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Find video protocols related to scientific articles indexed in Pubmed.
[Pathological mechanisms of chronic insomnia: Evidence from neuro-electrophysiology and neuroimaging research].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-02-2014
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As a widely recognized public health problem as well as prevalent and challenging to modern society, chronic insomnia is involved in wide brain areas (such as prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and thalamus) and emotion-cognition neuro-circuit. It is closely related to the conditioned hyperarousal and the increased information process and/or the impaired inhibitory ability to withdraw from awaking state. Thus, some specific abnormal mode may exist in the emotion-cognition circuit, which is associated with abnormal cognition load, such as repeated retrieval/intrusion of aversive memories during night. Studies through the combination of multiple techniques including psychology, electrophysiology and neuroimaging methods are needed to further enhance the understanding of chronic insomnia.
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Role of Kinase Epidermal Growth Factor Receptor and SRC in the Caerulein-Induced Acute Pancreatitis in Mice.
Pancreas
PUBLISHED: 09-16-2014
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In this study, we identified the protein kinases that play the most distinct roles in the occurrence of acute pancreatitis (AP).
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IFN-stimulated gene LY6E in monocytes regulates the CD14/TLR4 pathway but inadequately restrains the hyperactivation of monocytes during chronic HIV-1 infection.
J. Immunol.
PUBLISHED: 09-15-2014
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Owing to ongoing recognition of pathogen-associated molecular patterns, immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication, some might exert compensatory immune suppression to limit pathological dysfunctions, although the mechanisms are not fully understood. In this study, we report that the ISG lymphocyte Ag 6 complex, locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection, the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however, the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together, the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation, which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.
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[An expression analysis of miR-200a in serum and liver tissue during the process of liver cancer development in rats].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To explore whether microRNA-200a (miR-200a) could be used as a novel biomarker of liver cancer using a rat model system.
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A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.
PLoS ONE
PUBLISHED: 08-25-2014
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The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509-6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509-Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.
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WNK1 Activates Large-Conductance Ca2+-Activated K+ Channels through Modulation of ERK1/2 Signaling.
J. Am. Soc. Nephrol.
PUBLISHED: 08-21-2014
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With no lysine (WNK) kinases are members of the serine/threonine kinase family. We previously showed that WNK4 inhibits renal large-conductance Ca(2+)-activated K(+) (BK) channel activity by enhancing its degradation through a lysosomal pathway. In this study, we investigated the effect of WNK1 on BK channel activity. In HEK293 cells stably expressing the ? subunit of BK (HEK-BK? cells), siRNA-mediated knockdown of WNK1 expression significantly inhibited both BK? channel activity and open probability. Knockdown of WNK1 expression also significantly inhibited BK? protein expression and increased ERK1/2 phosphorylation, whereas overexpression of WNK1 significantly enhanced BK? expression and decreased ERK1/2 phosphorylation in a dose-dependent manner in HEK293 cells. Knockdown of ERK1/2 prevented WNK1 siRNA-mediated inhibition of BK? expression. Similarly, pretreatment of HEK-BK? cells with the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of WNK1 siRNA on BK? expression in a dose-dependent manner. Knockdown of WNK1 expression also increased the ubiquitination of BK? channels. Notably, mice fed a high-K(+) diet for 10 days had significantly higher renal protein expression levels of BK? and WNK1 and lower levels of ERK1/2 phosphorylation compared with mice fed a normal-K(+) diet. These data suggest that WNK1 enhances BK channel function by reducing ERK1/2 signaling-mediated lysosomal degradation of the channel.
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Two novel DNA motifs are essential for BACE1 gene transcription.
Sci Rep
PUBLISHED: 08-14-2014
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BACE1 gene encodes for ?-Site amyloid ? precursor protein (APP)-cleaving enzyme1, which is required for generating amyloid ? protein(A?). Deposition of A? in brain plays an essential role in Alzheimer's Disease (AD) pathogenesis. BACE1 gene has a tissue-specific expression pattern and its expression is tightly regulated at transcriptional level. Core promoter is a minimal DNA sequence to direct transcription initiation and serves as a converging platform for the vast network of regulatory events. Here we identified the core promoter of human BACE1 gene, which is a 71 nucleotides region absent of typical known core promoter elements and is sufficient to initiate a basal transcription. Two novel DNA motifs, designated TCE1 and TCE2, were found to be involved in activating the transcription of human BACE1 gene in a synergistic way. Two single nucleotide mutations in these motifs completely abolished the promoter activity. In conclusion, our studies have demonstrated that novel DNA motif TCE1 and TCE2 in human BACE1 gene promoter are two essential cis-acting elements for BACE1 gene transcription. Studies on how these two motifs being regulated by different stimuli could provide insights into the molecular mechanisms underlying AD pathogenesis and pharmaceutical potentials of targeting these motifs for AD treatment.
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MicroRNA-mRNA regulatory network study and apoptosis analysis on bone marrow endothelial cells induced by liver cirrhosis serum.
Clin Res Hepatol Gastroenterol
PUBLISHED: 06-24-2014
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As important components of bone marrow microenvironment, bone marrow endothelial cells (BMECs) have important roles in regulating haematopoietic functions of the bone marrow. In preliminary study, we found the humoral inhibitor in liver cirrhosis (LC) could lead to ultrastructure alterations of the bone marrow endothelium. The present study aimed to investigate functional changes occurred in BMECs during LC.
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Amyloid-? precursor protein facilitates the regulator of calcineurin 1-mediated apoptosis by downregulating proteasome subunit ? type-5 and proteasome subunit ? type-7.
Neurobiol. Aging
PUBLISHED: 06-05-2014
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Individuals with Down syndrome (DS), caused by trisomy of chromosome 21, inevitably develop characteristic Alzheimer's disease (AD) neuropathology, including neuritic plaques, neurofibrillary tangles, and neuronal loss. Amyloid-? protein, the major component of neuritic plaques, is the proteolytic product of amyloid-? precursor protein (APP). APP and the regulator of calcineurin 1 (RCAN1) genes on chromosome 21 play a pivotal role in promoting plaque formation and neuronal apoptosis. However, the mechanism underlying AD pathogenesis in DS is not well defined. In this study, we demonstrated that APP significantly increased RCAN1 level in both cells and transgenic mice. Overexpression of APP significantly reduced the expression of 2 proteasome subunits, proteasome subunit ? type-5 and proteasome subunit ? type-7, leading to the inhibition of proteasomal degradation of RCAN1. Furthermore, knockdown of RCAN1 expression attenuated APP-induced neuronal apoptosis. Taken together, the results clearly showed that APP has a previously unknown function in regulating RCAN1-mediated neuronal apoptosis through the proteasome pathway. Our study demonstrates a novel mechanism by which overexpression of APP and RCAN1 causes neurodegeneration and AD pathogenesis in DS, and it provides new insights into the potential of targeting APP-induced proteasomal impairment and RCAN1 accumulation for AD and DS treatment.
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Cost-sensitive learning for emotion robust speaker recognition.
ScientificWorldJournal
PUBLISHED: 04-19-2014
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In the field of information security, voice is one of the most important parts in biometrics. Especially, with the development of voice communication through the Internet or telephone system, huge voice data resources are accessed. In speaker recognition, voiceprint can be applied as the unique password for the user to prove his/her identity. However, speech with various emotions can cause an unacceptably high error rate and aggravate the performance of speaker recognition system. This paper deals with this problem by introducing a cost-sensitive learning technology to reweight the probability of test affective utterances in the pitch envelop level, which can enhance the robustness in emotion-dependent speaker recognition effectively. Based on that technology, a new architecture of recognition system as well as its components is proposed in this paper. The experiment conducted on the Mandarin Affective Speech Corpus shows that an improvement of 8% identification rate over the traditional speaker recognition is achieved.
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Pseudomonas aeruginosa injects NDK into host cells through a type III secretion system.
Microbiology (Reading, Engl.)
