Role of Schwann Cells in Preservation of Retinal Tissue Through Reduction of Oxidative Stress

The aim of this study was to evaluate the effect of subretinal injection of Schwann cells on preservation of retina by decreasing oxidative stress in Dystrophic Royal College of Surgeons (RCS) rats. Schwann cells were harvested from the sciatic nerve of postnatal day 5, RCS rats. Twenty-five RCS rats randomly assigned to cell and sham groups. Schwann cells injected in the sub-retinal space in one eye of the cell group and carrier medium was injected in one eye of the sham group. The proof for the appropriate site of injection of Schwann cells confirmed by the green fluorescent protein (GFP) positive cells. Electroretinogram (ERG) and enucleation for histopathology and enzymatic evaluation were performed 1, 2 and 3 months post-injection. The enzymatic evaluation included catalase, superoxide dismutase (SOD) and glutathione peroxidase 1 (GPx1) by enzyme-linked immunosorbent assay (ELISA) method. Three months after injection, histopathology assessments showed a complete absence of the outer nuclear layer (ONL), photoreceptors and obvious reduction of retinal pigment epithelium (RPE) in the sham group. Cell group showed marked preservation of RPE, choroidal congestion and mild presence of ONL. The green fluorescent protein positive Schwann cells remained in one integrated layer during the study under RPE. The enzymatic evaluation showed that in cell group expression of SOD and GPx1 until month 2 and catalase until month 1 were significantly more than the sham group. At the end of month 3, the amplitude of ERG waves significantly preserved in cell group in comparison to baseline waves and the sham group. We concluded that Schwan cells are able to preserve retinal in RCS rats by reducing oxidative stress. Epub: October 1, 2019

Clinical and Para clinical characteristics of non-classic Phenylketonuria

Abstract Objective Phenylketonuria (PKU) is one of the most common inherited metabolic diseases, classified as classic and non-classic forms.2% of children with PKU develop a severe and progressive neurologic disease called non classic (malignant) PKU. We aimed to demonstrate the clinical features and laboratory findings and the diagnostic and therapeutic properties of non-classic PKU patients referred to a tertiary level referral center of children in Tehran. Material and Method  In this study, we evaluate background information such as gender and age, clinical manifestations, laboratory findings, and response rates to conventional treatment of patients with non-classic PKU who referred to Mofid Children's' Hospital through neonatal screening.   Result Twenty patients with diagnosis of non-classic PKU were included. The mean age of them was 6.00 ± 2.81 years ranging from 2 to 12 years, and 45.0% were male. In patients with late diagnosis, the most common presentations were motor developmental delay (15.0%), skin and cutaneous manifestations (15.0%), seizure (5.0%), and restlessness (5.0%). An overall response to treatment was 85.0%. Factors that predict good response to treatment were female gender, higher neopterin level, and lower age at diagnosis and management. Conclusion In conclusion, about half of patients with non-classic PKU remain asymptomatic, which is due to early diagnosis via neonatal screening. Also, higher age at diagnosis and treatment, besides low neopterin levels, may be useful as prognostic factors. &nbsp

Survey on Ranking Functions in Keyword Search over Graph-Structured Data

Keyword search is known as an attractive alternative for structured query languages in querying over graph-structured data. A keyword query is expressed by a set of keywords and respond by a set of connected structures from the database, which totally or partially cover the queried keywords. These results show how the queried keywords are related in the database. Since there may be numerous results to a given query, a ranking function is essential to present top-k more relevant results to the user. The effectiveness of this function directly affected the effectiveness of the keyword search system. In this paper, we survey the proposed ranking functions in the context of keyword search. First, the proposed models for the results of a keyword query are discussed and a categorization of them is presented. Next, the effective factors in determining the relevance of results are examined. Then, various ranking functions for ordering the results of a query are described and categorized based on their main view in determining the semantic of the results. Finally, we present an analysis of these classes and discuss the evolution of new research strategies to resolve the issues associated with the ranking of results in the keyword search domain

Curcumin–silica nanocomplex preparation, hemoglobin and DNA interaction and photocytotoxicity against melanoma cancer cells

