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Find video protocols related to scientific articles indexed in Pubmed.
Reductive dechlorination of BCl3 for efficient ammonia borane regeneration.
Dalton Trans
PUBLISHED: 11-20-2014
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This paper reports a complete ammonia borane (AB) regeneration process in which Bu3SnH was utilized as a reductant for the reductive dechlorination of BCl3, and Et2PhN was selected as a 'helper ligand' to generate Et2PhN·BH3, which gives rise to a high yield of AB by a base-exchange reaction at ambient temperature.
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Evaluation of Plasma Exchange and Continuous Veno-Venous Hemofiltration for the Treatment of Severe Avian Influenza A (H7N9): A Cohort Study.
Ther Apher Dial
PUBLISHED: 11-04-2014
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Avian influenza A (H7N9) is a severe disease with high mortality. Hypercytokinemia is thought to play an important role in the pathogenesis. This study was to investigate the efficiency of plasma exchange (PE)?+?continuous veno-venous hemofiltration (CVVH) on the removal of inflammatory mediators and their benefits in the management of fluid overload and metabolic disturbance. In total, 40 H7N9-infected patients were admitted to our hospital. Sixteen critically ill H7N9-infected patients received combination of PE and CVVH. Data from these 16 patients were collected and analyzed. The effects of PE?+?CVVH on plasma cytokine/chemokine levels and clinical outcomes were examined. H7N9-infected patients had increased plasma levels compared to healthy controls. After 3?h of PE?+?CVVH treatment, the cytokine/chemokine levels descended remarkably to lower levels and were maintained thereafter. PE?+?CVVH also benefited the management of fluid, cardiovascular dysfunction and metabolic disturbance. Of the 16 critically ill patients who received PE?+?CVVH, 10 patients survived. PE?+?CVVH decreased the plasma cytokine/chemokine levels significantly. PE?+?CVVH were also beneficial to the management of severe avian influenza A (H7N9).
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Specific recognition of guanines in non-duplex regions of nucleic acids with potassium tungstate and hydrogen peroxide.
Nucleic Acids Res.
PUBLISHED: 10-31-2014
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Structural features of nucleic acids have become an integral part of current biomedical research. Highly selective and readily performed methods with little toxicity that target guanosines in non-duplex nucleic acids are needed, which led us to search for an effective agent for guanosine sequencing. Treatment of DNA or RNA with potassium tungstate and hydrogen peroxide produced damaged guanosines in DNA or RNA sequences. The damaged guanosines in non-duplex DNA could be cleaved by hot piperidine. Similarly, damaged guanosines in non-duplex RNA could be cleaved by aniline acetate. We could identify structural features of nucleic acid using this strategy instead of dimethyl sulphate and Ribonuclease T1.
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The analysis of deregulated expression and methylation of the PER2 genes in gliomas.
J Cancer Res Ther
PUBLISHED: 10-15-2014
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Growing evidence shows that disruption of circadian rhythm may be a risk factor in the development of glioma. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored and differential expression of the circadian clock genes in glioma and non-tumor cells may provide a molecular basis for manifesting this mechanism.
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Immune Activation and a 9-Year Ongoing Complete Remission Following CD40 Antibody Therapy and Metastasectomy in a Patient with Metastatic Melanoma.
Cancer Immunol Res
PUBLISHED: 09-24-2014
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Direct immune activation via agonistic mAbs is a potentially complementary approach to therapeutic blockade of inhibitory immune receptors in cancer. Here, we provide genetic analysis of the immunologic consequences associated with the use of an agonistic CD40 mAb in a patient with metastatic melanoma who responded, underwent a single metastasectomy, and then achieved a complete remission ongoing for more than 9 years after starting therapy. Tumor microenvironment after immunotherapy was associated with proinflammatory modulations and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T-cell receptors (TCR) in the tumor and blood. The de novo T-cell repertoire identified in the posttreatment metastasectomy sample was also present-and in some cases expanded-in the circulation years after completion of therapy. Comprehensive study of this "exceptional responder" highlights the emerging potential of direct immune agonists in the next wave of cancer immunotherapies and a potential role for TCR deep sequencing in cancer immune assessment. Cancer Immunol Res; 2(11); 1051-8. ©2014 AACR.
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Perfusion-weighted magnetic resonance imaging detects recurrent isolated vertigo caused by cerebral hypoperfusion.
Int. J. Neurosci.
PUBLISHED: 09-10-2014
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Aim of the study: The etiology of isolated vertigo has been a substantial diagnostic challenge for both neurologists and otolaryngologists. This study was designed to detect recurrent isolated vertigo due to cerebral hypoperfusion using perfusion-weighted magnetic resonance imaging (PWI). Methods: We recruited isolated vertigo patients whose clinical condition was suspected to be caused by hypodynamics of the brain; these individuals formed the case group. We generated two additional groups: a negative group composed of vertigo patients whose symptoms were caused by problems associated with the ear and a healthy control group. Each subject underwent PWI, and seven regions of interest (ROIs) were chosen. The relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) were obtained from each ROI. We further calculated the absolute difference of relative parameter values between two mirrored ROIs. Results: The significant difference in the relative MTT from the mirrored cerebellar ROI (|rMTTleft-right|) of the case group was larger than those from the negative and healthy control groups (p = 0.026 and p = 0.038, respectively). Signal differences in |rrCBVleft-right| and |rrCBFleft-right| were not found among the three groups. Conclusions: In summary, disequilibrium in the rMTT of the bilateral cerebellum in the case group implied that hypoperfusion of the posterior circulation could trigger recurrent isolated vertigo and could be shown efficiently using PWI.
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Somatic intronic microsatellite loci differentiate glioblastoma from lower-grade gliomas.
Oncotarget
PUBLISHED: 08-26-2014
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Genomic studies of glioma sub-types have amassed new disease specific mutations, yet these only partially explain how mutations are linked to predisposition or progression. We hypothesized that microsatellite variation could expand the understanding of glioma etiology. Furthermore, germline markers for gliomas are typically undetectable; therefore we also hypothesize that the predictability of cancer-associated microsatellite loci in germline DNA may support the current hypothesis of a glioma cell of origin. In this study, "normal" germline exome sequenced DNA from the 1000 Genomes Project (n=390) were compared with exome sequences from germlines of subjects with WHO grade II and III lower-grade glioma (LGG, n=136) and WHO grade IV glioblastoma (GBM, n=252) from The Cancer Genome Atlas to identify microsatellite loci non-randomly associated with glioma. From germline data, we identified 48 GBM-specific loci, 42 Lower-grade glioma specific loci and 29 loci that distinguish GBM from LGG (p? 0.01). We then attempted to distinguish WHO grade II glioma (n=67) from GBM resulting in 8 informative loci. Significantly, in all glioma grades, comparisons between tumor and matched germline sequences demonstrated no significant differences in these variants (p? 0.01). Therefore, these microsatellite loci are considered to be components of grade-specific signatures for glioma which distinguish germline sequences of individuals with cancer from those of individuals that are "normal". In order to better understand the significance of these loci, we identified biological processes enriched in genes with these variants. Most strikingly, six helicase genes were enriched in the GBM cohort (p? 1.0 x10?³). The preservation of these glioma-specific loci could therefore serve as valuable diagnostic and therapeutic markers; especially since the heterogeneity of tumor cell populations can obscure the identification of mutations preceding a metastatic phenotype.
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Composite photothermal platform of polypyrrole-enveloped Fe?O? nanoparticle self-assembled superstructures.
