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Find video protocols related to scientific articles indexed in Pubmed.
[Autologous peripheral blood CD34+ stem cells transplanted into 100 patients with advanced cirrhosis].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 11-05-2014
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To investigate whether transplantation of autologous peripheral blood CD34+ stem cells is a viable approach for treating patients with advanced cirrhosis,which is currently hindered by a shortage in liver donors.
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The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-28-2014
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Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5Gy ?-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose ?-ray. C57BL/6 mice were given nicaraven or placebo within 30min before exposure to 50mGy ?-ray daily for 30days in sequences (cumulative dose of 1.5Gy). Mice were victimized 24h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit(+) stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60-90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit(+) stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.
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Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients.
Lung Cancer
PUBLISHED: 04-19-2014
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A new histological classification by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) for lung adenocarcinoma (LAC) was proposed recently, in which a micropapillary pattern (MPP) was described.
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Clinical outcome of autologous hematopoietic stem cell infusion via hepatic artery or portal vein in patients with end-stage liver diseases.
Chin. Med. Sci. J.
PUBLISHED: 04-05-2014
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To investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD).
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Activation of hedgehog signaling pathway in human non-small cell lung cancers.
Pathol. Oncol. Res.
PUBLISHED: 03-27-2014
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The activation of the hedgehog pathway, which is an important signaling mechanism crucial in embryogenesis, has strong links to carcinogenesis. Aberrant regulation of this pathway can result in the development of tumors. The present study was designed to investigate Hh related protein expression in non-small cell lung cancers. Fifty five non-small cell lung cancers samples were used in the study. By reverse transcription-polymerase chain reaction (RT-PCR), the expression of Shh, Ptch-1, and Gli-1 in tumor and adjacent normal tissues was examined and associated to clinical pathologic features. The expression levels of Shh, Ptch-1, Gli-1 in non-small cell lung cancer tissues were 63.64, 69.09, 43.64 %, respectively, higher than that in the adjacent normal tissues. Survival analysis showed that both Ptch-1 and Gli-1 expression were associated with poor survival (both P?<0.05, log-rank test). Shh and Ptch-1 expression were correlated with lymph node metastasis. These results suggest that dysregulation of Hh signaling pathway plays an important role in the development of human NSCLCs. The expression of Ptch-1 and Gli-1 is possibly involved in NSCLCs progression, which may be a useful prognostic indicator of NSCLCs.
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Forsythin inhibits lipopolysaccharide-induced inflammation by suppressing JAK-STAT and p38 MAPK signalings and ROS production.
Inflamm. Res.
PUBLISHED: 03-17-2014
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Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages.
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Copper-organic/octamolybdates: structures, bandgap sizes, and photocatalytic activities.
Inorg Chem
PUBLISHED: 03-07-2014
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The structures, optical bandgap sizes, and photocatalytic activities are described for three copper-octamolybdate hybrid solids prepared using hydrothermal methods, [Cu(pda)]4[?-Mo8O26] (I; pda = pyridazine), [Cu(en)2]2[?-Mo8O26] (II; en = ethylenediamine), and [Cu(o-phen)2]2[?-Mo8O26] (III; o-phen = o-phenanthroline). The structure of I consists of a [Cu(pda)]4(4+) tetramer that bridges to neighboring [?-Mo8O26](4-) octamolybdate clusters to form two-dimensional layers that stack along the a axis. The previously reported structures of II and III are constructed from [Cu2(en)4Mo8O26] and [Cu2(o-phen)4Mo8O26] clusters. The optical bandgap sizes were measured by UV-vis diffuse reflectance techniques to be ?1.8 eV for I, ?3.1 eV for II, and ?3.0 eV for III. Electronic structure calculations show that the smaller bandgap size of I originates primarily from an electronic transition between the valence and conduction band edges comprised of filled 3d(10) orbitals on Cu(I) and empty 4d(0) orbitals on Mo(VI). Both II and III contain Cu(II) and exhibit larger bandgap sizes. Accordingly, aqueous suspensions of I exhibit visible-light photocatalytic activity for the production of oxygen at a rate of ?90 ?mol O2 g(-1) h(-1) (10 mg samples; radiant power density of ?1 W/cm(2)) and a turnover frequency per calculated surface [Mo8O26](4-) cluster of ?36 h(-1). Under combined ultraviolet and visible-light irradiation, I also exhibits photocatalytic activity for hydrogen production in 20% aqueous methanol of ?316 ?mol H2 g(-1) h(-1). By contrast, II decomposed during the photocatalysis measurements. The molecular [Cu2(o-phen)4(?-Mo8O26)] clusters of III dissolve into the aqueous methanol solution under ultraviolet irradiation and exhibit homogeneous photocatalytic rates for hydrogen production of up to ?8670 ?mol H2·g(-1) h(-1) and a turnover frequency of 17 h(-1). The clusters of III can be precipitated out by evaporation and redispersed into solution with no apparent decrease in photocatalytic activity. During the photocatalysis measurements, the dissolution of the clusters in III is found to occur with the reduction of Cu(II) to Cu(I), followed by subsequent detachment from the octamolybdate cluster. The lower turnover frequency, but higher photocatalytic rate, of III arises from the net contribution of all dissolved [Cu2(o-phen)4(?-Mo8O26)] clusters, compared to only the surface clusters for the heterogeneous photocatalysis of I.
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The effect of anti-inflammatory properties of ferritin light chain on lipopolysaccharide-induced inflammatory response in murine macrophages.
Biochim. Biophys. Acta
PUBLISHED: 02-17-2014
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Ferritin light chain (FTL) reduces the free iron concentration by forming ferritin complexes with ferritin heavy chain (FTH). Thus, FTL competes with the Fenton reaction by acting as an antioxidant. In the present study, we determined that FTL influences the lipopolysaccharide (LPS)-induced inflammatory response. FTL protein expression was regulated by LPS stimulation in RAW264.7 cells. To investigate the role of FTL in LPS-activated murine macrophages, we established stable FTL-expressing cells and used shRNA to silence FTL expression in RAW264.7 cells. Overexpression of FTL significantly decreased the LPS-induced production of tumor necrosis factor alpha (TNF-?), interleukin 1? (IL-1?), nitric oxide (NO) and prostaglandin E2 (PGE2). Additionally, overexpression of FTL decreased the LPS-induced increase of the intracellular labile iron pool (LIP) and reactive oxygen species (ROS). Moreover, FTL overexpression suppressed the LPS-induced activation of MAPKs and nuclear factor-?B (NF-?B). In contrast, knockdown of FTL by shRNA showed the reverse effects. Therefore, our results indicate that FTL plays an anti-inflammatory role in response to LPS in murine macrophages and may have therapeutic potential for treating inflammatory diseases.
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Association of liver X receptor ? (LXR?) gene polymorphism and coronary heart disease, serum lipids and glucose levels.
