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Find video protocols related to scientific articles indexed in Pubmed.
LIM and SH3 Protein 1 Induces TGF?-Mediated Epithelial-Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression.
Clin. Cancer Res.
PUBLISHED: 09-24-2014
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The expression of LIM and SH3 protein 1 (LASP1) was upregulated in colorectal cancer cases, thereby contributing to the aggressive phenotypes of colorectal cancer cells. However, we still cannot decipher the underlying molecular mechanism associated with colorectal cancer metastasis.
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Characteristics of CARMA1-BCL10-MALT1-A20-NF-?B expression in T cell-acute lymphocytic leukemia.
Eur. J. Med. Res.
PUBLISHED: 09-04-2014
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Knowledge of the oncogenic signaling pathways of T-cell acute lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation of the nuclear factor kappa B (NF-?B) signaling pathway has been detected in various lymphoid malignancies and plays a key role in the development of these carcinomas. The zinc finger-containing protein, A20, is a central regulator of multiple NF-?B-activating signaling cascades. A20 is frequently inactivated by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However, few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of interest to analyze the expression characteristics of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1.
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Attention-dependent early cortical suppression contributes to crowding.
J. Neurosci.
PUBLISHED: 08-08-2014
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Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.
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Annexin A5 promotes invasion and chemoresistance to temozolomide in glioblastoma multiforme cells.
Tumour Biol.
PUBLISHED: 05-28-2014
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Glioblastoma multiforme (GBM) is the prevalent and most fatal brain tumor in adults. Invasion and a high rate of recurrence largely contribute to the poor prognosis of GBM. The current standard therapy for GBM includes surgery with maximum feasible resection, radiotherapy, and treatment with chemotherapeutic agent temozolomide. Annexin A5 reportedly promotes progression and chemoresistance in a variety of cancers. In the present study, we explored the effects of annexin A5 on GBM cell invasion and chemoresistance to temozolomide. Stable overexpression and knockdown of annexin A5 were performed in both U-87 MG and U-118 MG human GBM cell lines. Overexpression of annexin A5 in both cell lines significantly increased cell invasion, matrix metalloproteinase-2 (MMP-2) expression/activity, Akt phosphorylation at serine 473, and the half maximal inhibitory concentration (IC50) values of temozolomide and markedly decreased temozolomide-induced apoptosis, all of which were abolished by selective PI3K inhibitor BKM120. On the other hand, knockdown of annexin A5 markedly decreased cell invasion, MMP-2 expression/activity, Akt phosphorylation at serine 473, and the IC50 values of temozolomide and significantly increased temozolomide-induced apoptosis. In conclusion, our study provides the first evidence that annexin A5 promotes GBM cell invasion, MMP-2 expression/activity, and chemoresistance to temozolomide through a PI3K-dependent mechanism. It adds new insights not only into the biological function of annexin A5 but also into the molecular mechanisms underlying GBM progression and chemoresistance.
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An investigation of cigarettes smoking behavior and nicotine dependence among Chinese methamphetamine users in two provinces.
Biomed Res Int
PUBLISHED: 04-03-2014
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To survey cigarette behaviors and nicotine dependence among Chinese MA users, explore risk factors for high nicotine dependence, and analyze the relationship between nicotine dependence and MA-related euphoria and sexual impulse.
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Tanshinones extend chronological lifespan in budding yeast Saccharomyces cerevisiae.
Appl. Microbiol. Biotechnol.
PUBLISHED: 03-03-2014
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Natural products with anti-aging property have drawn great attention recently but examples of such compounds are exceedingly scarce. By applying a high-throughput assay based on yeast chronological lifespan measurement, we screened the anti-aging activity of 144 botanical materials and found that dried roots of Salvia miltiorrhiza Bunge have significant anti-aging activity. Tanshinones isolated from the plant including cryptotanshione, tanshinone I, and tanshinone IIa, are the active components. Among them, cryptotanshinone can greatly extend the budding yeast Saccharomyces cerevisiae chronological lifespan (up to 2.5 times) in a dose- and the-time-of-addition-dependent manner at nanomolar concentrations without disruption of cell growth. We demonstrate that cryptotanshinone prolong chronological lifespan via a nutrient-dependent regime, especially essential amino acid sensing, and three conserved protein kinases Tor1, Sch9, and Gcn2 are required for cryptotanshinone-induced lifespan extension. In addition, cryptotanshinone significantly increases the lifespan of SOD2-deleted mutants. Altogether, those data suggest that cryptotanshinone might be involved in the regulation of, Tor1, Sch9, Gcn2, and Sod2, these highly conserved longevity proteins modulated by nutrients from yeast to humans.
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Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants.
Int J Pharm
PUBLISHED: 02-28-2014
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To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.
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Anti-inflammatory effects of three-dimensional graphene foams cultured with microglial cells.
