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Find video protocols related to scientific articles indexed in Pubmed.
Metformin Inhibits Angiogenesis Induced by Interaction of Hepatocellular Carcinoma with Hepatic Stellate Cells.
Cell Biochem. Biophys.
PUBLISHED: 10-19-2014
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Accumulated evidences indicate metformin is associated with reduced risk of hepatocellular carcinoma (HCC) in diabetic patients, which inspired researchers to explore its therapeutic potentials in HCC. Since Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC and promotes tumor development, here, we explored the effect of metformin on tumor angiogenesis induced by interplay of HCC and HSCs. Our results showed that conditional medium from co-culture of HCC/HSCs induced VEGF secretions and stimulated human umbilical vein endothelial cells (HUVEC) tube formation. However, 25 µM metformin could inhibit this angiogenesis effect. Furthermore, knockdown AMPK of HSCs, not HCC, could abolish inhibition caused by metformin. Our finding suggested that metformin could inhibit HCC angiogenesis through targeting on HSCs through AMPK pathway.
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Nickel exposure is associated with the prevalence of type 2 diabetes in Chinese adults.
Int J Epidemiol
PUBLISHED: 10-18-2014
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Nickel exposure can induce hyperglycaemia in rodents, but little is known about its association with abnormal glucose metabolism in humans. We aimed to investigate the association of nickel exposure with the prevalence of type 2 diabetes in Chinese adults.
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Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation.
J. Cell Biol.
PUBLISHED: 10-15-2014
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Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.
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Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns.
Expert Opin Drug Metab Toxicol
PUBLISHED: 09-30-2014
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PEGylation refers to covalent conjugation of one or more polyethylene glycol chains to a drug molecule. It also refers to formulation of a drug into PEGylated drug-delivery vehicles in pharmacy. It is well-known that PEGylation can greatly influence the pharmacokinetics and pharmacodynamics of drugs.
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Glucuronidation of capsaicin by liver microsomes and expressed UGT enzymes: reaction kinetics, contribution of individual enzymes and marked species differences.
Expert Opin Drug Metab Toxicol
PUBLISHED: 09-16-2014
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The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin.
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Design and evaluation of injectable niclosamide nanocrystals prepared by wet media milling technique.
Drug Dev Ind Pharm
PUBLISHED: 09-11-2014
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Abstract Niclosamide is an anthelmintic drug that also demonstrates great potential in fighting against cancers. However, parenteral delivery of niclosamide is challenged due to its insoluble property. This study aimed to develop an injectable formulation for niclosamide using nanocrystals. Niclosamide nanocrystals were prepared by wet media milling technique and characterized by electronic microscopes, differential scanning calorimetry, powder X-ray diffractometry and drug release, etc. The resulting nanocrystals using Tween 80 as the stabilizer were approximately 235?nm in particle size and showed a satisfactory stability. Pharmacokinetic studies revealed that there was no significant difference in plasma concentration-time profiles between nanocrystals and the control formulation (i.e. drug solution). By contrast, a significant difference in tissue distribution was observed at 2?h. Further, niclosamide nanocrystals presented a comparable antitumor effect to the drug solution against EC9076 cell line. We concluded that the nanocrystal formulation with solution-like behaviors should be a promising choice for intravenous delivery of niclosamide.
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Cathepsin L is involved in proliferation and invasion of ovarian cancer cells.
Mol Med Rep
PUBLISHED: 09-04-2014
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Cathepsin L (CTSL) is a lysosomal cysteine protease that has been found to be overexpressed in ovarian cancer (OC). The aim of the present study was to investigate the possible involvement of CTSL in the development of OC. In this study, RNA interference with a CTSL small hairpin RNA (CTSL?shRNA), and a plasmid carrying CTSL were used to identify the effects of this enzyme on the regulation of the malignant behavior of OC cells. OV?90 and SKOV3 human ovarian cancer cell lines were selected as cell models in vitro and in vivo. The results showed that downregulation of CTSL significantly inhibits the proliferative and invasive capability of SKOV3 cells, and that upregulation of CTSL in OV?90 cells leads to opposite effects. Compared with parental OC cells, cells in which CTSL was silenced exhibited a reduced capacity to develop into tumors in nude mice, while the growth of tumor xenografts derived from these cells was markedly constrained. In conclusion, the results suggested that CTSL contributes to the proliferation and metastasis of OC, and that CTSL may be a novel molecular target for OC treatment.
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CD33 rs3865444 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese, European, and North American Populations.
Mol. Neurobiol.
PUBLISHED: 09-04-2014
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The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 27 studies (N?=?86,759; 31,106 cases and 55,653 controls) by searching the PubMed, AlzGene, and Google Scholar databases. We identified significant heterogeneity and observed no significant association between the rs3865444 polymorphism and AD in pooled populations (P?=?0.264, odds ratio (OR)?=?0.97, 95 % confidence interval (CI) 0.93-1.02). In subgroup analysis, we identified significant heterogeneity only in East Asian population and observed no significant association between the rs3865444 polymorphism and AD. We further identified significant heterogeneity and observed significant association between the rs3865444 polymorphism and AD in Chinese population. We identified no significant heterogeneity and significant association in North American and European populations. Collectively, our analysis shows that the CD33 rs3865444 polymorphism is associated with AD susceptibility in Chinese, European, and North American populations. We believe that our findings will be very useful for future genetic studies on AD.
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Highly sensitive impedimetric aptasensor based on covalent binding of gold nanoparticles on reduced graphene oxide with good dispersity and high density.
Analyst
PUBLISHED: 08-29-2014
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A series of gold nanoparticles (AuNPs) that were covalently bound to 2-aminothiophenol-functionalized reduced graphene oxide (Au-ATP-rGO) composites have been synthesized with well-dispersed and controllable surface coverage of AuNPs. Aptamer immobilization capacity studies demonstrated that the surface density of AuNPs played a key role in increasing the amount of anchoring aptamers to enhance the sensitivity of affinity based detection. With the composites possessing dense surface coverage of AuNPs as a versatile signal amplified platform, a label-free aptasensor for the sensitive and selective detection of small molecules (ochratoxin A in this case) has been developed using electrochemical impedance spectroscopy (EIS). A wide linear range of 0.1-200 ng mL(-1) was obtained with a low detection limit of 0.03 ng mL(-1) (S/N = 3). This work provides a universal strategy for the sensitive detection of a variety of targets in a truly label-free manner by means of changing the corresponding aptamer. The promising platform based on the combination of Au-ATP-rGO composites, EIS technique, and aptamers would have great potential applications in clinical diagnosis, environmental analysis, and food safety monitoring.
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Label-free sensitive electrogenerated chemiluminescence aptasensing based on chitosan/Ru(bpy)?²?/silica nanoparticles modified electrode.
Anal. Chem.
PUBLISHED: 08-29-2014
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In this work, a label-free and sensitive electrogenerated chemiluminescence (ECL) aptasensing scheme for K(+) was developed based on G-rich DNA aptamer and chitosan/Ru(bpy)3(2+)/silica (CRuS) nanoparticles (NPs)-modified glass carbon electrode. This ECL aptasensing approach has benefited from the observation that the G-rich DNA aptamer at the unfolded state showed more ECL enhancing signal at CRuS NPs-modified electrode than the binding state with K(+), which folds into G-quadruplex structure. As such, the decreasing ECL signals could be used to detect K(+). Compared to other aptasensing K(+) approaches previously reported, the proposed ECL sensing scheme is a label-free aptasensing strategy, which eliminates the labeling, separation, and immobilization steps, and behaves in a simple, low-cost way. More importantly, because the proposed ECL sensing mechanism utilizes the nanosized ECL active CRuS NPs to sense the nanoscale conformation change from the aptamer binding to target, it is specific. In addition, due to the great conformation changes of the aptamer's G-bases on CRuS NPs and the excellent ECL enhancing effect of guanine bases to the Ru(bpy)3(2+) ECL reaction, a 0.3 nM detection limit for K(+) was achieved with the proposed ECL method. On the basis of these advantages, the proposed ECL aptasensing method was also successfully used to detect K(+) in colorectal cancer cells.