Abstract: Melanoma is a malignant cancer of the skin associated with a high mortality. Early medical diagnosis and surgical intervention are essential for the treatment of melanoma. The use of plant-based compounds is an important strategy for the prevention and treatment of different types of cancers. Curcumin is a promising natural anticancer compound used towards treatment for various kinds of cancers. Studies have shown that curcumin could be applied as a photosensitizer in cancer photodynamic therapy (PDT). PDT uses light and a photosensitizing agent which produce reactive oxygen species leading to cancer cell death. The main obstacle for using curcumin as photosensitizer is its low solubilization ability in an aqueous environment. To improve its application in cancer treatment, we synthetized curcumin–silica nanoparticles as photosensitizer for photodynamic treatment of human melanoma cancer cells. Scanning electron microscopy, Transmission electron microscopy, Powder Xray diffraction and Thermo geometric analysis indicated that curcumin was loaded on silica. The solubility of curcumin in water increased by using silica nanoparticles which wasconfirmed by spectroscopy results. The spectroscopy study confirmed the interaction of curcumin–silica nanocomplex with double strand DNA and no interaction with hemoglobin. The curcumin–silica nanocomplex and curcumin photodynamic effect was investigated on human melanoma cancer cells (A375) and also human fibroblast cells. The cell toxicity experiments showed that the curcumin–silica nanocomplex had greater photodynamic effects on cancer cell death as compared to free curcumin. The apoptotic assay by acridine orange/ethidium bromide (AO/EB) dual staining and colony forming ability confirmed the MTT results. Therefore, these results suggest that the curcumin–silica nanocomplex has great potential to be employed in photodynamic treatment of melanoma cancer

Methylation studies in Peromyscus: aging, altitude adaptation, and monogamy.

DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation in Peromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscus clocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude in Peromyscus. The human-Peromyscus epigenetic clocks are expected to provide a significant boost to the attractiveness of Peromyscus as a biological model

Erythropoietin in Treatment of Methanol Optic Neuropathy

Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90-0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90-0.00 logMAR). VA significantly increased in the last follow-up examination (P < 0.0001). Age and time to EPO treatment after methanol ingestion were not significantly related to final VA. No ocular or systemic complications occurred in our patient cohort. Intravenous EPO appears to improve VA in patients with methanol optic neuropathy and may represent a promising treatment for this disorder

Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability

Objective(s):The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively. This study investigated whether treatment of BM-MSCs with hypoxia-mimicking agents would increase expression of some chemokine receptors and cell migration. Materials and Methods: BM-MSCs were treated at passage 2 for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-96 Bio-Rad Real-Time PCR. The Boyden chamber assay was utilized to investigate BM-MSC homing. Results:Possible approaches to increasing the expression level of chemokine receptors by different hypoxia-mimicking agents such as valproic acid (VPA), CoCl2, and desferrioxamine (DFX) are described. Results show DFX efficiently up-regulate the CXCR7 and CXCR4 gene expression while VPA increase only the CXCR7 gene expression and no significant change in expression level of CXCR4 and the CXCR7 gene was detectable by CoCl2 treatment. Chemotaxis assay results show that pre-treatment with DFX, VPA, and Cocl2 enhances significantly the migration ability of BM-MSCs compared with the untreated control group and DFX treatment accelerates MSCs homing significantly with a higher rate than VPA and Cocl2 treatments. Conclusion: Our data supports the notion that pretreatment of MSC with VPA and DFX improves the efficiency of MSC therapy by triggering homing regulatory signaling pathways

Pretreatment of Mesenchymal Stem Cells and Stromal-derived Factor-1α Delivery from Chitosan-based Injectable Hydrogels for Better Cell Guidance and Retention

Clinical applications of mesenchymal stem cells (MSCs) rely on their capacity to home and engraft in the appropriate target tissues for a long time. Homing and engraftment capacity of these stem cells depend on the expression of Chemokines and their receptors. Ex vivo expanded MSCs exhibit homing potential when grafted to injury tissue but their homing efficiency has been observed very poor because of modifications in homing receptor expression and/or functions during culture and/or preparation steps. Hence, this study was designed to investigate the expression of surface CXCR4 by flow cytometric analysis (FACS) and in vitro modified Boyden chamber assay in adipose-derive MSCs (ASCs) stimulated with a hypoxia mimicking agents such as desferrioxamine mesilate (DFX), cobalt chloride (CoCl2), lithium chloride (LiCl), valproic acid (VPA) and hypoxia. Intracellular CXCR4 were also evaluated by conventional and real-time PCR. Then we evaluated the homing ability of DFX-pretreated human DiI-labeled ASCs in vivo, 2 weeks after intravenous (IV), local infusion towards subcutaneously implanted chitosan-glycerophophate-hydroxyethyl cellulose (CH-GP-HEC) injectable hydrogels releasing SDF1 in dorsum of Wistar Rats. Presence of human ASCs in the CH-GP-HEC injectable, spleen, and lung were analyzed histologically by fluorescent microscope, and also quantified by PCR for human specific CXCR4 gene, 2 weeks after transplantation in recipients' Rats. Results showed that short-term (24 hours) pretreatment to ASCs with the hypoxia mimicking agents up-regulate the CXCR4, increase in vitro migration capacity toward 100ng/ml SDF-1 (