Papers by Abdollah Allahverdi
Genes
Epigenetics has long been recognized as a significant field in biology and is defined as the inve... more Epigenetics has long been recognized as a significant field in biology and is defined as the investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA methylation, play crucial roles in gene regulation. Numerous studies in humans have been carried out on single-nucleotide resolution of DNA methylation, the CpG island, new histone modifications, and genome-wide nucleosome positioning. These studies indicate that epigenetic mutations and aberrant placement of these epigenetic marks play a critical role in causing the disease. Consequently, significant development has occurred in biomedical research in identifying epigenetic mechanisms, their interactions, and changes in health and disease conditions. The purpose of this review article is to provide comprehensive information about the different types of diseases caused by alterations in epigenetic factor...
This dataset contains RNA-seq data and supplementary data relating to the journal article "E... more This dataset contains RNA-seq data and supplementary data relating to the journal article "EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms" which was published in Ocogene on 25 Jan 2018.
Cellular and Molecular Research#R##N#(Iranian Journal of Biology), Nov 18, 2020
Cells, 2022
Inadequacy of most animal models for drug efficacy assessments has led to the development of impr... more Inadequacy of most animal models for drug efficacy assessments has led to the development of improved in vitro models capable of mimicking in vivo exposure scenarios. Among others, 3D multicellular spheroid technology is considered to be one of the promising alternatives in the pharmaceutical drug discovery process. In addition to its physiological relevance, this method fulfills high-throughput and low-cost requirements for preclinical cell-based assays. Despite the increasing applications of spheroid technology in pharmaceutical screening, its application, in nanotoxicity testing is still in its infancy due to the limited penetration and uptake rates into 3D-cell assemblies. To gain a better understanding of gold nanowires (AuNWs) interactions with 3D spheroids, a comparative study of 2D monolayer cultures and 3D multicellular spheroids was conducted using two lung cancer cell lines (A549 and PC9). Cell apoptosis (live/dead assay), metabolic activity, and spheroid integrity were e...
Article Type Original Research Authors Hashemzadeh H.1 PhD, Allahverdi A.2 PhD, Ertl P.3 PhD, Nad... more Article Type Original Research Authors Hashemzadeh H.1 PhD, Allahverdi A.2 PhD, Ertl P.3 PhD, Naderi-Manesh H.*1 PhD
International Journal of Hematology, 2007
Background. We have established a new method for the transplantation of allogeneic pancreatic isl... more Background. We have established a new method for the transplantation of allogeneic pancreatic islets obtained from two different rat strains in combination with a newly developed bone marrow transplantation (BMT) method in which bone marrow cells (BMCs) are directly injected into the bone marrow cavity (intra bone marrow BMT [IBM-BMT]). Methods. Streptozotocin-induced diabetic Brown Norway (BN: RT1A n) rats were injected with fludarabine, irradiated with 5.0 Gyϫ2, and BMCs from two allogeneic rat strains, Fischer 344 (F344: RT1A 1) and PVG (PVG: RT1A c), were then directly injected into the bone marrow cavity (IBM-BMT). Simultaneously, approximately 600 pancreatic islets (PIs) from F344 and PVG rats were mixed and transplanted into the liver by way of the portal vein. Results. All the recipients thus treated showed normoglycemia 30 days after the treatment. Hematolymphoid cells were completely reconstituted with the two donor-type cells, and immunologic tolerance to F344 and PVG major histocompatibility complex (MHC) determinants were induced. Conclusions. The transplantation of PIs from two MHC-disparate donors was completely achieved in combination with IBM-BMT, resulting in the improvement of blood glucose levels and the amelioration of diabetes mellitus.
Biophysical Journal, 2009
Ultra-short laser pulses, which allow for confinement of damage to the focal volume, are used rou... more Ultra-short laser pulses, which allow for confinement of damage to the focal volume, are used routinely to ablate organelles inside living cells, yet the phys
Biophysical Journal, 2010
The physical mechanism of the folding and unfolding of chromatin is fundamentally related to tran... more The physical mechanism of the folding and unfolding of chromatin is fundamentally related to transcription but is incompletely characterized and not fully understood. We experimentally and theoretically studied chromatin compaction by investigating the salt-mediated folding of an array made of 12 positioning nucleosomes with 177 bp repeat length. Sedimentation velocity measurements were performed to monitor the folding provoked by addition of cations Na þ , K þ , Mg 2þ , Ca 2þ , spermidine 3þ , Co(NH 3) 6 3þ , and spermine 4þ. We found typical polyelectrolyte behavior, with the critical concentration of cation needed to bring about maximal folding covering a range of almost five orders of magnitude (from 2 mM for spermine 4þ to 100 mM for Na þ). A coarse-grained model of the nucleosome array based on a continuum dielectric description and including the explicit presence of mobile ions and charged flexible histone tails was used in computer simulations to investigate the cation-mediated compaction. The results of the simulations with explicit ions are in general agreement with the experimental data, whereas simple Debye-Hü ckel models are intrinsically incapable of describing chromatin array folding by multivalent cations. We conclude that the theoretical description of the salt-induced chromatin folding must incorporate explicit mobile ions that include ion correlation and ion competition effects.
