JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Unprecedented Access to Strong and Ductile Poly(lactic acid) by Introducing In Situ Nanofibrillar Poly(butylene succinate) for Green Packaging.
Biomacromolecules
PUBLISHED: 10-08-2014
Show Abstract
Hide Abstract
The notion of toughening poly(lactic acid) (PLA) by adding flexible biopolymers has generated enormous interest but has yielded few desirable advances, mainly blocked by the sacrifice of strength and stiffness due to uncontrollable phase morphology and poor interfacial interactions. Here the phase control methodology, that is, intense extrusion compounding followed by "slit die extrusion-hot stretching-quenching" technique, was proposed to construct well-aligned, stiff poly(butylene succinate) (PBS) nanofibrils in the PLA matrix for the first time. We show that generating nanosized discrete droplets of PBS phase during extrusion compounding is key to enable the development of in situ nanofibrillar PBS assisted by the shearing/stretching field. The size of PBS nanofibrils strongly dependent on the PBS content, showing an increased average diameter from 83 to 116 and 236 nm for the composites containing 10, 20, and 40 wt % nanofibrils, respectively. More importantly, hybrid shish-kebab superstructure anchoring ordered PLA kebabs were induced by the PBS nanofibrils serving as the central shish, conferring the creation of tenacious interfacial crystalline ligaments. The exceptional combination of strength, modulus, and ductility for the composites loaded 40 wt % PBS nanofibrils were demonstrated, outperforming pure PLA with the increments of 31, 51, and 72% in strength, modulus, and elongation at break (56.4 MPa, 1702 MPa, and 92.4%), respectively. The high strength, modulus, and ductility are unprecedented for PLA and are in great potential need for packaging applications.
Related JoVE Video
Intense exercise can cause excessive apoptosis and synapse plasticity damage in rat hippocampus through Ca²? overload and endoplasmic reticulum stress-induced apoptosis pathway.
Chin. Med. J.
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
Intense exercise can cause injury and apoptosis, but few studies have reported its effect on the central nervous system (CNS). The initial reason for hippocampus injury is the excitotoxicity of glutamate and calcium overload. Intracellular free Ca(2+) ([Ca(2+)]i) overload may trigger the apoptosis pathway and neuron damage. The aim of this study was to investigate whether intense exercise could cause hippocampus apoptosis and neuron damage and then to determine which pathway was activated by this apoptosis.
Related JoVE Video
A Nanoparticle-Encapsulated non-Nucleoside Reverse-Transcriptase Inhibitor with Enhanced Anti-HIV-1 Activity and Prolonged Circulation Time in Plasma.
Curr. Pharm. Des.
PUBLISHED: 09-21-2014
Show Abstract
Hide Abstract
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs), major components of highly active antiretroviral therapy (HAART), are effective in suppressing viral replication and preventing the progress of HIV-1 infection to AIDS. However, rapid blood clearance in vivo could significantly impair the efficiency of the anti-HIV-1 activity and result in multiple daily doses which might lead to poor patient compliance. Here we attempted to employ biodegradable organic nanoparticles (NPs) to encapsulate DAAN15h, a derivative of 4-substituted 1,5-diarylaniline with potent anti-HIV activities. Nanoparticles encapsulating DAAN15h (NP-DAAN15h) displayed a spherical shape with a size of 97.01 ± 3.64 nm and zeta potential of -19.1 ± 3.78 mV, and they exhibited a sustained controlled release behavior in vitro. The cellular uptake of NPs on TZM-b1 cells, MT-2 cells and M7 cells, possibly through lipid raft-mediated and energy-dependent active transport processes, was significantly enhanced. NP-DAAN15h, which possessed no significant in vitro cytotoxicity, showed improved antiviral activity against laboratory-adapted and primary HIV-1 isolates with different subtypes and tropisms, including RT-resistant variants. NP-DAAN15h exhibited a significantly prolonged blood circulation time, decreased plasma elimination rate, and enhanced AUC(0-t). NP-DAAN15h, a nanoparticle-encapsulated NNRTI, exhibits enhanced cellular uptake, improved anti-HIV-1 efficacy and prolonged in vivo circulation time, suggesting good potential for further development as a new NNRTI formulation for clinical use.
Related JoVE Video
[Compound danshen injection regulated the expression of AQP3 in the human amnion epithelium cells through JNK signal pathway].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 09-17-2014
Show Abstract
Hide Abstract
To explore the role of Compound Danshen Injection (CDI) in regulating the expression of aquaporin 3 (AQP3) in human amnion epithelium cells (hAECs), and to study the relation between c-Jun N-terminal kinase (JNK) signal pathway and AQP3.
Related JoVE Video
C19MC microRNAs Regulate the Migration of Human Trophoblasts.
Endocrinology
PUBLISHED: 09-11-2014
Show Abstract
Hide Abstract
Early in pregnancy, trophoblast invasion into the decidua and inner myometrium is essential for establishment of proper implantation, maternal-fetal exchange, and immunological tolerance of the feto-placental allograft. Unlike villous trophoblasts, extravillous trophoblasts are unique in their capacity to invade the maternal decidua and myometrium. The largest human microRNA (miRNA) gene cluster, the chromosome 19 miRNA cluster (C19MC), is expressed almost exclusively in the placenta and, rarely, in certain tumors and undifferentiated cells. In the work reported here, we found that the expression of C19MC miRNAs is higher in villous trophoblasts than in extravillous trophoblasts. Using a BAC-mediated overexpression of C19MC miRNAs in an extravillous trophoblast-derived cell line, which does not naturally express these miRNAs, we found that C19MC miRNAs selectively attenuate cell migration without affecting cell proliferation or apoptosis. A microarray analysis revealed that C19MC miRNAs regulate target transcripts related to cellular movement. Our data also implicated a specific C19MC member, miR-519d, in directly regulating the extravillous trophoblast invasive phenotype by targeting CXCL6, NR4A2 and FOXL2 transcripts through a 3'UTR miRNA-responsive element. Together, our data suggest a role for C19MC miRNAs in modulating the migration of extravillous trophoblasts.
Related JoVE Video
Systematically labeling developmental stage-specific genes for the study of pancreatic ?-cell differentiation from human embryonic stem cells.
Cell Res.
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic ? cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP(+) cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature ? cells in vitro.
Related JoVE Video
[An approach for segmentation of X-ray angiographic image based on region-growing and structure inferring].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-22-2014
Show Abstract
Hide Abstract
We presented a new method for vessel segmentation and vascular structure recognition for coronary angiographic images. During vessel segmentation, a new vessel function was proposed to attain vessel feature map. Then the region growing algorithm was implemented with an automatic selection of seed point, extraction of main vessel branch, and vessel detail repairing. In the algorithm of vascular structure recognition, a fuzzy operator was used, which can detect the structures of vascular segments, bifurcations, crosses, and tips. The experimental results indicated that there was about 5 percent larger vessel region which was extracted by the proposed segmentation method than that by the simple region growing algorithm, and several thinner vessels were resumed from the lower gray region. The results also indicated that the fuzzy operator could correctly infer the simulative and real vessel structure with 100% and 90.59% correctness rate on the average, respectively.