Lipids Health Dis
PUBLISHED: 02-10-2014
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To explore the relationship between the liver X receptor ? gene (LXR?) rsl2221497 polymorphism and the susceptibility of coronary heart disease (CHD) and serum lipids and glucose levels.
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Characterization of an aphid-specific, cysteine-rich protein enriched in salivary glands.
Biophys. Chem.
PUBLISHED: 02-05-2014
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Aphids secrete saliva into the phloem during their infestation of plants. Previous studies have identified numerous saliva proteins, but little is known about the characteristics (physical and chemical) and functions of these proteins in aphid-plant interactions. This study characterized an unknown protein (ACYPI39568) that was predicted to be enriched in the salivary glands of pea aphid. This protein belongs to an aphid-specific, cysteine-rich protein family that contains 14 conserved cysteines. ACYPI39568 is a monomeric globular protein with a high beta strand extent. The binding stoichiometric ratios for Zn(2+) and ACYPI39568 were approximately 3:1 and 1:1 at two binding sites. ACYPI39568 was predominantly expressed in the first instar stage and in the salivary glands. Aphids required more ACYPI39568 when feeding on plants than when feeding on an artificial diet. However, the interference of ACYPI39568 expression did not affect the survival rate of aphids on plants.
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Effects of antioxidants on the quality and genomic stability of induced pluripotent stem cells.
Sci Rep
PUBLISHED: 01-22-2014
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Effects of antioxidants on the quality and genomic stability of induced pluripotent stem (iPS) cells were investigated with two human iPS cell lines (201B7 and 253G1). Cells used in this study were expanded from a single colony of each cell line with the addition of proprietary antioxidant supplement or homemade antioxidant cocktail in medium, and maintained in parallel for 2 months. The cells grew well in all culture conditions and kept "stemness". Although antioxidants modestly decreased the levels of intracellular reactive oxygen species, there were no differences in the expression of 53BP1 and pATM, two critical molecules related with DNA damage and repair, under various culture conditions. CGH analysis showed that the events of genetic aberrations were decreased only in the 253G1 iPS cells with the addition of homemade antioxidant cocktail. Long-term culture will be necessary to confirm whether low dose antioxidants improve the quality and genomic stability of iPS cells.
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Phosphorylation of heat shock protein 27 antagonizes TNF-? induced HeLa cell apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK signaling.
Cell. Signal.
PUBLISHED: 01-10-2014
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Tumor necrosis factor (TNF)-? is a potent cytokine that regulates critical cellular processes including apoptosis. TNF-? usually triggers both survival and apoptotic signals in various cell types. Heat shock protein 27 (HSP27), an important cellular chaperone, is believed to protect cells from apoptosis. HSP27 can be phosphorylated and changed its cellular function according to different stimuli. However, available reports on the role of HSP27 phosphorylation in apoptosis remain elusive. In this study, we investigated the role of HSP27 phosphorylation in TNF-? induced apoptosis in human cervical carcinoma (HeLa) cells. We found that TNF-? induced apoptosis was enhanced if we suppressed the TNF-? induced HSP27 phosphorylation by specific inhibitor CMPD1 or MAPKAPK2 (MK2) knockdown or by overexpression of non-phosphorylatable mutant HSP27-3A. Through co-immunoprecipitation and confocal microscopy, we observed that HSP27 associated with transforming growth factor-? (TGF-?)-activated kinase 1 (TAK1) in response to TNF-? stimulation. By blocking MK2 activity or overexpressing phospho-mimetic mutant Hsp27-3D, we further showed that HSP27 phosphorylation facilitated the TNF-? induced ubiquitination and phosphorylation of TAK1 and the activations of p38 MAPK and ERK, the TAK1 downstream pro-survival signaling. In addition, we also found that increased HSP27 phosphorylation inhibited TRADD ubiquitination but did not influence the binding between TRADD and FADD in a pro-apoptotic complex. Taken together, our data indicated that HSP27 phosphorylation was involved in modulating the TNF-? induced apoptosis via interacting with TAK1 and regulating TAK1 post-translational modifications in HeLa cells. This study demonstrates that HSP27 phosphorylation serves as a novel regulator in TNF-?-induced apoptosis, and provides a new insight into the cytoprotective role of HSP27 phosphorylation.
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Post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation: a single-center experience.
Ann. Transplant.
PUBLISHED: 01-09-2014
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Post-transplant lymphoproliferative disease (PTLD) is a rare and serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation.
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Clinical Application Evaluation of Two Fourth-Generation Human Immunodeficiency Virus (HIV) Screening Assays in West China Hospital.
J. Clin. Lab. Anal.
PUBLISHED: 01-08-2014
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Fourth-generation human immunodeficiency virus (HIV) screening assays have been used in many laboratories. The Elecsys® HIV combi PT assay is a new kind of fourth-generation HIV screening assay developed to allow earlier detection of seroconversion.
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Luteolin is effective in the non-small cell lung cancer model with L858R/T790M EGF receptor mutation and erlotinib resistance.
Br. J. Pharmacol.
PUBLISHED: 01-03-2014
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Non-small cell lung cancer (NSCLC) is one of the most commonly diagnosed malignancies in the world. Small-molecule inhibitors of the EGF receptor's tyrosine kinase domain (TKIs), including gefitinib and erlotinib, have been widely used for treating NSCLC. Unfortunately, nearly all patients after initially experiencing a marked improvement while on these drugs, eventually progress to acquire resistance to TKIs. Because there is no effective therapeutic strategy to treat TKI-resistant NSCLC, we evaluated the effects of luteolin, a naturally occurring flavanoid, on T790M mutant NSCLC cells.
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MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (?40%), BCL2 (?70%) and BCL6 (?50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.
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Pallidal index as biomarker of manganese brain accumulation and associated with manganese levels in blood: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The current study was designed to evaluate the sensitivity, feasibility, and effectiveness of the pallidal index (PI) serving as a biomarker of brain manganese (Mn) accumulation, which would be used as an early diagnosis criteria for Mn neurotoxicity.
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Vulnerability of welders to manganese exposure - A neuroimaging study.
Neurotoxicology
PUBLISHED: 01-01-2014
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Increased manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn exposure occurs in different occupational settings, where the airborne Mn level and the size of respirable particulates may vary considerably. Recently the importance of the role of the cerebral cortex in Mn toxicity has been highlighted, especially in Mn-induced neuropsychological effects. In this study we used magnetic resonance imaging (MRI) to evaluate brain Mn accumulation using T1 signal intensity indices and to examine changes in brain iron content using T2* contrast, as well as magnetic resonance spectroscopy (MRS) to measure exposure-induced metabolite changes non-invasively in cortical and deep brain regions in Mn-exposed welders, Mn-exposed smelter workers and control factory workers with no measurable exposure to Mn. MRS data as well as T1 signal intensity indices and T2* values were acquired from the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. Smelters were exposed to higher air Mn levels and had a longer duration of exposure, which was reflected in higher Mn levels in erythrocytes and urine than in welders. Nonetheless, welders had more significant metabolic differences compared to controls than did the smelter workers, especially in the frontal cortex. T1 hyperintensities in the globus pallidus were observed in both Mn-exposed groups, but only welders showed significantly higher thalamic and hippocampal T1 hyperintensities, as well as significantly reduced T2* values in the frontal cortex. Our results indicate that (1) the cerebral cortex, in particular the frontal cortex, is clearly involved in Mn neurotoxic effects and (2) in spite of the lower air Mn levels and shorter duration of exposure, welders exhibit more extensive neuroimaging changes compared to controls than smelters, including measurable deposition of Mn in more brain areas. These results indicate that the type of exposure (particulate sizes, dust versus fume) and route of exposure play an important role in the extent of Mn-induced toxic effects on the brain.
