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Find video protocols related to scientific articles indexed in Pubmed.
Physiological Characterization of the Chronic Bronchitis Phenotype in GOLD Grade 1B COPD.
Chest
PUBLISHED: 11-14-2014
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Smokers with persistent cough and sputum production [chronic bronchitis (CB)] represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiological impairment, dyspnea and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We therefore compared physiological abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction.
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A highly selective long-wavelength fluorescent probe for the detection of human carboxylesterase 2 and its biomedical applications.
Chem. Commun. (Camb.)
PUBLISHED: 10-11-2014
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A highly selective long-wavelength fluorescent probe TCFB has been developed for the detection of hCE2. The probe can be used for real-time monitoring of hCE2 activity in complex biological systems.
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Evaluation of post-traumatic anosmia with MRI and chemosensory ERPs.
Eur Arch Otorhinolaryngol
PUBLISHED: 09-25-2014
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Magnetic resonance imaging (MRI) and chemosensory event-related potentials (ERPs) are important methods to evaluate olfactory function, but there is lack of study to explore the application of MRI and chemosensory ERPs in the patients with traumatic anosmia. The data of 26 post-traumatic anosmic patients and 21 healthy controls were retrospectively surveyed; olfaction and olfactory pathway of all participants were measured clinically using the T&T olfactometer, the Sniffin' Sticks, chemosensory ERPs and MRI. All patients were anosmic based on complaints and clinical examinations. In five patients, the olfactory bulb volume was significantly lower than control group. In 18 patients, the olfactory sulcus (OS) depth was similar to control group, but all the participants had a deeper right OS (right = 7.79 ± 1.31, left = 7.06 ± 1.44, p < 0.01). Olfactory ERPs (oERPs) could be evoked in 17 patients, but these signals showed longer latencies and lower amplitude than controls in the N1 (latency p < 0.05, amplitude p < 0.01) and P2 (latency p < 0.01, amplitude p < 0.05) waves. Nine traumatic anosmic patients had no identifiable oERPs; most of them had olfactory center injury. Trigeminal ERPs were detected in all anosmic patients and controls; patients had longer latencies for N1 (p < 0.05) and P2 (p < 0.05) waves, while there was no similar change in amplitude. Older subjects had smaller OB volume and OS depth. Closed head injury could induce anosmia; the severity extent, injury site and subsequent consciousness are related to the olfaction. oERP is the gold standard for olfactory subjective examination; MRI could indicate the lesions on the olfactory pathway and reflect the possibility of detectable oERPs.
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Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-19-2014
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Context and Objective: Oxytocin can affect energy homeostasis and has interesting potential as a metabolic disease therapeutic. We detected serum oxytocin levels in obese and type 2 diabetes mellitus (T2DM) subjects and investigated the relationships between serum oxytocin levels and glycolipid metabolism, insulin resistance, pancreatic ?-cell function and inflammation. Patients and Methods: A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes(T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were divided into normal weight(NW) and obese(OB) subgroups separately. We analysed the concentrations of oxytocin by ELISA. OGTT, HbA1c, blood lipids and highly sensitive C-reactive protein(hs-CRP) were also detected. Insulin resistance and pancreas ? cell function were assessed by homeostasis model assessment(HOMA-IR, HOMA-?). Results: Serum oxytocin levels were lower in T2DM group than in NGT group (P<0.01). The levels of serum oxytocin in subjects with obesity were also lower than those in subjects with NW (P<0.01). Serum oxytocin levels were negatively correlated with BMI, WC, WHR, HbA1c, FPG, 2hPG, FINS, 2hINS, TC, TG, LDL-C, HOMA-IR and hs-CRP, while positively correlated with HOMA-?(P<0.05). Multiple stepwise regression analysis showed that 2hPG, BMI and TC were associated with serum oxytocin levels(P<0.05). Logistic regression analyses demonstrated that serum oxytocin was significantly associated with type 2 diabetes(P<0.01). Conclusions: Serum oxytocin levels were decreased in subjects with type 2 diabetes as well as in obesity.
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Species-associated differences in the inhibition of propofol glucuronidation by magnolol.
J. Am. Assoc. Lab. Anim. Sci.
PUBLISHED: 09-09-2014
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Magnolol, a major active constituent in herbal medicine, potently inhibits propofol glucuronidation in human liver microsomes, with inhibition constants in the nanomolar range. This study was conducted to investigate magnolol-induced inhibition of propofol glucuronidation in liver microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques. Results indicated that magnolol (10 ?M) inhibited propofol glucuronidation in liver microsomes from Bama pigs and cynomolgus macaques but not in those from mice or rats. Data from liver microsomes from Bama pigs indicated a competitive inhibition mechanism, with a Ki of 1.7 ?M. In contrast to that of pig liver microsomes, the inhibition of microsomes from cynomolgus macaques followed a noncompetitive mechanism, with a Ki of 3.4 ?M. In summary, this study indicates that magnolol-induced inhibition of propofol glucuronidation varies substantially among species, and the Ki values determined by using liver microsomes from various experimental animal species far exceed that for human liver microsomes. The inhibition of propofol glucuronidation by magnolol in liver microsomes from all animal species tested was significantly lower than the inhibition previously demonstrated in human liver microsomes. Hepatic microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques are not effective models of the inhibition of glucuronidation induced by magnolol in humans.
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Franck-Condon factors perturbed by damped harmonic oscillators: solvent enhanced X (1)Ag ? A(1)B1u absorption and fluorescence spectra of perylene.
J Chem Phys
PUBLISHED: 09-01-2014
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Damped harmonic oscillators are utilized to calculate Franck-Condon factors within displaced harmonic oscillator approximation. This is practically done by scaling unperturbed Hessian matrix that represents local modes of force constants for molecule in gaseous phase, and then by diagonalizing perturbed Hessian matrix it results in direct modification of Huang-Rhys factors which represent normal modes of solute molecule perturbed by solvent environment. Scaling parameters are empirically introduced for simulating absorption and fluorescence spectra of an isolated solute molecule in solution. The present method is especially useful for simulating vibronic spectra of polycyclic aromatic hydrocarbon molecules in which hydrogen atom vibrations in solution can be scaled equally, namely the same scaling factor being applied to all hydrogen atoms in polycyclic aromatic hydrocarbons. The present method is demonstrated in simulating solvent enhanced X (1)Ag ? A(1)B1u absorption and fluorescence spectra of perylene (medium-sized polycyclic aromatic hydrocarbon) in benzene solution. It is found that one of six active normal modes v10 is actually responsible to the solvent enhancement of spectra observed in experiment. Simulations from all functionals (TD) B3LYP, (TD) B3LYP35, (TD) B3LYP50, and (TD) B3LYP100 draw the same conclusion. Hence, the present method is able to adequately reproduce experimental absorption and fluorescence spectra in both gas and solution phases.
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Cloning and characterization of a novel Nicotiana tabacum ABC transporter involved in shoot branching.
Physiol Plant
PUBLISHED: 08-29-2014
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The ATP-binding cassette (ABC) superfamily is a large protein family with diverse physiological functions in all kingdoms of life. One distinguished subfamily, the pleiotropic drug resistance (PDR) transporters, has only been identified in plants and fungi. Here, we identified a Nicotiana tabacum PDR gene, NtPDR6, which is a homolog of Petunia hybrida PDR1. The full-length cDNA of NtPDR6 had a 4482-bp open reading frame encoding a full-size ABC transporter with 1493 amino acids. Sequence comparison showed that NtPDR6 had high homology with plant PDR proteins. NtPDR6 was strongly induced by phosphate starvation as well as by 1-naphthalene acetic acid. Tissue expression pattern analysis showed that NtPDR6 was detected in all surveyed tissues but preferentially in roots. We cloned the 1.3-kb NtPDR6 promoter and found that there was one phosphate starvation response-related element Pho-like and several root-specific expression-related elements rootmotiftapox1 in the NtPDR6 promoter. A tissue-specific pattern of NtPDR6 promoter-?-glucuronidase expression was dominantly observed in subepidermal cells and the elongation zone of lateral roots. RNA interference technology was used to knock down NtPDR6 expression, and there was a significantly increased branching phenotype in the NtPDR6 knockdown plants. These data suggest that NtPDR6 plays a key role in regulation of shoot branching processes.
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A Phase II, Open-Label Study of Ramucirumab in Combination with Paclitaxel and Carboplatin as First-Line Therapy in Patients with Stage IIIB/IV Non-Small-Cell Lung Cancer.