Related JoVE Video
Enantioselective Iron-Catalyzed Intramolecular Cyclopropanation Reactions.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-03-2014
Show Abstract
Hide Abstract
An iron-catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97?%?ee) by using the iron complexes of chiral spiro-bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions.
Related JoVE Video
Systematic profiling of mRNA and miRNA expression in the pancreatic islets of spontaneously diabetic Goto?Kakizaki rats.
Mol Med Rep
PUBLISHED: 07-01-2014
Show Abstract
Hide Abstract
Type 2 diabetes (T2DM) is a complex multifactorial metabolic disorder that affects >100 million individuals worldwide, yet the mechanisms involved in the development and progression of the disease have not yet been fully elucidated. The present study examined the mRNA and micro (mi)RNA expression profiles by microarray analysis in the pancreas islets of spontaneously diabetic Goto?Kakizaki rats with the aim to identify regulatory mechanisms underlying the pathogenesis of T2DM. A total of 9 upregulated and 10 downregulated miRNAs were identified, including miR?150, miR?497, miR?344?3p and let?7f, which were independently validated by quantitative polymerase chain reaction assays. In addition, differential expression of 670 genes was detected by mRNA microarray analysis, including 370 upregulated and 247 downregulated genes. The differentially expressed genes were statistically associated with major cellular pathways, including the immune response pathway and the extracellular matrix (ECM)?receptor interaction pathway. Finally, a reverse regulatory association of differentially expressed miRNAs and their predicted target genes was constructed, supported by analysis of their mRNA and miRNA expression profiles. A number of key pairs of miRNA?mRNA was proposed to have significant roles in the pathogenesis of T2DM rats based on bioinformatics analysis, one example being the let?7f/collagen, type II, alpha 1 pair that may regulate ECM?receptor interactions.
Related JoVE Video
Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-25-2014
Show Abstract
Hide Abstract
Using physicochemical property-driven optimization, twelve new diarylaniline compounds (DAANs) (7a-h, 11a-b and 12a-b) were designed and synthesized. Among them, compounds 12a-b not only showed high potency (EC50 0.96-4.92 nM) against both wild-type and drug-resistant viral strains with the lowest fold change (FC 0.91 and 5.13), but also displayed acceptable drug-like properties based on aqueous solubility and lipophilicity (LE>0.3, LLE>5, LELP<10). The correlations between potency and physicochemical properties of these DAAN analogues are also described. Compounds 12a-b merit further development as potent clinical trial candidates against AIDS.
Related JoVE Video
Structural basis for unique hierarchical cylindrites induced by ultrahigh shear gradient in single natural fiber reinforced poly(lactic acid) green composites.
Biomacromolecules
PUBLISHED: 04-24-2014
Show Abstract
Hide Abstract
A local shear flow field was feasibly generated by pulling the ramie fiber in single fiber reinforced poly(lactic acid) (PLA) composites. This was featured by an ultrahigh shear gradient with a maximum shear rate up to 1500 s(-1), a level comparable to that frequently occurring during the practical polymer processing. To distinguish shear-induced self-nucleation and ramie fiber-induced heterogeneous nucleation, the shear history was classified by pulling the fiber for 5 s (pulled sample) and pulling out the fiber during 10 s (pulled-out sample), while the static fiber-induced crystallization was carried out as the counterpart. As a result of the ultrahigh shear gradient, the combination of primary shear-induced nucleation in the central region and secondary nucleation in the outer layer assembled the unique hierarchical superstructures. By comparing the architectural configurations of interphases formed in the static, pulled, and pulled-out samples, it was shown that the hierarchical cylindrites underwent the process of self-nucleation driven by the applied shear flow, very different from the formation of fiber-induced transcrystallinity (TC) triggered by the heterogeneous nucleating sites at the static fiber surface. The twisting of transcrystallized lamellae may take place due to the spatial hindrance induced by the incredibly dense nuclei under the intense shearing flow, as observed in the synchrotron X-ray diffraction patterns. The influence of chain characteristics on the crystalline morphology was further explored by adding a small amount of poly(ethylene glycol) (PEG) to enhance the molecular mobility of PLA. It was of interest to find that the existence of PEG not only facilitated the growth rates of TC and cylindrites but also improved the preferential orientation of PLA chains and thus expanded the ordered regions. We unearthed lamellar units that were composed of rich fibrillar extended chain crystals (diameter of 50-80 nm). These results are of importance to shed light on tailoring crystalline morphology for natural fibers reinforced green composite materials. Of immense practical significance, too, is the crystalline evolution that has been tracked in the simple model penetrated with an ultrahigh shear gradient, which researchers have so far been unable to replicate during the practical melt processing, such as extrusion and injection molding.
Related JoVE Video
A Brønsted acid catalyzed redox arylation.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-03-2014
Show Abstract
Hide Abstract
A Brønsted acid catalyzed redox arylation of ynamides that employs aryl sulfoxides as the arylating agents is reported. This metal-free transformation proceeds at room temperature and efficiently affords ?-arylated oxazolidinones in a redox-neutral, atom-economic fashion.
Related JoVE Video
The construction of an interfacial valve-based microfluidic chip for thermotaxis evaluation of human sperm.
Biomicrofluidics
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
Thermotaxis has been demonstrated to be an important criterion for sperm evaluation, yet clinical assessment of thermotaxis capacity is currently lacking. In this article, the on-chip thermotaxis evaluation of human sperm is presented for the first time using an interfacial valve-facilitated microfluidic device. The temperature gradient was established and accurately controlled by an external temperature gradient control system. The temperature gradient responsive sperm population was enriched into one of the branch channels with higher temperature setting and the non-responsive ones were evenly distributed into the two branch channels. We employed air-liquid interfacial valves to ensure stable isolation of the two branches, facilitating convenient manipulation of the entrapped sperm. With this device, thermotactic responses were observed in 5.7%-10.6% of the motile sperm moving through four temperature ranges (34.0-35.3?°C, 35.0-36.3?°C, 36.0-37.3?°C, and 37.0-38.3?°C, respectively). In conclusion, we have developed a new method for high throughput clinical evaluation of sperm thermotaxis and this method may allow other researchers to derive better IVF procedure.
Related JoVE Video
Isolation, classification and transcription profiles of the AP2/ERF transcription factor superfamily in citrus.
Mol. Biol. Rep.
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
The AP2/ERF gene family encodes plant-specific transcription factors. In model plants, AP2/ERF genes have been shown to be expressed in response to developmental and environmental stimuli, and many function downstream of the ethylene, biotic, and abiotic stress signaling pathways. In citrus, ethylene is effective in regulation citrus fruit quality, such as degreening and aroma. However, information about the citrus AP2/ERF family is limited, and would enhance our understanding of fruit responses to environmental stress, fruit development and quality. CitAP2/ERF genes were isolated using the citrus genome database, and their expression patterns analyzed by real-time PCR using various orange organs and samples from a fruit developmental series. 126 sequences with homologies to AP2/ERF proteins were identified from the citrus genome, and, on the basis of their structure and sequence, assigned to the ERF family (102), AP2 family (18), RAV family (4) and Soloist (2). MEME motif analysis predicted the defining AP2/ERF domain and EAR repressor domains. Analysis of transcript accumulation in Citrus sinensis cv. 'Newhall' indicated that CitAP2/ERF genes show organ-specific and temporal expression, and provided a framework for understanding the transcriptional regulatory roles of AP2/ERF gene family members in citrus. Hierarchical cluster analysis and t tests identified regulators that potentially function during orange fruit growth and development.