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Amplified fluorescence quenching of lucigenin self-assembled inside silica/chitosan nanoparticles by Cl?.
Anal. Chem.
PUBLISHED: 08-26-2014
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Fluorescence sensing of an analyte based on the fluorophore collective effect is a reliable, sensitive sensing approach. Many ultralow targets can be detected on the basis of the high sensitivity and signal amplification of the fluorescence sensing system. However, the complicated synthesis procedures, harsh conditions required to design and control the fluorescence molecular probes and conjugated chain length, and the higher cost of synthesis are still challenges. To address these issues, we developed a simple, rapid, and sensitive collective effect based fluorescence sensing platform. In this sensing platform, the fluorophore unit was self-assembled on the wall of the nanopores of the porous structural silica/chitosan nanoparticles (SCNPs) on the basis of the electrostatic interaction and supermolecular interaction between the fluorophores and SiO(-) groups and chitosan. Since these self-assembled fluorophores are close enough to communicate with each other on the basis of the space confinement effect of the pore size, many fluorophore units could interact with a single analyte and produce an amplified fluorescence sensing ability. Chloride ion, an important anion in biological fluids, and lucigenin, a typical fluorescent dye, were used as a model to confirm the proof-of-concept strategy. Our results showed that, compared to free-state lucigenin in solution, the assembled-state lucigenin in SCNPs presented an about 10-fold increase in its Stern-Volmer constant when the concentration of Cl(-) was lower than 10 mM, and this fluorescence nanosensor was also successfully used to sense the chloride ion in living cells.
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Association study of TPH2 polymorphisms and bipolar disorder in the Han Chinese population.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 08-21-2014
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Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD.
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Controlled Growth of Few-Layer Hexagonal Boron Nitride on Copper Foils Using Ion Beam Sputtering Deposition.
Small
PUBLISHED: 08-18-2014
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Ion beam sputtering deposition (IBSD) is used to synthesize high quality few-layer hexagonal boron nitride (h-BN) on copper foils. Compared to the conventional chemical vapor deposition, the IBSD technique avoids the use of unconventional precursors and is much easier to control, which should be very useful for the large-scale production of h-BN in the future.
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Sample preparation for mass spectrometric analysis of human serum N-glycans using hydrophilic interaction chromatography-based solid phase extraction.
Analyst
PUBLISHED: 07-29-2014
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Expression levels of N-linked glycans derived from human serum glycoproteins have been shown to change during the progression of many diseases. Generally, N-glycans released from human serum proteins co-exist with endogenous serum peptides, salts, and other contaminants. Effective removal of these contaminants is essential to obtain the glycan profile of human serum proteins. Here, we developed a sample preparation method for mass spectrometry (MS) analysis of N-linked glycans derived from human serum glycoproteins based on a zwitterionic hydrophilic material named Click TE-Cys. The high hydrophilicity of Click TE-Cys, resulting from its unique surface structure and charge distribution, facilitated removal of co-existing salts and endogenous serum peptides. Furthermore, the present enrichment approach was handled in parallel, thus saving time. Using this method, a total of 47 unique N-glycans released from human serum proteins were identified. The intrabatch and interbatch coefficients of variation for the 47 N-linked glycans were 8.57% ± 0.96% and 9.22% ± 1.03%, respectively. These results demonstrate that the present method is suitable for fast purification of N-linked glycans derived from human serum glycoproteins, and has potential for clinical application.
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Prognostic significance of artemin and GFR?1 expression in laryngeal squamous cell carcinoma.
Exp Ther Med
PUBLISHED: 07-02-2014
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Artemin (ARTN) has been implicated in the development and progression of several human malignancies. However, the clinical and prognostic significance of ARTN and its receptors has not yet been investigated in human laryngeal squamous cell carcinoma (LSCC). Therefore, in the present study, the protein expression of ARTN and its receptor, namely GFR?1, was determined in 76 LSCC and 26 laryngeal polyp tissue samples using immunohistochemistry. Furthermore, the clinicopathological and prognostic significance of ARTN and GFR?1 expression was analyzed in patients with LSCC. The results revealed that the expression of ARTN and GFR?1 was significantly increased in LSCC compared with polyp tissue samples. Furthermore, the expression of ARTN and GFR?1 was positively associated with pTNM stage in LSCC. Kaplan-Meier survival analyses revealed a strong association between the expression of ARTN or GFR?1 and the survival of patients with LSCC. Correlation analysis demonstrated that the expression of ARTN was significantly correlated with the expression GFR?1. In conclusion, the results demonstrated that ARTN and GFR?1 may be useful predictors of disease progression and outcome in patients with LSCC.
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No association of SLC6A3 and SLC6A4 gene polymorphisms with schizophrenia in the Han Chinese population.
Neurosci. Lett.
PUBLISHED: 05-24-2014
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The SLC6A3 and SLC6A4 genes are members of a class of neurotransmitter transporters for the release, re-uptake and recycling of neurotransmitters in synapses. SLC6A3 and SLC6A4 encode a dopamine transporter and serotonin transporter, respectively. Abnormal expression and genetic polymorphism of SLC6A3 and SLC6A4 genes may increase the risk of developing mental illness, such as schizophrenia, bipolar disorder, ADHD, and aggressive behavior in Alzheimer disease, etc. Nevertheless, association between SLC6A3, SLC6A4 genes polymorphism and schizophrenia patients have not been well studied in Han Chinese people. In this study, we examined whether single nucleotide polymorphisms (SNPs) in SLC6A3, SLC6A4 were associated with schizophrenia in Han Chinese people (893 schizophrenia patients and 611 healthy controls). No significant difference in allelic or genotypic frequency was found between schizophrenia patients and healthy controls. No positive linkage disequilibrium (LD) was detected either. No haplotypic distributions were positive. Accordingly, our study suggests that the 10 SNPs within both genes we examined do not play a major role in schizophrenia in the Han Chinese population.
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Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-15-2014
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Fructose is a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Here we investigated whether WAY-362450 (WAY), a potent synthetic and orally active FXR agonist, protects against fructose-induced steatosis and the underlying mechanisms. C57BL/6J mice, fed 30% fructose for 8 weeks, were treated with or without WAY, 30 mg/kg, for 20 days. The elevation of serum and hepatic triglyceride in mice fed 30% fructose was reversed by WAY treatment. Histologically, WAY significantly reduced triglyceride accumulation in liver, attenuated microphage infiltration and protected the junction integrity in intestine. Moreover, WAY remarkably decreased portal endotoxin level, and lowered serum TNF? concentration. In lipopolysaccharide (LPS)-induced NAFLD model, WAY attenuated serum TNF? level. Moreover, WAY suppressed LPS-induced expression of hepatic lipid droplet protein adipose differentiation-related protein (ADRP), down-regulation of it in mice fed 30% fructose. Furthermore, WAY repressed lipid accumulation and ADRP expression in a dose-dependent manner in palmitic acid (PA)-treated HepG2 and Huh7 cells. WAY suppressed TNF?-induced ADRP up-regulation via competing with AP-1 for ADRP promoter binding region. Together, our findings suggest that WAY, an FXR agonist, attenuates liver steatosis through multiple mechanisms critically involved in the development of hepatosteatosis, and represents a candidate for NAFLD treatment.
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Exploring the potential of self-assembled mixed micelles in enhancing the stability and oral bioavailability of an acid-labile drug.