J Thorac Oncol
PUBLISHED: 08-28-2014
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The objective of this study was to determine whether the addition of ramucirumab to first-line paclitaxel-carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) resulted in a 6-month progression-free survival (PFS) rate that compares favorably with the historic rate for bevacizumab combined with paclitaxel-carboplatin in this patient population.
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Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing.
Fam. Cancer
PUBLISHED: 08-24-2014
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Hereditary cancers occur because of inherited gene mutations. Genetic testing has been approved to provide information for risk assessment and rationale for appropriate intervention. Testing methods currently available for clinical use have some limitations, including sensitivity and testing throughput, etc. Next generation sequencing (NGS) has been rapidly evolving to increase testing sensitivity and throughput. It can be potentially used to identify inherited mutation in clinical diagnostic setting. Here we develop an effective method employing target enrichment and NGS platform to detect common as well as rare mutations for all common hereditary cancers in a single assay. Single base substitution across 115 hereditary cancer related genes using YH (the first Asian genome) was characterized to validate our method. Sensitivity, specificity and accuracy of 93.66, 99.98 and 99.97 %, were achieved, respectively. In addition, we correctly identified 53 SNVs and indels of BRCA1 and BRCA2 in two breast cancer specimens, all confirmed by Sanger sequencing. Accuracy in detecting copy number variation (CNV) was corroborated in 4 breast cancer specimens with known CNVs in BRAC1. Application of the method to 85 clinical cases revealed 22 deleterious mutations, 11 of which were novel. In summary, our studies demonstrate that the target enrichment combined with NGS method provides the accuracy, sensitivity, and high throughput for genetic testing for patients with high risk of hereditary or familial cancer.
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Melatonin suppresses hypoxia-induced migration of HUVECs via inhibition of ERK/Rac1 activation.
Int J Mol Sci
PUBLISHED: 08-13-2014
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Melatonin, a naturally-occurring hormone, possesses antioxidant properties and ameliorates vascular endothelial dysfunction. In this study, we evaluate the impact of melatonin on the migratory capability of human umbilical vein endothelial cells (HUVECs) to hypoxia and further investigate whether ERK/Rac1 signaling is involved in this process. Here, we found that melatonin inhibited hypoxia-stimulated hypoxia-inducible factor-1? (HIF-1?) expression and cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF-1? expression and cell migration in response to hypoxia, as well, but constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1? expression, preventing the inhibition of melatonin on cell migration. Furthermore, the anti-Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken together, our work indicates that melatonin exerts an anti-migratory effect on hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1? upregulation.
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An intensity ratio of interlocking loops determines circadian period length.
Nucleic Acids Res.
PUBLISHED: 08-13-2014
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Circadian clocks allow organisms to orchestrate the daily rhythms in physiology and behaviors, and disruption of circadian rhythmicity can profoundly affect fitness. The mammalian circadian oscillator consists of a negative primary feedback loop and is associated with some 'auxiliary' loops. This raises the questions of how these interlocking loops coordinate to regulate the period and maintain its robustness. Here, we focused on the REV-ERB?/Cry1 auxiliary loop, consisting of Rev-Erb?/ROR-binding elements (RORE) mediated Cry1 transcription, coordinates with the negative primary feedback loop to modulate the mammalian circadian period. The silicon simulation revealed an unexpected rule: the intensity ratio of the primary loop to the auxiliary loop is inversely related to the period length, even when post-translational feedback is fixed. Then we measured the mRNA levels from two loops in 10-mutant mice and observed the similar monotonic relationship. Additionally, our simulation and the experimental results in human osteosarcoma cells suggest that a coupling effect between the numerator and denominator of this intensity ratio ensures the robustness of circadian period and, therefore, provides an efficient means of correcting circadian disorders. This ratio rule highlights the contribution of the transcriptional architecture to the period dynamics and might be helpful in the construction of synthetic oscillators.
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Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in two large Chinese families with autosomal dominant hearing loss.
PLoS ONE
PUBLISHED: 08-12-2014
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Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness.
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resistome analysis of Enterobacter cloacae CY01, an extensively drug-resistant strain producing VIM-1 metallo-?-lactamase from China.
Antimicrob. Agents Chemother.
PUBLISHED: 08-11-2014
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Resistome analysis of clinical VIM-1-producing Enterobacter cloacae strain CY01 from China revealed the presence of multiple resistance determinants. Two resistance plasmids were identified in CY01. The pCY-VIM plasmid was 14 kb in size and possessed a replicase gene (repA), a gene cluster encoding the partitioning function (parABC), and a carbapenemase gene (blaVIM-1). Another 5.9-kb plasmid, pCY-MdT, with an aac(6')-Ib gene, was very closely related (13 nucleotide differences) to pMdT1, a ColE1 plasmid carrying aac(6')-Ib-cr4.
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[Reconstruction of inferior alveolar nerve canal based on shape feature].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-22-2014
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It is difficult to distinguish the inferior alveolar nerve (IAN) from other tissues inside the IAN canal due to their similar CT values in the X image which are smaller than that of the bones. The direct reconstruction, therefore, is difficult to achieve the effects. The traditional clinical treatments mainly rely on doctors' manually drawing the X images so that some subjective results could not be avoided. This paper proposes the partition reconstruction of IAN canal based on shape features. According to the anatomical features of the IAN canal, we divided the image into three parts and treated the three parts differently. For the first, the directly part of the mandibular, we used Shape-driven Level-set Algorithm Restrained by Local Information (BSLARLI) segment IAN canal. For the second part, the mandibular body, we used Space B-spline curve fitting IAN canal's center, then along the center curve established the cross section. And for the third part, the mental foramen, we used an adaptive threshold Canny algorithm to extract IAN canal's edge to find center curve, and then along it established the cross section similarly. Finally we used the Visualization Toolkit (VTK) to reconstruct the CT data as mentioned above. The VTK reconstruction result by setting a different opacity and color values of tissues CT data can perspectively display the INA canal clearly. The reconstruction result by using this method is smoother than that using the segmentation results and the anatomical structure of mental foramen position is similar to the real tissues, so it provides an effective method for locating the spatial position of the IAN canal for implant surgeries.
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Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients.
Diabetes Care
PUBLISHED: 07-14-2014
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Betatrophin, a newly identified hormone, has been recently characterized as a potent stimulator that increases the production and expansion of insulin-secreting ?-cells in mice, but the physiological role of betatrophin remains poorly understood. This study measured for the first time serum betatrophin levels in newly diagnosed patients with type 2 diabetes (T2DM) and explored the correlations between its serum levels and various metabolic parameters in T2DM.
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Microwave irradiation induced changes in protein molecular structures of barley grains: relationship to changes in protein chemical profile, protein subfractions, and digestion in dairy cows.
J. Agric. Food Chem.
PUBLISHED: 07-02-2014
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The objectives of this study were to evaluate microwave irradiation (MIR) induced changes in crude protein (CP) subfraction profiles, ruminal CP degradation characteristics and intestinal digestibility of rumen undegraded protein (RUP), and protein molecular structures in barley (Hordeum vulgare) grains. Samples from hulled (n = 1) and hulless cultivars (n = 2) of barley, harvested from four replicate plots in two consecutive years, were evaluated. The samples were either kept as raw or irradiated in a microwave for 3 min (MIR3) or 5 min (MIR5). Compared to raw grains, MIR5 decreased the contents of rapidly degradable CP subfraction (from 45.22 to 6.36% CP) and the ruminal degradation rate (from 8.16 to 3.53%/h) of potentially degradable subfraction. As a consequence, the effective ruminal degradability of CP decreased (from 55.70 to 34.08% CP) and RUP supply (from 43.31 to 65.92% CP) to the postruminal tract increased. The MIR decreased the spectral intensities of amide 1, amide II, ?-helix, and ?-sheet and increased their ratios. The changes in protein spectral intensities were strongly correlated with the changes in CP subfractions and digestive kinetics. These results show that MIR for a short period (5 min) with a lower energy input can improve the nutritive value and utilization of CP in barely grains.
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[Effects of airborne fine particulate matters on pulmonary inflammation injury and Th17/Treg balance of sub-chronic exposure mice].
Wei Sheng Yan Jiu
PUBLISHED: 06-27-2014
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To explore effects of fine particulate matters (PM 2.5) onpulmonary inflammation, and the changes of Th17/Treg balance as well as related cytokines.
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Cytotoxic and anti-inflammatory prenylated benzoylphloroglucinols and xanthones from the twigs of Garcinia esculenta.