ACS Appl Mater Interfaces
PUBLISHED: 08-18-2014
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Photothermal nanoplatforms with small size, low cost, multifunctionality, good biocompatibility and in particular biodegradability are greatly desired in the exploration of novel diagnostic and therapeutic methodologies. Despite Fe3O4 nanoparticles (NPs) have been approved as safe clinical agents, the low molar extinction coefficient and subsequent poor photothermal performance shed the doubt as effective photothermal materials. In this paper, we demonstrate the fabrication of polypyrrole (PPy)-enveloped Fe3O4 NP superstructures with a spherical morphology, which leads to a 300-fold increase in the molar extinction coefficient. The basic idea is the optimization of Fe3O4 electronic structures. By controlling the self-assembly of Fe3O4 NPs, the diameters of the superstructures are tuned from 32 to 64 nm. This significantly enhances the indirect transition and magnetic coupling of Fe ions, thus increasing the molar extinction coefficient of Fe3O4 NPs from 3.65 × 10(6) to 1.31 × 10(8) M(-1) cm(-1) at 808 nm. The envelopment of Fe3O4 superstructures with conductive PPy shell introduces additional electrons in the Fe3O4 oscillation system, and therewith further enhances the molar extinction coefficient to 1.12 × 10(9) M(-1) cm(-1). As a result, the photothermal performance is greatly improved. Primary cell experiments indicate that PPy-enveloped Fe3O4 NP superstructures are low toxic, and capable to kill Hela cells under near-infrared laser irradiation. Owing to the low cost, good biocompatibility and biodegradability, the PPy-enveloped Fe3O4 NP superstructures are promising photothermal platform for establishing novel diagnostic and therapeutic methods.
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A phenome-guided drug repositioning through a latent variable model.
BMC Bioinformatics
PUBLISHED: 08-08-2014
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The phenome represents a distinct set of information in the human population. It has been explored particularly in its relationship with the genome to identify correlations for diseases. The phenome has been also explored for drug repositioning with efforts focusing on the search space for the most similar candidate drugs. For a comprehensive analysis of the phenome, we assumed that all phenotypes (indications and side effects) were inter-connected with a probabilistic distribution and this characteristic may offer an opportunity to identify new therapeutic indications for a given drug. Correspondingly, we employed Latent Dirichlet Allocation (LDA), which introduces latent variables (topics) to govern the phenome distribution.
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Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells.
Pigment Cell Melanoma Res
PUBLISHED: 08-06-2014
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We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAF(V600E) mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated ?-galactosidase (SA-?-gal), senescence associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence like SA-?-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail-vein colony forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance. This article is protected by copyright. All rights reserved.
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Interference-Free HER2 ECD as a Serum Biomarker in Breast Cancer.
J Mol Biomark Diagn
PUBLISHED: 08-05-2014
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Over-expression of the HER2/neu receptor occurs in 20 to 30 percent of breast tumors and is linked to poorer prognosis. The HER2/neu expression status determines whether or not patient will receive trastuzumab-based treatment. In clinical practice, over-expression of HER2/neu is routinely identified using Immunohistochemistry (IHC) or Fluorescence in Situ Hybridization (FISH), both of which are invasive approaches requiring tissue samples. Serum assays for the Extra Cellular Domain of HER2/neu receptor (HER2 ECD) have been reported but the use is very limited due to serum interference factors (e.g. human anti-animal immunoglobulin antibodies) that lead to false test results and inconsistency with tissue Her2 status. We have developed an ELISA based approach using an MBB buffer to eliminate false results and to obtain more accurate assessment of HER2 ECD levels. Using this refined assay we retroactively measured HER2/neu levels from breast cancer patients and controls. Abnormal HER2 ECD levels were detected in about 32% of invasive breast cancer patients but not in controls or patients with benign diseases. In addition, we also showed that patients with elevated serum HER2 levels appeared to have worse survival regardless of treatments. In a small group of 12 Ductal Carcinoma in situ (DCIS) patients who received HER2/neu peptide vaccination and surgery, only one patient showed constantly rising HER2 levels after treatment and this patient had recurrence of HER2 positive tumor within 5 years. Our studies indicate that once the serum interference issue is resolved, serum HER2 ECD can have potential clinical utility to supplement the tissue based tests.
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An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.
J. Exp. Bot.
PUBLISHED: 07-28-2014
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The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants.
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Computational methods to predict long noncoding RNA functions based on co-expression network.
Methods Mol. Biol.
PUBLISHED: 07-25-2014
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Although long noncoding RNAs (lncRNAs) have been recognized in recent years to constitute a significant portion of mammalian transcriptome, and the functional impact of several lncRNAs has been characterized by a few studies, yet it is still difficult to large-scale ascertain their functions from lab experiment or structure prediction. To address this deficit, we have developed a computational pipeline to large-scale annotate the functions of lncRNA based on coding-noncoding gene co-expression network. In this network, a node (circle) represents the protein-coding gene or lncRNA, and an edge (connecting line between nodes) indicates that the two genes are co-expressed (the correlation coefficients of connected genes reached the defined cutoff). In this chapter, we show how to use an lncRNA functional annotation pipeline to construct a co-expression network based on gene expression profiles in prostate cancer and how to further predict lncRNA functions using model-based and hub-based sub-networks.
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A single-center experience of non-bioartificial liver support systems among Chinese patients with liver failure.
Int J Artif Organs
PUBLISHED: 07-07-2014
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Liver failure is one of the most deadly, prevalent, and costly diseases worldwide. Non-bioartificial liver support systems (NBALs) have been shown to be effective in improving the clinical symptoms and laboratory parameters of patients with liver failure. The main aim of this large case series analysis was to investigate the status of NBALs and their effectiveness in improving survival in liver-failure patients.
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Vindel: a simple pipeline for checking indel redundancy.
BMC Bioinformatics
PUBLISHED: 06-28-2014
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BackgroundWith the advance of next generation sequencing (NGS) technologies, a large number of insertion and deletion (indel) variants have been identified in human populations. Despite much research into variant calling, it has been found that a non-negligible proportion of the identified indel variants might be false positives due to sequencing errors, artifacts caused by ambiguous alignments, and annotation errors.ResultsIn this paper, we examine indel redundancy in dbSNP, one of the central databases for indel variants, and develop a standalone computational pipeline, dubbed Vindel, to detect redundant indels. The pipeline first applies indel position information to form candidate redundant groups, then performs indel mutations to the reference genome to generate corresponding indel variant substrings. Finally the indel variant substrings in the same candidate redundant groups are compared in a pairwise fashion to identify redundant indels. We applied our pipeline to check for redundancy in the human indels in dbSNP. Our pipeline identified approximately 8% redundancy in insertion type indels, 12% in deletion type indels, and overall 10% for insertions and deletions combined. These numbers are largely consistent across all human autosomes. We also investigated indel size distribution and adjacent indel distance distribution for a better understanding of the mechanisms generating indel variants.ConclusionsVindel, a simple yet effective computational pipeline, can be used to check whether a set of indels are redundant with respect to those already in the database of interest such as NCBI¿s dbSNP. Of the approximately 5.9 million indels we examined, nearly 0.6 million are redundant, revealing a serious limitation in the current indel annotation. Statistics results prove the consistency of the pipeline on indel redundancy detection for all 22 chromosomes. Apart from the standalone Vindel pipeline, the indel redundancy check algorithm is also implemented in the web server http://bioinformatics.cs.vt.edu/zhanglab/indelRedundant.php.
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Lymphatic invasion as a prognostic biomarker in primary cutaneous melanoma.
Methods Mol. Biol.
PUBLISHED: 06-26-2014
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Melanoma has a propensity for lymph node metastasis. However, the incidence of lymphatic invasion detected by histology alone in primary melanoma is disproportionately low in comparison to the incidence of positive sentinel lymph nodes (SLN). With the discovery of lymphatic endothelial cell markers, such as podoplanin and LYVE-1, lymphatic vessels can be reliably detected in formalin-fixed paraffin-embedded (FFPE) tissues. There is a now consensus that lymphatic invasion detected by immunohistochemical stains in primary melanoma is much more common than previously reported by histological examination alone. Immunohistochemical stains show that lymphangiogenesis and lymphatic invasion in primary melanoma may occur intratumorally or peritumorally, and lymphatic invasion is common across the range of tumor thicknesses in primary vertical growth phase (VGP) melanomas. A number of studies have shown that lymphatic invasion in primary melanoma is associated with a positive sentinel lymph node biopsy and a worse clinical outcome. Although not currently a part of the standard of care for staging of melanoma, the detection of lymphatic invasion in primary melanoma using immunohistochemical markers may be helpful in planning of therapy in some cases and may find a routine role in primary melanoma microscopic attributes in future.
