Glioblastoma multiforme: a glance at advanced therapies based on nanotechnology.

Glioblastoma multiforme (GBM, grade IV) is the most common malignant and invasive central nervous system tumor with poor survival outcome. Various pathogenesis signatures such as genetic mutation, hypoxia, necrosis and neo-angiogenesis are involved in GBM. Standard treatment includes surgical resection along with radiation therapy and temozolomide (TMZ) chemotherapy that do not improve the overall survival of patients. In this review, we focused on the diagnosis, risk factors and novel therapies, using advanced therapies such as nanotechnology in drug delivery, gene therapy and hyperthermia that have promising roles in the treatment of aggressive brain tumors.

CRISPR System: A High-throughput Toolbox for Research and Treatment of Parkinson's Disease.

In recent years, the innovation of gene-editing tools such as the CRISPR/Cas9 system improves the translational gap of treatments mediated by gene therapy. The privileges of CRISPR/Cas9 such as working in living cells and organs candidate this technology for using in research and treatment of the central nervous system (CNS) disorders. Parkinson's disease (PD) is a common, debilitating, neurodegenerative disorder which occurs due to loss of dopaminergic neurons and is associated with progressive motor dysfunction. Knowledge about the pathophysiological basis of PD has altered the classification system of PD, which manifests in familial and sporadic forms. The first genetic linkage studies in PD demonstrated the involvement of Synuclein alpha (SNCA) mutations and SNCA genomic duplications in the pathogenesis of PD familial forms. Subsequent studies have also insinuated mutations in leucine repeat kinase-2 (LRRK2), Parkin, PTEN-induced putative kinase 1 (PINK1), as well as DJ-1 causing familial forms of PD. This review will attempt to discuss the structure, function, and development in genome editing mediated by CRISP/Cas9 system. Further, it describes the genes involved in the pathogenesis of PD and the pertinent alterations to them. We will pursue this line by delineating the PD linkage studies in which CRISPR system was employed. Finally, we will discuss the pros and cons of CRISPR employment vis-à-vis the process of genome editing in PD patients' iPSCs.

Resveratrol-loaded polyurethane nanofibrous scaffold: viability of endothelial and smooth muscle cells.

Acellular small-caliber tissue-engineered vascular grafts (SCTEVGs) have low patency rate due to complications including thrombosis and intimal hyperplasia. Rapid endothelialization, antithrombosis and antiproliferation approaches are suitable for dispelling these complications. Nevertheless, common antithrombosis and antiproliferation techniques are usually incompatible with rapid endothelialization on vascular grafts. To overcome these obstacles, we developed nanofibrous polyurethane scaffolds loaded with resveratrol drug, which is a natural compound extracted from plants and shows multifaceted effects in cardiovascular protection. It was found that the tensile strength and Young's modulus in modified scaffolds were significantly increased by resveratrol loading into membranes. The tensile strengths and breaking strains of resveratrol-loaded scaffolds were close to that of native vessels. The resveratrol release profile from the nanofibrous scaffolds occurred in a sustained manner. The anti-thrombogenicity of resveratrol-loaded nanofibers increased compared to polyurethane alone, with the result that prolonged human blood clotting time and lower hemolysis were detected on these scaffolds. The viability of human umbilical vein endothelial cells and smooth muscle cells on resveratrol-loaded scaffolds was evaluated. Our findings demonstrated that resveratrol-loaded nanofibers resulted in not only appropriate antithrombotic properties, but the formation of a monolayer of endothelial cells on the scaffold surface and lower smooth muscle cell growth. These resveratrol-loaded nanofibers are suggested as potential scaffolds for SCTEVGs.

Multipotency expression of human adipose stem cells in filament-like alginate and gelatin derivative hydrogel fabricated through visible light-initiated crosslinking.

Hydrogel fibers are structurally and biologically useful devices for differentiation of stem cells and fabrication of filament-like tissues. We established cell-laden degradable hydrogel fibers through visible light-initiated crosslinking to differentiate stem cells and fabricate filament-like tissue. Human adipose stem cell (hADSC)-laden fibers were fabricated by cross-linking phenolic-substituted alginate and gelatin (Alg-Ph and Gela-Ph respectively) in an aqueous solution containing cells. The crosslinking of phenolic moieties was mediated by ruthenium(II) tris-bipyridyl dication (Ru(II) bpy and sodium ammonium persulfate (SPS) and irradiating visible light. The hydrogel microfiber fabricated with desirable geometries and dimensions. The encapsulated hADSCs proliferated and grew within hydrogel microfiber, maintained their multipotency ability and formed filament-like constructs. The filament-like tissues covered with an additional heterogeneous cell layer was made by degrading the fiber membrane using alginate-lyase after covering the fiber surface with vascular endothelial cells. Cellular viability is preserved during Alg-Ph and Gela-Ph hydrogel fiber fabrication and filament-like tissue formation. These results demonstrate the feasibility of Alg-based hydrogel fibers obtained through the Ru/SPS-mediated crosslinking system and visible light irradiation for the engineering of filament-like tissues and cell-based therapeutic treatments.

Improved human endometrial stem cells differentiation into functional hepatocyte-like cells on a glycosaminoglycan/collagen-grafted polyethersulfone nanofibrous scaffold.