Eur J Pharm Sci
PUBLISHED: 05-09-2014
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Oral delivery of many drugs is plagued with limited solubility and/or poor stability. This paper aimed to explore the performance of polymeric mixed micelles on solubilization, stabilization and bioavailability enhancement with stiripentol as model drug. Stiripentol-loaded mixed micelles were prepared by solvent-diffusion method: rapid dispersion of an ethanol solution containing stiripentol, monomethoxy poly(ethylene glycol)-b-poly(?-caprolactone) and sodium oleate into water. Stiripentol micelles were characterized by the particle size, entrapment efficiency, in vitro drug release, TEM, DSC and FTIR. The pharmacokinetic profile of stiripentol was determined in rats after oral administration of stiripentol micelles. The obtained stiripentol micelles were 44.2 nm in size with an entrapment efficiency over 90%. It was shown that micelles substantially improved the solubility and gastric stability of stiripentol. The oral absorption of stiripentol was also enhanced to a great extent with a relative bioavailability of 157% and 444% to the commercial formulation (Diacomit®) and in-house suspensions. Mixed micelles assembled by di-block copolymer/sodium oleate exhibited a good potential in the improvement of drug stability and bioavailability. It should be a promising carrier for oral delivery of therapeuticals with solubility and stability issues.
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Vertical heterostructures of layered metal chalcogenides by van der Waals epitaxy.
Nano Lett.
PUBLISHED: 05-08-2014
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We report a facile chemical vapor deposition (CVD) growth of vertical heterostructures of layered metal dichalcogenides (MX2) enabled by van der Waals epitaxy. Few layers of MoS2, WS2, and WSe2 were grown uniformly onto microplates of SnS2 under mild CVD reaction conditions (<500 °C) and the heteroepitaxy between them was confirmed using cross-sectional transmission electron microscopy (TEM) and unequivocally characterized by resolving the large-area Moiré patterns that appeared on the basal planes of microplates in conventional TEM (nonsectioned). Additional photoluminescence peaks were observed in heterostructures of MoS2-SnS2, which can be understood with electronic structure calculations to likely result from electronic coupling and charge separation between MoS2 and SnS2 layers. This work opens up the exploration of large-area heterostructures of diverse MX2 nanomaterials as the material platform for electronic structure engineering of atomically thin two-dimensional (2D) semiconducting heterostructures and device applications.
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A GAMYB homologue CsGAMYB1 regulates sex expression of cucumber via an ethylene-independent pathway.
J. Exp. Bot.
PUBLISHED: 04-30-2014
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Cucumber (Cucumis sativus L.) is a typical monoecious vegetable with individual male and female flowers, and has been used as a model plant for sex determination. It is well known that sex differentiation of cucumber can be regulated by phytohormones, such as gibberellic acid (GA) and ethylene. The molecular mechanism of female sex expression modulated by ethylene has been widely understood, but how GA controls male sex expression remains elusive. In hermaphroditic Arabidopsis and rice, GA can regulate stamen and anther development via the transcriptional regulation of GAMYB. Here we characterized a GAMYB homologue CsGAMYB1 in cucumber. We found that CsGAMYB1 is predominantly expressed in male flower buds, where its expression is upregulated by GA3 treatment. CsGAMYB1 protein is localized in the nucleus. CsGAMYB1 can partially rescue stamen development and fertility phenotypes of an Arabidopsis myb33 myb65 double mutant. However, constitutive overexpression of CsGAMYB1 in wild-type Arabidopsis resulted in male sterility, which mimics the effect of GA overdose in flower development. Knockdown of CsGAMYB1 in cucumber decreases the ratio of nodes with male and female flowers, and ethylene is not involved in this process. Our data suggest that CsGAMYB1 regulates sex expression of cucumber via an ethylene-independent pathway.
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Increased levels of serum myeloperoxidase in patients with active rheumatoid arthritis.
Life Sci.
PUBLISHED: 04-25-2014
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The clinical significance of myeloperoxidase (MPO) has been the focus of investigation because it may contribute to the chronic, non-microbial inflammatory process in various diseases. Here, we determined serum MPO levels in rheumatoid arthritis (RA) and other autoimmune or inflammatory conditions, and investigated the associations between MPO levels and disease activity indicators in RA.
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Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.
Diabetologia
PUBLISHED: 04-25-2014
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Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations.
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SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor treatment response in the Chinese Han population.
J Clin Psychopharmacol
PUBLISHED: 04-19-2014
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Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.
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Allele-specific DNA methylation analyses associated with siRNAs in Arabidopsis hybrids.
Sci China Life Sci
PUBLISHED: 04-04-2014
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Accumulating evidence has suggested that epigenetic marks including DNA methylation, small RNA and histone modification may involve hybrid vigor in plants. However, knowledge about how epigenetic marks in hybrids regulate gene expression is still limited. Based on genome-wide DNA methylation landscapes of Arabidopsis thaliana Ler and C24 ecotypes and their reciprocal F1 hybrids which were obtained in our previous work, we analyzed allele-specific DNA methylation and distinguished cis- and trans-regulated DNA methylation in hybrids. Our study indicated that both cis- and trans-regulated DNA methylation played roles in hybrids, when cis-regulation played a major role in CG methylation and trans-regulation played major roles in CHG and CHH methylation. In addition, we observed correlations between trans-regulated DNA methylation and siRNA densities. Enriched siRNA regions were significantly concurrent with highly trans-regulated DNA methylation regions. Our results illustrated DNA methylation regulation patterns integrated with siRNAs in Arabidopsis hybrids, and shed light on understanding the mechanism of epigenetic reprogramming for hybrid vigor.
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Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.
Diabetes
PUBLISHED: 03-19-2014
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Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 × 10(-23)], HBS1L/MYB [8.5 × 10(-15)], MYO9B [9.0 × 10(-12)], and CYBA [1.1 × 10(-8)] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA1c (?6.5%), 36.1% had HbA1c <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA1c as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA1c for diagnosing diabetes in these populations.
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Elevated plasma retinol-binding protein 4 is associated with increased risk of type 2 diabetes in middle-aged and elderly Chinese adults.
J. Nutr.
PUBLISHED: 03-19-2014
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The association between circulating retinol-binding protein 4 (RBP4) and risk of type 2 diabetes has been inconsistent in cross-sectional studies, but prospective evidence is limited. We aimed to investigate whether plasma RBP4 is associated with future development of type 2 diabetes and whether the association could be explained by iron or other risk factors. A total of 2091 Chinese adults aged 50-70 y were followed up for 6 y. Baseline dietary intakes and fasting plasma RBP4, ferritin, adiponectin, C-reactive protein (CRP), ?-glutamyltransferase, creatinine, and erythrocyte fatty acids were determined. Self-reported doctor-diagnosed diabetes, or usage of antidiabetic agents, or fasting plasma glucose concentration at the follow-up visit ?7.0 mmol/L was defined as an incident diabetes case. Plasma RBP4 concentration was significantly associated with dietary heme iron intake, plasma ferritin concentration, and other established risk factors. After multivariate adjustment for demographic and lifestyle variables, relative risk (RR) for type 2 diabetes when the extreme quartiles of RBP4 were compared was 1.75 (95% CI: 1.30, 2.37; P-trend < 0.001). This association remained significant when the extreme quartiles were compared (RR = 1.48; 95% CI: 1.06, 2.05; P-trend = 0.036) after further controlling for ferritin and dietary factors, as well as other risk factors, including body mass index, adiponectin, CRP, lipids, liver and kidney function, insulin resistance, and hypertension. A threshold effect of RBP4 concentrations on incident diabetes was suggested by restricted quadratic spline analysis (P = 0.026 for nonlinearity). Our study indicates that plasma RBP4 is independently associated with the 6-y risk of developing type 2 diabetes.
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Development of serum parameters panels for the early detection of pancreatic cancer.
Int. J. Cancer
PUBLISHED: 03-12-2014
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Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross-validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19-9, albumin (ALB), C-reactive protein (CRP) and interleukin (IL)-8 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all-stage, 96.10% for early-stage and 98.80% for advanced-stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non-PDAC. The panel consisting of CA19-9, carbon dioxide, CRP and IL-6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all-stage, 75.30% for early-stage and 74.40% for advanced-stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.
