğe
    Association of clinical features with spike glycoprotein mutations in Iranian COVID-19 patients
    (MDPI, 2022) Ahangarzadeh, Shahrzad; Yousefi, Alireza; Ranjbar, Mohammad Mehdi; Dabiri, Arezou; Zarepour, Atefeh; Sadeghi, Mahmoud; Heidari, Elham; Mazrui, Fariba; Hosseinzadeh, Majid; Ataei, Behrooz; Zarrabi, Ali; Shariati, Laleh; Javanmard, Shaghayegh Haghjooy
    Background: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. Methods: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient's reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. Results: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. Conclusions: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease.
  • Öğe
    Antimicrobial activity of blow spun PLA/gelatin nanofibers containing green synthesized silver nanoparticles against wound ınfection-causing bacteria
    (MDPI, 2022) Sardareh, Elham Alinezhad; Shahzeidi, Moloud; Ardestani, Mohammad Taha Salmanifard; Mousavi-Khattat, Mohammad; Zarepour, Atefeh; Zarrabi, Ali
    One of the main challenges in wound healing is the wound infection due to various causes, of which moisture is the most important reason. Owing to this fact, wound dressings that can collect wound moisture in addition to showing antibacterial properties have provided an important basis for wound healing research. In this study, gelatin and poly lactic acid (PLA) polymers were used in a wound dressing textile to provide gelation and structure strength properties, respectively. Meanwhile, silver nanoparticles (SNPs) synthesized through the green method were integrated into these fibers to provide the formed textile with antibacterial properties. Nanoparticles were made using donkey dung extract, and nanofibers were produced by the solution blow spinning method which has high production efficiency and low energy consumption among spinning methods. The produced nanoparticles were characterized and evaluated by UV-Vis, DLS, XRD, and FTIR methods, and the production of silver nanoparticles that were coated with metabolites in the extract was proven. In addition, the morphology and diameter of the resulted fibers and presence of nanoparticles were confirmed by the SEM method. The size and size distribution of the synthesized fibers were determined through analyzing SEM results. Gelatin nanofibers demonstrated a mean size of 743 nm before and 773 nm after nanoparticle coating. PLA nanofibers demonstrated a mean size of 57 nm before and 182 nm after nanoparticle coating. Finally, 335 nm was the mean diameter size of gelatin/PLA/SNPs nanofibers. Also, the textiles synthesized by PLA and gelatin which contained silver nanoparticles showed higher antibacterial activity against both gram-positive and gram-negative species compared to PLA and gelatin tissues without nanoparticles. Cytotoxicity test on L929 cells showed that silver nanoparticles incorporated textiles of PLA and gelatin show a very low level and non-significant toxicity compared to the free particles.
  • Öğe
    Penicillin and oxacillin loaded on pegylated-graphene oxide to enhance the activity of the antibiotics against methicillin-resistant staphylococcus aureus
    (MDPI, 2022) Zarepour, Atefeh; Zarrabi, Ali; Tabar, Mohadeseh Mohammadi; Khaleghi, Moj; Bidram, Elham
    Infectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol (GO-PEG) nano-platform was synthesized and penicillin and oxacillin, two antibiotics that are ineffective against Methicillin-resistant S. aureus (MRSA), were loaded on it to improve their effectiveness. The nanocomposites were characterized using FTIR, XRD, UV-Vis, FE-SEM/EDX, and Zeta potential analyses, followed by an evaluation of their antibacterial activity toward MRSA. Based on the results, drug loaded GO-PEG nanocomposites with loading efficiencies of 81% and 92% for penicillin and oxacillin, respectively, were successfully synthesized. They showed a controlled release within six days. The zeta potential of GO-PEG-oxacillin and penicillin was -13 mV and -11 mV, respectively. The composites showed much more activity against MRSA (80-85% inhibition) in comparison to GO-PEG (almost 0% inhibition) and pure antibiotics (40-45% inhibition). SEM images of MRSA treated with GO-PEG-antibiotics showed a deformation in the structure of bacterial cells, which led to the collapse of their intracellular components. These results demonstrate the effectiveness of utilizing the GO-based nanoplatforms in enhancing the antibacterial activity of the antibiotics.
