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Find video protocols related to scientific articles indexed in Pubmed.
Inhibition of Transient Receptor Potential Channel 5 Reverses 5-Fluorouracil Resistance in Human Colorectal Cancer Cells.
J. Biol. Chem.
PUBLISHED: 11-19-2014
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5-Fluorouracil (5-Fu) is commonly used in the chemotherapy of colorectal cancer (CRC), but resistance to 5-Fu occurs in most cases, allowing cancer progression. Suppressing ABCB1 (ATP-binding cassette, sub-family B, member1), which is a pump overproduced in cancer cells to export cytotoxic drugs, is an attractive strategy to overcome drug resistance. In the present study, transient receptor potential channel TrpC5 was found to be overproduced at the mRNA and protein levels together with ABCB1 in 5-Fu-resistant human CRC HCT-8 (HCT-8/5-Fu) and LoVo (LoVo/5-Fu) cells. More nuclear-stabilized ?-catenin accumulation was found in HCT-8/5-Fu and LoVo/5-Fu cells than in HCT-8 and LoVo cells. Suppressing TrpC5 expression with TrpC5-specific siRNA inhibited the canonical Wnt/?-catenin signal pathway, reduced the induction of ABCB1, weakened the ABCB1 efflux pump, and caused a remarkable reversal of 5-Fu resistance in HCT-8/5-Fu and LoVo/5-Fu cells. On the contrary, enforcing TrpC5 expression resulted in an activated Wnt/?-catenin signal pathway and up-regulation of ABCB1. Taken together, we demonstrated an essential role of TrpC5 in ABCB1 induction and drug resistance in human CRC cells via promoting nuclear ?-catenin accumulation.
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Isolation of the Molecular Species of Monogalactosyldiacylglycerols from Brown Edible Seaweed Sargassum horneri and Their Inhibitory Effects on Triglyceride Accumulation in 3T3-L1 Adipocytes.
J. Agric. Food Chem.
PUBLISHED: 11-11-2014
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The chemical composition of monogalactosyldiacylglycerols (MGDGs) from brown alga Sargassum horneri and their inhibitory effects on lipid accumulation were investigated in this study. A total of 10 molecular species of MGDGs were identified using nuclear magnetic resonance, alkaline hydrolysis, gas chromatography-flame ionization detector, and high-performance liquid chromatography-tandem mass spectrometry methods. Individual molecular species of MGDGs, including (2S)-1-O-myristoyl-2-O-palmitoleoyl-3-O-?-d-galactopyranosyl-sn-glycerol (1), (2S)-1-O-myristoyl-2-O-linoleyl-3-O-?-d-galactopyranosyl-sn-glycerol (3), (2S)-1-O-palmitoyl-2-O-linolenoyl-3-O-?-d-galactopyranosyl-sn-glycerol (5), (2S)-1-O-myristoyl-2-O-oleyl-3-O-?-d-galactopyranosyl-sn-glycerol (7), (2S)-1-O-palmitoyl-2-O-palmitoleoyl-3-O-?-d-galactopyranosyl-sn-glycerol (8), (2S)-1-O-palmitoyl-2-O-linoleyl-3-O-?-d-galactopyranosyl-sn-glycerol (9), and (2S)-1-O-palmitoyl-2-O-oleyl-3-O-?-d-galactopyranosyl-sn-glycerol (10), were then furnished using semi-preparative high-performance liquid chromatography, and their inhibitory effects on triglyceride (TG) accumulation and free fatty acid (FFA) levels in 3T3-L1 adipocytes were evaluated. Compounds 3 and 9 showed inhibitory effects on TG and FFA accumulation, with TG levels of 1.568 ± 0.2808 and 1.701 ± 0.1460 ?mol/L and FFA levels of 0.149 ± 0.0258 and 0.198 ± 0.0229 mequiv/L, respectively, which were more effective than other compounds. The primary structure-activity relationship suggested that linoleyl [18:2(?-6)] in the sn-2 position played an important role on triglyceride accumulation inhibition.
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Towards more accurate prediction of ubiquitination sites: a comprehensive review of current methods, tools and features.
Brief. Bioinformatics
PUBLISHED: 09-13-2014
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Protein ubiquitination is one of the most important reversible post-translational modifications (PTMs). In many biochemical, pathological and pharmaceutical studies on understanding the function of proteins in biological processes, identification of ubiquitination sites is an important first step. However, experimental approaches for identifying ubiquitination sites are often expensive, labor-intensive and time-consuming, partly due to the dynamics and reversibility of ubiquitination. In silico prediction of ubiquitination sites is potentially a useful strategy for whole proteome annotation. A number of bioinformatics approaches and tools have recently been developed for predicting protein ubiquitination sites. However, these tools have different methodologies, prediction algorithms, functionality and features, which complicate their utility and application. The purpose of this review is to aid users in selecting appropriate tools for specific analyses and circumstances. We first compared five popular webservers and standalone software options, assessing their performance on four up-to-date ubiquitination benchmark datasets from Saccharomyces cerevisiae, Homo sapiens, Mus musculus and Arabidopsis thaliana. We then discussed and summarized these tools to guide users in choosing among the tools efficiently and rapidly. Finally, we assessed the importance of features of existing tools for ubiquitination site prediction, ranking them by performance. We also discussed the features that make noticeable contributions to species-specific ubiquitination site prediction.
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Endothelial dysfunction: the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis.
Curr. Opin. Lipidol.
PUBLISHED: 09-05-2014
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Great effort has been devoted to elucidate the molecular mechanisms by which inflammasome in macrophages contributes to atherosclerosis. Inflammasome in vascular endothelial cells and its causal relationship with endothelial dysfunction in atherosclerosis are less understood. Here, we review the recent studies of inflammasome and its activation in endothelial cells, and highlight such endothelial inflammatory response in atherosclerosis.
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Minimum important differences for scales assessing symptom severity and quality of life in patients with fecal incontinence.
Female Pelvic Med Reconstr Surg
PUBLISHED: 09-05-2014
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The objective of this study was to estimate the minimum important difference (MID) for the Fecal Incontinence Severity Index (FISI), the Colorectal-Anal Distress Inventory (CRADI) scale of the Pelvic Floor Distress Inventory, the Colorectal-Anal Impact Questionnaire (CRAIQ) scale of the Pelvic Floor Impact Questionnaire, and the Modified Manchester Health Questionnaire (MMHQ).
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Guided bone regeneration with tripolyphosphate cross-linked asymmetric chitosan membrane.
J Dent
PUBLISHED: 09-02-2014
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The objective of this study was to prepare a novel asymmetric chitosan guided bone regeneration (GBR) membrane, which is composed of a dense layer isolating the bone defect from the invasion of surrounding connective fibrous tissue and a loose layer which can improve cell adhesion and stabilize blood clots, thus guided bone regeneration.
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Effectiveness and complications of ultrasound guided fine needle aspiration for primary liver cancer in a Chinese population with serum ?-fetoprotein levels ?200 ng/ml--a study based on 4,312 patients.
PLoS ONE
PUBLISHED: 08-29-2014
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Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum ?-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies.
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[Preliminary experiences of "Waffle cone" technique for the treatment of intracranial aneurysm].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-22-2014
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To explore the preliminary experiences of "Waffle cone" technique for the treatment of intracranial aneurysm.
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Impact of storage solution formulation during refrigerated storage upon chondrocyte viability and cartilage matrix.
Cells Tissues Organs (Print)
PUBLISHED: 08-21-2014
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Various preservation solutions have been evaluated for longer hypothermic cartilage storage for tissue transplantation; however, the results are mixed. This research was carried out to determine whether phosphate-buffered saline (PBS) or organ preservation solutions would preserve both the extracellular matrix and chondrocytes of articular cartilage better than culture medium during refrigerated storage in the time frame that cartilage is stored for clinical use. Porcine cartilage plugs were stored, without the underlying bone, in culture medium with and without fetal bovine serum (FBS), PBS, Belzer's and Unisol solutions for 1 month at 4°C. Metabolic activity was tested using a resazurin reduction method, and matrix permeability was evaluated by measuring electrical conductivity. Storage in culture medium with 10% FBS was shown to provide good cartilage metabolic function for 7 days, decreasing to about 36% after 1 month of storage. There was no significant difference between samples stored in culture medium with and without FBS after 1 month of storage (p = 0.5005). Refrigerated storage of cartilage in PBS and two different solutions (Belzer's and Unisol) designed for optimal refrigerated tissue and organ storage results in loss of chondrocyte function and retention of matrix permeability. In contrast, the opposite, namely significantly better retention of chondrocyte function and loss of matrix permeability, was observed with culture medium. Future research should be focused on combining retention of chondrocyte function and matrix permeability by storage solution formulation.
