Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds for inhibiting the progression of liver fibrosis. In the present study, the simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl) and therapeutics (Nilotinib, Losartan, and combination therapy). In the end, serum parameters of the liver and gene expression analysis of transforming growth factor-β, its receptors (TβRII), platelet-derived growth factor, its receptors (PDGFR), matrix metalloproteinases (MMP-2 and MMP-9), tumor necrosis factor-α, cytochrome P450 2E1, and collagen1 type 1 were performed. The oxidant/antioxidant factors were also analyzed. Histopathology analysis along with α-SMA immunohistochemistry and hydroxyproline evaluation was also conducted for a more in-depth study. The overall results indicated a better therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the treatment of each of them alone. Interestingly, some gene and protein factors and fibrotic indices were reduced even to the normal levels of the control group. The results of this study suggest that co-administration of these two combinations, strengthens their anti-fibrotic properties and, due to the routine use of these compounds against AML and blood pressure, these compounds can be used with caution against human liver fibrosis.
The application of Tarkhineh texture to protect probiotics in potato chips has been investigated as the main goal in this paper. In this study, the probiotic assessments, morphological characteristics, sensory evaluation, and survival rates of the covered probiotic cells with Tarkhineh in potato chips during storage time were assessed. Based on results, T34 isolated from traditional Tarkhineh as a safe strain had a high tolerance to low pH and bile salt conditions, displayed acceptable anti-pathogenic activities, and also showed desirable antibiotic susceptibility. Two types of Tarkhineh formulations (plain Tarkhineh and turmeric Tarkhineh) were applied using a simple spraying method for covering T34 cells in potato chips. All formulations showed elliptical to spherical (480-770 μm) shape probiotic drops. Storage stability results revealed that T34 cells mixed with turmeric and plain Tarkhineh during 4 months of storage at 4°C displayed excellent protection abilities with about 3.70 and 2.85 log decreases in CFU/g respectively. Additionally, probiotic potato chips compared to non-probiotic and commercial potato chips, exhibited probiotic product criteria such as excellent quality and superior sensory properties during storage time. In conclusion, Tarkhineh showed high potential as a protective matrix for probiotic cells in potato chips.
Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca play important roles in different stages of this process. Because of the complicated roles of Ca in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca or 1.8 mM Ca plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca and in particular Ca plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.
This study comparatively investigated the effectiveness of calcium and other well-known inducers such as isobutylmethylxanthine (IBMX) and insulin in differentiating human adipose-derived stem cells (ADSCs) into neuronal-like cells. ADSCs were immunophenotyped and differentiated into neuron-like cells with different combinations of calcium, IBMX, and insulin. Calcium mobilization across the membrane was determined. Differentiated cells were characterized by cell cycle profiling, staining of Nissl bodies, detecting the gene expression level of markers such as neuronal nuclear antigen (NeuN), microtubule associated protein 2 (MAP2), neuron-specific enolase (NSE), doublecortin, synapsin I, glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) by quantitative real-time polymerase chain reaction (quantitative real-time polymerase chain reaction (qRT-PCR) and protein level by the immunofluorescence technique. Treatment with Ca + IBMX + Ins induced neuronal appearance and projection of neurite-like processes in the cells, accompanied with inhibition of proliferation and halt in the cell cycle. A significantly higher expression of MBP, GFAP, NeuN, NSE, synapsin 1, doublecortin, and MAP2 was detected in differentiated cells, confirming the advantages of Ca + IBMX + Ins to the other combinations of inducers. Here, we showed an efficient protocol for neuronal differentiation of ADSCs, and calcium fostered differentiation by augmenting the number of neuron-like cells and instantaneous increase in the expression of neuronal markers.
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