Germanium Dioxide Nanoparticles Mitigate Biochemical and Molecular Changes Characterizing Alzheimer's Disease in Rats.

Alzheimer's disease (AD) is a neurodegenerative disorder that jeopardizes the lives of diagnosed patients at late stages. This study aimed to assess, for the first time, the efficiency of germanium dioxide nanoparticles (GeO2NPs) in mitigating AD at the in vivo level compared to cerium dioxide nanoparticles (CeO2NPs). Nanoparticles were synthesized using the co-precipitation method. Their antioxidant activity was tested. For the bio-assessment, rats were randomly assigned into four groups: AD + GeO2NPs, AD + CeO2NPs, AD, and control. Serum and brain tau protein, phosphorylated tau, neurogranin, amyloid ß peptide 1-42, acetylcholinesterase, and monoamine oxidase levels were measured. Brain histopathological evaluation was conducted. Furthermore, nine AD-related microRNAs were quantified. Nanoparticles were spherical with diameters ranging from 12-27 nm. GeO2NPs exhibited a stronger antioxidant activity than CeO2NPs. Serum and tissue analyses revealed the regression of AD biomarkers to almost control values upon treatment using GeO2NPs. Histopathological observations strongly supported the biochemical outcomes. Then, miR-29a-3p was down-regulated in the GeO2NPs-treated group. This pre-clinical study substantiated the scientific evidence favoring the pharmacological application of GeO2NPs and CeO2NPs in AD treatment. Our study is the first report on the efficiency of GeO2NPs in managing AD. Further studies are needed to fully understand their mechanism of action.

Correlation Between Serum Cytokines, Interferons, and Liver Functions in Hepatitis C Virus Patients.

To provide fundamental insights into the mechanism of Hepatitis C virus (HCV), we conduct the present study to improve further understanding of the interaction between HCV and cytokines. Two hundred one patients were enrolled in this study. Seventy-eight patients matching the study group in terms of age and gender with negative serology for hepatitis viruses, HIV virus, and with liver enzyme levels within normal range were selected as the control group. Patients were diagnosed with positive hepatitis C by detection of positive HCV antibodies in serum. Interferon-gamma (IFN-γ) and interleukin (IL)-10 were measured in positive and negative patients. Also liver functions (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyl transferase [GGT], alkaline phosphatase [ALP], urea, total protein, albumin, total and direct bilirubin) were also measured. Our results indicated significant elevation in IL-10 and IFN-γ in positive hepatitis C patients. These elevations were accompanied by significant elevation in liver function biomarkers with significant regression in albumin and total protein content. Furthermore, IFN-γ significantly increased immune response of cellular immunity. IL-10 significantly decreased immune response of cellular immunity by inhibiting IFN-γ and other production of Th. Liver function levels can be used as a marker for HCV. The findings from our study recommend IL-10 pathway in HCV infection and use IFNs to increase immune response for viral hepatitis.

Mesenchymal stem cells: a future experimental exploration for recession of diabetic nephropathy.

BACKGROUND: The progresses made in stem cell therapy offer an innovative approach and exhibit great potential for the repair of damaged organs and tissues. This study was conducted with a view to find the mechanisms responsible for the effectiveness of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the suppression of diabetes and experimentally-induced diabetic nephropathy. METHODS: To realize this objective, diabetic and diabetic nephropathy subject groups that underwent MSC treatment were studied through numerous biochemistry and molecular genetics analyses. RESULTS: The findings show that, relative to the control groups, the rats in the diabetic and diabetic nephropathy groups treated with stem cells infused with BM-MSCs showed a significant reversal in the levels of their insulin, glucose, heme-oxygenase-1 (HO-1) serum, and advanced glycation end product (AGEP). Moreover, BM-MSC therapy was also found to have a definite positive effect on the kidney functions. In addition, it also corresponded with a significant decrease in the availability of certain growth factors, namely the fibroblast growth factor (FGF), the platelet-derived growth factor (PDGF), and the transforming growth factor-ß (TGF-ß). BM-MSC treatment also improved the levels of expression of monocyte chemoatractant-1 (MCP-1) and interleukin-8 (IL-8) genes within kidney tissues. Lastly, the treatment recovered the organizational structure of the kidney and pancreas, a result demonstrated by a histopathological analysis. These results greatly coincide with those obtained through the biochemistry and molecular genetics analyses. CONCLUSION: Treatment using BM-MSCs is determined to be definitely effective in cases of diabetes and diabetic nephropathy.