Biomaterials
PUBLISHED: 02-18-2014
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One of the key goals in nerve tissue engineering is to develop new materials which cause less or no neuroinflammation. Despite the rapid advances of using graphene as a neural interface material, it still remains unknown whether graphene could provoke neuroinflammation or not, and whether and how the topographical features of graphene influence the neuroinflammation induction. By immunofluorescence, Elisa technique, western blot, scanning electron microscope (SEM) methods, we investigated the pro- and/or anti-inflammatory responses of microglia in the graphene films (2D-graphene) or graphene foams (3D-graphene) culturing systems. Furthermore, the growth situations of the neural stem cells (NSCs) in the conditioned culture medium produced in the graphene substrates were evaluated. The results show that: 1) neither 2D nor 3D graphene induced distinct neuroinflammation when compared to the tissue culture polystyrene (TCPS) substrates; 2) the topographical structures of the graphene might affect the material/cell interactions, leading to disparate effects on lipopolysaccharide (LPS)-induced neuroinflammation; 3) 3D graphene exhibited a remarkable capability of rescuing LPS-induced neuroinflammation probably through the restriction of microglia morphological transformation by the unique topographical features on the surface, showing the ability of anti-inflammation against external insults, while 2D graphene failed to. These results provide insights into the diverse biological effects of the material's topographical structures and open new opportunity for the applications of graphene in neuroscience.
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Design, synthesis and evaluation of novel diaryl urea derivatives as potential antitumor agents.
Eur J Med Chem
PUBLISHED: 02-04-2014
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A novel series of diaryl ureas containing different linker groups were designed and synthesized. Their in vitro antitumor activity against MX-1, A375, HepG2, Ketr3 and HT-29 was evaluated using the standard MTT assay. Compounds having a rigid linker group such as vinyl, ethynyl and phenyl showed significant inhibitory activity against a variety of cancer cell lines. Specifically, compound 23 with a phenyl linker group demonstrated broad-spectrum antitumor activity with IC50 values of 5.17-6.46 ?M against five tested tumor cell lines. Compound 23 is more potent than reference drug sorafenib (8.27-15.2 ?M), representing a promising lead for further optimization.
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Hormesis of glyceollin I, an induced phytoalexin from soybean, on budding yeast chronological lifespan extension.
Molecules
PUBLISHED: 01-09-2014
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Glyceollin I, an induced phytoalexin isolated from soybean, has been reported to have various bioactivities, including anti-bacterial, anti-nematode, anti-fungal, anti-estrogenic and anti-cancer, anti-oxidant, anti-inflammatory, insulin sensitivity enhancing, and attenuation of vascular contractions. Here we show that glyceollin I has hormesis and extends yeast life span at low (nM) doses in a calorie restriction (CR)-dependent manner, while it reduces life span and inhibits yeast cell proliferation at higher (?M) doses. In contrast, the other two isomers (glyceollin II and III) cannot extend yeast life span and only show life span reduction and antiproliferation at higher doses. Our results in anti-aging activity indicate that glyceollin I might be a promising calorie restriction mimetic candidate, and the high content of glyceollins could improve the bioactivity of soybean as functional food ingredients.
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Diels-Alder/oxidative aromatization approach towards the all-carbon DEF tricyclic skeleton of daphenylline.
Chem Asian J
PUBLISHED: 01-01-2014
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Daphenylline is a recently isolated Daphniphyllum alkaloid with an unprecedented novel hexacyclic scaffold. In this study, the synthesis of the fused all-carbon DEF tricyclic skeleton of daphenylline has been accomplished. Key steps of the reported sequence involve Evans asymmetric allylation, aldol condensation, Diels-Alder reaction, and oxidative aromatization reactions. The developed strategy might lead to the total synthesis of daphenylline.
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Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.
PLoS ONE
PUBLISHED: 01-01-2014
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Nucleoside analogue reverse transcriptase inhibitor (NRTI), an integral component of highly active antiretroviral therapy (HAART), was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier (BBB) and the complex microenvironment of the central nervous system (CNS). In this study, the Balb/c mice were administered 50 mg/kg stavudine (D4T), 100 mg/kg zidovudine (AZT), 50 mg/kg lamivudine (3TC) or 50 mg/kg didanosine (DDI) per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA (mtDNA) levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver (except for 3TC) and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.
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Clinical outcomes of below knee amputations in diabetic foot patients.
Ann. Acad. Med. Singap.
PUBLISHED: 09-19-2013
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This study aims to evaluate the predictive factors affecting the clinical outcome of Below Knee Amputations (BKA) performed in diabetic foot patients admitted to National University Hospital (NUH) Multi-Disciplinary Diabetic Foot Team.
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Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor ?B signaling in glioblastoma cancer stem cells regulates the Notch pathway.
J. Biol. Chem.
PUBLISHED: 07-31-2013
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Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-?B signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-?B signaling pathway and up-regulation of STAT3- and NF-?B-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-?B inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-?B signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma.
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Identifying the trend of reactivity for sp2 materials: an electron delocalization model from first principles calculations.
Phys Chem Chem Phys
PUBLISHED: 05-20-2013
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The reactivity of sp(2) carbon materials is studied using the adsorption and dissociation of O2 on graphene and graphene oxide as model systems. The reactions on the basal plane, zigzag and armchair edges of graphene and graphene oxide with different oxygen-containing groups are calculated using first principles calculations. Two Brønsted-Evans-Polanyi relationships are identified and an electron delocalization model is suggested to understand the general trend of reactivity for sp(2) carbon materials.
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Enhancement of electrical signaling in neural networks on graphene films.