PUBLISHED: 04-03-2014
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Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen possessing a type III secretion system (T3SS) which injects toxic effector proteins into mammalian host cells. In previous studies, P. aeruginosa strains lacking all of the known type III effectors were shown to cause cytotoxicity upon prolonged infection time. In this study, we report the identification of a new cytotoxin, nucleoside diphosphate kinase (NDK), which is injected into eukaryotic cells in a T3SS-dependent manner. Injection of NDK is inhibited by the presence of previously known effectors of the T3SS, with an effectorless strain injecting the highest amount, suggesting active competition with the known T3SS effectors. NDK is shown to cause a cytotoxic response when expressed in eukaryotic cells, and P. aeruginosa strains harbouring NDK also show a greater toxicity than strains lacking it. Interestingly, the cytotoxic effect of intracellular NDK is independent of its kinase activity. In previous studies, NDK was shown to be secreted into culture supernatants via a type I secretion system and cause cytotoxicity in a kinase-dependent manner. Therefore, the current study highlights an alternative route of NDK secretion as well as two different cytotoxic mechanisms of NDK, depending on the extra- or intra-cellular location of the protein.
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B7-H4 expression and its role in interleukin-2/interferon treatment of clear cell renal cell carcinoma.
Oncol Lett
PUBLISHED: 03-11-2014
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The immunological mechanism mediated by T cells is the main therapeutic target in the treatment of renal cell carcinoma (RCC) with interleukin (IL)-2 and interferon (IFN)-?. The aim of the present study was to evaluate the role of B7-H4 in the IL-2, IFN-? and IFN-? treatment of clear cell RCC (ccRCC). A total of 154 paraffin-embedded ccRCC tissues were studied using immunohistochemistry, which subsequently indicated that positive B7-H4 expression is associated with adverse clinical features in ccRCC. The effects of IL-2, IFN-? and IFN-? on B7-H4 expression in a ccRCC cell line were evaluated at the mRNA and protein levels. In addition, the effect of B7-H4 on the killing activity of T cells was detected. B7-H4 expression was identified to be upregulated by IL-2, IFN-? and IFN-?, of which, IFN-? was the most capable. Additionally, blocking of B7-H4/B7-H4 ligand interactions may rescue the killing activity of T cells. Altogether, the observations of the current study showed that the immune escape pathway induced by B7-H4 may be one of the most important reasons for the low efficacy of IL-2 and IFN-? and the inability to observe the efficacy of IFN-? in mRCC. This indicates that B7-H4 may be used as a new molecular biology marker to select treatment options for patients with ccRCC.
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Genetics of type 2 diabetes: insights into the pathogenesis and its clinical application.
Biomed Res Int
PUBLISHED: 03-07-2014
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With rapidly increasing prevalence, diabetes has become one of the major causes of mortality worldwide. According to the latest studies, genetic information makes substantial contributions towards the prediction of diabetes risk and individualized antidiabetic treatment. To date, approximately 70 susceptibility genes have been identified as being associated with type 2 diabetes (T2D) at a genome-wide significant level (P < 5 × 10(-8)). However, all the genetic loci identified so far account for only about 10% of the overall heritability of T2D. In addition, how these novel susceptibility loci correlate with the pathophysiology of the disease remains largely unknown. This review covers the major genetic studies on the risk of T2D based on ethnicity and briefly discusses the potential mechanisms and clinical utility of the genetic information underlying T2D.
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Modular analysis of bioinformatics demonstrates a critical role for NF-?B in macrophage activation.
Inflammation
PUBLISHED: 03-01-2014
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To achieve the goal of identifying the gene groups that regulated macrophage activation, a total of 925 differentially expressed genes of activated macrophages were found at the intersection of the three series (GSE5099-1, GSE5099-2, and GSE18686) from the Gene Expression Omnibus (GEO) database, and a sub-network was constructed based on the protein-protein interaction (PPI) network. Four communities (K?=?3) were identified from the sub-network using the CFinder software. Community 1 was considered as the gene group of interest base on the heat map. GO-BP and KEGG enrichment analysis with the DAVID software showed that the functions of the 14 genes in community 1 were mainly related to the NF-?B pathway. A network was constructed using the Cytoscape software. The diagram showed that STAT1, NFKBIA, NFKAIB, JUN, and RELA were the key genes in the regulation of macrophage activation. Among these genes, RELA (NF-?B P65) was an important member of the NF-?B family, while NFKBIA (I?B?) and NFKAIB (I?B?) were the inhibitory factors of NF-?B. Small molecules capable of regulating these five genes were identified via the CMap software, and a network diagram was generated using the Cytoscape software to provide a reference for the development of new drugs that regulate macrophage activation.
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Bioinformatics screening regarding herbal components that targetedly regulate the function of tumour-associated macrophages.
Oncol. Rep.
PUBLISHED: 02-26-2014
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As an important component of tumour stroma, tumour-associated macrophages (TAMs) promote tumour development and progression. Herbs have been increasingly used in anticancer therapies due to their wide-ranging anticancer effects and minor side-effects. However, no herb-based treatments targeting TAMs have yet been proposed. To address this issue, screening using modular analysis bioinformatics techniques found 6 core functional modules for TAMs that contain 46 total genes. Moreover, 15 potential new anticancer drugs that regulate the genes in the 6 core modules were identified through bioinformatics techniques and Fisher's exact test. Our results provide a new research avenue for targeting TAMs in anticancer therapies.
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A novel oil-in-water emulsion as a potential adjuvant for influenza vaccine: development, characterization, stability and in vivo evaluation.
Int J Pharm
PUBLISHED: 02-15-2014
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Oil-in-water emulsions consisting of squalene, tween and/or span have shown significant benefits for the prevention and control of influenza, with their adjuvant efficacy enhancing the immunogenicities of influenza vaccines in high-risk groups. However, concerns have been raised following reports that post-immunization reactions associated with these adjuvanted vaccines are more frequent. In this work, a stable and biocompatible oil-in-water emulsion adjuvant containing squalene, egg lecithin and sodium oleate has been developed. Animal studies demonstrated that this adjuvant could induce strong immune responses in BALB/c mice, as measured by hemagglutinin inhibition titers, influenza-specific serum antibody titers and cytokine levels (IFN-? and IL-4). Different oil compositions, including squalene, medium chain triglyceride and long chain triglyceride, were also evaluated. Furthermore, in contrast to MF59(®) which can only be sterilized by aseptic filtration, this adjuvant remained stable during autoclaving, showing minimal changes in pH, particle size and lysolecithin concentration.
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High-intensity focused ultrasound ablation of myocardium in vivo and instantaneous biological response.
Echocardiography
PUBLISHED: 02-10-2014
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This study aimed to evaluate the instantaneous biological response of canine myocardium in vivo to high-intensity focused ultrasound (HIFU) ablation, and thereby determine the feasibility of this method.
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Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells.
Cell. Physiol. Biochem.
PUBLISHED: 02-05-2014
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Background/Aims: Parenteral nutrition-associated liver disease (PNALD) is a major complication for patients who require long-term parenteral nutrition. Treatment options for PNALD are limited and its pathogenesis is poorly understood. Tribbles homolog 3 (TRB3) is a pseudokinase that modulates many signal transduction cascades and may be involved in the pathogenesis of PNALD. The aim of this study was to examine the role of TRB3 in palmitate-induced endoplasmic reticulum (ER) stress, in the human liver cell line L02. Methods: L02 cells were treated with palmitate, and its effect on cell viability, mitochondrial membrane potential, apoptosis and TRB3 expression were assessed. The role of TRB3 was also studied using transient overexpression of TRB3 in L02 cells, as well as its interaction with Akt signaling. Results: We found that palmitate induced ER stress and apoptosis in L02 cells. Palmitate-associated ER stress was accompanied by a significant induction of TRB3 expression at the mRNA and protein level. Overexpression of TRB3 potentiated the deleterious effects of palmitate, which was associated with decreased levels of phospho-Akt. Conclusions: TRB3 is an important mediator of palmitate-induced apoptosis in human liver cells, suggesting that it may also be involved in the molecular mechanism underlying PNALD. © 2014 S. Karger AG, Basel.
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PrtR homeostasis contributes to Pseudomonas aeruginosa pathogenesis and resistance against ciprofloxacin.
Infect. Immun.
