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11.
Giovanna Distefano Ricardo Jose Ferrari Christopher Weiss Bridget M. Deasy Michael L. Boninger G. Kelley Fitzgerald Johnny Huard Fabrisia Ambrosio 《PloS one》2013,8(3)
Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle. 相似文献
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Gwenaelle Gueguen Marta E. Kalamarz Johnny Ramroop Jeffrey Uribe Shubha Govind 《PLoS pathogens》2013,9(8)
Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously influence fate choice in basal and parasite-activated hematopoiesis. These effects are blocked by the Vankyrin I2-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene. I2-vank-3 and P-vank-1 differentially obstruct cellular and humoral inflammation. Additionally, their maternal expression weakens ventral embryonic patterning. We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature. 相似文献
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Lina Abu-Tair Sarit Doron Mahmud Mahamid Johnny Amer Rifaat Safadi 《Mitochondrion》2013,13(5):473-480
We investigated leptin effects on lymphocyte interactions with hepatic-stellate-cells (HSCs). Leptin showed pro-fibrotic effects on HSCs with oxidative status imbalance.In co-cultures, leptin activates HSCs and consequently adhered HCV-lymphocytes more than healthy ones. Leptin also increased healthy and HCV lymphocyte proliferations; increased their reactive-oxygen-species; decreased antioxidants (reduced-glutathione) levels while inhibited apoptosis only of HCV-lymphocytes. The leptin-treated HCV-lymphocytes activated HSCs, increase interleukin-4 while decreased their apoptosis.Leptin-receptor-deficient (db–db)-HSCs did not adhere lymphocytes. db/db-lymphocytes however showed fewer adherences to HSCs when compared to WT-counterparts.This study presents immune and oxidative modulatory effects of leptin on lymphocytes and their consequent interaction with HSCs. 相似文献
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Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献
18.
Zhinxin Zhao Roberto Gambari Kenneth Ka-Ho Lee Stanton Hon-Lung Kok Raymond Siu-Ming Wong Fung-Yi Lau Johnny Cheuk-On Tang Kim-Hung Lam Chor-Hing Cheng Desmond Kwok Po Hau Chung-Hin Chui Wai-Yeung Wong Wai-Kwok Wong 《Bioorganic & medicinal chemistry letters》2013,23(8):2373-2376
We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified. 相似文献
19.
The fine structure of the symbiotic alga isolated from the formainiferan Archaias angulatus (Fichtel et Moll) DeMontfort is typical of the Chlorophyceae of the volvocalean and chlorococcalean lines. Spherical non-motile cells, 10–14 μm in diameter, characterise the dominant life cycle phase. Long oval motile forms with truncated apices are present 3–5 days after transfer to fresh medium. The pyrenoids are embedded anteriorly in the singly bilobed chloroplast and are surrounded by a sheath of starch platelets. In spite of the non-motile state of cells in older cultures (which is perhaps a reflection of its normally symbiotic condition), the alga is identified as a species of the volvocalean genus Chlamydomonas and is named C. hedleyi sp. nov. The symbiont has no vitamin or organic requirements but growth is increased threefold in the presence of thiamine, and twofold in the presence of 1 μm glutamic acid, histidine and methionine. Urea was the best nitrogen source tested. Purines and pyrimidines did not serve as nitrogen sources. Chlamydomonas hedleyi grows well in a salinity range of 6->52‰. and a pH range of 6–8·5, 7·04 × 10-7 m carbon h-1 g-1 was fixed by the symbiont, 57% being released into the medium as a chromatographically homogeneous organic molecule provisionally identified as mannitol. 相似文献