Related JoVE Video
Optimization of 4-(N-cycloamino)phenylquinazolines as a novel class of tubulin-polymerization inhibitors targeting the colchicine site.
J. Med. Chem.
PUBLISHED: 02-06-2014
Show Abstract
Hide Abstract
The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a-c and 5a-m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI50 1.9-3.2 nM), significant potency against tubulin assembly (IC50 0.77 ?M), and substantial inhibition of colchicine binding (99% at 5 ?M). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose.
Related JoVE Video
Enantioselective palladium-catalyzed insertion of ?-aryl-?-diazoacetates into the O-H bonds of phenols.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-05-2014
Show Abstract
Hide Abstract
A palladium-catalyzed asymmetric O-H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of ?-aryl-?-diazoacetates into the O-H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium-catalyzed asymmetric O-H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active ?-aryl-?-aryloxyacetates.
Related JoVE Video
Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS.
ChemMedChem
PUBLISHED: 01-30-2014
Show Abstract
Hide Abstract
Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the phenoxy C-ring were synthesized and evaluated for anti-HIV activity and certain drug-like properties. Ten compounds showed high anti-HIV activity (EC50 <10?nM). In particular, (E)-6-(2''-bromo-4''-cyanovinyl-6''-methoxy)phenoxy-N(2) -(4'-cyanophenyl)pyridin-2,3-diamine (8?c) displayed low-nanomolar antiviral potency (3-7?nM) against wild-type and drug-resistant viral strains bearing the E138K or K101E mutations, which are associated with resistance to rilvipirine (1?b). Compound 8?c exhibited much lower resistance fold changes (RFC: 1.1-2.1) than 1?b (RFC: 11.8-13.0). Compound 8?c also exhibited better metabolic stability (in vitro half-life) than 1?b in human liver microsomes, possessed low lipophilicity (clog?D: 3.29; measured log?P: 3.31), and had desirable lipophilic efficiency indices (LE>0.3, LLE>5, LELP<10). With balanced potency and drug-like properties, 8?c merits further development as an anti-HIV drug candidate.
Related JoVE Video
MKL1/2 and ELK4 co-regulate distinct serum response factor (SRF) transcription programs in macrophages.
BMC Genomics
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
Serum response factor (SRF) is a widely expressed transcription factor involved in multiple regulatory programs. It is believed that SRF can toggle between disparate programs of gene expression through association with different cofactors. However, the direct evidence as to how these factors function on a genome-wide level is still lacking.
Related JoVE Video
A novel synthetic dibenzocyclooctadiene lignan analog XLYF-104-6 attenuates lipopolysaccharide-induced inflammatory response in RAW264.7 macrophage cells and protects BALB/c mice from sepsis.
Eur. J. Pharmacol.
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
The wide range of inflammation mechanisms under control by NF-?B makes this pathway as an attractive target for new anti-inflammatory drugs. Herein, we showed that a new dibenzocyclooctadiene lignan analog XLYF-104-6, with a chemical name of 1,2,3,10,11-pentamethoxydibenzocycloocta-6,7-[c] pyrrole-1,3-dione, inhibited lipopolysaccharide (LPS)-induced NF-?B activation in RAW264.7 cells through preventing I?B? degradation and p65 nuclear translocation. The inhibitory activity of this compound on NF-?B activation contributes to the reduction of LPS-induced TNF-? and IL-6 productions. Notably, XLYF-104-6 suppressed LPS-induced iNOS expression and NO production in a NF-?B independent manner, since IKK inhibitor BAY 11-7082 has failed to exert similar inhibitory effect on iNOS expression and NO production. In addition, XLFY-104-6 also exerted anti-inflammatory action in endotoxemic mice by decreasing plasma LPS-induced TNF-? and IL-1? levels as well as increasing plasma LPS-induced IL-10 concentrations. These findings suggest XLYF-104-6 could act as a leading compound for developing a potential anti-inflammatory drug.
Related JoVE Video
Aberrant phenotypes in Kikuchi's disease.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Initial reports emphasized the immunophenotypic similarities between benign and malignant T cell populations, while some previous studies indicating that aberrant T-cell antigen loss is a good marker for detecting malignant T-cell proliferation. Recently, we found a very interesting and thought-provoking phenomenon: In benign disease-28 of 38 (73.7%) cases of Kikuchi's disease also showed aberrant phenotypes with loss of pan-T cell antigens, which makes the differential diagnosis between Kikuchi's disease and T cell lymphoma more challenging. In our study, 38 cases of Kikuchi's disease and 30 cases of reactive lymphoid hyperplasia (RLH) were studied by EliVision immunohistochemical staining. As well as TCR gene rearrangement using PCR was negative in 10 tested cases of the Kikuchi's disease. Among these cases, the most common antigen deficiency was CD5 (22 cases), then CD7 (11 cases), CD2 (8 cases) and CD3 (2 cases). Compared with proliferative and xanthomatous types of Kikuchi's disease, antigens tended to be lost in necrotizing type. Based on follow-up data, a correlation was not found between the occurrence of aberrant phenotypes and prognosis. In RLH, obvious pan-T cell antigen loss was also not found. In conclusion, this is the first study to demonstrate distinct patterns of antigen loss in Kikuchi's disease, suggesting that T cell antigen loss is not reliable as an auxiliary diagnostic standard for T cell lymphoma.
Related JoVE Video
PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
A small population of cancer stem cells named the "side population" (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells.
Related JoVE Video
Perinatal programming of emotional brain circuits: an integrative view from systems to molecules.
Front Neurosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional "scars" in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of "stress inoculation" is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.
Related JoVE Video
Toward Stronger Transcrystalline Layers in Poly(l-lactic acid)/Natural Fiber Biocomposites with the Aid of an Accelerator of Chain Mobility.
J Phys Chem B
PUBLISHED: 12-12-2013
Show Abstract
Hide Abstract
Formation of transcrystalline layer probably enhances the interfacial adhesion of poly(l-lactic acid) (PLLA)/natural fiber biocomposites as confirmed by this work. We found that a crystallization accelerator, poly(ethylene glycol) (PEG), improved chain mobility of PLLA and thus enhanced the growth kinetics of ramie fiber-induced transcrystallinity (TC). The direct observation of polarized optical microscopy during isothermal crystallization revealed that large-sized TC with rapid growth was produced after adding PEG. It could be exemplified by the case at 125 °C that the growth rate of TC developed in PLLA10 (containing 10 wt % PEG) achieved 6.1 ?m/min, which was nearly triple that of pure PLLA (2.1 ?m/min). And interestingly enough, spherulitic nucleation proceeding was largely restricted because it was difficult to fulfill the critical size for stable nuclei due to the increased chain mobility. Meanwhile, combining the effective nucleation activity of ramie fibers and acceleration virtue of PEG offered the chance to form prevailing TC texture, instead of rich spherulites dominated in pure PLLA. The local structure (including lamellar structure and molecular orientation) of transcrystalline layers was further determined, which indicated that TC presented ? crystal form and random lamellar packing derived from the moderate nucleating ability. To our surprise, the single fiber reinforced composite samples containing prevailing TC textures achieved remarkably higher strength compared to that of pure PLLA samples with poorly developed transcrystalline layers, as demonstrated by the single-fiber pull-out test.