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Perfluorochemicals and Human Semen Quality: The LIFE Study.
Environ. Health Perspect.
PUBLISHED: 08-15-2014
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Background: The relation between persistent environmental chemicals and semen quality is evolving, though limited data exist for men recruited from general populations. Objectives: To assess the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Methods: Utilizing population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005-2009. Baseline interviews and anthropometric assessments were conducted followed by blood collection for the quantification of 7 serum PFCs (perfluorosulfonates, perfluorocarboxylates and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately a month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality endpoints. Results: Six PFCs (2-N-methyl-perfluorooctane sulfonamide acetate [Me-PFOSA-AcOH], perfluorodecanoate [PFDeA], perfluorononanoate [PFNA], perfluorooctane sulfonamide [PFOSA], perfluorooctane sulfonate [PFOS], and perfluorooctanoate [PFOA]) were associated with 17 semen quality endpoints before Box Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Conclusions: Select PFCs were associated with certain semen endpoints, with the most significant associations observed for PFOSA though with results in varying directions.
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Cyr61 promotes growth of pancreatic carcinoma via nuclear exclusion of p27.
Tumour Biol.
PUBLISHED: 08-08-2014
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The molecular regulation of the growth of pancreatic carcinoma (PCC) is complicated and not defined yet. Here we show that the cysteine-rich protein 61 (Cyr61) levels were significantly higher in PCC than in the adjacent nontumor tissues from the same human patient. Overexpression of Cyr61 enhanced the proliferation of PCC cells, while inhibition of Cyr61 decreased the proliferation of PCC cells. Further analysis showed that Cyr61 seemed to activate phosphatidylinositol 3-kinase (PI3K) but not extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway in PCC cells, which subsequently induced nuclear exclusion of a major cell cycle inhibitor, p27, to increase cell proliferation. Taken together, these findings reveal the molecular basis underlying Cyr61-regulated PCC proliferation, suggest a potential role of Cyr61 in PCC growth, and highlight Cyr61 as a novel target for PCC therapy.
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Impact of ventriculoperitoneal shunting on chronic normal pressure hydrocephalus in consciousness rehabilitation.
J Rehabil Med
PUBLISHED: 08-01-2014
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To investigate the impact of ventriculoperitoneal shunting during clinical rehabilitation of chronic normal pressure hydrocephalus patients with disorders of consciousness following aneurysmal subarachnoid haemorrhage.
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Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women.
Ethn Dis
PUBLISHED: 07-29-2014
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Hypertension and cardiovascular disease rates vary by race/ethnicity in nonpregnant adults. We aimed to examine racial/ethnic differences in prevalence and severity of hypertensive diseases during pregnancy in nulliparous women.
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MicroRNA expression in salivary supernatant of patients with pancreatic cancer and its relationship with ZHENG.
Biomed Res Int
PUBLISHED: 07-14-2014
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In traditional Chinese medicine (TCM), diagnosis and prescriptions are based on the signs and symptoms which are recognized as ZHENG. The cornerstone of TCM is to differentially treat one ZHENG from others, which is also known as syndrome differentiation, and this relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, the expressions of 384 cancer-related miRNAs in salivary supernatant of patients with pancreatic cancer were assessed by miRNA polymerase chain reaction (PCR) array, and the different expression patterns of miRNA in three different groups of ZHENG were studied with use of real-time quantitative PCR (qRT-PCR). Some miRNAs were found to be specifically expressed in some ZHENGs, for instance, miR-17, miR-21, and miR-181b in Shi-Re ZHENG and miR-196a in Pi-Xu ZHENG. This indicates that these miRNAs may play important roles in different ZHENG condition. Therefore, this study to some extent revealed the molecular basis of TCM ZHENG in pancreatic cancer.
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Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 06-28-2014
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Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.
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24(S)-saringosterol from edible marine seaweed Sargassum fusiforme is a novel selective LXR? agonist.
J. Agric. Food Chem.
PUBLISHED: 06-20-2014
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Dietary phytosterols have been successfully used for lowering cholesterol levels, which correlates with the fact that some phytosterols are able to act as liver X receptor (LXR) agonists. Sargassum fusiforme is an edible marine seaweed well-known for its antiatherosclerotic function in traditional Chinese medicine. In this study, seven phytosterols including fucosterol (1), saringosterol (2), 24-hydroperoxy-24-vinyl-cholesterol (3), 29-hydroperoxy-stigmasta-5,24(28)-dien-3?-ol (4), 24-methylene-cholesterol (5), 24-keto-cholesterol (6), and 5?,8?-epidioxyergosta-6,22-dien-3?-ol (7) were purified and evaluated for their actions on LXR-mediated transcription using a reporter assay. Among these phytosterols, 2 was the most potent compound in stimulating the transcriptional activities of LXR? by (3.81±0.15)-fold and LXR? by (14.40±1.10)-fold, respectively. Two epimers of 2, 24(S)-saringosterol (2a) and 24(R)-saringosterol (2b), were subsequently separated by semipreparative high-performance liquid chromatography. Interestingly, 2a was more potent than 2b in LXR?-mediated transactivation ((3.50±0.17)-fold vs (1.63±0.12)-fold) compared with control. Consistently, 2a induced higher expression levels of LXR target genes including key players in reverse cholesterol transport in six cell lines. These data along with molecular modeling suggested that 2a acts as a selective LXR? agonist and is a potent natural cholesterol-lowering agent. This study also demonstrated that phytosterols in S. fusiforme contributed to the well-known antiatherosclerotic function.
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Competitive growth mechanisms of AlN on Si (111) by MOVPE.
Sci Rep
PUBLISHED: 06-17-2014
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To improve the growth rate and crystal quality of AlN, the competitive growth mechanisms of AlN under different parameters were studied. The mass transport limited mechanism was competed with the gas-phase parasitic reaction and became dominated at low reactor pressure. The mechanism of strain relaxation at the AlN/Si interface was studied by transmission electron microscopy (TEM). Improved deposition rate in the mass-transport-limit region and increased adatom mobility were realized under extremely low reactor pressure.
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Layer-by-layer self-assembly of minocycline-loaded chitosan/alginate multilayer on titanium substrates to inhibit biofilm formation.
J Dent
PUBLISHED: 05-29-2014
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Bacteria adhesion and subsequent biofilm formation are primary causes of implant associated infection. The biofilm makes the bacteria highly resistant to the host defense and antimicrobial treatment. Antibacterial coatings on the surface of titanium implant can prevent biofilm formation effectively, but it is still a challenge to accomplish relatively long lasting antibacterial effects before wound healing or formation of biological seal. The purpose of our work was to construct antibacterial multilayer coatings loaded with minocycline on surface of Ti substrates using chitosan and alginate based on layer-by-layer (LbL) self-assembly technique.
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Lipid concentrations and couple fecundity: the LIFE study.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-20-2014
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A role of lipids in human fecundity is hypothesized as cholesterol is the main substrate for steroid synthesis and has also been shown to affect the hormonal milieu and steroidogenesis in both men and women.
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A red phosphor BaTiF(6):Mn(4+): reaction mechanism, microstructures, optical properties, and applications for white LEDs.
Dalton Trans
PUBLISHED: 05-20-2014
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Red phosphors BaTiF6:Mn(4+) with microrod and polyhedron morphologies have been prepared respectively by etching TiO2 and Ti(OC4H9)4 in a HF solution with an optimized concentration of KMnO4 at 1.5 mmol L(-1) in hydrothermal conditions. The red phosphor BaTiF6:Mn(4+) exhibits a broad excitation band in the blue region and sharp emission peaks in the red region. A white LED (WLED) fabricated with the red phosphor BaTiF6:Mn(4+) shows "warm" white light that possesses a color rendering index of 93.13 at a color temperature of 4073.1 K.
