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Find video protocols related to scientific articles indexed in Pubmed.
[Exercise training in hypoxia prevents hypoxia induced mitochondrial DNA oxidative damage in skeletal muscle].
Sheng Li Xue Bao
PUBLISHED: 10-22-2014
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This study was undertaken to investigate the effect of exercise training on mitochondrial DNA (mtDNA) oxidative damage and 8-oxoguanine DNA glycosylase-1 (OGG1) expression in skeletal muscle of rats under continuous exposure to hypoxia. Male Sprague-Dawley rats were randomly divided into 4 groups (n = 8): normoxia control group (NC), normoxia training group (NT), hypoxia control group (HC), and hypoxia training group (HT). The hypoxia-treated animals were housed in normobaric hypoxic tent containing 11.3% oxygen for consecutive 4 weeks. The exercise-trained animals were exercised on a motor-driven rodent treadmill at a speed of 15 m/min, 5% grade for 60 min/day, 5 days per week for 4 weeks. The results showed that, compared with NC group, hypoxia attenuated complex I, II, IV and ATP synthase activities of the electron transport chain, and the level of mitochondrial membrane potential in HC group (P < 0.05 or P < 0.01). Moreover, hypoxia decreased mitochondrial OGG1, MnSOD, and GPx activities (P < 0.05 or P < 0.01), whereas elevated reactive oxygen species (ROS) generation and the level of 8-oxo-deoxyguanosine (8-oxodG) in mtDNA (P < 0.01). Furthermore, hypoxia attenuated muscle and mitochondrial [NAD(+)]/ [NADH] ratio, and SIRT3 protein expression (P < 0.05 or P < 0.01). Compared with HC group, exercise training in hypoxia elevated complex I, II, IV and ATP synthase activities, and the level of mitochondrial membrane potential in HT group (P < 0.05 or P < 0.01). Moreover, exercise training in hypoxia increased MnSOD and GPx activities and mitochondrial OGG1 level (P < 0.01), whereas decreased ROS generation and the level of 8-oxodG in mtDNA (P < 0.01). Furthermore, exercise training in hypoxia increased muscle and mitochondrial [NAD(+)]/[NADH] ratio, as well as SIRT3 protein expression (P < 0.05 or P < 0.01). These findings suggest that exercise training in hypoxia can decrease hypoxia-induced mtDNA oxidative damage in the skeletal muscle through up-regulating exercise-induced mitochondrial OGG1 and antioxidant enzymes. Exercise training in hypoxia may improve hypoxia tolerance in skeletal muscle mitochondria via elevating [NAD(+)]/[NADH] ratio and SIRT3 expression.
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[Analysis of SEDL gene mutation in a Chinese pedigree with X-linked spondyloepiphyseal dysplasia tarda].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 10-10-2014
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To explore the molecular mechanism for a family with hereditary X-linked spondyloepiphysealdysplasia tarda (SEDT).
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Evaluation of five methods for genome-wide circadian gene identification.
J. Biol. Rhythms
PUBLISHED: 09-21-2014
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Identification of circadian-regulated genes based on temporal transcriptome data is important for studying the regulation mechanism of the circadian system. However, various computational methods adopting different strategies for the identification of cycling transcripts usually yield inconsistent results even for the same dataset, making it challenging to choose the optimal method for a specific circadian study. To address this challenge, we evaluate 5 popular methods, including ARSER (ARS), COSOPT (COS), Fisher's G test (FIS), HAYSTACK (HAY), and JTK_CYCLE (JTK), based on both simulated and empirical datasets. Our results show that increasing the number of total samples (through improving sampling frequency or lengthening the sampling time window) is beneficial for computational methods to accurately identify circadian transcripts and measure circadian phase. For a given number of total samples, higher sampling frequency is more important for HAY and JTK, and the longer sampling time window is more crucial for ARS and COS, as testified on simulated and empirical datasets from which circadian signals are computationally identified. In addition, the preference of higher sampling frequency or the longer sampling time window is also obvious for JTK, ARS, and COS in estimating circadian phases of simulated periodic profiles. Our results also indicate that attention should be paid to the significance threshold that is used for each method in selecting circadian genes, especially when analyzing the same empirical dataset with 2 or more methods. To summarize, for any study involving genome-wide identification of circadian genes from transcriptome data, our evaluation results provide suggestions for the selection of an optimal method based on specific goal and experimental design.
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[Clinical features of sinonasal inverted papilloma with recurrence and malignant transformation].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-16-2014
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To investigate the clinical characteristics, treatment and the effectiveness of sinonasal inverting papilloma with recurrence and malignant transformation.
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[Effects and related mechanism of retinoid X receptor agonist bexarotene on atherosclerosis progression in diabetic apoE(-/-) mice].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 08-29-2014
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To explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE(-/-)) mice.
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Infection with MERS-CoV causes lethal pneumonia in the common marmoset.
PLoS Pathog.
PUBLISHED: 08-21-2014
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The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.
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Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo.
J. Virol.
PUBLISHED: 08-20-2014
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Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody transfer would prevent HIV-1 transmission in humans. To increase the protective efficacy of such monoclonal antibodies, we employed next-generation sequencing, computational bioinformatics, and structure-guided design to enhance the neutralization potency and breadth of VRC01, an antibody that targets the CD4 binding site of the HIV-1 envelope. One variant, VRC07-523, was 5- to 8-fold more potent than VRC01, neutralized 96% of viruses tested, and displayed minimal autoreactivity. To compare its protective efficacy to that of VRC01 in vivo, we performed a series of simian-human immunodeficiency virus (SHIV) challenge experiments in nonhuman primates and calculated the doses of VRC07-523 and VRC01 that provide 50% protection (EC50). VRC07-523 prevented infection in NHPs at a 5-fold lower concentration than VRC01. These results suggest that increased neutralization potency in vitro correlates with improved protection against infection in vivo, documenting the improved functional efficacy of VRC07-523 and its potential clinical relevance for protecting against HIV-1 infection in humans.
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Proteomic Profiling of Invasive Ductal Carcinoma (IDC) using Magnetic Beads-based Serum Fractionation and MALDI-TOF MS.
J. Clin. Lab. Anal.
PUBLISHED: 08-17-2014
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To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs.
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The Holocene temperature conundrum.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-11-2014
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A recent temperature reconstruction of global annual temperature shows Early Holocene warmth followed by a cooling trend through the Middle to Late Holocene [Marcott SA, et al., 2013, Science 339(6124):1198-1201]. This global cooling is puzzling because it is opposite from the expected and simulated global warming trend due to the retreating ice sheets and rising atmospheric greenhouse gases. Our critical reexamination of this contradiction between the reconstructed cooling and the simulated warming points to potentially significant biases in both the seasonality of the proxy reconstruction and the climate sensitivity of current climate models.
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Epigenetic modification agents improve genomic methylation reprogramming in porcine cloned embryos.
