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Find video protocols related to scientific articles indexed in Pubmed.
Epigenetic inactivation of transforming growth factor-?1 target gene HEYL, a novel tumor suppressor, is involved in the P53-induced apoptotic pathway in hepatocellular carcinoma.
Hepatol. Res.
PUBLISHED: 09-02-2014
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Hairy/enhancer-of-split related with YRPW motif-like (HEYL) protein was first identified as a transcriptional repressor. It is a downstream gene of the Notch and transforming growth factor-? pathways. Little is known about its role in the pathogenesis of hepatocellular carcinoma (HCC).
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Modified fluoroscopy-guided sacroiliac joint injection: a technical report.
Pain Med
PUBLISHED: 08-26-2014
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Sacroiliac joint (SIJ) injection can occasionally be challenging. We describe our experience in using conventional technique, and we developed an adjustment to overcome difficulties incurred.
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Indoxyl sulfate induces renin release and apoptosis of kidney mesangial cells.
J Toxicol Sci
PUBLISHED: 07-25-2014
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Indoxyl sulfate is considered to play a pathological role in the progression of chronic kidney disease. The aim of this study was to investigate the deleterious effects of indoxyl sulfate on kidney mesangial cells.
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Signal transducer and activator of transcription 3 as molecular therapy for non-small-cell lung cancer.
J Thorac Oncol
PUBLISHED: 04-17-2014
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Targeting signal transducer and activator of transcription 3 (STAT3), a transcription factor that modulates survival-directed transcription, is often persistently activated in epidermal growth factor receptor (EGFR) wild-type non-small-cell lung cancer (NSCLC). The aim of this study was to determine whether sorafenib and its derivative can inhibit EGFR wild-type NSCLC via STAT3 inactivation.
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The hormonal regulation of color changes in the sexually dichromatic frog Buergeria robusta.
Physiol. Biochem. Zool.
PUBLISHED: 04-14-2014
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During the breeding season, dynamic changes in body coloration are regularly observed in the male brown tree frog Buergeria robusta. This study investigated the hypothesis that this sexual dichromatism in male B. robusta is mediated through hormonal regulation. Frogs were exogenously injected with testosterone (T) or estradiol (E2). This manipulation revealed that the body coloration (hue, brightness, and saturation) of the male frog increased significantly (i.e., the brilliant yellow color developed) in response to T but not in response to E2. Concurrently, the levels of expression of brain-derived neurotrophic factor (BDNF) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the pituitary gland were reduced in frogs whose coloration was pale brown on a yellow background. In particular, the weakest expressions of BDNF, PACAP, and PACAP type II receptors (VPAC-1R) were found in male frogs with a brilliant yellow body color during the breeding season regardless of background color. These changes may decrease ?-melanocyte-stimulating hormone production associated with the PACAP receptors (VPAC-1R), resulting in the aggregation of black pigment in melanophores and the production of a brilliant yellow body color. The effects of hormones on skin coloration were further examined in isolated skin in vitro. The results of this investigation showed that the dispersion of xanthophores was stimulated by T or prolactin (PRL) and that the melanophores were aggregated by melatonin (MEL) but not by E2. Furthermore, yellow pigments in the xanthophores were significantly dispersed following the PRL+T treatment. In the T+MEL, PRL+MEL, and T+PRL+MEL treatments, xanthophores were dispersed, and melanophores were aggregated and subsequently moved to the low spongiosum layer of the dorsal skin, causing the increase in yellow coloration. These results reveal that multiple hormones play major roles in the regulation of the brilliant yellow coloration of male B. robusta by high plasma T during the breeding season.
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Antrodia cinnamomea profoundly exalted the reversion of activated hepatic stellate cells by the alteration of cellular proteins.
Food Chem. Toxicol.
PUBLISHED: 03-24-2014
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The direct modulation of Antrodia cinnamomea (AC) on the prominent role of liver fibrosis-hepatic stellate cells (HSCs) in situ remains unclear. Firstly, the administration of A. cinnamomea mycelial extract (ACME) could improve liver morphology and histological changes including collagen formation and GPT activity in the liver of thioacetamide (TAA)-injured rats. The morphology and fatty acid restore of TAA-induced HSCs (THSCs) returned to the non-chemical induced HSCs (NHSCs) type as measured by immunofluorescence and Oil Red O staining. PPAR? was upregulated associated with the lowering of ?-SMA protein in NHSC-ACME. ACME inhibited the MMP-2 activity in NHSCs by gelatin Zymography. After LC-MS/MS, the cytoskeleton (tubulin, lamin A) and heat shock protein 8 in NHSC-ACME, and guanylate kinase, brain-specific kinase, SG-II and p55 proteins were downregulated in THSC-ACME. Whereas MHC class II, SMC6 protein, and phospholipase D were upregulated in NHSC-ACME. Furthermore, PKG-1 was downregulated in NHSC-ACME and upregulated in THSC-ACME. SG-II and p55 proteins were downregulated in NHSC-ACME and THSC-ACME by Western blotting. Taken together, the beneficial effect of A. cinnamomea on the induction of HSC cellular proteins is potentially applied as an alternative and complementary medicine for the prevention and amelioration of a liver injury.
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Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells.
J. Nutr. Biochem.
PUBLISHED: 03-23-2014
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Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate cells (HSCs), previously termed fat- or vitamin A-storing cells, can transdifferentiate into myofibroblast-like cells and are the most relevant cell type for overproduction of extracellular matrix (ECM) and development of liver fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs remains unclear. This study investigates the regulatory effect of natural compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have shown a significant effect on cell proliferation with oil red O staining and Western blot confirming that OA and PA induce fat storage ability and autophagy protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and benzyl cinnamate treatment have shown no effect on the autophagy protein expression. Nevertheless, cells pretreated with OA and PA then treated with rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway, the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment. However, there were no significant changes in PI3K-Class III and Beclin-1 protein expressions found to imply that this autophagy is unrelated to the mTOR-independent pathway. Taken together, the present study unveils rutin and curcumin as a possible effective stimulation for fatty acid-induced autophagy via mTOR-dependent pathways in NHSC. We further suggest the benefits of these natural compounds for alleviating liver fibrosis.
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SMAD4 loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells.
BMC Cancer
PUBLISHED: 02-28-2014
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SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully characterized.
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Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation.
Mol Nutr Food Res
PUBLISHED: 02-24-2014
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We investigated whether rutin, a flavonoid isolated from Toona sinensis Roem, has the ability to enhance insulin-dependent receptor kinase (IRK) activity and glucose transporter 4 (GLUT4) translocation in differentiated myotubes. We also tested the effects of rutin treatment in insulin-resistant mice using an oral glucose tolerance test (OGTT).
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Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells.
Food Chem. Toxicol.
PUBLISHED: 02-10-2014
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Doxorubicin (DOX) is the best anticancer agent that has ever been used, but acquired tumor resistance and dose limiting toxicity are major road blocks. Concomitant use of natural compounds is a promising strategy to overcome this problem. Neferine, a proven anticancer agent is found in green embryos of lotus seed. The study demonstrates that neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-?B nuclear translocation. Cotreatment of cells with neferine significantly enhanced intracellular DOX-accumulation. Neferine and DOX in combination also triggered oxidative stress through intracellular Ca(2+) accumulation and dissipation of mitochondrial membrane potential in addition to significant loss of cellular antioxidant pool. The MAPK inhibitor effectively decreased the cell-death induced by neferine and DOX. Pretreatment of cells with glutathione reversed the apoptosis induced by combined regimen and recovered the Bcl2/Bax ratio. Moreover, neferine treatment significantly increased the cell viability of DOX-treated cardiomyocytes indicating a possible protective role of neferine towards DOX-induced cardiotoxicity. Taken together, our results suggest that a strategy of using neferine and DOX in combination could be helpful to increase the efficacy of DOX and to achieve anticancer synergism by curbing the toxicity.