Current concepts in pathophysiology and management of hepatocellular carcinoma.

Additional approaches to control malignancies are needed due to the emerging trends in the incidence of cancer of different organ sites. Due to the high frequency of hepatocellular carcinoma (HCC) and its poor prognosis, preventing HCC is an urgent priority. To explore the antioxidant and apoptotic pathways of grape seed extract (GSE) we induce HCC experimentally by diethylnitrosoamine (DEN) and treated the animals with low and high doses of GSE. The results indicate good therapeutic possibilities for GSE use in treatment of HCC., This was evidenced via regression of liver enzymes' function (ALT&AST), the HCC markers; α-fucosidase, α-fetoprotein and carcinoembrionic antigen (CEA) in HCC groups treated with the grape seed extract. Also, tumor necrosis factor (TNF-α) showed a significant decrease using GSE in HCC bearing animals. Regarding the apoptotic pathways of GSE, we found a significant down regulation of apoptosis enhancing nuclease (Aen), Bcl2-associated X protein (Bax), B-cell translocation gene 2(Btg2), Cyclin G1 (Ccng1) and Cyclin-dependent kinase inhibitor 1A (Cdkn1a) gene expression in HCC+GSE groups as compared to HCC bearing group. In the same trend, the necrotic/apoptotic rates were significantly higher in the HCC groups treated with GSE vs. the HCC bearing group. Finally, the 8-OHdG/2-dG generation decreased by 73.8% and 52.9% in HCC+GSE at low and high doses, respectively. Based on these encouraging observations, grape seed extract could be a promising natural remedy for attenuating hepatocellular carcinoma that has a great future in approaches directed towards control of HCC.

Characteristics of Immobilized Urease on Grafted Alginate Bead Systems

This study evaluated the biological importance of immobilized urease enzyme over the free urease. The support material used for urease immobilization was alginate. Generally, the immobilization of urease in alginate gel showed a marked increase in Km and Vmax. However, the immobilized urease showed higher thermal stability than that of free enzyme. The rate of thermal inactivation of the immobilized enzyme decreased due to entrapment in gel matrix. Also, the activity of the immobilized urease was more stable in retention than that of the free enzyme during the storage in solution, although the activity of the immobilized enzyme was lower in comparison with the free enzyme. A stable immobilized system and long storage life are convenient for applications that would not be feasible with a soluble enzyme system. These results highlighted the technical and biochemical benefits of immobilized urease over the free enzyme.

Molecular mechanisms of nano-selenium in mitigating hepatocellular carcinoma induced by N-nitrosodiethylamine (NDEA) in rats.

The possible molecular mechanisms of Nano-selenium (nano-se) in attenuating hepatocellular carcinoma (HCC) was investigated in this study. To achieve this target, the apoptotic/necrotic rate in hepatic cells was investigated morphologically by double staining with acridine orange/ethidium bromide to address the type of cell death induced by nano-Se in HCC-bearing rats. To predict the oxidative stress and DNA damage, the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 2-deoxyguanosine (2-dG) was examined. Moreover, the expression of some HCC-related genes was investigated such as aldo-keto reductase 1B10 (Akr1b10), ING3 and Foxp1 genes. As well as the histopathological study of liver tissue sections was performed. The results obtained from this study revealed that (HCC+Nano Se) group shows the highest number of damaged cancerous cells. Furthermore, the necrotic/apoptotic rate was significantly higher in (nano-Se+HCC), (HCC+Doxo) and (HCC+Doxo+nano-se) compared to that in the untreated HCC group. Treatment of HCC group with nano-se decreased the ratio of 8-OHdG/2-dG generation significantly with respect to the untreated HCC group. The opposite was observed regarding the gene expression of AKr1b10 and ING3. The treatment of HCC group with nano-se elicited significant increase in the expression of Akr1b10 and ING3 genes compared with untreated HCC group. On the other hand, the expression of Foxp1 gene was significantly decreased in HCC group treated with nano-se in comparison with the untreated HCC group. The histopathological study provided a supportive evidence for the molecular genetics study. Our data shed light on the molecular mechanisms of nano-se in attenuating HCC in the experimental model.