Therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been reported in several animal models of liver fibrosis. Interleukin (IL) 17A, IL6 and Stat3 have been described to ...play crucial roles in chronic liver injury. However, the modulatory effect of MSCs on these markers was controversial in different diseases. BM-MSCs might activate the IL6/STAT3 signaling pathway and promote cell invasion in hepatocellular carcinoma, but the immunomodulatory role of BM-MSCs on IL17A/IL6/STAT3 was not fully elucidated in liver fibrosis. In the present study, we evaluated the capacity of the BM-MSCs in the modulation of cytokines milieu and signal transducers, based on unique inflammatory genes Il17a and Il17f and their receptors Il17rc and their effect on the IL6/STAT3 pathway in CCl4-induced liver fibrosis in rats. A single dose of BM-MSCs was administered to the group with induced liver fibrosis, and the genes and proteins of interest were evaluated along six weeks after treatment. Our results showed a significant downregulation of Il17a, Il17ra, il17f and Il17rc genes. In accordance, BM-MSCs administration declined IL17, IL2 and IL6 serum proteins and downregulated IL17A and IL17RA proteins in liver tissue. Interestingly, BM-MSCs downregulated both Stat3 mRNA expression and p-STAT3, while Stat5a gene was downregulated and p-STAT5 protein was elevated. Also P-SMAD3 and TGFβR2 proteins were downregulated in response to BM-MSCs treatment. Collectively, we suggest that BM-MSCs might play an immunomodulatory role in the treatment of liver fibrosis through downregulation of IL17A affecting IL6/STAT3 signaling pathway.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Prediction of the dry-band arcing is a key point to identification of pre-flashover conditions in polluted insulators.•Wavelet transform can be used to obtain the dynamic behavior characteristics of ...leakage current of the polluted insulators.•A risk assessment approach can be used to predict dry-band arcing and flashover based on wavelet transform.•Development of the proposed method based on risk assessment can be used for online-monitoring of contaminated insulators.
In this paper, a novel approach for risk assessment of the outdoor polluted insulators is presented to predict dry band-arcing and flashover. Risk evaluation of the dry-band arcing and flashover are represented using leakage current (LC) behavior in order to understand pollution behavior of the pre-flashover conditions. Critical indexes of the dry-band arcing and flashover are extracted based on the presented risk assessment model using wavelet transform (WT). Then, the developed critical indexes are used for prediction of the operation risk of the composite insulators. In addition, the occurrence probabilities of the dry band arcing and flashover are calculated based on the analysis of critical indexes. Several sensitivity parameters including pollution level, wetting rate and geometry specification are considered in the presented model. Validation results show that risk of the insulator's service can be correlated to the represented critical indexes. The proposed approach can be adopted as an online monitoring tool in order to avoid pollution flashover of the outdoor insulators.
•A new partial discharge locating method based on using the frequency response assurance criterion (FRAC) has been proposed to estimate the PD location precisely.•A least means square (LMS) adaptive ...filter has been utilized to reduce the noise effects on estimating the PD location.•The method is applicable to any unknown transformer when PD propagation along the windings is obtained by simulating the winding and the PD pulses.
Transformers are one of the essential and costly pieces of equipment in power grids. Monitoring and detecting insulation faults in transformers at the shortest time helps prevent catastrophic failures. Partial discharge (PD) is one of the most significant insulation failures in power transformers. Due to the complex structures of the windings, the accurate location of a PD source is very difficult to determine. In this paper, a technique based on a frequency response assurance criterion (FRAC) is proposed to determine the location of a PD source in a transformer winding. The responses of the winding to the proposed Heidler function injected in parallel to all sections of the winding are considered as PD reference signals. Moreover, the winding responses of any arbitrary PD pulses applied along the various sections of the winding, are considered as PD test signals. The maximum FRAC value between the reference signals and test signal specifies the location of the PD source. The simulation case studies clarify the superior performance of the proposed method. A least mean square (LMS) adaptive filter is suggested to minimize background noise effects and increase the accuracy of the method. Finally, the proposed method is validated with a laboratory winding.