J. Reprod. Dev.
PUBLISHED: 07-21-2014
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Incomplete DNA methylation reprogramming in cloned embryos leads to low cloning efficiency. Our previous studies showed that the epigenetic modification agents 5-aza-2'-deoxycytidine (5-aza-dC) or trichostatin A (TSA) could enhance the developmental competence of porcine cloned embryos. Here, we investigated genomic methylation dynamics and specific gene expression levels during early embryonic development in pigs. In this study, our results showed that there was a typical wave of DNA demethylation and remethylation of centromeric satellite repeat (CenRep) in fertilized embryos, whereas in cloned embryos, delayed demethylation and a lack of remethylation were observed. When cloned embryos were treated with 5-aza-dC or TSA, CenRep methylation reprogramming was improved, and this was similar to that detected in fertilized counterparts. Furthermore, we found that the epigenetic modification agents, especially TSA, effectively promoted silencing of tissue specific genes and transcription of early embryo development-related genes in porcine cloned embryos. In conclusion, our results showed that the epigenetic modification agent 5-aza-dC or TSA could improve genomic methylation reprogramming in porcine cloned embryos and regulate the appropriate expression levels of genes related to early embryonic development, thereby resulting in high developmental competence.
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Uveal melanoma in the peripheral choroid masquerading as chronic uveitis.
Optom Vis Sci
PUBLISHED: 07-19-2014
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To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes.
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[Theoretical study on fluorescence spectra of four kinds of p-substituted curcumin analogues].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 07-11-2014
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Four kinds of p-substituted curcumin analogues were optimized at B3LYP/6-31G (d, p) level. On this basis, the excited states geometry structure was optimized by the CIS method, and finally the fluorescence emission spectra were calculated through the TD-DFT method. The results showed that: the four compounds, a large conjugated system, is preferably coplanar structure. Because of introducing hydroxyl and halogen atom on the benzene ring, the molecular pi-electron conjugation is relatively larger, emission wavelength is relatively longer, and fluorescence spectra show different degrees of red shift. As the electron donating group is hydroxy, the fluorescence phenomenon is more obviously red shifted.
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Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2-p53 Interaction.
ACS Med Chem Lett
PUBLISHED: 06-30-2014
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Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Compound 23 exhibits excellent pharmacokinetic properties and substantial in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft mouse model.
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[Remarks on the relationship between deqi and effect of acupuncture].
Zhongguo Zhen Jiu
PUBLISHED: 06-21-2014
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Acupuncturists have always paid high attention to deqi (needling sensation) in clinical. However, relationship between deqi and curative effect has not been elucidated yet. In order to have a further understanding on effect of deqi on clinical effect, through study on literature associated with deqi since the establishment of People's Republic of China in 1949, it is held that various factors can influence therapeutic effect of acupuncture treatment, including whether needling sensation appears or not, the speed of deqi, the intensity of deqi, different types of sensations as well as propagated sensation along meridians (PSM). Joint launched multidisciplinary researches should be carried out to reveal the influence principle of deqi on acupuncture effect, and to lay foundations for the further studies on mechanism of deqi.
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Toward a more accurate view of human B-cell repertoire by next-generation sequencing, unbiased repertoire capture and single-molecule barcoding.
Sci Rep
PUBLISHED: 06-16-2014
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B-cell repertoire analysis using next-generation sequencing has become a valuable tool for interrogating the genetic record of humoral response to infection. However, key obstacles such as low throughput, short read length, high error rate, and undetermined bias of multiplex PCR method have hindered broader application of this technology. In this study, we report several technical advances in antibody repertoire sequencing. We first demonstrated the ability to sequence antibody variable domains using the Ion Torrent PGM platform. As a test case, we analyzed the PGT121 class of antibodies from IAVI donor 17, an HIV-1-infected individual. We then obtained "unbiased" antibody repertoires by sequencing the 5'-RACE PCR products of B-cell transcripts from IAVI donor 17 and two HIV-1-uninfected individuals. We also quantified the bias of previously published gene-specific primers by comparing the repertoires generated by 5'-RACE PCR and multiplex PCR. We further developed a single-molecule barcoding strategy to reduce PCR-based amplification noise. Lastly, we evaluated several new PGM technologies in the context of antibody sequencing. We expect that, based upon long-read and high-fidelity next-generation sequencing technologies, the unbiased analysis will provide a more accurate view of the overall antibody repertoire while the barcoding strategy will facilitate high-resolution analysis of individual antibody families.
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Hexameric Mn(II) Dendrimer as MRI Contrast Agent.
Chemistry
PUBLISHED: 06-09-2014
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A Mn(II) chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine-derived [Mn(EDTA)(H2 O)](2-) moieties coupled to a cyclotriphosphazene core. Variable temperature (17) O?NMR spectroscopy revealed a single water co-ligand per Mn(II) that undergoes fast water exchange (kex =(3.0±0.1)×10(8) ?s(-1) at 37?°C). The 37?°C per Mn(II) relaxivity ranged from 8.2 to 3.8?mM(-1) ?s(-1) from 0.47 to 11.7?T, and is sixfold higher on a per molecule basis. From this field dependence a rotational correlation time was estimated as 0.45(±0.02)?ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H2 O)](2-) in mice at 4.7?T. On first pass, the higher per ion relaxivity of the dendrimer resulted in twofold greater blood signal than for [Gd(DTPA)(H2 O)](2-) . Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This Mn(II) containing dendrimer represents a potential alternative to Gd-based contrast agents, especially in patients with chronic kidney disease where the use of current Gd-based agents may be contraindicated.
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Targeting myeloid differentiation 2 for treatment of sepsis.
Front Biosci (Landmark Ed)
PUBLISHED: 06-05-2014
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Sepsis continues to be a leading cause of intensive care unit (ICU) death. Gram-negative bacteria are among the most important pathogens of sepsis and their LPS content is regarded to be an important stimulator that elicits the systemic inflammatory reaction. MD-2 is a small secreted glycoprotein that can bind to both the hydrophobic portion of LPS and to the extracellular domain of TLR4. The interaction between MD-2 and LPS bridges the two TLR4 molecules and induces the dimerization of LPS-MD-2-TLR4, which forms the structural basis for biological functions of TLR4/MD-2 complex. Due to its essential role in mediating the interaction between LPS and TLR4, MD-2 has been extensively explored as a therapeutic target for treatment of inflammatory disorders such as sepsis. Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site. Although eritoran showed positive results in phase I and phase II clinical trials of severe sepsis, a phase III clinical study for severe sepsis has failed. More effective therapeutic strategies are in need to treat this devastating clinical disorder.
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Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.
J. Virol.
PUBLISHED: 06-04-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir.
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Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells.
Nat. Biotechnol.
PUBLISHED: 05-14-2014
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Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.
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Optimization beyond AMG 232: discovery and SAR of sulfonamides on a piperidinone scaffold as potent inhibitors of the MDM2-p53 protein-protein interaction.
