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Currently a protein/peptide-mediated gene delivery has been considered a promising approach in non-viral gene transfer. The previous investigations have shown that histones and other nuclear proteins might be effective vectors for gene transfer into cells. Transfection of eukaryotic cells by nucleic acid and histone complexes (histonefection) effectively occurs with various histone proteins. The presence of DNA-binding domains and specific signal sequences of nuclear location allows to use histones (H1/H5, H2A, H2B, H3, H4) and other nuclear proteins (such as HMG family proteins and histonelike prokaryotic proteins) for recombinant genes transfer. The positive charge of histone protein molecules enables electrostatic interaction with negatively charged molecules of nucleic acids and charge neutralization that facilitates the complexes penetration through a negatively charged cell membrane. Thus, histonefection is a promising method for non-viral transfer of recombinant nucleic acids in gene therapy

The universal non-neuronal nature of parkinson's disease: a theory

Various recent developments of relevance to Parkinson's disease (PD) are discussed and integrated into a comprehensive hypothesis on the nature, origin and inter-cellular mode of propagation of late-onset sporadic PD. We propose to define sporadic PD as a characteristic pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. Although a universal cell-generic state, the PD-state deviation would be particularly damaging in a neuronal context, ultimately leading to neuron death and the ensuing observed clinical signs. We review why age accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We put forward hematopoietic cells could be the first to acquire the PD-state, at hematopoiesis, from the disruption in reactive oxygen species (ROS) homeostasis that arises with age in the hematopoietic stem-cell niche. We argue why, nonetheless, such a process is unlikely to explain the shift to the PD-state of all the subsequently affected cells in a patient, thus indicating the existence of a distinct mechanism of propagation of the PD-state. We highlight recent findings on the intercellular exchange of mitochondrial DNA and the ability of mitochondrial DNA to modulate the cellular global gene expression state and propose this could form the basis for the intercellular propagation of the PD-state

Current Trends in Regenerative Medicine: From Cell to Cell-Free Therapy

© 2016, Springer Science+Business Media New York.One of the most promising approaches to stimulate regeneration and angiogenesis in traumatic or ischemic tissue damage is stem cell therapy. Embryonic and fetal stem cells have the greatest potential of differentiation into different cell types; however, at the same time, they carry the highest risk of teratoma formation. Adult stem cells have the potential risk of transformation during prolonged cultivation in vitro, or as a result of genetic changes during gene-cell therapy applications. In this regard, technologies that can reduce the potential risks of cell and gene-cell therapy are of particular interest. According to the paracrine hypothesis, the beneficial effect of stem cell therapy is due to stimulation of resident cells by cell-to-cell contacts, secretion of bioactive molecules, and release of extracellular vesicles. In this review, we discuss the development of regenerative medicine from cell to cell-free therapy based on extracellular vesicles

農産物の最適貿易政策―最大値原理の応用による動学的最適化の視点から―

A reaction of bis(triphenylphosphine)palladium dibromide with white phosphorus in the presence of NaBPh4 selectively gives phosphorous acid H3PO3. The mechanism of the formation involves coordination of a white phosphorus molecule, ligand exchange, and hydrolysis of the coordinated P4 molecule in the coordination sphere of palladium. © 2010 Springer Science+Business Media, Inc

The effect of oxygen concentration on embryo development and assisted reproductive technologies efficiency

© 2018 Human Stem Cell Institute. All rights reserved. Many different factors have an effect on the preimplantation development of embryos under conditions in vitro. One of these factors is the oxygen concentration in the culture medium. Currently, IVF labs have ability to cultivate embryos either under conditions of atmospheric oxygen concentration or at low oxygen concentration (hypoxia). This review is focused on the analysis of up to date research and clinical results which are trying to establish an "optimal" composition of the gas mixture in the incubator to generate more viable embryos and increase the effectiveness of assisted reproductive technologies programs

Isolation and cultivation of myofibroblasts from rats' liver using explantation method