The Egyptian spiny mouse, Acomys cahirinus, is a recently described model organism for regeneration studies. It has surprising powers of regeneration with relatively fast repairing mechanisms and ...reduced inflammation form compared to other mammals. Although several studies have documented the exceptional capabilities of Acomys to regenerate different tissues after injury, its response to different cellular and genetic stresses is not yet investigated. Therefore, the current study aimed to investigate Acomys abilities to resist genotoxicity, oxidative stress and inflammation induced by acute and subacute treatments with lead acetate. Responses of Acomys were compared with those of the lab mouse (Mus musculus), which displays signatures of the "typical" mammalian response to various stressors. Cellular and genetic stresses were induced by using acute and subacute doses of Lead acetate (400 mg/kg and 50 mg/kg for 5 days, respectively). The assessment of genotoxicity was carried out by using comet assay, while oxidative stress was evaluated by measuring the biomarkers; MDA, GSH and antioxidant enzymes CAT and SOD. Moreover, inflammation was assessed by analyzing the expression of some inflammatory-regeneration-related genes: CXCL1, IL1-β, and Notch 2 and immunohistochemical staining of TNF-α protein in brain tissue, in addition to histopathological examination of brain, liver, and kidneys. The obtained results revealed a unique resistance potency of Acomys to genotoxicity, oxidative stress, and inflammation in certain tissues in comparison to Mus. Altogether, the results revealed an adaptive and protective response to cellular and genetic stresses in Acomys.
In this article, a novel dynamic approach is proposed to analyze pollution layer resistance of polymer insulators. One of the main challenges in dynamic modeling of pollution layer resistance is the ...effects of pollution layer conduction and pollution layer thickness on discharge length due to change in pollution layer thickness and wetting rate in real outdoor conditions. The represented approach investigates the effects of such parameters on variation of discharge length. Then, an artificial intelligence (AI) algorithm based on artificial neural network (ANN) is developed to predict flashover voltage (FOV) of polluted insulators according to the prediction of critical discharge length. Calculations are done based on experimental data of leakage current (LC) and voltage of insulators in different pollution conditions. Obtained results by the proposed approach show a close correlation with experimental results. In addition, various validation tests are performed to investigate the effects of hydrophobicity class (HC) of polymeric surface and pollution type on the quality of the represented analysis. Results of the validation also show a close correlation between calculations and real data.
Despite the high antioxidant and penetration ability of pomegranate seed oil (PSO), the in vivo antitumor activity of PSO nano-emulsion has not been well investigated. Therefore, this study was ...undertaken to estimate the antitumor activity and safety of PSO nano-emulsion in mice bearing Ehrlich solid carcinoma cells. For tumor inoculation, about 2 × 10
viable Ehrlich tumor cells (200 µl) were implanted intramuscularly in the left thigh of hind leg. Once a solid tumor appears on the 10th day of transplantation; the mice were randomly divided into five groups (5 animals/group). Characterization of the PSO nano-emulsion using a Zeta sizer Malvern instrument and transmission electron microscope (TEM) revealed that the PSO nano-droplets were well dispersed with an average particle size of 8.95 nm and a spherical shape. Treatment with PSO nano-emulsions caused a significant reduction in the tumor size and weight, in a dose dependent manner, compared to tumor control group. Marked dose dependent elevations in the DNA damage level together with significant increases in the tumor suppressor p53, Bax and Caspase genes and reductions in the anti-apoptotic Bcl2 gene were also observed in the tumor tissue of mice given PSO nano-emulsions. Histological examination also revealed apoptosis and necrosis of tumor cells and tumor infiltration with inflammatory cells after PSO nano-emulsion treatment. However, high DNA damage was noticed in the liver and kidney tissues of mice given the highest dose of PSO nano-emulsion (400 mg/kg). Therefore, we concluded that PSO nano-emulsion exhibited a potent antitumor activity through induction of DNA breaks that triggers apoptosis of tumor cells but the highest dose caused genotoxicity to liver and kidney tissues, thus it is recommended to use doses lower than 400 mg/kg of PSO nano-emulsion as an alternative drugs for chemotherapy.