J. Nat. Prod.
PUBLISHED: 06-24-2014
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Five new prenylated benzoylphloroglucinol derivatives, garciesculentones A-E (1-5), a new xanthone, garciesculenxanthone A (6), and 15 known compounds were isolated from the petroleum ether extract and the EtOAc-soluble fraction of a 80% (v/v) EtOH extract of Garcinia esculenta. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analysis and mass spectrometry. Experimental and calculated ECD and a convenient modified Mosher's method were used to determine the absolute configurations. The cytotoxicity of these compounds were evaluated by MTT assay against three human cancer cell lines (HepG2, MCF-7, and MDA-MB-231) and against normal hepatic cells (HL-7702). In addition, these isolates were evaluated for their inhibitory effects on interferon-? plus lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.
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Single-base-resolution methylomes of Populus trichocarpa reveal the association between DNA methylation and drought stress.
BMC Genet.
PUBLISHED: 06-20-2014
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DNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses.
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Regioselective Glucuronidation of Andrographolide and Its Major Derivatives: Metabolite Identification, Isozyme Contribution, and Species Differences.
AAPS J
PUBLISHED: 06-17-2014
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Andrographolide (AND) and two of its derivatives, deoxyandrographolide (DEO) and dehydroandrographolide (DEH), are widely used in clinical practice as anti-inflammatory agents. However, UDP-glucuronosyltransferase (UGT)-mediated phase II metabolism of these compounds is not fully understood. In this study, glucuronidation of AND, DEO, and DEH was characterized using liver microsomes and recombinant UGT enzymes. We isolated six glucuronides and identified them using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. We also systematically analyzed various kinetic parameters (K m, V max, and CLint) for glucuronidation of AND, DEO, and DEH. Among 12 commercially available UGT enzymes, UGT1A3, 1A4, 2B4, and 2B7 exhibited metabolic activities toward AND, DEO, and DEH. Further, UGT2B7 made the greatest contribution to glucuronidation of all three anti-inflammatory agents. Regioselective glucuronidation showed considerable species differences. 19-O-Glucuronides were present in liver microsomes from all species except rats. 3-O-Glucuronides were produced by pig and cynomolgus monkey liver microsomes for all compounds, and 3-O-glucuronide of DEH was detected in mouse and rat liver microsomes (RLM). Variations in K m values were 48.6-fold (1.93-93.6 ?M) and 49.5-fold (2.01-99.1 ?M) for 19-O-glucuronide and 3-O-glucuronide formation, respectively. Total intrinsic clearances (CLint) for 3-O- and 19-O-glucuronidation varied 4.8-fold (22.7-110 ?L min(-1) mg(-1)), 10.6-fold (94.2-991 ?L min(-1) mg(-1)), and 8.3-fold (122-1,010 ?L min(-1) mg(-1)), for AND, DEH, and DEO, respectively. Our results indicate that UGT2B7 is the major UGT enzyme involved in the metabolism of AND, DEO, and DEH. Metabolic pathways in the glucuronidation of AND, DEO, and DEH showed considerable species differences.
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[Study on gene-gene, gene-environmental interactions of DNA repair genes related with age-related cataract].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 06-14-2014
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To investigate the interaction between polymorphisms and environment factors in age related cataract (ARC).
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In vitro glucuronidation of Armillarisin A: UDP-glucuronosyltransferase 1A9 acts as a major contributor and significant species differences.
Xenobiotica
PUBLISHED: 06-11-2014
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Abstract 1. This study is performed to investigate liver microsomal glucuronidation of Armillarisin A (A.A), an effective cholagogue drug, aiming at characterizing the involved UDP-glucuronosyltranferases (UGT) and revealing potential species differences. 2. A.A glucuronidation in human liver microsomes (HLM) generates one metabolite (M2) glucuronidated at the phenol hydroxyl group, obeying Michaelis-Menten kinetic model. Multiple isoforms including UGT1A1, 1A7, 1A9 and 2B15 can catalyze A.A glucuronidation. Kinetic assays and chemical inhibition studies both demonstrate that UGT1A9 is responsible for A.A glucuronidation in HLM. A.A glucuronidation in Cynomolgus monkey microsomes (CyLM) also follows Michaelis-Menten model, but can additionally catalyze the traced glucuronosyl substitution at the alcohol hydroxyl group (M1). The reactions in liver microsomes from Sprague-Dawley rats (RLM), ICR/CD-1 mouse (MLM), Beagle dog (DLM) all display biphasic kinetics and only M2 is detected. HLM, RLM and CyLM exhibit very similar catalytic activities towards A.A glucuronidation, with the intrinsic clearance values of respective 38, 37 and 37??L/min/mg, which are much higher than MLM and DLM. 3. This in vitro study indicates that UGT1A9 acts as a major contributor to A.A glucuronidation in human liver, and the reaction displays large species differences.
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Profiling the interaction mechanism of quinoline/quinazoline derivatives as MCHR1 antagonists: an in silico method.
Int J Mol Sci
PUBLISHED: 05-22-2014
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Melanin concentrating hormone receptor 1 (MCHR1), a crucial regulator of energy homeostasis involved in the control of feeding and energy metabolism, is a promising target for treatment of obesity. In the present work, the up-to-date largest set of 181 quinoline/quinazoline derivatives as MCHR1 antagonists was subjected to both ligand- and receptor-based three-dimensional quantitative structure-activity (3D-QSAR) analysis applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The optimal predictable CoMSIA model exhibited significant validity with the cross-validated correlation coefficient (Q²) = 0.509, non-cross-validated correlation coefficient (R²(ncv)) = 0.841 and the predicted correlation coefficient (R²(pred)) = 0.745. In addition, docking studies and molecular dynamics (MD) simulations were carried out for further elucidation of the binding modes of MCHR1 antagonists. MD simulations in both water and lipid bilayer systems were performed. We hope that the obtained models and information may help to provide an insight into the interaction mechanism of MCHR1 antagonists and facilitate the design and optimization of novel antagonists as anti-obesity agents.
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TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis.
J. Clin. Invest.
PUBLISHED: 05-22-2014
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The MAP kinase kinase kinase TGF?-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGF? and in turn activates IKK-NF-?B and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor ? (PPAR?) target genes and ?-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and ?-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPAR? target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPAR? activity.
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Effects of all?trans retinoic acid on VEGF and HIF?1? expression in glioma cells under normoxia and hypoxia and its anti?angiogenic effect in an intracerebral glioma model.
Mol Med Rep
PUBLISHED: 05-21-2014
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All?trans retinoic acid (ATRA) is one of the most potent inducers of differentiation and is capable of inducing differentiation and apoptosis in glioma cells. However, the effect of ATRA on glioma angiogenesis is yet to be elucidated. The present study investigated the effects of ATRA on the expression of vascular endothelial growth factor (VEGF) and hypoxia?inducible factor?1? (HIF?1?) in various glioma cell lines under normoxia and hypoxia. The effect of ATRA on angiogenesis in a rat intracerebral glioma model was also investigated, with the aim of revealing the effect of ATRA on glioma angiogenesis. In the present study, U?87 MG and SHG44 glioma cells were treated with ATRA at various concentrations (0, 5, 10, 20 and 40 µmol/l) under normoxia or hypoxia. Quantitative polymerase chain reaction and western blot analysis were used to investigate VEGF and HIF?1? mRNA and protein expression, respectively. An intracerebral glioma model was generated using intracerebral implantation of C6 glioma cells into rats. Tumor?bearing rats were treated with ATRA at different doses (0, 5 and 10 mg/kg/day) for two weeks, and immunohistochemical assays were performed to detect the cluster of differentiation 34?positive cells in order to evaluate the microvessel density (MVD) in each group. Following ATRA treatment, the expression of VEGF and HIF?1? was found to vary among the different concentration groups. In the glioma cells in the lower concentration groups (5 and 10 µmol/l ATRA), a significant increase in VEGF and HIF?1? expression was observed. Conversely, a significant decrease in VEGF and HIF?1? expression was found in the glioma cells in the high ATRA concentration group (40 µmol/l), compared with that in the cells in the control group. Furthermore, in the rat intracerebral glioma model, ATRA decreased glioma MVD, particularly in the high?dose group (10 mg/kg/day), compared with the control group. These results suggest that ATRA may exhibit a dose?dependent effect on glioma angiogenesis and may inhibit glioma angiogenesis in vivo.
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Development and validation of a new HPV genotyping assay based on next-generation sequencing.
Am. J. Clin. Pathol.
PUBLISHED: 05-20-2014
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We developed a new human papillomavirus (HPV) genotyping assay based on multiplex polymerase chain reaction and next-generation sequencing (NGS) methods for large-scale cervical cancer screening.
