ABSTRACT
<p><b>BACKGROUND</b>Wallerian degeneration is a self-destructive process of axonal degeneration that occurs after an axonal injury or during neurodegenerative disorders such as Parkinson's or Alzheimer's disease. Recent studies have found that the activity of the nicotinamide adenine dinucleotide (NAD) synthase enzyme, nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) can affect the rate of Wallerian degeneration in mice and drosophila. NMNAT1 protects neurons and axons from degeneration. However, the role of NMNAT1 in neurons of central nervous system is still not well understood.</p><p><b>METHODS</b>We set up the culture of primary mouse neurons in vitro and manipulated the expression level of NMNAT1 by RNA interference and gene overexpression methods. Using electroporation transfection we can up-regulate or down-regulate NMNAT1 in cultured mouse dendrites and axons and study the neuronal morphogenesis by immunocytochemistry. In all functional assays, FK-866 (CAS 658084-64-1), a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase was used as a pharmacological and positive control.</p><p><b>RESULTS</b>Our results showed that knocking down NMNAT1 by RNA interference led to a marked decrease in dendrite outgrowth and branching and a significant decrease in axon growth and branching in developing cortical neurons in vitro.</p><p><b>CONCLUSIONS</b>These findings reveal a novel role for NMNAT1 in the morphogenesis of developing cortical neurons, which indicate that the loss of function of NMNAT1 may contribute to different neurodegenerative disorders in central nervous system.</p>
Subject(s)
Animals , Mice , Axons , Metabolism , Blotting, Western , Cells, Cultured , Dendrites , Metabolism , Immunohistochemistry , Morphogenesis , Genetics , Physiology , Neurons , Cell Biology , Metabolism , Nicotinamide-Nucleotide Adenylyltransferase , Genetics , MetabolismABSTRACT
Objective: To study the antifungal activity of triazole alcohols by introduction of cyclopropyl as side chain. Methods: Nine title compounds were synthesized and characterized by 1 HNMR, MS spectra and element analysis. Eight fungi were used for in vitro anti-fungal test. Results: All of the title compounds showed antifungal activities of different extents, especially to the deep infection ones,and they had a MIC value < 0.125 μg/ml against Candida albicans,showing an anti-fungal activity 4 times higher than that of fluconzole and similar to that of totraconazaole. Conclusion: 1-(1H-1,2,4-triazole-1-yl)-2-(2, 4-difluoro-phenyl)-3-[N-cyclopropyl-N-(3,4-dichlorobenzyl) amino]-2-propanols (6f) has a better activity ratio and is worth further studying.
ABSTRACT
<p><b>OBJECTIVE</b>To construct and identification of a lentiviral vector for RNA interference (RNAi) targeting STUB1 gene.</p><p><b>METHODS</b>A pair of complementary small hairpin RNA (shRNA) oligonucleotides targeting STUB1 gene was designed, synthesized and inserted into linearized pMagic 4.0 vector. The recombinant plasmid was identified by double restriction digestion with Age I/EcoR I and DNA sequencing.</p><p><b>RESULT</b>PCR and DNA sequencing showed that the shRNA sequence was successfully inserted into pMagic 4.0 vector. The pMagic 4.0 vector was successfully packaged into lentivirus particles.</p><p><b>CONCLUSION</b>A lentiviral shRNA expression vector and particles targeting STUB1 gene has been successfully constructed for the further study of the STUB1 gene.</p>
Subject(s)
Gene Targeting , Genetic Vectors , Lentivirus , Genetics , RNA Interference , RNA, Small Interfering , Genetics , Ubiquitin-Protein Ligases , GeneticsABSTRACT
Influenza is a major threat to millions of people worldwide. Vaccines and antiviral agents are two main options available to reduce the impact of the influenza virus, while anti-influenza agents are the most effective means to prevent the transmission of the highly contagious virus and to treat the epidemics of disease. At present, four anti-influenza agents have been approved by the FDA for the treatment of influenza, including two M2 protein ion channel inhibitors-amantadine and rimantadine and two neuraminidase inhibitors-zanamivir and oseltamivir. Arbidol hydrochloride, launched in Russia, is a potent inhibitor of influenza virus, too. Neuraminidase inhibitors could be classified generally by structure into six different kinds: sialic acid derivatives, benzoic acid derivatives, cyclohexene derivatives, cyclopentane derivatives, pyrrolidine derivatives and natural products. In this paper, recent progress in the research of the action mechanisms and structure-activity relationships of these anti-influenza virus agents were reviewed.
Subject(s)
Humans , Amantadine , Chemistry , Pharmacology , Therapeutic Uses , Antiviral Agents , Chemistry , Pharmacology , Therapeutic Uses , Cyclopentanes , Chemistry , Pharmacology , Therapeutic Uses , Guanidines , Chemistry , Pharmacology , Therapeutic Uses , Indoles , Chemistry , Pharmacology , Therapeutic Uses , Influenza, Human , Drug Therapy , Neuraminidase , Chemistry , Pharmacology , Therapeutic Uses , Orthomyxoviridae , Oseltamivir , Chemistry , Pharmacology , Therapeutic Uses , Pyrrolidines , Chemistry , Pharmacology , Therapeutic Uses , Rimantadine , Chemistry , Pharmacology , Therapeutic Uses , Structure-Activity Relationship , Viral Matrix Proteins , Chemistry , Pharmacology , Therapeutic Uses , Zanamivir , Chemistry , Pharmacology , Therapeutic UsesABSTRACT
@#Because of the population aging,the increase of the stroke patients and the need for rehabilitation,the treatment only in the rehabilitation department of the hospital is far from the satisfaction of people's demands of the service of rehabilitation.It is important to extend the community-based rehabilitation.Compared with the rehabilitation in hospitals,it is more economy,efficiency and convenience for stroke patients in community-based rehabilitation services,and further improve the rehabilitation effect of stroke patients.