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[Research on non-rigid registration of multi-modal medical image based on Demons algorithm].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 05-09-2014
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Non-rigid medical image registration is a popular subject in the research areas of the medical image and has an important clinical value. In this paper we put forward an improved algorithm of Demons, together with the conservation of gray model and local structure tensor conservation model, to construct a new energy function processing multi-modal registration problem. We then applied the L-BFGS algorithm to optimize the energy function and solve complex three-dimensional data optimization problem. And finally we used the multi-scale hierarchical refinement ideas to solve large deformation registration. The experimental results showed that the proposed algorithm for large de formation and multi-modal three-dimensional medical image registration had good effects.
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Randomized, placebo-controlled trial of K1 acupoint acustimulation to prevent cisplatin-induced or oxaliplatin-induced nausea.
Cancer
PUBLISHED: 05-08-2014
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Greater than 70% of patients with cancer experience chemotherapy-induced nausea and vomiting. In the current study, the authors examined the effects of electrostimulation of the K1 acupoint located on the sole of the foot because it is believed to have the potential to control chemotherapy-induced nausea and vomiting.
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Increased urinary cobalt and whole blood concentrations of cadmium and lead in women with uterine leiomyomata: Findings from the ENDO Study.
Reprod. Toxicol.
PUBLISHED: 05-06-2014
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Multiple trace elements have estrogen receptor activity, but the association of these elements with uterine leiomyoma has not been defined. A cohort of 473 women aged 18-44 undergoing surgery for benign gynecologic indications provided whole blood and urine specimens for trace element analysis, which was performed by inductively coupled plasma mass spectrometry. Twenty elements were analyzed in blood and 3 in urine. The surgeon documented whether fibroids were present. Geometric mean concentrations were compared between women with and without fibroids, and logistic regression models were generated to assess the impact of the concentration of each trace element on the odds of fibroids. In multivariate regressions, odds of a fibroid diagnosis were higher with increased whole blood cadmium (AOR 1.44, 95% CI 1.02, 2.04) and lead (AOR 1.31 95% CI 1.02, 1.69), and urine cobalt (AOR 1.31, 95% CI 1.02, 1.70). Urinary cadmium and lead were not related to fibroid diagnosis. Increased exposure to trace elements may contribute to fibroid growth, and fibroids may serve as a reservoir for these elements. Differences between urinary and whole blood findings merit further investigation, as urinary cadmium has been considered a superior marker of exposure.
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A photon thermal diode.
Nat Commun
PUBLISHED: 05-02-2014
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A thermal diode is a two-terminal nonlinear device that rectifies energy carriers (for example, photons, phonons and electrons) in the thermal domain, the heat transfer analogue to the familiar electrical diode. Effective thermal rectifiers could have an impact on diverse applications ranging from heat engines to refrigeration, thermal regulation of buildings and thermal logic. However, experimental demonstrations have lagged far behind theoretical proposals. Here we present the first experimental results for a photon thermal diode. The device is based on asymmetric scattering of ballistic energy carriers by pyramidal reflectors. Recent theoretical work has predicted that this ballistic mechanism also requires a nonlinearity in order to yield asymmetric thermal transport, a requirement of all thermal diodes arising from the second Law of Thermodynamics, and realized here using an 'inelastic thermal collimator' element. Experiments confirm both effects: with pyramids and collimator the thermal rectification is 10.9±0.8%, while without the collimator no rectification is detectable (<0.3%).
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The IL-8/CXCR1 axis is associated with cancer stem cell-like properties and correlates with clinical prognosis in human pancreatic cancer cases.
Sci Rep
PUBLISHED: 05-01-2014
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CXCR1, a receptor for CXCL8/IL-8, has recently been demonstrated to be associated with cancer stem cell (CSC) populations in certain types of human cancers. However, the effect of CXCR1 on CSC and its prognostic value in human pancreatic cancer remain unknown. In this study, we evaluated the expression of CXCR1 in human pancreatic duct adenocarcinoma (PDAC) and found that positive CXCR1 expression correlated with lymph node metastasis (P = 0.017) and a poor survival rate (HR, 3.748; 95% CI, 1.822 to 7.712; P < 0.001) in patients with PDAC. In addition, we identified significant positive correlations between CXCR1 and CD44 (P = 0.002) and CD133 (P = 0.017). Further functional studies confirmed that IL-8 addition increased sphere formation, CSC populations, and cell invasion of pancreatic cancer cells and that these effects could be reversed by antagonizing CXCR1 with a CXCR1-specific antibody. Therefore, our study demonstrated that the IL-8/CXCR1 axis is associated with the CSC-like properties of pancratic cancer cells and prognosis in human pancreatic cancer. This suggested a way of targeting pancreatic CSCs by disrupting IL-8/CXCR1 axis.
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Copper-catalyzed one-pot denitrogenative-dehydrogenative-decarboxylative coupling of ?-ketoacids with trifluorodiazoethane: facile access to trifluoromethylated aldol products.
Chemistry
PUBLISHED: 04-14-2014
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A novel copper-catalyzed one-pot cross-coupling of ?-ketoacids with in situ generated trifluorodiazoethane has been developed. This reaction provides a direct and efficient method, in which one C-C bond and one C-O bond were formed in a carbenoid center with concomitant denitrogenation-dehydrogenation-decarboxylation, to afford trifluoromethylated aldol products. In several preliminary experiments, good to high enantioselectivities were also obtained.
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Essential role for TrpC5-containing extracellular vesicles in breast cancer with chemotherapeutic resistance.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-14-2014
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A critical challenge for chemotherapy is the development of chemoresistance in breast cancer. However, the underlying mechanisms and validated predictors remain unclear. Extracellular vesicles (EVs) have gained attention as potential means for cancer cells to share intracellular contents. In adriamycin-resistant human breast cancer cells (MCF-7/ADM), we analyzed the role of transient receptor potential channel 5 (TrpC5) in EV formation and transfer as well as the diagnostic implications. Up-regulated TrpC5, accumulated in EVs, is responsible for EV formation and trapping of adriamycin (ADM) in EVs. EV-mediated intercellular transfer of TrpC5 allowed recipient cells to acquire TrpC5, consequently stimulating multidrug efflux transporter P-glycoprotein production through a Ca(2+)- and activated T-cells isoform c3-mediated mechanism and thus, conferring chemoresistance on nonresistant cells. TrpC5-containing circulating EVs were detected in nude mice bearing MCF-7/ADM tumor xenografts, and the level was lower after TrpC5-siRNA treatment. In breast cancer patients who underwent chemotherapy, TrpC5 expression in the tumor was significantly higher in patients with progressive or stable disease than in patients with a partial or complete response. TrpC5-containing circulating EVs were found in peripheral blood from patients who underwent chemotherapy but not patients without chemotherapy. Taken together, we found that TrpC5-containing circulating EVs may transfer chemoresistance property to nonchemoresistant recipient cells. It may be worthwhile to further explore the potential of using TrpC5-containing EVs as a diagnostic biomarker for chemoresistant breast cancer.
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Protective role of Klotho on cardiomyocytes upon hypoxia/reoxygenation via downregulation of Akt and FOXO1 phosphorylation.
Mol Med Rep
PUBLISHED: 04-12-2014
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Klotho is a novel anti-aging hormone involved in human coronary artery disease. The present study aimed to detect the effects and mechanism of Klotho on cardiomyocytes in a hypoxia/reoxygenation (H/R) model in vitro. Neonatal Sprague-Dawley rat cardiomyocytes were randomly distributed into experimental groups as follows: Control group; H/R group, 4?h hypoxia followed by 3?h reoxygenation; and H/R+Klotho group, incubated with 0.1, 0.2 or 0.4 µg/ml Klotho protein for 16 h and then subjected to 4?h hypoxia/3?h reoxygenation. In order to evaluate cardiomyocyte damage, cell viability and lactate dehydrogenase (LDH) levels were measured. Cell apoptosis was measured by flow cytometry. The 2',7'-dichlorofluorescein diacetate reagent was used to estimate the intracellular generation of reactive oxygen species (ROS). Immunofluorescence staining was used to test whether Klotho induced decreased nuclear translocation of forkhead box protein O1 (FOXO1). Western blot analysis was performed to detect protein levels of FOXO1, phospho-FOXO1, Akt, phospho-Akt and superoxide dismutase 2 (SOD2). Cell viability was significantly decreased, levels of LDH in the cardiomyocyte culture medium were significantly increased and the apoptotic rate was enhanced in the H/R group when compared with those of the control group. Compared with the H/R group, cell viability of the H/R+Klotho groups was significantly higher (P<0.05). Treatment with Klotho protein resulted in a significant resistance of cardiomyocytes to apoptosis and the release of LDH was decreased. Intracellular ROS levels in the H/R group were significantly elevated above those of the control group (P<0.05). Following treatment with Klotho, intracellular ROS levels were significantly decreased compared with those of the H/R group (P<0.05). Western blot analysis confirmed that Klotho protein treatment increased FOXO1 levels in the nucleus and decreased FOXO1 levels in the cytoplasm. Furthermore, exogenous Klotho protein promoted translocation of FOXO1 from cytoplasm to nucleus. In addition, the administration of Klotho protein suppressed phosphorylation of FOXO1 and Akt, and markedly increased the protein expression levels of SOD2. In conclusion, treatment with Klotho protein had beneficial effects on cardiomyocytes undergoing H/R injury. The mechanism of this effect may be associated with suppressed apoptosis of cardiomyocytes, inhibition of phosphorylation of FOXO1 and Akt as well as suppression of cytoplasm transfer of FOXO1.