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Electronic cigarettes: incorporating human factors engineering into risk assessments.
Tob Control
PUBLISHED: 04-16-2014
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A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes.
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Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.
Dev. Biol.
PUBLISHED: 04-15-2014
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Congenital bony syngnathia, a rare but severe human birth defect, is characterized by bony fusion of the mandible to the maxilla. However, the genetic mechanisms underlying this birth defect are poorly understood, largely due to limitation of available animal models. Here we present evidence that transgenic expression of Bmp4 in neural crest cells causes a series of craniofacial malformations in mice, including a bony fusion between the maxilla and hypoplastic mandible, resembling the bony syngnathia syndrome in humans. In addition, the anterior portion of the palatal shelves emerged from the mandibular arch instead of the maxilla in the mutants. Gene expression assays showed an altered expression of several facial patterning genes, including Hand2, Dlx2, Msx1, Barx1, Foxc2 and Fgf8, in the maxillary and mandibular processes of the mutants, indicating mis-patterned cranial neural crest (CNC) derived cells in the facial region. However, despite of formation of cleft palate and ectopic cartilage, forced expression of a constitutively active form of BMP receptor-Ia (caBmprIa) in CNC lineage did not produce the syngnathia phenotype, suggesting a non-cell autonomous effect of the augmented BMP4 signaling. Our studies demonstrate that aberrant BMP4-mediated signaling in CNC cells leads to mis-patterned facial skeleton and congenital bony syngnathia, and suggest an implication of mutations in BMP signaling pathway in human bony syngnathia.
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A new clade of Asian late Cretaceous long-snouted tyrannosaurids.
Nat Commun
PUBLISHED: 04-01-2014
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The iconic tyrannosaurids were top predators in Asia and North America during the latest Cretaceous, and most species had deep skulls that allowed them to generate extreme bite forces. Two unusual specimens of Alioramus from Mongolia seem to indicate a divergent long-snouted body plan among some derived tyrannosaurids, but the rarity and juvenile nature of these fossils leaves many questions unanswered. Here, we describe a remarkable new species of long-snouted tyrannosaurid from the Maastrichtian of southeastern China, Qianzhousaurus sinensis. Phylogenetic analysis places Qianzhousaurus with both species of Alioramus in a novel longirostrine clade, which was geographically widespread across latest Cretaceous Asia and formed an important component of terrestrial ecosystems during this time. The new specimen is approximately twice the size as both Alioramus individuals, showing that the long-snouted morphology was not a transient juvenile condition of deep-snouted species, but a characteristic of a major tyrannosaurid subgroup.
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Visualizing the structural evolution of LSM/xYSZ composite cathodes for SOFC by in-situ neutron diffraction.
Sci Rep
PUBLISHED: 03-26-2014
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Thermal stability of composite cathodes for solid oxide fuel cells, the mixtures of (La0.8Sr0.2)0.95MnO(3-?) (LSM) and (Y2O3)(x)(ZrO2)(1-x) (xYSZ, x = 3, 6, 8 and 10), is determined using in-situ neutron diffraction. Thanks to the most advanced high flux neutron source, our work highlights the visualization of the phase evolutions in heterogeneous material systems at high temperatures, along with the analysis of the diffusion activities of transition metal ions that reveal the reaction mechanism and kinetics. It is found that the tetragonal-to-cubic phase transition in YSZ at T > 900°C leads to a heterogeneous redistribution of Mn ions. The subsequent reaction of LSM and YSZ occurring at T > 1100°C is revealed as a three-stage kinetic process, yielding La2Zr2O7, SrZrO3 and MnO. The diffusion activities of Y, Mn and La ions in the heterogeneous systems at elevated temperatures are derived by the structural analysis, and the three-stage reaction of YSZ and LSM is found strongly correlated to ions' behaviors as functions of temperature.
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PER1 phosphorylation specifies feeding rhythm in mice.
Cell Rep
PUBLISHED: 03-25-2014
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Organization of circadian behavior, physiology, and metabolism is important for human health. An S662G mutation in hPER2 has been linked to familial advanced sleep-phase syndrome (FASPS). Although the paralogous phosphorylation site S714 in PER1 is conserved in mice, its specific function in circadian organization remains unknown. Here, we find that the PER1S714G mutation accelerates the molecular feedback loop. Furthermore, hPER1S714G mice, but not hPER2S662G mice, exhibit peak time of food intake that is several hours before daily energy expenditure peaks. Both the advanced feeding behavior and the accelerated clock disrupt the phase of expression of several key metabolic regulators in the liver and adipose tissue. Consequently, hPER1S714G mice rapidly develop obesity on a high-fat diet. Our studies demonstrate that PER1 and PER2 are linked to different downstream pathways and that PER1 maintains coherence between the circadian clock and energy metabolism.
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Temporal trends of main reproductive characteristics in ten urban and rural regions of China: the China Kadoorie Biobank study of 300 000 women.
Int J Epidemiol
PUBLISHED: 03-17-2014
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Chinese women's reproductive patterns have changed significantly over the past several decades. However, relatively little is known about the pace and characteristics of these changes either overall or by region and socioeconomic status.
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Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-?1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-?-induced NF-? B/Snail signaling pathway in human gastric adenocarcinoma.
BMC Complement Altern Med
PUBLISHED: 03-15-2014
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Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far.
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Safety and efficacy of sitagliptin in combination with transient continuous subcutaneous insulin infusion (CSII) therapy in patients with newly diagnosed type 2 diabetes.
Endocr. J.
PUBLISHED: 03-13-2014
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Sitagliptin was used as monotherapy or in combination with metformin, thiazolidinedione or sulfonylurea. It is not clear whether effects are enhanced or unique when in combination with transient continuous subcutaneous insulin infusion (CSII) therapy. The aim of this study was to assess the safety and efficacy of sitagliptin in combination with transient CSII therapy in patients with newly diagnosed type 2 diabetes. Eighty patients with newly diagnosed type 2 diabetes from July 2011 to May 2013 were recruited into the study. These patients were randomly divided into a CSII monotherapy group (group A, n = 40) or a sitagliptin in combination with CSII therapy group (group B, n = 40) and received insulin intensive therapy. Treatments were maintained for 2 weeks. 75g oral glucose tolerance test (OGTT) was performed before and after treatments, and the levels of glucose, insulin and C-peptide were examined. The results indicated that, compared with CSII therapy group, the level of plasma glucose significantly decreased, the levels of insulin and C-peptide strikingly increased and homeostasis model assessment for beta-cell function (HOMA-?) and Insulinogenic index (Ins index) were improved in the group of sitagliptin in combination with CSII therapy. Above all, the incidence of hypoglycemia was lower, insulin doses were less and the rate of recovery to normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) determined by 75gOGTT was higher in the latter. So, Sitagliptin in combination with CSII therapy can be a new safe and effective therapy in patients with newly diagnosed type 2diabetes.
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Immobilization of penicillin G acylase on paramagnetic aldehyde-functionalized mesostructured cellular foams.
Enzyme Microb. Technol.
PUBLISHED: 02-25-2014
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Paramagnetic aldehyde-functionalized mesostructured cellular foams (PAMCFs), synthesized by grafting 3-aminopropyltriethoxysilane modified Fe3O4 (NH2-Fe3O4) nanoparticles with larger particle size than the window pore size of MCFs on the outer surface of aldehyde-functionalized mesostructured cellular foams (AMCFs), were investigated as efficient supports for immobilization of penicillin G acylase (PGA). The results show that NH2-Fe3O4 nanoparticles were successfully grafted on the outer surface of AMCFs and PGA molecules were mainly immobilized covalently on the inner surface of PAMCFs, which was because amino groups of NH2-Fe3O4 nanoparticles or PGA molecules reacted with aldehyde groups of AMCFs or PAMCFs to form imine bonds. PGA/PAMCFs-15 showed a rather high initial activity of 9563Ug(-1) and retained 89.1% of its initial activity after recycled for 10 times. PGA/PAMCFs are easily recycled by magnetic field in order to replace tedious separation of high-speed centrifugation for mesoporous materials.
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Decreased PPAR-? expression in the conjunctiva and increased expression of TNF-? and IL-1? in the conjunctiva and tear fluid of dry eye mice.
