MicroRNA-4731-5p delivered by AD-mesenchymal stem cells induces cell cycle arrest and apoptosis in glioblastoma

Glioblastoma multiforme (GBM) exhibits the most malignant brain tumor with very poor prognosis. MicroRNAs (miRNAs) are regulatory factors that can downregulate the expression of multiple genes. Several miRNAs acting as tumor-suppressor genes have been identified so far. The delivery of miRNA by mesenchymal stem cell (MSC) due to their ability to specifically target tumors is a new, hopeful therapeutic approach for glioblastoma. The objective of our study is the investigation of the effect of lentivirus-mediated microRNA-4731 (miR-4731) genetic manipulated adipose-derived (AD)-MSC on GBM. The downregulation of miR-4731 in human GBM tumor was detected using the GEO dataset. To evaluate the function of miR-4731, we overexpressed miR-4731 using lentiviral vectors in U-87 and U-251 GBM cell lines. The effects of miR-4731 on cell proliferation and cell cycle of glioma cells were analyzed by wound test and flow-cytometry assay. miR-4731 inhibited the proliferation of GBM cancer cells. Coculturing was used to study the antiproliferative effect of miR-4731-AD-MSCs on GBM cell lines. Direct and indirect coculture of GBM cell lines with miR-4731-AD-MSCs induced cell cycle arrest and apoptosis. Our findings suggest that AD-MSCs expressing miR-4731 have favorable antitumor characteristics and should be further explored in future glioma therapy.     

Small molecule of sphingosine as a rescue of dopaminergic cells: A cell therapy approach in neurodegenerative diseases therapeutics

Multiple sclerosis (MS) patients should take medication such as fingolimod (FTY-720) for a long time, hence pharmaceutical effects on other neural cells such as dopaminergic cells are important. Dopaminergic cell line, BE(2)-M17, was treated by FTY-720 and then cell viability and genes involve in neurosurvival were investigated. It was disclosed that FTY-720 significantly stimulates Bcl2 overexpression. Whereas, it decreased intracellular reactive oxygen species production and cell membrane damage of dopaminergic cells. The increase in Bcl2/Bax ratio increased the cell metabolic activity and decreased propidium iodide-positive cells. Besides, FTY-720 induced the overexpression of CACNA1C, nNOS gene, and nitric oxide production. However, FTY-720 induced GABARA1 overexpression and eventually it could overcame to the cytotoxic effect of intracellular calcium. This cascade led to tyrosine hydroxylase and BDNF genes overexpression whereas FTY-720 did not change GDNF concentration in BE(2)-M17 cells. Concluding, it might be said that taking FTY-720 in MS patients did not induce adverse effect on dopaminergic cells.     

Morphometric Analysis of Sunflower (<Emphasis Type="Italic">Helianthus annuus</Emphasis> L.) Achenes from Mexico and Eastern North America<Superscript>1</Superscript>

Morphometric Analysis of Sunflower ( Helianthus annuus L.) Achenes from Mexico and Eastern North America. Sunflower (Helianthus annuus L.) has played a major role in the evolution of agricultural systems in the Americas. The discovery of ancient domesticated remains from archaeological deposits in pre-Columbian Mexico offers new dimensions to widely accepted viewpoints on the domestication pattern of H. annuus. Although American sunflower populations north of Mexico have been examined extensively, Mexican indigenous domesticated landraces have not been studied in any detail. In this study, we morphologically assessed wild and domesticated sunflower achenes from Mexico and compared them to similar datasets from eastern North America. Additionally, we evaluated the utility of four computer-assisted shape measurements in discriminating between wild and domesticated sunflower achenes (fruits) and compared variation in achene size among modern wild and cultivated populations from both Mexico and the U.S. We found that, of the shape parameters tested, none were informative in distinguishing wild achenes from domesticated varieties. Subsequent size analysis, using conventional parameters of length, width, and thickness, showed that modern wild populations from Mexico had smaller achenes compared to modern populations from eastern North America. Domesticated achenes unearthed from Mexican archaeological sites, however, were significantly larger than the early domesticated specimens recovered from eastern North America. Our methodological results indicate that variation in archaeological sunflower achenes is better described by conventional size parameters rather than computerized shape analysis.     