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-29-2014
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We recently reported on the discovery of AMG 232, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. AMG 232 is being evaluated in human clinical trials for cancer. Continued exploration of the N-alkyl substituent of this series, in an effort to optimize interactions with the MDM2 glycine-58 shelf region, led to the discovery of sulfonamides such as compounds 31 and 38 that have similar potency, hepatocyte stability and rat pharmacokinetic properties to AMG 232.
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A pre-breeding screening program for transgenic boars based on fluorescence in situ hybridization assay.
Transgenic Res.
PUBLISHED: 04-17-2014
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For efficient transgenic herd expansion, only the transgenic animals that possess the ability to transmit transgene into next generation are considered for breeding. However, for transgenic pig, practically lacking a pre-breeding screening program, time, labor and money is always wasted to maintain non-transgenic pigs, low or null transgenic transmission pigs and the related fruitless gestations. Developing a pre-breeding screening program would make the transgenic herd expansion more economical and efficient. In this technical report, we proposed a three-step pre-breeding screening program for transgenic boars simply through combining the fluorescence in situ hybridization (FISH) assay with the common pre-breeding screening workflow. In the first step of screening, combined with general transgenic phenotype analysis, FISH is used to identify transgenic boars. In the second step of screening, combined with conventional semen test, FISH is used to detect transgenic sperm, thus to identify the individuals producing high quality semen and transgenic sperm. In the third step of screening, FISH is used to assess the in vitro fertilization embryos, thus finally to identify the individuals with the ability to produce transgenic embryos. By this three-step screening, the non-transgenic boars and boars with no ability to produce transgenic sperm or transgenic embryos would be eliminated; therefore only those boars could produce transgenic offspring are maintained and used for breeding and herd expansion. It is the first time a systematic pre-breeding screening program is proposed for transgenic pigs. This program might also be applied in other transgenic large animals, and provide an economical and efficient strategy for herd expansion.
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Jumping phase control in interband photonic transition.
Opt Express
PUBLISHED: 03-26-2014
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Indirect interband photonic transition provides a nonmagnetic and linear scheme to achieve optical isolation in integrated photonics. In this paper, we demonstrate that the nonreciprocal transition can be induced through two pathways respectively by different modulation designs. At the end of those pathways, the two final modes have ? phaseshift. We call this phenomenon jumping phase control since this approach provides a method to control the mode phase after the conversion. This approach also yields a novel way to generate nonreciprocal phaseshift and may contribute to chip-scale optoelectronic applications.
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Translational selection in human: more pronounced in housekeeping genes.
Biol. Direct
PUBLISHED: 03-21-2014
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Translational selection is a ubiquitous and significant mechanism to regulate protein expression in prokaryotes and unicellular eukaryotes. Recent evidence has shown that translational selection is weakly operative in highly expressed genes in human and other vertebrates. However, it remains unclear whether translational selection acts differentially on human genes depending on their expression patterns.
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Passive smoke exposure was related to mean platelet volume in never-smokers.
Am J Health Behav
PUBLISHED: 03-19-2014
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To investigate the effect of passive smoking on the changes in mean platelet volume (MPV) in healthy adults.
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A randomized controlled trial of single point acupuncture in primary dysmenorrhea.
Pain Med
PUBLISHED: 03-17-2014
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Acupuncture is often used for primary dysmenorrhea. But there is no convincing evidence due to low methodological quality. We aim to assess immediate effect of acupuncture at specific acupoint compared with unrelated acupoint and nonacupoint on primary dysmenorrhea.
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Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway.
Acta Pharmacol. Sin.
PUBLISHED: 03-09-2014
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Aim:To investigate the role of extracellular signal-regulated kinases (ERKs) in sevoflurane post-conditioning induced cardioprotection in vitro.Methods:Isolated rat hearts were subjected to 30 min ischemia followed by 120 min reperfusion (I/R). Sevoflurane post-conditioning was carried out by administration of O2-enriched gas mixture with 3% sevoflurane (SEVO) for 15 min from the onset of reperfusion. Cardiac functions, myocardial infarct size, myocardial ATP and NAD(+) contents, mitochondrial ultrastructure, and anti-apototic and anti-oncosis protein levels were measured.Results:Sevoflurane post-conditioning significantly improved the heart function, decreased infarct size and mitochondria damage, and increased myocardial ATP and NAD(+) content in the I/R hearts. Furthermore, sevoflurane post-conditioning significantly increased the levels of p-ERK and p-p70S6K, decreased the levels of porimin, caspase-8, cleaved caspase-3, and cytosolic cytochrome c in the I/R hearts. Co-administration of the ERK1/2 inhibitor PD98059 (20 ?mol/L) abolished the sevoflurane-induced protective effects against myocardial I/R.Conclusion:Sevoflurane post-conditioning protects isolated rat hearts against myocardial I/R injury and inhibits cell oncosis and apoptosis via activation of the ERK1/2 pathway.
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Retinoid X receptor agonists inhibit hypertension-induced myocardial hypertrophy by modulating LKB1/AMPK/p70S6K signaling pathway.
Am. J. Hypertens.
PUBLISHED: 03-06-2014
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Retinoid X receptor (RXR) has been demonstrated to play an important role in cardiac development and has been implicated in cardiovascular diseases. This study aimed to examine the effects of RXR? agonist bexarotene on pathological left ventricular hypertrophy (LVH) in a spontaneously hypertensive rat (SHR) model and the underlying mechanism.
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Obstacle classification and 3D measurement in unstructured environments based on ToF cameras.
Sensors (Basel)
PUBLISHED: 02-14-2014
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Inspired by the human 3D visual perception system, we present an obstacle detection and classification method based on the use of Time-of-Flight (ToF) cameras for robotic navigation in unstructured environments. The ToF camera provides 3D sensing by capturing an image along with per-pixel 3D space information. Based on this valuable feature and human knowledge of navigation, the proposed method first removes irrelevant regions which do not affect robot's movement from the scene. In the second step, regions of interest are detected and clustered as possible obstacles using both 3D information and intensity image obtained by the ToF camera. Consequently, a multiple relevance vector machine (RVM) classifier is designed to classify obstacles into four possible classes based on the terrain traversability and geometrical features of the obstacles. Finally, experimental results in various unstructured environments are presented to verify the robustness and performance of the proposed approach. We have found that, compared with the existing obstacle recognition methods, the new approach is more accurate and efficient.
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Association between the transcriptional levels of Htr-1a and tryptophan hydroxylase-1 in the hippocampus and the antifatigue effects of leucine on rats with postoperative fatigue.