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CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis.
Gut
PUBLISHED: 06-22-2014
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Progastrin is the incompletely cleaved precursor of gastrin that is secreted by G-cells in the gastric antrum. Both gastrin and progastrin bind to the CCK2 receptor (Cckbr or CCK2R) expressed on a subset of gastric epithelial cells. Little is known about how gastrin peptides and CCK2R regulate gastric stem cells and carcinogenesis. Interconversion among progenitors in the intestine is documented, but the mechanisms by which this occurs are poorly defined.
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Chirality in Ordered Porous Organosilica Hybrid Materials.
Chem Asian J
PUBLISHED: 06-18-2014
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The ever-growing demand for chiral small molecules on a global scale has set a precedent for the proliferation of cost-effective and reliable methods for their synthesis and separation. Of these methods, those based on heterogeneous platforms present an unparalleled opportunity as they allow for the source of the chirality to be recycled. Chiral hybrid organosilica materials are one particularly interesting class of chiral heterogeneous platforms that creates a synergy between well-understood individual chiral molecules and the structural stability and inertness of the inorganic silicon scaffolds. This Focus Review summarizes the recent advances towards the incorporation of chirality into organosilica scaffolds, the synthesis of the chiral building blocks, and their promising applications towards facilitating asymmetric heterogeneous catalysis as well as chiral chromatography.
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Ovarian steroid cell tumor, not otherwise specified: A rare case of postmenopausal vaginal bleeding.
Oncol Lett
PUBLISHED: 06-13-2014
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Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS) are particularly rare ovarian tumors, which are composed of steroid-hormone secreting cells. The majority of patients with this tumor produce excessive quantities of testosterone and virilization is common. The current report presents a rare case of SCT in a 59-year-old female who presented with postmenopausal vaginal bleeding. The patient had experienced irregular vaginal bleeding for two months, 12 years after menopause. Transvaginal ultrasound and magnetic resonance imaging identified a solid adnexal mass and the pathological result of diagnostic curettage showed a proliferative endometrium. The patient's serum estrogen and testosterone levels were elevated (393.71 nmol/l and 22.28 nmol/l, respectively). The patient underwent an exploratory laparotomy, hysterectomy and bisalpingectomy. The neoplasm was well-circumscribed, solid, homogeneous and yellow in color. Microscopically, the tumor was predominantly composed of granular eosinophilic or vacuolated cytoplasm. Reinke's crystals, prominent nucleoli and Call-Exner bodies were not observed, and there was no mitotic figure. Immunohistochemistry demonstrated that the tumor cells were strongly positive for inhibin. The present rare case aims to expand the current knowledge of this type of ovarian tumor.
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Design, synthesis and biological evaluation of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel histone deacetylase inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 06-11-2014
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A series of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10r against HDAC1, HDAC3, HDAC6 was 1.14±0.03nM, 3.56±0.08nM, 11.43±0.12nM. Compound 10r noticeably up-regulated the level of histone H3 acetylation compared to the SAHA. Most of the compounds showed the strong anti-proliferative activity against human cancer cell lines including RMPI8226 and HCT-116. The IC50 values of Compounds 10r and 10t against RPMI8226 was 2.39±0.20?M, 1.41±0.44?M, respectively, and the HCT-116 was sensitive to the compounds 10h, 10m, 10r, 10w with the IC50 values <1.9?M.
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Variant rs1906591 on chromosome 4q25 confers increased risk of cardioembolic stroke in Chinese patients.
J Clin Neurosci
PUBLISHED: 06-03-2014
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Ischemic stroke (IS) is a heterogeneous multifactorial disorder caused by both genetic and environmental factors. A genome-wide association study on stroke in Caucasians identified a variant on chromosome 4q25 that is significantly associated with IS, with the strongest risk for cardioembolic stroke (CES). The current study aims to investigate the association of the rs1906591 variant on 4q25 with IS through a case-control study in a Chinese Han population. A total of 712 IS patients and 774 control subjects were involved in the current research. Stroke subtyping was performed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The genotypes were determined using the SNaPshot technique. The association of the genotypes with the risk of IS was estimated using logistic regression analysis. The rs1906591 single nucleotide polymorphism variant was associated with the CES subtype in both recessive and additive models (recessive model: odds ratio [OR]=2.58, 95% confidence interval [CI] 1.47-4.53, p=0.001, adjusted OR=2.71, 95% CI 1.48-4.96, p=0.001; additive model: OR=2.50, 95% CI 1.19-5.25, p=0.015, adjusted OR=2.83, 95% CI 1.24-6.50, p=0.013). This result indicates that patients with the AA genotype have a higher rate of CES than other genotypes. However, the rs1906591 variant was not significantly associated with the overall incidence of stroke or other stroke subtypes. The rs1906591 variant is significantly associated with CES in the Chinese Han population, but not with other stroke subtypes.
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Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses.
Neurosci. Lett.
PUBLISHED: 05-06-2014
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Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. In this study, Morris water maze test, ELISA and electrophysiological methods were used to examine the role and underling mechanisms of rosiglitazone on A?42 oligomer-induced memory impairments. We found that rosiglitazone attenuated A?42 oligomer-induced memory impairments in rats in a dose-dependent manner. The levels of inflammatory cytokines interleukin-1 beta (IL-1?) and interferon gamma (IFN?) were significantly increased 7 days after injection of A?42 oligomers into the rat hippocampus. Inhibition of microglia activation prevented A?42 oligomer-induced increases in IL-1? and IFN? levels. Rosiglitazone completely prevented the increase in the levels of IL-1? and IFN? induced by A?42 oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL-1? or IFN? significantly inhibited the production of long-term potentiation (LTP) in the dentate gyrus. Rosiglitazone prevented the inhibitory effects of inflammatory cytokines on LTP. Thus, inhibition of inflammatory responses may be part of the mechanisms of action of rosiglitazone on preventing memory deficits induced by A?42 oligmers.
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[Efficacy of BAHA softband in young children with bilateral congenital aural atresia].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-24-2014
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To retrospectively analyze the auditory and speech development of young children with bilateral congenital aural atresia after using bone-anchored hearing aid (BAHA) softband.
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Myricetin enhances osteogenic differentiation through the activation of canonical Wnt/?-catenin signaling in human bone marrow stromal cells.
Eur. J. Pharmacol.
PUBLISHED: 04-20-2014
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Myricetina flavonoid compound, has been reported to possess antioxidative, antiproliferative and anti-inflammatory effects. However, no study has yet investigated the effect of myricetin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). This study was designed to investigate the effects of myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP and Runt-related transcription factor 2 (RUNX2). Additionally, we found that myricetin activated the Wnt/?-catenin pathway and increased the expression of several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer factor-1 (LEF-1). Depletion of ?-catenin almost completely blocked the positive role of myricetin on osteogenic differentiation. Taken together, our findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by activating the Wnt/?-catenin signaling. The study may aid in the development of a therapeutic approach utilizing myricetin for the enhancement of bone health and prevention of osteoporosis.