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[Analysis of volatile oil from Gerbera piloselloides by GC-MS].
Zhong Yao Cai
PUBLISHED: 12-31-2013
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To identify the chemical components of volatile oil from Gerbera piloselloides.
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[B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 12-10-2013
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To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma).
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Impact of spatial aggregation error on the spatial scan analysis: a case study of colorectal cancer.
Geospat Health
PUBLISHED: 11-22-2013
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The paper aims to estimate the level and impact of spatial aggregation error for spatial scan statistics where disaggregated data below the zip code level are not available. Data on colorectal cancer cases in Cook county, Illinois, USA with a 5-year interval were used. An innovative procedure using SAS and Java was designed to make SaTScan auto-run. Characteristics of clusters at each reference level were compared to those at zip code level to observe differences related to spatial aggregation. The comparison reveals that spatial scan statistic at the zip code level can generate reliable clusters in areas with a large number of cases, but fail to detect clusters in areas where there are a sparse number of cases, since the spatial aggregation error is minimised in areas with sizeable numbers of cases. Without localised cancer data, zip code level data can be used effectively to identify dominant clusters. However, smaller clusters located in low-density areas may be missed.
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Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages.
Biochem. Biophys. Res. Commun.
PUBLISHED: 11-16-2013
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Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-?) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.
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Association study of angiotensin converting enzyme gene polymorphism with elderly diabetic hypertension and lipids levels.
Lipids Health Dis
PUBLISHED: 11-10-2013
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To investigate the relationship between angiotensin converting enzyme (ACE) gene insertion / deletion (I / D) polymorphism and diabetic essential hypertension in elderly population.
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[Study on chemical components in yiqing capsule based on UPLC-ESI-MS-MS and FTIR and its anti-inflammatory activity in vitro].
Zhong Yao Cai
PUBLISHED: 10-19-2013
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To study the chemical components in Yiqing capsule by UPLC-ESI-MS-MS and its anti-inflammatory activity in vitro.
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GSTpi protects against angiotensin II-induced proliferation and migration of vascular smooth muscle cells by preventing signal transducer and activator of transcription 3 activation.
Biochim. Biophys. Acta
PUBLISHED: 07-30-2013
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Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didnt affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation.
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Functional expression of hepassocin in Escherichia coli using SUMO fusion partner and molecular chaperones.
Protein Expr. Purif.
PUBLISHED: 07-23-2013
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Human hepassocin (HPS) is a hepatic growth factor which can accelerate hepatocyte proliferation in vivo and protect against liver injury. Previous reports have shown that HPS expressed in Escherichia coli resulted in inclusion bodies or low yield. In this study, the application of small ubiquitin-related modifier (SUMO) fusion technology in combined with four different chaperone teams on the soluble expression of recombinant HPS protein were explored and analyzed. The soluble expression of HPS was improved significantly by SUMO fusion and co-expression with trigger factor (Tf) chaperone, which was identified by SDS-PAGE and Western blotting. The fusion protein was purified to 90% purity by metal chelate chromatography with a yield of 98 mg per liter fermentation culture. Finally, about 19 mg HPS was obtained from 1l of fermentation culture with no less than 96% purity following purification of the SUMO protease cleavage and re-purified by the Ni-NTA resin chromatography, which was the highest yield of HPS reported so far with less time and effort. The recombinant HPS significantly stimulated the proliferation of human hepatic cell line L02 cells. The present work provides an effective system for soluble expression of functional HPS, which will facilitate the clinical developments of recombinant protein drugs.
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HSP27 phosphorylation modulates TRAIL-induced activation of Src-Akt/ERK signaling through interaction with ?-arrestin2.
Cell. Signal.
PUBLISHED: 07-05-2013
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Heat shock protein 27 (HSP27) regulates critical cellular functions such as development, differentiation, cell growth and apoptosis. A variety of stimuli induce the phosphorylation of HSP27, which affects its cellular functions. However, most previous studies focused on the role of HSP27 protein itself in apoptosis, the particular role of its phosphorylation state in signaling transduction remains largely unclear. In the present study, we reported that HSP27 phosphorylation modulated TRAIL-triggered pro-survival signaling transduction. In HeLa cells, suppression of HSP27 phosphorylation by specific inhibitor KRIBB3 or MAPKAPK2 (MK2) knockdown and by overexpression of non-phosphorylatable HSP27(3A) mutant demonstrated that hindered HSP27 phosphorylation enhanced the TRAIL-induced apoptosis. In addition, reduced HSP27 phosphorylation by KRIBB3 treatment or MK2 knockdown attenuated the TRAIL-induced activation of Akt and ERK survival signaling through suppressing the phosphorylation of Src. By overexpression of HSP27(15A) or HSP27(78/82A) phosphorylation mutant, we further showed that phosphorylation of HSP27 at serine 78/82 residues was essential to TRAIL-triggered Src-Akt/ERK signaling transduction. Co-immunoprecipitation and confocal microscopy showed that HSP27 interacted with Src and scaffolding protein ?-arrestin2 in response of TRAIL stimulation and suppression of HSP27 phosphorylation apparently disrupted the TRAIL-induced interaction of HSP27 and Src or interaction of HSP27 and ?-arrestin2. We further demonstrated that ?-arrestin2 mediated HSP27 action on TRAIL-induced Src activation, which was achieved by recruiting signaling complex of HSP27/?-arrestin2/Src in response to TRAIL. Taken together, our study revealed that HSP27 phosphorylation modulates TRAIL-triggered activation of Src-Akt/ERK pro-survival signaling via interacting with ?-arrestin2 in HeLa cells.
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Extracellular polysaccharide from Bacillus sp. strain LBP32 prevents LPS-induced inflammation in RAW 264.7 macrophages by inhibiting NF-?B and MAPKs activation and ROS production.
Int. Immunopharmacol.