Expression analysis and genotyping of DGKZ: a GWAS-derived risk gene for schizophrenia

Schizophrenia (SCZ) is a disabling and severe mental illness characterized by abnormal social behavior and disrupted emotions. Similar to other neuropsychological disorders, both genetics and environmental factors interplay so as to develop SCZ. It is acknowledged that genes such as DGKZ are involved in lipid signaling pathways that are the basis of neural activities, memory, and learning and are considered as candidate loci for SCZ. The aim of the present study was to evaluate the expression level and genotypes of DGKZ in patients with SCZ and controls. We used q-PCR to measure the relative expression of DGKZ in blood. To determine DGKZ–rs7951870 genotypes, tetra-ARMS PCR was used. Our results showed a significant difference in DGKZ mRNA ratio between SCZ patients and healthy controls (P?=?2?×?10^?4). Also, we showed that rs7951870-TT genotype was strongly associated with increased DGKZ expression level (P?=?0.038). In conclusion, our findings revealed dysregulation of DGKZ in SCZ patients and a significant correction between the gene expression and DGKZ variant rs7951870.

     

Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during the Prediabetic Phase

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells are destroyed in the islets of Langerhans. One of its main pathological manifestations is the hyper-expression of Major Histocompatibility Complex I (MHC-I) by beta cells, which was first described over 3 decades ago yet its cause remains unknown. It might not only be a sign of beta cell dysfunction but could also render the cells susceptible to autoimmune destruction; for example, by islet-infiltrating CD8 T cells. In this report, we studied pancreas tissue from a 22-year-old non-diabetic male cadaveric organ donor who had been at high risk of developing T1D, in which autoantibodies against GAD and IA-2 were detected. Pancreas sections were analyzed for signs of inflammation. Multiple insulin-containing islets were identified, which hyper-expressed MHC-I. However, islet density and MHC-I expression exhibited a highly lobular and heterogeneous pattern even within the same section. In addition, many islets with high expression of MHC-I presented higher levels of CD8 T cell infiltration than normal islets. These results demonstrate the heterogeneity of human pathology that occurs early during the pre-diabetic, autoantibody positive phase, and should contribute to the understanding of human T1D.     

Embryonic stem cells differentiated into neuron-like cells using SB431542 small molecule on nanofibrous PLA/CS/Wax scaffold

Electrospun nanofibrous scaffolds show huge potential to improve the neurological outcome in central nervous system disorders. In this study, we cultured mouse embryonic stem cells (mESCs) on an electrospun nanofibrous polylactic acid/Chitosan/Wax (PLA/CS/Wax) scaffold and surveyed the attachment, behavior, and differentiation of mESCs into neural cells. Differentiation in neural-like cells (NLCs) was investigated with a medium containing SB431542 as a small molecule and conjugated linolenic acid after 20 days. We used Immunocytochemistry and quantitative real-time polymerase chain reaction (RT-PCR) techniques to assess neural marker expression in differentiated cells. SEM imaging demonstrated that mESCs could strongly attach, stretch, and differentiate on PLA/CS/Wax scaffolds. MESCs that were cultured on PLA/CS/Wax scaffolds showed enhanced numbers of neural structures and neural markers including Nestin, NF-H, Tuj-1, and Map2 in neural induction medium compared to the control sample. These results revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. We hope that the development of new technologies in neural tissue engineering may pave a new avenue for neural tissue regeneration.     

A novel variant of t-PA resistant to plasminogen activator inhibitor-1; expression in CHO cells based on in silico experiments

Resistance to PAI-1 is a factor which confers clinical benefits in thrombolytic therapy. The only US FDA approved PAI-1 resistant drug is Tenecteplase?. Deletion variants of t-PA have the advantage of fewer disulfide bonds in addition to higher plasma half lives. A new variant was developed by deletion of the first three domains in t-PA in addition to substitution of KHRR 128-131 amino acids with AAAA in truncated t-PA. The specific activity of this new variant, 570 IU/μg, was found to be similar to those found in full length t-PA (Alteplase?), 580 IU/μg. A 65% and 85% residual activity after inhibition by rPAI-1 was observed for full length and truncated-mutant form, respectively. This new variant as the first PAI-1 resistant truncated t-PA may offer more advantages in clinical conditions in which high PAI-1 levels makes the thrombolytic system prone to re-occlusion.     

Social impact and social performance of paddy rice production in Iran and Malaysia

The International Journal of Life Cycle Assessment - Sustainable agri-food production is incredibly important for society. Despite Iran and Malaysia being one of the highest production countries...