PUBLISHED: 02-03-2014
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Pseudomonas aeruginosa is an opportunistic pathogen that causes acute and chronic infections in humans. Pyocins are bacteriocins produced by P. aeruginosa that are usually released through lysis of the producer strains. Expression of pyocin genes is negatively regulated by PrtR, which gets cleaved under SOS response, leading to upregulation of pyocin synthetic genes. Previously, we demonstrated that PrtR is required for the expression of type III secretion system (T3SS), which is an important virulence component of P. aeruginosa. In this study, we demonstrate that mutation in prtR results in reduced bacterial colonization in a mouse acute pneumonia model. Examination of bacterial and host cells in the bronchoalveolar lavage fluids from infected mice revealed that expression of PrtR is induced by reactive oxygen species (ROS) released by neutrophils. We further demonstrate that treatment with hydrogen peroxide or ciprofloxacin, known to induce the SOS response and pyocin production, resulted in an elevated PrtR mRNA level. Overexpression of PrtR by a tac promoter repressed the endogenous prtR promoter activity, and electrophoretic mobility shift assay revealed that PrtR binds to its own promoter, suggesting an autorepressive mechanism of regulation. A high level of PrtR expressed from a plasmid resulted in increased T3SS gene expression during infection and higher resistance against ciprofloxacin. Overall, our results suggest that the autorepression of PrtR contributes to the maintenance of a relatively stable level of PrtR, which is permissive to T3SS gene expression in the presence of ROS while increasing bacterial tolerance to stresses, such as ciprofloxacin, by limiting pyocin production.
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Occurrence and ecological potential of pharmaceuticals and personal care products in groundwater and reservoirs in the vicinity of municipal landfills in China.
Sci. Total Environ.
PUBLISHED: 01-28-2014
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Pharmaceutical and personal care products (PPCPs), including antibiotics, azole anti-fungals, non-steroid anti-inflammatory drugs, lipid regulators, parabens, antiseptics, and bisphenol A, were investigated in groundwater and reservoirs in the vicinity of two municipal landfills in the metropolis of Guangzhou, South China. Dehydroerythromycin, sulfamethoxazole, fluconazole, salicylic acid, methylparaben, triclosan, and bisphenol A were the mostly frequently detected PPCPs in the groundwater at low ng L(-1) levels. In the reservoirs, the PPCPs were widely detected at higher frequencies and concentrations, especially sulfamethoxazole, propiconazole, and ibuprofen, with maximal concentrations above 1 ?g L(-1). The PPCPs in the groundwater did not show significant seasonal differences or spatial trends. However, in the reservoirs, higher PPCP concentrations were observed in spring than in other seasons. The anti-bacterials in the groundwater posed medium risks to algae. In the reservoirs, the sulfonamides and macrolides posed low to high risks, while ibuprofen, salicylic acid, and clofibric acid presented low to medium risks to aquatic organisms. Overall, the results showed that the PPCP contaminants and subsequent ecological risks in the groundwater and surface water in the vicinity of the landfills may be of serious concern. More research is needed to better correlate the landfill leachates and PPCP contamination in the nearby aquatic environments.
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Anti-tumor efficacy of ultrasonic cavitation is potentiated by concurrent delivery of anti-angiogenic drug in colon cancer.
Cancer Lett.
PUBLISHED: 01-09-2014
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This study investigated the efficacy of concurrent delivery of an anti-angiogenic drug and ultrasonic cavitation therapy in a mouse model of human colon cancer. A biotinylated form of the anti-angiogenic drug Endostar was conjugated to a streptavidin-coated microbubble (MB). Mice bearing subcutaneous tumors (HT29) were divided into 4 groups. Group 1 served as an untreated control. Group 2 served as a cavitation control and received naked microbubbles and sham ultrasonic cavitation (MB+sham cavitation). Group 3 received naked microbubbles and ultrasonic cavitation (MB+cavitation). Group 4 received Endostar loaded microbubbles and ultrasonic cavitation (Endostar-MB+cavitation). Ultrasonic cavitation was performed using a high-power custom built sonicator. Contrast-enhanced ultrasound imaging (CEUS) was used to measure tumor blood flow before and after ultrasonic cavitation. In vivo fluorescence imaging was performed to monitor changes in tumor volume. Immunohistochemistry was performed to assess CD31, VEGFR-2 and alpha-v beta-3 integrin expression within the tumor. Apoptosis of the tumor cells was determined by TUNEL assay, and ultrastructural changes within the tumor were examined by electron microcopy. Ultrasonic cavitation with Endostar-MB demonstrated a significantly greater inhibition of tumor blood flow on day 7 and tumor growth on day 16 compared with naked MB and control groups. The Endostar-MB treated mice showed significantly decreased expression VEGFR-2 and alpha-v beta-3 integrin, and increased apoptosis of tumor cells and degradation of the tumor ultrastructure. Our findings indicated that the anti-vascular and anti-tumor effects of ultrasonic cavitation could be potentiated by simultaneously delivering an anti-angiogenic drug in colon cancer.
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Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: a potential therapeutic target of stem cell treatment for hepatocellular carcinoma.
Oncol. Rep.
PUBLISHED: 01-07-2014
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Recent findings suggest that clinical hepatocellular carcinoma (HCC) progression is driven by hepatic cancer stem cells (HCSCs) through their capacity for self-renewal, generation of heterogeneous lineages of cancer cells, resistance to chemotherapy and their ability to divide limitlessly, which may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, HCSC-directed therapeutic approaches might represent strategies to improve clinical HCC therapy. In previous studies, we showed that BC047440 was found to play a critical role in mediating HCC cell proliferation. The present study sought to determine whether BC047440 is involved in maintaining HCSC malignant behavior (including proliferation and differentiation). We demonstrated that BC047440 expression was markedly upregulated in HCSCs. Furthermore, we inhibited BC047440 in HCSCs using short hairpin RNA (shRNA). The effects of BC047440 on proliferation and differentiation were investigated. We also analyzed the involvement of critical molecular events known to regulate the proliferation and the differentiation machinery. Excluding apoptosis-related effects, we found that BC047440 inhibition resulted in enhanced cell proliferation through enhancing cytoplasmic accumulation of nuclear factor-?B (NF-?B) with a concomitant decrease in the nuclear fraction. BC047440 inhibition also resulted in inducing HCSC differentiation into hepatocytes. Furthermore, following downregulation of BC047440, the level of hepatocyte nuclear factor 4? (HNF4?) increased. Finally, tumorigenicity suppression following BC047440 depletion was confirmed in a nude mouse model. In conclusion, our findings indicate that BC047440 plays an important role in the proliferation and differentiation of HCSCs and may represent a novel therapeutic target for the treatment of HCC.
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Lithium ameliorates autistic-like behaviors induced by neonatal isolation in rats.
Front Behav Neurosci
PUBLISHED: 01-01-2014
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Neonatal isolation is a widely accepted model to study the long-term behavioral changes produced by the early life events. However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1-9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42-56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development.
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Modeling and computing of stock index forecasting based on neural network and Markov chain.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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The stock index reflects the fluctuation of the stock market. For a long time, there have been a lot of researches on the forecast of stock index. However, the traditional method is limited to achieving an ideal precision in the dynamic market due to the influences of many factors such as the economic situation, policy changes, and emergency events. Therefore, the approach based on adaptive modeling and conditional probability transfer causes the new attention of researchers. This paper presents a new forecast method by the combination of improved back-propagation (BP) neural network and Markov chain, as well as its modeling and computing technology. This method includes initial forecasting by improved BP neural network, division of Markov state region, computing of the state transition probability matrix, and the prediction adjustment. Results of the empirical study show that this method can achieve high accuracy in the stock index prediction, and it could provide a good reference for the investment in stock market.
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Bacterial delivery of TALEN proteins for human genome editing.
PLoS ONE
PUBLISHED: 01-01-2014
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Transcription Activator-Like Effector Nucleases (TALENs) are a novel class of sequence-specific nucleases that have recently gained prominence for its ease of production and high efficiency in genome editing. A TALEN pair recognizes specific DNA sequences and introduce double-strand break in the target site, triggering non-homologous end joining and homologous recombination. Current methods of TALEN delivery involves introduction of foreign genetic materials, such as plasmid DNA or mRNA, through transfection. Here, we show an alternative way of TALEN delivery, bacterial type III secretion system (T3SS) mediated direct injection of the TALEN proteins into human cells. Bacterially injected TALEN was shown to efficiently target host cell nucleus where it persists for almost 12 hours. Using a pair of TALENs targeting venus gene, such injected nuclear TALENs were shown functional in introducing DNA mutation in the target site. Interestingly, S-phase cells seem to show greater sensitivity to the TALEN mediated target gene modification. Accordingly, efficiency of such genome editing can easily be manipulated by the infection dose, number of repeated infections as well as enrichment of S phase cells. This work further extends the utility of T3SS in the delivery of functional proteins into mammalian cells to alter their characters for biomedical applications.