  • Öğe
    Synthesis and evaluation of novel xanthene-based thiazoles as potential antidiabetic agents
    (WILEY-V C H VERLAG GMBH, 2022) Naseem, Saira; Shafiq, Zahid; Taslimi, Parham; Hussain, Saghir; Taşkın Tok, Tuğba; Kısa, Dursun; Saeed, Aamer; Temirak, Ahmed; Tahir, Muhammad N.; Rauf, Khawar; El-Gokha, Ahmed
    A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance (H-1 NMR), carbon nuclear magnetic resonance (C-13 NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-amylase (alpha-Amy), and alpha-glycosidase (alpha-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC50: 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for alpha-Gly, and 152.48 and 124.84 nM for alpha-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, alpha-Amy, and alpha-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme.
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    Soybean oil based allyl acrylates and methacrylates: synthesis, characterization, and polymerization
    (WILEY-V C H VERLAG GMBH, 2022) Çaylı, Gökhan; Hatır, Pınar Çakır
    In this study, a simple synthesis method for the allylic acrylates and methacrylates of soybean oil is evaluated. As a model compound, allylic acrylation and methacrylation of methyl oleate is also studied. IR and H-1 NMR techniques are used in order to characterize all the allylic esters. Although homopolymerization of allylic esters is unsuccessful, copolymers of the allylic esters with acrylic acid, methacrylic acid, n butyl acrylate, and styrene are obtained as low load bearing solids. Copolymerization products of acrylated soybean oil (ACSO) and methacrylted soybean oil (METACSO with styrene show rubbery properties. METACSO-Styrene and ACSO-styrene copolymers exhibit 35.3 and 24.9 kPa tensile strengths with more than 200% of elongation. Thermal stabilities of the synthesized polymers are measured by TGA technique. The copolymers of methyl oleate-based allyl acrylates and methacrylates exhibit higher 5% weight loss temperature than the copolymers of allylic acrylate and methacrylate of soybean oil.
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    Non-coding RNAs targeting notch signaling pathway in cancer : from proliferation to cancer therapy resistance
    (Elsevier B.V., 2022) Hashemi, Mehrdad; Hasani, Sahar; Hajimazdarany, Shima; Mirmazloomi, Seyed Reza; Makvandy, Sara; Zabihi, Abbas; Goldoost, Yeganeh; Gholinia, Nazanin; Kakavand, Amirabbas; Tavakolpournegari, Alireza; Salimimoghadam, Shokooh; Nabavi, Noushin; Zarrabi, Ali; Taheriazam, Afshin; Entezari, Maliheh; Hushmandi, Kiavash
    Cancer is a challenging to treat disease with a high mortality rate worldwide, nevertheless advances in science has led to a decrease in the number of death cases caused by cancer. Aberrant expression of genes occurs during tumorigenesis therefore targeting the signaling pathways that regulate these genes' expression is of importance in cancer therapy. Notch is one of the signaling pathways having interactions with other vital cell signaling molecules responsible for cellular functions such as proliferation, apoptosis, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune evasion. Furthermore, the Notch pathway is involved in response to chemo- and radiotherapy. Thus, targeting the Notch signaling pathway in cancer therapy can be beneficial for overcoming the therapeutic gaps. Non-coding RNAs (ncRNAs) are a class of RNAs that include short ncRNAs (such as micro RNAs) and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are ~22 nucleotides in length while lncRNAs have more than 200 nucleotides. Both miRNAs and lncRNAs control vital cellular mechanisms in cells and affect various signaling pathways and Notch is among them. The current review aims to discuss the critical role of ncRNAs in the regulation of the Notch signaling pathway by focusing on different cancer hallmarks including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.