Mol Med Rep
PUBLISHED: 02-25-2014
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The aim of this study was to investigate the expression of peroxisome proliferator-activated receptor ? (PPAR-?), tumor necrosis factor (TNF)-? and interleukin (IL)-1? in the conjunctiva and the association between inflammatory cytokines and PPAR-? in dry eye mice. Dry eye was induced in 6-week-old female C57 mice. mRNA expression of PPAR-?, TNF-? and IL-1? were measured. PPAR-? protein expression in the conjunctiva, and the contents of TNF-? and IL-1? in the conjunctiva and tear-wash fluid were determined. A PPAR-? agonist, pioglitazone (PIO), was used to treat dry eye mice. Dry eye mice presented with similar manifestations as in humans. The PPAR-? expression in the conjunctiva of dry eye mice was downregulated, accompanied by increased contents of TNF-? and IL-1?. PIO treatment markedly reduced the contents of TNF-? and IL-1? in tear fluid of dry eye mice. Following PIO treatment, the PPAR-? expression increased markedly. PIO may activate PPAR-? to inhibit the expression of the inflammatory cytokines TNF-? and IL-1? in dry eye mice. This suppresses the inflammatory progression, increases the tear fluid production, elevates the tear film stability and reduces the damage to the ocular surface, exerting a therapeutic effect on dry eye.
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Novel ruthenium complexes ligated with 4-anilinoquinazoline derivatives: synthesis, characterisation and preliminary evaluation of biological activity.
Eur J Med Chem
PUBLISHED: 02-24-2014
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The ruthenium DMSO complexes cis-Ru(II)C12(DMSO)4 and [(DMSO)2H][trans-Ru(III)Cl4(DMSO)2] reacted with 4-(3'-chloro-4'-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline (L1), 4-(3'-chloro-4'-fluoroanilino)-6-(2-(1H-imidazol-1-yl)ethoxy)-7-methoxy quinazoline (L2), N-(benzo[d]imidazol-4-yl)-6,7-dimethoxyquinazolin-4-amine hydrochloride (L3), 5-(6,7-dimethoxyquinazolin-4-ylamino)quinolin-8-ol hydrochloride (L4), respectively, to afford [Ru(II)Cl2(DMSO)2(L1)] (1), [Ru(III)Cl3(DMSO)(L1)] (2), [Ru(III)Cl4(DMSO)(H-L2)] (3), [Ru(III)Cl4(DMSO)(H-L3)] (4), and [Ru(III)Cl3(DMSO)(H-L4)] (5), which were characterised by mass spectrometry, NMR, elementary analysis and single crystal X-ray diffraction (complex 1). Experimental screening (ELISA) showed that complexes 1, 2 and 3 are remarkably inhibitory towards epidermal growth factor receptor (EGFR) with IC50 values at submicromolar or nanomolar level. Docking studies indicated that complexation with ruthenium has little interference with the formation of the two essential H-bonds between the N3 of the quinazoline ring in L1 and L2 and O-H of Thr766 through a water molecule, and the N1 of the quinazoline ring and N-H of Met769 in EGFR. Moreover, complex 2 was shown to be more active against the EGF-stimulated proliferation of human breast cancer cell line MCF-7 than the better EGFR inhibitor 4-(3'-chloro-4'-fluoroanilino)-6,7-dimethoxyquinazoline, being more potential to induce early-stage apoptosis than gefitinib. These imply that apart from inhibiting EGFR, complex 2 may involve in regulating other biological events related to the proliferation of MCF-7, implicating a novel type of multi-targeting metal-based anticancer agents.
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Event-related potentials reveal linguistic suppression effect but not enhancement effect on categorical perception of color.
Scand J Psychol
PUBLISHED: 02-03-2014
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The present study used the event-related potential technique to investigate the nature of linguistic effect on color perception. Four types of stimuli based on hue differences between a target color and a preceding color were used: zero hue step within-category color (0-WC); one hue step within-category color (1-WC); one hue step between-category color (1-BC); and two hue step between-category color (2-BC). The ERP results showed no significant effect of stimulus type in the 100-200 ms time window. However, in the 200-350 ms time window, ERP responses to 1-WC target color overlapped with that to 0-WC target color for right visual field (RVF) but not left visual field (LVF) presentation. For the 1-BC condition, ERP amplitudes were comparable in the two visual fields, both being significantly different from the 0-WC condition. The 2-BC condition showed the same pattern as the 1-BC condition. These results suggest that the categorical perception of color in RVF is due to linguistic suppression on within-category color discrimination but not between-category color enhancement, and that the effect is independent of early perceptual processes.
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Patterns and correlates of polytobacco use in the United States over a decade: NSDUH 2002-2011.
Addict Behav
PUBLISHED: 01-25-2014
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Few studies have examined the patterns and correlates of polytobacco use among a large, nationally representative population over an extended period of time.
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Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay.
Proteomics
PUBLISHED: 01-23-2014
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Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. Quantitative analysis of CYP expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. At present, chemical probe-based assay is the most widely used approach for the evaluation of CYP activity although there are cross-reactions between the isoforms with high sequence homologies. Therefore, quantification of each isozyme is highly desired in regard to meeting the ever-increasing requirements for carrying out pharmacokinetics and personalized medicine in the academic, pharmaceutical, and clinical setting. Herein, an absolute quantification method was employed for the analysis of the seven isoforms CYP1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1 using a proteome-derived approach in combination with stable isotope dilution assay. The average absolute amount measured from twelve human liver microsomes samples were 39.3, 4.3, 54.0, 4.6, 10.3, 3.0, and 9.3 (pmol/mg protein) for 1A2, 2B6, 3A4, 3A5, 2C9, 2C19, and 2E1, respectively. Importantly, the expression level of CYP3A4 showed high correlation (r = 0.943, p < 0.0001) with the functional activity, which was measured using bufalin-a highly selective chemical probe we have developed. The combination of MRM identification and analysis of the functional activity, as in the case of CYP3A4, provides a protocol which can be extended to other functional enzyme studies with wide application in pharmaceutical research.
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LIFR?-CT3 induces differentiation of a human acute myelogenous leukemia cell line HL-60 by suppressing miR-155 expression through the JAK/STAT pathway.
Leuk. Res.
PUBLISHED: 01-22-2014
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The distal cytoplasmic motifs of the leukemia inhibitory factor receptor ?-chain (LIFR?-CT3) and its TAT fusion protein (TAT-CT3) can independently suppress cell viability and induce myeloid differentiation in human leukemia HL-60 cells in our previous studies. But its underlying mechanism remains undefined. Herein, we show that a prokaryotic expressed TAT-CT3 induced a rapid elevation of STAT3 phosphorylation (pSTAT3), and then suppress the transcription of miR-155 and induce the elevation of SOCS-1, which further inhibited STAT3 phosphorylation for a long-term period. Our result indicated a novel mechanism of TAT-CT3 to promote HL60 cells differentiation, which provides some potential therapeutic targets for future acute myelogenous leukemia therapy.
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BMPRIA mediated signaling is essential for temporomandibular joint development in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development.
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A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family.
PLoS ONE
PUBLISHED: 01-01-2014
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Mutations in the transmembrane channel-like gene 1 (TMC1) can cause both DFNA36 and DFNB7/11 hearing loss. More than thirty DFNB7/11 mutations have been reported, but only three DFNA36 mutations were reported previously. In this study, we found a large Chinese family with 222 family members showing post-lingual, progressive sensorineural hearing loss which were consistent with DFNA36 hearing loss. Auditory brainstem response (ABR) test of the youngest patient showed a special result with nearly normal threshold but prolonged latency, decreased amplitude, and the abnormal waveform morphology. Exome sequencing of the proband found four candidate variants in known hearing loss genes. Sanger sequencing in all family members found a novel variant c.1253T>A (p.M418K) in TMC1 at DFNA36 that co-segregated with the phenotype. This mutation in TMC1 is orthologous to the mutation found in the hearing loss mouse model named Bth ten years ago. In another 51 Chinese autosomal dominant hearing loss families, we screened the segments containing the dominant mutations of TMC1 and no functional variants were found. TMC1 is expressed in the hair cells in inner ear. Given the already known roles of TMC1 in the mechanotransduction in the cochlea and its expression in inner ear, our results may provide an interesting perspective into its function in inner ear.
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TCMSP: a database of systems pharmacology for drug discovery from herbal medicines.
J Cheminform
PUBLISHED: 01-01-2014
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Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.
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Growing Crystalline Zinc-1,3,5-benzenetricarboxylate Metal-Organic Frameworks in Different Surfactants.
