Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14–198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.
Extremely low-frequency electromagnetic field (ELF-EMF) induces biological effects on different cells through various signaling pathways. To study the impact of the ELF-EMF on living cells under an optimal physiological condition, we have designed and constructed a novel system that eliminates several limitations of other ELF-EMF systems. Apoptosis and cell number were assessed by flow cytometry and the Trypan Blue dye exclusion method, respectively. In vitro cell survival was evaluated by colony formation assay. The distribution of cells in the cell cycle, intracellular ROS level, and autophagy were analyzed by flow cytometer. Suspended cells differentiation was assessed by phagocytosis of latex particles and NBT reduction assay. Our results showed that response to the exposure to ELF-EMF is specific and depends on the biological state of the cell. For DU145, HUVEC, and K562 cell lines the optimum results were obtained at the frequency of 0.01 Hz, while for MDA-MB-231, the optimum response was obtained at 1 Hz. Long-term exposure to ELF-EMF in adherent cells effectively inhibited proliferation by arresting the cell population at the cell cycle G2/M phase and increased intracellular ROS level, leading to morphological changes and cell death. The K562 cells exposed to the ELF-EMF differentiate via induction of autophagy and decreasing the cell number. Our novel ELF-EMF instrument could change morphological and cell behaviors, including proliferation, differentiation, and cell death.
Inhibiting the interaction between the p53 tumor suppressor and its negative regulator murine double minute 2 (MDM2) is a promising therapeutic opportunity in cancer drug research. Herein, we describe the design, synthesis, and in vitro screening of phenyl chroman-based derivatives 7 a-l as MDM2 inhibitors. Among target compounds, 7 e, 7 h, and 7 j had considerable cytotoxicity activity at concentrations of 50 μM and 100 μM against MCF7 and HCT-116 cell lines. Designed compounds that demonstrated good toxicity, were selected for enzyme inhibition assay. The most potent MDM2 inhibitor in this series is compound 7 h, which showed a Ki value of 13.66 μM. Moreover, compound 7 h with acceptable safety profiles in normal cells was found the least effective compound against human umbilical vein endothelial cells (HUVECs). In addition, cell cycle analysis was also investigated for representative compound 7 h. Also, the docking study was done to predict the possible interaction between the synthesized compound and both MDM2 and murine double minute x (MDMX) proteins. Interestingly, the docking results were in good agreement with the experimental assay.
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