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Simplified process model discovery based on role-oriented genetic mining.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Process mining is automated acquisition of process models from event logs. Although many process mining techniques have been developed, most of them are based on control flow. Meanwhile, the existing role-oriented process mining methods focus on correctness and integrity of roles while ignoring role complexity of the process model, which directly impacts understandability and quality of the model. To address these problems, we propose a genetic programming approach to mine the simplified process model. Using a new metric of process complexity in terms of roles as the fitness function, we can find simpler process models. The new role complexity metric of process models is designed from role cohesion and coupling, and applied to discover roles in process models. Moreover, the higher fitness derived from role complexity metric also provides a guideline for redesigning process models. Finally, we conduct case study and experiments to show that the proposed method is more effective for streamlining the process by comparing with related studies.
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Information spread of emergency events: path searching on social networks.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Emergency has attracted global attentions of government and the public, and it will easily trigger a series of serious social problems if it is not supervised effectively in the dissemination process. In the Internet world, people communicate with each other and form various virtual communities based on social networks, which lead to a complex and fast information spread pattern of emergency events. This paper collects Internet data based on data acquisition and topic detection technology, analyzes the process of information spread on social networks, describes the diffusions and impacts of that information from the perspective of random graph, and finally seeks the key paths through an improved IBF algorithm. Application cases have shown that this algorithm can search the shortest spread paths efficiently, which may help us to guide and control the information dissemination of emergency events on early warning.
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Vocal emotion of humanoid robots: a study from brain mechanism.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Driven by rapid ongoing advances in humanoid robot, increasing attention has been shifted into the issue of emotion intelligence of AI robots to facilitate the communication between man-machines and human beings, especially for the vocal emotion in interactive system of future humanoid robots. This paper explored the brain mechanism of vocal emotion by studying previous researches and developed an experiment to observe the brain response by fMRI, to analyze vocal emotion of human beings. Findings in this paper provided a new approach to design and evaluate the vocal emotion of humanoid robots based on brain mechanism of human beings.
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Construction of network for protein kinases that play a role in acute pancreatitis.
Pancreas
PUBLISHED: 12-16-2013
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This study aimed to search for protein kinases that play a role in acute pancreatitis and analyze their potential connection with each other.
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MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-04-2013
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HIV-1 primarily infects activated CD4+ T cells and macrophages. Quiescent CD4+ T cells, however, possess cellular factors that limit HIV-1 infection at different postentry steps of the viral life cycle. Here, we show that the previously reported immune regulator monocyte chemotactic protein-induced protein 1 (MCPIP1) restricts HIV-1 production in CD4+ T cells. While the ectopic expression of MCPIP1 in cell lines abolished the production of HIV-1, silencing of MCPIP1 enhanced HIV-1 production. Subsequent analysis indicated that MCPIP1 imposes its restriction by decreasing the steady levels of viral mRNA species through its RNase domain. Remarkably, common T-cell stimuli induced the rapid degradation of MCPIP1 in both T-cell lines and quiescent human CD4+ T cells. Lastly, blocking the proteosomal degradation of MCPIP1 by MG132 abrogated HIV-1 production in phorbol 12-myristate 13-acetate/ionomycin-stimulated human CD4+ T cells isolated from healthy donors. Overall, MCPIP1 poses a potent barrier against HIV-1 infection at a posttranscriptional stage. Although the observed HIV restriction conferred by MCPIP1 does not seem to be overcome by any viral protein, it is removed during cellular stimulation. These findings provide insights into the mechanisms of cellular activation-mediated HIV-1 production in CD4+ T cells.
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SuhB is a regulator of multiple virulence genes and essential for pathogenesis of Pseudomonas aeruginosa.
MBio
PUBLISHED: 10-31-2013
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During initial colonization and chronic infection, pathogenic bacteria encounter distinct host environments. Adjusting gene expression accordingly is essential for the pathogenesis. Pseudomonas aeruginosa has evolved complicated regulatory networks to regulate different sets of virulence factors to facilitate colonization and persistence. The type III secretion system (T3SS) and motility are associated with acute infections, while biofilm formation and the type VI secretion system (T6SS) are associated with chronic persistence. To identify novel regulatory genes required for pathogenesis, we screened a P. aeruginosa transposon (Tn) insertion library and found suhB to be an essential gene for the T3SS gene expression. The expression of suhB was upregulated in a mouse acute lung infection model, and loss of suhB resulted in avirulence. Suppression of T3SS gene expression in the suhB mutant is linked to a defective translation of the T3SS master regulator, ExsA. Further studies demonstrated that suhB mutation led to the upregulation of GacA and its downstream small RNAs, RsmY and RsmZ, triggering T6SS expression and biofilm formation while inhibiting the T3SS. Our results demonstrate that an in vivo-inducible gene, suhB, reciprocally regulates genes associated with acute and chronic infections and plays an essential role in the pathogenesis of P. aeruginosa.
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White matter integrity alterations in young healthy adults reporting childhood trauma: A diffusion tensor imaging study.
Aust N Z J Psychiatry
PUBLISHED: 10-14-2013
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Objective: To date, insufficient studies have focused on the relationship between childhood trauma and white matter integrity changes in healthy subjects. The aim of the present study was to explore the potential effects of childhood trauma on white matter microstructural changes by using voxel-based diffusion tensor imaging (DTI) to examine alterations in fractional anisotropy (FA) values in a group of young healthy adults. Methods: A total of 21 healthy adults with a history of childhood trauma exposures and 21 age- and sex-matched individuals without childhood trauma were recruited in the present study. The Childhood Trauma Questionnaire was used to assess five aspects of childhood trauma exposures. DTI data were obtained on a Philips 3.0-Tesla scanner. Voxel-based analysis was conducted to compare white matter FA values between groups. Results: Adults with self-reported childhood trauma experiences showed decreased white matter FA values in the genu and body of the corpus callosum and the left occipital fusiform gyrus (p < 0.001 uncorrected, voxel > 100). There was no significant difference in FA values between individuals with single and multiple childhood trauma exposures at the defined threshold. Conclusion: Our findings suggest that childhood trauma is associated with reduced microstructural integrity of the white matter in adulthood. These effects are still evident even in the absence of current psychiatric or medical symptoms, which may represent the vulnerability for developing mental disorders after childhood trauma experiences.
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Association of Genetic Variants of BMP4 with Type 2 Diabetes Mellitus and Clinical Traits in a Chinese Han Population.
Biomed Res Int
PUBLISHED: 09-24-2013
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BMP4 is one of the transforming growth factor- ? superfamily, which can participate in adipogenesis. Gene encoding BMP4 is acknowledged as a convincing candidate that may contribute to both glucose and lipid metabolism. In this paper, we aimed to test the impacts of BMP4 variants on type 2 diabetes in a large sample of Chinese population. We genotyped 10 tagging single nucleotide polymorphisms within the BMP4 region in 6822 participants and acquired detailed clinical investigations and biochemistry measurements. We found that BMP4 rs8014363 showed nominal association towards type 2 diabetes, with the T allele conferring a high risk of type 2 diabetes (OR = 1.108, 95%CI 0.999-1.229, P = 0.051 for allele; OR = 1.110, 95%CI 1.000-1.231, P = 0.050 for genotype), but it was no longer statistically significant after adjusting for multiple testing (empirical P = 0.3689 for allele based on 10,000 permutations). Moreover, we observed a significant association of rs8014363 with triglyceride level and a trend towards association with high-density lipoprotein cholesterol after adjusting for age, gender, and BMI (P = 0.035 and 0.068, resp.). Our data suggested that the genetic variants of BMP4 may not play a dominant role in glucose metabolism in Chinese Han population, but a minor effect cannot be ignored.
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Mla- and Rom1-mediated control of microRNA398 and chloroplast copper/zinc superoxide dismutase regulates cell death in response to the barley powdery mildew fungus.
New Phytol.