Biomaterials
PUBLISHED: 04-24-2013
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One of the key challenges for neural tissue engineering is to exploit supporting materials with robust functionalities not only to govern cell-specific behaviors, but also to form functional neural network. The unique electrical and mechanical properties of graphene imply it as a promising candidate for neural interfaces, but little is known about the details of neural network formation on graphene as a scaffold material for tissue engineering. Therapeutic regenerative strategies aim to guide and enhance the intrinsic capacity of the neurons to reorganize by promoting plasticity mechanisms in a controllable manner. Here, we investigated the impact of graphene on the formation and performance in the assembly of neural networks in neural stem cell (NSC) culture. Using calcium imaging and electrophysiological recordings, we demonstrate the capabilities of graphene to support the growth of functional neural circuits, and improve neural performance and electrical signaling in the network. These results offer a better understanding of interactions between graphene and NSCs, also they clearly present the great potentials of graphene as neural interface in tissue engineering.
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Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains.
J. Med. Chem.
PUBLISHED: 04-19-2013
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Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra. The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis. The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase. The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.
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Surface-enhanced Raman scattering-based sensing in vitro: facile and label-free detection of apoptotic cells at the single-cell level.
Anal. Chem.
PUBLISHED: 02-18-2013
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Surface-enhanced Raman scattering (SERS) is well recognized as a powerful analytical tool, enabling ultrahigh sensitive detection of analytes at low concentrations, even down to single-molecule level. Of particular note, in comparison to sufficient investigations on SERS-based detection of biomolecules (e.g., DNA and protein), there has been relatively scanty information regarding in vitro and in vivo detection. In this Article, we demonstrate a kind of SERS-active substrate, i.e., AgNPs-decorated silicon wafer (AgNPs@Si), as a high-performance in vitro sensing platform for single-cell detection of apoptotic cells. The AgNPs@Si yields highly reproducible SERS signals with an enhancement factor of ?10(7). Remarkably, cellular experiments show that facile, noninvasive, label-free, and sensitive detection of apoptotic cells is readily realized using the high-performance SERS-active platform. Three kinds of apoptotic cells treated with apoptosis inducer are facilely and sensitively detected at the single-cell level, suggesting the exciting potential of AgNPs@Si for SERS-based in vitro analysis and detection.
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Curcumin potentiates rhabdomyosarcoma radiosensitivity by suppressing NF-?B activity.
PLoS ONE
PUBLISHED: 02-07-2013
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Ionizing radiation (IR) is an essential component of therapy for alveolar rhabdomyosarcoma. Nuclear factor-kappaB (NF-??) transcription factors are upregulated by IR and have been implicated in radioresistance. We evaluated the ability of curcumin, a putative NF-?? inhibitor, and cells expressing genetic NF- ?? inhibitors (I?B? and p100 super-repressor constructs) to function as a radiosensitizer. Ionizing radiation induced NF-?? activity in the ARMS cells in vitro in a dose- and time-dependent manner, and upregulated expression of NF-?? target proteins. Pretreatment of the cells with curcumin inhibited radiation-induced NF-?? activity and target protein expression. In vivo, the combination of curcumin and IR had synergistic antitumor activity against Rh30 and Rh41 ARMS xenografts. The greatest effect occurred when tumor-bearing mice were treated with curcumin prior to IR. Immunohistochemistry revealed that combination therapy significantly decreased tumor cell proliferation and endothelial cell count, and increased tumor cell apoptosis. Stable expression of the super-repressor, SR-I?B?, that blocks the classical NF-?B pathway, increased sensitivity to IR, while expression of SR-p100, that blocks the alternative pathway, did not. Our results demonstrate that curcumin can potentiate the antitumor activity of IR in ARMS xenografts by suppressing a classical NF-?? activation pathway induced by ionizing radiation. These data support testing of curcumin as a radiosensitizer for the clinical treatment of alveolar rhabdomyosarcoma. IMPACT OF WORK: The NF-?? protein complex has been linked to radioresistance in several cancers. In this study, we have demonstrated that inhibiting radiation-induced NF-?? activity by either pharmacologic (curcumin) or genetic (SR-I?B?) means significantly enhanced the efficacy of radiation therapy in the treatment of alveolar rhabdomyosarcoma cells and xenografts. These data suggest that preventing the radiation-induced activation of the NF-?? pathway is a promising way to improve the antitumor efficacy of ionizing radiation and warrants clinical trials.
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Design, synthesis and hepatoprotective activity of analogs of the natural product goodyeroside A.
Molecules
PUBLISHED: 01-29-2013
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Goodyeroside A, a natural product isolated from the Goodyera species, possesses significant hepatoprotective activity and has a novel skeleton not previously observed in other synthetic drugs used for the treatment of hepatitis. Herein, we report a highly stereoselective synthesis of goodyeroside A and related analogs with varying substituents at the ? position of the carbonyl group to explore the structure-activity relationships of goodyeroside A. The absolute configuration of analog 5d was confirmed by single crystal X-ray analysis. The results from in vitro and in vivo studies indicate that 5a, the fully acetylated compound of goodyeroside A, is worthy of further investigation as a lead to identify novel hepatoprotective agents.
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Independent and additive effects of glutamic Acid and methionine on yeast longevity.
PLoS ONE
PUBLISHED: 01-01-2013
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It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.