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Activation of VCAM-1 and its associated molecule CD44 leads to increased malignant potential of breast cancer cells.
Int J Mol Sci
PUBLISHED: 01-30-2014
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VCAM-1 (CD106), a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (?4?1). In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT) program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGF?1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.
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Resequencing and association study of the NFKB activating protein-like gene (NKAPL) in schizophrenia.
Schizophr. Res.
PUBLISHED: 01-24-2014
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Schizophrenia is a highly inheritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, in the Han Chinese population, a SNP rs1635 located within the exon of the NKAPL gene (encoding NFKB activating protein-like) achieved genome-wide significance in schizophrenia.
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Briarane diterpenoids isolated from gorgonian corals between 2011 and 2013.
Mar Drugs
PUBLISHED: 01-22-2014
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The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.
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Resveratrol inhibits glucose-induced migration of vascular smooth muscle cells mediated by focal adhesion kinase.
Mol Nutr Food Res
PUBLISHED: 01-21-2014
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Diabetes is a critical factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and subsequently contributes to the formation of atherosclerotic lesions. This study investigates whether resveratrol plays a regulatory role in the proliferation and migration of VSMCs under high glucose induction to imitate a hyperglycemic condition.
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Utilization of liquid chromatography mass spectrometry analyses to identify LKB1-APC interaction in modulating Wnt/?-catenin pathway of lung cancer cells.
Mol. Cancer Res.
PUBLISHED: 01-21-2014
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STK11/LKB1, a serine/threonine protein kinase and tumor suppressor, is a key upstream kinase of adenine monophosphate-activated protein kinase, which is a kinase involved in controlling cell polarity and maintaining cellular energy homeostasis. LKB1 is mutated in a significant number of Peutz-Jeghers syndrome (PJS) cases and sporadic cancers, and is most frequently mutated in lung adenocarcinomas; however, little is known about how LKB1 is involved in lung cancer progression. In this study, immunoprecipitation-HPLC tandem mass spectrometry (IP-LC-MS/MS) was performed to identify novel proteins interacting with LKB1 in lung cancer. Interestingly, many LKB1-interacting proteins acquired from the LC-MS/MS approach were mapped, using MetaCore pathway analysis, to the cystic fibrosis transmembrane conductance regulator activation pathway. Moreover, it was determined that LKB1 directly interacts with APC, and this LKB1-APC interaction was further confirmed by reverse immunoprecipitation assays, but GSK3? was dispensable for the association of LKB1 and APC. Importantly, LKB1 binds to APC to suppress the Wnt/?-catenin signaling pathway, which is known to be involved in cell proliferation and migration. Subsequent analysis of the downstream targets of the Wnt/TCF pathway led to the identification of several Wnt-regulated genes, such as CD44, COX-2, survivin, and c-Myc, whose expression levels are downregulated by LKB1. In summary, these results demonstrate that LKB1 regulates the Wnt pathway through a direct interaction with APC to suppress the tumorigenic/metastatic potential of lung tumors.
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A new phylogeographic pattern of endemic Bufo bankorensis in Taiwan Island is attributed to the genetic variation of populations.
PLoS ONE
PUBLISHED: 01-01-2014
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To comprehend the phylogeographic patterns of genetic variation in anurans at Taiwan Island, this study attempted to examine (1) the existence of various geological barriers (Central Mountain Ranges, CMRs); and (2) the genetic variation of Bufo bankorensis using mtDNA sequences among populations located in different regions of Taiwan, characterized by different climates and existing under extreme conditions when compared available sequences of related species B. gargarizans of mainland China.
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DPP-4 inhibitor attenuates toxic effects of indoxyl sulfate on kidney tubular cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Diabetic nephropathy is a common causative factor of chronic kidney disease (CKD). DPP-4 inhibitor has the ability to improve kidney function and renal microvasculature. In the present study, we investigate the deleterious effects of IS on proximal tubular cells and the protective role of DPP-4 inhibitor. Human kidney 2 (HK-2) cells were exposed to IS in the presence or absence of DPP-4 inhibitor. Effects of DPP-4 inhibitor on viability of HK-2 cells were determined by MTT assay. Reactive oxygen species (ROS) production was examined using fluorescent microscopy. Levels of cleaved caspase-3, transforming growth factor-beta (TGF-?), ?-smooth muscle actin (?-SMA) and NF-kappaB p65 and phosphorylation of AKT and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Production of ROS and level of cleaved caspase-3 were increased by IS in a dose-dependent manner. The phosphorylation of AKT and ERK p65 were decreased alongside activation of NF-?B. Expression of TGF-? and ?-SMA, were upregulated in IS-treated HK-2 cells. Treatment with DPP-4 inhibitor resulted in a significant increase in cell viability and a decrease of ROS production in IS-treated HK-2 cells. DPP-4 inhibitor restored IS-induced deactivations of AKT and ERK and inhibited activation of NF-?B in IS-treated HK-2 cells. Moreover, DPP-4 inhibitor could also attenuate IS-induced up-regulation of TGF-? and ?-SMA expression. These findings suggest that DPP-4 inhibitor possesses anti-apoptotic activity to ameliorate the IS-induced renal damage, which may be partly attributed to regulating ROS/p38MAPK/ERK and PI3K-AKT pathways as well as downstream NF-?B signaling pathway.
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Suppression of allergic reactions in ovalbumin-sensitized mice by yam storage proteins dioscorins.
J. Agric. Food Chem.
PUBLISHED: 11-18-2013
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To study the biomedical functions of dioscorins isolated from various species of Dioscorea , we investigated their antiallergic potential using an OVA-induced allergy mouse model. All the dioscorins suppressed allergic reactions by decreasing the serum IgE and histamine levels. The serum IFN-? and IgG2a levels increased in all the dioscorin-treated mice. The spleen cells from the dioscorin-treated mice also exhibited an up-regulation of IFN-? secretion in response to ConA stimulation. Although dioscorins did not affect the IgG1 levels, the IL-5 levels decreased to basal levels in mice treated with dioscorins of D. alata or D. japonica and in most of the lymphoid cells of the dioscorin-treated mice in response to ConA stimulation. The decrease of IgE and histamine levels was concomitant with an increase in IFN-? and IgG2a levels and with a decrease in IL-5 levels, suggesting that dioscorins suppressed the OVA-induced allergic reactions, possibly through modulating an imbalanced Th1/Th2 immune response.
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Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded protein response and heme oxygenase-1 expression in PC12 cells: Roles of ROS and MAPK pathways.
Toxicology
PUBLISHED: 10-21-2013
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This study investigates the roles of ROS overproduction and MAPK signaling pathways in the induction of unfolded protein response (UPR) and the expression of Phase II enzymes in response to 4-hydroxy-trans-2-nonenal (4-HNE) in a neuronal-like catecholaminergic PC12 cells. Our results showed that 4-HNE triggered three canonical pathways of UPR, namely IRE1-XBP1, PERK-eIF2?-ATF4 and ATF6, and induced the expression of UPR-targeted genes, GRP78, CHOP, TRB3, PUMA, and GADD34, as well as Phase II enzymes, HO-1 and GCLC. 4-HNE also induced apoptosis, intracellular calcium accumulation, caspase-3 activation, and G0/G1 cell cycle arrest, which was correlated with the increased expression of GADD45?. The addition of tiron, a cellular permeable superoxide scavenger, scavenged 4-HNE-mediated ROS formation, but did not alleviate cytotoxicity, or the expression of UPR-targeted genes or Phase II enzymes, indicating that ROS overproduction per se did not play a major role in 4-HNE-caused deleterious effects. HO-1 expression was attenuated by Nrf2 siRNA and chemical chaperone 4-phenylbutyrate (4-PBA), suggesting HO-1 expression was regulated by Nrf2-ARE, which may work downstream of ER stress. 4-HNE treatment promptly induced ERK, JNK and p38 MAPK activation. Addition of p38 MAPK specific inhibitor SB203580 attenuated HO-1 upregulation, but enhanced expression of CHOP, PUMA and TRB3, and cytotoxicity. These results indicate that 4-HNE-induced transient p38 MAPK activation may serve as an upstream negative regulator of ER stress and confer adaptive cytoprotection against 4-HNE-mediated cell injury.
