Simplified Intestinal Microbiota to Study Microbe-Diet-Host Interactions in a Mouse Model

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Applying neural networks to predict HPC-I/O bandwidth over seismic data on lustre file system for ExSeisDat

Cluster Computing - HPC or super-computing clusters are designed for executing computationally intensive operations that typically involve large scale I/O operations. This most commonly involves...     

Magnetoelectric nanocomposite scaffold for high yield differentiation of mesenchymal stem cells to neural-like cells

While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe₂O ₄ nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators.     

Intraovarian injection of miR-224 as a marker of polycystic ovarian syndrome declines oocyte competency and embryo development

miR-224 is associated with polycystic ovary syndrome (PCOS) that is an epidemic in reproductive age women. Most studies of miR-224 have focused on in vitro analyses, whereas the in vivo effects are not widely understood. In this study, we have conducted in silico analysis and found two potential miR-224 target genes, Ptx3 and Smad4 that have roles in folliculogenesis. Because patients with PCOS have decreased numbers of follicular cells related to cell apoptosis, we also investigated two apoptotic genes, Bax and Bcl2. We used the intraovarian injection method to deliver miR-224 into a mouse model. Histological examination of the ovaries was done by fluorescent microscope. Fertilization, cleavage, and developmental competence rates were counted under a stereomicroscope and compared between the studied groups. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of miR-224 was conducted to determine the levels of the studied genes in the oocytes, cumulus cells, and blastocysts. The numbers of oocytes and fertilization rate indicated a higher apoptosis index ( p < 0.05) and increased numbers of degenerated embryos with irregular blastomeres and fragmented cytoplasm in the experimental group. RT-PCR results indicated a significant increase in miR-224 levels in the manipulated group. Of the four analyzed genes, Ptx3, Smad4, and Bcl2 had decreased levels in the transfected group, with increased Bax expression ( p < 0.05). This data showed that miR-224 negatively affected ovulation in the mouse model by decreasing Ptx3 and Smad4 expressions. The changes in Bcl2 and Bax expression levels, as apoptosis biomarkers, showed that apoptosis was a secondary outcome of the effect of miR-224.     

Wnt lipidation: Roles in trafficking,modulation, and function

The Wnt signaling pathway consists of various downstream target proteins that have substantial roles in mammalian cell proliferation, differentiation, and development. Its aberrant activity can lead to uncontrolled proliferation and tumorigenesis. The posttranslational connection of fatty acyl chains to Wnt proteins provides the unique capacity for regulation of Wnt activity. In spite of the past belief that Wnt molecules are subject to dual acylation, it has been shown that these proteins have only one acylation site and undergo monounsaturated fatty acylation. The Wnt monounsaturated fatty acyl chain is more than just a hydrophobic coating and appears to be critical for Wnt signaling, transport, and receptor activation. Here, we provide an overview of recent findings in Wnt monounsaturated fatty acylation and the mechanism by which this lipid moiety regulates Wnt activity from the site of production to its receptor interactions.     

Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases

Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell-free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell-derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.     

Wnt pathway targeting reduces triple-negative breast cancer aggressiveness through miRNA regulation in vitro and in vivo

Triple-negative breast cancer, devoid of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is deprived of commonly used targeted therapies. MicroRNAs (miRNAs) are undergoing a revolution in terms of potentially diagnostic or therapeutic elements. Combining computational approaches, we enriched miRNA binding motifs of Wnt pathway-associated upregulated genes. Our in-depth bioinformatics, in vitro and in vivo analyses indicated that miR-381 targets main genes of the Wnt signaling pathway including CTNNB1, RhoA, ROCK1, and c-MYC genes. The expression level of miR-381 and target genes was assessed by quantitative real-time polymerase chain reaction (RT-qPCR) in MCF-7, MDA-MB-231, and MCF-10A as well as 20 breast cancer samples and normal tissues. Luciferase reporter assay was performed. Lentiviral particles containing miR-381 were used to evaluate the effect of miR-381 restoration on cell proliferation, migration, and invasion of the invasive triple-negative MDA-MB-231 cell line and also in a mouse model of breast cancer. The expression of miR-381 was lower than that of normal cells, especially in TNBC cell line and breast tissues. Luciferase assay results confirmed that miR-381 targets all the predicted 3′-untranslated regions (3′-UTRs). Upon miR-381 overexpression, the expression of target genes declined, and the migration and invasion potential of miR-381-receiving MDA-MB-231 cells decreased. In a mouse model of triple-negative breast cancer, miR-381 re-expression inhibited the invasion of cancer cells to lung and liver and prolonged the survival time of cancer cell-bearing mice. Therefore, miR-381 is a regulator of Wnt signaling and its re-expression provides a potentially effective strategy for inhibition of TNBC.     

Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor-κB translocation, upregulation of nuclear factor erythroid-derived 2(E2)-related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.