The protective effect of bone marrow-derived mesenchymal stem cells in liver ischemia/reperfusion injury via down-regulation of miR-370

Objective(s): Liver transplantation is the most important therapy for end-stage liver disease and ischemia reperfusion (I/R) injury is indeed a risk factor for hepatic failure after grafting. The role of miRNAs in I/R is not completely understood. The aim of this study was to investigate the potential protective role of the mesenchymal stem cells (MSCs) and ischemic preconditioning on miR-370 expression and tissue injury in hepatic I/R injury. Materials and Methods: In this study, 24 BALB/c mice were divided into 4 groups, including sham, I/R, I/R mouse that received MSCs (I/R+MSC) and ischemia preconditioning (IPC) The expression levels of hepatic miR-370, Bcl2 and BAX in male BALB/c mice in different groups including hepatic I/R, hepatic I/R received MSCs, and hepatic I/R with IPC were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic I/R was investigated by serum liver enzyme analysis and histological examination. Results: The expression of miR-370 was significantly up-regulated in the mice subjected to hepatic I/R injury as compared with the sham operated mice. Injection of MSCs led to the down-regulation of the serum liver enzymes, expression of miR-370 and BAX, up-regulation of Bcl2 as well as the improvement of hepatic histological damage. IPC led to similar results, but the difference was not significant. Conclusion: Our data suggest that miR-370 affected the Blc2/BAX pathway in hepatic I/R injury, and down- regulation of miR-370 by BM-MSCs efficiently attenuated the liver damage

The Effect of Mesenchymal Stem Cells on the Expression of IDOand Qa2 Molecules in Dendritic Cells

Purpose: Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immunecells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibitionof DCs is still unknown. In this study, the effect of mesenchymal cells on the expression ofindoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated.Methods: MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/cmice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides(LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigatedin DCs that were treated with MSCs.Results: The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did notsignificantly differ from the control group. The expression of IDO protein in DCs that were coculturedwith MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although theywere not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS wasincreased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively).Conclusion: Our results denied the possibility that MSCs led to the induction of tolerogenic DCsby increasing the expression of the IDO and Qa2 immunomodulatory molecules

Investigation of nitrate and nitrite concentration and other physicochemical parameters of drinking water sources in Saveh city during the year of 2018

Abstract   Background and Purpose:Qualitative parameters of drinking water such as concentration of nitrate, nitrite, sulfate, total soluble solids, sodium, magnesium, fluoride, total hardness and electrical conductivity can play an important role in groundwater resources and are mainly related to agriculture, waste disposal areas and sewage. The aim of this study was to determine these parameters in drinking groundwater resource of Saveh city using Geographic Information System during the year of 2018 and investigation of contaminant’s in the region’s aquifer. Materials and Methods:This research is a descriptive-analytic study. 120 samples of water from 12 drinking water wells were prepared in spring and two times in the morning and afternoon in different parts of the city of Saveh. The quality parameters of drinking water, including concentration of nitrate, nitrite, sulfate, total soluble solids, sodium, magnesium, fluoride, total hardness and electrical conductivity were entered into the GIS software and stored in a database and then processed by the information system software, color mapping was prepared and geographical maps (GIS) were mapped to qualitative status. Also, reverse interpolation was used to estimate the conditions of the whole region. Findings:The average concentration of chlorine, sulfate, electrical conductivity, total soluble solids, total hardness and sodium exceeds the permissible limits, and the non-qualitative water conditions are quite evident. Also, the amount of two magnesium and sulfate ions was above the standard 1053. It should be kept in mind that the high levels of these two ions can interfere with the digestive system. Fluoride and nitrate levels were also acceptable range in all areas. Conclusion:The highest deviation level from 1053 standard was for total soluble solids, sodium, magnesium, and sulfate. It is better to consider a comprehensive program to solve the problem, including use of nanotechnology, filtering or ion exchange

The Effect of Mesenchymal Stem Cells Derived-Conditioned Media in Combination with Oral Anti-Androgenic Drugs on Male Pattern Baldness: An Animal Study

