Electrospinning as an effective and accessible method is known to yield scaffolds with desired physical, chemical, and biological properties for tissue engineering. In the present study, captopril (CP)-loaded polycaprolactone (PCL)/carbon quantum dots (CQDs) nanocomposite scaffolds were fabricated for bone tissue regeneration. The microstructure and hydrophilicity/hydrophobicity ratio of scaffolds were assessed by scanning electron microscopy and wettability test, respectively. The results showed that the presence of CQDs and CP in the scaffolds decreased the fiber diameter (1180 ± 281.5-345 ± 110 nm) and also it led to an increase in the surface hydrophilicity (137-0) of scaffolds. Evaluation of the scaffolds' functional groups was performed using Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy. The ultimate tensile strength of scaffolds was in the range of 6.86 ± 0.00 to 22.09 ± 0.06 MPa. Distribution of CQDs in the scaffolds' fibers was investigated by transmission electron microscopy and fluorescent spectrometer. The cell viability, attachment, proliferation, and alkaline phosphatase (ALP) activity of scaffolds were assessed in vitro. Based on the overall results, the scaffold containing CQDs and CP led to a significant increase in the cells' proliferation and ALP activity. Therefore, the PCL/CQDs/CP is recommended as a potential nanocomposite scaffold for bone tissue regeneration.
Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that is identified with chronic inflammation and progressive destruction of the joints. The defective activity of regulatory T cells (Tregs) plays a crucial role in RA development. Oleuropein (OLEU) is the most common polyphenolic compound in olive leaf extracts with numerous pharmacological activities. In this study, the potential effects of OLEU in shifting CD4+ T cells toward Tregs are evaluated in patients with RA. Methods 32 healthy controls (HC) and 45 RA patients were included in two groups. The immunoturbidometric technique was used to measure serum levels of c-reactive protein (CRP) and rheumatoid factor (RF). Isolated CD4+ T cells from peripheral blood mononuclear cells (PBMCs) of HC and RA patients were cultured with appropriate concentrations of OLEU. The cytotoxicity effects of OLEU were determined using the MTT assay at 24, 48, and 72 h. The percentage of CD4+CD25 + FoxP3 regulatory T lymphocytes (Tregs) and the expressions of IL-10 and TGF-β were evaluated by flow cytometry and immunoassay techniques after treatment of cells with different concentrations of OLEU for 24 h. The serum levels of RF and CRP in patients with RA were 11.8 ± 5.32 IU/ml and 6.36 ± 5.82 mg/l, respectively. Results OLEU had a dose-dependent effect on the CD4+ T cells via increasing the frequency of CD4+CD25 + FoxP3 Tregs ( p = 0.0001). Moreover, it induced the production of IL-10 ( p = 0.0001) and TGF-β ( p < 0.01) in both HC and RA patients. Conclusion The findings of this study suggest that OLEU may have immunomodulatory effects by inducing Tregs, and it might help in developing a novel nutrition strategy for management of autoimmune diseases such as RA.
In silico study was performed to twelve 1,5-benzothiazepine chalcone derivatives with the protein target from the crystallographic structure modeling of the enzyme tyrosine kinase. The objective of this study is to execute and to estimate the biological activity of chalcone-based 1,5-benzothiazepine derivatives as potential inhibitors for breast cancer MCF7. To get insight into potential anticancer activities, molecular docking, molecular dynamic and ADME prediction were performed. Docking results reported that compound MA9 with binding free energy of -11.2 kcal / mol can interact through hydrogen bonds with amino acids Cys788 on 1T46 protein active site. In addition, the lowest binding free energy conformation indicated its stability during molecular dynamic simulation. MA9 is also shown to have drug likeness properties based on ADME prediction. In order to evaluate the modeling outcomes, MTT assay were performed for some of the most and least promising benzologs (i.e., MA1, MA6, MA8 and MA9). As expected, compound MA9 with the best calculated anticancer properties revealed the best inhibition against MCF7cell line in vitro. Thus, this compound was chosen as the reference for the next stage in the drug design.
Diabetic neuropathy is a well-known complication of diabetes. It has been recently confirmed that hyperglycemia-induced toxicity participates in multiple cellular pathways that are typical for neural deterioration. Nampt/PBEF/visfatin is a novel endogenous ligand, which some studies have shown its neuroprotective effects on neurodegenerative disease. Therefore, we hypothesized that visfatin might prevent high glucose (HG)-induced neurotoxicity via the inhibition of apoptosis, autophagy, and reactive oxygen species (ROS) responses properly. In this study, Pheochromocytoma Cell Line 12 (PC12) cells were exposed to both HG concentrations (50, 75, 100,125, 150 mM) and visfatin (50, 100, 150 ng/ml) in different time-points to determine the optimum time and dose of glucose and visfatin. To investigate the effects of visfatin on HG-induced damage in PC12 diabetic neuropathy model, we examined ROS response, apoptosis, and autophagy by using ROS detection kit, flow cytometry, and Real-time PCR/western blot, respectively. We determined that HG concentration significantly increased ROS level and apoptosis of diabetic PC12 cells. However, visfatin treatment significantly decreased ROS production (P < 0.05) and apoptosis of diabetic PC12 cells (P < 0.0001). Beclin-1 mRNA level (P < 0.05) and Lc3-II protein level (P < 0.05) showed that autophagy pathway is impaired by HG concentrations. We concluded that visfatin could sufficiently decrease neural damage caused by ROS production and apoptosis under HG-induced toxicity.
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