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Protein design and engineering of a de novo pathway for microbial production of 1,3-propanediol from glucose.
Biotechnol J
PUBLISHED: 04-11-2014
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Protein engineering to expand the substrate spectrum of native enzymes opens new possibilities for bioproduction of valuable chemicals from non-natural pathways. No natural microorganism can directly use sugars to produce 1,3-propanediol (PDO). Here, we present a de novo route for the biosynthesis of PDO from sugar, which may overcome the mentioned limitations by expanding the homoserine synthesis pathway. The accomplishment of pathway from homoserine to PDO is achieved by protein engineering of glutamate dehydrogenase (GDH) and pyruvate decarboxylase to sequentially convert homoserine to 4-hydroxy-2-ketobutyrate and 3-hydroxypropionaldehyde. The latter is finally converted to PDO by using a native alcohol dehydrogenase. In this work, we report on experimental accomplishment of this non-natural pathway, especially by protein engineering of GDH for the key step of converting homoserine to 4-hydroxy-2-ketobutyrate. These results show the feasibility and significance of protein engineering for de novo pathway design and overproduction of desired industrial products.
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Fast crystal growth from organic glasses: comparison of o-terphenyl with its structural analogs.
J Phys Chem B
PUBLISHED: 04-03-2014
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Crystal growth kinetics and liquid dynamics of 1,2-diphenylcyclopentene (DPCP) and 1,2-diphenylcyclohexene (DPCH) were characterized by optical microscopy and dielectric spectroscopy. These two molecules are structurally homologous and dynamically similar to the well-studied glassformer ortho-terphenyl (OTP). In the supercooled liquid states of DPCP and DPCH, the kinetic component of crystal growth ukin has a power law relationship with the primary structural relaxation time ??, ukin [proportionality] ??(–?) (? ? 0.7), similar to OTP and other fragile liquids. Near the glass transition temperature (Tg), both DPCP and DPCH develop much faster crystal growth via the so-called GC (glass to crystal) mode, again similar to the behavior of OTP. We find that the ?-relaxation process apparently controls the onset of GC growth, with GC growth possible only at sufficiently low fluidity. These results support the view that GC crystal growth can only occur in systems where the liquid and crystal exhibit similar local packing arrangements.
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A reduced graphene oxide supported Cu(3)SnS(4) composite as an efficient visible-light photocatalyst.
Dalton Trans
PUBLISHED: 04-02-2014
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In this study, a visible light responsive Cu3SnS4/reduced graphene oxide (RGO) photocatalyst has been synthesized by a facile one-step solvothermal method. The as-synthesized samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, N2 adsorption-desorption, UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission spectroscopy. The photocatalytic activity of the Cu3SnS4/RGO composite under visible-light irradiation (? > 420 nm) was evaluated by measuring the degradation of rhodamine B (RhB) and phenol. The results revealed that the Cu3SnS4 nanoplates dispersed uniformly on the RGO surface. The Cu3SnS4/RGO composite exhibited much higher photocatalytic activity than pure Cu3SnS4. The enhancement in photocatalytic activity is likely to be due to the synergistic effect of an improved adsorptivity of pollutants, an enhanced visible light absorption and an effective charge separation. In addition, the Cu3SnS4/RGO photocatalyst was stable during the reaction and could be used repeatedly.
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Cloning, purification, crystallization and preliminary X-ray studies of the putative type VI secretion immunity protein Tli5 (PA5088) from Pseudomonas aeruginosa.
Acta Crystallogr F Struct Biol Commun
PUBLISHED: 03-29-2014
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The putative protein PA5089 from Pseudomonas aeruginosa has recently been identified as a Tle5 phospholipase effector from a type VI secretion system (T6SS), and its toxicity can be neutralized by the cognate immunity protein Tli5 (PA5088). Here, the expression, purification, crystallization and preliminary crystallographic analysis of PA5088 are reported. X-ray diffraction data were collected from selenomethionine-derivatized PA5088 crystals to a resolution of 2.55?Å. The crystals belonged to space group P2?, with unit-cell parameters a=64.002, b=104.744, c=90.168?Å.
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Dynamic changes of histone H3 lysine 27 acetylation in pre-implantational pig embryos derived from somatic cell nuclear transfer.
Anim. Reprod. Sci.
PUBLISHED: 03-25-2014
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Histone H3 lysine 27 acetylation (H3K27ac) is an active epigenetic modification which has been revealed to be associated with active gene expression. It was hypothesized that H3K27ac might also participate in the porcine somatic reprogramming process during early development of SCNT-derived embryos. The spatial and temporal expression profiles of H3K27ac were investigated at different developmental stages in SCNT embryos compared with in vitro fertilization (IVF) and parthenogenetic activation (PA) counterparts. Specifically, results showed that amounts of H3K27ac gradually decreased from the earliest pronuclear stage to 8-cell stage, corresponding to the major embryonic genome activation (EGA), followed by re-acetylation of H3K27 from the morula stage onwards accompanying the first cell lineage specification in IVF embryos. Similar dynamic patterns of H3K27ac signal was observed at all developmental stages of porcine SCNT and PA embryos except for the hatched stage in which amounts of H3K27ac in SCNT and PA embryos was slightly less than that in IVF counterparts. Moreover, the gradual decrease of H3K27ac before EGA was demonstrated to be an active process independent of DNA replication, RNA and protein synthesis. The expression of HDAC1, HDAC2, MBD3 and CBP genes were well correlated with the dynamic changes of H3K27ac mark. Overall, these results indicate that H3K27ac is only defective in late SCNT blastocysts, and that the dynamic changes of this marker might also underlie the EGA and initial cell lineage specification during early embryo development.
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Prediction of outer membrane proteins by combining the position- and composition-based features of sequence profiles.
Mol Biosyst
PUBLISHED: 03-15-2014
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Locating the transmembrane regions of outer membrane proteins (OMPs) is highly important for deciphering their biological functions at both molecular and cellular levels. Here, we propose a novel method to predict the transmembrane regions of OMPs by employing the position- and composition-based features of sequence profiles. Furthermore, a simple probability-based prediction model, which is estimated by the secondary structures of structurally known OMPs, is also developed. Considering that these two methods are both effective and well complementary, we integrate them into a method called TransOMP, which is also capable of identifying OMPs. Furthermore, we develop an OMP identification measure I_CScore by considering transmembrane regions by TransOMP and secondary structural topology by SSEA-OMP. Our methods were benchmarked against state-of-the-art methods and assessed in the genome of Escherichia coli. Benchmark results confirmed that our methods were reliable and useful. Meanwhile, we constructed an OMP prediction web server, which can be used for OMP identification, transmembrane region location, and 3D model building.
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Induction of B7-H1 expression by human cytomegalovirus in extravillous cytotrophoblast cells and role of MAPK pathway.
Pak J Med Sci
PUBLISHED: 02-25-2014
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This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism.
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MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway.
FEBS Lett.
