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Find video protocols related to scientific articles indexed in Pubmed.
CD8 T Cells Are Involved in Skeletal Muscle Regeneration through Facilitating MCP-1 Secretion and Gr1high Macrophage Infiltration.
J. Immunol.
PUBLISHED: 10-22-2014
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Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8?-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8?-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8? deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8?-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8?-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.
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IL-17A produced by both ?? T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction.
J. Pathol.
PUBLISHED: 08-26-2014
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IL-17A-producing T lymphocytes play a crucial role in inflammatory kidney diseases, but their role in renal fibrosis remains to be explored. Here, we demonstrated that up-regulation of IL-17A was associated with the development of obstructive kidney injury. The primary source of IL-17A production in obstructed kidneys was infiltrating ?? T lymphocytes and CD4(+) T cells. IL-17A-deficient mice were protected from myofibroblast activation and extracellular matrix deposition, leading to reduced kidney fibrosis in response to obstructive injury. Mechanistically, IL-17A deficiency suppressed the expression of the chemokine RANTES in infiltrated CD3(+) T cells and peritubular inflammation following renal obstruction. Administration of RANTES-neutralizing antibody significantly reduced the accumulation of T cells and macrophages, and of collagen deposition in obstructed kidneys. Taken together, our results indicate that IL-17A contributes significantly to the pathogenesis of renal fibrosis by regulating RANTES-mediated inflammatory cell infiltration. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Akt2 is involved in loss of epithelial cells and renal fibrosis following unilateral ureteral obstruction.
PLoS ONE
PUBLISHED: 08-22-2014
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Obstructive nephropathy is an aggressive form of chronic kidney disease (CKD), which is characterized by an epithelial-to-mesenchymal transition (EMT) and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we investigated the contribution of Akt2 to experimental renal EMT and fibrosis using the well-established model of unilateral ureteral obstruction (UUO). We found that Akt2 and phosphor (p)-Akt protein levels were increased in the obstructed kidneys. UUO induced activation of transforming growth factor-?1 (TGF-?1) signaling. Importantly, knockout of Akt2 suppressed UUO-induced EMT, kidney fibrosis, increased GSK3? activity, and decreased expression of Snail and ?-catenin. Inhibition of GSK3? with LiCl (the inhibitor of GSK3?) increased the expression of Snail and ?-catenin in cultured kidney epithelial cells. Our findings suggest that Akt2 partially contributes to interstitial fibrosis following UUO and that inhibition of this signaling pathway may provide a novel approach of prevent progression of renal fibrosis.
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The Notch ?-secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-?/Smad2/3 signaling pathway activation.
Int. J. Biochem. Cell Biol.
PUBLISHED: 08-20-2014
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Kidney fibrosis is a common feature of chronic kidney disease (CKD). A recent study suggests that abnormal Notch signaling activation contributes to the development of renal fibrosis. However, the molecular mechanism that regulates this process remains unexplored. Unilateral ureteral obstruction (UUO) or sham-operated C57BL6 mice (aged 10 weeks) were randomly assigned to receive dibenzazepine (DBZ, 250?g/100g/d) or vehicle for 7 days. Histologic examinations were performed on the kidneys using Masson's trichrome staining and immunohistochemistry. Real-time PCR and western blot analysis were used for detection of mRNA expression and protein phosphorylation. The expression of Notch 1, 3, and 4, Notch intracellular domain (NICD), and its target genes Hes1 and HeyL were upregulated in UUO mice, while the increase in NICD protein was significantly attenuated by DBZ. After 7 days, the severity of renal fibrosis and expression of fibrotic markers, including collagen 1?1/3?1, fibronectin, and ?-smooth muscle actin, were markedly increased in UUO compared with sham mice. In contrast, administration of DBZ markedly attenuated these effects. Furthermore, DBZ significantly inhibited UUO-induced expression of transforming growth factor (TGF)-?, phosphorylated Smad 2, and Smad 3. Mechanistically, Notch signaling activation in tubular epithelial cells enhanced fibroblast proliferation and activation in a coculture experiment. Our study provides evidence that Notch signaling is implicated in renal fibrogenesis. The Notch inhibitor DBZ can ameliorate this process via inhibition of the TGF-?/Smad2/3 signaling pathway, and might be a novel drug for preventing chronic kidney disease.
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Multiple systemic transplantations of human amniotic mesenchymal stem cells exert therapeutic effects in an ALS mouse model.
Cell Tissue Res.