Exp Ther Med
PUBLISHED: 02-13-2014
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Leucine (Leu), a branched-chain amino acid (BCAA), is widely used in clinical practice following severe burns, gastrointestinal surgery, trauma and sepsis. In the present study, the antifatigue effects of BCAAs on a postoperative fatigue (POF) rat model, induced by 70% intestinal resection, were investigated. Leu (16.5 g/l) was administered intraperitoneally at a dose of 18 ml/kg/day. The fatigue level and antifatigue effects of Leu were evaluated by open-field testing on day 1, 3, 5 and 7 after surgery. In addition, mRNA specimens were extracted and measured using a quantitative polymerase chain reaction method. The open-field test results indicated that Leu exhibited a significant antifatigue effect. The total distance travelled and the number of times the rats passed from the outermost grids of an open-top case were greatly improved in the Leu treatment group when compared with the POF model group. With the exception of the normal group, the mRNA expression levels of Htr-1a exhibited a similar trend in all other groups, reaching a climax on day 3 and 5, while being restored to a normal level on day 7. With regard to the Leu intervention group, the mRNA expression level of Htr-1a decreased significantly on day 3 and 5 following surgery. The mRNA expression levels of tryptophan hydroxylase-1 were unchanged in this short time period; however, the levels were increased gradually in the Leu treatment group. Therefore, Leu exhibited an apparent antifatigue effect on various 5-hydroxytryptamine-associated genes.
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Effect of acupuncture on Deqi traits and pain intensity in primary dysmenorrhea: analysis of data from a larger randomized controlled trial.
BMC Complement Altern Med
PUBLISHED: 02-13-2014
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Deqi is a central concept in traditional Chinese acupuncture. We performed a secondary analysis on data from a larger randomized controlled trial (RCT) in order to assess the effect of acupuncture on deqi traits and pain intensity in primary dysmenorrhea.
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Genetic and epigenetic fine mapping of causal autoimmune disease variants.
Nature
PUBLISHED: 02-11-2014
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Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4(+) T-cell subsets, regulatory T cells, CD8(+) T cells, B cells, and monocytes. We find that ?90% of causal variants are non-coding, with ?60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10-20% directly alter recognizable transcription factor binding motifs. Rather, most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.
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The effect of superparamagnetic iron oxide with iRGD peptide on the labeling of pancreatic cancer cells in vitro: a preliminary study.
Biomed Res Int
PUBLISHED: 02-10-2014
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The iRGD peptide loaded with iron oxide nanoparticles for tumor targeting and tissue penetration was developed for targeted tumor therapy and ultrasensitive MR imaging. Binding of iRGD, a tumor homing peptide, is mediated by integrins, which are widely expressed on the surface of cells. Several types of small molecular drugs and nanoparticles can be transfected into cells with the help of iRGD peptide. Thus, we postulate that SPIO nanoparticles, which have good biocompatibility, can also be transfected into cells using iRGD. Despite the many kinds of cell labeling studies that have been performed with SPIO nanoparticles and RGD peptide or its analogues, only a few have applied SPIO nanoparticles with iRGD peptide in pancreatic cancer cells. This paper reports our preliminary findings regarding the effect of iRGD peptide (CRGDK/RGPD/EC) combined with SPIO on the labeling of pancreatic cancer cells. The results suggest that SPIO with iRGD peptide can enhance the positive labeling rate of cells and the uptake of SPIO. Optimal functionalization was achieved with the appropriate concentration or concentration range of SPIO and iRGD peptide. This study describes a simple and economical protocol to label panc-1 cells using SPIO in combination with iRGD peptide and may provide a useful method to improve the sensitivity of pancreatic cancer imaging.
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The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An Observation of "Deqi".
Evid Based Complement Alternat Med
PUBLISHED: 02-10-2014
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Background. Deqi sensation is a complex but an important component for acupuncture effect. In this study, we tried to observe the relationship between Deqi and skin temperature changes and whether there was some relativity between Deqi and needle stimulations on cold congealing and dysmenorrhea rat model. Thirty-two female Sprague Dawley (SD) rats were randomly divided into four groups (Saline Control Group, Model Group, Group A with strong stimulation, and Group B with small stimulation). Group A and Group B were performed with different stimulations. We found that, compared with saline control group, model group, and Group B, Group A showed that the skin temperature changes on right acupoint SP6 and SP10 increased significantly at 5?min-10?min interval. The skin temperature changes on left SP6 decreased at instant-5?min interval. The skin temperature changes on right SP10 decreased significantly at instant-5?min interval and 10?min-20?min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin was manifested as simultaneous skin temperature increase on right SP6 and SP10 at 5?min-10?min interval after needling SP6, which was helpful to illustrate the relationship between the characteristic of Deqi and needle stimulations.
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Do changes in electrical skin resistance of acupuncture points reflect menstrual pain? A comparative study in healthy volunteers and primary dysmenorrhea patients.
Evid Based Complement Alternat Med
PUBLISHED: 02-09-2014
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Electrical skin resistance (ESR) measurements were performed with a four-electrode impedance detector at 10 points bilaterally on the first day of and the third day after menstruation in 48 healthy volunteers and 46 primary dysmenorrhea (PD) patients, to assess whether ESR changes of acupuncture points can reflect menstrual pain or not. The results showed statistical reductions in ESR imbalance ratio between left and right side that were detected at SP8 (Diji) and GB39 (Xuanzhong) (P < 0.05), and a statistical increase was detected at SP6 (Sanyinjiao) (P = 0.05) on the first day of menstruation compared with those values on the third day after menstruation in dysmenorrhea group. No significant differences were detected at other points within and between two groups (P > 0.05). This study showed that the imbalance of ESR at uterine-relevant points in PD patients is not significantly different from those of healthy women on both the 1st day of and the 3rd day after menstruation. The ESR imbalance ratio of certain points can either be lower or higher during menstruation in PD patients. The ESR property of acupuncture points needs to be investigated in further clinical trials with appropriate points, diseases, larger sample sizes, and optimal device.
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An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Nat. Genet.
PUBLISHED: 02-06-2014
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The identification of activating NOTCH1 mutations in T cell acute lymphoblastic leukemia (T-ALL) led to clinical testing of ?-secretase inhibitors (GSIs) that prevent NOTCH1 activation. However, responses to these inhibitors have been transient, suggesting that resistance limits their clinical efficacy. Here we modeled T-ALL resistance, identifying GSI-tolerant 'persister' cells that expand in the absence of NOTCH1 signaling. Rare persisters are already present in naive T-ALL populations, and the reversibility of their phenotype suggests an epigenetic mechanism. Relative to GSI-sensitive cells, persister cells activate distinct signaling and transcriptional programs and exhibit chromatin compaction. A knockdown screen identified chromatin regulators essential for persister viability, including BRD4. BRD4 binds enhancers near critical T-ALL genes, including MYC and BCL2. The BRD4 inhibitor JQ1 downregulates expression of these targets and induces growth arrest and apoptosis in persister cells, at doses well tolerated by GSI-sensitive cells. Consistently, the GSI-JQ1 combination was found to be effective against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia resistance that may be addressed by incorporating epigenetic modulators in combination therapy.
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A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population.
BMC Med Genomics
PUBLISHED: 02-05-2014
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Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited.
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Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.