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[A project to improve psychiatric nursing station air quality].
Hu Li Za Zhi
PUBLISHED: 10-08-2013
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Ambient air at the psychiatric nursing station in our hospital had been notably poor for an extensive period of time. CO2 levels at the station averaged 1211 ppm during August, 2009 and a specialist team estimated a CO2 abnormality ratio of 32%. Analysis identified key issues in three problem areas, including (1) Environment: air at the station was not refreshed and electronic equipment was in constant operation; (2) Staff: the station had a high staff-to-space ratio and staffs lacked practical knowledge on indoor air quality maintenance; and (3) Policy: the hospital had no guidelines addressing indoor air quality maintenance.
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Functionalization of mesoporous silica nanoparticles for targeting, biocompatibility, combined cancer therapies and theragnosis.
J Nanosci Nanotechnol
PUBLISHED: 06-15-2013
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The advent of Nanotechnology has paved a way for improved disease treatment strategies, the most noteworthy being the mesoporous silica nanoparticles (MSNs) which have gained much recent attention in the field of cancer therapy and its diagnosis. The flaws of the current-day strategies can be overcome by this superior technology through its targeting ability in delivering drugs and image able agents specifically to the tumor sites. MSNs have unique biocompatibility features, its high surface area which contributes in large amount of drug loading and its facility to monitor size and shape of the nanoparticles are few of the positives which makes this technology an enormous asset for the field of Nanotechnology. This review paper is structured in such a way wherein we initially have discussed about the synthesis methods and various functionalization approaches for MSN followed by the different methods used for targeting cancer cells and the latest advances in controlled drug release. Some of the highlights of this review are the biocompatibility of MSNs, in vivo results of MSNs on cancer therapy. This review paper also shortly discuss about combined cancer therapies to overcome the challenges in current-day cancer treatment. Finally, we converge briefly on the recent advancements in the use of hybrid MSNs for obtaining multiple functions.
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Stem cell marker nestin is critical for TGF-?1-mediated tumor progression in pancreatic cancer.
Mol. Cancer Res.
PUBLISHED: 04-03-2013
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The stem cell marker nestin is an intermediate filament protein that plays an important role in cell integrity, migration, and differentiation. Nestin expression occurs in approximately one third of pancreatic ductal adenocarcinoma (PDAC), and its expression strongly correlates with tumor staging and metastasis. Little is known about the mechanisms by which nestin influences PDAC progression. Here, nestin overexpression in PDAC cells increased cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate and reverted cells to a more epithelial phenotype. Mouse xenograft studies showed that knockdown of nestin significantly reduced tumor incidence and volume. Nestin protein expression was associated with Smad4 status in PDAC cells; hence, nestin expression might be regulated by the TGF-?1/Smad4 pathway in PDAC. We examined nestin expression after TGF-?1 treatment in human pancreatic cancer PANC-1 and PANC-1 shSmad4 cells. The TGF-?1/Smad4 pathway induced nestin protein expression in PDAC cells in a Smad4-dependent manner. Moreover, increased nestin expression caused a positive feedback regulator of the TGF-?1 signaling system. In addition, hypoxia was shown to induce nestin expression in PDAC cells, and the hypoxia-induced expression of nestin is mediated by the TGF-?1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and withaferin A, exhibited anti-nestin activity; these inhibitors might be potential antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating TGF-?1-induced EMT. Anti-nestin therapeutics may serve as a potential treatment for PDAC metastasis.
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Arsenic trioxide induces unfolded protein response in vascular endothelial cells.
Arch. Toxicol.
PUBLISHED: 03-24-2013
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Chronic arsenic exposure has been linked to endothelial dysfunction and apoptosis. We investigate the involvement of unfolded protein response (UPR) signaling in the arsenic-mediated cytotoxicity of the SVEC4-10 mouse endothelial cells. The SVEC4-10 cells underwent apoptosis in response to As2O3 dose- and time-dependently, accompanied by increased accumulation of calcium, and activation of caspase-3. These phenomena were completely inhibited by ?-lipoic acid (LA), which did not scavenge ROS over-production, but were only partially or not ameliorated by tiron, a potent superoxide scavenger. Moreover, arsenic activated UPR, leading to phosphorylation of eukaryotic translation initiation factor 2 subunit ? (eIF2?), induction of ATF4, and processing of ATF6. Treatment with arsenic also triggered the expression of endoplasmic reticulum (ER) stress markers, GRP78 (glucose-regulated protein), and CHOP (C/EBP homologous protein). The activation of eIF2?, ATF4 and ATF6 and expression of GRP78 and CHOP are repressed by both LA and tiron, indicating arsenic-induced UPR is mediated through ROS-dependent and ROS-independent pathways. Arsenic also induced ER stress-inducible genes, BAX, PUMA (p53 upregulated modulator of apoptosis), TRB3 (tribbles-related protein 3), and SNAT2 (sodium-dependent neutral amino acid transporter 2). Consistent with intracellular calcium and cell viability data, ROS may not be important in arsenic-induced death, because tiron did not affect the expression of these pro-apoptotic genes. In addition, pretreatment with salubrinal, a selective inhibitor of eIF2? dephosphorylation, enhanced arsenic-induced GRP78 and CHOP expression and partially prevented arsenic cytotoxicity in SVEC4-10 cells. Taken together, these results suggest that arsenic-induced endothelial cytotoxicity is associated with ER stress, which is mediated by ROS-dependent and ROS-independent signaling.
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Immunomodulatory effect of marine cembrane-type diterpenoids on dendritic cells.
Mar Drugs
PUBLISHED: 02-26-2013
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Dendritic cells (DCs) are antigen presenting cells, which can present antigens to T-cells and play an important role in linking innate and adaptive immunity. DC maturation can be induced by many stimuli, including pro-inflammatory cytokines and bacterial products, such as lipopolysaccharides (LPS). Here, we examined the immunomodulatory effects of marine cembrane compounds, (9E,13E)-5-acetoxy-6-hydroxy-9,13-dimethyl-3- methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (1), (9E,13E)- 5-acetoxy-6-acetyl-9,13-dimethyl-3-methylene-3,3a,4,5,6,7,8,11,12,14a-decahydro-2H-cyclotrideca[b]furan-2-one (2), lobocrassin B (3), (-)14-deoxycrassin (4), cembranolide B (5) and 13-acetoxysarcocrassolide (6) isolated from a soft coral, Lobophytum crassum, on mouse bone marrow-derived dendritic cells (BMDCs). The results revealed that cembrane-type diterpenoids, especially lobocrassin B, effectively inhibited LPS-induced BMDC activation by inhibiting the production of TNF-?. Pre-treatment of BMDCs with Lobocrassin B for 1 h is essential to prohibit the following activation induced by various toll-like receptor (TLR) agonists, such as LPS, zymosan, lipoteichoic acid (LTA) and Pam2CSK4. Inhibition of NF-?B nuclear translocation by lobocrassin B, which is a key transcription factor for cytokine production in TLR signaling, was evident as assayed by high-content image analysis. Lobocrassin B attenuated DC maturation and endocytosis as the expression levels of MHC class II and the co-stimulatory molecules were downregulated, which may affect the function of DCs to initiate the T-cell responses. Thus, lobocrassin B may have the potential in treatment of immune dysregulated diseases in the future.
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Enhanced prostacyclin synthesis by adenoviral gene transfer reduced glial activation and ameliorated dopaminergic dysfunction in hemiparkinsonian rats.