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Protectin D1 promotes resolution of inflammation in a murine model of lipopolysaccharide-induced acute lung injury via enhancing neutrophil apoptosis.
Chin. Med. J.
PUBLISHED: 02-28-2014
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Protectin D1 (PD1), derived from docosahexaenoic acid, has been shown to control and resolve inflammation in some experimental models of inflammatory disorders. We investigated the protective roles of protectin D1 in pulmonary inflammation and lung injury induced by lipopolysaccharide (LPS).
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Ligand-mediated active targeting for enhanced oral absorption.
Drug Discov. Today
PUBLISHED: 02-21-2014
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Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioavailability and therapeutic effect still needs to be further improved by innovative delivery technologies. Recently, various novel strategies, for instance using ligand-decorated carriers, have been investigated for delivery of poorly absorptive therapeutics orally. In this review, we will discuss the state of the art of ligand-mediated targeting to intestinal epithelia for oral delivery of drugs with low bioavailability.
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P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats.
Xenobiotica
PUBLISHED: 02-20-2014
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1.?The promising anticancer agent SNX-2112 (a novel Hsp90 inhibitor) is poorly bioavailable after oral administration. Here, we aim to determine the role of P-glycoprotein (P-gp) in the intestinal absorption of SNX-2112. 2.?We found that SNX-2112 significantly stimulated P-gp ATPase activity in in vitro ATPase assay with a small EC50 (the half-maximal effective concentration) value of 0.32?µM. 3.?In the single-pass perfused rat intestine model, absorption of SNX-2112 was not favored in the small intestine with a [Formula: see text] (the wall permeability) value of 0.38-0.64. By contrast, the compound was well absorbed in the colon with a [Formula: see text] value of 1.19. The P-gp inhibitors cyclosporine and elacridar (i.e. GF120918A) markedly enhanced SNX-2112 absorption in all four intestinal segments (i.e. duodenum, jejunum, ileum and colon) and the fold change ranged from 3.1 to 14.1. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of SNX-2112 by a 2.5-fold after oral administration. 4.?This is the first report that P-gp-mediated efflux is a limiting factor for intestinal absorption of SNX-2112 in rats.
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Identification of glucuronidation and biliary excretion as the main mechanisms for gossypol clearance: in vivo and in vitro evidence.
Xenobiotica
PUBLISHED: 02-20-2014
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1.?The natural polyphenol gossypol possesses many therapeutic benefits. Here we aim to determine the elimination pathways of gossypol in vivo and in vitro. 2.?Metabolite elucidation of gossypol was performed using UPLC-QTOF/MS coupled with Metabolynx analysis. Clearance of gossypol was evaluated in bile duct cannulated rats and in the single-pass perfused rat intestine model. In vitro glucuronidation of gossypol was characterized using liver and intestine microsomes as well as recombinant UDP-glucuronosyltransferase (UGT) enzymes. 3.?Analysis of rat plasma, urine, and feces revealed glucuronidation as the only metabolic pathway for gossypol. In bile duct cannulated rats, considerable amounts of glucuronides (G1, G2 and G3; 58.8-83.2% of dose) and parent compound (5.0-20%) were excreted into bile after IV administration. In the perfused rat intestine model, gossypol was well absorbed with a [Formula: see text] (the dimensionless effective permeability) value of 4.4. Significant amounts of glucuronides (G1, G2 and G3) were excreted into the gut lumen (2.5%) and into the bile (4.8%). Biliary excretion of unchanged gossypol (6.0%) was comparable to that of glucuronides. Further, gossypol was subjected to rapid glucuronidation by liver and intestine microsomes. Reaction phenotyping showed that multiple UGT1A enzymes (including UGT1A1, 1A3, 1A7 and 1A8) are mainly responsible for gossypol metabolism. 4.?In conclusion, glucuronidation was the only metabolic pathway for gossypol in rats. Excretion of unchanged gossypol into bile was also an important clearance mechanism.
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Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese.
Diabetologia
PUBLISHED: 02-16-2014
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Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women.
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Label-free electrochemiluminescence detection of specific-sequence DNA based on DNA probes capped ion nanochannels.
Analyst
PUBLISHED: 02-15-2014
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As one of the powerful molecular recognition elements, the functional DNA probes have been successfully utilized to construct various biosensors. However, the accurate readout of the recognition event of DNA probe binding to the specific target by label-free means is still challenging. Here, a simple and label-free electrochemiluminescence (ECL) method for sensing the recognition event of DNA probe to sequence-specific DNA is developed. Oxalate is used as an ECL co-reactant and p53 tumor suppressor gene as a model of target analyte. In the ECL sensing platform, the nanochannel structural film, which contains silica-sol, chitosan and Ru(bpy)3(2+), is prepared by an electrochemical deposition method. Then, DNA probes are attached onto the surface of the nanochannel-based composite film electrode based on the stronger interaction between DNA probes and chitosan embedded in the ECL composite film. These nanochannels were capped by the DNA probes. As a result, the mass-transfer channel between the Ru(bpy)3(2+) embedded in the nanochannel-based composite film and the ECL co-reactant in the bulk solution was greatly blocked and a weak ECL signal was observed. Conversely, in the presence of target sequences, the hybridizing reaction of targets with DNA probes could result in the escape of the DNA probes from the composite film due to the rigid structure of the duplex DNA. Thus, these nanochannels were uncapped and a stronger ECL signal was detected. Our results show that this ECL method could effectively discriminate complementary from single-base mismatch DNA sequences. Under the optimal conditions, the linear range for target DNA was from 1.0 × 10(-11) to 1.0 × 10(-9) mol L(-1) with a detect limit of 2.7 × 10(-12) mol L(-1). This work demonstrates that porous structures on the silica-chitosan composite film can provide a label-free and general platform to measure the change of DNA configuration.
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Common variants in the CDH7 gene are associated with major depressive disorder in the Han Chinese population.
Behav. Genet.
PUBLISHED: 01-31-2014
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Cadherin-7 (CDH7) gene encodes a calcium dependent cell-cell adhesion glycoprotein. Gene loci of cadherins family have been supposed to be involved in the pathogenesis of psychiatric disorders. Recent genome-wide association study also demonstrated that CDH7 was significant associated with bipolar disorder. Due to the fact that the same genetic risk factor can be shared by different kinds of psychiatric disorders, we examined whether CDH7 is also associated with major depressive disorder (MDD) in this study, with a large Han Chinese sample set. We carried out a 2-stage case-control study to examine the association between CDH7 and MDD in the Han Chinese population. Ten tag SNPs were genotyped using Taqman technology in 1,045 MDD patients and 1,520 healthy controls. Single-nucleotide polymorphisms with significance were additionally genotyped in another independent sample set with 576 MDD cases and 576 healthy controls. Among ten genotyped SNPs, rs1444067 and rs12605720 was found to be significantly associated with MDD (rs1444067: P(allele) = 0.00571, OR 0.830, 95 % CI 0.728-0.947; rs12605720: P(allele) = 0.00321, OR 1.245, 95 % CI 1.076-1.441). We successfully replicated these two SNPs association with independent sample sets (rs1444067: P(allele) = 0.00518; rs12605720: P(allele) = 0.0227). Finally we have combined these results by a meta-analysis (rs1444067: P(allele) = 0.000174, OR 0.817; rs12605720: P(allele) = 0.000199, OR 1.255). Our results support CDH7 to be a risk factor of MDD in the Han Chinese population. However, further studies with more markers and independent samples were suggested to validate our findings.
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Polyoxometalate@magnetic graphene as versatile immobilization matrix of Ru(bpy)3(2+) for sensitive magneto-controlled electrochemiluminescence sensor and its application in biosensing.