J. Med. Chem.
PUBLISHED: 02-05-2014
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We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Continued research investigation of the N-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency. Further investigation produced AMG 232 (2), which is currently being evaluated in human clinical trials for the treatment of cancer. Compound 2 is an extremely potent MDM2 inhibitor (SPR KD = 0.045 nM, SJSA-1 EdU IC50 = 9.1 nM), with remarkable pharmacokinetic properties and in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft model (ED50 = 9.1 mg/kg).
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Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone.
Hum. Pathol.
PUBLISHED: 01-23-2014
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Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs (miRs) in the pathogenesis of DLBCL. We report here that low expression of miR-146b-5p and miR-320d is associated with poor prognosis of DLBCL patients treated with the standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen and that this is related to the inhibitory effect of these miRs on DLBCL cell proliferation. Analysis of a retrospective cohort of 106 primary nodal DLBCL samples from patients who were treated with CHOP showed that, when the median survival period (40.8 months) was used as the cutoff point, miR-146b-5p and miR-320d were expressed at lower levels in DLBCLs with poor prognosis. Indeed, whereas low expression of miR-146b-5p was correlated with reduced progression-free survival, low expression of miR-320d was associated with decreases in both progression-free survival and overall survival. Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels in DLBCLs with the MYC t(8;14) translocation. Functional studies demonstrated that overexpression of miR-146b-5p or miR-320d inhibited DLBCL cell proliferation, wheareas knockdown of miR-146b-5p or miR-320d promoted proliferation of DLBCL cells. Taken together, these results suggest that low expression of miR-146b-5p and miR-320d may be predictive of compromised responses of a subset of DLBCL patients to treatment with the CHOP regimen and that restoration of these miRs may be useful to improve the therapeutic efficacy of CHOP.
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Prevention of cell death by antibodies selected from intracellular combinatorial libraries.
Chem. Biol.
PUBLISHED: 01-16-2014
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One of the most important phenotypes in biology is cell death. One way to probe the mechanism(s) of cell death is to select molecules that prevent it and learn how this was accomplished. Here, intracellular combinatorial antibody libraries were used to select antibodies that protected cells from killing by rhinovirus infection. These rare antibodies functioned by inhibiting the virus-encoded protease that is necessary for viral maturation. Snapshots of the selection process after each round could be obtained by deep sequencing the ever-enriching populations. This detailed analysis of the enrichment process allowed an interesting look at a "test tube" selection process that pitted two replicating systems against each other. Thus, initially a minority of cells containing protective antibodies must compete against a majority of unprotected cells that continue to produce large amounts of virus.
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Effects of acupuncture applied to sanyinjiao with different stimuli on uterine contraction and microcirculation in rats with dysmenorrhea of cold coagulation syndrome.
Evid Based Complement Alternat Med
PUBLISHED: 01-13-2014
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In this study, we try to evaluate the effects of acupuncture stimulation with different amounts at Sanyinjiao (SP6) on uterine contraction and uterus microcirculation in rats with dysmenorrhea of cold coagulation syndrome and to explore whether there is direct relativity between "De qi" and needle stimulus intensity. Diestrus female rats were randomly divided into 4 groups, including saline control group, model control group, "A" stimulus group (with strong stimulus), and "B" stimulus group (with weak stimulus). We found that dysmenorrhea rats of the cold coagulation syndrome present a high intensity in uterine tension and high contraction of microvascular diameter. Acupuncture applied with two different stimuli could relieve the symptoms, but, compared with "B" stimulus, "A" stimulus leads to better outcomes on reducing uterine contraction and increasing diameter of uterine microvascular; moreover, hand manipulation during needling mediates the curative effect on the microvascular diameter. Our finding indicates that using thick needles and deep insertion with hand manipulation are more effective and achieve desired level of "De qi" in dysmenorrhea rats.
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Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils.
Proteomics
PUBLISHED: 01-11-2014
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Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference.
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RIG-I modulates Src-mediated AKT activation to restrain leukemic stemness.
Mol. Cell
PUBLISHED: 01-09-2014
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Retinoic acid (RA)-inducible gene I (RIG-I) is highly upregulated and functionally implicated in the RA-induced maturation of acute myeloid leukemia (AML) blasts. However, the underlying mechanism and the biological relevance of RIG-I expression to the maintenance of leukemogenic potential are poorly understood. Here, we show that RIG-I, without priming by foreign RNA, inhibits the Src-facilitated activation of AKT-mTOR in AML cells. Moreover, in a group of primary human AML blasts, RIG-I reduction renders the Src family kinases hyperactive in promoting AKT activation. Mechanistically, a PxxP motif in RIG-I, upon the N-terminal CARDs' association with the Src SH1 domain, competes with the AKT PxxP motif for recognizing the Src SH3 domain. In accordance, mutating PxxP motif prevents Rig-I from inhibiting AKT activation, cytokine-stimulated myeloid progenitor proliferation, and in vivo repopulating capacity of leukemia cells. Collectively, our data suggest an antileukemia activity of RIG-I via competitively inhibiting Src/AKT association.
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Discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel gpr119 agonists.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-08-2014
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We describe the discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel agonists of GPR119. Previously described aniline 2 had suboptimal efficacy in signaling assays using cynomolgus monkey (cyno) GPR119 making evaluation of the target in preclinical models difficult. Replacement of the aniline ring with a tetrahydroquinoline ring constrained the rotation of the aniline C-N bond and gave compounds with increased efficacy on human and cyno receptors. Additional optimization led to the discovery of 10, which possesses higher free fraction in plasma and improved pharmacokinetic properties in rat and cyno compared to 2.
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Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-? in human lung adenocarcinoma A549 cells.
Molecules
PUBLISHED: 01-06-2014
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Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPAR? activation. Meanwhile, PPAR? is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPAR? activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPAR?. DNA binding activity of PPAR? was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPAR? antagonist GW9662. Our findings also showed that the expression of PPAR? was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPAR? was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPAR? activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPAR? synthesis.
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Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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The epithelial-to-mesenchymal transition (EMT) is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC). In our previous studies, we found that neuropilin-1 (NRP1) is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-?B) plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-?B activation.
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Transplanting supersites of HIV-1 vulnerability.
PLoS ONE
PUBLISHED: 01-01-2014
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One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env) of the human immunodeficiency virus type 1 (HIV-1) involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting) antibodies similar to the template collection of effective antibodies. Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER) on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2) on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3) on gp120. We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ? 25 Env residues, can be segregated into acceptor scaffolds away from the immune-evading capabilities of the rest of HIV-1 Env, thereby providing a means to focus the immune response on the scaffolded supersite.
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Role of Na+/Ca2+ exchanger (NCX) in modulating postovulatory aging of mouse and rat oocytes.