Oxid Med Cell Longev
PUBLISHED: 02-10-2013
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Prostacyclin (PGI2), a potent vasodilator and platelet antiaggregatory eicosanoid, is cytoprotective in cerebral circulation. It is synthesized from arachidonic acid (AA) by the sequential action of cyclooxygenase- (COX-) 1 or 2 and prostacyclin synthase (PGIS). Because prostacyclin is unstable in vivo, PGI2 analogs have been developed and demonstrated to protect against brain ischemia. This work attempts to selectively augment PGI2 synthesis in mixed glial culture or in a model of Parkinsons disease (PD) by direct adenoviral gene transfer of prostacyclin biosynthetic enzymes and examines whether it confers protection in cultures or in vivo. Confluent mixed glial cultures actively metabolized exogenous AA into PGE2 and PGD2. These PGs were largely NS398 sensitive and considered as COX-2 products. Gene transfer of AdPGIS to the cultures effectively shunted the AA catabolism to prostacyclin synthesis and concurrently reduced cell proliferation. Furthermore, PGIS overexpression significantly reduced LPS stimulation in cultures. In vivo, adenoviral gene transfer of bicistronic COX-1/PGIS to substantia nigra protected 6-OHDA- induced dopamine depletion and ameliorated behavioral deficits. Taken together, this study shows that enhanced prostacyclin synthesis reduced glial activation and ameliorated motor dysfunction in hemiparkinsonian rats. Prostacyclin may have a neuroprotective role in modulating the inflammatory response in degenerating nigra-striatal pathway.
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Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest.
Biofactors
PUBLISHED: 02-05-2013
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Neferine is the major bisbenzylisoquinoline alkaloid isolated from the seed embryo of a traditional medicinal plant Nelumbo nucifera (Lotus). Epidemiological studies have revealed the therapeutic potential of lotus seed embryo. Although several mechanisms have been proposed, a clear anticancer action mechanism of neferine on lung cancer cells is still not known. Lung cancer is the most common cause of cancer death in the world, and the patients with advanced stage of nonsmall lung cancer require adjunct chemotherapy after surgical resection for the eradication of cancer cells. In this study, the effects of neferine were evaluated and characterized in A549 cells. Neferine induced apoptosis in a dose-dependent manner with the hypergeneration of reactive oxygen species, activation of MAPKs, lipid peroxidation, depletion of cellular antioxidant pool, loss of mitochondrial membrane potential, and intracellular calcium accumulation. Furthermore, neferine treatment leads to the inhibition of nuclear factor kappaB and Bcl2, upregulation of Bax and Bad, release of cytochrome C, activation of caspase cascade, and DNA fragmentation. In addition, neferine could induce p53 and its effector protein p21 and downregulation of cell cycle regulatory protein cyclin D1 thereby inducing G1 cell cycle arrest. These results suggest a novel function of neferine as an apoptosis inducer in lung cancer cells. © 2013 BioFactors, 2013.
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Curcuminoids distinctly exhibit antioxidant activities and regulate expression of scavenger receptors and heme oxygenase-1.
Mol Nutr Food Res
PUBLISHED: 02-05-2013
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Curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) have been demonstrated as having antioxidant, anticarcinogenic, and hypocholesterolemic activities. We report the diverse antiatherogenic effects and mechanisms of curcuminoids.
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Neutralization of five subgenotypes of Enterovirus 71 by Taiwanese human plasma and Taiwanese plasma derived intravenous immunoglobulin.
Biologicals
PUBLISHED: 01-31-2013
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Enterovirus 71 (EV71) commonly occurs in children, causing hand, foot and mouth disease (HFMD) in about 29% of patients. Studies have suggested that patients develop meningitis and encephalopathy with a mortality rate of 4-26%. EV71 subgenotypes including B4, B5, C2, C4 and C5 have caused HFMD epidemics in Taiwan. In terms of therapeutical strategy, intravenous immunoglobulin (IVIG) has been shown to improve patient conditions. In this study, the EV71 neutralizing titer was evaluated in 75 human plasmas and 8 lots of Taiwanese plasma derived IVIG. Results showed that human plasmas and IVIG significantly neutralized B4 and C2 subgenotypes. Four percent of human plasma contained neutralizing antibody titer of 1:128 against B4 and C2. Most IVIG lots possessed a median effective dose of over 100 against B4 and C2. IVIG lots had an average neutralizing capacity of 5.60, 0.90, 4.30, 1.12 and 0.77 log10 CCID50/ml against B4, B5, C2, C4 and C5, respectively. In conclusion, effective neutralization of B4 and C2 could be due to their earlier appearance in the EV71 epidemiology timeline of Taiwan. IVIG derived from Taiwanese plasma may be desirable for treatment of patients infected with EV71 of specific subgenotypes.
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Effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3,4-hexamethoxyflavone and 3,5,6,7,8,3,4-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor.
Food Funct
PUBLISHED: 01-31-2013
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Epidemiological and animal studies point to a possible protective effect of citrus flavonoids against cardiovascular diseases. The aim of this study is to investigate the effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3,4-hexamethoxyflavone (5-OH-HxMF) and 3,5,6,7,8,3,4-heptamethoxyflavone (HpMF), on the activities and expressions of macrophage scavenger receptors and the hepatic LDL receptor. Treatment of HpMF (20 ?M) during THP-1 differentiation successfully attenuated 12-myristate 13-acetate (PMA)-mediated DiI-labeled oxidized low-density lipoprotein (oxLDL) uptake as evidenced by flow cytometry, indicating that the functions of scavenger receptors were blocked. RT-Q-PCR analysis suggests that the decrease in oxLDL uptake was due to the down-regulation of PMA-induced SR-A mRNA expression. In terminally differentiated THP-1 macrophages, 5-OH-HxMF and HpMF could significantly reduce DiI-oxLDL uptake, with the former having a greater effect. 5-OH-HxMF attenuated oxLDL-mediated CD36 and SR-A expression; while HpMF only decreased CD36 expression. The effects of these two flavonoids on the activity and expression of the hepatic LDL receptor (LDLR) were further investigated in HepG2 cells. 5-OH-HxMF (10-20 ?M) enhanced DiI-LDL uptake by 1.33-fold due to the enhanced LDLR expression. These results imply that HpMF is better at inhibiting PMA-induced oxLDL uptake during THP-1 differentiation, while 5-OH-HxMF is more powerful in attenuating oxLDL-induced scavenger receptor expression and activity in terminally differentiated THP-1 macrophages. Furthermore, 5-OH-HxMF may have hypolipidemic activity due to its up-regulating hepatic LDLR expression.
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A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking.
Biochim. Biophys. Acta
PUBLISHED: 01-25-2013
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Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine plays an important role in a number of cell signaling pathways, including cell migration, proliferation, and cell survival. This study was aimed to identify novel and specific inhibitors from natural compounds via molecular docking of FAK (Y397).
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Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells.
Food Chem
PUBLISHED: 01-17-2013
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Previously we have reported that neferine from the medicinal plant Nelumbo nucifera, inhibited cancer cell proliferation by inducing apoptosis. The present study was focused on the action mechanism of neferine in inducing autophagy in lung cancer cells. Neferine markedly inhibited A549 cell proliferation in a dose dependent manner. Acidic vesicular accumulation was observed in neferine treated cells as an indication of autophagy. Neferine could induce the conversion of LC3B-I to LC3B-II without affecting the expression levels of PI3KCIII and Beclin1. It has been observed that neferine mediated autophagy is dependent on inhibition of PI3K/Akt/mTOR signaling by neferine. Neferine treatment could also lead to the ROS hypergeneration and depletion of cellular antioxidant, GSH. The results demonstrate that neferine-induced autophagy is mediated through ROS hypergeneration and mTOR inhibition. Taken together, the present study unveils a novel mechanism of action of neferine on lung cancer cells in the induction of autophagy.
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Natural product chemistry of gorgonian corals of genus Junceella--part II.
Mar Drugs
PUBLISHED: 11-10-2011
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The structures, names, bioactivities, and references of 81 new secondary metabolites obtained from gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from sea whip gorgonian corals Junceella fragilis and Junceella juncea, collected from the tropical and subtropical Indo-Pacific Ocean.