Biosens Bioelectron
PUBLISHED: 01-28-2014
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We demonstrated here the exploration of polyoxometalate (POM) coated magnetic Fe3O4/reduced graphene oxide (POM@mrGO) composite as the versatile immobilization matrix for the electrochemiluminescence (ECL) agent Ru(bpy)3(2+). The effective modification of Ru(bpy)3(2+)/POM@mrGO hybrid simply involved using magnetic electrode showed 10-fold ECL intensity increase than that observed for Ru(bpy)3(2+)/Nafion@mrGO to the same concentration of nicotinamide adenine dinucleotide (NADH), which is largely due to POM?s good electrocatalytic activity towards NADH oxidation. These findings allowed the stable and ultrasensitive ECL detection of NADH as low as 0.1 nM. The good stability and high sensitivity of the magneto-controlled ECL sensor enabled us to explore the feasibility of applying the sensing platform to fabricating the ECL biosensors in which the NADH was produced from the dehydrogenase-based enzymatic reaction in the presence of NAD(+) cofactor. With L-lactate dehydrogenase as a model, a L-lactate biosensor was successfully constructed where we showed that the ECL intensity of the biosensor increased with the increasing L-lactate concentration. Excellent performance of the presented biosensor has been achieved including a wide linear range extended from 5.0×10(-9) M to 5.0×10(-4) M and an extremely low detection limit of 0.4 nM. Such sensing strategy combines enzymatic selectivity with simple sensor preparation can be used as a new and biocompatible platform for dehydrogenase-based ECL biosensing.
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[Inhibition of Fasudil on lipopolysaccharide-induced TNF-? and IL-1? expressions through TLR4 pathway in murine BV-2 cells in vitro].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 01-11-2014
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To evaluate the effects of Fasudil on the production of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.
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Enhancement of oral bioavailability of tripterine through lipid nanospheres: preparation, characterization, and absorption evaluation.
J Pharm Sci
PUBLISHED: 01-09-2014
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Oral delivery of anticancer drugs remains challenging because of limited water-solubility and/or poor permeability. Here, we aimed to enhance the oral bioavailability of tripterine (TRI, a plant-derived anticancer compound) using lipid nanospheres (LNs) and to determine the mechanisms of oral absorption. TRI-loaded LNs (TRI-LNs) were prepared by rapid dispersion of an ethanol mixture of TRI, lecithin, sodium oleate, and soybean oil into water. The obtained LNs were 150 nm in size with a high value of entrapment efficiency (99.95%). TRI-LNs were fairly stable and the drug release was negligible (<0.2%) in simulated physiological fluid. The pharmacokinetic results showed that LNs significantly enhanced the oral bioavailability of TRI with a relative bioavailability of 224.88% (TRI suspensions was used as a reference). The mechanistic studies demonstrated that improved intestinal permeability and post-enterocyte lymphatic transport were mainly responsible for the enhanced oral absorption. Our findings suggested that LNs may be a viable oral carrier for poorly bioavailable drugs.
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Poor vitamin D status is prospectively associated with greater muscle mass loss in middle-aged and elderly Chinese individuals.
J Acad Nutr Diet
PUBLISHED: 01-08-2014
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Poor vitamin D status can increase age-related muscle mass loss. However, existing prospective evidence is limited and controversial.
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KCTD10 Is Involved in the Cardiovascular System and Notch Signaling during Early Embryonic Development.
PLoS ONE
PUBLISHED: 01-01-2014
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As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase ?, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10+/- mice were viable and fertile, while the homozygous KCTD10-/- mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.
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A review of cancer risk prediction models with genetic variants.
Cancer Inform
PUBLISHED: 01-01-2014
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Cancer risk prediction models are important in identifying individuals at high risk of developing cancer, which could result in targeted screening and interventions to maximize the treatment benefit and minimize the burden of cancer. The cancer-associated genetic variants identified in genome-wide or candidate gene association studies have been shown to collectively enhance cancer risk prediction, improve our understanding of carcinogenesis, and possibly result in the development of targeted treatments for patients. In this article, we review the cancer risk prediction models that have been developed for popular cancers and assess their applicability, strengths, and weaknesses. We also discuss the factors to be considered for future development and improvement of models for cancer risk prediction.
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Development of a new risk score for incident type 2 diabetes using updated diagnostic criteria in middle-aged and older chinese.
PLoS ONE
PUBLISHED: 01-01-2014
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Type 2 diabetes mellitus (T2DM) reaches an epidemic proportion among adults in China. However, no simple score has been created for the prediction of T2DM incidence diagnosed by updated criteria with hemoglobin A1c (HbA1c) ? 6.5% included in Chinese. In a 6-year follow-up cohort in Beijing and Shanghai, China, we recruited a total of 2529 adults aged 50-70 years in 2005 and followed them up in 2011. Fasting plasma glucose (FPG), HbA1c, and C-reactive protein (CRP) were measured and incident diabetes was identified by the recently updated criteria. Of the 1912 participants without T2DM at baseline, 924 were identified as having T2DM at follow-up, and most of them (72.4%) were diagnosed using the HbA1c criterion. Baseline body mass index, FPG, HbA1c, CRP, hypertension, and female gender were all significantly associated with incident T2DM. Based upon these risk factors, a simple score was developed with an estimated area under the receiver operating characteristic curve of 0.714 (95% confidence interval: 0.691, 0.737), which performed better than most of existing risk score models developed for eastern Asian populations. This simple, newly constructed score of six parameters may be useful in predicting T2DM in middle-aged and older Chinese.
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Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect of formulation variables, intracellular trafficking, and cytotoxicity.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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Peroral protein/peptide delivery has been one of the most challenging, but encouraging topics in pharmaceutics. This article was intended to explore the potential of biotin-modified liposomes (BLPs) as oral insulin delivery carriers. By incorporating biotin-DSPE into the lipid bilayer, we prepared BLPs using reverse evaporation/sonication method. We investigated hypoglycemic effects in normal rats after oral administration of BLPs, and the possible absorption mechanism by a series of in vitro tests. The relative pharmacological bioavailability of BLPs was up to 11.04% that was as much as 5.28 folds of conventional liposomes (CLPs). The results showed that the enhanced oral absorption of insulin mainly attributed to biotin ligand-mediated endocytosis. The results provided proof of BLPs as effective carriers for oral insulin delivery.
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Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a Chinese Han population.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent large-scale genome-wide association studies have identified multiple loci robustly associated with BMI, predominantly in European ancestry (EA) populations. However, associations of these loci with obesity and related traits have not been well described in Chinese Hans. This study aimed to investigate whether BMI-associated loci are, individually and collectively, associated with adiposity-related traits and obesity in Chinese Hans and whether these associations are modified by physical activity (PA).
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Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma.
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Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.
PLoS ONE
PUBLISHED: 01-01-2014
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Generally, most of ovarian cancer cannot be detected until large scale and remote metastasis occurs, which is the major cause of high mortality in ovarian cancer. Therefore, it is urgent to discover metastasis-related biomarkers for the detection of ovarian cancer in its occult metastasis stage. Altered glycosylation is a universal feature of malignancy and certain types of glycan structures are well-known markers for tumor progressions. Thus, this study aimed to reveal specific changes of N-glycans in the secretome of the metastatic ovarian cancer. We employed a quantitative glycomics approach based on metabolic stable isotope labeling to compare the differential N-glycosylation of secretome between an ovarian cancer cell line SKOV3 and its high metastatic derivative SKOV3-ip. Intriguingly, among total 17 N-glycans identified, the N-glycans with bisecting GlcNAc were all significantly decreased in SKOV3-ip in comparison to SKOV3. This alteration in bisecting GlcNAc glycoforms as well as its corresponding association with ovarian cancer metastatic behavior was further validated at the glycotransferase level with multiple techniques including real-time PCR, western blotting, transwell assay, lectin blotting and immunohistochemistry analysis. This study illustrated metastasis-related N-glycan alterations in ovarian cancer secretome in vitro for the first time, which is a valuable source for biomarker discovery as well. Moreover, N-glycans with bisecting GlcNAc shed light on the detection of ovarian cancer in early peritoneal metastasis stage which may accordingly improve the prognosis of ovarian cancer patients.
