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Breast cancer is one of the leading causes of cancer deaths in women worldwide. Magnetic fields have shown anti-tumor effects in vitro and in vivo as a non-invasive therapy method that can affect cellular metabolism remotely. Doxorubicin (DOX) is one of the most commonly used drugs for treating breast cancer patients. It can be assumed that combining chemotherapy and magnetotherapy is one of the most effective treatments for breast cancer. This study aimed to investigate the potential cytotoxic effect of DOX at low concentrations in combination with extremely low-frequency electromagnetic fields (ELF-EMF; 50 Hz; 20 mT). The breast cancer cell line MCF-7 was examined for oxidative stress, cell cycle, and apoptosis. MCF-7 cells were treated with various concentrations of DOX as an apoptosis-inducing agent and ELF-EMF. Cytotoxicity was examined using the MTT colorimetric assay at 12, 24, and 48 h. Consequently, concentration- and time-dependent cytotoxicity was observed in MCF-7 cells for DOX within 24 h. The MTT assay results used showed that a 2 μM concentration of DOX reduced cell viability to 50% compared with control, and as well, the combination of ELF-EMF and DOX reduced cell viability to 50% compared with control at > 0.25 μM doses for 24 h. In MCF-7 cells, combining 0.25 μM DOX with ELF-EMF resulted in increased ROS levels and DOX-induced apoptosis. Flow cytometry analysis, on the other hand, revealed enhanced arrest of MCF-7 cells in the G0-G1 phase of the cell cycle, as well as inducing apoptotic cell death in MCF-7 cells, implying that the synergistic effects of 0.25 μM DOX and ELF-EMF may represent a novel and effective agent against breast cancer., (© 2023. The Author(s).)

Application of cost-effective pretreatment of wheat straw is an important stage for massive bioethanol production. A new approach is aimed to enhance the pretreatment of wheat straw by using low-cost ionic liquid [TEA][HSO 4 ] coupled with ultrasound irradiation. The pretreatment was conducted both at room temperature and at 130 °C with a high biomass loading rate of 20% and 20% wt water assisted by ultrasound at 100 W-24 kHz for 15 and 30 min. Wheat straw pretreated at 130 °C for 15 and 30 min had high delignification rates of 67.8% and 74.9%, respectively, and hemicellulose removal rates of 47.0% and 52.2%. Moreover, this pretreatment resulted in producing total reducing sugars of 24.5 and 32.1 mg/mL in enzymatic saccharification, respectively, which corresponds to saccharification yields of 67.7% and 79.8% with commercial cellulase enzyme CelluMax for 72 h. The ethanol generation rates of 38.9 and 42.0 g/L were attained for pretreated samples for 15 and 30 min, equivalent to the yields of 76.1% and 82.2% of the maximum theoretical yield following 48 h of fermentation. This demonstration provided a cheap and promising pretreatment technology in terms of efficiency and shortening the pretreatment time based on applying low-cost ionic liquid and efficient ultrasound pretreatment techniques, which facilitated the feasibility of this approach and could further develop the future of biorefinery., (© 2023. The Author(s).)

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 Mg 2+ 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 designing biomimetic devices. In the following, we examined the effect of cations on the interaction between siRNA modified by cholesterol and the membrane surface. Our MD simulations showed that in the presence of Mg 2+ , the electrostatic and vdW energy between the membrane and siRNA were higher compared to those in the presence of NA + . We showed that the electrostatic interaction between membrane and siRNA cannot be facilitated only by cholesterol conjugated. Indeed, cations are essential to create coulomb repulsion and enable membrane attachment. This study provides important insight into liposome carriers for siRNA delivery and could help us in the development of siRNA-based therapeutics. Due to the coronavirus pandemic outbreak, these results may shed light on the new approach for treating these diseases and their molecular details., (© 2022. The Author(s).)