PUBLISHED: 02-13-2014
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To investigate the role of microRNAs in the development of chemoresistance and related epithelial-mesenchymal transition (EMT), we examined the effect of miR-489 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). MiR-489 was significantly suppressed in MCF-7/ADM cells compared with chemosensitive parental control MCF-7/WT cells. Forced-expression of miR-489 reversed chemoresistance. Furthermore, Smad3 was identified as the target of miR-489 and is highly expressed in MCF-7/ADM cells. Forced expression of miR-489 both inhibited Smad3 expression and Smad3 related EMT properties. Finally, the interactions between Smad3, miR-489 and EMT were confirmed in chemoresistant tumor xenografts and clinical samples, indicating their potential implication for treatment of chemoresistance.
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Effect of lianhuaqingwen capsules on airway inflammation in patients with acute exacerbation of chronic obstructive pulmonary disease.
Evid Based Complement Alternat Med
PUBLISHED: 01-23-2014
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Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory response that is worsened by acute exacerbations. Lianhuaqingwen (LHQW) has anti-inflammatory and immune regulatory functions and may inhibit the airway inflammation that occurs during an acute exacerbation of COPD. In this study, 100 participants were recruited and randomly assigned, 1?:?1, to the LHQW and the conventional groups, which were treated, respectively, with LHQW capsules and conventional Western medicine or only conventional Western medicine. The scores of the CAT scale and levels of inflammatory cytokines in blood and sputum were measured during treatment. In addition, subjects were subdivided into high-risk and low-risk subgroups. The CAT scores in the LHQW group and high-risk subgroup were clearly improved from the 5th day, but the other groups improved only after treatment was completed. Expression levels of IL-8, TNF- ? , IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were significantly decreased after treatment, and similar results were found in subgroups. These data suggested that LHQW capsules can accelerate the improvement of AECOPD patients, especially for the high-risk subgroup, and the mechanism of action may be related to the decreased release of inflammatory mediators.
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High expression of erythropoietin-producing hepatoma cell line-B2 (EphB2) predicts the efficiency of the Qingyihuaji formula treatment in pancreatic cancer CFPAC-1 cells through the EphrinB1-EphB2 pathway.
Oncol Lett
PUBLISHED: 01-23-2014
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Our previous study demonstrated that inhibition of erythropoietin-producing hepatoma cell line-B2 (EphB2) expression resulted in the promotion of cancer growth, with EphB2 acting as a tumor suppressor in pancreatic cancer. Qingyihuaji formula (QYHJ), a traditional Chinese medicine, acts as an independent protective factor for pancreatic cancer patient survival and different patients have shown various responses to QYHJ treatment. In the current study, the different effects on tumor growth inhibition following QYHJ treatment in cells with different levels of EphB2 expression were investigated to reveal the mechanism. A subcutaneously transplanted tumor model using cancer cells with different levels of EphB2 expression were established in vivo and received a four-week QYHJ intervention. Tumor weight inhibitory rate and tumor volume deflation were evaluated. The cell cycle and apoptosis were analyzed by flow cytometry, and reverse transcription polymerase chain reaction and western blot analysis were used to assess mRNA and protein levels. The results showed that the tumor weight inhibitory rate was 31.40, 31.33 and 18.36% in CFPAC-1, CFPAC-1 control RNAi and CFPAC-1 EphB2 RNAi cells following QYHJ treatment, respectively. A statistically significant difference was identified in CFPAC-1 (P<0.05) and CFPAC-1 control RNAi (P<0.01) cells. In addition, a statistically significant increase was identified in the G0/G1 phase population (P<0.05) and a statistically significant decrease was identified in the S phase population (P<0.05) in CFPAC-1 and CFPAC-1 control RNAi cells; however, no significant difference was identified in the CFPAC-1 EphB2 RNAi cells following QYHJ treatment. QYHJ upregulated the mRNA and protein level of Eph receptor-interacting B1 (EphrinB1) in the cells that were expressing different levels of EphB2, however, QYHJ did not regulate EphB2 expression. In CFPAC-1 and CFPAC-1 control RNAi cells, the QYHJ treatment resulted in a statistically significant decrease in cyclin-dependent kinase 6 (CDK6) mRNA (P<0.05) and protein (P<0.05) levels. The high expression of EphB2 predicted the superior response rate to the QYHJ treatment through a mechanism of inhibiting the cell cycle by an EphrinB1-EphB2-induced CDK6 decrease in CFPAC-1 cells. Therefore, EphB2 acts as a predictive factor for QYHJ treatment in pancreatic cancer CFPAC-1 cells.
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Persistent organic pollutants (POPs) and fibroids: results from the ENDO study.
J Expo Sci Environ Epidemiol
PUBLISHED: 01-15-2014
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To evaluate the association between persistent organic pollutants (POPs) and uterine fibroids, we used previously collected data from a cohort of women aged 18-44 years undergoing laparoscopy or laparotomy at 14 participating hospital surgical centers (n=473). POP concentrations were measured in omental fat and serum. Presence of fibroids was defined on the basis of a postoperative diagnosis (n=99). Odds ratios (OR) and 95% confidence interval (CI) for each POP by biologic medium were estimated using unconditional logistic regression adjusted for identified covariates. Concentrations were higher in omental fat than in serum for all POPs. Serum p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) was the only POP associated with fibroids (per 1-SD increase in log-transformed p,p'-DDE OR (95% CI): 1.37 (1.05-1.80)). In analyses excluding women diagnosed with endometriosis, a number of polychlorinated biphenyls (PCBs) measured in omental fat were associated with fibroids (PCB 99: 1.64 (1.08, 2.49); PCB 138: 1.64 (1.03, 2.59); PCB 146: 1.54 (1.01, 2.37); PCB 153: 1.88 (1.12, 3.13); PCB 196: 1.60 (1.02, 2.51); PCB 206: 1.52 (1.01, 2.29)). Although exploratory, our study suggests that PCBs may be associated with fibroids in the absence of other gynecologic disorders such as endometriosis, but the associations varied by biologic media with more POPs emerging when quantified in fat.Journal of Exposure Science and Environmental Epidemiology advance online publication, 7 May 2014; doi:10.1038/jes.2014.31.
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Neonatal outcomes in early term birth.
Am. J. Obstet. Gynecol.
PUBLISHED: 01-06-2014
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To determine neonatal morbidity rates for early term birth compared with full term birth by precursor leading to delivery.
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Antitumor effect of water decoctions of taxus cuspidate on pancreatic cancer.
Evid Based Complement Alternat Med
PUBLISHED: 01-05-2014
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The Taxus cuspidate has been used as a traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. As we know that taxol isolated from the Taxus cuspidate has been approved for the treatment of ovarian cancer, it has also shown its antitumor abilities against other kinds of cancers. But the antitumor activity of other components which are free of paclitaxel and hydrophilic paclitaxel derivatives from Taxus cuspidate has not been fully understood. In this study, we investigated the effect of the water decoctions from the leaves of Taxus cuspidate on pancreatic cancer cell proliferation and the potential mechanism(s); though its antitumor activity and mechanism in vitro remain to be elucidated, the water soluble constituents from Taxus cuspidate could be used in clinical for cancer patients.
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A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase.
Metab. Eng.
PUBLISHED: 01-03-2014
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Engineering the cofactor availability is a common strategy of metabolic engineering to improve the production of many industrially important compounds. In this work, a de novo NADPH generation pathway is proposed by altering the coenzyme specificity of a native NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to NADP, which consequently has the potential to produce additional NADPH in the glycolytic pathway. Specifically, the coenzyme specificity of GAPDH of Corynebacterium glutamicum is systematically manipulated by rational protein design and the effect of the manipulation for cellular metabolism and lysine production is evaluated. By a combinatorial modification of four key residues within the coenzyme binding sites, different GAPDH mutants with varied coenzyme specificity were constructed. While increasing the catalytic efficiency of GAPDH towards NADP enhanced lysine production in all of the tested mutants, the most significant improvement of lysine production (~60%) was achieved with the mutant showing similar preference towards both NAD and NADP. Metabolic flux analysis with (13)C isotope studies confirmed that there was no significant change of flux towards the pentose phosphate pathway and the increased lysine yield was mainly attributed to the NADPH generated by the mutated GAPDH. The present study highlights the importance of protein engineering as a key strategy in de novo pathway design and overproduction of desired products.