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Comparative analyses of lipoprotein lipase, hepatic lipase, and endothelial lipase, and their binding properties with known inhibitors.
PLoS ONE
PUBLISHED: 01-01-2013
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The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad "Ser-Asp-His", a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis.
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Dietary restriction depends on nutrient composition to extend chronological lifespan in budding yeast Saccharomyces cerevisiae.
PLoS ONE
PUBLISHED: 01-01-2013
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The traditional view on dietary restriction has been challenged with regard to extending lifespan of the fruit fly Drosophila melanogaster. This is because studies have shown that changing the balance of dietary components without reduction of dietary intake can increase lifespan, suggesting that nutrient composition other than dietary restriction play a pivotal role in regulation of longevity. However, this opinion has not been reflected in yeast aging studies. Inspired by this new finding, response surface methodology was applied to evaluate the relationships between nutrients (glucose, amino acids and yeast nitrogen base) and lifespan as well as biomass production in four Saccharomyces cerevisiae strains (wild-type BY4742, sch9?, tor1?, and sir2? mutants) using a high throughput screening assay. Our results indicate that lifespan extension by a typical dietary restriction regime was dependent on the nutrients in media and that nutrient composition was a key determinant for yeast longevity. Four different yeast strains were cultured in various media, which showed similar response surface trends in biomass production and viability at day two but greatly different trends in lifespan. The pH of aging media was dependent on glucose concentration and had no apparent correlation with lifespan under conditions where amino acids and YNB were varied widely, and simply buffering the pH of media could extend lifespan significantly. Furthermore, the results showed that strain sch9? was more responsive in nutrient-sensing than the other three strains, suggesting that Sch9 (serine-threonine kinase pathway) was a major nutrient-sensing factor that regulates cell growth, cell size, metabolism, stress resistance and longevity. Overall, our findings support the notion that nutrient composition might be a more effective way than simple dietary restriction to optimize lifespan and biomass production from yeast to other organisms.
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A high throughput screening assay for determination of chronological lifespan of yeast.
Exp. Gerontol.
PUBLISHED: 06-15-2011
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A high throughput screening assay was developed based on the yeast chronological aging model and applied in evaluating several factors that mediate lifespan, including inoculum size, cellular state in nutrient-rich medium, and calorie level. Using our assay, we confirmed the previously reported genetic mimics of calorie restriction, including deletion of TOR1, SCH9 or RAS2. In contrast, deletion of SIR2 had longevity effect but seemed to produce only small beneficial effect on the response to calorie restriction. Overall, this new high throughput screening assay may facilitate identification of calorie restriction mimetics with a rapid and simple protocol, uncomplicated data analysis, and high sensitivity. In addition, the assay also provides quantifiable data including lag-time, growth rate, doubling time, and survival percentage.
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The Medicago genome provides insight into the evolution of rhizobial symbioses.
Nevin D Young, Frédéric Debellé, Giles E D Oldroyd, Rene Geurts, Steven B Cannon, Michael K Udvardi, Vagner A Benedito, Klaus F X Mayer, Jérôme Gouzy, Heiko Schoof, Yves Van de Peer, Sebastian Proost, Douglas R Cook, Blake C Meyers, Manuel Spannagl, Foo Cheung, Stéphane De Mita, Vivek Krishnakumar, Heidrun Gundlach, Shiguo Zhou, Joann Mudge, Arvind K Bharti, Jeremy D Murray, Marina A Naoumkina, Benjamin Rosen, Kevin A T Silverstein, Haibao Tang, Stephane Rombauts, Patrick X Zhao, Peng Zhou, Valérie Barbe, Philippe Bardou, Michael Bechner, Arnaud Bellec, Anne Berger, Hélène Berges, Shelby Bidwell, Ton Bisseling, Nathalie Choisne, Arnaud Couloux, Roxanne Denny, Shweta Deshpande, Xinbin Dai, Jeff J Doyle, Anne-Marie Dudez, Andrew D Farmer, Stéphanie Fouteau, Carolien Franken, Chrystel Gibelin, John Gish, Steven Goldstein, Alvaro J González, Pamela J Green, Asis Hallab, Marijke Hartog, Axin Hua, Sean J Humphray, Dong-Hoon Jeong, Yi Jing, Anika Jöcker, Steve M Kenton, Dong-Jin Kim, Kathrin Klee, Hongshing Lai, Chunting Lang, Shaoping Lin, Simone L Macmil, Ghislaine Magdelenat, Lucy Matthews, Jamison McCorrison, Erin L Monaghan, Jeong-Hwan Mun, Fares Z Najar, Christine Nicholson, Céline Noirot, Majesta O'Bleness, Charles R Paule, Julie Poulain, Florent Prion, Baifang Qin, Chunmei Qu, Ernest F Retzel, Claire Riddle, Erika Sallet, Sylvie Samain, Nicolas Samson, Iryna Sanders, Olivier Saurat, Claude Scarpelli, Thomas Schiex, Béatrice Ségurens, Andrew J Severin, D Janine Sherrier, Ruihua Shi, Sarah Sims, Susan R Singer, Senjuti Sinharoy, Lieven Sterck, Agnès Viollet, Bing-Bing Wang, Keqin Wang, Mingyi Wang, Xiaohong Wang, Jens Warfsmann, Jean Weissenbach, Doug D White, Jim D White, Graham B Wiley, Patrick Wincker, Yanbo Xing, Limei Yang, Ziyun Yao, Fu Ying, Jixian Zhai, Liping Zhou, Antoine Zuber, Jean Dénarié, Richard A Dixon, Gregory D May, David C Schwartz, Jane Rogers, Francis Quetier, Christopher D Town, Bruce A Roe.