Related JoVE Video
[Synthesis and biological evaluation of diarylamines with antitumor activity].
Yao Xue Xue Bao
PUBLISHED: 11-06-2013
Show Abstract
Hide Abstract
By structural modifications of our previous leads 1-3, 18 diarylamines were designed, synthesized and evaluated with a human tumor cell line panel, including A549, DU145, KB, and KB-vin cell lines, resulting in the discovery of new antitumor agents A6 and B2 with low micromolar G50 values ranging from 1.55-2.10 micromol x L(-1) for above cell lines, and A9 with GI50 values ranging from 1.55-2.10 micromol x L(-1) specially for DU145, KB, and KB-vin cells. Current structure-activity relationships are helpful for further lead optimization.
Related JoVE Video
Discovery of novel antitumor dibenzocyclooctatetraene derivatives and related biphenyls as potent inhibitors of NF-?B signaling pathway.
Bioorg. Med. Chem.
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
Several dibenzocyclooctatetraene derivatives (5-7) and related biphenyls (8-11) were designed, synthesized, and evaluated for inhibition of cancer cell growth and the NF-?B signaling pathway. Compound 5a, a dibenzocyclooctatetraene succinimide, was discovered as a potent inhibitor of the NF-?B signaling pathway with significant antitumor activity against several human tumor cell lines (GI50 1.38-1.45?M) and was more potent than paclitaxel against the drug-resistant KBvin cell line. Compound 5a also inhibited LPS-induced NF-?B activation in RAW264.7 cells with an IC50 value of 0.52?M, prevented I?B-? degradation and p65 nuclear translocation, and suppressed LPS-induced NO production in a dose-dependent manner. The antitumor data in cellular assays indicated that relative positions and types of substituents on the dibenzocyclooctatetraene or acyclic biphenyl as well as torsional angles between the two phenyls are of primary importance to antitumor activity.
Related JoVE Video
Copper-catalyzed B-H bond insertion reaction: a highly efficient and enantioselective C-B bond-forming reaction with amine-borane and phosphine-borane adducts.
J. Am. Chem. Soc.
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
A copper-catalyzed B-H bond insertion reaction with amine- and phosphine-borane adducts was realized with high yield and enantioselectivity under mild reaction conditions. The B-H bond insertion reaction provides a new C-B bond-forming methodology and an efficient approach to chiral organoboron compounds.
Related JoVE Video
[The role of MAPK signal pathway in the regulation of AQP3 expression induced by compound danshen injection in human amniotic epithelial cells].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-29-2013
Show Abstract
Hide Abstract
To investigate the role of mitogen-activated protein kinases (MAPKs)-extracellular signal regulated kinase1/2 (ERK1/2) signal pathway in the regulation of Compound Danshen Injection (CDI) induced AQP3 expression in the human amniotic epithelial cells (hAECs).
Related JoVE Video
[Investigation of characteristic microstructures of adhesive interface in wood/bamboo composite material by synchrotron radiation X-ray phase contrast microscopy].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-28-2013
Show Abstract
Hide Abstract
Third-generation synchrotron radiation X-ray phase-contrast microscopy(XPCM)can be used for obtaining image with edge enhancement, and achieve the high contrast imaging of low-Z materials with the spatial coherence peculiarity of X-rays. In the present paper, the characteristic microstructures of adhesive at the interface and their penetration in wood/bamboo composite material were investigated systematically by XPCM at Shanghai Synchrotron Radiation Facility (SSRF). And the effect of several processing techniques was analyzed for the adhesive penetration in wood/bamboo materials. The results show that the synchrotron radiation XPCM is expected to be one of the important precision detection methods for wood-based panels.
Related JoVE Video
Serum response factor indirectly regulates type I interferon-signaling in macrophages.
J. Interferon Cytokine Res.
PUBLISHED: 05-25-2013
Show Abstract
Hide Abstract
Serum response factor (SRF) is required for diverse aspects of development and homeostasis, but potential roles in the regulation of inflammation and immunity have not been systematically investigated. Here, we demonstrate that SRF is unexpectedly required for optimal responses of elicited peritoneal macrophages to type I interferons. Knockdown of SRF expression in these cells impairs induction of numerous interferon (IFN)-stimulated genes (ISGs) in response to zymosan, LPS, and poly I:C. This effect is primarily due to a defect in the ability of induced type I interferons to mediate secondary activation of ISGs. SRF does not appear to be required for expression of established components of the type I interferon signaling pathway, with IFN-?-dependent phosphorylation of STAT1 and STAT2 normally occurring in SRF-depleted macrophages. Collectively, these findings suggest that SRF can indirectly modulate type I interferon-signaling, without interfering with the classic JAK/STAT/ISGF3 pathway.
Related JoVE Video
Methylenetetrahydrofolate reductase gene polymorphisms association with the risk of diffuse large B cell lymphoma: a meta-analysis.
Tumour Biol.
PUBLISHED: 05-09-2013
Show Abstract
Hide Abstract
To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) and diffuse large B cell lymphoma (DLBCL) have provided either controversial or inconclusive results. To clarify the effect of MTHFR on the risk of diffuse large B cell lymphoma, a meta-analysis of all case-control observational studies was performed. The fixed effects and random effects model showed that the C677T polymorphism was associated with a risk of DLBCL among East Asian populations, and A1298C polymorphism was not associated with a risk of DLBCL among Caucasian and East Asian populations. Our pooled data suggest evidence for a major role of MTHFR C677T polymorphism in the carcinogenesis of DLBCL among East Asian populations.
Related JoVE Video
[Effects of compound salvia miltiorrhiza injection on aquaporin 3 expression in human amniotic epithelial cells].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 04-20-2013
Show Abstract
Hide Abstract
To study the effects of Compound Salvia miltiorrhiza Injection (CSI) on aquaporin 3 (AQP3) expression in human amniotic epithelial cells (hAECs), and to explore its mechanisms for treating oligohydramnios.
Related JoVE Video
N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines: a novel class of antitumor agents targeting the colchicine site on tubulin.
Eur J Med Chem
PUBLISHED: 04-19-2013
Show Abstract
Hide Abstract
Structural optimizations of the prior lead 1a led to the discovery of a series of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinoline derivatives as a novel class of tubulin polymerization inhibitors targeted at the colchicine binding site. The most active compound 6d showed extremely high cytotoxicity against a human tumor cell line panel (A549, KB, KBvin, and DU145) with GI50 values ranging from 1.5 to 1.7 nM, significantly more potent than paclitaxel, especially against the drug-resistant KBvin cell line, in the same assays. Analogs 5f, 6b, 6c, and 6e were also quite potent, with a GI50 range of 0.011-0.19 ?M. In further studies, active compounds 6b-e and 5f significantly inhibited tubulin assembly, with IC50 values of 0.92-1.0 ?M and strongly inhibited colchicine binding to tubulin, with inhibition rates of 75-99% (at 5 ?M), comparable with or more potent than combretastatin A-4 (IC50 0.96 ?M). Current studies included design, synthesis, and biological evaluations of 24 new compounds (series 3-6). Related SAR analysis, molecular modeling, and evaluation of essential drug-like properties, i.e. water solubility, log P, and in vitro metabolic stability, were also performed.