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Highly efficient photocatalytic H? evolution from water using visible light and structure-controlled graphitic carbon nitride.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 04-15-2014
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The major challenge of photocatalytic water splitting, the prototypical reaction for the direct production of hydrogen by using solar energy, is to develop low-cost yet highly efficient and stable semiconductor photocatalysts. Herein, an effective strategy for synthesizing extremely active graphitic carbon nitride (g-C3N4) from a low-cost precursor, urea, is reported. The g-C3N4 exhibits an extraordinary hydrogen-evolution rate (ca. 20,000??mol?h(-1) g(-1) under full arc), which leads to a high turnover number (TON) of over 641 after 6?h. The reaction proceeds for more than 30?h without activity loss and results in an internal quantum yield of 26.5% under visible light, which is nearly an order of magnitude higher than that observed for any other existing g-C3N4 photocatalysts. Furthermore, it was found by experimental analysis and DFT calculations that as the degree of polymerization increases and the proton concentration decreases, the hydrogen-evolution rate is significantly enhanced.
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Free transplantation of autogenous palmaris longus tendon in the repair of cicatricial ectropion of lower eyelid.
J Plast Surg Hand Surg
PUBLISHED: 04-03-2014
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Abstract Treatment of cicatricial lower eyelid ectropion is often difficult and requires surgical intervention. Numerous techniques have been developed over the years to treat the cicatricial lower eyelid ectropion. This article describes an effective surgical technique using the free transplantation of autogenous palmaris longus tendon in the repair of cicatricial lower eyelid ectropion. The operation was performed with the patient under local anaesthesia. After the contracture of the lower eyelid skin or conjunctiva had been thoroughly released, a palmaris longus tendon graft was obtained through small transverse incisions along the non-dominant forearm. The graft is suspended between the medial canthal ligament and lateral orbital rim with proper tension. Then a local skin flap was transferred to cover the wound at the lower eyelid. In this study, 15 patients were treated using autogenous palmaris longus tendon between December 2008 and October 2012. At the 9-18 months of follow-up assessment, there were no major complications reported with any of the cases, and all have achieved good function and satisfactory appearance of the lower eyelid. However, five patients (33%) still had lagophthalmos, but it was in remission. In conclusion, free transplantation of autogenous palmaris longus tendon in the repair of cicatricial ectropion of the lower eyelid is an effective procedure for cicatricial ectropion, the functional and cosmetic results were satisfactory, the recurrence rate is low. Especially for the moderate and severe ectropion this method is a good choice.
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Infiltrating adenomyosis of the cervix with features of a low-grade stromal sarcoma: a case report and a literature review.
Int. J. Gynecol. Pathol.
PUBLISHED: 04-01-2014
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Adenomyosis is a common, non-neoplastic, chronic gynecologic disorder that is detected in 5% to 70% of hysterectomy specimens. It is characterized by the presence of ectopic endometrial glands and stroma within the myometrium, and it occurs mostly in late reproductive age women. Adenomyosis has a propensity to present in the uterine fundus and is rarely seen in the cervix. At present, the most reliable way to diagnose adenomyosis is by pathologic examination of the hysterectomy specimens. Herein, we report a case of infiltrating adenomyosis in the cervix with unusual clinical and pathologic findings.
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Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging.
Nucl. Med. Biol.
PUBLISHED: 03-31-2014
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Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with (99m)Tc by formulated kit for SPECT imaging of hepatic function.
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.
Catherine A Brownstein, Alan H Beggs, Nils Homer, Barry Merriman, Timothy W Yu, Katherine C Flannery, Elizabeth T DeChene, Meghan C Towne, Sarah K Savage, Emily N Price, Ingrid A Holm, Lovelace J Luquette, Elaine Lyon, Joseph Majzoub, Peter Neupert, David McCallie, Peter Szolovits, Huntington F Willard, Nancy J Mendelsohn, Renee Temme, Richard S Finkel, Sabrina W Yum, Livija Medne, Shamil R Sunyaev, Ivan Adzhubey, Christopher A Cassa, Paul I W de Bakker, Hatice Duzkale, Piotr Dworzynski, William Fairbrother, Laurent Francioli, Birgit H Funke, Monica A Giovanni, Robert E Handsaker, Kasper Lage, Matthew S Lebo, Monkol Lek, Ignaty Leshchiner, Daniel G MacArthur, Heather M McLaughlin, Michael F Murray, Tune H Pers, Paz P Polak, Soumya Raychaudhuri, Heidi L Rehm, Rachel Soemedi, Nathan O Stitziel, Sara Vestecka, Jochen Supper, Claudia Gugenmus, Bernward Klocke, Alexander Hahn, Max Schubach, Mortiz Menzel, Saskia Biskup, Peter Freisinger, Mario Deng, Martin Braun, Sven Perner, Richard J H Smith, Janeen L Andorf, Jian Huang, Kelli Ryckman, Val C Sheffield, Edwin M Stone, Thomas Bair, E Ann Black-Ziegelbein, Terry A Braun, Benjamin Darbro, Adam P DeLuca, Diana L Kolbe, Todd E Scheetz, Aiden E Shearer, Rama Sompallae, Kai Wang, Alexander G Bassuk, Erik Edens, Katherine Mathews, Steven A Moore, Oleg A Shchelochkov, Pamela Trapane, Aaron Bossler, Colleen A Campbell, Jonathan W Heusel, Anne Kwitek, Tara Maga, Karin Panzer, Thomas Wassink, Douglas Van Daele, Hela Azaiez, Kevin Booth, Nic Meyer, Michael M Segal, Marc S Williams, Gerard Tromp, Peter White, Donald Corsmeier, Sara Fitzgerald-Butt, Gail Herman, Devon Lamb-Thrush, Kim L McBride, David Newsom, Christopher R Pierson, Alexander T Rakowsky, Ales Maver, Luca Lovrecic, Anja Palandačić, Borut Peterlin, Ali Torkamani, Anna Wedell, Mikael Huss, Andrey Alexeyenko, Jessica M Lindvall, Måns Magnusson, Daniel Nilsson, Henrik Stranneheim, Fulya Taylan, Christian Gilissen, Alexander Hoischen, Bregje Van Bon, Helger Yntema, Marcel Nelen, Weidong Zhang, Jason Sager, Lu Zhang, Kathryn Blair, Deniz Kural, Michael Cariaso, Greg G Lennon, Asif Javed, Saloni Agrawal, Pauline C Ng, Komal S Sandhu, Shuba Krishna, Vamsi Veeramachaneni, Ofer Isakov, Eran Halperin, Eitan Friedman, Noam Shomron, Gustavo Glusman, Jared C Roach, Juan Caballero, Hannah C Cox, Denise Mauldin, Seth A Ament, Lee Rowen, Daniel R Richards, F Anthony San Lucas, Manuel L Gonzalez-Garay, C Thomas Caskey, Yu Bai, Ying Huang, Fang Fang, Yan Zhang, Zhengyuan Wang, Jorge Barrera, Juan M García-Lobo, Domingo González-Lamuño, Javier Llorca, María C Rodriguez, Ignacio Varela, Martin G Reese, Francisco M De La Vega, Edward Kiruluta, Michele Cargill, Reece K Hart, Jon M Sorenson, Gholson J Lyon, David A Stevenson, Bruce E Bray, Barry M Moore, Karen Eilbeck, Mark Yandell, Hongyu Zhao, Lin Hou, Xiaowei Chen, Xiting Yan, Mengjie Chen, Cong Li, Can Yang, Murat Günel, Peining Li, Yong Kong, Austin C Alexander, Zayed I Albertyn, Kym M Boycott, Dennis E Bulman, Paul M K Gordon, A Micheil Innes, Bartha M Knoppers, Jacek Majewski, Christian R Marshall, Jillian S Parboosingh, Sarah L Sawyer, Mark E Samuels, Jeremy Schwartzentruber, Isaac S Kohane, David M Margulies.
Genome Biol.
PUBLISHED: 03-25-2014
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There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance.
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Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up.
Am. J. Surg. Pathol.