During liver fibrosis development connective tissue is produced by myofibroblasts that could originate from two hepatic populations: hepatic stellate cells and portal fibroblasts. A marker of myofibroblasts is the expression of α-smooth muscle actin (α-SMA). Distinctive feature of myofibroblasts, derived from hepatic stellate cells, is the preservation of the hepatic stellate cells marker expression - desmin. The processes of activation, proliferation and cells trans-differentiation into myofibroblasts are closely related to the activity of transcription factor NF-kB and its inhibitor IkBα. The aim of our work was to obtain a culture of hepatic myofibrobasts, to study their origin, phenotype, relations between NF-kB and IkBα expression and the processes of activation and cells trans-differentiation into myofibroblasts. For this purpose we isolated heterogeneous population of cells from rat liver by the method of explantation. Almost all the cells had desmin and α-SMA expression. On this basis, we suppose that these myofibroblasts were hepatic stellate cells derivatives, and singular desmin-negative cells originated from portal fibroblasts. Thus, hepatic stellate cells have major potential to activation, growth, proliferation and transdifferentiation into myofibroblasts in comparison to portal fibroblasts. Activated state of the cells was confirmed by stable expression of NF-kB and its inhibitor IkBα in all the cells throughout the whole experiment

Endogenous secretion of vascular endothelial growth factor by multipotent mesenchymal stromal cells derived from human third molar dental follicles

Human stem cells secretome is currently a very hot area of research. We report that multipotent mesenchymal stromal cells isolated from human third molar dental follicles (MMSC-TMDF), are able to secrete high levels of vascular endothelial growth factor (VEGF) when cultured in vitro. Due to the fact that VEGF is a well known angiogenic and neuroprotective factor, the use of MMSC-TMDF is promising for the development of stem cell therapy of various degenerative human diseases

Promising new therapeutic targets for regulation of inflammation and immunity: RING-type E3 ubiquitin ligases

© 2018 European Federation of Immunological Societies Ubiquitin–proteasome system (UPS) is a primary signaling pathway for regulation of protein turnover and removal of misfolded proteins in eukaryotic cells. Enzymes of the UPS pathway - E1 activating, E2 conjugating, E3 ligating - act together to covalently tag substrate proteins with a chain of ubiquitins, small regulatory proteins. The poly-ubiquitin chain then serves as a recognition motif for 26S proteasome to recognize and degrade the substrate. In recent years UPS has emerged as attractive enzymatic cascade for development of novel therapeutics against various human diseases. Building on the previous success of targeting this pathway in cancer – the broader scientific community is currently looking for ways to elucidate functions of E3 ligases, substrate-specific members of the UPS. RING-type E3 ubiquitin ligases, the largest class of E3s, represent prospective targets for small molecule modulation and their importance is reinforced by ever growing evidence of playing role in non-cancer diseases, primarily associated with inflammatory and immune disorders. In this review, we aim to briefly cover the current knowledge of biological functions of RING-type E3 ligases in inflammation and immunity

Investigation into Whether Proximal Suspensory Desmitis of the Hindlimb Could Predispose Horses to Sacroiliac Disease

Proximal suspensory desmopathy/desmitis (PSD) of the hindlimb is a well understood condition with widely accepted treatment protocols; however, there is little research demonstrating understanding or potential correlation between hindlimb PSD and sacroiliac disease (SID). Several studies have examined the co-existence of hindlimb PSD and SID each investigating unique predisposing factors. This has led to little direct correlation of cause and effect with no definitive conclusions drawn. The need to be objective is highlighted by the limited number of studies and that two studies used anecdotal evidence to support their hypothesis and thus creating the question does hindlimb proximal suspensory desmopathy predispose horses to sacroiliac disease? This review looks at the two conditions and compares the literature for each, including the incidence, biomechanics, anatomy, and treatment. The review further discusses whether one disorder predisposes horses/equids to the other

Retrogradely transported siRNA silences human mutant SOD1 in spinal cord motor neurons

The transgenic mouse model of familial amyotrophic lateral sclerosis (ALS) expressing human mutant (G93A) copper/zinc superoxide dismutase (SOD1) is an attractive model for studying the therapeutic effects of RNA interference (RNAi) because of the specific silencing of the mutant gene expression. We studied small interfering RNA (siRNA)-mediated down-regulation of human mutant G93A SOD1 gene in lumbar spinal cord of ALS mice. siRNA was applied onto the proximal nerve stump of severed sciatic nerves. One day after surgery the lumbar spinal cords were processed for RT-PCR examination. Treatment with specific siRNA resulted in 48% decrease in human SOD1 mRNA levels in lumbar spinal cord, but had no effect on the abundance of mouse ChAT and SNAP25 mRNAs which were used as randomly selected internal controls, the mark of a specific silencing of SOD1. Our findings demonstrate for the first time that siRNA, targeting mutant human SOD1 mRNA, is taken up by the sciatic nerve, retrogradely transported to the perikarya of motor neurons, and inhibits mutant SOD1 mRNA in G93A transgenic ALS mice. © 2009 Springer-Verlag