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    Optimization of curcumin loaded niosomes for drug delivery applications
    (Elsevier B.V., 2022) Esmaeili Rad, Monireh; Egil, Abdurrahim Can; Ozaydin Ince, Gozde; Yuce, Meral; Zarrabi, Ali
    Controlled drug delivery is an important and challenging issue in pharmacology. The aim is to improve efficacy and reduce the side effects of drugs. Nanotechnology suggests applying various nanoparticles as carriers to overcome drug delivery limitations. The current study introduces an optimum formulation of niosomes to carry and deliver curcumin (CUR) as a hydrophobic drug to cancerous cells. In spite of numerous pharmacological properties of this natural polyphenolic compound, including anti-microbial, antioxidant, and anti-inflammatory effects, it suffers from poor stability and solubility. This work studies the optimum formulation for CUR-loaded niosome and investigates its stability based on hydrodynamic size and zeta-potential measurements. The optimum blank noisome, formulated according to a three-level Box–Behnken design, was used to load CUR as an anticancer drug. The fabricated niosomes (blank/loaded) were characterized by dynamic light scattering, Fourier transforms infrared spectroscopy and scanning electron microscopy. Prepared particles showed stability at 4 °C for up to two months. In addition, particles were durable against temperature changes from 5° to 40°C. Drug-loaded niosomes reached 99.8% drug entrapment efficiency and up to 68.33% loading capacity. Sustained-release behaviour was observed in CUR-loaded niosomes up to 25.49 ± 0.70% of CUR during 336 h. Based on cytotoxicity studies, blank niosome showed no significant toxicity effect on cells at high concentrations and after 72 h, confirming cytocompatibility of the particles. CUR-loaded niosomes had dose-dependent toxicity against cancerous cells. The concentration of 200 µg/ml of the drug-loaded carrier, containing 66.75 µg CUR, showed an IC50 effect after 48 h of exposure to cells
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    Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA
    (IOP Publishing, 2022) Elkhoury, Kamil; Chen, Mo; Koçak, Polen; Enciso-Martínez, Eduardo; Bassous, Nicole Joy; Chul Lee, Myung; Byambaa, Batzaya; Rezaei, Zahra; Li, Yang; Ubina López , María Elizabeth; Gurian, Melvin; Sobahi, Nebras; Asif Hussain, Mohammad; Sanchez-Gonzalez, Laura; Leijten, Jeroen; Hassan, Shabir; Arab-Tehrany, Elmira; Ellis Ward, Jennifer; Shin, Su Ryon
    In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells' gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field.
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    Advances in aptamer-based drug delivery vehicles for cancer therapy
    (Elsevier, 2022) Ghasemi, Kousar; Darroudi, Mahdieh; Rahimmanesh, Ilnaz; Ghomi, Matineh; Hassanpour, Mahnaz; Sharifi, Esmaeel; Yousefiasl, Satar; Ahmadi, Sepideh; Zarrabi, Ali; Borzacchiello, Assunta; Rabiee, Mohammad; Paiva-Santos, Ana Cláudia; Rabiee, Navid
    Overall, aptamers are special classes of nucleic acid-based macromolecules that are beginning to investigate because of their capability of avidity binding to a specific target for clinical use. Taking advantage of target-specific medicine led to more effective therapeutic and limitation of side effects of drugs. Herein, we discuss several aptamers and their binding capability and capacity for selecting tumor biomarkers and usage of them as targeting ligands for the functionalization of nanomaterials. We review recent applications based on aptamers and several nanoparticles to rise efficacy and develop carrier systems such as graphene oxide, folic acid, gold, mesopores silica, and various polymers and copolymer, polyethylene glycol, cyclodextrin, chitosan. The nanocarriers have been characterized by particle size, zeta potential, aptamer conjugation, and drug encapsulation efficiency. Hydrodynamic diameter and Zeta potential can used in order to monitor aptamers' crosslinking, in-vitro drug release, intracellular delivery of nanocarriers, and cellular cytotoxicity assay. Also, they are studied for cellular uptake and internalization to types of cancer cell lines such as colorectal, breast, prostate, leukemia and etc. The results are investigated in in-vivo cytotoxicity assay and cell viability assay. Targeted cancer therapy seems a good and promising strategy to overcome the systemic toxicity of chemotherapy.
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    Stimuli-responsive liposomal nanoformulations in cancer therapy: Pre-clinical & clinical approaches
    (Elsevier, 2022) Ashrafizadeh, Milad; Delfi, Masoud; Zarrabi, Ali; Sharifi, Esmaeel; Rabiee, Navid; Paiva-Santos, Ana Cláudia; Kumar, Alan Prem; Hushmandi, Kiavash; Nazarzadeh Zare, Ehsan; Makvandi, Pooyan
    The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.