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Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Human serum albumin (HSA) is extensively used in clinics to treat a variety of diseases, such as hypoproteinemia, hemorrhagic shock, serious burn injuries, cirrhotic ascites and fetal erythroblastosis. To address supply shortages and high safety risks from limited human donors, we recently developed recombinant technology to produce HSA from rice endosperm. To assess the risk potential of HSA derived from Oryza sativa (OsrHSA) before a First-in-human (FIH) trial, we compared OsrHSA and plasma-derived HSA (pHSA), evaluating the potential for an immune reaction and toxicity using human peripheral blood mononuclear cells (PBMCs). The results indicated that neither OsrHSA nor pHSA stimulated T cell proliferation at 1x and 5x dosages. We also found no significant differences in the profiles of the CD4(+) and CD8(+) T cell subsets between OsrHSA- and pHSA-treated cells. Furthermore, the results showed that there were no significant differences between OsrHSA and pHSA in the production of cytokines such as interferon-gamma (IFN-?), tumor necrosis factor-alpha (TNF-?), interleukin (IL)-10 and IL-4. Our results demonstrated that OsrHSA has equivalent immunotoxicity to pHSA when using the PBMC model. Moreover, this ex vivo system could provide an alternative approach to predict potential risks in novel biopharmaceutical development.
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Chinese herbal medicine suppresses invasion-promoting capacity of cancer-associated fibroblasts in pancreatic cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Pancreatic cancer remains one of the leading causes of cancer-related deaths, due to aggressive growth, high metastatic rates during the early stage and the lack of an effective therapeutic approach. We previously showed that Qingyihuaji (QYHJ), a seven-herb Chinese medicine formula, exhibited significant anti-cancer effects in pancreatic cancer, associated with modifications in the tumor microenvironment, particularly the inhibition of cancer-associated fibroblast (CAF) activation. In the present study, we generated CAF and paired normal fibroblast (NF) cultures from resected human pancreatic cancer tissues. We observed that CAFs exhibited an enhanced capacity for inducing pancreatic cancer cell migration and invasion compared with NFs, while QYHJ-treated CAFs exhibited decreased migration and invasion-promoting capacities in vitro. The results of further analyses indicated that compared with NFs, CAFs exhibit increased CXCL1, 2 and 8 expression, contributing to the enhanced invasion-promoting capacities of these cells, while QYHJ treatment significantly suppressed CAF proliferation activities and the production of CAF-derived CXCL1, 2 and 8. These in vitro observations were confirmed in mice models of human pancreatic cancer. Taken together, these results suggested that suppressing the tumor-promoting capacity of CAFs through Chinese herbal medicine attenuates pancreatic cancer cell invasion.
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Rational Design of Allosteric Regulation of Homoserine Dehydrogenase by a Non-Natural Inhibitor L-Lysine.
ACS Synth Biol
PUBLISHED: 12-19-2013
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Allosteric proteins which can sense different signals are interesting biological parts for synthetic biology. In particular, the design of an artificial allosteric enzyme to sense an unnatural signal is both challenging and highly desired, e.g. for a precise and dynamical control of fluxes of growth-essential but byproduct pathways in metabolic engineering of industrial microorganisms. In this work, we used homoserine dehydrogenase (HSDH) of Corynebacterium glutamicum, which is naturally allosterically regulated by threonine and isoleucine, as an example to demonstrate the feasibility of reengineering an allosteric enzyme to respond to an unnatural inhibitor L-lysine. For this purpose, the natural threonine binding sites of HSD were first predicted and verified by mutagenesis experiments. The threonine binding sites were then engineered to a lysine binding pocket. The reengineered HSD only responds to lysine inhibition but not to threonine. This is a significant step towards the construction of artificial molecular circuits for dynamic control of growth-essential byproduct formation pathway for lysine biosynthesis.
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Acute kidney injury induced by aristolochic acid in patients with primary glomerular nephritis.
Ren Fail
PUBLISHED: 12-17-2013
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Abstract Background: Acute kidney injury induced by aristolochic acid (AA) might occur in patients with chronic glomerular nephritis (CGN). In this study, the clinical and pathological features of patients with acute aristolochic acid nephropathy (AAN) superimposing CGN (AAN-CGN) were investigated. Methods: Eighteen patients diagnosed as acute AAN were included in this retrospective study, from January 2001 to December 2009. According to the pre-existing CGN, 13 patients were identified as the AAN-CGN group, and 5 isolated AAN patients as the control group. Clinical and pathological features were compared between the two groups. Results: In the AAN-CGN group, six patients complained with gastrointestinal symptoms, such as nausea, vomiting, or loss of appetite. The rest of seven cases were asymptomatic or minimally uncomfortable, who were found with elevated serum creatinine (Scr) in the follow up of CGN. Compared with the control group, the patients in AAN-CGN group had higher levels of serum uric acid, urine n-acetyl-?-d-glucosaminidase, and urine protein excretion (366.2?±?122.8 vs. 218.0?±?125.8??mol/L, p?=?0.037; 9.74?±?4.4 vs. 1.38?±?1.01?g/d, p?=?0.001; 61.2?±?21.9 vs. 27.4?±?15.8??/g???cr, p?=?0.007, respectively). In addition to, the AAN-CGN patients had an absolutely prominent percentage of macromolecule substance in the urine protein electrophoresis (25.0?±?6.32 vs. 15.8?±?7.8%, p?=?0.029). The occurrence of hypokalemia and excretion of aminoaciduria were lower than that in the control group. Pathologically, 84.6% of patients were found with tubular brush border dropping, 30.8% with naked tubular basement membrane, and 15.4% with different stages of vascular lesion. There were no statistical differences in the above-mentioned pathological parameters between the two groups. In the follow-up, 10 patients with AAN-CGN recovered with normal Scr, accounting for 76.9%, which was better than the recovery in the control group. Conclusion: Patients with acute AAN-CGN manifested with a great mass of urine protein excretion, low incidence of hypokalemia and aminoaciduria, however, the tubular-interstitial lesions were similar to the isolated AAN.
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Deregulation of feedback inhibition of phosphoenolpyruvate carboxylase for improved lysine production in Corynebacterium glutamicum.
Appl. Environ. Microbiol.
PUBLISHED: 12-13-2013
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Allosteric regulation of phosphoenolpyruvate carboxylase (PEPC) controls the metabolic flux distribution of anaplerotic pathways. In this study, the feedback inhibition of PEPC of Corynebacterium glutamicum was rationally deregulated and its effect on metabolic flux redistribution was evaluated. Based on rational protein design, six PEPC mutants were designed and all of them showed significantly reduced sensitivity towards aspartate and malate inhibition. Introducing one of the point mutations (N917G) into the ppc gene, encoding PEPC of the lysine producing strain C. glutamicum LC298, resulted in ? 37 % improved lysine production. In vitro enzyme assays and (13)C based metabolic flux analysis showed about 20 % and 30 % increase in the PEPC activity and corresponding flux in the mutant strain respectively. Higher demand for NADPH in the mutant strain increased the flux towards pentose phosphate pathway (PPP) which increased the supply of NADPH for enhanced lysine production. The present study highlights the importance of allosteric regulation on the flux control of central metabolism. The strategy in this study can also be implemented to improve other oxaloacetate derived products.
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[Emdogain regulates the expression of bone sialoprotein gene in human dental pulp cells].
Zhonghua Kou Qiang Yi Xue Za Zhi
PUBLISHED: 12-10-2013
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To analyze the effects of emdogain(EMD) on the expression of the bone sialoprotein(BSP) gene in human dental pulp cells and to elucidate the molecular mechanism of BSP gene regulated by EMD.
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The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.
Hum. Reprod.
PUBLISHED: 12-04-2013
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What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant?
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A tubular europium-organic framework exhibiting selective sensing of Fe3+ and Al3+ over mixed metal ions.
Chem. Commun. (Camb.)
PUBLISHED: 11-02-2013
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A luminescent europium-organic framework with tubular channels based on the H4BTMIPA ligand (H4BTMIPA = 5,5-methylenebis(2,4,6-trimethylisophthalic acid)) was assembled and characterized. The [H2N(CH3)2](+) ions as counterions are located in the channels. The cation exchange between [H2N(CH3)2](+) and metal ions resulted in complex that can selectively sense Fe(3+) and Al(3+) ions through fluorescence quenching and enhancement, respectively.
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MicroRNA targets autophagy in pancreatic cancer cells during cancer therapy.