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Specialty differences in the association between health care climate and patient trust.
Med Educ
PUBLISHED: 08-19-2011
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Previous studies have suggested that there is a positive correlation between doctors emotional intelligence (EI) and patients trust in their attending physicians; however, there is only limited evidence of specialty differences between internists and surgeons for such an association.
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Associations between emotional intelligence and doctor burnout, job satisfaction and patient satisfaction.
Med Educ
PUBLISHED: 07-15-2011
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The occupational health literature has long been dominated by stress-related topics. A more contemporary perspective suggests using a positive approach in the form of a health model focused on what is right with people, such as feelings of well-being and satisfaction.
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Lobocrassins A-E: new cembrane-type diterpenoids from the soft coral Lobophytum crassum.
Mar Drugs
PUBLISHED: 07-05-2011
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Five new cembrane-type diterpenoids, lobocrassins A-E (1-5), were isolated from the soft coral Lobophytum crassum. The structures of cembranes 1-5 were established by spectroscopic and chemical methods and by comparison of the spectral data with those of known cembrane analogues. Lobocrassin A (1) is the first cembranoid possessing an ?-chloromethyl-?-hydroxy-?-lactone functionality and is the first chlorinated cembranoid from soft corals belonging to the genus Lobophytum. Lobocrassins B (2) and C (3) were found to be the stereoisomers of the known cembranes, 14-deoxycrassin (6) and pseudoplexaurol (7), respectively. Lobocrassin B (2) exhibited modest cytotoxicity toward K562, CCRF-CEM, Molt4, and HepG2 tumor cells and displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.
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3,4-didemethylnobiletin induces phase II detoxification gene expression and modulates PI3K/Akt signaling in PC12 cells.
Free Radic. Biol. Med.
PUBLISHED: 05-18-2011
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Oxidative stress is considered a major cause of neurodegenerative disorders. In this work, we investigated the cytoprotective effects and mechanisms of the citrus flavonoid nobiletin (NOB) and its metabolite, 3,4-didemethylnobiletin (3,4-dihydroxy-5,6,7,8-tetramethoxyflavone; DTF), in PC12 cells. Both NOB and DTF exhibited strong potency in attenuating serum withdrawal- and H(2)O(2)-caused cell death and increased intracellular GSH level via upregulation of both catalytic and modifier subunits of glutamate-cysteine ligase (GCL). However, only DTF suppressed intracellular ROS accumulation in H(2)O(2)-treated cells, induced heme oxygenase-1 (HO-1) expression, and enhanced nuclear factor E2-related factor 2 (Nrf2) binding to the ARE. Nevertheless, DTF-mediated HO-1 upregulation was independent of Nrf2 activation because knockdown of Nrf2 expression by siRNA did not affect its expression. DTF suppressed NF-?B activation, and addition of NF-?B inhibitor, pyrrolidine dithiocarbamate or Bay 11-7082, synergistically enhanced DTF-mediated HO-1 expression, indicating that HO-1 induction is associated with NF-?B suppression. NOB and DTF also activated the ERK, JNK, and Akt pathways in PC12 cells that had undergone serum starvation. Addition of pharmacological kinase inhibitors, U0126, SP600125, and LY294002, caused cytotoxicity and the last significantly attenuated NOB- and DTF-mediated antiapoptotic actions, indicating the involvement of PI3K/Akt signaling in their cytoprotective effects. In conclusion, HO-1 and GCL upregulation and intrinsic ROS-scavenging activity may contribute to DTF-mediated cytoprotection. Furthermore, modulation of PI3K/Akt signaling is involved in channeling the DTF stimulus for cell survival against oxidative insults.
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Discovery of new eunicellins from an Indonesian octocoral Cladiella sp.
Mar Drugs
PUBLISHED: 04-14-2011
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Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (-)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study.
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Lipoic acid ameliorates arsenic trioxide-induced HO-1 expression and oxidative stress in THP-1 monocytes and macrophages.
Chem. Biol. Interact.
PUBLISHED: 01-28-2011
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Inorganic arsenic is a common environmental contaminant; chronic exposure to arsenic can alter the physiology of various key immune cells, particularly macrophages. The aim of this research is to elucidate the key parameters associated with arsenic-induced toxicity and investigate the potential and mechanism of ?-lipoic acid (LA), a potent thioreducant, for reducing the toxicity in human promonocytic THP-1 cells. We found that a non-lethal concentration of arsenic trioxide (1 ?M) significantly induced the expression of heme oxygenase-1 (HO-1), a response biomarker to arsenic, without stimulating measurable superoxide production. Co-treatment of cells with the HO-1 competitive inhibitor zinc protoporphyrin (Znpp) potentiated arsenic-induced cytotoxicity, indicating that HO-1 confers a cytoprotective effect against arsenic toxicity. In addition, low concentrations of arsenic trioxide (1 and 2.5 ?M) markedly inhibited monocyte-to-macrophage differentiation and expression of macrophage markers. Treatment of cells with LA attenuated arsenic trioxide-induced cytotoxicity and HO-1 over-expression and restored the redox state. In addition, LA neutralized arsenic trioxide-inhibition of monocyte maturation into macrophages and reversed the expression and activity of scavenger receptors. In conclusion, the cytotoxicity of arsenic trioxide is associated with an imbalance of the cellular redox state, and LA can protect cells from arsenic-induced malfunctions either through its reducing activity, direct interacting with arsenic or stimulating other unidentified signaling pathways.
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The effect of surgeon empathy and emotional intelligence on patient satisfaction.
Adv Health Sci Educ Theory Pract
PUBLISHED: 01-14-2011
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We investigated the associations of surgeons emotional intelligence and surgeons empathy with patient-surgeon relationships, patient perceptions of their health, and patient satisfaction before and after surgical procedures. We used multi-source approaches to survey 50 surgeons and their 549 outpatients during initial and follow-up visits. Surgeons emotional intelligence had a positive effect (r = .45; p < .001) on patient-rated patient-surgeon relationships. Patient-surgeon relationships had a positive impact on patient satisfaction before surgery (r = .95; p < .001). Surgeon empathy did not have an effect on patient-surgeon relationships or patient satisfaction prior to surgery. But after surgery, surgeon empathy appeared to have a significantly positive and indirect effect on patient satisfaction through the mediating effect of patients self-reported health status (r = .21; p < .001). Our study showed that long-term patient satisfaction with their surgeons is affected less by emotional intelligence than by empathy. Furthermore, empathy indirectly affects patient satisfaction through its positive effect on health outcomes, which have a direct effect on patients satisfaction with their surgeons.
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Citrus flavonoid 5-demethylnobiletin suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells.
Mol Nutr Food Res
PUBLISHED: 01-10-2011
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Nobiletin, a polymethoxyflavone from the peel of citrus fruits, has been reported to inhibit modified LDL uptake in macrophages and enhance hepatic LDL receptor expression and activity. We report the anti-atherogenic effect and mechanism of 5-demethylnobiletin, an auto-hydrolysis product of nobiletin.
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Web-based healthcare hand drawing management system.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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The paper addresses Medical Hand Drawing Management System architecture and implementation. In the system, we developed four modules: hand drawing management module; patient medical records query module; hand drawing editing and upload module; hand drawing query module. The system adapts windows-based applications and encompasses web pages by ASP.NET hosting mechanism under web services platforms. The hand drawings implemented as files are stored in a FTP server. The file names with associated data, e.g. patient identification, drawing physician, access rights, etc. are reposited in a database. The modules can be conveniently embedded, integrated into any system. Therefore, the system possesses the hand drawing features to support daily medical operations, effectively improve healthcare qualities as well. Moreover, the system includes the printing capability to achieve a complete, computerized medical document process. In summary, the system allows web-based applications to facilitate the graphic processes for healthcare operations.