PUBLISHED: 04-28-2014
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Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease involving degeneration of motor neurons in the central nervous system. Stem cell treatment is a potential therapy for this fatal disorder. The human amniotic membrane (HAM), an extremely rich and easily accessible tissue, has been proposed as an attractive material in cellular therapy and regenerative medicine because of its advantageous characteristics. In the present study, we evaluate the long-term effects of a cellular treatment by intravenous administration of human amniotic mesenchymal stem cells (hAMSCs) derived from HAM into a hSOD1(G93A) mouse model. The mice received systemic administration of hAMSCs or phosphate-buffered saline (PBS) at the onset, progression and symptomatic stages of the disease. hAMSCs were detected in the spinal cord at the final stage of the disease, in the form of isolates or clusters and were negative for ?-tubulin III and GFAP. Compared with the treatment with PBS, multiple hAMSC transplantations significantly retarded disease progression, extended survival, improved motor function, prevented motor neuron loss and decreased neuroinflammation in mice. These findings demonstrate that hAMSC transplantation is a promising cellular treatment for ALS.
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[Involvement of chemokine CXCL16 in myocardial infarction and its influence on phagocyticactivity of macrophage in vitro].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-16-2014
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To explore whether chemokine CXCL16 is up-regulated after myocardial infarction and promotes the phagocytic activity of macrophage in vitro.
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Crystallization, preliminary X-ray crystallographic and cryo-electron microscopy analysis of a bifunctional enzyme fucokinase/L-fucose-1-P-guanylyltransferase from Bacteroides fragilis.
Acta Crystallogr F Struct Biol Commun
PUBLISHED: 02-04-2014
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Fucokinase/L-fucose-1-P-guanylyltransferase (FKP) is a bifunctional enzyme which converts L-fucose to Fuc-1-P and thence to GDP-L-fucose through a salvage pathway. The molecular weights of full-length FKP (F-FKP) and C-terminally truncated FKP (C-FKP, residues 300-949) are 105.7 and 71.7?kDa, respectively. In this study, both recombinant F-FKP and C-FKP were expressed and purified. Size-exclusion chromatography experiments and analytical ultracentrifugation results showed that both F-FKP and C-FKP are trimers. Native F-FKP protein was crystallized by the vapour-diffusion method and the crystals belonged to space group P212121 and diffracted synchrotron X-rays to 3.7?Å resolution. The crystal unit-cell parameters are a = 91.36, b = 172.03, c = 358.86?Å, ? = ? = ? = 90.00°. The three-dimensional features of the F-FKP molecule were observed by cryo-EM (cryo-electron microscopy). The preliminary cryo-EM experiments showed the F-FKP molecules as two parallel disc-shaped objects stacking together. Combining all results together, it is assumed that there are six FKP molecules in one asymmetric unit, which corresponds to a calculated Matthews coefficient of 2.19?Å(3)?Da(-1) with 43.83% solvent content. These preliminary crystallographic and cryo-EM microscopy analyses provide basic structural information on FKP.
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Species-dependent neuropathology in transgenic SOD1 pigs.
Cell Res.
PUBLISHED: 01-13-2014
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Mutations in the human copper/zinc superoxide dismutase 1 (hSOD1) gene cause familial amyotrophic lateral sclerosis (ALS). It remains unknown whether large animal models of ALS mimic more pathological events seen in ALS patients via novel mechanisms. Here, we report the generation of transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects, which are germline transmissible, and motor neuron degeneration in dose- and age-dependent manners. Importantly, in the early disease stage, mutant hSOD1 did not form cytoplasmic inclusions, but showed nuclear accumulation and ubiquitinated nuclear aggregates, as seen in some ALS patient brains, but not in transgenic ALS mouse models. Our findings revealed that SOD1 binds PCBP1, a nuclear poly(rC) binding protein, in pig brain, but not in mouse brain, suggesting that the SOD1-PCBP1 interaction accounts for nuclear SOD1 accumulation and that species-specific targets are key to ALS pathology in large mammals and in humans.
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Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-12-2013
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Cell recognition molecule L1 (CD171) plays an important role in neuronal survival, migration, differentiation, neurite outgrowth, myelination, synaptic plasticity and regeneration after injury. Our previous study has demonstrated that overexpressing L1 enhances cell survival and proliferation of mouse embryonic stem cells (ESCs) through promoting the expression of FUT9 and ST3Gal4, which upregulates cell surface sialylation and fucosylation. In the present study, we examined whether sialylation and fucosylation are involved in ESC differentiation through L1 signaling. RNA interference analysis showed that L1 enhanced differentiation of ESCs into neurons through the upregulation of FUT9 and ST3Gal4. Furthermore, blocking the phospholipase C? (PLC?) signaling pathway with either a specific PLC? inhibitor or knockdown PLC? reduced the expression levels of both FUT9 and ST3Gal4 mRNAs and inhibited L1-mediated neuronal differentiation. These results demonstrate that L1 promotes neuronal differentiation from ESCs through the L1-mediated enhancement of FUT9 and ST3Gal4 expression.
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Disruption of the Dapper3 gene aggravates ureteral obstruction-mediated renal fibrosis by amplifying Wnt/?-catenin signaling.