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ABCB6, ABCB1 and ABCG1 genetic polymorphisms and antidepressant response of SSRIs in Chinese depressive patients.
Pharmacogenomics
PUBLISHED: 11-07-2013
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Major depressive disorder is a common psychiatric disorder with worldwide prevalence. The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). ATP-binding cassette proteins are responsible for the membrane transport of various molecules including antidepressive drugs. We investigated whether SNPs in ABCB6, ABCB1 and ABCG1 were associated with the treatment response of SSRIs.
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Genotypic relationships between Taenia saginata, Taenia asiatica and their hybrids.
Parasitology
PUBLISHED: 10-12-2013
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Partial sequences of the DNA polymerase delta (pold) gene from Taenia saginata-like adult worms were sequenced. Phylogenetic analysis revealed that pold gene sequences were clearly divided into two clades, differing from each other in five to seven nucleotides. There is little doubt that T. saginata and Taenia asiatica were once separated into two distinct taxa as has been concluded in previous studies. On the other hand, most of the adult worms, which were identified as T. asiatica using mitochondrial DNA, were homozygous for an allele that originated from the allele of T. saginata via single nucleotide substitution. These results indicate that most of the adult worms, which had been called T. asiatica, are not actually pure T. asiatica but instead originated from the hybridization of pure T. saginata and pure T. asiatica.
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Replication Protein A2c Coupled with Replication Protein A1c Regulates Crossover Formation during Meiosis in Rice.
Plant Cell
PUBLISHED: 10-11-2013
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Replication protein A (RPA) is a conserved heterotrimeric protein complex comprising RPA1, RPA2, and RPA3 subunits involved in multiple DNA metabolism pathways attributable to its single-stranded DNA binding property. Unlike other species possessing a single RPA2 gene, rice (Oryza sativa) possesses three RPA2 paralogs, but their functions remain unclear. In this study, we identified RPA2c, a rice gene preferentially expressed during meiosis. A T-DNA insertional mutant (rpa2c) exhibited reduced bivalent formation, leading to chromosome nondisjunction. In rpa2c, chiasma frequency is reduced by ?78% compared with the wild type and is accompanied by loss of the obligate chiasma. The residual ?22% chiasmata fit a Poisson distribution, suggesting loss of crossover control. RPA2c colocalized with the meiotic cohesion subunit REC8 and the axis-associated protein PAIR2. Localization of REC8 was necessary for loading of RPA2c to the chromosomes. In addition, RPA2c partially colocalized with MER3 during late leptotene, thus indicating that RPA2c is required for class I crossover formation at a late stage of homologous recombination. Furthermore, we identified RPA1c, an RPA1 subunit with nearly overlapping distribution to RPA2c, required for ?79% of chiasmata formation. Our results demonstrate that an RPA complex comprising RPA2c and RPA1c is required to promote meiotic crossovers in rice.
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Enhanced peroxydisulfate electrochemiluminescence for dopamine biosensing based on Au nanoparticle decorated reduced graphene oxide.
Analyst
PUBLISHED: 10-09-2013
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This work reports a novel strategy to amplify the electrochemiluminescence (ECL) signal of peroxydisulfate solution based on the Au nanoparticle decorated reduced graphene oxide (Au NP-RGO), and further an ECL biosensor for sensitive and selective detection of dopamine (DA) was constructed. Due to the synergistic amplification of Au NPs and RGO, the ECL signal of peroxydisulfate solution on the Au NP-RGO modified electrode was about 5-fold enhanced compared to that of the bare electrode with the ECL onset potential positively shifted from -1.2 V to -0.9 V. More interestingly, the ECL intensity of peroxydisulfate solution increased with the increase of DA concentration, based on which an ECL biosensor for DA determination was fabricated. The as-prepared solid-state ECL DA sensor showed a wide linear response of 0.02-40 ?M with a detection limit of 6.7 nM (S/N = 3). Moreover, we expect this work would open up a new field in the application of peroxydisulfate solution ECL for highly sensitive bioassays.
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A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.
Hum. Mol. Genet.
PUBLISHED: 10-08-2013
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Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.
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GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy.
Mol. Biol. Rep.
PUBLISHED: 09-14-2013
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Golgi protein-73 (GP73) is upregulated in cancers and viral infections; however, its role in human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) remains undetermined. GP73 was evaluated as a biomarker of HIV progression and AIDS treatment efficacy. Forty-eight HIV patients (? 350 CD4 + T cells/?L) undergoing highly active antiretroviral therapy (HAART group) and 18 HIV patients expected to undergo HAART within 9 months (>350 CD4 + T cells/?L) (control group) were enrolled in a prospective, single center, cohort study from May 2009 to Jun 2012. Blood aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglycerides, and total bilirubin were assessed at baseline, 2 weeks, and 1, 3, 6, 9, and 12 months (HAART group) or 3 month intervals (control group). Serum HIV RNA level (viral load) was determined by reverse-transcriptase polymerase chain reaction (RT-PCR), and serum and peripheral blood mononuclear cell (PBMC) GP73 concentration were determined by chemiluminescent immunoassay kit and western blot, respectively. Significant positive and negative correlations in baseline serum GP73 concentration and HIV viral load (r = 0.39, P < 0.001) and CD4 + T cell count (r = -0.501, P < 0.001) were observed, respectively. In receiver operator characteristic (ROC) analysis, area under the curve (AUC) was 0.79 (95 % CI 0.66-0.92). The sensitivity and specificity of GP73 for correct identification of patients with ?350 CD4 + T cells/?L were 76.09 and 75.0 %, respectively, with an ROC-derived cut-off of 100.6 ng/mL. For HIV patients undergoing antiretroviral therapy, GP73 may be a potential biomarker treatment efficacy useful in AIDS management.
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Ultrasensitive electrochemical aptasensor for ochratoxin A based on two-level cascaded signal amplification strategy.
Bioelectrochemistry
PUBLISHED: 09-11-2013
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Ochratoxin A (OTA) has a number of toxic effects to both humans and animals, so developing sensitive detection method is of great importance. Herein, we describe an ultrasensitive electrochemical aptasensor for OTA based on the two-level cascaded signal amplification strategy with methylene blue (MB) as a redox indicator. In this method, capture DNA, aptamers, and reporter DNA functionalized-gold nanoparticles (GNPs) were immobilized on the electrode accordingly, where GNPs were used as the first-level signal enhancer. To receive the more sensitive response, a larger number of guanine (G)-rich DNA was bound to the GNPs surface to provide abundant anchoring sites for MB to achieve the second-level signal amplification. By employing this novel strategy, an ~8.5 (±0.3) fold amplification in signal intensity was obtained. Afterward, OTA was added to force partial GNPs/G-rich DNA to release from the sensing interface and thus decreased the electrochemical response. An effective sensing range from 2.5pM to 2.5nM was received with an extremely low detection limit of 0.75 (±0.12) pM. This amplification strategy has the potential to be the main technology for aptamer-based electrochemical biosensor in a variety of fields.
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Dairy consumption, type 2 diabetes, and changes in cardiometabolic traits: a prospective cohort study of middle-aged and older chinese in beijing and shanghai.
Diabetes Care
PUBLISHED: 09-11-2013
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OBJECTIVE To prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19-1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5-1 serving/day and >1 serving/day were 0.70 (95% CI 0.55-0.88) and 0.65 (0.49-0.85), respectively, after multivariate adjustment (Ptrend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65-1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.
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Advances in diagnosis and spatial analysis of cysticercosis and taeniasis.