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Semantic similarity measure in biomedical domain leverage web search engine.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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Semantic similarity measure plays an essential role in Information Retrieval and Natural Language Processing. In this paper we propose a page-count-based semantic similarity measure and apply it in biomedical domains. Previous researches in semantic web related applications have deployed various semantic similarity measures. Despite the usefulness of the measurements in those applications, measuring semantic similarity between two terms remains a challenge task. The proposed method exploits page counts returned by the Web Search Engine. We define various similarity scores for two given terms P and Q, using the page counts for querying P, Q and P AND Q. Moreover, we propose a novel approach to compute semantic similarity using lexico-syntactic patterns with page counts. These different similarity scores are integrated adapting support vector machines, to leverage the robustness of semantic similarity measures. Experimental results on two datasets achieve correlation coefficients of 0.798 on the dataset provided by A. Hliaoutakis, 0.705 on the dataset provide by T. Pedersen with physician scores and 0.496 on the dataset provided by T. Pedersen et al. with expert scores.
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Comparing clinical outcomes following percutaneous vertebroplasty with conservative therapy for acute osteoporotic vertebral compression fractures.
Pain Med
PUBLISHED: 11-04-2010
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To compare the efficacy of percutaneous vertebroplasty (PV) with conservative therapy for patients with acute vertebral compression fractures.
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Cladielloides A and B: new eunicellin-type diterpenoids from an Indonesian octocoral Cladiella sp.
Mar Drugs
PUBLISHED: 10-29-2010
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Two new eunicellin-type diterpenoids, cladielloides A (1) and B (2), which were found to possess a 2-hydroxybutyroxy group in their structures, were isolated from an Indonesian octocoral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods. Cladielloide B (2) exhibited moderate cytotoxicity toward CCRF-CEM tumor cells and this compound displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils.
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Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles.
Mutat. Res.
PUBLISHED: 09-25-2010
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Antroquinonol a derivative of Antrodia camphorata has been reported to have antitumor effects against various cancer cells. However, the effect of antroquinonol on cell signalling and survival pathways in non-small cell lung cancer (NSCLC) cells has not been fully demarcated. Here we report that antroquinonol treatment significantly reduced the proliferation of three NSCLC cells. Treatment of A549 cells with antroquinonol increased cell shrinkage, apoptotic vacuoles, pore formation, TUNEL positive cells and increased Sub-G1 cell population with respect to time and dose dependent manner. Antroquinonol treatment not only increased the Sub-G1 accumulation but also reduced the protein levels of cdc2 without altering the expression of cyclin B1, cdc25C, pcdc2, and pcdc25C. Antroquinonol induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of Caspase 3 and PARP cleavage in A549 cells. Moreover, antroquinonol treatment down regulated the expression of Bcl2 proteins, which was correlated with the decreased PI3K and mTOR protein levels without altering pro apoptotic and anti apoptotic proteins. Results from the microarray analysis demonstrated that antroquinonol altered the expression level of miRNAs compared with untreated control in A549 cells. The data collectively suggested the antiproliferative effect of antroquinonol on NSCLC A549 cells, which provides useful information for understanding the anticancer mechanism influenced by antroquinonol and is the first report to suggest that antroquinonol may be a promising chemotherapeutic agent for lung cancer.
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Excavatoids O and P, new 12-hydroxybriaranes from the octocoral Briareum excavatum.
Mar Drugs
PUBLISHED: 09-07-2010
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Two new 12-hydroxybriarane diterpenoids, designated as excavatoids O (1) and P (2), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1 and 2 were established on the basis of extensive spectral data analysis. Excavatoid P (2) is the first metabolite which possesses a 6? -chlorine atom in briarane analogues.
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Enhanced expression of glycine N-methyltransferase by adenovirus-mediated gene transfer in CNS culture is neuroprotective.
Ann. N. Y. Acad. Sci.
PUBLISHED: 07-17-2010
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Glycine N-methyltransferase (GNMT) is the most abundant hepatic methyltransferase and plays important roles in regulating methyl group metabolism. In the central nervous system, GNMT expression is low and its function has not been revealed. The present study examines the effect of GNMT overexpression by adenovirus-mediated transfer in cortical mixed neuron-glial cultures. Infection of adenovirus encoding green fluorescence protein to cultures demonstrates high preference for non-neuronal cells. Optimal GNMT overexpression in cultures by adenoviral GNMT (Ad-GNMT) infection not only induces protein kinase C phosphorylation, but also increases neuronal/oligodendroglial survival. Furthermore, these Ad-GNMT-infected cultures are significantly resistant to H(2)O(2) toxicity and lipopolysaccharide stimulation. Conditioned media from Ad-GNMT-infected microglia also significantly enhance neuronal survival. Taken together, enhanced GNMT expression in mixed neuronal-glial cultures is neuroprotective, most likely mediated through non-neuronal cells.
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Chlorinated briarane diterpenoids from the sea whip gorgonian corals Junceella fragilis and Ellisella robusta (Ellisellidae).
Chem. Pharm. Bull.
PUBLISHED: 07-08-2010
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A new chlorinated briarane, fragilide J (1), has been isolated from the sea whip gorgonian coral Junceella fragilis. In addition, the sea whip gorgonian coral Ellisella robusta yielded two chlorinated briaranes, including a new compound, robustolide L (2), and a known metabolite, robustolide H (3). The structures of these compounds were determined using spectroscopic methods. The structure, including the absolute configuration of 3, was further confirmed by X-ray data analysis for the first time.
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Esophagogastric varices predict mortality in hospitalized patients with alcoholic liver disease in Taiwan.
Hepatogastroenterology
PUBLISHED: 06-30-2010
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Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in Western countries. The present study investigated the status and the risk factors for predicting mortality of ALD in Taiwan.
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Grape seed extract ameliorates tumor necrosis factor-?-induced inflammatory status of human umbilical vein endothelial cells.
Eur J Nutr
PUBLISHED: 06-24-2010
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Inflammation has played a key role in the causation of atherosclerosis. However, the effects of grape seed extract (GSE) on the pro-inflammatory intracellular signaling, enzyme activity, and inflammatory mediators of endothelial cells have not been sufficiently studied, and less information exists on the comparison between GSE and vitamin C, a well-known antioxidant compound, on their anti-inflammatory properties.
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Hypoglycaemic effects of fermented mycelium of Paecilomyces farinosus (G30801) on high-fat fed rats with streptozotocin-induced diabetes.
Indian J. Med. Res.
PUBLISHED: 06-03-2010
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Paceilomyces farinosus is an entomogenous fungus with a powerful insecticidal activity against the larvae of Lipidoptera, Coleoptera and Hymenoptera. However, the hypoglycaemic activity of P. farinosus extract has not been studied. This study was undertaken to investigate the hypoglycaemic and anti-diabetic effects of P. farinosus (G30801) in rats with streptozotocin (STZ)-induced diabetes given a high-fat and compared with normal rats.
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Naringenin more effectively inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in macrophages than in microglia.
Nutr Res
PUBLISHED: 05-31-2010
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Macrophages and microglia are thought to account for initial disease progression in acute myocardial infarction and acute ischemic stroke. Before our study, the inhibitory effects of naringenin, a flavonoid, on lipopolysaccharide (LPS)-induced inflammation in macrophages and microglia have not been fully reported and compared. We hypothesized that naringenin can effectively inhibit LPS-induced inflammation of macrophages and microglia at different concentrations, the range of which is broader, with the lowest concentration more easily achieved in macrophages. In this study, we compared the anti-inflammatory effects of naringenin on LPS-stimulated RAW 274.6 macrophages and BV2 microglia and the suppression effects of naringenin and vitamin C (a well-known anti-inflammatory agent) on LPS-induced nitrite production. The results show that macrophages could maintain cell viability at higher naringenin concentrations and were more easily activated by LPS in comparison to microglia (200 vs 100 ?mol/L; 0.1 vs 1 ?g/mL). Under LPS (1 ?g/mL) stimulation in both cell types, naringenin (up to 200 ?mol/L in macrophages and 100 ?mol/L in microglia) inhibited nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner. The range of naringenin concentrations for inhibition was broader, and the lowest concentration was more easily achieved in macrophages; the lowest effective concentrations of naringenin to achieve constant suppression effect were 50 ?mol/L in macrophages and 100 ?mol/L in microglia, respectively. Vitamin C (100 ?mol/L), compared with naringenin (100 ?mol/L), had less and no suppression effect on LPS (1 ?g/mL)-induced nitrite production in macrophages and microglia, respectively. In conclusion, naringenin more effectively inhibits the LPS-induced inflammatory status, including nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression, in macrophages than in microglia. The findings of the present study suggest that consumption of naringenin-containing flavonoids might be beneficial to the cardiovascular and cerebrovascular inflammatory process.