Liver tissue engineering (TE) is rapidly emerging as an effective technique which combines engineering and biological processes to compensate for the shortage of damaged or destroyed liver tissues. We examined the viability, differentiation, and integration of hepatocyte-like cells on an electrospun polyethersulfone (PES) scaffold, derived from human endometrial stem cells (hEnSCs). Natural polymers were separately grafted on plasma-treated PES nanofibers, that is, collagen, heparan sulfate (HS) and collagen-HS. Galactosilated PES (PES-Gal) nanofibrous were created. The engineering and cell growth parameters were considered and compared with each sample. The cellular studies revealed increased cell survival, attachment, and normal morphology on the bioactive natural polymer-grafted scaffolds after 30 days of hepatic differentiation. The chemical and molecular assays displayed hepatocyte differentiation. These cells were also functional, showing glycogen storage, α-fetoprotein, and albumin secretion. The HS nanoparticle-grafted PES nanofibers demonstrated a high rate of cell proliferation, differentiation, and integration. Based on the observations mentioned above, engineered tissue is a good option in the future, for the commercial production of three-dimensional liver tissues for clinical purposes. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2516-2529, 2017.

Human endometrial stem cells differentiation into functional hepatocyte-like cells.

In spite of certain clinical limitations, such as teratoma formation, the use of stem cells is considered as an appropriate source in cell therapy and tissue engineering. This study shows human endometrial stem cells (hEnSCs) has exceptional differentiation ability in hepatocyte formation. hEnSCs have high purification rate and immune-tolerance, and can be used as an appropriate substitute for hepatocytes in liver disorders. Differentiation required hepatogenic medium. Quantitative reverse transcription-polymerase chain reaction and immunofluorescent staining of hepatic genes and proteins including cytokeratin 18 (ck18), alpha-fetoprotein (afp), and albumin (alb) were used to assess differentiation. Cells differentiated with a hepatocyte-like morphology and expressed hepatic markers on 30 days of differentiation. The Periodic Acid-Schiff (PAS) reaction showed storage of glycogen, and albumin and afp secretions were also detected. In vitro hEnSCs behave like hepatocyte after differentiation and may be a suitable source of cells in liver regeneration.

Effects of quince leaf extract on biochemical markers and coronary histopathological changes in rabbits.

BACKGROUND: Atherosclerosis is the main cause of cardiovascular disease which is caused by a high-fat diet. Many of these patients use boiled quince leaves for their treatment. However, the supporting scientific information is limit. The aim of this study was to evaluate the effect of quince leaf on the progression of atherosclerosis and whether it can be an appropriate alternative to statins. METHODS: 24 male rabbits were randomly divided into two groups: normal diet (6 n) and high-cholesterol diet (2% cholesterol, 18 n) for 8 weeks. At the end of the 8 weeks, both groups underwent blood sampling and their biochemical markers were measured. Then, all animals in the normal-diet group and three of the high-cholesterol diet group were killed to investigate atheromic plaque in their coronary artery. The 15 remaining rabbits of the high-cholesterol diet group were randomly divided into 3 groups (5 n) after discontinuation of the fatty diet. The first group was not given any treatment, the second received atorvastatin (0.5 mg/kg) orally, and the third received quince leaf extract (50 mg/kg) orally for 12 weeks. At the end of this period, after blood sampling, biopsy of coronary artery was performed for histological study. RESULTS: The results showed that atorvastatin and quince leaf significantly decreased total cholesterol, triglyceride, LDL, AST, ALT, AP, BUN, and Cr levels compared with the first group of the high-cholesterol diet group (P < 0.05). No significant difference was found between atorvastatin and quince leaf extract groups in biochemical markers and atherosclerotic plaque in coronary artery. CONCLUSION: Atorvastatin and quince leaf extract can effectively prevent the progression of atherosclerosis in coronary arteries. According to the results of this study and also lower toxic effects of herbal medication compared to synthetic medication, leaf extract can be a substitute for statins in treatment and prevention of cardiovascular disease. The anti-atherosclerotic effect of quince leaf is most likely related to its antioxidant components.

The comparative effects of atorvastatin and quince leaf extract on atherosclerosis.

BACKGROUND: This study investigates the ability of quince leaf extract to prevent progression of atherosclerosis and to determine the lipid-lowering effect of it. OBJECTIVES: This study suggested that quince leaf effects on progression of atherosclerosis, and performed comparison with atorvastatin as a standard medication. MATERIALS AND METHODS: The effect of 50mg/kg of the quince leaf extract on lipid profiles was assessed by measuring the levels of totalcholesterol, triglyceride, LDL, HDL, and liver enzymes (AST, ALT, and AP) in plasma and were evaluated the thickness of aortic plaques in the hypercholesterolemic rabbits after stopping. These assessments were performed using 0.5 mg/kg of atorvastatin. RESULTS: Oral administration of cholesterol for 8 weeks resulted in a significant increase (P < 0.05) in plasma markers. Treatment with the extract at dose of 50 mg/kg and 0.5 mg/kg of atorvastatin not only were reduced lipid profile in plasma (P < 0.05) but also were increased HDL-cholesterol levels. There were decrease (P = 0.04) in the liver enzymes in extract treated rabbits. However, plaque thickness had no significant difference in the aorta of treated rabbits compared with studied control. CONCLUSIONS: These results indicate the lipid-lowering effects of quince leaf similar to atorvastatin and it can probably serve as a new potential natural product for atherosclerosis treatment.