PUBLISHED: 08-26-2013
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Barley (Hordeum vulgare L.) Mildew resistance locus a (Mla) confers allele-specific interactions with natural variants of the ascomycete fungus Blumeria graminis f. sp. hordei (Bgh), the causal agent of powdery mildew disease. Significant reprogramming of Mla-mediated gene expression occurs upon infection by this obligate biotrophic pathogen. We utilized a proteomics-based approach, combined with barley mla, required for Mla12 resistance1 (rar1), and restoration of Mla resistance1 (rom1) mutants, to identify components of Mla-directed signaling. Loss-of-function mutations in Mla and Rar1 both resulted in the reduced accumulation of chloroplast copper/zinc superoxide dismutase 1 (HvSOD1), whereas loss of function in Rom1 re-established HvSOD1 levels. In addition, both Mla and Rom1 negatively regulated hvu-microRNA398 (hvu-miR398), and up-regulation of miR398 was coupled to reduced HvSOD1 expression. Barley stripe mosaic virus (BSMV)-mediated over-expression of both barley and Arabidopsis miR398 repressed accumulation of HvSOD1, and BSMV-induced gene silencing of HvSod1 impeded Mla-triggered H2 O2 and hypersensitive reaction (HR) at barley-Bgh interaction sites. These data indicate that Mla- and Rom1-regulated hvu-miR398 represses HvSOD1 accumulation, influencing effector-induced HR in response to the powdery mildew fungus.
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Genome-wide association study identifies three novel loci for type 2 diabetes.
Hum. Mol. Genet.
PUBLISHED: 08-14-2013
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Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17], GPSM1 [rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15] and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.
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Whole genome expression profiling and screening for differentially expressed cytokine genes in human bone marrow endothelial cells treated with humoral inhibitors in liver cirrhosis.
Int. J. Mol. Med.
PUBLISHED: 06-06-2013
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Bone marrow endothelial cells (BMECs) are important components of the hematopoietic microenvironment in bone marrow, and they can secrete several types of cytokines to regulate the functions of hematopoietic stem/progenitor cells. To date, it is unknown whether BMECs undergo functional changes and lead to hematopoietic abnormalities in cases of liver cirrhosis (LC). In the present study, whole genome microarray analysis was carried out to detect differentially expressed genes in human BMECs treated for 48 h with medium supplemented with 20% pooled sera from 26 patients with LC or 10 healthy volunteers as the control group. A total of 1,106 upregulated genes and 766 downregulated genes were identified. In Gene Ontology analysis, the most significant categories of genes were revealed. A large number of the upregulated genes were involved in processes, such as cell-cell adhesion, apoptosis and cellular response to stimuli and the downregulated genes were involved in the negative regulation of secretion, angiogenesis, blood vessel development and cell growth. Pathway analysis revealed that the upregulated genes were either cell adhesion molecules or parts of the apoptotic signaling pathway and the downregulated genes were involved in the Wnt signaling pathway and MAPK signaling pathway. These were the pathways with the highest enrichment scores. The results of apoptosis assays revealed that the humoral inhibitors in the sera of patients with LC induced the apoptosis of BMECs, which confirmed the accuracy of bioinformatic analysis. Moreover, we screened and verified 21 differentially expressed cytokine genes [transforming growth factor (TGF)B1, tumor necrosis factor (TNF)B, TNF receptor superfamily, member 11b (TNFRSF11B), TNF (ligand) superfamily, member 13b (TNFSF13B), interleukin (IL)1A, IL6, IL11, IL17C, IL24, family with sequence similarity 3, member B (FAM3B), Fas ligand (FASLG), matrix metallopeptidase (MMP)3, MMP15, vitronectin (VTN), insulin-like growth factor 1 (IGF1), fibroblast growth factor 22 (FGF22), slit homolog 2 (Drosophila) (SLIT2), thrombospondin (THBS)2, THBS3, chemokine (C-C motif) ligand 28 (CCL28) and macrophage stimulating 1 (MST1)] from 97 cytokine genes in BMECs treated with serum from patients with LC. The results from our study demonstrate that the humoral inhibitors in the sera of patients with LC induce the dysfunction and abnormal cytokine secretion by BMECs, which may be a novel mechanism responsible for hematological abnormalities in patients with LC.
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Reconstitution of kidney side population cells after ischemia-reperfusion injury by self-proliferation and bone marrow-derived cell homing.
Evid Based Complement Alternat Med
PUBLISHED: 05-16-2013
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The aim of this study was to examine the contribution of side population (SP) cells from kidney and bone marrow for reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). The SP and non-SP cells in kidneys following IRI were isolated and serially assessed by fluorescence-activated cell sorting. The apoptosis, proliferation, phenotype, and paracrine actions of SP cells were evaluated in vitro and in vivo. Results indicated that the SP cells from ischemic kidney were acutely depleted within one day following renal IRI and were progressively restored to baseline within 7 days after IRI, through both proliferation of remaining kidney SP cells and homing of bone marrow-derived cells to ischemic kidney. Either hypoxia or serum deprivation alone increased apoptosis of SP cells, and a combination of both further aggravated it. Furthermore, hypoxia in vivo and in vitro induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1 ? in kidney SP but not non-SP cells. In summary, these results suggest that following renal IRI, kidney SP cells are acutely depleted and then progressively restored to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing.
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Profile and behavior of antiviral drugs in aquatic environments of the Pearl River Delta, China.
Sci. Total Environ.
PUBLISHED: 05-04-2013
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Occurrence and behavior of six antiviral pharmaceuticals (acyclovir, ganciclovir, oseltamivir, ribavirin, stavudine and zidovudine) and one active metabolite oseltamivir carboxylate were investigated in wastewater, landfill leachate, river water, reservoir and well water in the vicinity of municipal landfills in the Pearl River Delta, China. Acyclovir was the only antiviral detected in the wastewater at 177-406 (mean=238) and 114-205 (mean=154) ng L(-1) in the influent and final effluent, respectively. Aerobic biodegradation appeared to be the main process for the elimination of acyclovir in the wastewater. Acyclovir was also the only antiviral quantitatively detected in the Pearl River and its tributaries, with a maximum concentration up to 113 ng L(-1). Treated wastewater was a major source of acyclovir in the rivers. The highest concentration of acyclovir was observed in winter in the river water and the dilution effect by precipitation was suggested to be the dominant factor impacting the seasonal pattern of acyclovir in the rivers. No antivirals were quantitatively detected in the well water whereas acyclovir was frequently detected in the reservoirs at a maximal concentration of 33.6 ng L(-1) in the vicinity of the municipal landfills. However, source identification and fate of acyclovir in the reservoirs pend on further research.
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Stereoisomeric profiling of pharmaceuticals ibuprofen and iopromide in wastewater and river water, China.
Environ Geochem Health
PUBLISHED: 04-02-2013
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Stereoisomeric compositions can provide insights into sources, fate, and ecological risks of contaminants in the environment. In this study, stereoisomeric profiles of ibuprofen and iopromide were investigated in wastewater and receiving surface water of the Pearl River Delta, south China. The enantiomeric fraction (EF) of ibuprofen was 0.108-0.188 and 0.480, whereas the isomer ratio (IR) of iopromide was 1.426-1.673 and 1.737-1.898 in the influent and final effluent, respectively, suggesting stereoselective degradation occurred for both pharmaceuticals during wastewater treatment. Ibuprofen showed enantioselective degradation in the anaerobic, anoxic, and aerobic conditions, whereas iopromide displayed isomer-selective degradation only under the aerobic condition. In the river waters, the EF of ibuprofen was 0.130-0.327 and the IR of iopromide was 1.500-2.531. The results suggested that pharmaceuticals in the mainstream Pearl River were mainly from discharge of treated wastewater, whereas in the tributary rivers and urban canals, direct discharge of untreated wastewater represented a significant contribution. The IR of iopromide can be an applicable and efficient tracer for wastewater discharge in the environment.
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Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate.