Autophagy
PUBLISHED: 10-08-2013
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The therapeutic outcome of pancreatic cancer is generally poor due to the inherent or acquired resistance of cancer cells to treatment. Pancreatic cancer cells have higher basal autophagy levels than other cancer cell types, which may correlate with their nonresponsiveness to the available cancer therapy. Therefore, understanding the mechanisms behind autophagy activation in pancreatic cancer cells may ultimately improve therapeutic outcomes. Here we demonstrated that MIR23B is a potent inhibitor of autophagy. MIR23B targets the 3?UTR of the autophagy-related gene ATG12, thereby decreasing autophagic activity and ultimately promoting radiation-induced pancreatic cancer cell death. Thus, our study clarified some of the underlying molecular mechanisms of activated autophagy in response to cancer therapy in pancreatic cancer.
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High Intensity Focused Ultrasound Treatment for Patients with Local Advanced Pancreatic Cancer.
Hepatogastroenterology
PUBLISHED: 10-04-2013
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:Background/Aims: To evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) therapy in patients with local advanced pancreatic cancer. Methodology: 39 patients with local advanced pancreatic cancer were treated with HIFU, including 26 male and 13 female patients. The locations of the tumours were as follows: head of pancreas in 7 patients, body and/or tail of pancreas in 32 patients. Pain relief, time to progression (TTP), median survival and complications were analysed after HIFU treatment. Results: There were no severe complications or adverse events related to HIFU therapy in any of the patients treated. Pain relief was achieved in 79.5% of patients. Median TTP was 5.0 months. The median overall survival time was 11 months. 6-month and 1-year survival rate for patients were 82.1% and 30.8% respectively. Conclusions: Although this study may have limitations, preliminary results demonstrate the safety of clinical application of HIFU for pancreatic cancer and reveal it to be a promising mode of treatment for local advanced pancreatic cancers.
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Effects of Endothelin-1 Chronic Stimulation on Electrical Restitution, Beat-to-beat Variability of Repolarization, and Ventricular Arrhythmogenesis.
J. Cardiovasc. Pharmacol.
PUBLISHED: 10-03-2013
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: Chronically elevated levels of endothelin-1 (ET-1) have been detected in several cardiovascular diseases. In this study, we investigated the chronic effects of ET-1 on the electrophysiological characteristics expected to influence the genesis and maintenance of ventricular arrhythmia (VA). Rabbits were randomized to ET-1 (ET-1 group) or 0.9% saline (control group) for 2 weeks. The S1-S2 protocol and S1-S1 dynamic pacing were performed to assess the action potential duration restitution (APDR) and to induce APD alternans or VA in 4 sites of Langendorff-perfused rabbit hearts. The beat-to-beat variability of repolarization was quantified as short-term variability and long-term variability. Compared with the control group, chronic ET-1 administration significantly prolonged QT intervals, APD at 90% repolarization (APD90), and effective refractory period (ERP), steepened the maximum slopes of the APDR curve, decreased the ERP/APD90 ratio, and increased the spatial dispersions of APD90, ERP, and maximum slopes (P < 0.05 for all). Moreover, chronic ET-1 administration markedly increased the short-term variability and long-term variability (P < 0.01 for all). APD alternans occurred in both groups, but the threshold of APD alternans was decreased at all sites in the ET-1 group (P < 0.01 for all). We also observed that chronic ET-1 stimulation significantly increased the incidence and duration of the VA episodes. These results suggest that chronic stimulation with ET-1 facilitated VA by steepening the APDR curve and increasing the spatial dispersion of APDR and beat-to-beat variability of repolarization.
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Bayesian Hierarchical Poisson Regression Models: An Application to a Driving Study with Kinematic Events.
J Am Stat Assoc
PUBLISHED: 10-01-2013
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Although there is evidence that teenagers are at a high risk of crashes in the early months after licensure, the driving behavior of these teenagers is not well understood. The Naturalistic Teenage Driving Study (NTDS) is the first U.S. study to document continuous driving performance of newly-licensed teenagers during their first 18 months of licensure. Counts of kinematic events such as the number of rapid accelerations are available for each trip, and their incidence rates represent different aspects of driving behavior. We propose a hierarchical Poisson regression model incorporating over-dispersion, heterogeneity, and serial correlation as well as a semiparametric mean structure. Analysis of the NTDS data is carried out with a hierarchical Bayesian framework using reversible jump Markov chain Monte Carlo algorithms to accommodate the flexible mean structure. We show that driving with a passenger and night driving decrease kinematic events, while having risky friends increases these events. Further the within-subject variation in these events is comparable to the between-subject variation. This methodology will be useful for other intensively collected longitudinal count data, where event rates are low and interest focuses on estimating the mean and variance structure of the process. This article has online supplementary materials.
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Graphene sheets grafted three-dimensional BiOBr0.2I0.8 microspheres with excellent photocatalytic activity under visible light.
J. Hazard. Mater.
PUBLISHED: 08-14-2013
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A series of graphene sheets grafted three-dimensional BiOBr0.2I0.8 microspheres with different graphene contents have been synthesized by a simple one-step solvothermal method. The BiOBr0.2I0.8 microspheres were composed of numerous nanoplates with a thickness of about 10nm and dispersed uniformly on the surface of graphene. The assembled BiOBr0.2I0.8/graphene composites exhibited excellent photocatalytic activity in the degradation of rhodamine B (RhB) and phenol under visible light irradiation (?>420nm). The optimal graphene content was found to be 10.0wt.%, and the corresponding photocatalytic activity in degradation of RhB and phenol was 3.19 and 3.27 times that of pure BiOBr0.2I0.8, respectively. The enhanced photocatalytic activity could be attributed to more effective charge transportations and separations, larger specific surface areas and the increased light absorption. A possible photocatalytic mechanism of the BiOBr0.2I0.8/graphene composites was also proposed.
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Electron relaxation effect on the sub-100-fs laser interaction with gold thin film.
Opt Lett
PUBLISHED: 08-14-2013
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The heating of a gold thin film by a single 10 fs laser pulse is modeled by a combined continuum-atomistic method considering the electron relaxation effect. Numerical results show that the temperature evolution and stress propagation proceed in the same manners as those for the subpicosecond laser irradiation. It is also found that the electron relaxation effect is insignificant and could be considerably overestimated by neglecting the ballistic energy transfer in the film.
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Uniextrapedicular kyphoplasty for the treatment of thoracic osteoporotic vertebral fractures.
Orthopedics
PUBLISHED: 08-14-2013
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Osteoporotic vertebral compression fractures are common and cause pain and disability. Most osteoporotic vertebral compression fractures occur in the lower thoracic and thoracolumbar spine. Percutaneous balloon kyphoplasty through a transpedicular approach is a classic procedure performed to treat osteoporotic vertebral compression fractures. However, due to the slender morphology of the pedicles, small pedicle size, and the angular severity of thoracic kyphosis, performing kyphoplasty in middle and high thoracic levels is technically challenging. The purpose of this retrospective study was to evaluate the clinical outcomes of single-balloon kyphoplasty for the treatment of thoracic osteoporotic vertebral compression fractures via an extrapedicular approach. Between July 2004 and May 2008, thirty-eight patients with thoracic osteoporotic vertebral compression fractures underwent percutaneous kyphoplasty via a unilateral extrapedicular approach. Average patient age was 60.3 years. Symptomatic levels ranged from T4 to T12. All affected vertebrae were identified via physical examination, magnetic resonance imaging, and radiographs. Pain relief, vertebral height restoration, and kyphosis correction were compared pre- and postoperatively using the visual analog scale and radiographs. The operation was successful in all patients. Average injected bone cement volume was 3.2±1.4 mL. Mean follow-up was 9.5 months. Visual analog scale pain score improved in 36 of 38 patients postoperatively. Mean visual analog scale pain score was 8.92±0.682 preoperatively and 2.40±0.31 postoperatively and remained at 2.80±0.34 until last follow-up. Mean middle body height correction ratio was 50.9%±34.6%. No lateral wedging was found in the coronal alignment of the treated vertebrae. Three (7.9%) patients sustained cement extravasation with no adverse events. Kyphoplasty through a unilateral extrapedicular approach can achieve convergent and proper cement filling in the affected vertebrae to effectively restore stiffness, relieve pain, and correct kyphosis in fractured vertebrae.
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shRNA-mediated Slc38a1 silencing inhibits migration, but not invasiveness of human pancreatic cancer cells.
Chin. J. Cancer Res.