Parasitology
PUBLISHED: 08-28-2013
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Human cysticercosis, caused by accidental ingestion of eggs of Taenia solium, is one of the most pathogenic helminthiases and is listed among the 17 WHO Neglected Tropical Diseases. Controlling the life-cycle of T. solium between humans and pigs is essential for eradication of cysticercosis. One difficulty for the accurate detection and identification of T. solium species is the possible co-existence of two other human Taenia tapeworms (T. saginata and T. asiatica, which do not cause cysticercosis in humans). Several key issues for taeniasis/cysticercosis (T/C) evidence-based epidemiology and control are reviewed: (1) advances in immunological and molecular tools for screening of human and animals hosts and identification of Taenia species, with a focus on real-time detection of taeniasis carriers and infected animals in field community screenings, and (2) spatial ecological approaches that have been used to detect geospatial patterns of case distributions and to monitor pig activity and behaviour. Most recent eco-epidemiological studies undertaken in Sichuan province, China, are introduced and reviewed.
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Amplified impedimetric aptasensor based on gold nanoparticles covalently bound graphene sheet for the picomolar detection of ochratoxin A.
Anal. Chim. Acta
PUBLISHED: 08-08-2013
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An amplified electrochemical impedimetric aptasensor for ochratoxin A (OTA) was developed with picomolar sensitivity. A facile route to fabricate gold nanoparticles covalently bound reduced graphene oxide (AuNPs-rGO) resulted in a large number of well-dispersed AuNPs on graphene sheets with tremendous binding sites for DNA, since the single rGO sheet and each AuNP can be loaded with hundreds of DNA strands. An aptasensor with sandwich model was fabricated which involved thiolated capture DNA immobilized on a gold electrode to capture the aptamer, then the sensing interface was incubated with OTA at a desired concentration, followed by AuNPs-rGO functionalized reporter DNA hybridized with the residual aptamers. By exploiting the AuNPs-rGO as an excellent signal amplified platform, a single hybridization event between aptamer and reporter DNA was translated into more than 10(7) redox events, leading to a substantial increase in charge-transfer resistance (Rct) by 7? orders of magnitude compared with that of the free aptamer modified electrode. Such designed aptasensor showed a decreased response of Rct to the increase of OTA concentrations over a wide range of 1pgmL(-1)-50ngmL(-1) and could detect extremely low OTA concentration, namely, 0.3pgmL(-1) or 0.74pM, which was much lower than that of most other existed impedimetric aptasensors. The signal amplification platform presented here would provide a promising model for the aptamer-based detection with a direct impedimetric method.
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Elevated plasma ferritin is associated with increased incidence of type 2 diabetes in middle-aged and elderly Chinese adults.
J. Nutr.
PUBLISHED: 07-31-2013
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Epidemiological studies suggest that elevated circulating ferritin is associated with heightened incident diabetes in mainly Western populations, although the results were not entirely consistent. We aimed to prospectively investigate the ferritin-diabetes association in an Asian population for the first time, to our knowledge, and also to examine this association with an updated meta-analysis. Our prospective study included 2198 community-living Chinese between 50 and 70 y of age in 2005. All individuals participated in a 6-y follow-up survey in 2011. Fasting plasma ferritin, high-sensitivity C-reactive protein (hsCRP), adiponectin, and ?-glutamyltransferase (GGT) were measured at baseline. A total of 538 incident diabetes cases were documented by self-reports and/or fasting glucose ?7.0 mmol/L at the follow-up survey. After multiple adjustments, the RR of type 2 diabetes was 1.90 (95% CI: 1.37, 2.65) when comparing the highest with the lowest sex-specific ferritin quintile. The association remained significant after further controlling for BMI, hsCRP, adiponectin, and GGT. To update the evidence reported in previous meta-analyses, we searched all prospective studies evaluating the association between blood ferritin and incident diabetes on PubMed prior to October 24, 2012. Besides our prospective study, 9 additional studies were also included. The pooled RR was 1.60 (95% CI: 1.25, 2.04) when comparing the highest with the lowest category of ferritin with a moderate heterogeneity (I(2) = 49.0%; P = 0.03). A significant linear dose-response relationship was detected in this meta-analysis. Overall, our results indicate an independent and significant positive association between higher plasma ferritin, a marker of elevated body iron stores, and increased risk of developing type 2 diabetes in middle-aged and elderly Chinese adults, which is similar to Western populations.
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L-Proline: an efficient N,O-bidentate ligand for copper-catalyzed aerobic oxidation of primary and secondary benzylic alcohols at room temperature.
Chem. Commun. (Camb.)
PUBLISHED: 07-30-2013
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A novel and highly practical copper-catalyzed aerobic alcohol oxidation system with L-proline as the ligand at room temperature has been developed. A wide range of primary and secondary benzylic alcohols tested have been smoothly transformed into corresponding aldehydes and ketones with high yields and selectivities.
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Quantitative analysis of serum IgG galactosylation assists differential diagnosis of ovarian cancer.
J. Proteome Res.
PUBLISHED: 07-26-2013
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CA-125, the most frequently used biomarker for ovarian cancer detection, cannot provide accurate diagnosis due to its poor specificity as it may also increase in many benign gynecological conditions. Thus, reducing the false-positive outcomes is urgently needed. Decrease in terminal galactosylated N-glycans of serum IgG has been found in various malignancies compared to healthy controls. Here, this alteration of IgG galactosylation was extended to be investigated between ovarian cancer and benign conditions with similar elevated CA-125 levels, in an attempt to effectively distinguish between false-positive subjects and ovarian cancer patients. In the study of 58 patients with elevated CA-125 levels (>35 U/mL), the degree of IgG galactosylation was measured from the relative intensities of IgG digalactosyl (G2), monogalactosyl (G1), and agalactosylated (G0) N-glycans according to the formula G0/(G1+G2·2). This ratio was found significantly higher in the malignant group than in the benign group (0.74 vs 0.34; p<0.0001). ROC analysis demonstrated an improved specificity from 65.2% (by CA-125 test alone) to 84.6%, while maintaining sensitivity at 90% by incorporating quantitative analysis of IgG galactosylation in the current assay. The results suggest that combining quantitative alteration of IgG galactosylation with CA-125 may generate an overall more robust approach for differential diagnosis of ovarian cancer.
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Detection of human taeniases in Tibetan endemic areas, China.
Parasitology
PUBLISHED: 07-18-2013
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Detection of taeniasis carriers of Taenia solium is essential for control of cysticercosis in humans and pigs. In the current study, we assessed the positive detection rate of a self-detection tool, stool microscopy with direct smear and coproPCR for taeniasis carriers in endemic Tibetan areas of northwest Sichuan. The self-detection tool through questioning about a history of proglottid expulsion within the previous one year showed an overall positive detection rate of more than 80% for Taenia saginata, T. solium and T. asiatica. The positive detection rate was similar for T. saginata and T. solium. In 132 taeniid tapeworm carriers, 68 (51·5%) were detected by microscopy and 92 (69·7%) were diagnosed by coproPCR. A combination of microscopy and coproPCR increased the positive detection rate to 77·3%. There remained 10 cases (7·6%) coproPCR negative but microscopy positive. Due to the high cost and complicated process, coproPCR is required for the identification of Taenia species only when necessary, though it had a significant higher positive detection rate than microscopy. Combined use of self-detection and stool microscopy are recommended in community-based mass screening for taeniases in this Tibetan area or in other situation-similar endemic regions.
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Multiplexed cytokine profiling of serum for detection of colorectal cancer.
Future Oncol
PUBLISHED: 07-11-2013
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To evaluate the concentrations of eight cytokines in order to identify potential biomarkers for assisting in the detection of colorectal cancer.
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Cullin-RING ubiquitin ligase family in plant abiotic stress pathways(F).