Related JoVE Video
[Investigation of iron deficiency status in the newborns of gestational diabetes mellitus women].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 03-28-2013
Show Abstract
Hide Abstract
To investigate the iron status in the newborns of maternal gestational diabetes mellitus (GDM) women, and explore the mechanism of iron deficiency in these newborns.
Related JoVE Video
Construction of a novel oligonucleotide array-based transcription factor interaction assay platform and its uses for profiling STAT1 cofactors in mouse fibroblast cells.
Proteomics
PUBLISHED: 03-14-2013
Show Abstract
Hide Abstract
Here, we describe a novel oligonucleotide array-based transcription factor (TF) interaction assay platform that can directly identify cointeracting TF complexes following binding to their regulatory DNA elements. This platform that combines immuno-coprecipitation technology with our previously reported oligonucleotide array-based TF assay (OATFA), is named targeted immuno-coprecipitation OATFA (TIC-OATFA). We illustrate use of the system to identify interaction partners of STAT1 (signal transducer and activator of transcription proteins 1) in mouse fibroblasts. Several previously known partners of STAT1, as well as new partners, were identified by TIC-OATFA, including the upstream stimulatory factors 1 and 2 (USF1, USF2), nuclear factor of activated T cells, TATA box-binding protein, nuclear factor erythroid-derived 2, nuclear factor-kappa B, and nuclear factor 1. Both USF1 and nuclear factor-kappa B are well known to interact with STAT1, but the other five TFs are previously unreported STAT1 interaction partners. We examined interactions between one new TF, USF2, and STAT1 in detail. USF2 belongs to the group of bHLH-zip transcription factors, which in a number of diseases including cancers, has enhanced activity. In summary, a novel oligonucleotide array-based assay platform was developed and used to study interactions between STAT1 and functional TF binding partners, revealing that USF2 and potentially four other new TFs are partners of STAT1 in an IFN-? stimulated mouse fibroblast cell line.
Related JoVE Video
Small molecule fusion inhibitors: design, synthesis and biological evaluation of (Z)-3-(5-(3-benzyl-4-oxo-2-thioxothiazolidinylidene)methyl)-N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrroles and related derivatives targeting HIV-1 gp41.
Bioorg. Med. Chem.
PUBLISHED: 02-02-2013
Show Abstract
Hide Abstract
By a scaffold elongation strategy, a series of (Z)-3-(5-(3-benzyl-4-oxo-2-thioxothiazolidinylidene)methyl)-N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrroles and related derivatives with a linear multi-aromatic-ring skeleton were designed, synthesized, and evaluated in HIV-1 gp41 and cellular assays. Among them, the most active compounds, 12e, 12g, and 12k with a one-carbon linker (n=1) between the rhodanine (C) and phenyl (D) rings, exhibited very promising inhibitory potency with IC50 values of 1.8-2.6 ?M and EC50 values of 0.3-1.5 ?M against gp41 6-HB formation and HIV-1 replication in MT-2 cells, respectively. Additionally, they were almost equally effective against both T20-sensitive and resistant strains. The related SAR studies and molecular modeling results provided potential for further developing a new class of non-peptide small molecular fusion inhibitors targeting the HIV-1 gp41.
Related JoVE Video
Enantioselective copper-catalyzed intramolecular phenolic O-H bond insertion: synthesis of chiral 2-carboxy dihydrobenzofurans, dihydrobenzopyrans, and tetrahydrobenzooxepines.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-31-2013
Show Abstract
Hide Abstract
Efficient: A copper-catalyzed enantioselective intramolecular insertion of carbenoids into phenolic O-H bonds has been developed. This method can be used for the synthesis of the title compounds in high yields and excellent enantioselectivities under mild and neutral conditions. NaBAr(F)=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.
Related JoVE Video
Early life stress-induced histone acetylations correlate with activation of the synaptic plasticity genes Arc and Egr1 in the mouse hippocampus.
J. Neurochem.
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
Early life stress (ELS) programs the developing organism and influences the development of brain and behavior. We tested the hypothesis that ELS-induced histone acetylations might alter the expression of synaptic plasticity genes that are critically involved in the establishment of limbic brain circuits. Maternal separation (MS) from postnatal day 14-16 was applied as ELS and two immediate early genes underlying experience-induced synaptic plasticity, Arc and early growth response 1 (Egr1) were analyzed. We show here that repeated ELS induces a rapid increase of Arc and Egr1 in the mouse hippocampus. Furthermore, immunoblotting revealed that these changes are paralleled by histone modifications, reflected by increased acetylation levels of H3 and H4. Most importantly, using native Chromatin immunoprecipitation quantitative PCR (nChIP-qPCR), we show for the first time a correlation between elevated histone acetylation and increased Arc and Egr1 expression in response to ELS. These rapid epigenetic changes are paralleled by increases of dendritic complexity and spine number of hippocampal CA3 pyramidal neurons in ELS animals at weaning age. Our results are in line with our working hypothesis that ELS induces activation of synaptic plasticity genes, mediated by epigenetic mechanisms. These events are assumed to represent early steps in the adaption of neuronal networks to a stressful environment.
Related JoVE Video
Inactivation of PTEN increases ABCG2 expression and the side population through the PI3K/Akt pathway in adult acute leukemia.
Cancer Lett.
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
Both the occurrence and recurrence of acute leukemia (AL) might suggest the presence of leukemia stem cells. Side population (SP) cells, exhibiting stem cell-like properties, express ABCG2 (breast cancer resistance protein [BCRP]). This study revealed that over-expression of ABCG2 in Jurkat and HL60 cells led to an increased SP fraction, up-regulated levels of phosphorylated-PI3K and phosphorylated-Akt, and enhanced drug resistance, all of which could be attenuated by treatment with either the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin. ABCG2 expression and SP cell counts were further characterized in 222 adult AL patients at three disease stages: upon diagnosis, at remission and at refractory/relapse (R/R), while 10 healthy donors served as the normal controls. Only a small fraction of the ABCG2+population (0.05-12.3%) and SP cells (0.02-1.60%) were observed in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. In the normal control population, the SP cell fraction represented a statistically higher percentage of total cells compared to the fraction of SP cells upon diagnosis or relapse in both AML and ALL. In addition, we demonstrated that ABCG2 expression and SP cell ratios can be upregulated by the inactivation of phosphatase and tensin homolog (PTEN) protein, achieved in this study by removing inhibition of the PI3K/Akt pathway. Collectively, this study suggests that the PTEN/PI3K/Akt pathway up-regulates ABCG2 expression and the SP cell population and is a potential AL-specific treatment target worth investigating further.
