168 research outputs found

    Compartmentalized, multiphasic nanocolloids with potential applications in drug delivery and biomedical imaging

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    Nanoparticles are excellent candidates for drug delivery or biomedical imaging, because they often exhibit superb tuneability of critical properties, such as size, surface characteristics, degradation rate, and therefore drug release rates. We have recently developed a route towards fabrication of sub-micron particles that relies on electrohydrodynamic co-jetting. In this process, fluid manipulation in an electrical field is used to fabricate large quantities of multi-compartment particles, where individual compartments can be independently loaded with different drugs or selectively surface-modified. In this contribution, aspects of multifunctional particles for biomedical applications are reviewed and a specific focus is given to recent progress with compartmentalized, multiphasic nanocolloids in our laboratory.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57529/1/1008_ftp.pd

    Towards Designer Microparticles: Simultaneous Control of Anisotropy, Shape, and Size

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    Biodegradable, compositionally anisotropic microparticles with two distinct compartments that exhibit controlled shapes and sizes are fabricated. These multifunctional particles are prepared by electrohydrodynamic co-jetting of poly(lactide-co-glycolide) polymer solutions. By varying different solution and process parameters, namely, concentration and flow rate, a variety of non-equilibrium bicompartmental shapes, such as discoid and rod-shaped microparticles are produced in high yields. Optimization of jetting parameters, combined with filtration, results in near-perfect, bicompartmental spherical particles in the size range of 3–5 µm. Simultaneous control over anisotropy, size, shape, and surface structure provides an opportunity to create truly multifunctional microparticles for a variety of biological applications, such as drug delivery, diagnostic assays, and theranostics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65050/1/404_ftp.pd

    In vitro homology search array comprehensively reveals highly conserved genes and their functional characteristics in non-sequenced species

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    <p>Abstract</p> <p>Background</p> <p>With the increase in genomic and transcriptomic data produced by the recent advancements in next generation sequencers and microarrays, it is now easier than ever to conduct large-scale comparative genomic studies for familiar species. However, there are more than ten million species on earth, and the study of all remaining species is not realistic in terms of cost and time. There have been a number of attempts at using microarrays for cross-species hybridization; however, those approaches only utilized the same probes for each species or different probes designed from orthologous genes. To establish easier and cheaper methods for the large-scale comparative genomic study of non-sequenced species, we developed an <it>in vitro</it> homology search array with the aid of a bioinformatic approach to probe design.</p> <p>Results</p> <p>To perform large-scale genomic comparisons of non-sequenced species, we chose squid, one of the most intelligent species among Protostomes, for comparison with human genes. We designed a microarray using human single copy genes and conducted microarray experiments with mRNAs extracted from the squid. Multi-copy genes could not be detected using the microarray in this study because their sequence similarity caused cross-hybridization. A search for squid homologous genes among human genes revealed that 68% of the human probes tested showed the expression of squid homolog genes and 95 genes were confirmed to be expressed highly in squid. Functional classification analysis showed that these highly expressed genes comprise DNA binding proteins, which are under pressure of DNA level mutation and, consequently, show high similarity at the nucleotide level.</p> <p>Conclusions</p> <p>Our array could detect homologous genes in squids and humans in spite of the distant phylogenic relationships between the species. This experimental method will be useful for identifying homologs in non-sequenced species, for the development of genetic resources and for the collection of information on biodiversity, particularly when using the genome of sibling or closely related species.</p

    Differentiation of Human Bone Marrow Mesenchymal Stem Cells to Chondrocytes for Construction of Three-dimensional Cartilage Tissue

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    A differentiation method of human bone marrow mesenchymal stem cells (MSCs) to chondrocytes was developed for the construction of a three-dimensional (3D) cartilage tissue. The adhesive cells, which were isolated from a human bone marrow aspirate were embedded in type I collagen in a poly-l-lactate-glycolic acid copolymer (PLGA) mesh and cultivated for 4 week together with growth factors. The degree of cellular differentiation was estimated by quantitative RT-PCR of aggrecan and type II collagen mRNAs and by staining with Safranin O. The 3D culture showed a higher degree of differentiation even without growth factors than the conventional pellet culture with growth factors, namely, dexamethasone and transforming growth factor (TGF)-β 3. The 3D culture for 2 week with the combined addition of dexamethasone, TGF-β 3, and insulin-like growth factor (IGF)-I reached a 30% expression of aggrecan mRNA compared with that in primary human chondrocytes, while the aggrecan mRNA expression in the conventional pellet culture was less than 2%. The sequential two-step differentiation cultivation, during which the cells were cultivated in 3D for 1 week after the conventional two-dimensional (2D) culture for 1 week, could markedly accelerate the expression of aggrecan mRNA compared with the 3D cultivation for 2 week

