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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.

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 6 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 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 .

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.

Fibulin-2 (FBLN2) is a secreted extracellular matrix glycoprotein which has been associated with tissue development and remodelling. In the mouse mammary gland, FBLN2 can be detected during ductal morphogenesis in cap cells and myoepithelial cells at puberty and early pregnancy, respectively. In an attempt to assign its function, we knocked down Fbln2 in the mouse mammary epithelial cell line EpH4. FBLN2 reduction led to an increase in the size of spheroidal structures when compared to scrambled control shRNA-transduced cells plated on Matrigel matrix. This phenotype was associated with a disruption of the collagen IV sheath around the epithelial spheroids and downregulation of integrin β1, suggesting a role for FBLN2 in stabilizing the basement membrane (BM). In contrast to mice, in normal adult human breast tissue, FBLN2 was detected in ductal stroma, and in the interlobular stroma, but was not detectable within the lobular regions. In tissue sections of 65 breast cancers FBLN2 staining was lost around malignant cells with retained staining in the neighbouring histologically normal tissue margins. These results are consistent with a role of FBLN2 in mammary epithelial BM stability, and that its down-regulation in breast cancer is associated with loss of the BM and early invasion.

Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

Background Lactobacillus plantarum ( L. plantarum ) is widely acknowledged for its ability to inhibit the proliferation of various cancer cells, including those associated with hepatocellular carcinoma (HCC). This study aimed to explore the anticancer effects of an extract from a newly isolated strain of L. plantarum on HCC using HepG2 cells. Its effects were also compared with normal Vero cells to assess selectivity. The investigation included a comparison of the impacts of bacterial cell pellets and their supernatant, with cisplatin serving as a reference chemotherapy drug. Results The findings revealed that the L. plantarum supernatant exhibited a notably lower IC50 value, indicating greater potency compared to both the bacterial cell pellets and cisplatin. Flow cytometry analysis showed that the supernatant caused cell cycle arrest at the G2/M phase and promoted apoptosis in HepG2 cells. Furthermore, the supernatant significantly altered the expression of key genes involved in HCC progression. It upregulated the tumor suppressor gene p53, enhancing apoptotic activity and potentially inhibiting tumor growth. Additionally, it reduced the expression of VEGFR2, a key factor in angiogenesis, and IL-17, which is associated with inflammation, highlighting its multifaceted anticancer potential. Conclusion This study underscores the potential of the newly isolated L. plantarum strain's supernatant in managing HCC by promoting tumor suppression, inhibiting angiogenesis, and reducing inflammatory responses. These promising results indicate its potential as a supplementary treatment option for HCC. Nevertheless, further research, particularly in vivo studies, is essential to confirm its therapeutic application and safety in clinical settings.

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.

Background The triacylglycerols in milk fat determine the physical and functional properties of dairy products rich in milk fat. Therefore, understanding the variability of genes related to fat synthesis is important for food production. We investigated the effect of diacylglycerol O-acyltransferase 1 (DGAT1) gene polymorphism on milk production parameters of the Zaraibi goat. Milk components were estimated by infrared spectroscopy. Moreover, Restriction Fragment Length Polymorphisms (RFLP) were used to detect genetic variants in DGAT1 genes. The amplified products were sequenced and aligned to the caprine reference sequence of this gene. Results Two alleles (T and C) were identified in Zaraibi goats. The T allele resulted in one silent mutation while the C allele specified two-point mutations: one was located within a non-coding region (T703C) and the other (T713C) causing a Ile → Thr substitution in the deduced amino acid sequence. Moreover, the DGAT1 polymorphism significantly ( p < 0.05) affected total solid content of milk, wherein harboring CC genotype had significantly higher amount of total solid than those with TC genotype. Milk contents and yields did not differ significantly between goats with CC and TC genotype. Conclusion These results advance our understanding of the genetic architecture of Zaraibi milk composition and will help to improve the management and breeding program of the Egyptian dairy goat. Graphical Abstract

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 .