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Spinal tuberculosis in non-HIV-infected patients: 10 year experience of a medical center in central Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 04-20-2010
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Tuberculosis (TB) is an endemic disease in Taiwan and it usually affects the lung. Spinal TB accounts for 1-3% of all TB infections. The purpose of this study was to investigate the clinical manifestations, management, outcomes and drug susceptibility of Mycobacterium tuberculosis in non-HIV-infected patients with spinal TB.
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Inhibition of extracellular signal-regulated kinases 1/2 provides neuroprotection in spinal cord ischemia/reperfusion injury in rats: relationship with the nuclear factor-kappaB-regulated anti-apoptotic mechanisms.
J. Neurochem.
PUBLISHED: 04-09-2010
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Previously we demonstrated benefits of inhibiting the extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway in spinal cord ischemia/reperfusion (I/R) injury. To further identify the underlying mechanisms, we investigated the impact of ERK inhibition on apoptosis and cellular protective mechanisms against cell death. Spinal cord I/R injury induced ERK1/2 phosphorylation, followed by neuronal loss through caspase 3-mediated apoptosis. Pre-treatment with U0126, a specific inhibitor of MAPK/ERK kinases 1/2 (MEK1/2), inhibited ERK1/2 phosphorylation, and significantly attenuated apoptosis and increased neuronal survival. MEK/ERK inhibition also induced I-kappaB phosphorylation and enhanced nuclear factor (NF)-kappaB/DNA binding activity, leading to expression of cellular inhibitors of apoptosis protein 2 (c-IAP2), a known nuclear factor-kappaB (NF-kappaB)-regulated endogenous anti-apoptotic molecule. Pyrrolidine dithiocarbamate, an NF-kappaB inhibitor, by blocking I-kappaB phosphorylation, NF-kappaB activation, and c-IAP2 synthesis, abolished the protective effects of U0126. The MEK/ERK pathway appears to mediate cellular death following I/R injury. The U0126 neuroprotection appears related to NF-kappaB-regulated transcriptional control of c-IAP2. MEK/ERK inhibition at the initial stage of I/R injury may cause changes in c-IAP2 gene expression or c-IAP2/caspase 3 interactions, resulting in long lasting therapeutic effects. Future research should focus on the possible cross-talk between the MEK/ERK pathway and the NF-kappaB transcriptional cascade.
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Antiproliferative effect of Toona sinensis leaf extract on non-small-cell lung cancer.
Transl Res
PUBLISHED: 02-12-2010
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Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC(50) value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.
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Relationship between injury severity and serum tau protein levels in traumatic brain injured rats.
Resuscitation
PUBLISHED: 02-09-2010
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Although serum tau protein levels increase following TBI, the time course is unknown. The aim of the present study was to determine whether serum tau protein levels increased in both a severity-dependent and time-dependent manner in an experimental model of rat traumatic brain injury (TBI).
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Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma.
J Med Food
PUBLISHED: 02-09-2010
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Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.
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Insulin secretagogue bioactivity of finger citron fruit (Citrus medica L. var. Sarcodactylis Hort, Rutaceae).
J. Agric. Food Chem.
PUBLISHED: 09-19-2009
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Finger citron [Citrus medica L. var. Sarcodactylis Hort, Rutaceae] (FC) fruits, widely cultivated in Japan, the southern provinces of China and Taiwan, are commonly used as functional vegetables and preserved as sweetmeats. Previously we identified the major compounds in essential oils (% in EO) of FC fruits to be d-limonene (51.24), gamma-terpenene (33.71), alpha-pinene (3.40), and beta-pinene (2.88). Documented evidence on its insulin secretion characteristics is still lacking. In parallel to compositional analysis, we performed in vivo the safety, hypoglycemic, and antidiabetic tests in Sprague-Dawley-SPF rats and Wistar DIO rats respectively. By kinetic analysis on the hypoglycemic patterns of the intraperitoneal glucose tolerance (IPGTT) and the insulin-glucose tolerance tests (IGTT), its insulin secretagogue effect was confirmed. In conclusion, FC fruits that concomitantly possess insulin secretagogue and slimming effects would be very beneficial to type 2 diabetes mellitus patients.
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An atrophic crossed fused kidney with an ectopic vaginal ureter causing urine incontinence.
Urology
PUBLISHED: 07-20-2009
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An ectopic vaginal ureter is an infrequent cause of urinary incontinence. Most cases are associated with a duplex kidney in which the lower moiety ureter drains into the bladder. Occasionally, some cases of ectopic kidney with single vaginal ectopic ureter can occur. In this study, we present a case of chronic continuous urine incontinence caused by the extremely rare combination of a fused-crossed kidney and a single vaginal ectopic ureter. Laparoscopic nephroureterectomy was carried out smoothly and uneventfully. In our experience, laparoscopic navigation and surgery can be valuable tools to delineate and manage unusual congenital anomalies.
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The difference in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan.
Int. J. Infect. Dis.
PUBLISHED: 07-18-2009
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To identify the differences in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan.
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The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells.
Br. J. Nutr.
PUBLISHED: 07-09-2009
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Diabetes mellitus is an important risk factor for CVD. A previous study showed that high glucose induced the apoptosis of human umbilical vein endothelial cells (HUVEC) via the sequential activation of reactive oxygen species, Jun N-terminal kinase (JNK) and caspase-3. The apoptosis cascade could be blocked by ascorbic acid at the micromolar concentration (100 microm). In addition to ascorbic acid, quercetin, the most abundant dietary flavonol, has been recently actively studied in vascular protection effects due to its antioxidant effect at low micromolar concentrations (10-50 microm). Quercetin sulfate/glucuronide, the metabolite of quercetin in blood, however, has been rarely evaluated. In the present study, we investigated the effect of quercetin sulfate/glucuronide on the prevention of high glucose-induced apoptosis of HUVEC. HUVEC were treated with media containing high glucose (33 mm) in the presence or absence of ascorbic acid (100 microm) or quercetin sulfate/glucuronide (100 nm, 300 nm and 1 microm). For the detection of apoptosis, a cell death detection ELISA assay was used. The level of intracellular H2O2 was measured by flow cytometry. JNK and caspase-3 were evaluated by a kinase activity assay and Western blot analysis. The results showed that high glucose-induced apoptosis was inhibited by quercetin sulfate/glucuronide in a dose-dependent manner. The effect of quercetin sulfate/glucuronide on H2O2 quenching, inhibition of JNK and caspase-3 activity at the nanomolar concentration (300 nm) was similar to that of ascorbic acid at the micromolar concentration (100 microm). The findings of the present study may shed light on the pharmacological application of quercetin in CVD.
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Expression and in vitro regulation of pituitary adenylate cyclase-activating polypeptide (pacap38) and its type I receptor (pac1-r) in the gonads of tilapia (Oreochromis mossambicus).
