Search

Immunitary bioeconomy encompasses a significant share of the bioeconomy that is accompanied by a ‎high degree of complexity and various religious and ethical controversies for both customers and the ‎service providers. Compared to blood banking, these complexities are more substantial for the ‎new state-of-the-art technology of umbilical cord blood (UCB) banking, in which the viable ‎therapeutically active substance of cord blood (i.e., cord blood stem cells (CBSCs)) is banked for much ‎less likely future demand. It became even more complicated when we knew that the main three types ‎of cord blood banking industry (i.e., private, public, or hybrid models) are not the same regarding ‎economic, ‎ethical, and even social considerations. The present paper aims to review and discuss the ‎main drivers of behavioral intention among the customers of private UCB banking. We focused on ‎private UCB banking because, although there is a low likelihood of childs' future need for their siblings' ‎CBSCs, there is an unnecessary growing demand for using private UCB banking services. Based on the ‎previously published pieces of research, we discussed five main influential factors (i.e., awareness, ‎reference group, usability, disease history, and price) that can affect the customers' risk perception ‎‎(and further their behavioral intention) to preserve their child UCB for private applications. Finally, we ‎concluded that private UCB banking must not be considered a commercial activity, and ethically healthcare ‎managers must be more actively involved in ‎facilitating the proper flow of information among the ‎customers. [ABSTRACT FROM AUTHOR]

Growing evidence demonstrates that cancer-associated fibroblasts (CAF) are responsible for tumor genesis, growth, metastasis, and treatment response. Therefore, targeting these cells may contribute to tumor control. It has been proposed that targeting key molecules and pathways of proliferative functions can be more effective than killing CAFs. In this regard, multicellular aggregates, like spheroids, can be used as human tumor models. Spheroids closely resemble human tumors and mimic many of their features. Microfluidic systems are ideal for cultivation and study of spheroids. These systems can be designed with different biological and synthetic matrices in order to have a more realistic simulation of the tumor microenvironment (TME). In this study, we investigated the effect of all-trans retinoic acid (ATRA) on 3D spheroid invasion of MDA-MB cells exposed to hydrogel matrix derived from CAFs. The number of invasive cells significantly decreased in CAF-ECM hydrogel treated with ATRA (p < 0.05), which indicates that ATRA could be effective for CAFs normalization. This experiment was done using an agarose-alginate microfluidic chip. As compared with common methods, such hydrogel casting is an easier method for chip fabrication and can even reduce costs. [ABSTRACT FROM AUTHOR]

Background: The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties. Methods: MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network. Results: Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers. Conclusions: We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most prevalent types of cancer in Iranian women and the second cause of death in women worldwide. Gene mutations are the key determinants of the disease; therefore, the genetic study of this disease is of paramount importance. One of the genetic evaluation methods of this disease is microarray technology, which allows the examination of the simultaneous expression of thousands of genes. Clustering is the method for analyzing high-dimension data, which we used in the present research for collecting similar genes in separated clusters. Method: A descriptive and inferential statistical analysis was carried out to evaluate unsupervised learning models of gene expression analysis and five bi-clustering methods (including PLAID (PL), Fabia, Bimax, Cheng & Church (CC), and Xmotif) were compared. For this purpose, we obtained the microarray gene expression data for lapatinib-resistant breast cancer cell lines from previously published research. The enrichment efficacy of the clusters was evaluated with gene ontology, and the results of these five models were compared with the Jaccard index, variance stability, least-square error, and goodness of fit indices. Furthermore, the results of the best model were assessed for building a genes sets network with Bayesian networks. Results: After preprocessing, clustering was performed on the data with the dimension (4710 x 18) of the genes. Four models, except for CC, successfully found bi-clusters in the data set. The data evaluation revealed that the results of the models were almost the same, but the PL model performed better than the others, finding 11 bi-clusters; this model was used to build the network of gene sets. Conclusion: According to the results, the PL method was suitable for clustering the data. Accordingly, it could be recommended for data analysis. In addition, the gene sets network formed on gene expression data was incompetent. [ABSTRACT FROM AUTHOR]