PUBLISHED: 06-21-2013
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Extracellular polysaccharides (EPSs) are high-molecular weight sugar-based polymers that are synthesized and secreted by many microorganisms. Recently, EPSs have attracted particular attention due to their multiple biological functions including anti-inflammation. However, studies rarely reported the molecular mechanisms underlying their functions. We previously purified an EPS from an oligotrophic bacteria (Bacillus sp. LBP32) found in Lop Nur Desert, which possesses a potent antioxidant activity, while the anti-inflammatory effects of EPS and signaling mechanisms underlying its action have not been clarified. In this study, we demonstrated that EPS significantly inhibited the LPS-induced release of pro-inflammatory mediators, such as nitric oxide (NO), IL-6 and TNF-?, without any significant cytotoxicity. EPS also downregulated the expression of nitric oxide synthase (iNOS) induced by LPS. Furthermore, activation of nuclear factor ?B (NF-?B) was abrogated by EPS through inhibited the phosphorylation of I?B kinase (IKK). Activations of Mitogen-activated protein kinases (MAPKs), including p38 MAPK and c-Jun N-terminal kinase (JNK), were also found to be inhibited by EPS. In addition, the level of intracellular reactive oxygen species (ROS) was also significantly decreased with the treatment of EPS. In vivo experiments were conducted and showed that EPS could greatly improve the outcome of mice with LPS-induced endotoxic shock. Taken together, our data indicate that EPS prevents LPS-induced inflammatory response by inhibiting NF-?B and MAPKs activation and ROS production.
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[Different expression of cytokines induced by Actinobacillus actinomycetemcomitans lipopolysaccharide in monocytes/macrophages from different organs of rabbits].
Zhonghua Kou Qiang Yi Xue Za Zhi
PUBLISHED: 06-12-2013
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To investigate the expression of cytokines induced by Actinobacillus actinomycetemcomitans lipopolysaccharide (Aa-LPS) in monocytes/macrophages from different organs of rabbits.
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Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux.
Mol Med Rep
PUBLISHED: 05-24-2013
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The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by ?50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.
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Baicalein reduces lipopolysaccharide-induced inflammation via suppressing JAK/STATs activation and ROS production.
Inflamm. Res.
PUBLISHED: 05-22-2013
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To investigate the precise molecular mechanisms by which baicalein exerts beneficial biochemical activities in RAW264.7 macrophages treated with LPS.
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Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups.
Diagn Pathol
PUBLISHED: 05-05-2013
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The revised 2008 World Health Organization classification maintains a histological grading system (grades 1-3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosis of Chinese FL subgroups.
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[The molecular epidemiology characteristics of norovirus in environment and clinical samples in Guangzhou from 2009 to 2011].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 04-23-2013
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To investigate the molecular epidemiological characteristics of norovirus in Guangzhou from 2009 to 2011.
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Basophilic round bodies in gastric biopsies little known by pathologists: iatrogenic yttrium 90 microspheres deriving from selective internal radiation therapy.
Int. J. Surg. Pathol.
PUBLISHED: 04-05-2013
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Selective internal radiation therapy is a relatively new technique that irradiates primary and metastatic liver cancer using yttrium 90 microspheres. Increasing reports have shown this to be a useful treatment for unresectable primary hepatocellular carcinoma and others metastases from colon, lung, breast, sarcoma, and ocular melanoma. On the other hand, more and more therapy-related complications have been described. Since the morphologic description of injured organs are relatively uncommon, we report 2 cases of selective internal radiation therapy-related gastric injury, which represent basophilic round bodies in gastric biopsies little known by pathologists. The appearances in esophagogastroduodenoscopy include gastrointestinal ulcer, edema, and bleeding. Histological findings are mucosal atrophy, mild to moderate cytologic atypia, edema of the stroma, and inflammatory infiltration. The most characteristic feature is the presence of round blue and dark microspheres in the stromal blood vessels.
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A distinct pattern of memory and attention deficiency in patients with depression.
Chin. Med. J.
PUBLISHED: 03-20-2013
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Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy.
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Hyperlipidemia modifies innate immune responses to lipopolysaccharide via the TLR-NF-?B signaling pathway.
Inflammation
PUBLISHED: 03-19-2013
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The objective of this study was to investigate the effect of hyperlipidemia (HLP) on innate immune responses to lipopolysaccharide (LPS). Male New Zealand white rabbits were fed a normal diet (ND) or a high-fat diet (HFD) for 8 weeks. In vivo, the rabbits were injected intravenously with LPS for 24 h. In vitro, peripheral mononuclear cells were collected and stimulated (or unstimulated) with LPS for 24 h. Assay results were analyzed with one-way ANOVA or an equivalent non-parametric test. A P value of 0.05 was considered statistically significant. Despite having no influence in body weight, the HFD intake significantly increased serum lipids, C-reactive protein (CRP), nuclear factor (NF)-?B subunit p65, Toll-like receptor (TLR)-4, SR-A and FAS. Although we found increased circulating tumor necrosis factor (TNF)-?, interleukin (IL)-6, CRP, IL-1?, and IL-10 in the ND-fed rabbits, no significant difference was found in the LPS-stimulated production of TNF-?, IL-6, and CRP in the HFD-fed rabbits. The macrophages harvested from the HFD-fed rabbits developed a blunted inflammatory response, with lower mRNA expression of TNF-?, IL-6, CRP, TLR-4, SR-A, FAS, and Bcl-2 than that expressed by the ND group. In the HFD-fed animals, LPS incubation decreased NF-?B subunit p65 expression, whereas the cytoplasmic phosphorylation of the inhibitor of NF-?B protein was enhanced. These data indicate that HLP displayed a form of innate immune paralysis, including reduced pro- and anti-inflammatory cytokine release to external stimulus, which was related to the altered TLR-NF-?B signaling pathway and altered pro- and anti-apoptotic processes in macrophages.
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Principles of biopsy in suspected lung cancer: priority still based on invasion in the era of targeted therapy?
J Thorac Dis
PUBLISHED: 03-14-2013
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There are multiple ways to obtain a biopsy for patients with suspected lung cancer under clinical circumstances. Diagnostic goals described previously in literature should be achieved preferably by using the safest, least invasive, and least costly biopsies. Insight into molecular profile and era of targeted therapy challenged the previous concepts on tumor biopsy. Distinct principles of biopsy should be revisited to adopt the advances in clinical research. A 53-year-old gentleman with 10-year history of dust exposure consulted to our hospital because of bloody sputum. PET/CT scanning revealed a 3.2-centimeter mass with an increased (18)F-FDG uptake in right upper lung lobe, metabolically active lesions in multiple stations of mediastinal or bilateral hilar lymph nodes and an intramuscular nodule in the left gluteus maximus. He underwent transthoracic core needle biopsy of the lung mass, resection of intramuscular nodule, bronchoscopy and right upper lung lobectomy in sequence. The final diagnosis was considered as systemic lipid deposition. Principles of biopsy in suspected lung cancer should be prioritized in sequence based on weight in clinical management, acquisition of tissue, invasion, efficiency and cost.
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Genetic variation among Clonorchis sinensis isolates from different hosts and geographical locations revealed by sequence analysis of mitochondrial and ribosomal DNA regions.
