Neurochemical Ameliorating of the Hippocampus in Dyslipidemic Alzheimer Patients Following Silymarin; a Double-Blind Placebo-Controlled Randomized Clinical Trial.

Background: Amyloid-beta (Aß) production is a normal physiological process, and an imbalance in Aß production/excretion rate is the basis of the plaque load increase in AD. LRP1 is involved in both central clearance of Aß from the CNS and transport of Aß toward peripheral organs. In this study, the effect of silymarin combination compared to rosuvastatin and placebo on neuro-metabolites and serum levels of LRP1 and Aß1-42 proteins and oxidative stress enzymes and lipid and cognitive tests of Iranian AD patients. Methods: In this double-blind placebo-controlled study, thirty-six mild AD patients were divided into groups (n=12) of silymarin 140mg, placebo, and rosuvastatin 10mg. Medications were administered 3 times a day for 6 months. Clinical tests, lipid profile (TG, HDL, TC, and LDL), Aß1-42, and LRP1 markers were measured at the beginning and end of the intervention. Magnetic resonance spectroscopy (MRS) was used to measure metabolites. Using SPSS software a one-way ANOVA test was used to compare the means of the quantitative variables and Pearson and Spearman's correlations to measure the correlation. GraphPad Prism software was used for drawing graphs. P < 0.05 was considered a significant. Results: The levels of LRP1 and Aß1-42 in the silymarin group were significantly increased compared to the other groups (P < 0.05). NAA/mI in the silymarin group had a significant increase compared to both placebo and rosuvastatin groups (P < 0.05). Right and left hippocampal mI/Cr directly correlated with TG (r = 0.603, P = 0.003 and r = 0.595, P = 0.004, respectively). NAA/Cr of the right and left hippocampus was inversely related to TG (r = -0.511, P = 0.0033, and r = -0.532, P = 0.0021, respectively). NAA/Cr and NAA/mI of bilateral hippocampi directly correlated with HDL (P < 0.05). An inverse correlation was observed between the Aß1-42 and mI/Cr of the right and left hippocampus (r = -0.661, P = 0.000 and r = -0.638, P = 0.000, respectively). Conclusion: Donepezil and silymarin improved lipid profile associated with increased NAA/Cr, and decreased mI/Cr, in AD patients. Biomarker NAA/mI can be clinically significant in examining AD pathology. Measurement of the lipid factors and neurometabolites can be a suitable method for monitoring this disease.

Nonlinear optical response of cancer cells following conventional and nano-technology based treatment strategies: Results of chemo-, thermo- and radiation therapies.

BACKGROUND: Although traditional treatments are able to increase cancer survival rate, undesirable impact on off-target tissues are considered a limitation of these approaches. Nanotechnology-based treatments have been proposed as a possible option to enhance targeting., Further,current methods for evaluating cellular damage, are time consuming, highly dependent on the operator skills, and expensive. The aim of this study was to evaluate the capability of nonlinear optical response of cells to determine cellular damages during conventional and nano-technology based treatments. METHODS: Three different cancer cell lines, CT26, KB, and MCF-7 were used in this study. The alginate hydrogel co-loaded with cisplatin and Au nanoparticle (ACA) nanocomplex and gold-coated iron oxide nanoparticle (Au@IONP) were considered for chemo- and chemo-photothermal therapies, and thermo-radiation therapy, respectively. The sign and value of nonlinear optical absorption coefficient and imaginary part of the third-order nonlinear susceptibility of cells were computed. MTT assay was utilized as a reference method. RESULTS: The value of nonlinear optical indices increased with increasing cellular damage and cell death. The linear regression analysis indicated high correlation between nonlinear optical indices and MTT results, in all treatments. CONCLUSION: The nonlinear optical indices are robust from confounding factors, namely treatment approach (traditional and nano-technology based), treatment modality (chemotherapy, thermotherapy, photothermal therapy, and radiation therapy), and cell types. Nonlinear optical properties of cells can be used as a rapid estimation method for cell damage, at the nanoscale level.

Magneto-plasmonic nanoparticle mediated thermo-radiotherapy significantly affects the nonlinear optical properties of treated cancer cells.

In order to determine the level of cell damage in cancerous cells, current cytogenetic tests have limitations such as time consumption and high cost. The aim of this study was to demonstrate the ability of nonlinear refractive (NLR) index as a predictor of breast cell damage caused by magneto-plasmonic nanoparticle based thermo-radiotherapy treatments. MCF-7 breast cancer cells were subjected individually to the treatment of radiation, radio-frequency (RF) hyperthermia, and radiation + RF hyperthermia. These treatments were repeated in the presence of magneto-plasmonic nanoparticle (Au@IONP). The MTT and nonlinear optical assays were used to evaluate the damage induced by different treatment modalities. The results of MTT were correlated with Z-scan, as the magnitude of nonlinear refraction increased with higher intensity of induced cell damages. In this regard, the lowest cell viability (38 %,) and highest magnitude of NLR index (+28.12) were obtained from combination of radiation (at 4 Gy dose) and hyperthermia treatment in the presence of nanoparticles. The proposed optical index (NLR) indicated high capability and can be used as an auxiliary tool to monitor induced cell damage during different treatment strategies. This technique is fast, noninvasive, does not impose cost, and finally does not waste materials.

Repair of Critical-Sized Rat Calvarial Defects With Three-Dimensional Hydroxyapatite-Gelatin Scaffolds and Bone Marrow Stromal Stem Cells.

INTRODUCTION: The repair of critical-sized defects (CSDs) are one of the most challenging orthopedic problems and the attempts for development of an ideal scaffold for treatment of large bone defect are ongoing. AIM: The aim of this study was the effectiveness of hydroxyapatite-gelatin seeded with bone marrow stromal cells construct for healing of critical-sized bone defect in vivo. MATERIAL AND METHODS: In this experimental study, the bone marrow stromal cells (BMSCs) were isolated by flushing method. For in vitro study, the cells were seeded on the scaffold and the cell viability as well as cytotoxicity were tested by MTT and LDH specific activity. The scaffold-cell construct was implanted into the critical-sized bone defect created in calvaria of Wistar male rats.15 rats were randomly divided into 3 groups (n=5), group 1 (control group): Injury without transplantation, group 2: implanted with hydroxyapatite-gelatin scaffold, group 3: hydroxyapatite-gelatin scaffold seeded with BMSCs. At different days post-implantation, the implanted site was collected and the bone healing was evaluated through H&E and Masson's Trichrome staining. ANOVA and paired t-test were used for data comparison and P<0.05 was considered significant. RESULTS: The results of MTT showed that the scaffold has no toxic effects on stromal cells. The first signs of ossification in hydroxyapatite-gelatin with BMSCs cells group appeared in the first week. However, in the fourth week, ossification was completed and the scaffold remaining was found as embedded islands in the spongy bone tissue. The greatest number of lymphocytes in the experimental group was observed after one week of planting scaffold. CONCLUSION: Hydroxyapatite-gelatin scaffold coated with BMSCs cells has a potential role in the healing process of bone and would be a possible new therapeutic strategy to repair extensive bone lesions.