Reproduction
PUBLISHED: 06-16-2009
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Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic neuropeptide, has diverse functions in mammals. However, studies of the expression and function of PACAP and its receptor in fish, particularly in the reproductive system, are still limited. In this report, semi-quantitative RT-PCR and immunohistochemical staining were performed to identify expression domains of commercially important tilapia (Oreochromis mossambicus). PACAP (tpacap(38)) and its type I receptor (tpac(1)-r). Transcripts were detected in the brain, gallbladder, gill, heart, intestine, kidney, muscles, pancreas, spleen, stomach, testes, and ovaries, but not in the liver. Expression of tpacap(38) and tpac(1)-r mRNA in brain tissue was significantly higher in both sexes compared with other tissues. Addition of exogenous ovine PACAP(38) (0.25-5 nM), cAMP analog (dibutyryl-cAMP, 0.25-1.5 mM) or forskolin (adenylate cyclase activator, 1-10 microM) significantly upregulated tpacap(38) in the gonads via a dose- and time-dependent fashion. This effect reached a maximal level at 2 h after induction, and then decreased with prolonged culture for up to 4 or 8 h. Additionally, the expression levels of tpac(1)-r were not significantly affected by ovine PACAP(38) or dibutyryl-cAMP in either sex. Forskolin had a slightly inductive effect and its function could be suppressed with the addition of protein kinase A (PKA) inhibitor, H89 (10 microM), indicating involvement of the cAMP-PKA signaling pathway in the regulation of tpacap(38). Expression of tpacap(38) and tpac(1)-r in the gonads of tilapia suggests that PACAP may mediate gonadotropin action via paracrine/autocrine mechanisms in this bony fish.
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Comparative atomic force and scanning electron microscopy: an investigation of structural differentiation of hepatic stellate cells.
J. Struct. Biol.
PUBLISHED: 06-09-2009
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The molecular mechanism leading to the transdifferentiation of hepatic stellate cells (HSC) into myofibroblast-like cells following liver injury is not well understood. The state of cultured rat HSCs was determined using primarily fluorescence microscopy (UV), immunofluorescence (IF) (Glial fibrillary acidic protein (GFAP), Desmin, alpha-smooth muscle actin (alpha-SMA), F-actin) and immunocytochemistry (ICC) (GFAP, Desmin, alpha-SMA, Fibulin-2). Additionally, tapping-mode atomic force microscopy (TM-AFM) and field-emission scanning electron microscopy (FE-SEM) with low-resistivity indium-tin-oxide (ITO) thin-film were performed to observe the micro-morphological character of cells during HSC differentiation. Quiescent HSCs changed to the activated state were identified via UV, IF, and ICC observations. Normal rat HSCs (NHSCs) and thioacetamide-induced rat HSCs (THSCs) were demonstrated to be UV(-), GFAP(+), Desmin(+), alpha-SMA(+) and Fibulin-2(-). After F-actin staining, lamellipodia and filopodia were found in both NHSCs and THSCs, but membrane ruffles were only seen in THSCs. The micro-structures of lamellipodia and filopodia in both NHSCs and THSCs were confirmed using FE-SEM and TM-AFM with ITO; in contrast, the micro-projection was not found. Moreover, "aerial root" structures were observed for the first time in the filopodia of THSCs using TM-AFM. These results reveal that HSC transdifferentiation to a myofibroblastic-like cell (activated HSC) from thioacetamide-induced rat HSC induces extensive changes in the cytoskeleton.
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Magnetic-bead-based microfluidic system for ribonucleic acid extraction and reverse transcription processes.
Biomed Microdevices
PUBLISHED: 05-27-2009
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This paper presents a new integrated microfluidic chip that automatically performs ribonucleic acid (RNA) extraction and reverse transcription (RT) processes. The microfluidic system consists of a microfluidic control module and a magnetic bio-separator. The microfluidic control module can perform pumping and mixing of small amount of fluids and subsequent purification and concentration of RNA samples by incorporating with the magnetic bio-separator consisting of 2-dimension twisted microcoils. Notably, the magnetic bio-separators are developed either to generate the required magnetic field to perform the separation of magnetic beads or to work as a micro-heater to control the temperature field for the following RT process. Experimental results show that the total RNA can be successfully purified and extracted by using magnetic beads and the subsequent RT processing of the RNA can be performed automatically. Total RNA is successfully extracted and purified from T98 cells utilizing the microfluidic system, which is comparable with the conventional methods. The whole automatic procedure of RNA sample extraction only takes 35 min, which is much faster than the conventional method (more than 2 h). As a whole, the developed microfluidic system may provide a powerful platform for rapid RNA extraction and RT processes for further biomedical applications.
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A multisource and repeated measure approach to assessing patient-physician relationship and patient satisfaction.
Eval Health Prof
PUBLISHED: 05-19-2009
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The object of this study is to compare the multisource assessments of patient-physician relationship with assessments by their patients at two time points. In this observational study, 1,747 outpatients nested under 64 internists and 70 surgeons are surveyed by face-to-face interview at initial patient- physician visits and then in a telephone interview 2 weeks later. On the first evaluation, physicians self-assessments are not correlated their patients assessments. At follow-up, physicians self-assessments correlated with the perceived improvements in patients health status (p < .05). We also find a positive association (p < .05) between patient satisfaction with their surgeons and perceived improvements of health status at the 2-week follow-up, suggesting that patient satisfaction may be a proxy for symptom or functional improvement. Although most of the ratings of nursing directors, physician peers, administrators, and nonclinical observers are positively associated with the patients first ratings, the significance of that association disappear by the 2-week follow-up.
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Epidemiology of acute q Fever, scrub typhus, and murine typhus, and identification of their clinical characteristics compared to patients with acute febrile illness in southern taiwan.
J. Formos. Med. Assoc.
PUBLISHED: 05-16-2009
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In Taiwan, acute Q fever, scrub typhus, and murine typhus (QSM diseases) are the most common rickettsioses, but their epidemiology and clinical characteristics have not been clarified. Diagnosis of these three diseases based on clinical manifestations is difficult, and most of their reported characteristics are identified by describing the predominant manifestations, without being compared with other diseases.
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Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica exhibit distinct immunomodulatory activities in mice.
J. Agric. Food Chem.
PUBLISHED: 04-22-2009
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The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.
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Effects of serum on phagocytic activity and proteomic analysis of tilapia (Oreochromis mossambicus) serum after acute osmotic stress.
Fish Shellfish Immunol.
PUBLISHED: 03-05-2009
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The objective of the study was to analyze the effect of serum from freshwater (FW) exposed tilapia or from 25 ppt seawater (SW) exposed tilapia on the ability to mediate the phagocytic activity of tilapia phagocytes. To analyze the phagocytic activity, head kidney (HK) and spleen leukocytes were tested in 300 or 500 mOsm medium using three different treatment groups (a) control, (b) addition of 25% serum from freshwater (FW) exposed tilapia, and (c) addition of 25% of serum from 25 ppt seawater (SW) exposed tilapia. HK leukocytes cultured in 300 and 500 mOsm media for 4 h showed an increase of phagocytic ability in the control group as compared to the addition of serum from either FW or SW exposed tilapia. HK leukocytes exposed to 500 mOsm medium showed a higher phagocytic ability than those leukocytes exposed to 300 mOsm medium in each corresponding group. Concurrently, spleen leukocytes in the control group showed a higher phagocytic ability than those leukocytes with the addition of serum from FW or SW exposed tilapia. As compared to spleen leukocytes cultured in 300 mOsm medium, leukocytes cultured in 500 mOsm medium showed an increase of phagocytic ability within their respective group. To further investigate the observed phenomenon, 2D-gel electrophoresis was performed for analyzing the differentially expressed proteins in serum that was thought to influence the phagocytic ability. Up-regulated serum proteins in SW exposed tilapia contained complement C3 protein, NADH dehydrogenase (Ubiquinone) Fe-S protein 3, Mg(2+)-dependent neutral sphingomyelinase, Semaphorins, and Caspase 3. Taken together these results suggest that addition of serum decreased the phagocytic activity in HK and spleen leukocytes in vitro, furthermore, induced proteins semaphorin, complement C3, Mg(2+)-dependent neutral sphingomyelinase, and Caspase 3 are up-regulated in the serum, which might have decreased the phagocytic activity upon exposure to hyperosmotic solutions.
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