Biochemical and Biophysical Research Communications, 2012
Condensation of model chromatin in the form of fully saturated 12-mer nucleosome arrays, induced ... more Condensation of model chromatin in the form of fully saturated 12-mer nucleosome arrays, induced by addition of cationic ligands (e-oligolysines with charge varied from +4 to +11), was studied in a range of KCl concentrations (10-500 mM) using light scattering and precipitation assay titrations. The dependence of EC 50 (ligand concentration at the midpoint of the array condensation) on C KCl displays two regimes, a salt-independent at low C KCl and a salt-dependent at higher salt concentrations. In the saltdependent regime EC 50 rises sharply with increase of C KCl. Increase of ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher salt. In the nucleosome array system, due to the partial neutralization of the DNA charge by histones, a lower oligocation concentration is needed to provoke condensation in the salt-independent regime compared to the related case of DNA condensation by the same cation. In the physiological range of salt concentrations (C KCl = 50-300 mM), K + ions assist array condensation by shifting EC 50 of the e-oligolysines to lower values. At higher C KCl , K + competes with the cationic ligands, which leads to increase of EC 50. Values of salt-dependent dissociation constant for the e-oligolysine-nucleosome array interaction were obtained, by fitting to a general equation developed earlier for DNA, describing the dependence of EC 50 on dissociation constant, salt and polyelectrolyte concentrations.
Angewandte Chemie International Edition, 2011
Scientific Reports
SiRNA is a new generation of drug molecules and a new approach for treating a variety of diseases... more SiRNA is a new generation of drug molecules and a new approach for treating a variety of diseases such as cancer and viral infections. SiRNA delivery to cells and translocation into cytoplasm are the main challenges in the clinical application of siRNA. Lipid carriers are one of the most successful carriers for siRNA delivery. In this study, we investigated the interaction of siRNA with a zwitterionic bilayer and how ion concentration and lipid conjugation can affect it. The divalent cation such as Mg2+ ions could promote the siRNA adsorption on the bilayer surface. The cation ions can bind to the head groups of lipids and the grooves of siRNA molecules and form bridges between the siRNA and bilayer surface. Our findings demonstrated the bridges formed by divalent ions could facilitate the attachment of siRNA to the membrane surface. We showed that the divalent cations can regulate the bridging-driven membrane attachment and it seems the result of this modulation can be used for des...
Scientific Reports
The simulated liposome models provide events in molecular biological science and cellular biology... more The simulated liposome models provide events in molecular biological science and cellular biology. These models may help to understand the cell membrane mechanisms, biological cell interactions, and drug delivery systems. In addition, the liposomes model may resolve specific issues such as membrane transports, ion channels, drug penetration in the membrane, vesicle formation, membrane fusion, and membrane protein function mechanism. One of the approaches to investigate the lipid membranes and the mechanism of their formation is by molecular dynamics (MD) simulations. In this study, we used the coarse-grained MD simulation approach and designed a liposome model system. To simulate the liposome model, we used phospholipids that are present in the structure of natural cell membranes (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)). Simulation conditions such as temperature, ions, water, lipid concentration were performed based o...
The β<sub>42</sub> amyloid peptides (Aβ) are identified as a candidate target for Alz... more The β<sub>42</sub> amyloid peptides (Aβ) are identified as a candidate target for Alzheimer's drugs. Phenolic compounds can bind to the Aβ and inhibit amyloid formation. However, the inhibitory mechanism of phenolic compounds remains unclear. In this study, the molecular dynamic simulation and docking program were used to characterize the molecular details of inhibitory mechanism of the phenolic compounds. Our Results show that the phenolic compounds can bind to hydrophobic region in Aβ<sub>42</sub> monomer and alter hydrophobic interactions network at Aβ<sub>42</sub> which play a key role in β-sheet formation. The cluster analysis and interactions network analysis were used to probe conformational changes in Aβ<sub>42</sub>. In most populated clusters of Aβ<sub>42</sub>-phenolic compounds complexes, the sheet structures were not observed or reduced. It seems that the binding of phenolic compounds can induce larger conf...
The eukaryotic genome is highly compacted into a protein-DNA complex called chromatin. The cell c... more The eukaryotic genome is highly compacted into a protein-DNA complex called chromatin. The cell controls access of transcriptional regulators to chromosomal DNA via several mechanisms that act on chromatin-associated proteins and provide a rich spectrum of epigenetic regulation. Elucidating the mechanisms that fold chromatin fibers into higher-order structures is therefore key to understanding the epigenetic regulation of DNA accessibility. Here, using histone H4-V21C and histone H2A-E64C mutations, we employed single-molecule force spectroscopy to measure the unfolding of individual chromatin fibers that are reversibly cross-linked through the histone H4 tail. Fibers with covalently linked nucleosomes featured the same folding characteristics as fibers containing wild-type histones but exhibited increased stability against stretching forces. By stabilizing the secondary structure of chromatin, we confirmed a nucleosome repeat length (NRL)-dependent folding. Consistent with previous crystallographic and cryo-EM studies, the obtained force-extension curves on arrays with 167-bp NRLs best supported an underlying structure consisting of zig-zag, two-start fibers. For arrays with 197-bp NRLs, we previously inferred solenoidal folding, which was further corroborated by force-extension curves of the cross-linked fibers. The different unfolding pathways exhibited by these two types of arrays and reported here extend our understanding of chromatin structure and its potential roles in gene regulation. Importantly, these findings imply that chromatin compaction by nucleosome stacking protects nucleosomal DNA from external forces up to 4 piconewtons.