The rapidly growing interest in using graphene-based nanoparticles in a wide range of applications increases human exposure and risk. However, very few studies have investigated the genotoxicity and ...mutagenicity of the widely used graphene oxide (GO) nanoparticles in vivo. Consequently, this study estimated the possible genotoxicity and mutagenicity of GO nanoparticles as well as possible oxidative stress induction in the mice liver and brain tissues. Nano-GO particles administration at the dose levels of 10, 20, or 40 mg/kg for one or five consecutive days significantly increased the DNA breakages in a dose-dependent manner that disrupts the genetic material and causes genomic instability. GO nanoparticles also induced mutations in the p53 (exons 6&7) and presenilin (exon 5) genes as well as increasing the expression of p53 protein. Positive p53 reaction in the liver (hepatic parenchyma) and brain (cerebrum, cerebellum, and hippocampus) sections showed significant increase of p53 immunostaining. Additionally, induction of oxidative stress was proven by the significant dose-dependent increases in the malondialdehyde level and reductions in both the level of reduced glutathione and activity of glutathione peroxidase observed in GO nanoparticles administered groups. Acute and subacute oral administration of GO nanoparticles induced genomic instability and mutagenicity by induction of oxidative stress in the mice liver and brain tissues.
Several in vitro studies have revealed that zinc oxide nanoparticles (ZnO-NPs) were able to target cancerous cells selectively with minimal damage to healthy cells.
In the current study, we aimed to ...evaluate the antitumor activity of ZnO-NPs in Ehrlich solid carcinoma (ESC) bearing mice by measuring their effect on the expression levels of
and
genes as indicators of apoptotic induction in tumor tissues. Also, we assessed the potential ameliorative or potentiation effect of 100 mg/kg N-acetyl cysteine (NAC) in combination with ZnO-NPs.
ESC bearing mice were gavaged with three different doses of ZnO-NPs (50, 300 and 500 mg/kg body weight) alone or in combination with NAC for seven consecutive days. In addition to measuring the tumor size, pathological changes, zinc content, oxidative stress biomarkers and DNA damage in ESC, normal muscle, liver and kidney tissues were assessed.
Data revealed a significant reduction in tumor size with a significant increase in
and
and decrease in
expression levels in the tissues of ZnO-NPs treated ESC bearing mice. Moreover, a significant elevation of MDA accompanied with a significant reduction of CAT and GST. Also, a marked increase in all comet assay parameters was detected in ZnO-NPs treated groups. On the other hand, the combined treatment with ZnO-NPs and NAC significantly reduced reactive oxygen species production and DNA damage in liver and kidney tissues in all ZnO-NPs treated groups.
ZnO-NPs exhibited a promising anticancer efficacy in ESC, this could serve as a foundation for developing new cancer therapeutics. Meanwhile, the combined treatment with ZnO-NPs and NAC could act as a protective method for the healthy normal tissue against ZnO-NPs toxicity, without affecting its antitumor activity.
The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks ...including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.
The Egyptian spiny mouse, Acomyscahirinus, is a recently described model organism for regeneration studies. It has surprising powers of regeneration with relatively fast repairing mechanisms and ...reduced inflammation form compared to other mammals. Although several studies have documented the exceptional capabilities of Acomys to regenerate different tissues after injury, its response to different cellular and genetic stresses is not yet investigated. Therefore, the current study aimed to investigate Acomys abilities to resist genotoxicity, oxidative stress and inflammation induced by acute and subacute treatments with lead acetate. Responses of Acomys were compared with those of the lab mouse (Musmusculus), which displays signatures of the “typical” mammalian response to various stressors. Cellular and genetic stresses were induced by using acute and subacute doses of Lead acetate (400 mg/kg and 50 mg/kg for 5 days, respectively). The assessment of genotoxicity was carried out by using comet assay, while oxidative stress was evaluated by measuring the biomarkers; MDA, GSH and antioxidant enzymes CAT and SOD. Moreover, inflammation was assessed by analyzing the expression of some inflammatory-regeneration-related genes: CXCL1, IL1-β, and Notch2 and immunohistochemical staining of TNF-α protein in brain tissue, in addition to histopathological examination of brain, liver, and kidneys. The obtained results revealed a unique resistance potency of Acomys to genotoxicity, oxidative stress, and inflammation in certain tissues in comparison to Mus. Altogether, the results revealed an adaptive and protective response to cellular and genetic stresses in Acomys.
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