Mol Med Rep
PUBLISHED: 02-27-2013
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Trypsinogen activation is the initial factor involved in the development of all types of acute pancreatitis (AP) and has been suggested to be regulated by protein kinases. In the present study, AR42J rat pancreatic acinar cells were treated with taurolithocholic acid 3-sulfate (TLC-S), and trypsinogen activation was detected with bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide) dihydrochloride (BZiPAR) staining and flow cytometry. Differentially expressed protein kinase genes were screened by Gene Chip analysis, and the functions of these kinases were analyzed. A significantly increased activation of trypsinogen in AR42J cells following treatment with TLC-S was observed. A total of 22 differentially expressed protein kinase genes were found in the TLC-S group, among which 19 genes were upregulated and 3 were downregulated. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, kinase genes of the same KEGG pathways were connected to create a network through signaling pathways, and 10 nodes of kinases were identified, which were mitogen-activated protein kinase (Mapk)8, Mapk14, Map2k4, interleukin-1 receptor-associated kinase 3 (Irak3), ribosomal protein S6 kinase, 90 kDa, polypeptide 2 (Rps6ka2), protein kinase C, alpha (Prkca), v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), protein tyrosine kinase 2 beta (Ptk2b), p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) and FYN oncogene related to SRC, FGR, YES (Fyn). The interactions between signaling pathways were further analyzed and a network was created. MAPK and calcium signaling pathways were found to be located at the center of the network. Thus, protein kinases constitute potential drug targets for AP treatment.
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Proteomic analysis of apoptotic and oncotic pancreatic acinar AR42J cells treated with caerulein.
Mol. Cell. Biochem.
PUBLISHED: 02-23-2013
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This study aims to determine the differentially expressed proteins in the pancreatic acinar cells undergoing apoptosis and oncosis stimulated with caerulein to explore different cell death process of the acinar cell. AR42J cells were treated with caerulein to induce cell model of acute pancreatitis. Cells that were undergoing apoptosis and oncosis were separated by flow cytometry. Then differentially expressed proteins in the two groups of separated cells were detected by shotgun liquid chromatography-tandem mass spectrometry. The results showed that 11 proteins were detected in both apoptosis group and oncosis group, 17 proteins were detected only in apoptosis group and 29 proteins were detected only in oncosis group. KEGG analysis showed that proteins detected only in apoptosis group were significantly enriched in 10 pathways, including ECM-receptor interaction, cell adhesion molecules, and proteins detected only in oncosis group were significantly enriched in three pathways, including endocytosis, base excision repair, and RNA degradation. These proteins we detected are helpful for us to understand the process of cell death in acute pancreatitis and may be useful for changing the death mode of pancreatic acinar cells, thus attenuating the severity of pancreatitis.
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Beneficial effects of an 8-week, very low carbohydrate diet intervention on obese subjects.
Evid Based Complement Alternat Med
PUBLISHED: 02-18-2013
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Aim. To investigate the effects of weight loss during an 8-week very low carbohydrate diet (VLCD) on improvement of metabolic parameters, adipose distribution and body composition, and insulin resistance and sensitivity in Chinese obese subjects. Methods. Fifty-three healthy obese volunteers were given an 8-week VLCD. The outcomes were changes in anthropometry, body composition, metabolic profile, abdominal fat distribution, liver fat percent (LFP), and insulin resistance and sensitivity. Results. A total of 46 (86.8%) obese subjects completed the study. The VLCD caused a weight loss of -8.7 ± 0.6?kg (mean?±?standard error (SE), P < 0.0001) combined with a significant improvement of metabolic profile. In both male and female, nonesterified fatty acid (NEFA) significantly decreased (-166.2 ± 47.6? ? mol/L, P = 0.001) and ? -hydroxybutyric acid (BHA) increased (0.15 ± 0.06?mmol/L, P = 0.004) after eight weeks of VLCD intervention. The significant reductions in subcutaneous fat area (SFA), visceral fat area (VFA), and LFP were -66.5 ± 7.9?cm(2), -35.3 ± 3.9?cm(2), and -16.4 ± 2.4%, respectively (all P values P < 0.0001). HOMA IR and HOMA ? significantly decreased while whole body insulin sensitivity index (WBISI) increased (all P values P < 0.001). Conclusion. Eight weeks of VLCD was an effective intervention in obese subjects. These beneficial effects may be associated with enhanced hepatic and whole-body lipolysis and oxidation.
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Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect.
Hum Brain Mapp
PUBLISHED: 02-13-2013
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Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole-brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting-state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole-brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph-theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal-limbic-thalamic-cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole-brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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Real-time 3-dimensional echocardiographic assessment of ventricular volume, mass, and function in human fetuses.
PLoS ONE
PUBLISHED: 02-05-2013
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We sought to determine the feasibility and reproducibility of real-time 3-dimensional echocardiography (RT3DE) for evaluation of cardiac volume, mass, and function and to characterize maturational changes of these measurements in human fetuses.
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Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.
Compr Psychiatry
PUBLISHED: 01-18-2013
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Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.
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Cancer incidence and mortality in patients with type 2 diabetes treated with human insulin: a cohort study in Shanghai.
PLoS ONE
PUBLISHED: 01-07-2013
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The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.
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Downregulation of miR-200a Induces EMT Phenotypes and CSC-like Signatures through Targeting the ?-catenin Pathway in Hepatic Oval Cells.
PLoS ONE
PUBLISHED: 01-01-2013
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Hepatocellular carcinoma (HCC) can be derived from malignant transformed adult hepatic progenitor cells. However, the regulatory factors and molecular mechanisms underlying the process are not well defined. Our previous microRNA (miRNA) microarray analysis revealed a significant decrease of miR-200a level in F344 rat HCC side population (SP) fraction cells versus their normal counterparts. In the present study, we further investigated the effect of miR-200a on hepatic oval cell (HOC) phenotypes. We first confirmed downregulated miR-200a levels in rat hepatoma cells compared with WB-F344 cells. Next, by lentivirus-mediated loss-of-function studies, we showed that stable knockdown of miR-200a confers a mesenchymal phenotype to WB-F344 cells, including an elongated cell morphology, enhanced cell migration ability and expression of epithelial mesenchymal transition (EMT)-representative markers. Concomitantly, several cancer stem cell (CSC)-like traits appeared in these cells, which exhibit enhanced spheroid-forming capacity, express putative hepatic CSC markers and display superior resistance to chemotherapeutic drugs in vitro. Furthermore, bioinformatics analysis, luciferase assays and western blot analysis identified ?-catenin (CTNNB1) as a direct and functional target of miR-200a. Knockdown of miR-200a partially activated Wnt/?-catenin signaling, and silencing of ?-catenin functionally attenuated anti-miR-200a effects in vitro in WB-F344 cells. At length, in vivo xenograft assay demonstrated the acquisition of tumorigenicity of WB-F344 cells after miR-200a siliencing. Collectively, our findings indicate that miR-200a may function as an important regulatory factor in neoplastic transition of HOCs by targeting the ?-catenin pathway.
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iTRAQ-based proteomic profiling of human serum reveals down-regulation of platelet basic protein and apolipoprotein B100 in patients with hematotoxicity induced by chronic occupational benzene exposure.
Toxicology
PUBLISHED: 10-21-2011
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Benzene is an important industrial chemical and an environmental contaminant, but the pathogenesis of hematotoxicity induced by chronic occupational benzene exposure (HCOBE) remains to be elucidated. To gain an insight into the molecular mechanisms and developmental biomarkers for HCOBE, isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) were utilized. Identification and quantitation of differentially expressed proteins between HCOBE cases and healthy control were thus made. Expressions of selected proteins were confirmed by western blot and further validated by ELISA. A total of 159 unique proteins were identified (?95% confidence), and relative expression data were obtained for 141 of these in 3 iTRAQ experiments, with fifty proteins found to be in common among 3 iTRAQ experiments. Plasminogen (PLG) was found to be significantly up-regulated, whereas platelet basic protein (PBP) and apolipoprotein B100 (APOB100) were significantly down-regulated in the serum of HCOBE cases. Additionally, the altered proteins were associated with the molecular functions of binding, catalytic activity, enzyme regulator activity and transporter activity, and involved in biological processes of apoptosis, developmental and immune system process, as well as response to stimulus. Furthermore, differential expressions of PLG, PBP and APOB100 were confirmed by western blot, and the clinical relevance of PBP and APOB100 with HCOBE was validated by ELISA. Overall, our results showed that lowered expression of PBP and APOB100 proteins served as potential biomarkers of HCOBE, and may play roles in the benzene-induced immunosuppressive effects and disorders in lipid metabolism.
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[Functional magnetic resonance imaging of brain of college students with internet addiction].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-23-2011
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To explore the functional locations of brain regions related to internet addiction (IA)with task-functional magnetic resonance imaging (fMRI).
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CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.
Diabetes
PUBLISHED: 09-12-2011
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Diabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients.
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Subcutaneous fascial bands--a qualitative and morphometric analysis.