PLoS ONE
PUBLISHED: 01-01-2014
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We studied the role of the Na+/Ca2+ exchanger (NCX) in modulating oocyte postovulatory aging by observing changes in NCX contents and activities in aging mouse and rat oocytes. Whereas the NCX activity was measured by observing oocyte activation following culture with NCX inhibitor or activator, the NCX contents were determined by immunohistochemical quantification. Although NCX was active in freshly-ovulated rat oocytes recovered 13 h post hCG injection and in aged oocytes recovered 19 h post hCG in both species, it was not active in freshly-ovulated mouse oocytes. However, NCX became active when the freshly-ovulated mouse oocytes were activated with ethanol before culture. Measurement of cytoplasmic Ca2+ revealed Ca2+ increases always before NCX activation. Whereas levels of the reactive oxygen species (ROS) and the activation susceptibility increased, the density of NCX member 1 (NCX1) decreased significantly with oocyte aging in both species. While culture with H2O2 decreased the density of NCX1 significantly, culture with NaCl supplementation sustained the NCX1 density in mouse oocytes. It was concluded that (a) the NCX activity was involved in the modulation of oocyte aging and spontaneous activation; (b) ROS and Na+ regulated the NCX activity in aging oocytes by altering its density as well as functioning; and (c) cytoplasmic Ca2+ elevation was essential for NCX activation in the oocyte.
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Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC), and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin ?4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.
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[Theoretical study on nuclear magnetic resonance spectra of the four kinds of curcumin analogues].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 12-28-2013
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Abstract The structure of four kinds of curcumin analogues was optimized at the level of B3LYP/6-31G(d, p), under which the stability was verified by means of vibration analysis. Moreover, NMR spectra of urcumin analogues compounds were studied at the level of B3LYP/6-311G(d,p) by GIAO method. The results show that the structure of four kinds of compounds, a larger conjugated system, has good planarity. Because of introducing hydroxyl and methoxy, the compound-B/C/D-C3, C4 and compoud-A and compound-D-Cs have greater 8 value. delta value of compound-A-C4. C4 is relatively smaller, and delta value of C3 is relatively larger. In the conjugated carbonyl compounds, compared with the acetaldehyde delta value (201 ppm), carbonyl C13 delta value (183 ppm) decreases relatively, C(11, 15) (alpha-carbon) delta value(122 ppm) decreases relatively, and C(9, 17) (beta-carbon) delta value(145 ppm) increases relatively. Finally, the correlation between experimental delta value and theoretical delta value of the 1H NMR was analyzed through the linear regression method. Results show that they have good correlation, and the experimental values coincide with the theoretical values.
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[Cumulative analgesic effects of EA stimulation of sanyinjiao (SP 6) in primary dysmenorrhea patients: a multicenter randomized controlled clinical trial].
Zhen Ci Yan Jiu
PUBLISHED: 12-07-2013
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To compare the cumulative analgesic effect of electroacupuncture (EA) stimulation of Sanyinjiao (SP 6), Xuanzhong (GB 39) and non-acupoint for primary dysmenorrhea patients.
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[Ovarian function reconstruction by orthotopic transplantation of novel vitrification cryopreserved ovaries in chemotherapy-induced ovary damage rat model].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 11-28-2013
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To investigate the effects of ovarian tissue cryopreservation by needle immersed vitrification (NIV) method and subsequently orthotopic transplantation on ovarian function reconstruction in chemotherapy-induced ovary damage rat model.
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Non-frozen preservation protocols for mature mouse oocytes dramatically extend their developmental competence by reducing oxidative stress.
Mol. Hum. Reprod.
PUBLISHED: 11-26-2013
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The objective of this study was to test whether aging induces oxidative stress (OS) during oocyte preservation at different temperatures and whether the oocyte competence can be extended by antioxidant supplementation. The increase in activation susceptibility was efficiently prevented when oocytes were preserved at 37°C for 9 h in HCZB medium with 10.27 mM pyruvate and 10 µM ?-tocopherol, at 25°C for 30 h with 20.27 mM pyruvate, and at 15°C for 96 h and at 5°C for 48 h with 10.27 mM pyruvate. Satisfactory blastocyst development was achieved after oocyte preservation at 37°C for 9 h, at 25°C for 30 h, at 15°C for 48 h and at 5°C for 24 h using the above protocols but with cysteamine/cystine supplementation. Transfer of blastocysts obtained from the above protocols showed no difference in pregnancy outcome between newly ovulated and preserved oocytes. Because oocytes preserved at 15°C for 48 h were fertilized after a 6-h recovery culture, aging of ovulated mouse oocytes has been successfully prevented for 54 h. Assays for ROS and glutathione indicated that in vitro preservation caused marked OS in oocytes. In conclusion, marked OS was observed following in vitro preservation of mature oocytes at different temperatures. Whereas any protocol that reduced OS could inhibit activation susceptibility, only those protocols that decreased OS while increasing glutathione synthesis could sustain oocyte competence.
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[Progress of researches on specificity of acupoints in China in recent 10 years].
Zhen Ci Yan Jiu
PUBLISHED: 11-23-2013
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After searching for literature about the specificity of acupoints from China National Knowledge Infrastructure (CNKI) database (in Chinese) and MEDLINE (in English), published by Chinese scholars from June 2003 to June 2012, the authors made a systemic analysis on the retrieved papers. It was found that most Chinese scholars took a positive viewpoint about the specificity of acupoints in morphological structure, biophysical characters, pathological reactions, acupuncture stimulation-induced responses in different brain regions and therapeutic effects. However, the research methods and comprehensive analysis of abundant research results need being improved, and the conclusion should be validated extensively. Moreover, the research on the affecting factors of specificity of acupoints will be one of the major directions.
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[Doctor HUANG Shi-pings acupuncture with golden needles].
Zhongguo Zhen Jiu
PUBLISHED: 11-08-2013
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Taking Doctor HUANG Shi-ping as the representative, the school of Huangs golden needle is based on Chinese martial art. Golden needles are adopted as main tool. Attaching great importance on the combination of acupuncture and moxibustioin, it is also characterized with penetrating needling with long needles. Through the development of three generations, it once outshone other schools in the field of acupuncture, and became famous all over the world. It made great contribution to the development of the course of acupuncture. However, with the development of the history, the form of acupuncture education as well as apparatus were all undergone an unified reform. Therefore, Doctor HUANG Shi-pings acupuncture school be lost gradually.
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Discovery and optimization of N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamides as novel GPR119 agonists.
Bioorg. Med. Chem. Lett.
PUBLISHED: 10-26-2013
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The discovery and optimization of novel N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamide GPR119 agonists is described. Modification of the pyridylphthalimide motif of the molecule with R(1)=-Me and R(2)=-(i)Pr substituents, incorporated with a 6-fluoro substitution on the central phenyl ring offered a potent and metabolically stable tool compound 22.
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Direct Measurement of the Mn(II) Hydration State in Metal Complexes and Metalloproteins through (17)O NMR Line Widths.