Mitochondrial DNA
PUBLISHED: 03-06-2013
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The present study examined genetic variability among Clonorchis sinensis isolates from four different geographical localities (Guangzhou, Nanning, Jiamusi and Daqing) and host species (cats, dogs, human and rabbits) in Mainland China by sequence analyses of two mitochondrial DNA (mtDNA) genes, namely NADH dehydrogenase subunits 2, 5 (nad2 and nad5) and ribosomal internal transcribed spacer 1 (ITS1). A portion of the ITS1, nad2 (pnad2) and nad5 (pnad5) was amplified by polymerase chain reaction separately from adult C. sinensis individuals and the amplicons were subjected to sequencing from both directions. The length of the sequences of ITS1, pnad2 and pnad5 was 643, 666 and 771 bp, respectively. The intraspecific sequence variations within C. sinensis were 0-1.7% for ITS1, 0-1.4% for pnad2 and 0-0.9% for pnad5. The interspecific sequence variations within other zoonotic trematodes, which were published previously, were 4.5-84.9% for ITS1, 21.9-43.6% for pnad2 and 19.2-48.9% for pnad5. The A+T contents of the sequences were 45.26-45.88% (ITS1), 62.91-63.51% (pnad2) and 58.24-58.63% (pnad5). Phylogenetic analyses using ribosomal and mitochondrial sequence data set, with three different computational algorithms (Bayesian inference, maximum parsimony and maximum likelihood), all revealed distinct groups with high statistical support. These findings demonstrated the existence of low-level intraspecific variations in ribosomal DNA (rDNA) and mtDNA sequences among C. sinensis isolates from four different regions and hosts in China and elucidated that mtDNA sequences and rDNA sequences provided reliable genetic markers for phylogenetic studies of zoonotic trematodes.
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Multinucleated cells are involved in normal development and apoptosis in mouse testes.
Mol Med Rep
PUBLISHED: 03-01-2013
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Multinucleated cells are present in impaired spermatogenesis and in the senescent testis. Following accumulating evidence from our previous studies on the identification of multinucleated cells during normal testicle development, the current study further investigated the possible mechanism and role of these multinucleated cells. Healthy male Kunming mice were used in the present study. The association between multinucleated cells and cell apoptosis were analyzed using TUNEL analysis and immunohistochemistry. The results showed that multinucleated cells are widespread in the testicular tissue of seminiferous tubules on postnatal days 23, 27, 30, 33, 36, 40, 47, 50 and 54 suggesting that these cells are involved in the process of normal development of mouse testis. Histochemical analysis revealed a lack of proliferating cell nuclear antigen, cyclin D1 protein expression in multinucleated cells, suggesting that these cells are not involved in the G1 and S phases of the cell cycle and cell proliferation. Increased expression of Bax and caspase 3 was detected, revealing that multinucleated cells may be associated with cell apoptosis during testicular development. To the best of our knowledge, this study demonstrated for the first time that multinucleated cells are present during normal testicular development and may be associated with spermatogonial stem cell apoptosis. Therefore, multinucleated cells may be important in the spermatogenesis process.
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Parthenolide reverses doxorubicin resistance in human lung carcinoma A549 cells by attenuating NF-?B activation and HSP70 up-regulation.
Toxicol. Lett.
PUBLISHED: 02-28-2013
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Chemotherapy resistance represents a major problem for the treatment of patients with lung carcinomas. Parthenolide (PN), a naturally occurring small molecule found in herb feverfew, has been used in clinical treatment. Although its importance in treating the chemotherapy resistance has been shown, the pharmacological benefits of PN for lung cancer with multidrug resistance are underappreciated. Using human lung epithelial carcinoma A549 and A549 derived DOX-resistant A549/DOX cell lines, we found that PN enhanced the apoptotic cytotoxicity of DOX in A549/DOX cells. PN inhibited P-glycoprotein (P-gp) up-regulation and promoted the intracellular accumulation of DOX in A549/DOX cells. PN also exhibited inhibitory effect on NF-?B activation in A549/DOX cells, suggesting that inhibition of NF-?B was involved in attenuating P-gp expression by PN. Moreover, we found that PN could also effectively inhibit the HSP70 up-regulation in A549/DOX cells. Further studies revealed a positive correlation between HSP70 and P-gp expression. Overexpression of HSP70 upregulated P-gp expression independently of NF-?B activation in A549 cells, and knockdown of HSP70 caused a reduced expression of P-gp in A549/DOX cells. RT-PCR experiments showed that HSP70 modulated the P-gp expression mainly at transcription level. Taken together, PN can reverse DOX resistance through suppressing P-gp expression by mechanisms involving attenuation of NF-?B activation and HSP70 up-regulation. Our results not only provide insight into potential use of PN in reversing P-gp mediated MDR to facilitate lung cancer chemotherapy, but also highlight a potential role of HSP70 in the development of drug resistance.
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Cyclosporin A attenuates weight gain and improves glucose tolerance in diet-induced obese mice.
Mol. Cell. Endocrinol.
PUBLISHED: 02-23-2013
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Inflammation is a main factor responsible for obesity induced insulin resistance and type 2 diabetes. Since immunosuppressant activity is closely related with low level of inflammation, we predict that Cyclosporin A (CsA), an immunosuppressant drug, might have a protective role for combating inflammation-associated disorders such as obesity and type 2 diabetes. To address this issue, obese or lean mice were received CsA via gavage at the dose of 10mg/kg/day for 3 weeks. Our results show that CsA treatment remarkably attenuates food intake and body weight gain in the obese mice. CsA treatment down-regulates expression of gluconeogenic gene including Pepck, G6Pase and Pgc1?, leading to a decrease in blood glucose level and an improvement of glucose tolerance in the obese animals. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue reveal that CsA application reduces expression of Ppar?, Fas and Scd 1. The productions of pro-inflammatory cytokines (IL-1?, IL-2, IL-12 and TNF?) and JNK activity were remarkably reduced in the CsA-treated obese animals. These results suggest that CsA treatment might play beneficial effects against obesity and obesity related hyperglycemia.
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A core cross-linked polymeric micellar platium(IV) prodrug with enhanced anticancer efficiency.
Macromol Biosci
PUBLISHED: 02-07-2013
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A core cross-linked polymeric micellar cisplatin(IV) conjugate prodrug is prepared by attaching the cisplatin(IV) to mPEG-b-PLL biodegradable copolymers to form micellar nanoparticles that can disintegrate to release the active anticancer agent cisplatin(II) in a mild reducing environment. Moreover, in vitro studies show that this cisplatin(IV) conjugate prodrug displays enhanced cytotoxicity against HepG2 cancer cells compared with cisplatin(II). Further studies demonstrate that the high cellular uptake and platinum-DNA adduct of this cisplatin(IV) conjugate prodrug can induce more cancer-cell apoptosis than cisplatin(II), which is responsible for its enhanced anticancer activity.