Objective: The receptor-binding domain (RBD) of the S1 domain of the SARS-CoV- 2 Spike protein pe... more Objective: The receptor-binding domain (RBD) of the S1 domain of the SARS-CoV- 2 Spike protein performs a key role in the interaction with Angiotensin-converting enzyme 2 (ACE2), leading to both subsequent S2 domain-mediated membrane fusion and incorporation of viral RNA in host cells. Methods: In this study, we investigated the inhibitor’s targeted compounds through existing human ACE2 drugs to use as a future viral invasion. 54 FDA approved drugs were selected to assess their binding affinity to the ACE2 receptor. The structurebased methods via computational ones have been used for virtual screening of the best drugs from the drug database. Key Findings: The ligands “Cinacalcet” and “Levomefolic acid” highaffinity scores can be a potential drug preventing Spike protein of SARS-CoV-2 and human ACE2 interaction. Levomefolic acid from vitamin B family was proved to be a potential drug as a spike protein inhibitor in previous clinical and computational studies. Besides that, in this s...
Biomechanical and morphological analysis of the cells is a novel approach for monitoring the envi... more Biomechanical and morphological analysis of the cells is a novel approach for monitoring the environmental features, drugs, and toxic compounds’ effects on cells. Graphene oxide (GO) has a broad range of medical applications such as tissue engineering and drug delivery. However, the effects of GO nanosheets on biological systems have not been completely understood. In this study, we focused on the biophysical characteristics of cells and their changes resulting from the effect of GO nanosheets. The biophysical properties of the cell population were characterized as follows: cell stiffness was calculated by atomic force microscopy, cell motility and invasive properties were characterized in the microfluidic chip in which the cells are able to visualize cell migration at a single-cell level. Intracellular actin was stained to establish a quantitative picture of the intracellular cytoskeleton. In addition, to understand the molecular interaction of GO nanosheets and actin filaments, co...
Microfluidics and Nanofluidics
Abstract The low membrane permeability of lipophilic drugs was resolved using liposomes as a solu... more Abstract The low membrane permeability of lipophilic drugs was resolved using liposomes as a solubilizing agent and the precise size control of them is a significant parameter in drug carrier technology. Here, we have established a microfluidic octanol-assisted liposome assembly method to produce a surfactant-assisted liposome which has merged by the cytoskeleton drug (Taxotere) encapsulation in a single process step, then a complete microfluidic cellular analysis was performed in trapping cell device with an optofluidic assay for quantifying drug permeability. The optimization of process variables resulted in the formation of liposomes with particle size 6.75 ± 0.5 µm and monodispersity 6.2%, representing encapsulation efficiency and loading capacity of 65.49 ± 3.08% and 10.16 ± 0.32%, respectively. Qualitative and quantitative studies of cellular uptake in MCF-7 cell line that was cultured in the cell trapping chip indicated a significant increase in cellular uptake of carboxyfluorescein-loaded liposomes, suggesting endocytic mechanisms. The drug-loaded liposomes with an IC 50 value of 0.55 ± 0.04 μg mL −1 have shown a higher level of cellular inhibition and apoptosis in cells than free Taxotere (2.48 ± 0.01). Furthermore, real-time analysis of the dynamic labeling assay for live/dead cells was investigated. Our data revealed that lab-on-a-chip platforms for the time-lapse fluorescence imaging were applied for drug screening routines. Graphic abstract Cytoskeleton drugs encapsulated in liposome using microfluidic approaches and investigation of programmed cell death assay.
Scientific Reports
Lung cancer is a leading cause of cancer death in both men and women worldwide. The high mortalit... more Lung cancer is a leading cause of cancer death in both men and women worldwide. The high mortality rate in lung cancer is in part due to late-stage diagnostics as well as spread of cancer-cells to organs and tissues by metastasis. Automated lung cancer detection and its sub-types classification from cell’s images play a crucial role toward an early-stage cancer prognosis and more individualized therapy. The rapid development of machine learning techniques, especially deep learning algorithms, has attracted much interest in its application to medical image problems. In this study, to develop a reliable Computer-Aided Diagnosis (CAD) system for accurately distinguishing between cancer and healthy cells, we grew popular Non-Small Lung Cancer lines in a microfluidic chip followed by staining with Phalloidin and images were obtained by using an IX-81 inverted Olympus fluorescence microscope. We designed and tested a deep learning image analysis workflow for classification of lung cancer ...
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Papers by Abdollah Allahverdi