AimsThe proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. Methods and resultsFemale domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n ¼ 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 + 16.4 g vs. 183.1 + 24.2 g, P , 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 + 0.6 vs. 1.8 + 0.1, P , 0.05). The EF tended to be lower (46 + 12% and 53 + 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 + 1.1 vs. 4.7 + 1.1 L/min, P , 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. ConclusionThe current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic-restrictive cardiomyopathy phenotype.--
The social amoeba Dictyostelium discoideum has long served as a model system for studying fundamental processes in cell and developmental biology. This eukaryotic microbe is also recognized as a model organism for biomedical and human disease research since the genome encodes homologs of genes linked to human disease, such as those linked to cancer and neurodegeneration. Dictyostelium has a unique life cycle composed of a unicellular growth phase and a multicellular developmental phase that is induced by starvation. During its life cycle, Dictyostelium undergoes conserved cellular processes including, but not limited to, cell proliferation, phagocytosis, intercellular signaling, cell adhesion and motility, chemotaxis, and cell differentiation. The history of the organism, the resources available to researchers in the community, and the diverse ways that Dictyostelium is used in the contemporary research lab are discussed. © 2017 by John Wiley & Sons, Inc.
Placenta-derived mesenchymal stem/stromal cells (PMSC) present several aspects that make them more attractive as cellular therapy than their counterparts from other tissues, such as MSC from bone marrow or adipose tissue in regenerative medicine. Placenta-derived MSC have been used to treat a variety of disorders, such as, cancer, liver and cardiac diseases, ulcers, bone repair, and neurological diseases. Placenta-derived MSC are relatively new types of MSC with specific immunomodulatory properties and whose mechanisms are still unknown. Placenta-derived MSC secrete some soluble factors that seem to be responsible for their therapeutic effects, i.e., they have paracrine effects. On the other hand, Placentaderived MSC can also serve as cellular vehicles and/or delivery systems for medications due to their migration capacity and their tropism for injury sites. Nanotechnology is an important field, which has undergone rapid development in recent years for the treatment of injured organs. Due to the special characteristics of placenta-derived MSC, the combination of these cells with nanotechnology will be a significant and highly promising field that will provide significant contributions in the regenerative medicine field in the near future.
Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and with immunoregulatory cells (regulatory T-lymphocytes and dendritic T-cells) opens up new expectations for their use in these diseases. The goal for stem cell-based therapy is to provide a permanent cure. To achieve this, it will be necessary to obtain a cellular product, original or genetically modified, that has a high migration capacity and homes into the intestine, has high survival after transplantation, regulates the immune reaction while not being visible to the patient's immune system, and repairs the injured tissue. Core tip: Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract. A limited experience is available with hematopoietic and mesenchymal stem cell transplantation for the treatment of these conditions. Research is ongoing with other cell lines which have been used in conditions alike to inflammatory bowel disease and which will possibly have a therapeutic role in this condition. INTRODUCTIONInflammatory bowel disease (IBD) mainly consists of two clinical conditions, Crohn's disease (CD) and ulcerative colitis (UC). It is mainly characterized by chronic, destructive inflammation of the gastrointestinal tract for which no curative treatment is currently available.Its etiology is unknown, but it is accepted that it could be the result of loss of tolerance to intraluminal bowel antigens [1] . Genetic, environmental, and microbiological factors are involved in its development, Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?Ana I Flores, Gonzalo J Gómez-Gómez, Ángeles Masedo-González, M Pilar Martínez-Montiel together with morphological and functional changes in the intestinal barrier associated to an impaired immune response [2] . Early data supporting genetic involvement in the pathogenesis of IBD come from familial clinical studies showing a greater incidence in twins [3,4] , first-degree relatives [5,6] and given ethnic groups [7,8] . Genome-wide association scan studies have allowed for identification of more than 163 loci associated to IBD [9] , 73 genes associated to CD and 47 to UC [10] , and overlapping genes for both conditions have also been found [11] . Genetic factors would however account for less than 25% of cases [12] . The exception is represented by a monogenic disorder referred to as IBD-like diseases, which are associated with severe colitis in childhood and have at most three loci alternatives [13] . On the other hand the increase of the incidence of IBD suggests that environmental factors are more important than genetic factors in the development of IBD [14] . Since IBD etiology is currently unknown, current treatment is intended to control the inflammatory intestinal process, thus avoiding irreversible structural damage. However, current therapeutic results are di...
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