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Phosphorylated Hsp27 activates ATM-dependent p53 signaling and mediates the resistance of MCF-7 cells to doxorubicin-induced apoptosis.
Cell. Signal.
PUBLISHED: 01-21-2013
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DNA damage activates p53 and its downstream target genes, which further leads to apoptosis or survival either by the cell cycle arrest or by DNA repair. In many tumors, the heat shock protein 27 (Hsp27) is expressed at high levels to provide protection against anticancer drugs. However, the roles of Hsp27 in p53-mediated cellular responses to DNA damage are controversial. Here, we investigated the interplay between the phosphorylation status of Hsp27 and p53 in kidney 293A (HEK293A) cells and found that over-expressing phosphorylated Hsp27 mimics (Hsp27-3D) activated p53/p21 in an ATM-dependent manner. In addition, incubation with doxorubicin (Dox), an anticancer drug, induced Hsp27 phosphorylation in human adenocarcinoma cells (MCF-7). In contrast, inhibition of Hsp27 phosphorylation retarded both p53 induction and p21 accumulation, and led to cell apoptosis. Furthermore, phosphorylated Hsp27 increased p53 nuclear importing and its downstream target gene expression such as p21 and MDM2, while de-phosphorylated Hsp27 impeded this procession. Taken together, our data suggest that Hsp27, in its phosphorylated or de-phosphorylated status, plays different roles in regulating p53 pathway and cell survival.
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Comparison of physicochemical characteristics and anticoagulant activities of polysaccharides from three sea cucumbers.
Mar Drugs
PUBLISHED: 01-09-2013
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In order to search for sulfated polysaccharides in different invertebrate connective tissues and to examine their biological activities, we have isolated three types of polysaccharides from the body wall of the three sea cucumbers Holothuria edulis, Apostichopus japonicas and Holothuria nobilis. The physicochemical properties and anticoagulant activities of these polysaccharides were examined and compared. The chemical composition analysis and nuclear magnetic resonance (NMR) analysis indicate that two types of polysaccharides, sulfated fucan and fucosylated chondroitin sulfate (FuCS), were found in all of the three species and in addition a neutral glycan was observed in H. edulis. The neutral ?-glucan was firstly obtained from sea cucumber. The same type of polysaccharides from different species of sea cucumbers have similar physicochemical properties and anticoagulant activities, but those of different types of glycans are significantly different, possibly due to their different monosaccharide compositions, electric charges and average molecular weights. The FuCSs have stronger anticoagulant activities than the sulfated fucans, although the molecular sizes of the FuCSs are lower than those of the sulfated fucans, whereas the neutral glucan has no activity, as expected from the absence of sulfate. Thus, anticoagulant activities of the different type of polysaccharides are likely to relate to monosaccharide composition and sulfate content. Preliminary analysis suggests that the sulfation patterns of the FuCSs may result in the difference in anticoagulant activities. Our data could help elucidate the structure-activity relationship of the sea cucumber polysaccharides.
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Differences in microcystin production and genotype composition among Microcystis colonies of different sizes in Lake Taihu.
Water Res.
PUBLISHED: 01-04-2013
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The cyanobacterium Microcystis, which occurs as colonies of different sizes under natural conditions, can produce toxic microcystins (MCs). To monitor the toxicity and assess the risk of Microcystis blooms in Lake Taihu, it is important to investigate the relationship between MC production and Microcystis colony size. In this study, we classified Microcystis collected from Zhushan Bay of Lake Taihu during blooms into four classes with size of <50 ?m, 50-100 ?m, 100-270 ?m and >270 ?m and studied their differences in MC production and genetic structure. The results showed that colonies with size of <50, 50-100, 100-270 and >270 ?m produced 12.2 ± 11.2%, 19.5 ± 7.9%, 61.3 ± 12.6%, and 7.0 ± 9.6% of total MC, respectively. The proportion of cell density of colonies with size of 50-100, 100-270 and >270 ?m was positively correlated with MC concentration during blooms, while that of colonies with size of <50 ?m was negatively correlated. The MC cell quota tended to be higher during blooms in colonies with larger size except that of colonies with size of 100-270 ?m was higher than that of colonies with size of >270 ?m from June 11 to September 16. Colonies with size of <50 ?m showed the highest proportion of the less toxic MC congener MC-RR, and colonies with size of >100 ?m showed higher proportion of the most toxic MC congener MC-LR than colonies with size of <100 ?m. Real-time PCR indicated that larger colonies had higher proportion of potential toxic genotype. Principal component analysis of PCR-denaturing gradient gel electrophoresis profile showed that cpcBA and mcyJ genotype compositions were different between colonies with size of <50 ?m and colonies with size of >50 ?m, and cpcBA genotype composition was also different among colonies with size of 50-100 ?m, 100-270 ?m and >270 ?m. These results indicated that MC cell quota and congener composition were different in Microcystis colonies with different sizes in Lake Taihu during blooms, and the differences in MC production in colonies with different size resulted chiefly from the difference in their genotype composition. Therefore, the authorities of water quality monitoring and drinking water supply service in Lake Taihu should be alert that the toxicity of Microcystis colony with different size was different during blooms, and the high abundance of colonies larger than 50 ?m could be an indicator of relatively high bloom toxicity.
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[Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 12-20-2011
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To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly.
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Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-?B signaling pathways.
Int. Immunopharmacol.
PUBLISHED: 10-09-2011
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Ampelopsin (AMP), a plant flavonoid, has potent anti-inflammatory properties in vitro and in vivo. The molecular mechanisms of ampelopsin on pharmacological and biochemical actions of RAW264.7 macrophages in inflammation have not been clearly elucidated yet. In the present study, non-cytotoxic level of ampelopsin significantly inhibited the release of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1?, IL-6 and tumor necrosis factor (TNF)-? in a dose-dependent manner. Consistent with NO inhibition, ampelopsin suppressed lipopolysaccharide (LPS)-induced expression of inducible NO synthase (iNOS) by inhibiting nuclear factor ?B (NF-?B) activation, which highly correlated with its inhibitory effect on I?B kinase (IKK) phosphorylation, I?B phosphorylation and NF-?B nuclear translocation. Further study demonstrated that ampelopsin suppressed LPS-induced activation of Akt without effecting mitogen-activated protein kinases (MAPKs) phosphorylation. A pharmacological inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt pathway, LY294002, abrogated IKK/I?B/NF-?B-mediated iNOS gene expression. Finally, we certificated that ampelopsin reduced reactive oxygen species (ROS) accumulation and an anti-oxidant N-acetyl-L-cysteine (NAC) significantly repressed LPS-induced PI3K/Akt phosphorylation and the downstream IKK/I?B activation. NAC thereby inhibited LPS-induced iNOS expression and NO production. The present results suggest that the anti-inflammatory effect of ampelopsin is due to inhibiting the interconnected ROS/Akt/IKK/NF-?B signaling pathways.
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Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge.
Int. Immunopharmacol.