J. Am. Chem. Soc.
PUBLISHED: 10-24-2013
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Here we describe a simple method to estimate the inner-sphere hydration state of the Mn(II) ion in coordination complexes and metalloproteins. The line width of bulk H2(17)O is measured in the presence and absence of Mn(II) as a function of temperature, and transverse (17)O relaxivities are calculated. It is demonstrated that the maximum (17)O relaxivity is directly proportional to the number of inner-sphere water ligands (q). Using a combination of literature data and experimental data for 12 Mn(II) complexes, we show that this method provides accurate estimates of q with an uncertainty of ±0.2 water molecules. The method can be implemented on commercial NMR spectrometers working at fields of 7 T and higher. The hydration number can be obtained for micromolar Mn(II) concentrations. We show that the technique can be extended to metalloproteins or complex:protein interactions. For example, Mn(II) binds to the multimetal binding site A on human serum albumin with two inner-sphere water ligands that undergo rapid exchange (1.06 × 10(8) s(-1) at 37 °C). The possibility of extending this technique to other metal ions such as Gd(III) is discussed.
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Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis.
Med. Oncol.
PUBLISHED: 10-13-2013
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The expression of survivin, an inhibitor of apoptosis can be seen in most tumors and is correlated with the angiogenic factor vascular endothelial growth factor (VEGF). But little is known about their contribution in small-cell lung cancer (SCLC). This study was designed to investigate the expression of survivin and VEGF in SCLC, and to explore their correlation with clinical-pathological feature and prognosis. Forty-five patients with pathological histology of SCLC were entered into this study. Forty-five cases of matched adjacent non-tumor samples and 10 samples of operated patients with benign lung tumor were also included as control. The expression of survivin and VEGF was detected by immunohistochemistry (IHC, SP). These two sets of data were processed and tested for correlation with major patients characteristics, and overall survival. The correlations between survivin and VEGF expressions and the clinical-pathological features were evaluated by chi-square test. The correlation between survivin and VEGF expressions was analyzed by Spearmans rank correlation test; the overall survival was analyzed by the Kaplan-Meier method; and the relationship between clinical and pathological features and overall survival was analyzed by the Cox proportional hazard models. Positive expression rate of survivin and VEGF was significantly higher in SCLC than those of adjacent non-tumor tissues and benign lung tumor tissues (73.3 vs. 15.6 vs. 0 %, P < 0.05) and (75.6 vs. 20 vs. 0 %, P < 0.05), respectively. Survivin and VEGF expressions were significantly associated with lymph node metastasis (P = 0.003, 0.011) and clinical stage (P = 0.006, 0.021). The expression of survivin was significantly coincident with the expression of VEGF (r = 0.644, P = 0.000). The median overall survival in survivin positive group and VEGF positive group was significantly shorter than those in survivin negative and VEGF negative group, respectively (log-rank P = 0.000). Moreover, multivariate analysis showed that survivin expression (HR 0.224; 95 % CI 0.074-0.675; P = 0.008) and VEGF expression (HR 0.172; 95 % CI 0.054-0.559; P = 0.003) were statistically independent predictive factors of poorer prognosis for SCLC patients. Our results indicated that survivin and VEGF were over-expressed in small-cell lung cancer, each of them may be an independent poor prognostic factor.
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De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-08-2013
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Next-generation sequencing of antibody transcripts provides a wealth of data, but the ability to identify function-specific antibodies solely on the basis of sequence has remained elusive. We previously characterized the VRC01 class of antibodies, which target the CD4-binding site on gp120, appear in multiple donors, and broadly neutralize HIV-1. Antibodies of this class have developmental commonalities, but typically share only ?50% amino acid sequence identity among different donors. Here we apply next-generation sequencing to identify VRC01 class antibodies in a new donor, C38, directly from B cell transcript sequences. We first tested a lineage rank approach, but this was unsuccessful, likely because VRC01 class antibody sequences were not highly prevalent in this donor. We next identified VRC01 class heavy chains through a phylogenetic analysis that included thousands of sequences from C38 and a few known VRC01 class sequences from other donors. This "cross-donor analysis" yielded heavy chains with little sequence homology to previously identified VRC01 class heavy chains. Nonetheless, when reconstituted with the light chain from VRC01, half of the heavy chain chimeric antibodies showed substantial neutralization potency and breadth. We then identified VRC01 class light chains through a five-amino-acid sequence motif necessary for VRC01 light chain recognition. From over a million light chain sequences, we identified 13 candidate VRC01 class members. Pairing of these light chains with the phylogenetically identified C38 heavy chains yielded functional antibodies that effectively neutralized HIV-1. Bioinformatics analysis can thus directly identify functional HIV-1-neutralizing antibodies of the VRC01 class from a sequenced antibody repertoire.
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Genome-wide association study on serum alkaline phosphatase levels in a Chinese population.
BMC Genomics
PUBLISHED: 09-24-2013
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Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated.
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Urothelial differentiation of human umbilical cord-derived mesenchymal stromal cells in vitro.
Anal Cell Pathol (Amst)
PUBLISHED: 09-14-2013
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Human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) are the most primitive of those isolated from other post-natal tissue source. The hUCMSCs possess the capability of differentiating along multi-lineage. This study aimed to investigate whether hUCMSCs can differentiate into urothelium-like cells. The hUCMSCs were isolated from fresh human umbilical cord postpartum and expanded at least to passage 3 in vitro. Subsequently, they were cultured with conditioned medium from urothelial cells (UC-CM) supplemented with 20 ng/ml exogenous epidermal growth factor (EGF). Urothelial cell specific marker uroplakin II (UPII) and cytokeratins were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence technology. During culture, hUCMSCs started to express UPII and cytokeratins weakly at 7 days and were significantly up-regulated at 2 weeks post-induction. Additionally, morphology of hUCMSCs changed from spindle-shape to a polygonal epithelial-shape similar to that of urothelial cells after 7 days. The study results indicated that hUCMSCs can differentiate into urothelium-like cells in a defined micro-environment in vitro constituted by UC-CM and exogenous EGF.
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Herbal medicines for fatty liver diseases.
Cochrane Database Syst Rev
PUBLISHED: 08-27-2013
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Fatty liver disease is potentially a reversible condition that may lead to end-stage liver disease. Since herbal medicines such as Crataegus pinnatifida and Salvia miltiorrhiza have increasingly been used in the management of fatty liver disease, a systematic review on herbal medicine for fatty liver disease is needed.
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[Progress on research of specificity of acupoint effects during "the 11th five-year"].
Zhongguo Zhen Jiu
PUBLISHED: 08-24-2013
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With retrieval in CNKI and MEDLINE data base, the articles in Chinese and English that were written by Chinese authors, which were about the specificity of acupoint effects during "the Eleventh Five-Year (2006-2010)", are included. Researchers have studied about the specificity of acupoint effects by cerebral function imaging technique and it turns out that from the perspective of central mechanism, there are differences among aupoint stimulatory effect. The curative effect of acupoints is significantly better than that of nonacupoints, different acupoints have different curative effects, the effect of disease-related acupoints is better than that of unrelated acupoints, those above have intitally proved the existence of specificity of acupoint effects. However, part of the research results need futher summaries, analysis and promotion as well as try to avoid low-level repeat in research design.
