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Find video protocols related to scientific articles indexed in Pubmed.
Unsaturated free fatty acids: a potential biomarker panel for early detection of gastric cancer.
Biomarkers
PUBLISHED: 10-30-2014
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Abstract Changes in the levels of free fatty acids (FFAs) are closely associated with physiological status. Serum levels of C16:1, C18:3, C18:2, C18:1, C20:4, and C22:6 in 164 gastric cancer (GC) patients and 111 benign gastric disease (BGD) patients were significantly decreased compared with 252 healthy controls. Receiver operating characteristic analysis showed that the biomarker panel including C16:1, C18:3, C18:2, C20:4, and C22:6 presents a high diagnostic ability to differentiate early-stage GC patients from healthy controls plus BGD patients, with a sensitivity of 80.6% and a specificity of 72.7%.
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LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b.
Hum. Mol. Genet.
PUBLISHED: 10-06-2014
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Recently, a large number of long non-coding RNAs (lncRNAs) have been reported in mammalian genomes and are evolutionarily conserved and presumably function in many biological events, especially in the pathogenesis of diverse human cancers. A lncRNA, named HOST2 (human ovarian cancer-specific transcript 2), was once reported to specifically be expressed at high level in human ovarian cancer. However, how HOST2 acts to regulate gene functions in ovarian carcinogenesis has remained enigmatic. Here we report, for the first time, that HOST2 promotes tumor cell migration, invasion and proliferation in epithelial ovarian cancer by working in key aspects of biological behaviors. In the present study, bioinformatics analysis indicated that HOST2 binds with microRNA let-7b, a potent tumor suppressor, which was then verified to target HOST2. Our results showed that HOST2 harbors a let-7b binding site and modulates let-7b availability by acting as a molecular sponge. HOST2 inhibits let-7b functions, which post-transcriptionally suppress the expression of targets, including some oncogenes that regulate cell growth and motility. Additionally, understanding HOST2/let-7b-dependent regulation may lead to alternative approaches for the diagnosis and cure of this deadly disease.
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[A family with two children diagnosed with aspartylglucosaminuria-case report and literature review].
Zhonghua Er Ke Za Zhi
PUBLISHED: 09-06-2014
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The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria.
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In vivo length change patterns of the medial and lateral collateral ligaments along the flexion path of the knee.
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 09-03-2014
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The knowledge of the function of the collateral ligaments-i.e., superficial medial collateral ligament (sMCL), deep medial collateral ligament (dMCL) and lateral collateral ligament (LCL)-in the entire range of knee flexion is important for soft tissue balance during total knee arthroplasty (TKA). The objective of this study was to investigate the length changes of different portions (anterior, middle and posterior) of the sMCL, dMCL and LCL during in vivo weightbearing flexion from full extension to maximal knee flexion.
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Two histone/protein acetyltransferases, CBP and p300, are indispensable for Foxp3+ T-regulatory cell development and function.
Mol. Cell. Biol.
PUBLISHED: 08-25-2014
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T-regulatory (Treg) cells are important to immune homeostasis, and Treg cell deficiency or dysfunction leads to autoimmune disease. A histone/protein acetyltransferase (HAT), p300, was recently found to be important for Treg function and stability, but further insights into the mechanisms by which p300 or other HATs affect Treg biology are needed. Here we show that CBP, a p300 paralog, is also important in controlling Treg function and stability. Thus, while mice with Treg-specific deletion of CBP or p300 developed minimal autoimmune disease, the combined deletion of CBP and p300 led to fatal autoimmunity by 3 to 4 weeks of age. The effects of CBP and p300 deletion on Treg development are dose dependent and involve multiple mechanisms. CBP and p300 cooperate with several key Treg transcription factors that act on the Foxp3 promoter to promote Foxp3 production. CBP and p300 also act on the Foxp3 conserved noncoding sequence 2 (CNS2) region to maintain Treg stability in inflammatory environments by regulating pCREB function and GATA3 expression, respectively. Lastly, CBP and p300 regulate the epigenetic status and function of Foxp3. Our findings provide insights into how HATs orchestrate multiple aspects of Treg development and function and identify overlapping but also discrete activities for p300 and CBP in control of Treg cells.
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Mechanical tests on the reconstructed anterior cruciate ligament fixed with allogenetic cortical bone cross-pin on the femoral side.
Chin. Med. J.
PUBLISHED: 08-23-2014
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Anterior cruciate ligament reconstruction (ACLR) has developed dramatically in the last century. Now, ACLR has become a reliable and productive procedure. Patients feel satisfied in >90% cases. The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin (ACBCP) used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro.
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Clinical outcomes of early weight-bearing after arthroscopic microfracture during the treatment of osteochondral lesions of the talus.
Chin. Med. J.
PUBLISHED: 07-03-2014
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The time until weight-bearing after arthroscopic microfracture when treating osteochondral lesions of the talus (OLT) is very important to the clinical outcomes of the operation. However, there have been no consistent opinions regarding the optimal time to start weight-bearing postoperatively. Many opinions advocate that weight-bearing should begin not earlier than the sixth or eighth week postoperatively, whereas others point out that earlier weight-bearing could also obtain satisfactory outcomes. The purpose of our study was to evaluate the clinical outcomes of early weight-bearing after arthroscopic microfracture during the treatment of OLT.
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Intravenous lipopolysaccharide challenge alters ruminal bacterial microbiota and disrupts ruminal metabolism in dairy cattle.
