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Designed AMP exhibited promising antimicrobial activities with low minimum inhibitory concentration, in the range of 64-256 µg/mL. P24 showed potent antimicrobial activity preferably against Gram-positive bacteria, and more potent than pexiganan as a successful Magainin II analog for topical infections. In general, further modification can be applied to improve its therapeutic index.Researchers add serum to a classical medium at concentrations of 5 to 10% (v/v) to grow cells in-vitro culture media. Unfortunately, serum is a poorly defined culture medium component as its composition can vary considerably while serum-free cell culture media are an excellent alternative to standard serum-containing media and offer several major advantages. Advantages of using serum-free media include a lower risk of infectious agents, lower risk of interfering components, less contaminant, avoids ethical issues. According to previous studies insulin, selenium, transferrin and glucose are important component of serum that affect cell growth. In the present study, we optimized amount of these factors in order to serum free culture medium fabrication. Response surface methodology (RSM) was employed for optimization of key factors in serum free medium to enhance recombinant human GM-CSF (rhGM-CSF) production in CHO cell line. Four important process parameters including insulin concentration (0-2 g/L), transferrin concentration (0-1 g/L), selenium concentration (0-0.001 g/L) and glucose concentration (0-5 g/L) were optimized to obtain the best response of rhGM-CSF production using the statistical Box-Behnken design. The experimental data obtained were analyzed by analysis of variance (ANOVA) and fitted to a second-order polynomial equation using multiple regression analysis. Numerical optimization applying desirability function was used to identify the optimum conditions for maximum production of rhGM-CSF. The optimum conditions were found to be insulin concentration = 1.1 g/L, transferrin concentration = 0.545 g/L, selenium concentration = 0.000724 g/L and glucose = 1. 4 g/L. Maximum rhGM-CSF production was found to be 3.5 g/L.T-cell acute lymphoblastic leukemia is an aggressive hematologic malignancy which is usually associated with unfavorable prognosis particularly in patients with refractory/relapsed disease. Therefore, development of novel therapeutic strategies is highly required for improving the outcome of these patients. Although there are several studies evaluating the efficacy of proteasome inhibitors on acute lymphoblastic leukemia of B-cell lineage, the data are still limited regarding T-cell acute lymphoblastic leukemia. Here, we tried to investigate the effects of the proteasome inhibition by carfilzomib on the induction of apoptosis and autophagy in Molt4 cells. The effect of carfilzomib in combination with dexamethasone in Molt4, as a glucocorticoid-resistant T-cell acute lymphoblastic leukemia cell line, was also assessed. Our data showed that carfilzomib can induce both apoptosis and autophagy in Molt4 cells. Furthermore, we found that carfilzomib is a potent inducer of reactive oxygen species production and also induces G2/M phase cell cycle arrest in Molt4 cells. Concomitant treatment with carfilzomib and dexamethasone demonstrated that carfilzomib can synergistically enhance the cytotoxic effect of dexamethasone on Molt4 cells. Furthermore, co-treatment of the cells with carfilzomib and dexamethasone increased the induction of autophagy as compared with each drug alone. In conclusion, our results are suggestive of the effectiveness of carfilzomib on Molt4 cells as a model of GC-resistant T-cell acute lymphoblastic leukemia.The strong storyline behind the critical role of cyclin-dependent kinase (CDK) inhibitor proteins in natural defense against malignant transformation not only represents a heroic perspective for these proteins, but also provides a bright future for the application of small molecule inhibitors of CDKs in the novel cancer treatment strategies. The results of the present study revealed that the inhibition of CDKs using pan-CDK inhibitor AT7519, as revealed by the induction of G1 cell cycle arrest as well as the reduction of cyclins expression, resulted in decreased survival in acute myeloid leukemia (AML)-derived KG-1 cells, either in the context of single agent or in combination with arsenic trioxide (ATO). https://www.selleckchem.com/products/sd-208.html Apart from alterations in the expression of proliferation and apoptotic genes, the anti-survival property of AT7519 was coupled with the inhibition of autophagy-related genes. Notably, we found that the blockage of autophagy system in KG-1 cells resulted in a superior cytotoxic effect, introducing autophagy as a probable suppressor of cell death. As far as we are aware, to date, no study has reported the contributory mechanisms correlated with the less sensitivity of acute leukemia cells to AT7519 and our study suggested for the first time that the activation of both PI3K and c-Myc signaling pathways could overshadow, at least partly, the efficacy of this agent in KG-1 cells. Overall, due to the pharmacologic safety of AT7519, our study proposed this inhibitor as a promising agent for the treatment of AML either as a single agent or in a combined-modal strategy.An important field of bone tissue engineering (BTE) concerns the design and fabrication of smart scaffolds capable of inducing cellular interactions and differentiation of osteo-progenitor cells. One of these additives that has gained growing attention is metallic ions as therapeutic agents (MITAs). The specific biological advantage that these ions bring to scaffolds as well as other potential mechanical, and antimicrobial enhancements may vary depending on the ion entity, fabrication method, and biomaterials used. Therefore, this article provides an overview on current status of In-vivo application of MITAs in BTE and the remaining challenges in the field. Electronic databases, including PubMed, Scopus, Science direct and Cochrane library were searched for studies on MITAs treatments for BTE. We searched for articles in English from January-2000 to October-2019. Abstracts, letters, conference papers and reviews, In-vitro studies, studies on alloys and studies investigating effects other than enhancement of new bone formation (NBF) were excluded.
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