Nature
PUBLISHED: 06-13-2011
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Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ?94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfas genomic toolbox.
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Food grade fungal stress on germinating peanut seeds induced phytoalexins and enhanced polyphenolic antioxidants.
J. Agric. Food Chem.
PUBLISHED: 05-17-2011
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The effects of food grade fungus Rhizopus oligosporus stress on phytochemicals and phytoalexins of germinating peanut seeds were investigated by comparing the metabolic profiles of ungerminated (UG), germinated (G), and germinated seeds under fungal stress (GS). Three types of peanut seeds with different skin color (red, reddish brown, and black) were compared in the process. The polyphenolic contents were analyzed and correlated with antioxidant capacity for specific free radicals including peroxyl radical ROO(•) (ORAC), hydroxyl radical HO(•) (HORAC), superoxide radical O(2)(•-) (SORAC), and DPPH radical. The polyphenolic fingerprints analyzed by HPLC and LC-MS(n) showed that phenolic acids (coumaric, sinapinic, and ferulic acids derivatives) were the major group of phenolic compounds in ungerminated seeds. G or GS increased the level of phenolic acids, phytoalexins, and antioxidant capacity values in reddish and red peanuts but not in black peanuts. From the LC-MS(n) spectral data, 45 compounds were identified tentatively in the germinated peanuts, including 14 coumaric acids, 3 ferulic acids, 4 sinapinic acids, 2 hydroxybenzoic acids, 1 caffeic acid, 2 flavonoids, and 19 stilbenoids derivatives. Reddish brown germinated peanuts produced the highest amount of phytoalexins after GS with 55 compounds detected. Forty-five of these compounds were suggested as stilbenoid phytoalexins derivatives. The high content of phytoalexins may enhance the bioactivity of peanut seeds as functional food ingredients.
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In vivo distribution, pharmacokinetics, and toxicity of aqueous synthesized cadmium-containing quantum dots.
Biomaterials
PUBLISHED: 04-08-2011
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Fluorescent ?-? Quantum dots (QDs) have demonstrated to be highly promising biological probes for various biological and biomedical applications due to their many attractive merits, such as robust photostabilty, strong photoluminescence, and size-tunable fluorescence. Along with wide ranging bioapplications, concerns about their biosafety have attracted increasingly intensive attentions. In comparison to full investigation of in vitro toxicity, there has been only scanty information regarding in vivo toxicity of the QDs. Particularly, while in vivo toxicity of organic synthesized QDs (orQDs) have been investigated recently, there exist no comprehensive studies concerning in vivo behavior of aqueous synthesized QDs (aqQDs) up to present. Herein, we investigate short- and long-term in vivo biodistribution, pharmacokinetics, and toxicity of the aqQDs. Particularly, the aqQDs are initially accumulated in liver after short-time (0.5-4 h) post-injection, and then are increasingly absorbed by kidney during long-time (15-80 days) blood circulation. Moreover, obviously size-dependent biodistribution is observed: aqQDs with larger sizes are more quickly accumulated in the spleen. Furthermore, histological and biochemical analysis, and body weight measurement demonstrate that there is no overt toxicity of aqQDs in mice even at long-time exposure time. Our studies provide invaluable information for the design and development of aqQDs for biological and biomedical applications.
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Agglomeration response of nanoparticles in magnetic fluid via monitoring of light transmission.
Appl Opt
PUBLISHED: 03-12-2011
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We systemically investigate the chain formation speed in magnetic fluid (MF) at various volume fractions, temperatures, and magnetic fields. Experiments are carried out on a water-based Fe(3)O(4) MF to investigate the agglomeration response of the nanoparticles under an applied magnetic field. The transmission of light is monitored to determine the response time undergoing a squared pulsed external magnetic field. The results reveal that enhancement of the response performance of photonic devices based on MF can be realized by properly adjusting the physical parameters, which are essential for both the physics of chain formation and practical applications.
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Pro-inflammatory genes as biomarkers and therapeutic targets in oral squamous cell carcinoma.
J. Biol. Chem.
PUBLISHED: 08-11-2010
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Oral squamous cell carcinoma (OSCC) is a major health problem worldwide, and patients have a particularly poor 5-year survival rate. Thus, identification of the molecular targets in OSCC and subsequent innovative therapies are greatly needed. Prolonged exposure to alcohol, tobacco, and pathogenic agents are known risk factors and have suggested that chronic inflammation may represent a potential common denominator in the development of OSCC. Microarray analysis of gene expression in OSCC cell lines with high basal NF-?B activity and OSCC patient samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation. In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated in OSCC. Moreover, IL-8 protein levels were significantly higher in OSCC cell lines as compared with normal human oral keratinocytes. Targeting IL-8 expression by siRNA significantly reduced the survival of OSCC cells, indicating that it plays an important role in OSCC development and/or progression. Inhibiting the inflammatory pathway by aspirin and the proteasome/NF-?B pathway by bortezomib resulted in marked reduction in cell viability in OSCC lines. Taken together our studies indicate a strong link between inflammation and OSCC development and reveal IL-8 as a potential mediator. Treatment based on prevention of general inflammation and/or the NF-?B pathway shows promise in OSCCs.