PUBLISHED: 03-13-2014
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Predicting clinical behavior of atypical Spitz tumors remains problematic. In this study, we assessed interobserver agreement of diagnosis by 13 expert dermatopathologists for atypical Spitz tumors (n=75). We determined which histomorphologic features were most heavily weighted for their diagnostic significance by the experts and also which histomorphologic features had a statistically significant correlation with clinical outcome. There was a low interobserver agreement among the experts in categorizing lesions as malignant versus nonmalignant (?=0.30). The histomorphologic features that were given the most diagnostic significance by the experts were: consumption of the epidermis, atypical mitoses, high-grade cytologic atypia, and mitotic rate. Conversely, the histomorphologic features that most correlated with disease progression were: frequent mitoses, deep mitoses, asymmetry, high-grade cytologic atypia, and ulceration. The presence and/or pattern of pagetoid spread, consumption of the epidermis, and lymphoid aggregates demonstrated no association with clinical behavior. The results support the assertion that there is a lack of consensus in the assessment of atypical Spitz tumors by expert dermatopathologists. Importantly, many features used to distinguish conventional melanoma from nevi were not useful in predicting the behavior of atypical Spitz tumors. This study may provide some guidance regarding histologic assessment of these enigmatic tumors.
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The VGF-derived peptide TLQP62 produces antidepressant-like effects in mice via the BDNF/TrkB/CREB signaling pathway.
Pharmacol. Biochem. Behav.
PUBLISHED: 02-28-2014
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Recent studies demonstrate that the neuropeptide VGF (nonacronymic)-derived peptide is regulated in the hippocampus by antidepressant therapies. Brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), cAMP response element-binding protein (CREB) signaling, and monoamine transmitter pathways mediate the behavioral effects of antidepressants, but it is not known if these pathways also contribute to the antidepressant-like effects of VGF-derived peptide TLQP62. Here the antidepressant-like effects of TLQP62 were evaluated by measuring immobility time in the forced swimming and tail suspension tests (FST and TST) following acute microinjection of the TLQP62 (0.25, 0.5 and 1 nmol/side) into the hippocampal CA1 regions. This treatment dose-dependently reduced immobility in the FST and TST compared to phosphate-buffered saline (PBS) infusion without affecting locomotor activity in the open field test (OFT). In addition, daily intrahippocampal microinfusion of TLQP62 (1 nmol/side/day; 21 days) also upregulated the expression of BDNF and the phosphorylation of CREB (pCREB) and TrkB (pTrkB) without altering CREB or TrkB. Blocking tissue plasminogen activator (tPA) by microinfusion of tPASTOP or TrkB activation by microinfusion of K252a 60 min prior to TLQP62 infusion almost completely abolished TLQP62-induced antidepressant-like effects, BDNF upregulation, and CREB/TrkB phosphorylation. In contrast, none of these effects were diminished by pretreatment with the non-specific 5-HT receptor antagonist metergoline, the selective 5-HT1A receptor antagonist NAN-190, the 5-HT synthase inhibitor parachlorophenylalanine, the selective ?1-adrenoceptor antagonist prazosin, the ? receptor antagonist propranolol, or the D2 receptor antagonist raclopride. Moreover, our study was also to investigate the antidepressant-like effects of TLQP62 (50, 250 and 500 nmol/kg; i.p.) on depression-related behaviors in comparison with fluoxetine (10mg/kg; i.p.). While TLQP62 and fluoxetine showed similar antidepressant-like behavioral effects in the FST of mice. Our present results strongly suggest that activation of BDNF/TrkB/CREB signaling may be involved in the antidepressant-like effects of TLQP62.
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Cytological diagnosis of angiosarcoma arising in an immunosuppressed patient 6 years after multi-visceral transplantation: a case report and literature review.
Diagn. Cytopathol.
PUBLISHED: 02-28-2014
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Angiosarcoma is a rare and aggressive malignant tumor of soft tissue. It can arise in almost any part of the body, most commonly in the skin and the superficial soft tissue in the head and neck region. Although the etiology of angiosarcoma is unknown, there are several well-known risk factors, such as chronic lymphedema, exposure to radiation, toxins, and foreign bodies. It rarely occurs in transplant patients. Cytological criteria for the diagnosis of angiosarcoma have not been fully established, having been described only in a few cases, mostly fine-needle aspiration biopsies (FNAB). Herein, we present a case of angiosarcoma arising in an immunosuppressed patient status post multi-visceral transplantation and diagnosed by cytology. To the best of our knowledge, this is the first report of such a case in the English literature. The cytological findings from endoscopic ultrasound-guided FNAB and ascites fluid are discussed.
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Effects of acidic oligosaccharide sugar chain on amyloid oligomer-induced impairment of synaptic plasticity in rats.
Metab Brain Dis
PUBLISHED: 02-26-2014
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Soluble amyloid-? protein (A?) oligomers have been recognized to be early and key intermediates in Alzheimer's disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, with oligomeric A?. We found that the inhibition of long-term potentiation (LTP) induced by A? oligomers can be dose dependently reversed by the application of AOSC, whereas AOSC alone did not alter normal LTP induction. Interestingly, treatment with A? monomers with or without AOSC did not affect LTP induction. Additionally, when fresh-made A? was co-incubated with AOSC before in vitro testing, there was no impairment of LTP induction. The results from Western blots demonstrated that AOSC prevent the aggregation of A? oligomers. These findings indicate that AOSC may reverse A? oligomer-mediated cytotoxicity by directly disrupting the amyloid oligomer aggregation, and this action is concentration dependent. Thus, we propose that AOSC might be a potential therapeutic drug for Alzheimer's disease due to its protection against oligomeric A?-induced dysfunction of synaptic plasticity.
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Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma.
J. Clin. Invest.
PUBLISHED: 02-24-2014
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Melanomas that result from mutations in the gene encoding BRAF often become resistant to BRAF inhibition (BRAFi), with multiple mechanisms contributing to resistance. While therapy-induced autophagy promotes resistance to a number of therapies, especially those that target PI3K/mTOR signaling, its role as an adaptive resistance mechanism to BRAFi is not well characterized. Using tumor biopsies from BRAF(V600E) melanoma patients treated either with BRAFi or with combined BRAF and MEK inhibition, we found that BRAFi-resistant tumors had increased levels of autophagy compared with baseline. Patients with higher levels of therapy-induced autophagy had drastically lower response rates to BRAFi and a shorter duration of progression-free survival. In BRAF(V600E) melanoma cell lines, BRAFi or BRAF/MEK inhibition induced cytoprotective autophagy, and autophagy inhibition enhanced BRAFi-induced cell death. Shortly after BRAF inhibitor treatment in melanoma cell lines, mutant BRAF bound the ER stress gatekeeper GRP78, which rapidly expanded the ER. Disassociation of GRP78 from the PKR-like ER-kinase (PERK) promoted a PERK-dependent ER stress response that subsequently activated cytoprotective autophagy. Combined BRAF and autophagy inhibition promoted tumor regression in BRAFi-resistant xenografts. These data identify a molecular pathway for drug resistance connecting BRAFi, the ER stress response, and autophagy and provide a rationale for combination approaches targeting this resistance pathway.
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microRNA?125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis.
Mol Med Rep
PUBLISHED: 02-17-2014
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microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP?1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.
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Synthesis and preliminary evaluation of novel (99m)Tc-labeled folate derivative via click reaction for SPECT imaging.
Appl Radiat Isot
PUBLISHED: 02-11-2014
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The folate receptor is over expressed in a wide variety of human tumors. In this study, a novel (99m)Tc-labeled folate derivative ((99m)Tc-HYNIC-T-FA) was synthesized as a potential FR-targeting imaging probe and its efficiency was evaluated. This (99m)Tc-complex could be obtained through practical manner and showed improved in vivo characteristics compared with other radiofolates. Thus, this novel (99m)Tc-HYNIC-T-FA compound could serve as a potential imaging agent for folate receptor positive tumors.
