Silica Magnetic Graphene Oxide Improves the Effects of Stem Cell-Conditioned Medium on Acute Liver Failure.

OBJECTIVE: Acute liver failure (ALF) is usually associated with inflammation and oxidation of hepatocytes and has high mortality and resource costs. Although mesenchymal stem cell-conditioned medium (MSC-CM) has therapeutic effects similar to MSC transplant in treating liver failure, it may not increase survival. On the other hand, graphene-based nanostructures have been proven useful in biomedicine. In this study, we investigated whether silica magnetic graphene oxide (SMGO) improved the effects of MSC-CM in protecting hepatocytes and stimulating the regeneration of damaged liver cells. MATERIALS AND METHODS: To provide a rat model of ALF, male rats were injected intraperitoneally with carbon tetrachloride (CCl4). The rats were randomly divided into six groups, namely control, sham, CCl4, MSC-CM, SMGO, and MSC-CM + SMGO. In the experimental groups, the rats received, depending on the group, 2 mL/kg body weight CCl4 and either MSC-CM with 5 × 106 MSCs or 300 µg/kg body weight SMGO or both. Symptoms of ALF appeared 4 days after the injection. All groups were compared and analyzed both histologically and biochemically 4 days after the injection. RESULTS: The results indicated that the use of SMGO enhanced the effect of MSC-CM in reducing necrosis, inflammation, aspartate transaminase, alanine aminotransferase, and alkaline phosphatase in the CCl4-induced liver failure of the rat model. Also, the expression of vascular endothelial growth factor and matrix metalloproteinase-9 (MMP-9) was significantly upregulated after treatment with SMGO. CONCLUSION: SMGO improved the hepatoprotective effects of MSC-CM on acute liver damage, probably by suppressing necrosis, apoptosis, and inflammation of hepatocytes.

Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells.

Metformin is commonly prescribed as a hypoglycemic agent following the onset of type 2 diabetes mellitus. This study aimed to investigate pro- and/or anti-angiogenic effects of Metformin on human bone marrow mesenchymal stem cells. Cells were incubated with different doses of Metformin including 0.5, 1, 10, 50, 100, 200 and 500 µM for 14 days. Cell viability and total fatty acids profile were examined by MTT and gas chromatography methods. Differentiation of cells to endothelial lineage was studied by monitoring the expression of VEGFR-2 and Tie-2 receptors and VE-cadherin via real-time PCR and western blotting. Angiogenic potential and migration of cells were assessed by tubulogenesis and Transwell migration assays. PCR array was performed to analyze mTOR signaling. CD133+ and VEGFR-2+ cells were detected in blood samples of non-diabetic control, diabetic subjects and diabetics received Metformin. Metformin dose-dependently reduced cell survival. Decreased content of palmitate and oleate coincided increased level of stearate, palmitoleate, and linoleate (p < 0.05). Metformin decreased the angiogenic potential of cells by decreasing VEGFR-2 and Tie-2 expression (p < 0.05). The protein level of VE-cadherin decreased in cells received Metformin. Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p < 0.05). Non-significant differences were observed regarding the number of CD133 and VEGFR-2 cells in blood samples (p > 0.05). These data support a notion that Metformin could blunt the angiogenic behavior of human mesenchymal stem cells by modulating mTOR signaling pathway.

Survey of the Antibiofilm and Antimicrobial Effects of Zingiber officinale (in Vitro Study).

BACKGROUND: Candidiasis is one of the most prevalent and important opportunistic fungal infections of the oral cavity caused by Candida yeast species like Candida albicans, C. glabrata, and C. krusei. In addition, several bacteria can cause oral infections. The inhibition of microbial biofilm is the best way to prevent oral infections. OBJECTIVES: The aim of the present study is to evaluate the antifungal, antimicrobial, and anti-biofilm properties of ginger (Zingiber officinale) extract against Candida species and some bacterial pathogens and the extract's effects on biofilm formation. MATERIALS AND METHODS: Ginger ethanolic extract as a potential mouthwash was used to evaluate its effect against fungi and bacteria using the microdilution method, and biofilm was evaluated using the crystal violet staining method and dead/alive staining. MTT assay was used to evaluate the possible cytotoxicity effects of the extract. RESULTS: The minimum inhibitory concentrations (MICs) of ginger extract for evaluated strains were 40, 40, 20, 20, 20, 20, 10, and 5 mg/mL for Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Bacillus cereus, Acinetobacter baumannii, C. albicans, and C. krusei, respectively. Ginger extract successfully inhibited biofilm formation by A. baumannii, B. cereus, C. krusei, and C. albicans. MTT assay revealed no significant reduction in cell viability after 24 hours. The minimum inhibitory biofilm concentrations (MIBCs) of ginger extract for fungi strains (C. krusei and C. albicans) were greater than those of fluconazole and nystatin (P = 0.000). CONCLUSIONS: The findings of the present study indicate that ginger extract has good antifungal and antibiofilm formation by fungi against C. albicans and C. Krusei. Concentrations between 0.625 mg/mL and 5 mg/mL had the highest antibiofilm and antifungal effects. Perhaps, the use of herbal extracts such as ginger represents a new era for antimicrobial therapy after developing antibiotic resistance in microbes.