J Integr Plant Biol
PUBLISHED: 07-09-2013
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The ubiquitin-proteasome system is a key mechanism that plants use to generate adaptive responses in coping with various environmental stresses. Cullin-RING (CRL) complexes represent a predominant group of ubiquitin E3 ligases in this system. In this review, we focus on the CRL E3s that have been implicated in abiotic stress signaling pathways in Arabidopsis. By comparing and analyzing these cases, we hope to gain a better understanding on how CRL complexes work under various settings in an attempt to decipher the clues about the regulatory mechanism of CRL E3s.
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Associations of erythrocyte fatty acids in the de novo lipogenesis pathway with risk of metabolic syndrome in a cohort study of middle-aged and older Chinese.
Am. J. Clin. Nutr.
PUBLISHED: 06-26-2013
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Experimental studies suggest that elevated de novo lipogenesis (DNL) might be involved in the pathogenesis of metabolic disorders. Few prospective studies have been conducted, especially among populations with a high carbohydrate intake, to determine whether DNL fatty acids are associated with the risk of the metabolic syndrome (MetS).
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Highly sensitive fluorescent protein FRET detection using optofluidic lasers.
Lab Chip
PUBLISHED: 04-03-2013
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We achieved optofluidic protein lasing using genetically encoded fluorescent protein FRET pairs linked by length-tunable peptides. Up to 25-fold reduction in the donor laser emission was observed when the donor and the acceptor were brought to close proximity, as compared to only 17% reduction in the donor emission using the conventional FRET detection. Our work opens a door to a broad range of applications in studying protein-protein interactions and protein-drug interactions.
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Effects of a low-carbohydrate diet on weight loss and cardiometabolic profile in Chinese women: a randomised controlled feeding trial.
Br. J. Nutr.
PUBLISHED: 03-25-2013
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Little is known about the potential adherence to and the effectiveness of a low-carbohydrate (LC) diet on weight loss and cardiometabolic risk factors in Chinese adults with a habitually high carbohydrate intake. In the present controlled feeding trial, fifty overweight or obese women (age 47·9 (sem 0·9) years; BMI 26·7 (sem 0·3) kg/m²) were randomly assigned to a LC non-energy-restricted diet (initial carbohydrate intake 20 g/d, with a 10 g increase weekly) or an energy-restricted (ER) diet (carbohydrate intake 156-205 g/d, ER to 5021 or 6276 kJ/d, 35% average energy reduction) for 12 weeks. Over the intervention period, the two diets had comparable compliance (96%) and self-reported acceptability. At week 12, carbohydrate intake in the LC and ER groups contributed to 36·1 and 51·1% of total energy, respectively (P < 0·001). Although both diets showed similarly decreased mean body weight (LC - 5·27 (95% CI - 6·08, - 4·46) kg; ER - 5·09 (95% CI - 5·50, - 4·67) kg, P = 0·67) and percentage of fat mass measured by dual-energy X-ray absorptiometry (LC - 1·19 (95% CI - 1·88, - 0·50)%; ER - 1·56 (95% CI - 2·20, - 0·92)%, P = 0·42), participants in the LC group had greater reductions in the ratio of total cholesterol:HDL-cholesterol (P= 0·03) and also in the ratio of TAG:HDL-cholesterol (P = 0·01) than those in the ER group. The present 12-week diet trial suggested that both a LC non-energy-restricted diet and an ER diet were acceptable to Chinese women and both diets were equally effective in reducing weight and fat mass. Moreover, the LC diet showed beneficial effects on blood lipid profiles.
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Biotinylated liposomes as potential carriers for the oral delivery of insulin.
Nanomedicine
PUBLISHED: 03-18-2013
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This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin.
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Development of three PCR assays for the differentiation between Echinococcus shiquicus, E. granulosus (G1 genotype), and E. multilocularis DNA in the co-endemic region of Qinghai-Tibet plateau, China.
Am. J. Trop. Med. Hyg.
PUBLISHED: 02-25-2013
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To investigate echinococcosis in co-endemic regions, three polymerase chain reaction (PCR) assays based on the amplification of a fragment within the NADH dehydrogenase subunit 1 (ND1) mitochondrial gene were optimized for the detection of Echinococcus shiquicus, Echinococcus granulosus G1, and Echinococcus multilocularis DNA derived from parasite tissue or canid fecal samples. Specificity using parasite tissue-derived DNA was found to be 100% except for E. shiquicus primers that faintly detected E. equinus DNA. Sensitivity of the three assays for DNA detection was between 2 and 10 pg. Ethanol precipitation of negative PCR fecal samples was used to eliminate false negatives and served to increase sensitivity as exemplified by an increase in detection from 0% to 89% of E. shiquicus coproDNA using necropsy-positive fox samples.
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Bohlers angles role in assessing the injury severity and functional outcome of internal fixation for displaced intra-articular calcaneal fractures: a retrospective study.
BMC Surg
PUBLISHED: 02-15-2013
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Controversy exits over the role of Böhlers angle in assessing the injury severity of displaced intra-articular calcaneal fractures and predicting the functional outcome following internal fixation. This study aims to investigate whether a correlation exists between Böhlers angle and the injury severity of displaced calcaneal fractures, and between surgical improvement of Böhlers angle and functional outcome.
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Serum GP73, a marker for evaluating progression in patients with chronic HBV infections.
PLoS ONE
PUBLISHED: 02-13-2013
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This study was designed to investigate the role of serum GP73 for diagnosing significant fibrosis in patients with chronic hepatitis B virus (HBV) infections. Two populations were enrollment. All subjects were patients with chronic HBV infections. First population included 761 patients, who received liver stiffness measurement; the second population included 633 patients, who undertaken liver biopsy, in which 472 patients with nearly normal ALT. All patients received serum GP73 test. The effect of GP73 recombinant protein to HepG2 cells and LX2 cells were observed in vitro. Results showed that serum GP73 concentration is correlated with liver stiffness (r?=?0.601). The area under ROC curve is 0.76. The sensitivity and specificity of GP73 for significant fibrosis (?F2) diagnosis were 62.81%, 80.05% respectively (cut off: 76.6 ng/ml). Serum GP73 concentration was significantly correlated with the grading of fibrosis (r?=?0.32, and 0.35, in 633 and 472 patients, respectively.) GP73 had a striking performance for diagnosing S2 in patients with chronic HBV infections. In 472 patients with nearly normal ALT, the sensitivity and specificity of GP73 for S2 diagnosis were 62.5% and 80.0% respectively, where the cut-off was set at 82 ng/ml. GP73 recombinant protein may prompt LX2 cells proliferation at the concentration 10-100 ng/ml. The present results indicated that GP73 may be a marker for diagnosing significant fibrosis in patients with chronic HBV infections, and may be a new contributor to fibrogensis.
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Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.
J. Lipid Res.
PUBLISHED: 02-08-2013
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Little is known about the associations of FADS1 genetic variants with circulating levels of PUFA and lipids in Asian populations who have a different dietary pattern and dyslipidemia prevalence compared with Western populations. In a population-based sample of 3,210 unrelated Han Chinese living in Beijing and Shanghai, we examined a FADS1 genetic variant, rs174550, in relation to blood PUFA and lipid levels. C-allele of rs174550 was significantly associated with levels of erythrocyte PUFAs in upstream and downstream pathways of delta-5 desaturase (D5D) (P ? 0.003). Moreover, rs174550 C-allele was associated with a lower HDL cholesterol level (P = 0.02) in total population and a higher triglyceride level (P = 0.0002) in Beijing residents. Interestingly, erythrocyte levels of 18:2n-6 and 18:3n-3 modified the effect of rs174550 on HDL cholesterol level: stronger associations between rs174550 C-allele and lower HDL cholesterol levels were exhibited when erythrocyte 18:2n-6 or 18:3n-3 level was low (P for interaction = 0.02 and 0.03, respectively). These data suggested that FADS1 genetic variant was associated with circulating PUFA and lipid levels and that its effect on HDL cholesterol might depend on PUFA status in the Han Chinese population.
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What is Visualize?

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

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

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.