PLoS ONE
PUBLISHED: 04-20-2011
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Although fascial bands within the subcutaneous (SQ) layer are commonly seen in ultrasound images, little is known about their functional role, much less their structural characteristics. This studys objective is to describe the morphological features of SQ fascial bands and to systematically evaluate the bands using image analyses tools and morphometric measures.
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Neglected aspect of the strategy for human breast diseases: trans-areolar drug delivery.
Med. Hypotheses
PUBLISHED: 04-08-2011
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Breast cancer is the most common malignancy in women worldwide. Oncoplastic surgery and partial-breast reconstruction have already developed to improve cosmetic outcomes. However, new strategies for breast diseases are still needed. The principles of evolutionary biology and phylogeny can help solve specific medical problems. But the phylogeny of human breast areola had not been researched ever since proposed. The breast areola has a unique phylogeny, it has all different types of skin glands and includes a few hairs towards the periphery. These skin appendages, including Montgomerys glands - whose miniature mammary acini are in the subcutaneous tissue - make the dermal microvascular "sink" phenomenon imperfect, resulting in that more drug molecules can penetrate into deeper tissue. Meanwhile, the wrinkled skin of the areola increases the total delivery area. Here, we emphasize that the human breast areola has the potential to increase transdermal drug delivery to the breast. We anticipate that our hypothesis may help to provide new, optimized therapeutic and prophylactic strategies for the human breast diseases.
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Transcriptional Regulation of TMP21 by NFAT.
Mol Neurodegener
PUBLISHED: 03-07-2011
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TMP21 is a member of the p24 cargo protein family, which is involved in protein transport between the Golgi apparatus and ER. Alzheimers Disease (AD) is the most common neurodegenerative disorder leading to dementia and deposition of amyloid ? protein (A?) is the pathological feature of AD pathogenesis. Knockdown of TMP21 expression by siRNA causes a sharp increase in A? production; however the underlying mechanism by which TMP21 regulates A? generation is unknown, and human TMP21 gene expression regulation has not yet been studied.
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Increased NF-?B signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimers disease.
Int. J. Neuropsychopharmacol.
PUBLISHED: 02-18-2011
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Elevated levels of ?-site APP cleaving enzyme 1 (BACE1) were found in the brain of some sporadic Alzheimers disease (AD) patients; however, the underlying mechanism is unknown. BACE1 cleaves ?-amyloid precursor protein (APP) to generate amyloid ? protein (A?), a central component of neuritic plaques in AD brains. Nuclear factor-kappa B (NF-?B) signalling plays an important role in gene regulation and is implicated in inflammation, oxidative stress and apoptosis. In this report we found that both BACE1 and NF-?B p65 levels were significantly increased in the brains of AD patients. Two functional NF-?B-binding elements were identified in the human BACE1 promoter region. We found that NF-?B p65 expression resulted in increased BACE1 promoter activity and BACE1 transcription, while disruption of NF-?B p65 decreased BACE1 gene expression in p65 knockout (RelA-knockout) cells. In addition, NF-?B p65 expression leads to up-regulated ?-secretase cleavage and A? production, while non-steroidal anti-inflammatory drugs (NSAIDs) inhibited BACE1 transcriptional activation induced by strong NF-?B activator tumour necrosis factor-alpha (TNF-?). Taken together, our results clearly demonstrate that NF-?B signalling facilitates BACE1 gene expression and APP processing, and increased BACE1 expression mediated by NF-?B signalling in the brain could be one of the novel molecular mechanisms underlying the development of AD in some sporadic cases. Furthermore, NSAIDs could block the inflammation-induced BACE1 transcription and A? production. Our study suggests that inhibition of NF-?B-mediated BACE1 expression may be a valuable drug target for AD therapy.
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A common polymorphism of CYP4A11 is associated with blood pressure in a Chinese population.
Hypertens. Res.
PUBLISHED: 02-17-2011
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Variants of the human CYP4A11, which belongs to the cytochrome P450, family 4, have been reported to be associated with hypertension in general populations. However, data in the Chinese population are limited. This study sought to assess the effect of CYP4A11 on the prevalence of hypertension and blood pressure in a Chinese population. Three tagging single nucleotide polymorphisms, rs9332982, rs4660980 and rs3890011, were genotyped in 1734 community-based participants. Individuals with secondary hypertension were excluded. Sex-pooled and sex-specific analysis for genotype-phenotype association were both conducted. We found rs9332982 T allele was nominally associated with higher prevalence of hypertension in women after adjustment for covariates (OR: 1.38, 95%CI: 1.06-1.81, P = 0.0183). The significance did not retain after Bonferroni correction. In blood pressure analysis restricted to normotensive individuals, rs4660980 was associated with both systolic (? = -3.17, P = 0.0011) and diastolic blood pressure (? = -1.75, P = 0.0010) in men. A common variant on CYP4A11 was associated with blood pressure in a Chinese population. Future studies are needed to confirm our findings.
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Dysfunctional beliefs and attitudes on sleep and sleep disturbances pre- and post-antidepressant treatments in patients with major depression.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 02-12-2011
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To explore the relationship between dysfunctional beliefs and attitudes on sleep and sleep disturbances before and after a short-term pharmacotherapy in patients with major depression.
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Abnormal baseline brain activity in posttraumatic stress disorder: a resting-state functional magnetic resonance imaging study.
Neurosci. Lett.
PUBLISHED: 02-09-2011
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Little is known about how spontaneous brain activity during the resting state may be altered in posttraumatic stress disorder (PTSD) compared to traumatized individuals. In the current study, we used a measure of amplitude of low-frequency (0.01-0.08 Hz) fluctuation (ALFF) to investigate the regional baseline brain function of this disorder. Fifty-four medication-naive PTSD patients and seventy-two matched traumatized comparison subjects who experienced the Sichuan major earthquake participated in a functional magnetic resonance imaging (fMRI) scan. We analyzed the difference between the PTSD and comparison groups during a resting state using ALFF. PTSD patients showed decreased ALFF values in right lingual gyrus, cuneus, middle occipital gyrus, insula, and cerebellum, and increased ALFF values in right medial and middle frontal gyri, relative to traumatized individuals without PTSD. The ALFF value in the right medial frontal gyrus was positively correlated with severity of the disorder. Our findings show that abnormality of intrinsic brain activity exists under resting conditions in PTSD patients exposed to a major earthquake. Altered ALFF in predominantly right hemisphere cortical and subcortical regions and in cerebellum potentially contribute to the neural mechanisms underlying traumatic memory and symptoms in PTSD.
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Tg737 inhibition results in malignant transformation in fetal liver stem/progenitor cells by promoting cell-cycle progression and differentiation arrest.
Mol. Carcinog.
PUBLISHED: 02-04-2011
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Cancer stem/progenitor cells (CSPCs) may originate from the malignant transformation of normal stem cells. However, the mechanism by which normal stem cells undergo such transformation is not understood. Our previous studies provided evidence that Tg737 may play an important role in carcinogenesis of liver stem cells. In this study, we investigated the role of Tg737 in the malignant transformation of fetal liver stem/progenitor cells (FLSPCs). We inhibited Tg737 in FLSPCs using short hairpin RNA (shRNA). The microscopic observations of freshly purified Tg737 normal FLSPCs (nFLSPCs) and Tg737-silent FLSPCs (sFLSPCs), which showed high expression levels of stem cell markers, revealed no significant morphological changes in sFLSPCs. Following RNAi of Tg737, the mRNA and protein levels of sFLSPCs decreased by 81.81% and 80.10% as shown by PCR, Western blot and immunocytochemistry analyses. Excluding apoptosis-related effects, we found that silencing of Tg737 resulted in enhanced cell proliferation through promoting cell-cycle progression via upregulation of cyclin D1 and cyclin B expression (P??0.05) and quiescent ultrastructure. Assessment of cell malignant traits by transwell migration assays and by growth of xenograft tumors in athymic mice showed that reduced expression of Tg737 greatly promoted cell invasion and hepatocarcinogenesis of FLSPCs (P?
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NF-?B signaling inhibits ubiquitin carboxyl-terminal hydrolase L1 gene expression.
