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Proper solubilization after precipitation and keeping the purified proteins in solution during the whole separation process are very critical to achieve accurate and high resolution patterns in two-dimensional gel electrophoresis (2-DE). Chaotropes and detergents are embedded in the sample and rehydration buffers in order to prevent hydrophobic interactions between the hydrophobic protein domains and avoid loss of proteins due to aggregation and precipitation. Unfortunately, detergents used for IEF must bear no net electrical charge and only week nonionic and zwitterionic detergents may be used in this process. Because of the low solubility of proteins at or very close to their isoelectric point, it seems that choice of chaotropes and detergents can dramatically affect on2D separations, especially in the case of very hydrophobic proteomes. Considering the physico-chemical heterogeneity of tear film protein content, it is deemed that solubilization can play an important role in 2D tear proteome analysis. So herein, we investigated the effect of some various detergents and chaotropes on the solubility of tear proteome during the sample preparation and IEF process. The results illustrated a very poor performance of non-ionic detergents (Triton­X-100 and Tween­80). Zwitterionic detergents (CHAPS and SB­3-10) had a better solubilization power and provided more reliable 2D maps. Last of all a great improvement in spot number and 2D resolution is achieved using a combination of urea/Thiourea in rehydration buffer and application of SDS in the sample buffer with a modified protocol, which ensures complete removal of anionic detergent during the first step of IEF and its replacement with the zwitterionic CHAPS.  

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The increasing rate of depositing new protein sequences and structures to biological databases such as Protein Data Bank (PDB) indicates the importance of structural comparison to explore the evolutionary relationship among different protein families, prediction of function in annotated proteins and classification of protein structure and folds. Due to the high computational cost, protein multiple structural alignment programs in comparison with the conventional multiple sequence alignment programs are slower and represent approximate answers. Therefore, designing new algorithms is an open problem. In this paper, a novel algorithm named PSNetAl for multiple structural alignments of proteins based on graph matching is introduced. PSNetAl inputs are protein structural files in PDB format. Undirected, distance-based graphs are constructed from pdb input files and multiple alignments of graphs are performed by a progressive algorithm. The largest common subgraph as the output of multiple alignment includes the common nodes among all networks. If there is any structural or evolutionary similarity among networks, it will be expected after multiple alignments structural motifs to be present in the largest common subgraph. To evaluate the functionality of PSNetAl, a dataset containing 76 protein families with 50-90% sequence identity and at least 3 members were extracted from HOMSTRAD database. The obtained results show in 67 out of 76 families more than 90% of structural motifs are observed in the largest common subgraph of the multiple alignment.

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Diatoms biosilica shell, frustule, is substitute biostructures to mesoporous silica particles, which possesses their wide surfaces, nano-diameter porosity, mechanical strength, and thermal stability, optical capabilities, and the ability to bind to biomolecules can be used in biosensing applications. In this study, diatom species called Chaetoceros muelleri, was used for the fabrication of the Fe₂O₃-Au-Biosilica magnetic package. After micro-algae cultivation, the synthesis of gold nanoparticles (AuNPs) on silica walls was carried out using the bio-synthesis method, which evaluations have demonstrated the continuous formation of spherical AuNPs on the walls and its surfaces. After this step, the magnetic iron oxide nanoparticles were attached to the silica surface of the diatom, this, in turn, leads to system guiding using a magnetic field. Surface modification of diatoms magnetic complex, by using the APTES, allowed the attachment of fluorescence Rhodamine and the Herceptin antibody (Trastuzumab) to the structure. As well as the attachment of the fabricated system to target cells (SKBR3) was confirmed by fluorescence microscopic analysis. The results of this study indicate the ability and specificity of the diatom silicone shell as a "multipurpose" package for diagnostic and therapeutic activities.

