Current Issue : April - June Volume : 2018 Issue Number : 2 Articles : 5 Articles
Theproliferation and apoptosis of pulmonary artery smoothmuscle cells (PASMCs) are considered to be key steps in the progression\nof pulmonary arterial hypertension (PAH). MicroRNAs (e.g., miR-29b) have been identified in various diseases to be critical\nmodulators of cell growth and apoptosis by targetingMcl-1 and CCND2. However, the role of miR-29b in PAH remains unknown.\nSo we try to investigate the effect of miR-29b on Mcl-1 and CCND2 protein in PASMCs, analyze the effect of miR-29b on the\nproliferation of PASMCs, and explore the significance of miR-29b in the proliferation, apoptosis, and gene therapy of PAH. It\nwas observed that gene chip analysis showed miR-29b expression in pulmonary artery tissue. The expression of miR-29b was\nsignificantly reduced in PAHmodel mice.MiR-29b inhibited the proliferation of PASMCs and promoted the apoptosis of PASMCs.\nMechanically, miR-29b could inhibit the expression of Mcl-1 and CCND2 protein and silenced Mcl-1 and CCND2 could abolish\nthe change of proliferation and apoptosis of PASMCs. These results demonstrate that miR-29b suppressed cellular proliferation and\npromoted apoptosis of PASMCs, possibly through the inhibition of Mcl-1 and CCND2. Therefore, miR-29b may serve as a useful\ntherapeutic tool to treat PAH....
Late Infantile Neuronal Ceroid Lipofuscinoses is an inherited neurodegenerative condition caused by a mutation\nin the CLN2 gene that codes for an enzyme, tripeptidyl peptidase I (TPP-1). Deficiencies in TPP-1 lead to protein\naccumulation within lysosomes and subsequent neuronal death, which produce the clinical features of the disease.\nGene therapy is considered a potential treatment option to allow functional administration of CLN2 to restore\nTPP-1 activity and distribution in the CNS. Adeno- associated viruses are being trialed as a vector for gene therapy\ndelivery. They are relatively safe and efficacious in their ability to mediate long-term gene expression at high levels\nof activity. This parallels improvements in both functional and clinical outcomes in human and animal models.\nThis article outlines the potential clinical benefits of using gene therapy, and discusses some of the limitations of\nthe trials to date....
The influenza virus causes annual epidemics and occasional pandemics and is thus a\nmajor public health problem. Development of vaccines and antiviral drugs is essential\nfor controlling influenza virus infection. We previously demonstrated the use of vectored\nimmune-prophylaxis against influenza virus infection. We generated a plasmid encoding\nneutralizing IgG monoclonal antibodies (mAbs) against A/PR/8/34 influenza virus\n(IAV) hemagglutinin (HA). We then performed electroporation of the plasmid encoding\nneutralizing mAbs (EP) in mice muscles and succeeded in inducing the expression of\nneutralizing antibodies in mouse serum. This therapy has a prophylactic effect against\nlethal IAV infection in mice. In this study, we established a new method of passive\nimmunotherapy after IAV infection. We performed hydrodynamic injection of the plasmid\nencoding neutralizing mAbs (HD) involving rapid injection of a large volume of plasmid-\nDNA solution into mice via the tail vein. HD could induce neutralizing antibodies\nin the serum and in several mucosal tissues more rapidly than in EP. We also showed\nthat a single HD completely protected the mice even after infection with a lethal dose\nof IAV. We also established other isotypes of anti-HA antibody (IgA, IgM, IgD, and IgE)\nand showed that like anti-HA IgG, anti-HA IgA was also effective at combating upper\nrespiratory tract IAV infection. Passive immunotherapy with HD could thus provide a new\ntherapeutic strategy targeting influenza virus infection....
The transferrin (TfR) and epidermal growth factor receptors (EGFR) are known to be\noverexpressed on the surface of a wide variety of tumor cells. Therefore, the peptides B6 (TfR\nspecific) and GE11 (targeted to the EGFR) were linked to the PAMAM (polyamidoamine) structure\nvia a polyethylenglycol (PEG) 2 kDa chain with the aim of improving the silencing capacity of\nthe PAMAM-based dendriplexes. The complexes showed an excellent binding capacity to the\nsiRNA with a maximal condensation at nitrogen/phosphate (N/P) 2. The nanoparticles formed\nexhibited hydrodynamic diameters below 200 nm. The zeta potential was always positive, despite\nthe complexes containing the PEG chain in the structure showing a drop of the values due to the\nshielding effect. The gene silencing capacity was assayed in HeLa and LS174T cells stably transfected\nwith the eGFPLuc cassette. The dendriplexes containing a specific anti luciferase siRNA, assayed at\ndifferent N/P ratios, were able to mediate a mean decrease of the luciferase expression values of 14%\nfor HeLa and 20% in LS174T cells, compared to an unspecific siRNA-control. (p < 0.05). In all the\nconditions assayed, dendriplexes resulted to be non-toxic and viability was always above 75%....
Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology\nremains mysterious, but tremendous advances have been made with the discovery of the most\nfrequent mutations of its more common familial form linked to the C9ORF72 gene. Although\nmost cases are still considered sporadic, these genetic mutations have revealed the role of RNA\nproduction, processing and transport in ALS, and may be important players in all ALS forms.\nThere are no disease-modifying treatments for adult human neurodegenerative diseases, including\nALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential\nstrategies for treating this neurodegenerative disorder. Successes achieved in various animal models\nof ALS have proven that RNA therapies are both safe and effective. With careful consideration of the\napplicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and\nclinical trial development of RNA therapies for treating ALS....
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