PUBLISHED: 09-13-2011
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As a natural alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. Here we show that lycorine dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also inhibited NO, PGE(2), TNF-? and IL-6 release from LPS-treated RAW264.7 cells. RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. Moreover, lycorine decreased LPS-induced mortality in mice. Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed significantly by lycorine. In addition, lycorine did not interfere with the phosphorylation of ERK1/2, JNK1/2 and NF-?B pathways. In conclusion, lycorine inhibits LPS-induced production of pro-inflammatory mediators and increases the survival rate of mice after LPS challenge, suggesting that lycorine could play an anti-inflammatory role in response to LPS.
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l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes.
Food Chem. Toxicol.
PUBLISHED: 07-31-2011
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l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.
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Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells.
PLoS ONE
PUBLISHED: 07-27-2011
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It was well known that the clinical use of chemotherapeutic drugs is restricted by severe adverse reactions and drug resistances. Thus it is necessary to figure out a strategy to increase the specific anti-tumor efficiency of chemotherapeutic drugs. Apigenin, a kind of flavonoids, has been reported to possess anticancer activities with very low cytotoxicity to normal tissue.
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[Neuroprotective effect of ferulic acid in vitro].
Zhong Yao Cai
PUBLISHED: 07-25-2011
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To investigate the neuroprotective effect of ferulic acid on PC12 cells injuries.
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[Association of HER2 protein expression with clinicopathologic features and prognosis in Chinese patients with gastric carcinoma].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 07-16-2011
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To evaluate the epidemiological status of HER2 protein expression in Chinese patients with gastric carcinoma, and to study its clinical and prognostic significance and the association with the clinicopathological features.
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[Effect of sodium para-aminosalicylic on concentrations of amino acid neurotransmitters in basal ganglia of manganese-exposed rats].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 07-16-2011
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To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats.
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Seizure prediction with spectral power of EEG using cost-sensitive support vector machines.
Epilepsia
PUBLISHED: 06-21-2011
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We propose a patient-specific algorithm for seizure prediction using multiple features of spectral power from electroencephalogram (EEG) and support vector machine (SVM) classification.
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[Effects of low level manganese exposure on the serum neuroendocrine hormones in the welders].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 05-31-2011
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To study the effects of low level manganese (Mn) exposure on the serum neuroendocrine hormones levels of the welders.
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Expression and purification of antimicrobial peptide buforin IIb in Escherichia coli.
Biotechnol. Lett.
PUBLISHED: 05-28-2011
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A novel production method in Escherichia coli for an antimicrobial peptide of 21 amino acids, buforin IIb, which is a synthetic analog of buforin II, has been developed. The buforin IIb gene was cloned into the vector pET32a to construct an expression vector pET32a-buforin IIb. The fusion protein Trx-buforin IIb, purified by nickel nitrilo-triacetic acid (Ni-NTA) resin chromatography, was cleaved by hydroxylamine hydrochloride to release recombinant buforin IIb. Purification of recombinant buforin IIb was achieved by HPLC: about 3.1 mg/l active recombinant buforin IIb with purity >99% was obtained. The recombinant buforin IIb showed antimicrobial activities that were similar to the synthetic one.
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[Immunophenotypes and prognosis of diffuse large B-cell lymphoma: a study of 500 cases].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 05-28-2011
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To study the immunophenotype and overall survival of diffuse large B-cell lymphoma (DLBCL) classified according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues.
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Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.
J. Cell. Biochem.
PUBLISHED: 05-25-2011
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Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-?B). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment.
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Knowledge, attitudes, and practices on malaria prevention among Chinese international travelers.
J Travel Med
PUBLISHED: 04-06-2011
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To address the lack of understanding in malaria prevention among Chinese international travelers, we have conducted knowledge, attitudes, and practices (KAP) study in five different Chinese geographic areas. This survey represents one part of the background information needed to analyze imported malaria.
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Pulmonary embolus from acute superior sagittal sinus thrombosis secondary to skull fracture: case report.
Neurosurgery
PUBLISHED: 03-11-2011
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Pulmonary embolus (PE) occurring concurrent with-and as a result of-traumatic superior sagittal sinus thrombosis (SSST) has never before been reported. We report the first case of a patient who presented with acute traumatic SSST and concomitant PE.
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Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.
Int. Immunopharmacol.
PUBLISHED: 03-01-2011
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Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1?, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 ?M). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages.
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Production of bioactive ?-glutamyl transpeptidase in Escherichia coli using SUMO fusion partner and application of the recombinant enzyme to L-theanine synthesis.
Curr. Microbiol.
PUBLISHED: 01-31-2011
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The amino acid L-theanine (?-glutamylethylamide) has potential important applications in the food and pharmaceutical industries and increased demand for this compound is expected. It is the major "umami" (good taste) component of tea and its favorable physiological effects on mammals have been reported. An enzymatic method for the synthesis of L-theanine involving recombinant Escherichia coli ?-glutamyltranspeptidase (GGT) has been developed. We report here the application of small ubiquitin-related modifier (SUMO) fusion technology to the expression and purification of recombinant Escherichia coli ?-GGT. In order to obtain ?-GGT with high theanine-forming activity, safety, and low cost for food and pharmaceutics industry, M9 (consisting of glycerol and inorganic salts) and 0.1% (w/v) lactose were selected as culture medium and inducer, respectively. The fusion protein was expressed in soluble form in E. coli, and expression was verified by SDS-PAGE and western blot analysis. The fusion protein was purified to 90% purity by nickel-nitrilotriacetic acid (Ni-NTA) resin chromatography with a yield of 115 mg per liter fermentation culture. After the SUMO/?-GGT fusion protein was cleaved by the SUMO protease, the cleaved sample was reapplied to a Ni-NTA column. Finally, about 62 mg recombinant ?-GGT was obtained from 1 l fermentation culture with no less than 95% purity. The recombinant ?-GGT showed great transpeptidase activity, with 1500 U of purified recombinant ?-GGT in a 1-l reaction system, a biosynthesis yield of 41 g of L-theanine was detected by paper chromatography or high pressure liquid chromatography (HPLC). Thus, the application of SUMO technology to the expression and purification of ?-GGT potentially could be employed for the industrial production of L-theanine.
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Rural - urban inequalities in late-stage breast cancer: spatial and social dimensions of risk and access.
Environ Plann B Plann Des
PUBLISHED: 01-01-2011
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Rural - urban inequalities in health and access to health care have long been of concern in health-policy formulation. Understanding these inequalities is critically important in efforts to plan a more effective geographical distribution of public health resources and programs. Socially and ethnically diverse populations are likely to exhibit different rural - urban gradients in health and well-being because of their varying experiences of place environments, yet little is known about the interplay between social and spatial inequalities. Using data from the Illinois State Cancer Registry, we investigate rural - urban inequalities in late-stage breast cancer diagnosis both for the overall population and for African-Americans, and the impacts of socioeconomic deprivation and spatial access to health care. Changes over time are analyzed from 1988 - 92 to 1998 - 2002, periods of heightened breast cancer awareness and increased access to screening. In both time periods, the risk of late-stage diagnosis is highest among patients living in the most urbanized areas, an indication of urban disadvantage. Multilevel modeling results indicate that rural - urban inequalities in risk are associated with differences in the demographic characteristics of area populations and differences in the social and spatial characteristics of the places in which they live. For African-American breast cancer patients, the rural - urban gradient is reversed, with higher risks among patients living outside the city of Chicago, suggesting a distinct set of health-related risks and place experiences that inhibit early breast cancer detection. Findings emphasize the need for combining spatial and social targeting in locating cancer prevention and treatment programs.