Over the last decade, mesenchymal stem cells (MSCs) have been considered a suitable source for cell-based therapy, especially in regenerative medicine. First, the efficacy and functions of MSCs in clinical applications have been attributed to their differentiation ability, called homing and differentiation. However, it has recently been confirmed that MSCs mostly exert their therapeutic effects through soluble paracrine bioactive factors and extracellular vesicles, especially secretome. These secreted components play critical roles in modulating immune responses, improving the survival, and increasing the regeneration of damaged tissues. The secretome content of MSCs is variable under different conditions. Oxidative stress (OS) is one of these conditions that is highly important in MSC therapy and regenerative medicine. High levels of reactive oxygen species (ROS) are produced during isolation, cell culture, and transplantation lead to OS, which induces cell death and apoptosis and limits the efficacy of their regeneration capability. In turn, the preconditioning of MSCs in OS conditions contributes to the secretion of several proteins, cytokines, growth factors, and exosomes, which can improve the antioxidant potential of MSCs against OS. This potential of MSC secretome has turned it into a new promising cell-free tissue regeneration strategy. This review provides a view of MSC secretome under OS conditions, focusing on different secretome contents of MSCs and thier possible therapeutic potential against cell therapy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air‐exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real‐time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function. [ABSTRACT FROM AUTHOR]

In situations where the molecular mechanism of many ocular disorders is unknown, owing to the difficulties associated with sampling from ocular tissues, human tear film can be a promising medium in ophthalmic research. The present study demonstrates an in-depth gel-based proteome optimization survey to approach more appropriate and efficient systems in various situations such as normal and dry-eye syndromes. Therefore, systematic and statistical evaluations were performed on different preparation methods, including acetone, acetone-methanol, chloroform-methanol-water, trichloroacetic acid (TCA)-acetone, tri- n-butylphosphate-acetone-methanol precipitations and ammonium sulfate fractionation at three different percentages of saturations (50, 70 and 90%). Methods were compared quantitatively on both one- and two-dimensional patterns. Some important parameters such as total protein recovery yield, densitometric analysis of some protein contaminants, banding patterns and total spot numbers along with statistical models for proper clustering were considered. Findings revealed noticeable impacts of preparation methods on all aspects of gel-based separations as well as recovery yield (ranging from 5.29 ± 0.96 to 22.56 ± 1.77 µg/mm) and banding and pattern resolution. In addition to all these, the most important point is that the total protein spot number on the final two-dimensional patterns (varied from 528.00 ± 19.00 to 657.00 ± 21.52 for different methods) were also noticeably increased in comparison with previously published reports (maximum of 250 spots), which is essential for a more comprehensive analysis. Increasing the proteome coverage in the present study is supposed to originate from improved solubility and effective rehydration during the sample application and isoelectric focusing (IEF) procedure along with proper sample preparation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. [ABSTRACT FROM AUTHOR]

Patterns obtained in two-dimensional gel electrophoresis (2- DE) in the previously published articles suggest a varying number of proteins. To seek the cause of this variation, we investigated the effect of reduction power on the overall tear proteome maps. To this end, the buffers of two reducing agents, dithiothreitol ( DTT) at nine different concentrations and di-(2-hydroxyethyl) disulfide ( HED), were examined. The assay showed that HED clearly improved 2- DE resolution, increased the number of detectable protein spots, and offered well-resolved chain regions in comparison with those treated with DTT. Furthermore, this study introduced increasing the reduction power as a remedy to increase the reproducibility of two-dimensional human tear proteome maps. In addition, the results of our assessment showed that improved reduction efficiency was accompanied by increased procedure reproducibility from 42% to 89%. [ABSTRACT FROM AUTHOR]

Thirty-eight different milk and milk powder samples from Tehran-Iran were collected and analyzed for Sr activity using a method in which the daughter product of Sr decay (Y) was extracted by tributyl phosphate from ashed milk. Y was then back extracted with water, and oxalate was precipitated . Following the sample analyzing, beta counting was performed with an ultralow-level liquid scintillation spectrometer. The quality control and assurance of the method were obtained by standard samples prepared with an IAEA-certified reference material. The mean determined Sr activity concentration in the analyzed milk and milk powder (0.225 ± 0.042 and 0.216 ± 0.024 Bq kg, respectively) showed that the radioactivity concentration in our samples was too low to induce biological hazards. These data can provide useful information of the background level of contamination, which in turn can be used in the following environmental monitoring programs. [ABSTRACT FROM AUTHOR]