Related JoVE Video
[Expression of DNA-dependent protein kinase catalytic subunit in adult acute leukemia and its significance].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 11-02-2011
Show Abstract
Hide Abstract
This study was aimed to explore the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in adult acute leukemia and its correlation with clinical characteristics, karyotype and prognosis. Indirect immunofluorescent cytometry was used to detect the expression of DNA-PKcs in bone marrow mononuclear cells of 105 patients with acute leukemia before chemotherapy and 41 of them after 2 cycles of chemotherapy. Cytogenetic data were obtained from 26 of them by R band karyotypic analysis. The results showed that the expression of DNA-PKcs was correlated with higher WBC count level in peripheral blood (p < 0.05), but was not obviously associated with median age, gender, percentage of bone marrow blasts, clinical classification, median hemoglobin level and median platelet count (p > 0.05). The middle and strong positive expression of DNA-Pkcs in non-remission group was significantly higher than that in remission group (p < 0.05). The positive rate of DNA-PKcs in abnormal chromosome group was significantly higher than that in chromosome normal group (p < 0.05). It is concluded that the DNA-PKcs expression level is closely related with the increased WBC count, and the expression of DNA-PKcs is correlated also with karyotype and clinical prognosis in adult acute leukemia.
Related JoVE Video
Metabolism of novel anti-HIV agent 3-cyanomethyl-4-methyl-DCK by human liver microsomes and recombinant CYP enzymes.
Acta Pharmacol. Sin.
PUBLISHED: 10-06-2011
Show Abstract
Hide Abstract
To investigate the metabolism of 3-cyanomethyl-4-methyl-DCK (CMDCK), a novel anti-HIV agent, by human liver microsomes (HLMs) and recombinant cytochrome P450 enzymes (CYPs).
Related JoVE Video
[Loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchis disease].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 09-03-2011
Show Abstract
Hide Abstract
To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchis disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions.
Related JoVE Video
Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 08-10-2011
Show Abstract
Hide Abstract
Based on the structure of HIV-1 gp41 binding site for small-molecule inhibitors, optimization of lead 2 resulted in the discovery of a new series of 2,5-dimethyl-3-(5-(N-phenylrhodaninyl)methylene)-N-(3-(1H-tetrazol-5-yl)phenyl)pyrrole compounds with improved anti-HIV-1 activity. The most active compounds 13a and 13j exhibited significant potency against gp41 6-HB formation with IC(50) values of 4.4 and 4.6 ?M and against HIV-1 replication in the MT-2 cells with EC(50) values of 3.2 and 2.2 ?M, respectively, thus providing a new starting point to develop highly potent small-molecule HIV fusion inhibitors targeting gp41.
Related JoVE Video
2-[(4-Meth-oxy-anilino)meth-yl]phenol.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 08-02-2011
Show Abstract
Hide Abstract
In the title compound, C(14)H(15)NO(2), the dihedral angle between the two benzene rings is 71.10?(5)°. In the crystal, mol-ecules are linked by inter-molecular N-H?O, and O-H?N hydrogen bonds into a chain running parallel to the b axis.
Related JoVE Video
[Outcome and prognosis of isolated mild fetal ventriculomegaly in uterus].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 07-26-2011
Show Abstract
Hide Abstract
To investigate outcome and prognosis of isolated mild fetal ventriculomegaly (IMV) of fetus in uterus.
Related JoVE Video
The GH18 family of chitinases: their domain architectures, functions and evolutions.
Glycobiology
PUBLISHED: 07-12-2011
Show Abstract
Hide Abstract
The glycoside hydrolase 18 (GH18) family of chitinases is a multigene family that plays various roles, such as ecdysis, embryonic development, allergic inflammation and so on. Efforts are still needed to reveal their functional diversification in an evolutionary and systematic manner. We collected 85 GH18 genes from eukaryotic representatives. The domain architectures of GH18 proteins were analyzed and several conserved patterns were identified. It was observed that some (11 proteins) GH18 members in Ecdysozoa or fungi possess repeats of catalytic domains and/or chitin-binding domains (ChtBs). The domain repeats are likely to meet requirements for higher efficiency of chitin degradation in chitin-containing species. On the contrary, all vertebrate GH18 proteins contain no more than one catalytic domain or ChtB. The results from homologous analysis, domain architectures, exon arrangements and synteny loci supported two evolutionary paths for the GH18 family. One path experienced gene expansion and contraction several times during evolution, covering most of GH18 members except CHID1 (stabilin-1 interacting partner) and its homologs. Proteins in this path underwent frequent domain gain and loss, as well as domain recombination, that could achieve versatility in function. The other path is comparatively conserved. The CHID1 gene evolved without gene duplication except in Danio rerio. Domain architectures of CHID1 orthologs are all identical. The diverse phylogeny of the GH18 family in arthropod is also presented.
Related JoVE Video
[Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 05-28-2011
Show Abstract
Hide Abstract
To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).
Related JoVE Video
MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B.
Hepatology
PUBLISHED: 05-10-2011
Show Abstract
Hide Abstract
MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dysregulation in hepatitis virus infection; however, the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study we identified that miR-373 was up-regulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-up-regulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.3×HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by small interfering RNA (siRNA) promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.3×HBV-transfected HepG2 cells. Conclusion: Our study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction.
Related JoVE Video
Genetic variants in MARCO are associated with the susceptibility to pulmonary tuberculosis in Chinese Han population.
PLoS ONE
PUBLISHED: 03-28-2011
Show Abstract
Hide Abstract
Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk.
Related JoVE Video
In vitro fertilization on a single-oocyte positioning system integrated with motile sperm selection and early embryo development.
Anal. Chem.
PUBLISHED: 03-23-2011
Show Abstract
Hide Abstract
In vitro fertilization (IVF) technology has been broadly applied to solve human infertility in recent years. However, the physical tools for IVF remain unchanged over several decades before microfluidic technology was introduced in this field. Here, we report a novel microdevice that integrates each step of IVF, including oocyte positioning, sperm screening, fertilization, medium replacement, and embryo culture. Oocytes can be singly positioned in a 4 × 4 array of octacolumn units. The four symmetrical straight channels, crossing at the oocyte positioning region, allowed efficient motile sperm selection and facilitated rapid medium replacement. The fertilization process and early embryonic development of the individual zygote was traced with microscopic recording and analyzed by in situ fluorescent staining. The murine sperm motility was increased from 60.8 ± 3.4% to 96.1 ± 1.9% through the screening channels. The embryo growth rate and blastocyst formation were similar between the routine Petri dish group and the microdevice group. The healthy blastocysts developed in the microdevice could be conveniently retrieved through a routine pipetting operation and used for further embryo transfer.
Related JoVE Video
Short-term sleep deprivation increases intrinsic excitability of prefrontal cortical neurons.
Brain Res.