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Quinaphos and Dihydro-Quinaphos phosphine-phosphoramidite ligands for asymmetric hydrogenation.
Chemistry
PUBLISHED: 05-19-2010
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New derivatives of the Quinaphos ligands and the related Dihydro-Quinaphos ligands based on the more flexible 1,2,3,4-tetrahydroquinoline backbone have been prepared and fully characterised. A general and straightforward separation protocol was devised, which allowed for the gram-scale isolation of the R(a),S(c) and S(a),R(c) diastereomers. These new phosphine-phosphoramidite ligands have been applied in the Rh-catalysed asymmetric hydrogenation of functionalised olefins with the achievement of excellent enantioselectivities (> or = 99%) in most cases and turnover frequency (TOF) values of up to > or = 20,000 h(-1). These results substantiate the practical utility of readily accessible Quinaphos-type ligands, which belong to the most active and selective category of ligands for Rh-catalysed hydrogenation known to date.
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Interferon-resistant Daudi cell line with a Stat2 defect is resistant to apoptosis induced by chemotherapeutic agents.
J. Biol. Chem.
PUBLISHED: 08-17-2009
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Interferon-alpha (IFNalpha) has shown promise in the treatment of various cancers. However, the development of IFN resistance is a significant drawback. Using conditions that mimic in vivo selection of IFN-resistant cells, the RST2 IFN-resistant cell line was isolated from the highly IFN-sensitive Daudi human Burkitt lymphoma cell line. The RST2 cell line was resistant to the antiviral, antiproliferative, and gene-induction actions of IFNalpha. Although STAT2 mRNA was present, STAT2 protein expression was deficient in RST2 cells. A variant STAT2 mRNA, which resulted from alternative splicing within the intron between exon 19 and 20, was expressed in several human cell lines but at relatively high levels in RST2 cells. Most importantly, the RST2 line showed an intrinsic resistance to apoptosis induced by a number of chemotherapeutic agents (camptothecin, staurosporine, and doxorubicin). Expression of STAT2 in RST2 cells not only rescued their sensitivity to the biological activities of IFNs but also restored sensitivity to apoptosis induced by these chemotherapeutic agents. The intrinsic resistance of the RST2 cells to IFN as well as chemotherapeutic agents adds a new dimension to our knowledge of the role of STAT2 as it relates to not only biological actions of IFN but also resistance to chemotherapy-induced apoptosis.
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Large two-photon absorption of terpyridine-based quadrupolar derivatives: towards their applications in optical limiting and biological imaging.
Chem Asian J
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Developing organic chromophores with large two-photon absorption (TPA) in both organic solvents and aqueous media is crucial owing to their applications in solid-state photonic devices and biological imaging. Herein, a series of novel terpyridine-based quadrupolar derivatives have been synthesized. The influences of electron-donating group, type of conjugated bridge, as well as solvent polarity on the molecular TPA properties have been investigated in detail. In contrast to the case in organic solvents, bis(thienyl)-benzothiadiazole as a rigid conjugated bridge will completely quench molecular two-photon emission in aqueous media. However, the combination of alkylcarbazole as the donor and bis(styryl)benzene as a conjugation bridge can enlarge molecular TPA cross-sections in both organic solvent and aqueous media. The reasonable two-photon emission brightness for the organic nanoparticles of chromophores 3-5 in the aqueous media, prepared by the reprecipitation method, enables them to be used as probes for in vivo biological imaging.
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LncRNADisease: a database for long-non-coding RNA-associated diseases.
Nucleic Acids Res.
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In this article, we describe a long-non-coding RNA (lncRNA) and disease association database (LncRNADisease), which is publicly accessible at http://cmbi.bjmu.edu.cn/lncrnadisease. In recent years, a large number of lncRNAs have been identified and increasing evidence shows that lncRNAs play critical roles in various biological processes. Therefore, the dysfunctions of lncRNAs are associated with a wide range of diseases. It thus becomes important to understand lncRNAs roles in diseases and to identify candidate lncRNAs for disease diagnosis, treatment and prognosis. For this purpose, a high-quality lncRNA-disease association database would be extremely beneficial. Here, we describe the LncRNADisease database that collected and curated approximately 480 entries of experimentally supported lncRNA-disease associations, including 166 diseases. LncRNADisease also curated 478 entries of lncRNA interacting partners at various molecular levels, including protein, RNA, miRNA and DNA. Moreover, we annotated lncRNA-disease associations with genomic information, sequences, references and species. We normalized the disease name and the type of lncRNA dysfunction and provided a detailed description for each entry. Finally, we developed a bioinformatic method to predict novel lncRNA-disease associations and integrated the method and the predicted associated diseases of 1564 human lncRNAs into the database.
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Development of amphotericin B-loaded cubosomes through the SolEmuls technology for enhancing the oral bioavailability.