J. Biol. Chem.
PUBLISHED: 04-11-2013
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Wnt/?-catenin signaling plays key roles in embryonic development and tissue homeostasis. Dapper3/Dact3, one of the three members of the Dapper gene family, is transcriptionally repressed in colorectal cancer and may function as a negative regulator of Wnt/?-catenin signaling. To investigate its physiological functions, we generated a mouse strain harboring conditional null alleles of Dapper3 (Dapper3(flox/flox)), and homozygous Dapper3-deficient (Dapper3(-/-)) mice were produced after crossing with EIIa-cre transgenic mice. We found that Dapper3 is not essential for mouse embryogenesis, postnatal survival, and reproduction. However, adult Dapper3(-/-) mice exhibited a mild reduction in body weight compared with their wild-type littermates, suggesting a functional role of Dapper3 in postnatal growth. To investigate the role of Dapper3 in renal fibrosis, we employed the unilateral ureteral obstruction model. Dapper3 mRNA expression was up-regulated in kidney after unilateral ureteral obstruction. Loss of the Dapper3 gene enhanced myofibroblast activation and extracellular matrix overproduction in the obstructed kidney. Moreover, this aggravated fibrotic phenotype was accompanied with accumulation of Dishevelled2 and ?-catenin proteins and activation of Wnt-targeted fibrotic genes. In primary renal tubular cells, Dapper3 inhibits Wnt-induced epithelial-to-mesenchymal transition. Consistently, Dapper3 interacted with and down-regulated Dishevelled2 protein and attenuated the Wnt-responsive Topflash reporter expression. These findings together suggest that Dapper3 antagonizes the fibrotic actions of Wnt signaling in kidney.
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Upregulation of blood proBDNF and its receptors in major depression.
J Affect Disord
PUBLISHED: 03-01-2013
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In recent decades, the role of brain-derived neurotrophic factor (BDNF) in depression has received intensive attention. However, the relationship between proBDNF and depression has not been clearly elucidated.
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The cell adhesion molecule L1 regulates the expression of FGF21 and enhances neurite outgrowth.
Brain Res.
PUBLISHED: 01-12-2013
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L1 plays a role in neural development. However, it remains unclear how L1 plays this role. In the present study, we have shown extensive outgrowth of long neurites in cerebellar neurons after treatment with either L1 or L1 antibody. Notably, the mRNA level of FGF21 was significantly increased in both L1 and L1 antibody treated neurons compared to control group. Consistently, the neurite outgrowth promoted by L1 was strongly inhibited by siRNA against FGF21 gene or a treatment of cells with FGFR inhibitor. These results demonstrate that FGF21/FGFR signaling promotes the neurite outgrowth in a L1-dependent manner.
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Recombinant DNA vaccine against neurite outgrowth inhibitors attenuates behavioral deficits and decreases Abeta in an Alzheimers disease mouse model.
Neuropharmacology
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Alzheimers disease (AD) is a chronic neurodegenerative disease that causes a progressive loss in learning and memory capabilities and eventually results in dementia. The non-renewable nature of neurons in the central nervous system leads to the basic pathological changes that are related to the various behavioral and psychological symptoms of AD. Oligodendrocyte- and myelin-related neurite outgrowth inhibitors (NOIs) tend to hinder the regeneration of neurons. We designed a recombinant DNA vaccine composed of multiple specific inhibitory domains of NOIs. Vaccination induced effective antibodies against the specific domains in the sera of mice treated with a DNA primed-vaccinia virus boost regimen. The vaccine attenuated neuronal degeneration in the mouse brain and protected the model mice from behavioral deficits. Vaccination also decreased the formation of soluble A? oligomer and amyloid plaques in the co-transgenic mice brain. Whats more, astrocytosis in brains of APP/PS1 co-transgenic mice was also relieved. The results suggested that immunotherapy with multiple specific domains of myelin- and oligodendrocyte-related NOIs may be a promising approach for Alzheimers disease and other degenerative central nervous system diseases.
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Rolipram promotes remyelination possibly via MEK-ERK signal pathway in cuprizone-induced demyelination mouse.
Exp. Neurol.
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Rolipram, a 3-5-cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase 4 (PDE4) inhibitor, has long been studied for its immune modulating effects in the treatment of experimental autoimmune encephalomyelitis (EAE). In the current study, we investigated the effects of rolipram on remyelination after cuprizone- or lysolecithin-induced demyelination and the signal transduction pathways potentially modulating this response.
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Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signalling in Alzheimers disease.
J Clin Neurosci
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Alzheimers disease (AD) is one of the most common causes of dementia in the elderly. It is characterized by extracellular deposition of the neurotoxic peptide, amyloid-beta (A?) peptide fibrils, and is accompanied by extensive loss of neurons in the brains of affected individuals. However, the pathogenesis of AD is not fully understood. The aim of this review is to discuss the possible role of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signalling in the development of AD, focusing on BDNF/TrkB signalling in the production of A?, tau hyperphosphorylation and cognition decline, and exploring new possibilities for AD intervention.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.