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    Customizing nano-chitosan for sustainable drug delivery
    (PMC, 2022) Mostafa Saeedi 1, Omid Vahidi 1, Mohammadreza Moghbeli 1, Sepideh Ahmadi 2, Mohsen Asadnia 3, Omid Akhavan 4, Farzad Seidi 5, Mohammad Rabiee 6, Mohammad Reza Saeb 7, Thomas J Webster 8, Rajender S Varma 9, Esmaeel Sharifi 10, Ali Zarrabi 11, Navid Rabiee 12 Affiliations collapse; Saeedi, Mostafa; Vahidi, Omid; Moghbeli, Mohammadreza; Ahmadi, Sepideh; Asadnia, Mohsen; Akhavan, Omid; Seidi, Farzad; Rabiee, Mohammad; Saeb, Mohammad Reza; Webster, Thomas J.; Zarrabi, Ali; Rabiee, Navid; Varma, Rajender S.; Sharifi, Esmaeel
    Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, the various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article
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    Combination therapy using nanomaterials and stem cells to treat spinal cord injuries
    (Elsevier Science, 2022) Zarepour, Arezou; Bal Öztürk, Ayça; Koyuncu Irmak, Duygu; Yaşayan, Gökçen; Gökmen, Aylin; Karaöz, Erdal; Zarepour, Atefeh; Zarrabi, Ali; Mostafavi, Ebrahim
    As a part of the central nervous system, the spinal cord (SC) provides most of the communications between the brain and other parts of the body. Any damage to SC interrupts this communication, leading to serious problems, which may remain for the rest of their life. Due to its significant impact on patients’ quality of life and its exorbitant medical costs, SC injury (SCI) is known as one of the most challengeable diseases in the world. Thus, it is critical to introduce highly translatable therapeutic platforms for SCI treatment. So far, different strategies have been introduced, among which utilizing various types of stem cells is one of the most interesting ones. The capability of stem cells to differentiate into several types of cell lines makes them promising candidates for the regeneration of injured tissues. One of the other interesting and novel strategies for SCI treatment is the appli- cation of nanomaterials, which could appear as a carrier for therapeutic agents or as a platform for culturing the cells. Combining these two approaches, stem cells and nanomaterials, could provide promising therapeutic strategies for SCI management. Accordingly, in this review we have summarized some of the recent advance- ments in which the applications of different types of stem cells and nanomaterials, alone and in combination forms, were evaluated for SCI treatment.
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    Molecular landscape of LncRNAs in prostate cancer: A focus on pathways and therapeutic targets for intervention
    (PMC, 2022) Mirzaei, Sepideh; Abad Paskeh, Mahshid Deldar; Okina, Elena; Gholami, Mohammad Hossein; Hushmandi, Kiavash; Hashemi, Mehrdad; Kalu , Azuma; Zarrabi, Ali; Nabav, Noushin; Rabiee, Navid; Sharifi, Esmaeel; Karimi-Maleh, Hassan; Ashrafizadeh, Milad; Kumar, Alan Prem; Wang, Yuzhuo
    Background: One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterog? enous and progressive natures. Genetic and epigenetic changes play signifcant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation. Aim of review: The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined. Key scientifc concepts of review: The aberrant expression of lncRNAs in prostate cancer has been well-docu? mented and progression rate of tumor cells are regulated via afecting STAT3, NF-?B, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker
  • Öğe
    The apoptotic effect of ozone therapy on mitochondria of highly metastatic breast cancer cell line MDA-MB-231 using in vitro approaches
    (KeAi, 2022) Inac, Elif; Unsal, Naz; Yilmaz, Hazal; Erkisi, Selena; Yildirim, Merve; Tanriver, Yildiray; Koçak, Polen
    Ozone (O3) gas is the triatomic state of oxygen and it is used as a disinfection agent due to its strong oxidizing effect, since its discovery in the mid-nineteenth century. Ozone therapy is also an alternative therapeutic approach for some diseases like circulatory disorders, AIDS, asthma, cardiovascular diseases, and certain types of cancer by increasing the oxygen levels in the blood by external addition of ozone to the body. In this study, the therapeutic potential of ozone therapy was examined by inhibiting the growth of breast cancer cells in a dose-dependent procedure. Ozone concentrations varying from 5 to 20 ?g/ml were applied to the MDA-MB-231, human breast adenocarcinoma and HUVEC, human umbilical vein endothelium, cell lines, and MDA cells demonstrated an increased rate of death while its migration potential decreases. RT-PCR analysis showed mRNA expression levels of pro-apoptotic genes demonstrated higher folds in MDA cells after 10 ?g/ml treatment. In the same context, Annexin V/PI and cell cycle analysis also concluded that ozone therapy causes apoptotic cell death on breast tumor cells. The use of ozone therapy for cancer treatment requires further and extensive research. However, this research has shown that ozone therapy is a promising source for cancer treatment in a way by inhibiting the proliferation of breast tumor cells