AAPS PharmSciTech
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The oral administration of amphotericin B (AmB) has the major drawback of poor bioavailability. The aim of this work was to evaluate the potential of AmB-loaded cubosomes as an oral formulation with improved bioavailability. This manuscript firstly developed AmB-loaded cubosomes by using the SolEmuls technology. The encapsulation efficiency, the in vitro release, and stability studies in simulated gastrointestinal fluid were used to evaluate AmB-loaded cubosomes. The acute nephrotoxicity, bioavailability, and tissue distribution study of AmB-loaded cubosomes were assayed upon oral administration to rats. SAXS and cryo-TEM exhibited AmB-loaded cubosomes as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and the results of in vitro release and stability studies in simulated gastrointestinal fluid further demonstrated that AmB was successfully encapsulated in cubosomes. AmB-loaded cubosomal formulation orally administrated in rats did not show nephrotoxicity and its relative bioavailability was approximately 285% as compared to Fungizone®. The AmB-loaded cubosomal formulation presented an effective potential approach for enhancing the oral bioavailability of AmB.
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An integrated tunable interferometer controlled by liquid diffusion in polydimethylsiloxane.
Opt Express
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We demonstrated an integrated tunable interferometer in Polydimethylsiloxane (PDMS). In contrast to most on-chip interferometers which require complex fabrication, our design is realized by conventional soft lithography fabrication. The optical path difference occurs during propagation across a fluid-fluid interface. The diffusion level of the two miscible liquids which is controlled by liquid flow rates provides tunability. Different ratio of two liquid flow rates result in the interference spectral shift. Interference peak numbers are varied with flow rate ratio of two liquids. Mutual diffusion between two liquids changes the profile of the refractive index across the fluidic channel. The two arms structure of our design provides convenience for sensing and detection in biology system. This device not only offers the convenience for microfluidic networks but also paves the way for sensing in chemical microreactors.
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Posttraumatic pulmonary pseudocyst: computed tomography findings and management in 33 patients.
J Trauma Acute Care Surg
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Posttraumatic pulmonary pseudocyst (PPP) is a complication of blunt chest trauma and poorly documented. A retrospective review of PPPs observed during the past 6 years in our hospitals is presented in this report.
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Germination dramatically increases isoflavonoid content and diversity in chickpea (Cicer arietinum L.) seeds.
J. Agric. Food Chem.
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The effect of germination on bioactive components in legume seeds was investigated in terms of the antioxidant capacity and total phenolic contents. Germination increased the total phenolic content and antioxidant capacity of most seeds. Particularly in chickpea seeds, the isoflavone contents increased by over 100 fold, mainly due to the increase of formononetin and biochanin A level. As a result, these two compounds were conveniently isolated from the germinated seeds in preparative scale and structurally confirmed by UV-vis, ESI-MS, and (1)H NMR spectroscopies. Isoflavonoid fingerprints analyzed by HPLC-PDA and LC-ESI-MS demonstrated that germination could significantly increase isoflavonoids diversity. Twenty-five isoflavonoids were detected and identified tentatively. These include 20 isoflavones, 2 isoflavanones, and 3 pterocarpan phytoalexins. Total isoflavonoid content of germinated chickpea was approximately 5-fold of that of germinated soybean. Our findings suggest that the germinated chickpea seeds could serve as a promising functional food rich in isoflavonoids.
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Inhibition of type I interferon-mediated antiviral action in human glioma cells by the IKK inhibitors BMS-345541 and TPCA-1.
J. Interferon Cytokine Res.
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The nuclear factor-kappa B (NF?B) signal transduction pathway plays an important role in immunity, inflammation, cell growth, and survival. Since dysregulation of this pathway results in high, constitutive NF?B activation in various cancers and immune disorders, the development of specific drugs to target this pathway has become a focus for treating these diseases. NF?B regulates various aspects of the cellular response to interferon (IFN). However, the role of the upstream regulator of the NF?B signaling pathway, the inhibitor of ?B kinase (IKK) complex, on IFN function has not been examined. In the present study, we examined the effects of 2 IKK inhibitors, N-(1,8-Dimethylimidazo[1,2-a]quinoxalin-4-yl)-1,2-ethanediamine hydrochloride (BMS-345541) and 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), on IFN action in several human glioma cell lines. IKK inhibitors inhibit glioma cell proliferation, as well as TNF-induced RelA (p65) nuclear translocation and NF?B-dependent IL8 gene expression. Importantly, BMS-345541 and TPCA-1 differentially inhibit IFN-induced gene expression, completely suppressing MX1 and GBP1 gene expression, while having only a minor effect on ISG15 expression. Furthermore, these IKK inhibitors displayed marked differences in blocking IFN-induced antiviral action against cytopathic effects and replication of vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). Our results show that the IKK complex plays an important function in IFN-induced gene expression and antiviral activity. Since VSV and EMCV are oncolytic viruses used in cancer therapy, our results indicate the potential synergy in combining IKK inhibitors with oncolytic viruses.
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[Apoptosis and proliferation of corpus cavernosum smooth muscle cells in diabetic rats].
Nan Fang Yi Ke Da Xue Xue Bao
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To explore the characteristics of cell apoptosis and proliferation of corpus cavernosum smooth muscle (CCSM) cells in diabetic rats.
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Optimization of orthotropic distributed-mode loudspeaker using attached masses and multi-exciters.