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[Briefing on the 61st academic conference of Japanese Acupuncture Association].
Zhongguo Zhen Jiu
PUBLISHED: 08-24-2013
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The main content of the 61st Academic Conference of Japanese Acupuncture Association is introduced and summarized in this article. Different from former conferences, it focuses on the academic activity which take patient into the major consideration, and on the feasibility study of aerospace acupuncture treatment. Meanwhile, study on Japanese technique of shallow insertion with fine needle and its results are also introduced. The developing tendency of Japanese Acupuncture Association is discussed at the meeting as well.
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A Rapid Automatic Processing Platform for Bead Label-Assisted Microarray Analysis: Application for Genetic Hearing-Loss Mutation Detection.
J Lab Autom
PUBLISHED: 08-23-2013
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Molecular diagnostics using microarrays are increasingly being used in clinical diagnosis because of their high throughput, sensitivity, and accuracy. However, standard microarray processing takes several hours and involves manual steps during hybridization, slide clean up, and imaging. Here we describe the development of an integrated platform that automates these individual steps as well as significantly shortens the processing time and improves reproducibility. The platform integrates such key elements as a microfluidic chip, flow control system, temperature control system, imaging system, and automated analysis of clinical results. Bead labeling of microarray signals required a simple imaging system and allowed continuous monitoring of the microarray processing. To demonstrate utility, the automated platform was used to genotype hereditary hearing-loss gene mutations. Compared with conventional microarray processing procedures, the platform increases the efficiency and reproducibility of hybridization, speeding microarray processing through to result analysis. The platform also continuously monitors the microarray signals, which can be used to facilitate optimization of microarray processing conditions. In addition, the modular design of the platform lends itself to development of simultaneous processing of multiple microfluidic chips. We believe the novel features of the platform will benefit its use in clinical settings in which fast, low-complexity molecular genetic testing is required.
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[Discussion on the influence of factors related organic on Deqi in acupuncture treatment].
Zhongguo Zhen Jiu
PUBLISHED: 07-04-2013
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To discuss the influence of factors related organic on deqi in acupuncture treatment and provide scientific evidence for further research on the influencing factors of deqi sensation.
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[Review of studies on Deqi of acupuncture mainly in foreign countries].
Zhen Ci Yan Jiu
PUBLISHED: 07-04-2013
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Deqi (needle sensation), is closely related to clinical therapeutic effect of acupuncture in the treatment of different clinical conditions. In the present paper, the authors summarized various components or concepts of Deqi mainly in the foreign studies collected from Pubmed database. At present, foreign researches about Deqi mainly include 1) the subjects subjective qualitative and quantitative descriptions about Deqi, 2) correlation between acupuncture stimulation induced Deqi and clinical therapeutic effects, and 3) responses of different brain regions or the connectivity of brain network shown by functional magnetic resonance imaging (fMRI) during Deqi by needling different acupoints. According to the current commonly used 6 questionnaires, aching, tingling, numbness, heaviness, dull pain, throbbing, and deep pressure sensation are the most frequently seen components of Deqi of acupuncture stimulation. The factors influencing Deqi are psychological state, personal previous experience and cultural background. Regarding the degree of Deqi and clinical effects or outcomes, the conclusions are controversial.
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[Influence of electroacupuncture stimulation of delivery-facilitating acupoints with different stimulating parameters on serum endocrine hormones of late-stage pregnant rats].
Zhen Ci Yan Jiu
PUBLISHED: 07-04-2013
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To observe the influence of electroacupuncture (EA) stimulation of "Hegu" (LI 4) and "Sanyinjiao"(SP 6; a classical delivery-facilitating acupoint recipe) at different parameters on endocrine hormone levels of late-stage pregnant rats, so as to find the better stimulation parameters for delivery facilitation.
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Polaritonic solitons in a Bose-Einstein condensate trapped in a soft optical lattice.
Phys. Rev. Lett.
PUBLISHED: 06-17-2013
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We investigate the ground state (GS) of a collisionless Bose-Einstein condensate (BEC) trapped in a soft one-dimensional optical lattice (OL), which is formed by two counterpropagating optical beams perturbed by the BEC density profile through the local-field effect (LFE). We show that LFE gives rise to an envelope-deformation potential, a nonlocal potential resulting from the phase deformation, and an effective self-interaction of the condensate. As a result, stable photon-atomic (polaritonic) lattice solitons, including an optical component, in the form of the deformation of the soft OL, in a combination with a localized matter-wave component, are generated in the blue-detuned setting, without any direct interaction between atoms. These self-trapped modes, which realize the systems GS, are essentially different from the gap solitons supported by the interplay of the OL potential and collisional interactions between atoms. A transition to tightly bound modes from loosely bound ones occurs with the increase of the number of atoms in the BEC.
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Treating cloned embryos, but not donor cells, with 5-aza-2-deoxycytidine enhances the developmental competence of porcine cloned embryos.
J. Reprod. Dev.
PUBLISHED: 06-10-2013
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The efficiency of cloning by somatic cell nuclear transfer (SCNT) has remained low. In most cloned embryos, epigenetic reprogramming is incomplete, and usually the genome is hypermethylated. The DNA methylation inhibitor 5-aza-2-deoxycytidine (5-aza-dC) could improve the developmental competence of cow, pig, cat and human SCNT embryos in previous studies. However, the parameters of 5-aza-dC treatment among species are different, and whether 5-aza-dC could enhance the developmental competence of porcine cloned embryos has still not been well studied. Therefore, in this study, we treated porcine fetal fibroblasts (PFF) that then were used as donor nuclei for nuclear transfer or fibroblast-derived reconstructed embryos with 5-aza-dC, and the concentration- and time-dependent effects of 5-aza-dC on porcine cloned embryos were investigated by assessing pseudo-pronucleus formation, developmental potential and pluripotent gene expression of these reconstructed embryos. Our results showed that 5-aza-dC significantly reduced the DNA methylation level in PFF (0 nM vs. 10 nM vs. 25 nM vs. 50 nM, 58.70% vs. 37.37% vs. 45.43% vs. 39.53%, P<0.05), but did not improve the blastocyst rate of cloned embryos derived from these cells. Treating cloned embryos with 25 nM 5-aza-dC for 24 h significantly enhanced the blastocyst rate compared with that of the untreated group. Furthermore, treating cloned embryos, but not donor cells, significantly promoted pseudo-pronucleus formation at 4 h post activation (51% for cloned embryos treated, 34% for donor cells treated and 36% for control, respectively, P<0.05) and enhanced the expression levels of pluripotent genes (Oct4, Nanog and Sox2) up to those of in vitro fertilized embryos during embryo development. In conclusion, treating cloned embryos, but not donor cells, with 5-aza-dC enhanced the developmental competence of porcine cloned embryos by promotion of pseudo-pronucleus formation and improvement of pluripotent gene expression.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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