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Total-Internal-Reflection Fluorescence Microscopy (TIRFM) is a useful tool to visualize and record the phenomena that happens below 100 nm thickness of the sample surface. This unique property of TIRFM help to perform a "qualitative" study of cytoskeleton near the cell-substrate contact. Here,   distribution of actin filaments at cell-substrate interface was imaged by a TIRFM set up. Then, staining the actins cytoskeleton of the human melanoma cell and implementing the prism-based total-internal-reflection fluorescence microscope.  A method to "quantify" distribution of fluorophores at cell-substrate contact is proposed.

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Chemotherapy is one of the most effective and common treatments for cancer. Multi-drug resistance and drug side effects are one of the major obstacles to successful chemotherapy. To address these limitations and achieve better drug efficacy, nanosystem-based combination therapy offers a promising approach. This study aimed to synthesize, characterize, and investigate the synergistic effect of nanoliposomes loaded with doxorubicin and epigallocatechin-3-gallate (EGCG) on MCF-7 breast cancer cell lines. In the present study, nanoliposomes were prepared by passive loading and thin-film hydration. The characterization of nanoliposomes such as size distribution, zeta potential, the loading rate, drug release profile, and toxicity were measured. The mean diameter of nanoliposomes was 82.5 nm, their surface charge was -24.2 mV and drug loading was about 80%. The interaction of doxorubicin and EGCG with nanoliposomes was mediated by electrostatic and van der Waals bonds and EGCG has a deceasing effect on the doxorubicin release profile but the observed differences are not significant. The toxicity and viability data indicate that the simultaneous use of these two drugs increased the toxicity of the cells. Nanoliposomes containing doxorubicin were not able to reduce viability to below 50% in monotherapy with 5×10^-3 μM. While, the amount of viability dramatically reduced to below 50%, in combination with EGCG, resulting as combination chemotherapy. Consequently, the concomitant administration of EGCG with doxorubicin may be a suitable candidate for chemotherapy.

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Abstract. FZD7 receptor is considered as an emerging target for the treatment of Wnt-βcatenin related cancers. This transmembrane receptor is overexpressed in many cancer types like breast cancer and ovarian carcinoma, and so selective targeting of this receptor has a great therapeutic capacity. On the other hand, one of the mechanisms proposed for the anticancer effect of Atrial natriuretic peptide (ANP) that known as a heart hormone at first, is Wnt-βcatenin inhibition through an FZD dependent manner but, the molecular mechanism of this inhibition is not clear. Here, using computational methods including molecular docking and molecular dynamics simulation, also designing a cellular system that enabled us to trace Wnt-βcatenin kinetics directly, we investigated the mechanism of the peptide inhibitory potential against the pathway. Our computational results show that ANP can directly interact with FZD7 and also, its binding site on FZD7 overlap to the binding region of the Wnt carboxyl-terminal domain (Wnt-CTD). The finding of the silencing experiments demonstrates the dependency of Wnt-βcatenin signaling of the cellular system to FZD7. The decrease of βcatenin in cells treated to ANP and Wnt is also significant to compare to the control experiments. Finally, our results show that ANP is a potential scaffold to design selective peptide against FZD7.

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Cell substrates play a crucial role in tissue engineering and biomaterial science. Various studies are performed to develop the appropriate cell substrates for using in vitro and in vivo. Therefore, a biocompatible substrate that mimics the native extracellular matrix properties with specified surface topography as a biomimicry factor is necessary under ''the novel cell substrates development'' approaches. Our aim in the current study was to design, synthesize, and characterize a substrate with aligned nanometric arrays on the surface. The rapid and easy capabilities of Polydimethylsiloxane to receive chemical and physical characteristics with simple modifications, make it a promised candidate for the cell substrate. The obtained results from the atomic force and scanning electron microscopy showed the formation of 305±19 and 571±141 nanometers wrinkled nanoarrays after regulating the substrate under lateral traction during the plasma treatment times of 100 and 200s. Then, the behavior of a human foreskin fibroblast cell, in terms of adhesion, growth, viability, and morphology on this substrate was investigated. Increasing the plasma treatment time increased both nanoarray size and surface hydrophilicity, resulting in improved 17 and 46% of cell attachment quality, respectively. Additionally, the presence of the designed nanowrinkles surprisingly improved the number of the attached cells. The nanowrinkles caused the cells to align perfectly through the substrate's surface due to the contact guidance phenomena. Consequently, the biocompatible Polydimethylsiloxane substrate of this study with suitable chemical, mechanical, and physical properties showed fit capacities as a novel aligned cell culture platform. 