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A novel aggregation-induced emission fluorescent probe for nucleic acid detection and its applications in cell imaging.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-04-2014
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A new kind of aggregation-induced emission compound was synthesized and used as the probe of nucleic acid. The characterization of this compound was studied. Both the RNA and DNA were detected by using this probe. And the detection scope of DNA and RNA was different. We researched the selectivity of our probe in double and single strand DNA sequences. The visualization of gel electrophoresis and the cell nucleus imaging were researched as well. Compared with the traditional nucleus dye Hoechst 33258, our probe also has the potential to be nucleus dye. And the cell toxicity was well performed by MTT assays.
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Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells.
Nat Commun
PUBLISHED: 01-29-2014
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Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200(+)/ITGA6(+) EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200(+)/ITGA6(+) cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200(+)/ITGA6(+) cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15(+) stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.
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Severe sepsis: Low expression of the renin-angiotensin system is associated with poor prognosis.
Exp Ther Med
PUBLISHED: 01-24-2014
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Severe sepsis has a high fatality rate, but no clinical indices for prognosis have been established. In recent years, the renin-angiotensin system (RAS) has received considerable attention. However, clinical data on RAS are inconsistent. Therefore, the aim of the present study was to assess the significance of RAS in the prognosis of sepsis. Blood samples were collected from patients, who met the diagnostic criteria of severe sepsis, on day 1 (D1) and 3 (D3). For each sample, the levels of angiotensin II (AngII), angiotensin-converting enzyme (ACE) and additional indices were measured. Patients were monitored for 28 days. On the D1 of inclusion, the average Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.2 and the Sepsis-related Organ Failure Assessment (SOFA) score was 6.1. Logistic regression analysis revealed that mortality-associated variables included the APACHE II score on D1, the SOFA score on D1, high lactic acid levels on D3 and low AngII and ACE levels on D1 and D3. AngII levels (<86.1 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 77.3% for predicting mortality. ACE levels (<39.2 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 72.7% for predicting mortality. These two indices were better than the APACHE II and SOFA scores. Therefore, low expression levels of AngII and ACE are valuable in predicting the mortality of patients with severe sepsis.
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N-arylated-lactam-type iminosugars as new immunosuppressive agents: discovery, optimization, and biological evaluation.
Chem Asian J
PUBLISHED: 01-04-2014
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We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in?vitro and in?vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12?f. Subsequently, the systematic modification of compound 12?f afforded compounds 21?h, 21?k, 21?n, 21?t, and 21?x with improved activities (IC50 =12-30??M) and low Jurkat cytotoxicities (IC50 >100??M). These new compounds also inhibited the secretion of IFN-? and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.
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Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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The heterogeneity among multiple ductal carcinoma in situ (DCIS) lesions within the same patient also diagnosed with invasive ductal carcinoma (IDC) has not been well evaluated, leaving research implications of intra-individual DCIS heterogeneity yet to be explored. In this study formalin-fixed paraffin embedded sections from 36 patients concurrently diagnosed with DCIS and IDC were evaluated by immunohistochemistry. Ten DCIS lesions from each patient were then randomly selected and scored. Our results showed that expression of PR, HER2, Ki-67, and p16 varied significantly within DCIS lesions from a single patient (P<0.05 for PR; P<1×10(-8) for HER2, Ki-67 and p16). In addition, seventy-two percent of the individuals had heterogeneous expression of at least 2/6 markers. Importantly, by evaluating the expression of promising DCIS risk biomarkers (Ki-67, p53 and p16) among different DCIS subgroups classified by comparing DCIS molecular subtypes with those of adjacent normal terminal duct lobular units (TDLU) and IDC, our results suggest the existence of a highly-aggressive DCIS subgroup, which had the same molecular subtype as the adjacent IDC but not the same subtype as the adjacent normal TDLU. By using a systematic approach, our results clearly demonstrate that intra-individual heterogeneity in DCIS is very common in patients concurrently diagnosed with IDC. Our novel findings of a DCIS subpopulation with aggressive characteristics will provide a new paradigm for mechanistic studies of breast tumor progression and also have broad implications for prevention research as heterogeneous pre-invasive lesions are present in many other cancer types.
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Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration.
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Deep profiling of the novel intermediate-size noncoding RNAs in intraerythrocytic Plasmodium falciparum.
PLoS ONE
PUBLISHED: 01-01-2014
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Intermediate-size noncoding RNAs (is-ncRNAs) have been shown to play important regulatory roles in the development of several eukaryotic organisms. However, they have not been thoroughly explored in Plasmodium falciparum, which is the most virulent malaria parasite infecting human being. By using Illumina/Solexa paired-end sequencing of an is-ncRNA-specific library, we performed a systematic identification of novel is-ncRNAs in intraerythrocytic P. falciparum, strain 3D7. A total of 1,198 novel is-ncRNA candidates, including antisense, intergenic, and intronic is-ncRNAs, were identified. Bioinformatics analyses showed that the intergenic is-ncRNAs were the least conserved among different Plasmodium species, and antisense is-ncRNAs were more conserved than their sense counterparts. Twenty-two novel snoRNAs were identified, and eight potential novel classes of P. falciparum is-ncRNAs were revealed by clustering analysis. The expression of randomly selected novel is-ncRNAs was confirmed by RT-PCR and northern blotting assays. An obvious different expressional profile of the novel is-ncRNA between the early and late intraerythrocytic developmental stages of the parasite was observed. The expression levels of the antisense RNAs correlated with those of their cis-encoded sense RNA counterparts, suggesting that these is-ncRNAs are involved in the regulation of gene expression of the parasite. In conclusion, we accomplished a deep profiling analysis of novel is-ncRNAs in P. falciparum, analysed the conservation and structural features of these novel is-ncRNAs, and revealed their differential expression patterns during the development of the parasite. These findings provide important information for further functional characterisation of novel is-ncRNAs during the development of P. falciparum.
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NOV-002, A Glutathione Disulfide Mimetic, Suppresses Tumor Cell Invasion and Metastasis.
J Carcinog Mutagen
PUBLISHED: 12-31-2013
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Metastasis is the major cause of death in cancer. Most therapies currently in the clinic aim to eradicate primary tumor, but do not have ideal effects on metastasis. The lack of effective therapy in metastasis prevention and treatment results in high mortality rate in cancer patients with advanced diseases. Here we report the oxidized glutathione small molecule compound NOV-002 reduces cancer cell invasion in vitro and metastasis in an animal model in combination with chemotherapy drug gemcitabine. NOV-002 regulates cell signaling pathways by suppressing ErbB2 and PI3K phosphorylation and subsequent inhibition of Akt and RhoA activation. Our results suggest that NOV-002 affects cell signaling pathways that are critical for invasion and metastasis and can potentially be effective in metastasis treatment in combination of other chemotherapies.
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Investigation of Sm0.2Ce0.8O1.9/Na2CO3 Nanocomposite Electrolytes: Preparation, Interfacial Microstructures, and Ionic Conductivities.
ACS Appl Mater Interfaces
PUBLISHED: 12-09-2013
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With the analytical grade Ce(NO3)3·6H2O, Sm(NO3)3·6H2O, and Na2CO3 as starting materials, Sm0.2Ce0.8O1.9(SDC)/Na2CO3 nanocomposite electrolytes were prepared through a rare-earth/sodium carbonate complex precipitation, prefiring, and sintering operations. The phase components and microstructures were studied and characterized by XRD, FESEM, TEM, and TG-DSC. In particular, the interfacial interactions between the phases of SDC crystallites and amorphous Na2CO3 were deliberately probed by Raman and infrared spectroscopies. It has been found that the amorphous carbonates in the SDC/Na2CO3 composites are tightly bound to the surface of SDC nanocrystals to form an intimate shell-layer via a long-range interface interaction, characterized by ?8 nm in thickness and a red-shift of 15 cm(-1) for the Raman symmetrical vibration mode of carbonate ions with reference to the crystalline Na2CO3, which is practically enabled to frustrate the crystallization of Na2CO3 and enhance the transport properties of oxide ions in the SDC/Na2CO3 composite electrolytes because of the disordered interface microstructures. Moreover, smaller SDC nanocrystals were found to achieve higher conductivity enhancements for the SDC/Na2CO3 composite electrolytes and the {100} facets on the surface of SDC nanocrystals are believed to be more important than the other facets because of their strong electropositivity. This effect makes the SDC/Na2CO3 composite sample prefired at 600 °C realize a much higher ionic conductivity than the samples prefired at the other temperatures.