PUBLISHED: 08-12-2013
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Early metastasis is a major biological feature of pancreatic cancer. The current study examined whether silencing Slc38a1, a gene involved in energy metabolism, using short hairpin RNA (shRNA) could inhibit the growth, migration, and invasiveness of pancreatic cancer cells.
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Comparison of microfabricated hexagonal and lamellar post arrays for DNA electrophoresis.
Electrophoresis
PUBLISHED: 08-09-2013
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We used Brownian dynamics simulations to compare DNA separations in microfabricated post arrays containing either hexagonal or lamellar lattices. Contrary to intuition, dense hexagonal arrays with frequent DNA post collisions do not yield the optimal separation. Rather, hexagonal arrays with pore sizes commensurate with the radius of gyration of the DNA lead to increased separation resolution due to a molecular weight dependent collision probability that increases with molecular weight. However, when the hexagonal array is too sparse, this advantage is lost due to the low number of collisions. Lamellar lattices, such as the DNA nanofence, appear to be superior to a hexagonal array at the same post density, since the lamellar lattice combines regions for DNA relaxation with locally dense post regions for collisions. The relative advantages of different post arrays designs are explained in terms of the statistics for the number of collisions and the holdup time, providing guidelines for designing post arrays for separating long DNA.
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Shear stress activation of nuclear receptor PXR in endothelial detoxification.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-22-2013
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Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-? and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics.
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Evaluation of the effectiveness of semen storage and sperm purification methods for spermatozoa transcript profiling.
Syst Biol Reprod Med
PUBLISHED: 07-19-2013
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Different semen storage and sperm purification methods may affect the integrity of isolated spermatozoal RNA. RNA-Seq was applied to determine whether semen storage methods (pelleted vs. liquefied) and somatic cell lysis buffer (SCLB) vs. PureSperm (PS) purification methods affect the quantity and quality of sperm RNA. The results indicate that the method of semen storage does not markedly impact RNA profiling whereas the choice of purification can yield significant differences. RNA-Seq showed that the majority of mitochondrial and mid-piece associated transcripts were lost after SCLB purification, which indicated that the mid-piece of spermatozoa may have been compromised. In addition, the number of stable transcript pairs from SCLB-samples was less than that from the PS samples. This study supports the view that PS purification better maintains the integrity of spermatozoal RNAs.
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ZincExplorer: an accurate hybrid method to improve the prediction of zinc-binding sites from protein sequences.
Mol Biosyst
PUBLISHED: 07-18-2013
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As one of the most important trace elements within an organism, zinc has been shown to be involved in numerous biological processes and closely implicated in various diseases. The zinc ion is important for proteins to perform their functional roles. To provide in-depth functional annotation of zinc-binding proteins, an initial but crucial step is the accurate recognition of zinc-binding sites. Motivated by the biological importance of zinc, we propose a new method called ZincExplorer to predict zinc-binding sites from protein sequences. ZincExplorer is a hybrid method that can accurately predict zinc-binding sites from protein sequences. It integrates the outputs of three different types of predictors, namely, SVM-, cluster- and template-based predictors. Four types of zinc-binding amino acids CHEDs (i.e. CYS, HIS, ASP and GLU) could be predicted using ZincExplorer. It achieved a high AURPC (Area Under Recall-Precision Curve) of 0.851, and a precision of 85.6% (specificity = 98.4%, MCC = 0.747) at the 70.0% recall for the CHEDs on the 5-fold cross-validation test. When tested on an independent dataset containing 2023 zinc-binding CHEDs and 14,493 non-zinc-binding CHEDs, it achieved about 3-8% higher AURPC in comparison to two other sequence-based predictors. Moreover, ZincExplorer could also identify the interdependent relationships (IRs) of the predicted zinc-binding sites bound to the same zinc ion, which makes it a useful tool for providing in-depth zinc-binding site annotation.
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Complete genome sequence of a duck hepatitis a virus 1 isolated from a pigeon in china.
Genome Announc
PUBLISHED: 07-13-2013
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We report here the complete genome sequence of a duck hepatitis A virus 1 (DHAV-1), strain FJ1220, isolated from a dead pigeon in eastern China. DHAV-1 FJ1220 has high homology of up to 99.6% to the DHAV-1 strain Du/CH/LGD/111238 but relatively low homology to strains FFZ05 and FZ05. An amino acid hypervariable region in the VP1 protein of FJ1220 has the motif (180)TPSGR(184) replaced by (180)ALSRG(184) compared to strains FFZ05 and FZ05.
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Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility.
Circulation
PUBLISHED: 07-09-2013
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The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2).
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Traditional Chinese medicine ZHENG and Omics convergence: a systems approach to post-genomics medicine in a global world.
OMICS
PUBLISHED: 07-09-2013
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Traditional Chinese medicine (TCM) is a comprehensive system of medical practice that has been used to diagnose, treat, and prevent illnesses for more than 3000 years. ZHENG (also known as "syndrome") differentiation remains the essence of TCM. In China, TCM shares equal status, and integrated with Western medicine in the healthcare system to treat many types of diseases. Yet, compared to biomolecular science and Western medicine, the ZHENG/TCM approach to diagnostics might appear unobjective, but offers at the same time long-standing clinical and phenotypic-rich insights. With the current globalization of life sciences and the arrival of "Big Data" research and development, these two silos of medical lore are rapidly coalescing. The applications of multi-omics strategies to TCM have begun to provide novel insights into the essence and molecular basis of TCM ZHENG. We searched the Chinese electronic databases and PubMed for published articles related to "Omics" and "TCM ZHENG" and observed a dramatic increase in studies over the past few years. In this article, we provide a timely synthesis of the lessons learned, and the emerging applications of omics science in TCM ZHENG research. We suggest that the global health scholarship and the field of "developing world Omics" can usefully draw from TCM, and vice versa.
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Ca2+/calmodulin-dependent protein kinase kinase ? phosphorylation of Sirtuin 1 in endothelium is atheroprotective.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-10-2013
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Atheroprotective flow exerts antioxidative and anti-inflammatory effects on vascular endothelial cells (ECs), in part through the induction of Sirtuin 1 (SIRT1), a class III histone deacetylase. The role of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)? in flow induction of SIRT1 both in vitro and in vivo was investigated. Pulsatile shear stress mimicking atheroprotective flow increased the level of SIRT1 in cultured ECs by enhancing its stability, and this effect was abolished by inhibition or knockdown of CaMKK?. Flow-enhanced SIRT1 stability was primarily mediated by CaMKK? phosphorylation of SIRT1 at Ser-27 and Ser-47, as evidenced by in vitro kinase assay, mass spectrometry, and experiments using loss- or gain-of-function SIRT1 mutants. Flow-induced CaMKK? phosphorylation of SIRT1 Ser-27 and Ser-47 increased antioxidative and anti-inflammatory capacities. Ablation of CaMKK? or SIRT1 in mice with an apolipoprotein E-null background showed increased atherosclerosis both in athero-prone and in athero-protective areas. The results suggest that the CaMKK?-SIRT1 axis in ECs is mechanosensitive, antioxidative, and anti-inflammatory.
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Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort.
J. Clin. Endocrinol. Metab.
PUBLISHED: 06-06-2013
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Thyroid diseases are inconsistently reported to increase risk for pregnancy complications.
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Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state.
Free Radic. Biol. Med.
PUBLISHED: 05-22-2013
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Endothelial functions are highly regulated by imposed shear stress in vivo. The characteristics of shear stress determine mechanotransduction events that regulate phenotypic outcomes including redox and inflammatory states. Recent data indicate that microRNAs (miRs) in vascular endothelial cells play an essential role in shear stress-regulated endothelial responses. More specifically, atheroprotective pulsatile flow (PS) induces miRs that inhibit mediators of oxidative stress and inflammation while promoting those involved in maintaining vascular homeostasis. Conversely, oscillatory flow (OS) elicits the opposing networks. This is exemplified by the PS-responsive transcription factor Krüppel-like factor 2 (KLF2), which regulates miR expression but is also regulated by OS-sensitive miRs to ultimately regulate the oxidative and inflammatory state of the endothelium. In this review, we outline important findings demonstrating the multifaceted roles of shear stress-regulated miRs in endothelial redox and inflammatory balance. Furthermore, we discuss the use of algorithms in deciphering signaling networks differentially regulated by PS and OS.
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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.

How does it work?

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

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

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