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Vitamins D and E are two common medicines for diabetes treatment. Among the main issues in this field is the release of insulin into the circulatory system. Increasing the stability of insulin hexamer is an evolving strategy in improving insulin secretion efficiency. Insulin protein is commonly found in three forms: monomer, dimer, and hexamer. In this study, for the first time, computational approaches were used to investigate the effect of vitamins D3 and E on the stability of insulin hexamer. The molecular docking results indicate six specific binding sites for these vitamins. These bind to the hydrophobic sites of insulin subunits due to their structural rings and hydrophobic properties. The G-mmpbsa analysis indicates the stabilizing role of both vitamins. The binding of these vitamins to the hexamer has significantly increased the binding energy between insulin subunits. Also, the number of hydrogen bonds between monomeric subunits of each insulin homodimer increased in the presence of the vitamins. It also significantly increases the number of internal hydrogen bonds of hexamer protein. Accordingly, vitamins D3 and E bind to and stabilize the insulin hexamer, resulting in a slower and more balanced insulin release as well as a longer half-life for the dimer in the bloodstream. These findings will pave the way to design a new strategy to regulate insulin release and increase its half-life in the blood for type II diabetes treatment. Besides, hexamer stabilization can be an effective treatment strategy for type I diabetes through slow release from an implanted biosensor system.

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Stem cells are characterized by their capacity for self-renewal and their ability to differentiate into specific cell types under the influence of their microenvironment. It is known that matrix chemistry controls stem cell differentiation. Single cell encapsulations of the Mesenchymal stem cells into a semi-permeable microgel, allows a greater control of the stem cell fate. In this study, a chip for single-cell encapsulation was designed and fabricated using microfluidic technology. By using microfluidic chip, human bone marrow mesenchymal stem cells (hBMSCs) are encapsulated inside alginate and alginate-poly-l lysine (PLL) microgels. The results of long-term viability of MSCs inside alginate-PLL microgels, shows a significant increase compared to alginate microgels. Mesenchymal stem cell proliferation in alginate-PLL microgels also increased significantly on days 14 and 21. It seems that PLL improves cell adhesion and function by creating a positively charged matrix. Microscopic studies indicate that the morphology of the cells inside the microgels is spherical. However, the average diameter and volume of cells in microgels containing PLL are smaller than others, which indicates more proliferation and space limitation inside the microgels. Therefore, single cell alginate-PLL microgels provide a suitable substrate in clinical studies for tissue engineering, organ transplantation and cell therapy.

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The COVID-19 pandemic has created a global health crisis, and developing effective treatments is essential to prevent the spread of the disease and save millions of lives. One of the key proteins involved in the replication cycle of SARS-CoV-2, the virus that causes COVID-19, is the main protease enzyme, 3CL^pro. Due to its high importance, this enzyme is the subject of molecular, structural, and clinical investigations, and efforts have been made to develop drugs that can inhibit its activity. One such drug is the chemical compound N3, which has been found to have a high inhibitory effect against 3CL^pro. However, traditional medicine perspectives on this issue have been less explored. In this research, molecular docking interaction simulation and all-atom molecular dynamics (MD) simulation were conducted to study the potential inhibitory capability of generally available 21 plant-extracted compounds against the 3CL^pro enzyme. Three compounds with the highest inhibition probability were selected from the molecular docking results and subjected to 100 ns of MD simulation to investigate their stability and structural-dynamic-energetic features. Beside the complexes stability, the results from the simulation demonstrated that, all our selected three compounds induce N3 comparable structural-dynamics characteristics to 3CL^pro and, therefore, are expected to have a similar inhibitory ability against this enzyme. Compound number 5 was found to have the most favorable binding energy and was proposed as the best plant substitute for N3. The results from this research can be directly used to design experimental research for 3CLpro enzyme inhibition, saving the time-financial cost.