Objective: Androgenetic alopecia (AGA) is a prevalent form of hair loss, mainly caused by follicular sensitivity toandrogens. Despite developing different anti-androgen treatment options, the success rate of these treatments hasbeen limited. Using animal models, this study evaluated the therapeutic effects of umbilical cord (UC) stem cellconditioned media (CM) combined with oral anti-androgens for hair regeneration.Materials and Methods: In this experimental study, Poloxamer 407 (P407) was used as a drug carrier forsubcutaneous testosterone injection. AGA models were treated with oral finasteride, oral flutamide, and CMinjections. Samples were thoroughly evaluated and compared using histological, stereological, and molecularanalyses.Results: Injecting CM-loaded hydrogel alone or combined with oral intake of anti-androgens improved hair regeneration.These treatments could promote hair growth by inducing hair follicles in the anagen stage and shortening the telogenand catagen phases. Furthermore, the combination treatment led to an upregulation of hair induction gene expressionwith a downregulation of inflammation genes.Conclusion: Through a reduction in inflammation, injection of CM-loaded hydrogel alone or combined with oral intakeof anti-androgens induces the hair cell cycle with regeneration in damaged follicles. Hence, this could be a promisingtherapeutic method for AGA patients

Thiol-reducing agents abate cholestasis-induced lung inflammation, oxidative stress, and histopathological alterations

Cholestasis is not only influences the hepatic function but also damages many other organs. Lung injury is a critical secondary organ damage associated with cholestasis/cirrhosis. Pulmonary histopathological alterations, respiratory distress, and hypoxia are related to cholestasis/cirrhosis-induced lung injury. It has been found that oxidative stress plays a crucial role in this complication. The current study was designed to investigate the effect of N-acetyl cysteine (NAC) and dithiothreitol (DTT) as thiol-reducing and antioxidant agents against cholestasis-induced lung injury. Bile duct ligated (BDL) rats were monitored for the presence of inflammatory cells, TNF-α, and IgG levels in their broncho-alveolar fluid (BALF) at scheduled time intervals (3, 7, 14, and 28 days post-BDL surgery). These markers reached their highest level in the BALF of BDL rats on day 28 after the surgery. Therefore, in another set of experiments, the BDL animals were treated with NAC (100 and 300 mg/kg/day, i.p, for 28 consecutive days) and DTT (10 and 20 mg/kg/day, i.p, for 28 consecutive days). Meanwhile, a significant increase in the levels of TNF-α and IgG was detected in the BALF of BDL rats. The BALF level of neutrophils, monocytes, and lymphocytes was also significantly increased in cholestatic animals. A significant increase in lung tissue biomarkers of oxidative stress was detected in the BDL rats. It was found that NAC and DTT could significantly blunt pulmonary damage induced by cholestasis. The effects of these agents on oxidative stress biomarkers and inflammatory response seem to play a pivotal role in their mechanisms of protective properties

Lignin monomer production integrated into the γ-valerolactone sugar platform

We demonstrate an experimental approach for upgrading lignin that has been isolated from corn stover via biomass fractionation using c-valerolactone (GVL) as a solvent. This GVL-based approach can be used in parallel with lignin upgrading to produce soluble carbohydrates at high yields (>= 70%) from biomass without the use of enzymes, ionic liquids, or concentrated acids. The lignin was isolated after an initial hydrolysis step in which corn stover was treated in a high-solids batch reactor at 393 K for 30 min in a solvent mixture consisting of 80 wt% GVL and 20 wt% water. Lignin was isolated by precipitation in water and characterized by 2D HSQC NMR, showing that the extracted lignin was similar to native lignin, which can be attributed to the low acid level and the low extraction temperatures that are achievable using GVL as a solvent. This lignin was upgraded using a two-stage hydrogenolysis process over a Ru/C catalyst. The isolated lignin was first dissolved to form a mixture of 10% lignin, 80% THF, 8.5% H3PO4 and 1.5% H2O, and treated at 423 K under hydrogen. The THF was removed by evaporation and replaced with heptane, forming a biphasic mixture. This mixture was then treated at 523 K in the presence of Ru/C and H-2. The resulting heptane phase contained soluble lignin-derived monomers corresponding to 38% of the carbon in the original lignin. By adding 5% methanol during the second catalytic step, we produced additional monomers containing methyl esters and increased carbon yields to 48%. This increase in yield can be attributed to stabilization of carboxylic acid intermediates by esterification. The yield reported here is comparable to yields obtained with native lignin and is much higher than yields obtained with lignin isolated by other processes. These results suggest that GVL-based biomass fractionation could facilitate the integrated conversion of all three biomass fractions