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Successfully ablated atrioventricular nodal reentrant tachycardia in unconventional presentation.
J Cardiovasc Dis Res
PUBLISHED: 12-29-2010
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#ENTITYSTARTX02014; Sometime, its difficult to distinguish the electrophysiological mechanism of some tachycardia, and so, influencing the efficacy and safety of ablation operation. Therefore, its helpful to analysis some tachycardia in particular mechanism, as in this case.
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Asymmetric cyclopropanation of ?,?-unsaturated ?-ketoesters with stabilized sulfur ylides catalyzed by C2-symmetric ureas.
J. Org. Chem.
PUBLISHED: 12-08-2010
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A novel organocatalytic asymmetric cyclopropanation of ?,?-unsaturated ?-ketoesters with stabilized sulfur ylides using C(2)-symmetric urea as a hydrogen-bond catalyst has been described. This reaction allows an efficient access to 1,2,3-trisubstituted cyclopropane derivatives in moderate to good yields with up to 16:1 dr and 90:10 er under mild reaction conditions. The mechanism study proved that the high stereoinduction originated from the cooperative effect of the hydrogen-bond catalyst.
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Molecular diversity and functional evolution of scorpion potassium channel toxins.
Mol. Cell Proteomics
PUBLISHED: 09-30-2010
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Scorpion toxins affecting K(+) channels (KTxs) represent important pharmacological tools and potential drug candidates. Here, we report molecular characterization of seven new KTxs in the scorpion Mesobuthus eupeus by cDNA cloning combined with biochemical approaches. Comparative modeling supports that all these KTxs share a conserved cysteine-stabilized ?-helix/?-sheet structural motif despite the differences in protein sequence and size. We investigated functional diversification of two orthologous ?-KTxs (MeuTXK?1 from M. eupeus and BmP01 from Mesobuthus martensii) by comparing their K(+) channel-blocking activities. Pharmacologically, MeuTXK?1 selectively blocked Kv1.3 channel with nanomolar affinity (IC(50), 2.36 ± 0.9 nM), whereas only 35% of Kv1.1 currents were inhibited at 3 ?M concentration, showing more than 1271-fold selectivity for Kv1.3 over Kv1.1. This peptide displayed a weak effect on Drosophila Shaker channel and no activity on Kv1.2, Kv1.4, Kv1.5, Kv1.6, and human ether-a-go-go-related gene (hERG) K(+) channels. Although BmB01 and MeuTXK?1 have a similar channel spectrum, their affinity and selectivity for these channels largely varies. In comparison with MeuTXK?1, BmP01 only exhibits a submicromolar affinity (IC(50), 133.72 ± 10.98 nM) for Kv1.3, showing 57-fold less activity than MeuTXK?1. Moreover, it lacks the ability to distinguish between Kv1.1 and Kv1.3. We also found that MeuTXK?1 inhibited the proliferation of activated T cells induced by phorbol myristate acetate and ionomycin at micromolar concentrations. Our results demonstrate that accelerated evolution drives affinity variations of orthologous ?-KTxs on Kv channels and indicate that MeuTXK?1 is a promising candidate to develop an immune modulation agent for human autoimmune diseases.
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DrTx(1-42), a C-terminally truncated analogue of drosotoxin, is a candidate of analgesic drugs.
Biochem. Pharmacol.
PUBLISHED: 09-08-2010
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Drosotoxin is an engineered tetrodotoxin-resistant (TTX-R) sodium channel-specific blocker with a non-toxic structural core (Zhu et al. Biochem Pharmacol 2010; 80:1296-302). Here, we report the discovery and functional characterization of a carboxyl-terminally truncated analogue of drosotoxin (named DrTx(1-42)) which selectively inhibited dorsal root ganglion (DRG) neuron TTX-R sodium current (I(Na)) with an IC(50) value of 1.74±0.07?M. Consistent with this effect, DrTx(1-42) significantly attenuates inflammatory hyperalgesia of mice in a formalin-induced pain model with stronger potency than indomethacin, a nonsteroidal anti-inflammatory and analgesic drug. Our mutational experiments indicate that the N-turn insertion is an essential functional determinant for the emergence of neurotoxicity from a non-toxic antifungal scaffold.
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Modification of atrioventricular node in a special condition treating paroxysmal supraventricular tachycardia.
J Cardiovasc Dis Res
PUBLISHED: 09-07-2010
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Modification of atrioventricular node is a usual and necessary operation to cure atrioventricular nodal reentrant tachycardia (AVNRT). In this operation, atrioventricular block is the most severe complication and its prevention is of our great concern. This complication always occurs under some special circumstances with potential risk. So, it is very important to realize such conditions, as in this paper. A patient with paroxysmal palpitation for 10 years, aggravating to shortness of breath with chest distress for 1 year; cardiac electrophysiological examination found slow conduction in both antegrade and retrograde paths of reentrant loop, and typical AVNRT could be induced. During effective ablation there was no junctional rhythm. In some special cases, modification of atrioventricular node should not only rely on the junctional rhythm to determine the ablation effect, but also on the time of cardiac electrophysiological examination, as such to avoid the severe complication of atrioventricular block caused by excessive ablation.
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Curcumin promotes degradation of inducible nitric oxide synthase and suppresses its enzyme activity in RAW 264.7 cells.
Int. Immunopharmacol.
PUBLISHED: 08-02-2010
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Curcumin, a natural polyphenolic compound, has been reported to possess anti-inflammatory properties. Previous works showed that curcumin decreased lipopolysaccharide (LPS)-induced iNOS up-regulation at transcription level. However, whether curcumin could regulate iNOS at the post-translational level is still unclear. In the present study, we demonstrated that curcumin promoted the degradation of iNOS which is expressed under LPS stimulation in murine macrophage-like RAW 264.7 cells. Mechanically, such degradation of iNOS protein is due to ubiquitination and proteasome-dependency since it was almost completely blocked by N-benzoyloxycarbonyl-Leu-Leu-leucinal (MG132), a specific inhibitor of proteasome. Furthermore, curcumin decreased iNOS tyrosine phosphorylation through inhibiting ERK 1/2 activation and subsequently suppressed iNOS enzyme activity. In conclusion, our research displays a new finding that curcumin can promote the ubiqitination and degradation of iNOS after LPS stimulation.
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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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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.