    Effect of Subcultivation of Human Bone Marrow Mesenchymal Stem on their Capacities for Chondrogenesis, Supporting Hematopoiesis, and Telomea Length

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    Effects of subcultivation of human bone marrow mesenchymal stem cells on their capacities for chondrogenesis and supporting hematopoiesis, and telomea length were investigated. Mesenchymal stem cells were isolated from human bone marrow aspirates and subcultivated several times at 37℃ under a 5% CO2 atmosphere employing DMEM medium containing 10% FCS up to the 20th population doubling level (PDL). The ratio of CD45- CD105+ cells among these cells slightly increased as PDL increased. However, there was no marked change in the chondrogenic capacity of these cells, which was confirmed by expression assay of aggrecan mRNA and Safranin O staining after pellet cell cultivation. The change in capacity to support hematopoiesis of cord blood cells was not observed among cells with various PDLs. On the other hand, telomere length markedly decreased as PDL increased at a higher rate than that at which telomere length of primary mesenchymal stem cells decreased as the age of donor increased

    Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

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    We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl2-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCβII expression prevented this cell death mode switch. Collectively, these results suggest that ProTα is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors

    Flower visitor fauna of the narrow endemic lily Lilium rubellum Baker in a lowland habitat in Yamagata, northern Japan

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    Floral visitor fauna of the narrow endemic lily Lilium rubellum was examined in a lowland habitat in Kaminoyama City, Yamagata Prefecture, northern Japan. Flowers of L. rubellum bloomed from early to late June. During 23 h of observing floral visitors, 64 insects were detected on L. rubellum flowers. Although coleopteran insects were most frequently found on L. rubellum flowers, they did not seem to be effective pollinators because of their body size. Bees were less frequently observed than coleopteran insects, but all individuals contacted sexual organs in L. rubellum flowers. Syrphid flies were seen less frequently, but they were also considered effective pollinators. From our observations, L. rubellum is a bee-pollinated species of the genus Lilium. Bee pollination has also been recorded in a species of Lilium sect. Archelirion, L. japonicum var. abeanum. The floral characteristics of L. japonicum var. abeanum (e.g., pinkish color, relatively small and tubular corolla, and lateral insertion of anthers into the corolla) were similar to those of L. rubellum and the character combination may be related to the bee-pollination mode in Lilium. key words: bee pollination, Bombus, Ceratina, flower visitor fauna, Lilium japonicum var. abeanum, Lilium rubellum, nitidulid beetle, syrphid fl

    急性心筋梗塞にて突然死したFibromuscular Dysplasiaの1例

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    We have recently encountered a patient presenting an sudden cardiac death secondary to acute myocardial infarction as a complication of fibromuscular dysplasia (FMD) involving the coronary artery. A 30 years old woman, who had a 6 year history of hyperthyroidism, was carried to our hospital because of sudden cardiac arrest. With no vital signs at arrival, advanced life support make her heart beat and gave a stable hemodynamic condition, which allowed us to make a diagnosis of acute broad anterior myocardial infarction with electrocardiography, echocardiography and serum CK-MB isoenzyme. Her brain activity did not recovered. She died on day 6 of hospitalization. Postmortem examination confirmed a broad anterior wall infarction of a histologic age of several days. Histologic examination also revealed intimal fibrous thickening with an increase of smooth muscle cells and elastic fibers in the right coronary and the anterior descending branch of the left coronary arteries, as well as the vertebral, bronchial, intra-renal and superior mesenteric arteries. Whereas no complete obstruction in the coronary artery was found at autopsy, it seems likely that the intracoronary luminal narrowing induced by fibromuscular hyperplasia might have precipitated a myocardial ischemic insult which caused the sudden cardiac death. Although FMD of the coronary artery has been rare in literature, it is necessary to consider FMD in the differential diagnosis of identifiable causes of sudden death, particularly in the young generation
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