PUBLISHED: 03-01-2011
Show Abstract
Hide Abstract
Short-term sleep deprivation (SD) has been shown to enhance cortical activity. However, alterations in the cellular excitability of cortical neurons following SD are not yet fully understood. The present study investigated the effects of 4-hour SD on pyramidal neurons in the prefrontal cortex (PFC) of rats using whole-cell patch-clamp recording. SD led to an increase in the initial slope of firing frequency-current curve and a decrease in frequency adaptation, which were reversed by recovery sleep (RS). Correspondingly, the total afterhyperpolarization (AHP) was reduced in the SD group and returned in the RS group. Furthermore, the component of AHP changed after SD seemed to be sensitive to Ca(2+). These observations indicate an enhancement in intrinsic excitability due to short-term SD, and suggest a role for Ca(2+)-dependent AHP in this change. The findings of the present study may provide a possible explanation for the SD-induced increase in cortical activity.
Related JoVE Video
[Intravascular NK-cell lymphoma: a clinicopathologic study and literature review].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 02-01-2011
Show Abstract
Hide Abstract
To study the clinicopathologic features and disease outcome of intravascular natural killer-cell lymphoma (IVNKL).
Related JoVE Video
Screening adulteration of polypropylene bottles with postconsumer recycled plastics for oral drug package by near-infrared spectroscopy.
Anal. Chim. Acta
PUBLISHED: 01-21-2011
Show Abstract
Hide Abstract
Adulteration of pharmaceutical packaging containers with postconsumer recycled plastic materials was considerably difficult to identify due to the similar chemical compositions of virgin and recycled plastics. In the present study, near-infrared (NIR) spectroscopy coupled with conformity test was proposed to screen the adulteration of pharmaceutical packaging containers. Two kinds of representative screening models were investigated on polypropylene (PP) bottles for oral drug package. The reliability of the screening models was validated through studying the identification reliability, specificity, and robustness of the methods. The minimum spiking level of two modeled adulterants at the proportion of 20% could be detected, and the unqualified sample from a domestic manufacturer was rejected by this developed method. This strategy represents a rapid and promising analytical method for screening the adulteration of pharmaceutical plastic packaging containers with postconsumer recycled plastics.
Related JoVE Video
[Expression of angiotensin-II type 1 receptor at1 mRNA in myeloid leukemia].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-24-2010
Show Abstract
Hide Abstract
This study was aimed to explore the expression level of angiotensin-II type 1 receptor (AT1) mRNA in bone marrow of myeloid leukemic patients, and its correlation with the proportion of leukemia cells in samples and Hb, WBC, Plt counting in peripheral blood. 51 samples, including 36 AML, 7 CML, and 8 samples of non-malignant hematological diseases as control group were collected. The expression of at1 mRNA was detected by real time-PCR; the expression levels of at1 gene in AML and CML groups were relatively quantitatively analyzed by using 2(-??CT) and were compared with control group. The results showed that the expression levels of at1 mRNA in AML, CML and control groups were 0.038 ± 0.076, 0.033 ± 0.039, 0.281 ± 0.366, respectively. at1 gene expression in the myeloid leukemic group was significantly lower than that in the control group. The expression level of at1 mRNA in AML was negatively correlated with the proportion of leukemia cells and positively with Hb level in peripheral blood. It is concluded that at1 gene may play a minor role in leukaemogenesis, however, may promote erythropoiesis.
Related JoVE Video
Serum response factor utilizes distinct promoter- and enhancer-based mechanisms to regulate cytoskeletal gene expression in macrophages.
Mol. Cell. Biol.
PUBLISHED: 12-06-2010
Show Abstract
Hide Abstract
Cells of the monocyte/macrophage lineage play essential roles in tissue homeostasis and immune responses, but mechanisms underlying the coordinated expression of cytoskeletal genes required for specialized functions of these cells, such as directed migration and phagocytosis, remain unknown. Here, using genetic and genomic approaches, we provide evidence that serum response factor (SRF) regulates both general and cell type-restricted components of the cytoskeletal gene expression program in macrophages. Genome-wide location analysis of SRF in macrophages demonstrates enrichment of SRF binding at ubiquitously expressed target gene promoters, as expected, but also reveals that the majority of SRF binding sites associated with cell type-restricted target genes are at distal inter- and intragenic locations. Most of these distal SRF binding sites are established by the prior binding of the macrophage- and the B cell-specific transcription factor PU.1 and exhibit histone modifications characteristic of enhancers. Consistent with this, representative cytoskeletal target genes associated with these elements require both SRF and PU.1 for full expression. These findings suggest that SRF uses two distinct molecular strategies to regulate programs of cytoskeletal gene expression: a promoter-based strategy for ubiquitously expressed target genes and an enhancer-based strategy at target genes that exhibit cell type-restricted patterns of expression.
Related JoVE Video
[Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 11-25-2010
Show Abstract
Hide Abstract
To study the clinical and pathologic features of 4 cases of the so-called blastic natural killer (NK)-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.
Related JoVE Video
[Metabolism of 3-cyanomethyl-4-methyl-DCK, a new anti-HIV candidate, in human intestinal microsomes].
Yao Xue Xue Bao
PUBLISHED: 11-10-2010
Show Abstract
Hide Abstract
The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.
Related JoVE Video
[Discovery and development of diarylpyrimidines (DAPYs) as next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs)].
Yao Xue Xue Bao
PUBLISHED: 11-10-2010
Show Abstract
Hide Abstract
The new HIV-1 NNRTI drug Etravirine (TMC125) and a promising drug candidate Rilpivirine (TMC278) in phase III clinical trial are compounds belonging to the diarylpyrimidine (DAPY) family. They are extremely high potent against both wild-type and many drug-resistant HIV-1 strains, providing new hope for HIV-infected patients who fail to use current drugs due to the emergence of drug-resistant HIV mutants. The discovery and development of DAPY derivatives as next-generation NNRTI drugs depend on multidisciplinary coordination and their success has encouraged new researches to explore more next-generation NNRTIs with new scaffolds. This review described the story of discovery and development of DAPY derivatives as next-generation NNRTIs and related progress.
Related JoVE Video
[Clinicopathologic study of 128 cases of T-lymphoblastic lymphoma/leukemia].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 11-09-2010
Show Abstract
Hide Abstract
To clarify clinical and morphological features and immunophenotype of T lymphoblastic lymphoma/leukaemia (T-LBL/ALL) and to further improve the knowledge and diagnostic accuracy for T-ALL/LBL.
Related JoVE Video
[Intralymphatic accumulation of lymphocytes mimicking intravascular lymphomatosis].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 11-09-2010
Show Abstract
Hide Abstract
To study the significance and differential diagnosis of intralymphatic accumulation of lymphocytes.
Related JoVE Video
Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
J. Med. Chem.
PUBLISHED: 11-04-2010
Show Abstract
Hide Abstract
On the basis of the structures and activities of our previously identified non-nucleoside reverse transcriptase inhibitors (NNRTIs), we designed and synthesized two sets of derivatives, diarylpyridines (A) and diarylanilines (B), and tested their anti-HIV-1 activity against infection by HIV-1 NL4-3 and IIIB in TZM-bl and MT-2 cells, respectively. The results showed that most compounds exhibited potent anti-HIV-1 activity with low nanomolar EC50 values, and some of them, such as 13m, 14c, and 14e, displayed high potency with subnanomolar EC50 values, which were more potent than etravirine (TMC125, 1) in the same assays. Notably, these compounds were also highly effective against infection by multi-RTI-resistant strains, suggesting a high potential to further develop these compounds as a novel class of NNRTIs with improved antiviral efficacy and resistance profile.