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A simple constrained uniaxial tensile apparatus for in situ investigation of film stretching processing.
Rev Sci Instrum
PUBLISHED: 12-03-2013
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A simple constrained uniaxial tensile apparatus was designed and constructed to obtain stress-strain curve during stretching and subsequent structural evolution of polymeric films. Stretch is carried out through two motor driven clamps in the machine direction and scissor-like clamps in the transverse direction keeping the sample width constant. The force information during film stretching process is recorded by a tension sensor and structural evolution can be obtained by in situ X-ray scattering technique. All parameters related to film stretching manufacturing, such as temperature, draw ratio, and stretching speed can be set independently, making the apparatus an effective method to explore the relationship between processing parameters and structure.
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Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib.
Clin. Cancer Res.
PUBLISHED: 10-16-2013
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Platelet-derived growth factor receptor ? (PDGFRA) is a target for tyrosine kinase inhibitor (TKI)-based targeted therapy. Dysregulation of PDGFRA has been reported in many cancers. However, PDGFRA mutations in melanomas have not been well studied. We analyzed the genetic mutations of PDGFRA in Chinese patients with melanoma and determined the inhibitory potency of TKIs, such as imatinib and crenolanib, on mutant PDGFRA.
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A systems approach for analysis of high content screening assay data with topic modeling.
BMC Bioinformatics
PUBLISHED: 10-09-2013
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High Content Screening (HCS) has become an important tool for toxicity assessment, partly due to its advantage of handling multiple measurements simultaneously. This approach has provided insight and contributed to the understanding of systems biology at cellular level. To fully realize this potential, the simultaneously measured multiple endpoints from a live cell should be considered in a probabilistic relationship to assess the cells condition to response stress from a treatment, which poses a great challenge to extract hidden knowledge and relationships from these measurements.
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Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2.
Cancer Discov
PUBLISHED: 10-08-2013
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An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the noncanonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Furthermore, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF inhibitors. In patients with melanoma treated with the BRAF inhibitor vemurafenib, Wnt5A expression correlates with clinical response and therapy resistance. These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance.
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[Prevention and treatment of common complications of ear reconstruction].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-01-2013
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To explore the prevention and treatment of common complications of ear reconstruction.
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Near infrared Ag/Au alloy nanoclusters: Tunable photoluminescence and cellular imaging.
J Colloid Interface Sci
PUBLISHED: 09-22-2013
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The fluorescent nanomaterials play an important role in cellular imaging. Although the synthesis of fluorescent metal nanoclusters (NCs) have been developing rapidly, there are many technical issues in preparing metal alloy NCs. Herein, we used a facile galvanic replacement reaction to prepare Ag/Au alloy NCs. The characterizations of UV, PL, HRTEM, EDX and XPS confirm one fact the Ag/Au alloy NCs are carried out. As-prepared Ag/Au alloy NCs display near-infrared (NIR) fluorescence centered at 716nm and show tunable luminescence from visible red (614nm) to NIR (716nm) by controlling the experimental Ag/Au ratios. Moreover, as-prepared Ag/Au alloy NCs are protected by glutathione (GSH) whose some functional groups including thiol, carboxyl and amino groups make the as-prepared alloy NCs exhibit good dispersion in aqueous solution, high physiological stability and favorable biocompatibility. Together with NIR fluorescence, these advantages make alloy NCs be promising candidate in biological labeling.
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Discrimination between 5-hydroxymethylcytosine and 5-methylcytosine in DNA by selective chemical labeling.
Bioorg. Med. Chem. Lett.
PUBLISHED: 09-15-2013
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Detection of DNA damage has been greatly improved following the development of equipment and techniques, however, discrimination between 5-hydroxymethylcytosine (5-hmC) and 5-methylcytosine (5-mC) is still a thorny problem. In the present study, an approach to oxidize and selective label (Ox-Labeling) 5-hmC in native DNA has been reported, which conveniently distinguishes 5-hmC from 5-mC using simple and effective processes.
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The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma.
Mol. Cell. Biol.
PUBLISHED: 09-09-2013
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Cyclin D1-cyclin-dependent kinase 4/6 (CDK4/6) dysregulation is a major contributor to melanomagenesis. Clinical evidence has revealed that p16(INK4A), an allosteric inhibitor of CDK4/6, is inactivated in over half of human melanomas, and numerous animal models have demonstrated that p16(INK4A) deletion promotes melanoma. FBXO4, a specificity factor for the E3 ligase that directs timely cyclin D1 proteolysis, has not been studied in melanoma. We demonstrate that Fbxo4 deficiency induces Braf-driven melanoma and that this phenotype depends on cyclin D1 accumulation in mice, underscoring the importance of this ubiquitin ligase in tumor suppression. Furthermore, we have identified a substrate-binding mutation, FBXO4 I377M, that selectively disrupts cyclin D1 degradation while preserving proteolysis of the other known FBXO4 substrate, TRF1. The I377M mutation and Fbxo4 deficiency result in nuclear accumulation of cyclin D1, a key transforming neoplastic event. Collectively, these data provide evidence that FBXO4 dysfunction, as a mechanism for cyclin D1 overexpression, is a contributor to human malignancy.
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Fertilization and uniparental chromosome elimination during crosses with maize haploid inducers.
Plant Physiol.
PUBLISHED: 09-06-2013
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Producing maternal haploids via a male inducer can greatly accelerate maize (Zea mays) breeding process. However, the mechanism underlying haploid formation remains unclear. In this study, we constructed two inducer lines containing cytogenetic marker B chromosome or alien centromeric histone H3 variant-yellow fluorescent protein vector to investigate the mechanism. The two inducer lines as the pollinators were crossed with a hybrid ZhengDan958. B chromosomes were detected in F1 haploids at a low frequency, which was direct evidence to support the occurrence of selective chromosome elimination during haploid formation. We found that most of the inducer chromosomes were eliminated in haploid embryonic cells during the first week after pollination. The gradual elimination of chromosomes was also detected in the endosperm of defective kernels, although it occurred only in some endosperm cells as late as 15 d after pollination. We also performed a genome-wide identification of single nucleotide polymorphism markers in the inducers, noninducer inbred lines, and 42 derived haploids using a 50K single nucleotide polymorphism array. We found that an approximately 44-Mb heterozygous fragment from the male parent was detected in a single haploid, which further supported the occurrence of paternal introgression. Our results suggest that selective elimination of uniparental chromosomes leads to the formation of haploid and possible defective kernels in maize as well, which is accompanied with unusual paternal introgression in haploid cells.
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Synthesis, structures and hydrogen storage properties of two new H-enriched compounds: Mg(BH4)2(NH3BH3)2 and Mg(BH4)2·(NH3)2(NH3BH3).
Dalton Trans
PUBLISHED: 09-05-2013
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The synthesis, crystal structure and dehydrogenation performances of two new H-enriched compounds, Mg(BH4)2(NH3BH3)2 and Mg(BH4)2·(NH3)2(NH3BH3), are reported. Due to the introduction of ammonia ligands, the Mg(BH4)2·(NH3)2(NH3BH3) exhibits dramatically improved dehydrogenation properties over its parent compound.
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Prognosis of Patients with Melanoma and Microsatellitosis Undergoing Sentinel Lymph Node Biopsy.
Ann. Surg. Oncol.