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Rapid and sensitive diagnosis of breast cancer, especially in the early stages of its formation, is very important. One of the methods of detecting cancer cells is the use of electrochemical sensors. Here, a new nanocomposite including an organic metal framework and silver nanoclusters are used. The resulting nanocomposite can be used as a scaffold to attach antibodies for the detection of HER2-positive cells. In the final nanocomposite structure, silver nanoclusters are placed in the internal cavities of the metal-organic framework, leading to strong electron transport, good biocompatibility, and high electrochemical activity. Our results showed that the designed electrochemical sensor has a high sensitivity in identifying HER2 positive cells, with a detection limit of 3 cells and a linear range of 100 to 5000 cells/ml. Also, the investigations showed that the introduced sensor has stability, good selectivity and acceptable application. The proposed strategy for the development of sensors based on metal-organic frameworks provides a promising approach for early detection of cancer markers and living cancer cells.
 

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In recent years, targeted drug delivery systems have emerged as a promising approach to increase the efficacy and minimize side effects of therapeutic agents. Cerasomes are a special type of liposomes with covalent siloxane networks on the surface that provide exceptional morphological stability while retaining all the beneficial properties of liposomes. Cerosomes provide a unique platform for drug encapsulation and delivery due to their biocompatibility, stability, controllable release, and long-term storage. In this research, an attempt has been made to engineer the surface of cerosomes to increase the selectivity and efficiency of drug delivery. In such a way that the Herceptin antibody is placed on the surface of the serosa and allows the precise targeting of HER²⁺ cells. Then, the physicochemical characteristics of antibody-functionalized cerosomes, including size and surface charge 229±15.6 nm and 13.5±1.2 mV were respectively obtained. The results of IR and fluorescence spectrum showed that the antibody was successfully attached to the surface of cerasome with a binding efficiency of 64%. These results prove the basic mechanisms governing the synthesis of immunocerasomes and provide a valuable approach for future developments in targeted drug delivery systems.
 

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Objective: In order to improve the water solubility and bioavailability of curcumin in cancer therapy, we prepared and tested a novel waterborne cationic polyurethane (PU) as a nano-carrier for curcumin loading (CU-PU). We studied the effect of this prepared nano-drug on melanoma (F10B16) and fibroblasts cells (L929). Methods: Morphology, size and cell internalization ability of the prepared nanoparticles were analyzed by zetasizer, SEM, AFM and fluorescent microscopy, respectively. We anticipated that curcumin was loaded in the hydrophobic core of the PU carrier. Next, the suitable dose and therapeutic effects of CU-PU for both skin cancer and normal cell lines were evaluated by the MTT assay and real-time PCR. Results: The average diameters and polydispersity of the nanoparticles were 62.37 ± 1.7 nm and 0.080 ± 2.1 at 25 ̊C, respectively. The drug encapsulation efficiency was 87 ± 0.2%. The morphological analysis confirmed both a spherical shape and good dispersion without remarkable aggregation. The MTT assay results showed that the IC50 at 24 hours was 36.2 µM, whereas it was 25.4 µM at 48 hours. Real-time PCR results indicated that the CU-PU significantly decreased mRNA expressions of VEGF, Bcl-2, MMP-9 and COX-2 genes. An increase in mRNA expression of the BAX gene was also observed. Conclusion: Our result provided acceptable evidence for cell proliferation inhibition and the apoptotic effect of CU-PU on skin cancer cells. There were no adverse effects detected for normal cells.