J. Acoust. Soc. Am.
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Based on the orthotropic model of the plate, the method to optimize the sound response of the distributed-mode loudspeaker (DML) using the attached masses and the multi-exciters has been investigated. The attached masses method will rebuild the modes distribution of the plate, based on which multi-exciter method will smooth the sound response. The results indicate that the method can be used to optimize the sound response of the DML.
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Fascin expression in skull base chordoma: correlation with tumor recurrence and dura erosion.
Med. Oncol.
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Skull base chordomas are invasive tumors, with high rate of local recurrence even when totally extracted. The aggressive biological behavior in chordoma remains unclear. The purpose of this study was to investigate the relationship between fascin expression and tumor biological behavior in skull base chordoma. Using immunohistochemical techniques, we investigated the expression of fascin in 34 patients with skull base chordomas (19 primary tumors and 20 recurrent tumors). Correlation between fascin expression and clinicopathological factors such as patients age, sex, tumor locations, and fascin expression in recurrent tumor and in tumor with dura mater erosion was analyzed. Various extent of fascin expression was observed in all tumors. There was a higher fascin expression in recurrent chordoma than in primary chordoma, and the difference was statistically significant (p=0.031). No difference of fascin expression was found between histology types. Interestingly, in 8 tumors where the cranial base dura was eroded, there was a high level of fascin expression (p=0.047). These immunohistochemical findings suggest that fascin expression was correlated with tumor recurrence and high invasiveness, and that fascin overexpression may play an important role in the biologic behavior of skull base chordomas.
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Stability and aerosolization of pressurized metered dose inhalers containing thymopentin nanoparticles produced using a bottom-up process.
Int J Pharm
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The objective of this study was to investigate the stability and aerosolization of pressurized metered dose inhalers (pMDIs) containing thymopentin nanoparticles. Thymopentin nanoparticles, fabricated by a bottom-up process, were suspended in hydrofluoroalkane (HFA) 134a together with cineole and/or n-heptane to produce pMDI formulations. The stability study of the pMDIs obtained was carried out at ambient temperature for 6 months. The amount of thymopentin and the aerosolization properties of pMDIs were determined using high-performance liquid chromatography (HPLC) and a twin-stage impinger (TSI), respectively. Based on the results, thymopentin nanoparticles were readily suspended in HFA 134a with the aid of cineole and/or n-heptane to form physically stable pMDI formulations, and more than 98% of the labeled amount of thymopentin and over 50% of the fine particle fraction (FPF) of the pMDIs were achieved. During storage, it was found that for all pMDIs more than 97% of the labeled amount of thymopentin and FPF greater than 47% were achieved. Moreover, the size of thymopentin nanoparticles in propellant containing cineole and n-heptane showed little change. It is, therefore, concluded that the pMDIs comprising thymopentin nanoparticles developed in this study were stable and suitable for inhalation therapy for systemic action.
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Abnormally long-range diamagnetic anisotropy induced by cyclic d(?)-p(?) ? conjugation within a six-membered dimolybdenum/chalcogen ring.
Inorg Chem
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Incorporating two quadruply bonded dimolybdenum units [Mo(2)(DAniF)((3))](+) (ancillary ligand DAniF = N,N-di-p-anisylformamidinate) with two hydroselenides (SeH(-)) gave rise to [Mo(2)(DAniF)(3)](2)(?-SeH)(2) (1). With the molecular scaffold remaining unchanged, aerobic oxidation of 1, followed by autodeprotonation, generated [Mo(2)(DAniF)(3)](2)(?-Se)(2) (2). The two complexes share a common cyclic six-membered Mo(2)/Se core, but compound 2 is distinct from 1 by having structural, electronic, and magnetic properties that correspond with aromaticity. Importantly, the aromatic behaviors for this non-carbon system are ascribable to the bonding analogy between the ? component in a Mo-Mo quadruple bond and the ? component in a C-C double bond. Cyclic ? delocalization via d(?)-p(?) conjugation within the central unit, which involves six ? electrons with one electron from each of the Mo(2) units and two electrons from each of the bridging atoms, has been confirmed in a previous work on the oxygen- and sulfur-bridged analogues (Fang, W.; et al. Chem.-Eur. J.2011, 17, 10288). Of the three members in this family, compound 2 exhibits an enhanced aromaticity because of the selenium bridges. The remote in-plane and out-of-plane methine (ArNCHNAr) protons resonate at chemical shifts (?) 9.42 and 7.84 ppm, respectively. This NMR displacement, ?? = 1.58 ppm, is larger than that for the oxygen-bridged (1.30 ppm) and sulfur-bridged (1.49 ppm) derivatives. The abnormally long-range shielding effects and the large diamagnetic anisotropy for this complex system can be rationalized by the induced ring currents circulating the Mo(2)/chalcogen core. By employment of the McConnell equation {?? = ??[(l - 3 cos 2?)/3R(3)N]}, the magnetic anisotropy (?? = ?(?) - ?(||)) is estimated to be -414 ppm cgs, which is dramatically larger than -62.9 ppm cgs for benzene, the paradigm of aromaticity. In addition, it is found that the magnitude of ?? is linearly related to the radius of the bridging atoms, with the selenium analogue having the largest value. This aromaticity sequence is in agreement with that for the chalcogen-containing aromatic family, e.g., furan < thiophene < selenophene.
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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.