PUBLISHED: 08-21-2013
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Melanoma microsatellitosis is classified as stage IIIB/C disease and is associated with a poor prognosis. Prognostic factors within this group, however, have not been well characterized.
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Large-scale study of long non-coding RNA functions based on structure and expression features.
Sci China Life Sci
PUBLISHED: 08-14-2013
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Mammals and other complex organisms can transcribe an abundance of long non-coding RNAs (lncRNAs) that fulfill a wide variety of regulatory roles in many biological processes. These roles, including as scaffolds and as guides for protein-coding genes, mainly depend on the structure and expression level of lncRNAs. In this review, we focus on the current methods for analyzing lncRNA structure and expression, which is basic but necessary information for in-depth, large-scale analysis of lncRNA functions.
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Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells.
Cell. Immunol.
PUBLISHED: 08-10-2013
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The aim of the present study was to investigate the effects of piperine on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. RAW264.7 cells were pretreated with piperine at 10, 50 or 100 ?g/ml and subsequently stimulated with LPS (1 ?g/ml) for 24 h. We found that piperine inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO) induced by LPS. Piperine significantly decreased LPS-stimulated gene expression and production of tumor necrosis factor-alpha (TNF), inducible NO synthase (iNOS) and COX-2 in RAW264.7 cells. Piperine inhibited the LPS-mediated activation of nuclear factor-kappa B (NF-kappaB) by suppressing the degradation of inhibitor-?B proteins (I?B) and the translocations of p65 subunit of NF-kB from the cytosol to the nucleus. Our results demonstrate the anti-inflammatory activity of piperine in RAW264.7 cells; suggesting that piperine may be a potential agent in the treatment of inflammation.
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Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.
PLoS Genet.
PUBLISHED: 08-01-2013
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Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.
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Exo70 Isoform Switching upon Epithelial-Mesenchymal Transition Mediates Cancer Cell Invasion.
Dev. Cell
PUBLISHED: 07-31-2013
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Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here, we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2 and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoform expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal-but not the epithelial-isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion.
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MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.
Am J Dermatopathol
PUBLISHED: 07-28-2013
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Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P < 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P < 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.
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Auditory development after placement of bone-anchored hearing aids Softband among Chinese Mandarin-speaking children with bilateral aural atresia.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 07-22-2013
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To evaluate auditory developments of Chinese Mandarin-speaking children with congenital bilateral aural atresia after using Bone-anchored hearing aids (Baha) Softband and to compare them with matched peers with normal hearing.
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Progastrin stimulates colonic cell proliferation via CCK2R- and ?-arrestin-dependent suppression of BMP2.
Gastroenterology
PUBLISHED: 07-12-2013
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Progastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R)-partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R.
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Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma.
Cell Rep
PUBLISHED: 07-10-2013
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Although BRAF and MEK inhibitors have proven clinical benefits in melanoma, most patients develop resistance. We report a de novo MEK2-Q60P mutation and BRAF gain in a melanoma from a patient who progressed on the MEK inhibitor trametinib and did not respond to the BRAF inhibitor dabrafenib. We also identified the same MEK2-Q60P mutation along with BRAF amplification in a xenograft tumor derived from a second melanoma patient resistant to the combination of dabrafenib and trametinib. Melanoma cells chronically exposed to trametinib acquired concurrent MEK2-Q60P mutation and BRAF-V600E amplification, which conferred resistance to MEK and BRAF inhibitors. The resistant cells had sustained MAPK activation and persistent phosphorylation of S6K. A triple combination of dabrafenib, trametinib, and the PI3K/mTOR inhibitor GSK2126458 led to sustained tumor growth inhibition. Hence, concurrent genetic events that sustain MAPK signaling can underlie resistance to both BRAF and MEK inhibitors, requiring novel therapeutic strategies to overcome it.
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Outcomes of atypical spitz tumors with chromosomal copy number aberrations and conventional melanomas in children.
Am. J. Surg. Pathol.
PUBLISHED: 06-26-2013
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Death due to melanoma in childhood (up to 20 y of age) is a rare event, with an average of 18 cases reported annually in the United States. In this study we evaluated 2 subgroups of high-risk melanocytic neoplasms in childhood, specifically atypical Spitz tumors (ASTs) with chromosomal copy number changes and conventional melanomas. We analyzed the clinical, histologic, and molecular features of all cases and performed the Fisher exact test, logistic regression, and multivariate analysis to evaluate features associated with aggressive clinical behavior in these cases. Among the ASTs, all of which had 1 or more chromosomal copy number aberrations, the presence of homozygous 9p21 deletions and a positive sentinel lymph node were each found to be correlated with tumor extension beyond the sentinel lymph node, with P-values of 0.046 and 0.01, respectively. Two patients with ASTs that had homozygous 9p21 deletions developed brain metastasis, one of whom died of disease. Among the 21 conventional melanomas, 3 patients developed distant metastasis and died of disease. Chromosomal copy number aberrations evaluated by fluorescence in situ hybridization were present in the majority of the cases (16/18). Among conventional melanomas, we did not identify any clinical, histologic, or molecular features associated with aggressive behavior. The presence of 8q24 gains was seen almost exclusively in 6 amelanotic small cell melanomas in children of whom 1 died of disease. Characteristic chromosomal copy number aberrations may occur in specific subtypes of melanocytic neoplasms in children and may help with the classification and prognostication of these rare tumors.
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Citrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1? signaling.
Mol Med Rep
PUBLISHED: 06-25-2013
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The present study aimed to investigate the anti-tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl-2, caspases-3 and -9, hypoxia-inducible factor 1? (HIF?1?) and its target gene GLUT-1, were assayed by western blotting and the role of HIF?1? was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl-2, while it induces the activation of caspases-3 and -9. In addition, citrate induces U937 apoptosis in a dose- and time-dependent manner by regulating the expression of HIF?1? and its downstream target GLUT-1. The results suggest that citrate performs an anti-acute monocytic leukemia action by targeting HIF?1? signaling and may be a promising clinical approach.
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Clark Level Risk Stratifies Patients with Mitogenic Thin Melanomas for Sentinel Lymph Node Biopsy.
Ann. Surg. Oncol.
PUBLISHED: 06-14-2013
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The role for sentinel lymph node biopsy (SLNB) in patients with thin melanoma (?1 mm) remains controversial. We examined a large cohort of patients with thin melanoma to better define predictors of SLN positivity.
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Joint analysis of expression profiles from multiple cancers improves the identification of microRNA-gene interactions.
Bioinformatics
PUBLISHED: 06-14-2013
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MicroRNAs (miRNAs) play a crucial role in tumorigenesis and development through their effects on target genes. The characterization of miRNA-gene interactions will lead to a better understanding of cancer mechanisms. Many computational methods have been developed to infer miRNA targets with/without expression data. Because expression datasets are in general limited in size, most existing methods concatenate datasets from multiple studies to form one aggregated dataset to increase sample size and power. However, such simple aggregation analysis results in identifying miRNA-gene interactions that are mostly common across datasets, whereas specific interactions may be missed by these methods. Recent releases of The Cancer Genome Atlas data provide paired expression profiling of miRNAs and genes in multiple tumors with sufficiently large sample size. To study both common and cancer-specific interactions, it is desirable to develop a method that can jointly analyze multiple cancers to study miRNA-gene interactions without combining all the data into one single dataset.
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Selective detection of 5-formyl-2-deoxycytidine in DNA using a fluorogenic hydroxylamine reagent.
Org. Lett.
PUBLISHED: 06-14-2013
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Fluorogenic hydroxylamine reagents were used for detecting 5-fC through a labeling pathway. Chemical synthesis, HPLC, denaturing PAGE, and DNA MS were applied to testify that the probe reacted with 5-fC with oligodeoxynucleotide selectivity to achieve 5-fC detection conveniently and quantificationally with the method of fluorescence. The feasibility of fluorescently detecting 5-fC in a genome was also investigated.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.