J. Neurochem.
PUBLISHED: 01-28-2011
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Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that plays a regulatory role in targeting proteins for proteasomal degradation. UCH-L1 is highly expressed in neurons and has been demonstrated to promote cell viability and maintain neuronal integrity. Reduced UCH-L1 levels have been observed in various neurodegenerative diseases, and expression of UCH-L1 can rescue synaptic dysfunction and memory deficits in Alzheimers Disease model mice. However, the mechanisms regulating UCH-L1 expression have not been determined. In this study, we cloned a 1782 bp of the 5 flanking region of the human UCH-L1 gene and identified a 43 bp fragment containing the transcription start site as the minimal region necessary for promoter activity. Sequence analysis revealed several putative regulatory elements including NF-?B, NFAT, CREB, NRSF, YY1, AP1, and STAT in the UCH-L1 promoter. A functional NF-?B response element was identified in the UCH-L1 promoter region. Expression of NF-?B suppressed UCH-L1 gene transcription. In the RelA knockout system where NF-?B activity is ablated, UCH-L1 expression was significantly increased. Furthermore, activation of NF-?B signaling by the inflammatory stimulator lipopolysaccharide and TNF? resulted in a decrease of UCH-L1 gene expression by inhibiting its transcription. As NF-?B is an important signaling module in inflammatory response, our study suggests a possibility that inflammation might compromise neuronal functions via the interaction of NF-?B and UCH-L1. A better understanding of the NF-?B-regulated UCH-L1 transcription will provide insights to the role of inflammatory responses in Alzheimers disease and Parkinsons disease.
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Isolation and identification of a distinct side population cancer cells in the human epidermal squamous cancer cell line A431.
Arch. Dermatol. Res.
PUBLISHED: 01-15-2011
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Side population (SP) cells have been suggested to be multipotent cancer stem cells. To address whether SP cells exist in epidermal squamous cancer cell line A431, A431 cells dyed with Hoechst 33342 were sorted through flow cytometry. The SP cells were then analyzed by colony-forming and cell proliferation assay. Further, tumorigenicity and microarray analysis were used to compare biological difference between SP and non-SP (NSP) cells. Our results showed that SP cells existed in the A431 cell line, showing higher proliferating and colony-forming ability than NSP cells. Tumors generated from SP cells were larger than those from the NSP cells in NOD/SCID mice. The mRNA microarray profiling revealed that five cancer marker gene expressions were up-regulated and one tumor suppressor gene expression was down-regulated. These findings suggest that SP cells in A431 could contribute to self-renewal, neoplastic transformation, and cancer metastasis of human epidermal squamous cell carcinoma.
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Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation.
J. Biol. Chem.
PUBLISHED: 01-07-2011
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Individuals with Down syndrome (DS) will inevitably develop Alzheimer disease (AD) neuropathology sometime after middle age, which may be attributable to genes triplicated in individuals with DS. The characteristics of AD neuropathology include neuritic plaques, neurofibrillary tangles, and neuronal loss in various brain regions. The mechanism underlying neurodegeneration in AD and DS remains elusive. Regulator of calcineurin 1 (RCAN1) has been implicated in the pathogenesis of DS. Our data show that RCAN1 expression is elevated in the cortex of DS and AD patients. RCAN1 expression can be activated by the stress hormone dexamethasone. A functional glucocorticoid response element was identified in the RCAN1 isoform 1 (RCAN1-1) promoter region, which is able to mediate the up-regulation of RCAN1 expression. Here we show that overexpression of RCAN1-1 in primary neurons activates caspase-9 and caspase-3 and subsequently induces neuronal apoptosis. Furthermore, we found that the neurotoxicity of RCAN1-1 is inhibited by knock-out of caspase-3 in caspase-3(-/-) neurons. Our study provides a novel mechanism by which RCAN1 functions as a mediator of stress- and A?-induced neuronal death, and overexpression of RCAN1 due to an extra copy of the RCAN1 gene on chromosome 21 contributes to AD pathogenesis in DS.
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Global protein-protein interaction network in the human pathogen Mycobacterium tuberculosis H37Rv.
J. Proteome Res.
PUBLISHED: 11-10-2010
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Analysis of the protein-protein interaction network of a pathogen is a powerful approach for dissecting gene function, potential signal transduction, and virulence pathways. This study looks at the construction of a global protein-protein interaction (PPI) network for the human pathogen Mycobacterium tuberculosis H37Rv, based on a high-throughput bacterial two-hybrid method. Almost the entire ORFeome was cloned, and more than 8000 novel interactions were identified. The overall quality of the PPI network was validated through two independent methods, and a high success rate of more than 60% was obtained. The parameters of PPI networks were calculated. The average shortest path length was 4.31. The topological coefficient of the M. tuberculosis B2H network perfectly followed a power law distribution (correlation = 0.999; R-squared = 0.999) and represented the best fit in all currently available PPI networks. A cross-species PPI network comparison revealed 94 conserved subnetworks between M. tuberculosis and several prokaryotic organism PPI networks. The global network was linked to the protein secretion pathway. Two WhiB-like regulators were found to be highly connected proteins in the global network. This is the first systematic noncomputational PPI data for the human pathogen, and it provides a useful resource for studies of infection mechanisms, new signaling pathways, and novel antituberculosis drug development.
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[Effect of different water treatments on quality and yield of spadix in Prunella vulgaris].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-14-2010
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Prunalla vulgaris was used as the experimental material to study the effects of water stress on the related quality charaters of spadix in P. vulgaris.
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Regional myocardial function and response to acute afterload increase in chronically anemic fetal sheep: evaluation by two-dimensional strain echocardiography.
Ultrasound Med Biol
PUBLISHED: 08-20-2010
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We hypothesized that in chronic fetal anemia, remodeling of the myocardium is related to abnormalities in regional wall motion and acutely increased afterload further disturbs myocardial strain. Chronic anemia was induced in one fetus of each of seven sheep twin pregnancies. The fetuses were studied by two-dimensional (2-D) strain echocardiography at baseline and during increased afterload via angiotensin II (AT II) infusion. At baseline, the peak systolic longitudinal, radial and circumferential strains in the left ventricular lateral wall in anemic fetuses were lower than those in the controls (all p<0.05). During AT II, the circumferential strain of right ventricular free wall decreased significantly both in the control and anemic fetuses. Left ventricular free wall systolic strains were not affected by AT II. Fetal myocardial remodeling in chronic anemia decreases left ventricular systolic free wall strains. The myocardial adaptation does not change ventricular responses to acutely increased afterload.
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Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese.
PLoS ONE
PUBLISHED: 08-18-2010
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Recent meta-analysis of genome-wide association studies in European descent samples identified novel loci influencing glucose and insulin related traits. In the current study, we aimed to evaluate the association between these loci and traits related to glucose metabolism in the Chinese.
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The relationship between three heat shock protein 70 gene polymorphisms and susceptibility to lung cancer.
Clin. Chem. Lab. Med.
PUBLISHED: 08-13-2010
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Heat shock protein 70 (Hsp70) has been shown to act as a chaperone and be associated with a variety of tumors. We investigated HSP70-1 G+190C, HSP70-2 A+1267G, and HSP70-hom T+2437C polymorphisms to assess whether genetic variation in HSP70 plays a role in the occurrence and development of lung cancer.
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Assessment of interventricular dyssynchrony by real time three-dimensional echocardiography: an in vitro study in a porcine model.
Echocardiography
PUBLISHED: 07-27-2010
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Loss of synchronous contraction between or within the right and left ventricle (RV, LV) leads to adverse ventricular function. We used real time three-dimensional echocardiography (RT3DE) for evaluation of severity of interventricular dyssynchrony and function in a porcine heart model.
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[Research on direct forming of comminuted fracture surgery orienting model by selective laser melting].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-24-2010
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In order to simplify the distal femoral comminuted fracture surgery and improve the accuracy of the parts to be reset, a kind of surgery orienting model for the surgery operation was designed according to the scanning data of computer tomography and the three-dimensional reconstruction image. With the use of DiMetal-280 selective laser melting rapid prototyping system, the surgery orienting model of 316L stainless steel was made through orthogonal experiment for processing parameter optimization. The technology of direct manufacturing of surgery orienting model by selective laser melting was noted to have obvious superiority with high speed, precise profile and good accuracy in size when compared with the conventional one. The model was applied in a real surgical operation for thighbone replacement; it worked well. The successful development of the model provides a new method for the automatic manufacture of customized surgery model, thus building a foundation for more clinical applications in the future.
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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.