Inorg Chem
PUBLISHED: 12-27-2013
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Six new zinc-1,3,5-benzenetricarboxylate-based metal-organic frameworks (MOFs) have been successfully synthesized using three different surfactants (PEG 400, octanoic acid, and hexadecyltributylphosphonium bromide) as reaction media. These surfactants with different characteristics, such as being neutral, acidic, and cationic, have been demonstrated to show strong effects on directing the crystals growth and resulted in different secondary building units (SBUs) including an unusual SBU unit [Zn4(?4-O)(CO2)7]. Our results clearly indicated that the surfactant-thermal method could offer exciting opportunities for preparing novel MOFs or other inorganic crystalline materials with diverse structures and interesting properties.
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Serum leptin concentrations in Mongolian women.
Obes Res Clin Pract
PUBLISHED: 12-17-2013
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Summary: Objective: The aim of our study is to elucidate the association between leptin and obesity in Mongolian women.Method: Total 181 women participated in the study including 118 Mongolians and 63 Han. Body mass index (BMI) was calculated by weight (kg) divided by square height (m(2)). Percent body fat (%fat) was detected by bioelectrical impedance analysis (BIA). Fasting serum leptin was determined by ELISA.Result: The average BMI and %fat of Mongolian and Han women was 25.14 ± 4.48 kg/m(2), 24.30 ± 3.62 kg/m(2) and 36.10 ± 6.23%, 33.84 ± 5.98%, respectively. Fasting serum leptin level in obese women (BMI ? 25) was remarkably higher than in normal weight women (18.5 < BMI < 25) in Mongolian and Han ethnic groups (all P < 0.001). Fasting serum leptin level in Mongolian women had borderline significance compared with it in Han women (P = 0.049). Multiple linear regression models revealed that ethnicity, %fat and BMI were associated with serum leptin concentrations independent of age.Conclusion: In Mongolian and Han women, fasting serum leptin level was positively associated with BMI and %fat (all P < 0.001).
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[Experimental study on the treatment of non-tuberculous mycobacterial keratitis].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 12-17-2013
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To explore the optimal treatment for non-tuberculous mycobacterial keratitis (NTMK).
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[Clinical application of Sniffin Sticks olfactory psychophysical measurements].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 12-17-2013
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To establish the normal value of Sniffin Sticks test in Chinese population and to explore its clinical application in China.
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The correlation between the comprehensive nutrition index and quality of life of patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy.
Nutr Cancer
PUBLISHED: 12-13-2013
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The purpose of this study was to compare the changing tendency of nutrition with 54 nasopharyngeal carcinoma patients during intensity-modulated radiation therapy (IMRT), and to investigate the correlation between comprehensive nutritional status and quality of life (QoL), which was assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. The nutritional index, including body mass index, ideal body weight percentage, usual body weight percentage, albumin, hemoglobin, and total lymphocyte count (TLC), was evaluated at 2 time points: within 48 h after admission (T1) and at the end of treatment with IMRT (T2). A statistically significant downgrade of every index was observed during IMRT. A comprehensive nutritional model was established by principal components analysis at T2. QoL scores of functional (P = 0.002) and the global QoL scales (P = 0.001) existed a positive correlation with comprehensive nutritional status. QoL scores of symptom scales (P = 0.002) and 6 single items (P = 0.005) had a negative correlation with it. The scores of global QoL scales in comprehensive nutrition of normal (20.4%), moderate (55.6%), and severe malnutrition (24.1%) were 69.70 ± 17.98, 48.33 ± 19.25, and 37.18 ± 24.67, respectively. Patients with different nutritional status had different QoL (B = 10.405, SE = 2.828, t = 3.680, P = 0.001). Multiaspect nutritional supports should be enhanced to improve patients comprehensive nutritional status during treatment.
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Defective TGFb signaling in bone marrow-derived cells prevents Hedgehog-induced skin tumors.
Cancer Res.
PUBLISHED: 11-26-2013
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Hedgehog (Hh) signaling in cancer cells drives changes in the tumor microenvironment that are incompletely understood. Here we report that Hh- driven tumors exhibit an increase in myeloid-derived suppressor cells (MDSC) and a decrease in T cells, indicative of an immune suppressive tumor microenvironment. This change was associated with activated TGFbeta signaling in several cell types in BCCs. We determined that TGFbeta signaling in bone marrow (BM)-derived cells, not keratinocytes, regulates MDSC and promotes tumor development. Tgfbr2 deficiency in the BM-derived cells also reduced the size of previously developed tumors in mice. We identified CCL2 as the major chemokine attracting MDSC to tumor, whose expression was Tgfbr2-dependent, whereas its receptor CCR2 was highly expressed in MDSC population. CCL2 alone was sufficient to induce migration of MDSC. Moreover, the CCR2 inhibitors prevented MDSC migration towards skin cells in vitro, reduced MDSC accumulation and Hh signaling-driven tumor development in mice. Our results reveal a signaling network critical for Hh signaling in cancer cells to establish an effective immune suppressive microenvironment during tumor development.
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Investigating the Molecular Structural Features of Hulless Barley (Hordeum vulgare L.) in Relation to Metabolic Characteristics Using Synchrotron-Based Fourier Transform Infrared Microspectroscopy.
J. Agric. Food Chem.
PUBLISHED: 11-18-2013
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The synchrotron-based Fourier transform infrared microspectroscopy (SR-FTIRM) technique was used to quantify molecular structural features of the four hulless barley lines with altered carbohydrate traits [amylose, 1-40% of dry matter (DM); ?-glucan, 5-10% of DM] in relation to rumen degradation kinetics, intestinal nutrient digestion, and predicted protein supply. Spectral features of ?-glucan (both area and heights) in hulless barley lines showed a negative correlation with protein availability in the small intestine, including truly digested protein in the small intestine (DVE) (r = -0.76, P < 0.01; r = -0.84, P < 0.01) and total metabolizable protein (MP) (r = -0.71, P < 0.05; r = -0.84, P < 0.01). Variation in absorption intensities of total carbohydrate (CHO) was observed with negative effects on protein degradation, digestion, and potential protein supply (P < 0.05). Molecular structural features of CHO in hulless barley have negative effects on the supply of true protein to ruminants. The results clearly indicated the impact of the carbohydrate-protein structure and matrix.
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Deoxyschizandrin, a Naturally Occurring Lignan, Is a Specific Probe Substrate of Human Cytochrome P450 3A.
Drug Metab. Dispos.
PUBLISHED: 10-16-2013
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To accurately predict the modifications done during metabolic processes by cytochrome P450 (P450) 3A enzyme, selecting substrates that best represent a broad range of substrate substitutions and that follow the Michaelis-Menten kinetic properties is highly necessary. In the present study, the oxidative pathways of deoxyschizandrin (DS), the most abundant lignan in Fructus Schisandrae fruit extract, were characterized with liver microsomes from human (HLM) and rat (RLM). Only one monohydroxylated metabolite 7(S)-hydroxylated metabolite (isoschizandrin, ISZ), was identified using liquid chromatography-mass spectrometry and nuclear magnetic resonance techniques. CYP3A4 and CYP3A5 were found to be the major isoforms involved in the monohydroxylation of DS. Also, the kinetic studies showed that DS hydroxylation obeyed Michaelis-Menten kinetics both in HLM and in RLM. However, the subsequent metabolism of ISZ was nearly nonexistent when DS was present. More importantly, the interactions between DS and three well characterized CYP3A probe substrates, testosterone (TST), midazolam (MDZ), and nifedipine (NIF), were studied. TST and MDZ were shown to compete with DS for the mutual binding site, causing Km to be increased. The presence of DS also lowered the binding affinities for MDZ and TST. However, DS showed only slight inhibitory effects on nifedipine (NIF) oxidation even though NIF was able to inhibit DS hydroxylation in a noncompetitive fashion. These results show that DS is a good representative substrate of MDZ and TST primarily due to their shared, large binding regions on CYP3A. Therefore, DS is an attractive candidate as a novel CYP3A probe substrate for predicting the metabolic modifications in CYP3A activity.
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[In Process Citation].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-25-2013
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To establish a comprehensive geriatric assessment scale which fit the situations of Chinese old people most, and to provide an evaluation tool for the proposal and intervention of functional health problems for the elderly.
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A highly selective probe for human cytochrome P450 3A4: isoform selectivity, kinetic characterization and its applications.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2013
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Bufalin 5?-hydroxylation was found to be an isoform-specific biotransformation probe substrate for cytochrome P450 3A4 (CYP3A4). The probe reaction was well-characterized and it can be used for measuring the real catalytic activities of CYP3A4 from different enzyme sources.
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Identification and Characterization of Human UDP-Glucuronosyltransferases Responsible for the Glucuronidation of Fraxetin.