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 on experimental conditions. Our results showed a liposome model (ellipse vesicle structure) during the 2100 ns was formed. Moreover, the analysis confirmed that the stretched and ellipse structure is the best structure that could be formed. The eukaryotic and even the bacterial cells have elliptical and flexible structures. Usually, an elliptical structure is more stable than other assembled structures. The results indicated the assembly of the lipids is directed through short-range interactions (electrostatic interactions and, van der Waals interactions). Total energy (Van der Waals and electrostatic interaction energy) confirmed the designed elliptical liposome structure has suitable stability at the end of the simulation process. Our findings confirmed that phospholipids DOPC and DOPE have a good tendency to form bilayer membranes (liposomal structure) based on their geometric shapes and chemical-physical properties. Finally, we expected the simulated liposomal structure as a simple model to be useful in understanding the function and structure of biological cell membranes. Furthermore, it is useful to design optimal, suitable, and biocompatible liposomes as potential drug carriers., (© 2022. The Author(s).)

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, coarse-grained (CG) molecular dynamics (MD) simulations were carried out. Our results showed that GO nanosheets can reduce cell stiffness in MCF7 cells and MDA-MB-231 cell lines and highly inhibited cell migration (39.2%) in MCF-7 and (38.6%) in MDA-MB-231 cell lines through the GO nanosheets-mediated disruption of the intracellular cytoskeleton. In the presence of GO nanosheets, the cell migration of both cell lines, as well as the cell stiffness, significantly decreased. Moreover, after GO nanosheets treatment, the cell actin network dramatically changed. The experimental and theoretical approaches established a quantitative picture of changes in these networks. Our results showed the reduction of the order parameter in actin filaments was 23% in the MCF7 cell line and 20.4% in the MDA-MB-231 cell line. The theoretical studies also showed that the GO nanosheet-actin filaments have stable interaction during MD simulation. Moreover, the 2D free energy plot indicated the GO nanosheet can induce conformational changes in actin filaments. Our findings showed that the GO nanosheets can increase the distance of actin-actin subunits from 3.22 to 3.5 nm and in addition disrupt native contacts between two subunits which lead to separate actin subunits from each other in actin filaments. In this study, the biomechanical characteristics were used to explain the effect of GO nanosheets on cells which presents a novel view of how GO nanosheets can affect the biological properties of cells without cell death. These findings have the potential to be applied in different biomedical applications., (© 2021. The Author(s).)

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 cell-line images into six classes, including five different cancer cell-lines (P-C9, SK-LU-1, H-1975, A-427, and A-549) and normal cell-line (16-HBE). Our results demonstrate that ResNet18, a residual learning convolutional neural network, is an efficient and promising method for lung cancer cell-lines categorization with a classification accuracy of 98.37% and F1-score of 97.29%. Our proposed workflow is also able to successfully distinguish normal versus cancerous cell-lines with a remarkable average accuracy of 99.77% and F1-score of 99.87%. The proposed CAD system completely eliminates the need for extensive user intervention, enabling the processing of large amounts of image data with robust and highly accurate results.

It is well known that chromatin structure is highly sensitive to the ionic environment. However, the combined effects of a physiologically relevant mixed ionic environment of K(+), Mg(2+) and Na(+), which are the main cations of the cell cytoplasm, has not been systematically investigated. We studied folding and self-association (aggregation) of recombinant 12-mer nucleosome arrays with 177 bp DNA repeat length in solutions of mixtures of K(+) and Mg(2+) or Na(+) and Mg(2+). In the presence of Mg(2+), the addition of sodium ions promotes folding of array into 30-nm fibres, whereas in mixtures of K(+) and Mg(2+), potassium ions abrogate folding. We found that self-association of nucleosome arrays in mixed salt solutions is synergistically promoted by Mg(2+) and monovalent ions, with sodium being slightly more efficient than potassium in amplifying the self-association. The results highlight the importance of a mixed ionic environment for the compaction of chromatin under physiological conditions and demonstrate the complicated nature of the various factors that determine and regulate chromatin compaction in vivo.