Related JoVE Video
[Research on a new method and index for evaluating cardiac function of the athletes].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 11-03-2010
Show Abstract
Hide Abstract
To explore the new indexes and new methods for the noninvasive measuring and evaluating cardiac function detection of the athletes.
Related JoVE Video
Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device.
Lab Chip
PUBLISHED: 09-15-2010
Show Abstract
Hide Abstract
In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.
Related JoVE Video
[Clinicopathologic features of 66 cases of anaplastic lymphoma kinase positive and negative systemic anaplastic large cell lymphoma: a comparative study].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 07-27-2010
Show Abstract
Hide Abstract
To study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.
Related JoVE Video
Integration of sperm motility and chemotaxis screening with a microchannel-based device.
Clin. Chem.
PUBLISHED: 06-15-2010
Show Abstract
Hide Abstract
Sperm screening is an essential step in in vitro fertilization (IVF) procedures. The swim-up method, an assay for sperm motility, is used clinically to select the ideal sperm for subsequent manipulation. However, additional parameters, including acrosome reaction capability, chemotaxis, and thermotaxis, are also important indicators of mammalian sperm health. To monitor both sperm motility and chemotaxis simultaneously during sperm screening, we designed and constructed a microdevice comprising a straight channel connected with a bibranch channel that mimics the mammalian female reproductive tract.
Related JoVE Video
Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors.
J. Med. Chem.
PUBLISHED: 06-10-2010
Show Abstract
Hide Abstract
By using structure-based drug design and isosteric replacement, diarylaniline and 1,5-diarylbenzene-1,2-diamine derivatives were synthesized and evaluated against wild type HIV-1 and drug-resistant viral strains, resulting in the discovery of diarylaniline derivatives as a distinct class of next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) agents. The most promising compound 37 showed significant EC(50) values of 0.003-0.032 microM against HIV-1 wild-type strains and of 0.005-0.604 microM against several drug-resistant strains. Current results also revealed important structure-activity relationship (SAR) conclusions for diarylanilines and strongly support our hypothesis that an NH(2) group on the central benzene ring ortho to the aniline moiety is crucial for interaction with K101 of the NNRTI binding site in HIV-1 RT, likely by forming H-bonds with K101. Furthermore, molecular modeling studies with molecular mechanism/general Born surface area (MM/GBSA) technology demonstrated the rationality of our hypothesis.
Related JoVE Video
Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3.
Org. Biomol. Chem.
PUBLISHED: 06-04-2010
Show Abstract
Hide Abstract
Ergot alkaloids are toxins and important pharmaceuticals which are produced biotechnologically on an industrial scale. A putative gene fgaFS has been identified in the biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid of the clavine-type. The deduced gene product FgaFS comprises 290 amino acids with a molecular mass of about 32.1 kDa. The coding region of fgaFS consisting of three exons was amplified by PCR from a cDNA library of Aspergillus fumigatus, cloned into pQE70 and overexpressed in E. coli. The soluble monomeric His(6)-FgaFS was purified by affinity chromatography and used for enzyme assays. It has been shown that FgaFS is responsible for the conversion of chanoclavine-I aldehyde to festuclavine in the presence of the old yellow enzyme FgaOx3. The structure of festuclavine including the stereochemistry was unequivocally elucidated by NMR and MS analyses. Festuclavine formation was only observed when chanoclavine-I aldehyde was incubated with FgaOx3 and FgaFS simultaneously or as a tandem-reaction with a sequence of FgaOx3 before FgaFS. In the absence of FgaFS, two shunt products were formed and did not serve as substrates for FgaFS reaction.
Related JoVE Video
Simultaneous C7- and N1-prenylation of cyclo-L-Trp-L-Trp catalyzed by a prenyltransferase from Aspergillus oryzae.
Org. Biomol. Chem.
PUBLISHED: 05-14-2010
Show Abstract
Hide Abstract
A putative prenyltransferase gene cTrpPT was amplified from Aspergillus oryzae DSM1147, cloned into pQE70 and overexpressed in Escherichia coli. The overproduced His(6)-CTrpPT was purified to near homogeneity and incubated with L-tryptophan or tryptophan-containing cyclic dipeptides in the presence of dimethylallyl diphosphate. The formation of the enzyme products was monitored with HPLC. It was shown that CTrpPT differed clearly from other known indole prenyltransferases in several aspects. This enzyme showed higher substrate specificity towards aromatic substrates, but lower regioselectivity regarding the prenylation position than other indole prenyltransferases. Cyclo-L-Trp-L-Trp was much better accepted than other cyclic dipeptides tested in this study. In comparison to other indole prenyltransferases with one dominant enzyme product, at least two product peaks were detected in the reaction mixtures of CTrpPT. (1)H- and (13)C-NMR analyses, including long-range (1)H-(13)C connectivities in Heteronuclear Multiple-Bond Correlation (HMBC) and Nuclear Overhauser Effect Spectroscopy (NOESY), proved the structures of the enzyme products as C7- and N1-prenylated derivatives with a ratio of 1:1.2 using cyclo-L-Trp-L-Trp as substrate. The K(M) values were determined at about 2.5 mM for dimethylallyl diphosphate and 0.3 mM for cyclo-L-Trp-L-Trp with a turnover number of 0.33 s(-1).
Related JoVE Video
Toll-like receptors, tumor necrosis factor-?, and interleukin-10 gene polymorphisms in risk of pulmonary tuberculosis and disease severity.
Hum. Immunol.
PUBLISHED: 04-26-2010
Show Abstract
Hide Abstract
Toll-like receptors (TLRs) and cytokines play key roles in innate and adaptive immunity against Mycobacterium tuberculosis (M.TB). The aim of this study was to investigate whether the functional genetic variations at position 1805 G/T in TLR1, 2258 A/G in TLR2, -857 C/T, and -863 A/C in tumor necrosis factor-? (TNF-?), as well as -819 C/T in interleukin-10 (IL-10) confer susceptibility to pulmonary tuberculosis (PTB). We performed a hospital-based case-control study using 543 case patients and 544 controls. Multivariate logistic regression analysis revealed that the TT genotype of -857 C/T in TNF-? gene was significantly associated with lower risk of PTB, in comparison with other genotypes (odds ratios [OR] = 0.68, 95% confidence interval [CI] = 0.53-0.86, p = 0.001). Conversely, the genetic variants of -863 A/C in TNF-? gene was associated with susceptibility to PTB (OR = 2.42%, 95% CI = 1.28-4.59, p = 0.007) and clinical severity of disease (OR = 3.59%, 95% CI = 1.41-9.11, p = 0.007). Our results indicated that the variants in TNF-? gene were associated with susceptibility to PTB and clinical severity of disease, whereas no significance could be inferred from TLRs and IL-10 genes polymorphisms.
Related JoVE Video
[Clinicopathological study on the follicular dendritic cell sarcoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 04-21-2010
Show Abstract
Hide Abstract
To investigate the clinicopathologic features and differential diagnostic methods for follicular dendritic cell sarcoma.
Related JoVE Video

What is Visualize?

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

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.