Drug Metab. Pharmacokinet.
PUBLISHED: 09-10-2013
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  Fraxetin, a major constitute from traditional medicine plant Fraxinus rhynchophylla Hance (Oleaceae), have been found to possess multiple bioactivities. However, the metabolic pathway(s) of fraxetin in human tissues have not been reported yet. This study aimed to characterize the glucuronidation pathway(s) of fraxetin in human tissues. Fraxetin could be metabolized to two glucuronides in human liver microsomes (HLMs). These two glucuronides were biosynthesized and characterized as 7-O-glucuronide (7-O-G) and 8-O-glucuronide (8-O-G), respectively. UGT1A1, -1A6, -1A7, -1A8, -1A9 and -1A10 participated in the formation of 7-O-G, while the formation of 8-O-G was catalyzed selectively by UGT1A6 and UGT1A9. UGT1A9 showed the highest catalytic activities in the formation of 7-O-G and 8-O-G. Both kinetic characterization and inhibition assays demonstrated that UGT1A9 played important roles in fraxetin glucuronidations in HLMs, especially in the formation of the major metabolite 8-O-G. Furthermore, the intrinsic clearance of fraxetin in both human liver microsomes and UGT1A9 was greater than that of 7, 8-dihydroxylcoumarin, revealing that the addition of C-6 methoxy group lead to the higher metabolic clearance. In summary, the glucuronidation pathways of fraxetin in human liver microsomes were well-characterized, and UGT1A9 was the major isoform responsible for the glucuronidations of fraxetin.
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Alcohol consumption in 0.5 million people from 10 diverse regions of China: prevalence, patterns and socio-demographic and health-related correlates.
Int J Epidemiol
PUBLISHED: 08-07-2013
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Drinking alcohol has a long tradition in Chinese culture. However, data on the prevalence and patterns of alcohol consumption in China, and its main correlates, are limited.
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Prevalence and characterization of quinolone resistance in Laribacter hongkongensis from grass carp and Chinese tiger frog.
J. Med. Microbiol.
PUBLISHED: 08-01-2013
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Laribacter hongkongensis is a food-borne bacterium associated with community-acquired gastroenteritis and diarrhoea. Quinolone resistance was recently reported in bacterial isolates from aquatic products, but the molecular mechanisms for resistance were still unknown. In this study, a total of 157 L. hongkongensis strains were isolated from grass carps (n = 443) and Chinese tiger frogs (n = 171). Twenty-one ciprofloxacin-resistant strains were analysed for mutations in quinolone resistance-determining regions (QRDR), acquired quinolone resistance (AQR) genes and the role of efflux pumps in resistance. All QRDR mutations in gyrA (codons 85 and 89) and parC (codons 83 and 231) were found to be closely associated with ciprofloxacin resistance. The AQR gene aac(6)-Ib-cr was found in 42.9% (9/21) of the resistant strains, but qnrA, qnrB, qnrC, qnrD, qnrS and qepA were not detected. No significant change of MICs to ciprofloxacin was observed in the presence of an efflux pump inhibitor, indicating the role of efflux pump was probably absent. All 21 ciprofloxacin-resistant strains showed different electrophoretic patterns, which suggested they were not genetically related. These data highlight the importance of QRDR mutations and the AQR gene aac(6)-Ib-cr during the development of quinolone resistance in a heterogeneous population of L. hongkongensis.
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An in silico exploration of the interaction mechanism of pyrazolo[1,5-a]pyrimidine type CDK2 inhibitors.
Mol Biosyst
PUBLISHED: 07-19-2013
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CDK2, which interacts with cyclin A and cyclin E, is an important member of the CDK family. Having been proved to be associated with many diseases for its vital role in cell cycle, CDK2 is a promising target of anti-cancer drugs dealing with cell cycle disorders. In the present work, a total of 111 pyrazolo[1,5-a]pyrimidines (PHTPPs) as CDK2/cyclin A inhibitors were studied to conduct three-dimensional quantitative structure-activity (3D-QSAR) analyses. The optimal comparative molecular similarity indices analysis (CoMSIA) model shows that Q(2) = 0.516, Rncv(2) = 0.912, Rpre(2) = 0.914, Rm(2) = 0.843, SEP = 0.812, SEE = 0.347 with 10 components using steric, hydrophobic and H-bond donor field descriptors, indicating its effective internal and external predictive capacity. The contour maps further indicate that (1) bulky substituents in R1 are beneficial while H-bond donor groups at this position are detrimental; (2) hydrophobic contributions in the R2 area are favorable; (3) large and hydrophilic groups are well tolerated at the R3 position (a close H-bond donor moiety is favorable while a distal H-bond donor moiety in this area is disfavored); (4) bulky and hydrophobic features in the R4 region are beneficial for the biological activities and (5) the 7-N-aryl substitution is crucial to boost the inhibitory activities of the PHTPP inhibitors. Finally, docking and MD simulations demostrate that PHTPP derivatives are stabilized in a flying bat conformation mainly through the H-bond interactions and hydrophobic contacts. Comparative studies indicate that PHTPP derivatives fit well within the ATP binding cleft in CDK2, with the core heterocyclic ring overlapping significantly with the adenine group of ATP despite a small deflection. In comparison to numerous other inhibitors binding to the ATP pocket, PHTPP analogues follow the binding fashion of purine inhibitors of this kinase. It is anticipated that the binding mechanism and structural features of PHTPP inhibitors studied in the present work will benefit the discovery of more potent CDK2 inhibitors, and the valid pyrazolo[1,5-a]pyrimidine-7-N-yl inhibitors will soon emerge from the large number of screening programmes to enter in clinical studies.
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Complexation with organometallic ruthenium pharmacophores enhances the ability of 4-anilinoquinazolines inducing apoptosis.
Chem. Commun. (Camb.)
PUBLISHED: 07-16-2013
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The complexation with organoruthenium fragments confers 4-anilinoquinazoline pharmacophores with higher potential for inducing cellular apoptosis while the highly inhibitory activity of 4-anilinoquinazolines against EGFR and the reactivity of the ruthenium centre to 9-ethylguanine are well preserved.
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Highly potent dipeptidyl peptidase IV inhibitors derived from Alogliptin through pharmacophore hybridization and lead optimization.
Eur J Med Chem
PUBLISHED: 07-08-2013
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The superposition of the DPP-IV complex revealed that the butynyl group of Linagliptin can be freely switched with the cyanobenzyl group of Alogliptin. Thus, a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor, 11a. Although it did not exhibit the desired activity (IC50=0.2 ?M), compound 11a acts as a lead compound, which triggered a resulting structural optimization and the formation of compound 11m. A novel series of potent DPP-IV inhibitors represented by compound 11m (IC50=0.4 nM) was ultimately obtained with a robust pharmacokinetic profile and superior in vitro and in vivo efficacy compared to Alogliptin.
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Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation.
Mol. Cell. Biochem.
PUBLISHED: 07-03-2013
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Rare genetic mutations in the DJ-1 and Parkin genes cause recessive Parkinsonism, however, the relationship between these two genes is not fully elucidated. Current emerging evidence suggests that these genes are involved in mitochondrial homeostasis, and that a deficiency in either of these two genes is associated with damages in mitochondrial function and morphology. In this study, we demonstrated that knockdown of DJ-1 expression or the overexpression of the DJ-1 L166P mutation results in a damaged phenotype in mitochondria and a hypersensitivity to H2O2-induced cell apoptosis. These phenotypes result from increased levels of endogenous oxidative stress. However, overexpression of wild-type Parkin rescued the phenotypes observed in the mitochondria of DJ-1 knockdown and DJ-1 L166P mutant cells. We also determined that there were differences between the two cell models. Furthermore, both H2O2 treatment and the DJ-1 L166P mutation weakened the interaction between DJ-1 and Parkin. Taken together, these findings suggested that DJ-1 and Parkin were linked through oxidative stress, and that overexpression of Parkin protects DJ-1 protein-deficient and DJ-1 L166P mutant-expressing cells via inhibition of oxidative stress.
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Structural features of falcipain-3 inhibitors: an in silico study.
