Influence of Different Glucose Concentrations on the Expression of miR-29c-3p microRNA in Mesenchymal Stem Cells.

Background: miR-29c-3p manages a set of genes involved in regenerative medicine, and It seems that hyperglycemia in diabetic patients influences the power of stem cells to tissue regeneration the difficulties of diabetes by affecting the expression miR-29c-3p in mesenchymal stem cells. The study aims to analyze the effect of various glucose concentrations on the miR-29c-3p expression in mesenchymal stem cells. Materials and Methods: After receiving donated mesenchymal stem cells from Tarbiat Modares University, these cells were cultivated in a DMEM culture medium, including three different concentrations of glucose 250, 140, and 100 mg/dl. RNA was extracted from these cells after 72 hours, the Real-Time PCR technique assessed the expression of miR-29c-3p, and the results were analyzed by REST software. Results: miR-29c-3p expression in cells at concentrations of 140 and 250 mg/dL compared to typical situations (100 mg/dl) was significantly decreased (P˂0.05), which declined at a concentration of 250 mg/dl was more. Conclusion: Reduced miR-29c-3p expression in mesenchymal stem cells in chronic and mild diabetic situations demonstrated that diabetes might be one of the significant reasons for mesenchymal stem cells' reduced ability to repair tissue damage.

Recent progress in the manipulation of biochemical and biophysical cues for engineering functional tissues.

Tissue engineering (TE) is currently considered a cutting-edge discipline that offers the potential for developing treatments for health conditions that negatively affect the quality of life. This interdisciplinary field typically involves the combination of cells, scaffolds, and appropriate induction factors for the regeneration and repair of damaged tissue. Cell fate decisions, such as survival, proliferation, or differentiation, critically depend on various biochemical and biophysical factors provided by the extracellular environment during developmental, physiological, and pathological processes. Therefore, understanding the mechanisms of action of these factors is critical to accurately mimic the complex architecture of the extracellular environment of living tissues and improve the efficiency of TE approaches. In this review, we recapitulate the effects that biochemical and biophysical induction factors have on various aspects of cell fate. While the role of biochemical factors, such as growth factors, small molecules, extracellular matrix (ECM) components, and cytokines, has been extensively studied in the context of TE applications, it is only recently that we have begun to understand the effects of biophysical signals such as surface topography, mechanical, and electrical signals. These biophysical cues could provide a more robust set of stimuli to manipulate cell signaling pathways during the formation of the engineered tissue. Furthermore, the simultaneous application of different types of signals appears to elicit synergistic responses that are likely to improve functional outcomes, which could help translate results into successful clinical therapies in the future.

Variants in ACE2; potential influences on virus infection and COVID-19 severity.

The third pandemic of coronavirus infection, called COVID-19 disease, was first detected in November 2019th. Various determinants of disease progression such as age, sex, virus mutations, comorbidity, lifestyle, host immune response, and genetic background variation have caused clinical variability of COVID-19. The causative agent of COVID-19 is an enveloped coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that invades host cells using an endocytic pathway. The SARS-CoV-2 spike protein is the main viral protein that contributes to the fusion of the virus particle to the host cell through angiotensin-converting enzyme 2 (ACE2). The highly conserved expression of ACE2 is found in various animals, which indicates its pivotal physiological function. The ACE2 has a crucial role in vascular, renal, and myocardial physiology. Genetic factors contributing to the outcome of SARS-CoV-2 infection are unknown; however, variants in the specific sites of ACE2 gene could be regarded as a main genetic risk factor for COVID-19. Given that ACE2 is the main site for virus landing on host cells, the effect of amino acid sequences of ACE2 on host susceptibility to COVID-19 seems reasonable. It would likely have a substantial role in the occurrence of a wide range of clinical symptoms. Several ACE2 variants can affect the protein stability, influencing the interaction between spike protein and ACE2 through imposing conformational changes while some other variants are known to cause a decrease or an increase in the ligand-receptor affinity. The other variations are located at the proteolytic cleavage site, which can influence virus infection; because soluble ACE2 can act as a decoy receptor for virus and decrease virus intake by cell surface ACE2. Notably, polymorphisms of regulatory and non-coding regions such as promoter in ACE2, can play crucial role in different expression levels of ACE2 among different individuals. Many studies should be performed to investigate the involvement of ACE2 polymorphism with susceptibility to COVID-19. Herein, we discuss some reported associations between variants of ACE2 and COVID-19 in details. In addition, the mode of action of ACE2 and its role in SARS-CoV-2 infection are highlighted which is followed by addressing the effects of several ACE2 variants on its protein stability, viral tropism or ligand-receptor affinity, secondary and tertiary structure or protein conformation, proteolytic cleavage site, and finally inter-individual clinical variability in COVID-19. The polymorphisms of regulatory regions of ACE2 and their effect on expression levels of ACE2 are also provided in this review. Such studies can improve the prediction of the affinity of mutant ACE2 variations with spike protein, and help the biopharmaceutical industry to design effective approaches for recombinant hACE2 therapy and vaccination of COVID-19 disease.

Efficacy of pegylated liposomal etoposide nanoparticles on breast cancer cell lines.

BACKGROUND/AIM: This study aimed to investigate the efficacy of pegylated liposomal etoposide nanoparticles (NPs) against T-47D and MCF-7 breast cancer cell lines. MATERIALS AND METHODS: Pegylated liposomal etoposide NPs were prepared by reverse phase evaporation method. The size, size distribution, and zeta potential of the NPs was measured by a Zetasizer instrument. The cytotoxicity of NPs was inspected by methyl thiazol tetrazolium assay. The release pattern of the drug from the vesicles was studied by the dialysis method. Drug loading and encapsulation efficiency (EE) were also measured. RESULTS: The mean size, size distribution, and zeta potential of pegylated liposomal etoposide NPs were 491 ± 15.5 nm, 0.504 ± 0.14, and -35.8 ± 2.5 mV, respectively. Drug loading and EE were 10.3 ± 1.6% and 99.1 ± 2.8%, respectively. The etoposide release in the formulation was estimated at about 3.48% after 48 h. The cytotoxicity effect of etoposide NPs on T-47D and MCF-7 cell lines of breast cancer showed higher antitumor activity as compared with those of the free drug. CONCLUSION: Liposome-based NPs may hold great potential as a drug delivery system.