Mol Biosyst
PUBLISHED: 06-15-2013
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Falcipain-3, the major cysteine hemoglobinase from the human malaria parasite Plasmodium falciparum, is critical for parasite development and is considered as a promising chemotherapeutic target. In order to understand the structure-activity correlation of falcipain-3 inhibitors, a set of ligand- and receptor-based 3D-QSAR models were developed in the present work employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for 247 2-pyrimidinecarbonitrile derivatives. An optimum ligand-based CoMSIA model yielded a cross validation Q(2) = 0.501, non-cross validation Rncv(2) = 0.821 and predictive Rpred(2) = 0.750. In addition, docking analysis and molecular dynamics simulation were applied to elucidate the probable binding modes of the ligand in the falcipain-3 binding pocket. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules. (1) Bulky substituents at the 3-position, and rings B and D increase the biological activity; (2) electrostatic groups at rings B, C and D are likely helpful to increase the falcipain-3 inhibition; (3) hydrophobic groups at rings B and D are favored; (4) Gly92, Ile94 and Thr95 which formed several H-bonds and a water-bridged H-bond are crucial for falcipain-3 inhibitors. This model, we hope, will be of help in designing and predicting novel falcipain-3 inhibitors.
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Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis.
J. Med. Genet.
PUBLISHED: 06-04-2013
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Investigating variations in gene expression, which can be quantitatively measured on a genome-wide scale, is essential to understand and interpret phenotypic differences among human populations. Several previous studies have examined and compared variations in gene expression between continental populations. However, differences in gene expression variation between closely related populations have not been studied yet.
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Systems pharmacology in drug discovery and therapeutic insight for herbal medicines.
Brief. Bioinformatics
PUBLISHED: 06-03-2013
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Systems pharmacology is an emerging field that integrates systems biology and pharmacology to advance the process of drug discovery, development and the understanding of therapeutic mechanisms. The aim of the present work is to highlight the role that the systems pharmacology plays across the traditional herbal medicines discipline, which is exemplified by a case study of botanical drugs applied in the treatment of depression. First, based on critically examined pharmacology and clinical knowledge, we propose a large-scale statistical analysis to evaluate the efficiency of herbs used in traditional medicines. Second, we focus on the exploration of the active ingredients and targets by carrying out complex structure-, omics- and network-based systematic investigations. Third, specific informatics methods are developed to infer drug-disease connections, with purpose to understand how drugs work on the specific targets and pathways. Finally, we propose a new systems pharmacology method, which is further applied to an integrated platform (Herbal medicine Systems Pharmacology) of blended herbal medicine and omics data sets, allowing for the systematization of current and traditional knowledge of herbal medicines and, importantly, for the application of this emerging body of knowledge to the development of new drugs for complex human diseases.
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Analysis of hepatitis B virus genotyping and drug resistance gene mutations based on massively parallel sequencing.
J. Virol. Methods
PUBLISHED: 05-17-2013
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Drug resistance to nucleoside analogs is a serious problem worldwide. Both drug resistance gene mutation detection and HBV genotyping are helpful for guiding clinical treatment. Total HBV DNA from 395 patients who were treated with single or multiple drugs including Lamivudine, Adefovir, Entecavir, Telbivudine, Tenofovir and Emtricitabine were sequenced using the HiSeq 2000 sequencing system and validated using the 3730 sequencing system. In addition, a mixed sample of HBV plasmid DNA was used to determine the cutoff value for HiSeq-sequencing, and 52 of the 395 samples were sequenced three times to evaluate the repeatability and stability of this technology. Of the 395 samples sequenced using both HiSeq and 3730 sequencing, the results from 346 were consistent, and the results from 49 were inconsistent. Among the 49 inconsistent results, 13 samples were detected as drug-resistance-positive using HiSeq but negative using 3730, and the other 36 samples showed a higher number of drug-resistance-positive gene mutations using HiSeq 2000 than using 3730. Gene mutations had an apparent frequency of 1% as assessed by the plasmid testing. Therefore, a 1% cutoff value was adopted. Furthermore, the experiment was repeated three times, and the same results were obtained in 49/52 samples using the HiSeq sequencing system. HiSeq sequencing can be used to analyze HBV gene mutations with high sensitivity, high fidelity, high throughput and automation and is a potential method for hepatitis B virus gene mutation detection and genotyping.
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A systems-pharmacology analysis of herbal medicines used in health improvement treatment: predicting potential new drugs and targets.
Evid Based Complement Alternat Med
PUBLISHED: 04-29-2013
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For thousands of years, tonic herbs have been successfully used all around the world to improve health, energy, and vitality. However, their underlying mechanisms of action in molecular/systems levels are still a mystery. In this work, two sets of tonic herbs, so called Qi-enriching herbs (QEH) and Blood-tonifying herbs (BTH) in TCM, were selected to elucidate why they can restore proper balance and harmony inside body, organ and energy system. Firstly, a pattern recognition model based on artificial neural network and discriminant analysis for assessing the molecular difference between QEH and BTH was developed. It is indicated that QEH compounds have high lipophilicity while BTH compounds possess high chemical reactivity. Secondly, a systematic investigation integrating ADME (absorption, distribution, metabolism, and excretion) prediction, target fishing and network analysis was performed and validated on these herbs to obtain the compound-target associations for reconstructing the biologically-meaningful networks. The results suggest QEH enhance physical strength, immune system and normal well-being, acting as adjuvant therapy for chronic disorders while BTH stimulate hematopoiesis function in body. As an emerging approach, the systems pharmacology model might facilitate to understand the mechanisms of action of the tonic herbs, which brings about new development for complementary and alternative medicine.
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Robust cell size checkpoint from spatiotemporal positive feedback loop in fission yeast.
Biomed Res Int
PUBLISHED: 04-29-2013
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Cells must maintain appropriate cell size during proliferation. Size control may be regulated by a size checkpoint that couples cell size to cell division. Biological experimental data suggests that the cell size is coupled to the cell cycle in two ways: the rates of protein synthesis and the cell polarity protein kinase Pom1 provide spatial information that is used to regulate mitosis inhibitor Wee1. Here a mathematical model involving these spatiotemporal regulations was developed and used to explore the mechanisms underlying the size checkpoint in fission yeast. Bifurcation analysis shows that when the spatiotemporal regulation is coupled to the positive feedback loops (active Cdc2 promotes its activator, Cdc25, and suppress its inhibitor, Wee1), the mitosis-promoting factor (MPF) exhibits a bistable steady-state relationship with the cell size. The switch-like response from the positive feedback loops naturally generates the cell size checkpoint. Further analysis indicated that the spatial regulation provided by Pom1 enhances the robustness of the size checkpoint in fission yeast. This was consistent with experimental data.
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Atypical imaging observations of branchial cleft cysts.
Oncol Lett
PUBLISHED: 04-26-2013
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The aim of the present study was to assess the atypical imaging manifestations of branchial cleft cysts (BCCs) confirmed by pathology. Computerized tomography (CT) or magnetic resonance imaging (MRI) of 17 BCC cases were reviewed. The imaging features, including laterality, location, border, attenuation and internal architecture, were evaluated. All 17 cases were second BCCs, including 5 cases of Bailey type I classification cysts and 12 cases of type II classification cysts. The atypical imaging features included signal and morphological abnormalities. The abnormal signal intensities were caused by intracapsular bleeding (n=2) or solidification of cystic fluid (n=2). Intracystic hemorrhaging revealed homogeneous hyperintensity on T1-weighted image (T1WI) and T2-weighted image (T2WI). Solidification of cystic fluid revealed slightly homogeneous hyperintensity compared with muscle on T1WI and homogeneous hypointensity on T2WI without enhancement. The aberrant morphology mainly presented as thickening of the cystic wall (n=13). Thickened walls of BCCs with ill- (n=5) or well- (n=8) defined borders were observed in 13 patients. In 3 patients, significant enhancement was identified following intravenous gadolinium administration (n=4). When with atypical CT or MRI features are presented, the typical location of BCCs can help in the diagnosis, as it is located at the lateral portion of the neck adjacent to the anterior border of the mandibular angle or sternocleidomastoid muscle. The atypical observations, including variable signals, imply that the cystic content has changed. Thickened walls indicate inflammation or cancerous tendency and patients with ill-defined margins, vascular involvement or lymphadenopathy atelectasis indicate malignant conversion.
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Newborn hearing concurrent genetic screening for hearing impairment-A clinical practice in 58,397 neonates in Tianjin, China.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 04-24-2013
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Newborn hearing screening (NHS) is used worldwide due to its feasibility and cost-efficiency. However, neonates with late-onset and progressive hearing impairment will be missed by NHS. Genetic factors account for an estimated 60% of congenital profound hearing loss. Our previous cohort studies were carried out in an innovative mode, i.e. hearing concurrent genetic screening, in newborns to improve the abilities or early diagnosis and intervention for the hearing defects. In this study, we performed the first clinical practice of this mode in Tianjin city.
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