Br. J. Nutr.
PUBLISHED: 04-28-2014
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In the present study, three primiparous lactating Holstein cows (260-285 d in lactation) were used in a 3 × 3 Latin square design to assess the effects of three doses (0.0, 0.4 and 0.8 ?g/kg body weight) of lipopolysaccharide (LPS, Escherichia coli 0111:B4) on changes in ruminal microbiota and ruminal fermentation. Ruminal pH was linearly decreased (P< 0.001) by LPS challenge, and the concentrations of acetate, propionate, butyrate, total volatile fatty acids and amino N increased linearly (P< 0.001) according to the LPS dose. LPS infusion linearly decreased (P< 0.001) the organic matter degradability of alfalfa hay and soyabean meal in the rumen, but did not affect (P>0.10) the gene expression of Na?/K?-ATPase and monocarboxylic acid transporter-1, -2 and -4. A plot of principal coordinate analysis based on unweighted UniFrac values and analysis of molecular variance revealed that the structure of ruminal bacterial communities in the control was distinct from that of the ruminal microbiota in the cattle exposed to LPS. At the phylum level, when compared with the control group, LPS infusion in the tested cows linearly increased (P< 0.05) the abundance of Firmicutes, and linearly decreased (P< 0.05) the percentage of Bacteroidetes, Tenericutes, Spirochaetes, Chlorobi and Lentisphaerae. To our knowledge, this is the first study to report that intravenously LPS challenge altered the ruminal bacterial microbiota and fermentation profiles. The present data suggest that systemic LPS could alter ruminal environment and ruminal microbiota composition, leading to a general decrease in fermentative activity.
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Autophagy may protect MC3T3-E1 cells from fluoride-induced apoptosis.
Mol Med Rep
PUBLISHED: 02-04-2014
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Fluoride is an essential trace element for all mammalian species; however, excess fluoride intake is known to be toxic to cells in animals and humans. The toxicity of fluoride is mainly exerted via induction of apoptosis. Autophagy is induced by numerous cytotoxic stimuli; however, it is often unclear whether, under specific conditions, autophagy has a pro?survival or a pro?apoptotic role. To answer this critical question, the present study assessed autophagy and apoptosis simultaneously in single cells. It was demonstrated that fluoride was able to inhibit cell proliferation and induce apoptosis and autophagy, whereas autophagy appeared to be protective. Further analysis revealed that MAPK/JNK?dependent autophagy may be protective in fluoride?induced apoptosis. It is anticipated that the presented single?cell approach may be a powerful tool for gaining a quantitative understanding of the complex regulation of autophagy, its effect on cell fate and its association with other cellular pathways.
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Highly conductive ribbons prepared by stick-slip assembly of organosoluble gold nanoparticles.
ACS Nano
PUBLISHED: 01-13-2014
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Precisely positioning and assembling nanoparticles (NPs) into hierarchical nanostructures is opening opportunities in a wide variety of applications. Many techniques employed to produce hierarchical micrometer and nanoscale structures are limited by complex fabrication of templates and difficulties with scalability. Here we describe the fabrication and characterization of conductive nanoparticle ribbons prepared from surfactant-free organosoluble gold nanoparticles (Au NPs). We used a flow-coating technique in a controlled, stick-slip assembly to regulate the deposition of Au NPs into densely packed, multilayered structures. This affords centimeter-scale long, high-resolution Au NP ribbons with precise periodic spacing in a rapid manner, up to 2 orders-of-magnitude finer and faster than previously reported methods. These Au NP ribbons exhibit linear ohmic response, with conductivity that varies by changing the binding headgroup of the ligands. Controlling NP percolation during sintering (e.g., by adding polymer to retard rapid NP coalescence) enables the formation of highly conductive ribbons, similar to thermally sintered conductive adhesives. Hierarchical, conductive Au NP ribbons represent a promising platform to enable opportunities in sensing, optoelectronics, and electromechanical devices.
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Serum unsaturated free Fatty acids: potential biomarkers for early detection and disease progression monitoring of non-small cell lung cancer.
J Cancer
PUBLISHED: 01-01-2014
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Lung cancer (LC) is the deadliest cancer, with earlier stage patients having a better opportunity of long-term survival. The goal of this study is to screen less-invasive and efficient biomarkers for early detection of non-small cell LC (NSCLC).
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A comparative study of four types of free flaps from the ipsilateral extremity for finger reconstruction.
PLoS ONE
PUBLISHED: 01-01-2014
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To compare the outcomes of finger reconstruction using arterialized venous flap (AVF), superficial palmar branch of the radial artery (SPBRA) flap, posterior interosseous perforator flap (PIPF), and ulnar artery perforator free (UAPF) flap harvested from the ipsilateral extremity.
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CCAAT enhancer binding protein and nuclear factor of activated T cells regulate HIV-1 LTR via a novel conserved downstream site in cells of the monocyte-macrophage lineage.
PLoS ONE
PUBLISHED: 01-01-2014
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Transcriptional control of the human immunodeficiency virus type 1 (HIV-1) promoter, the long terminal repeat (LTR), is achieved by interactions with cis-acting elements present both upstream and downstream of the start site. In silico transcription factor binding analysis of the HIV-1 subtype B LTR sequences revealed a potential downstream CCAAT enhancer binding protein (C/EBP) binding site. This binding site (+158 to+172), designated DS3, was found to be conserved in 67% of 3,858 unique subtype B LTR sequences analyzed in terms of nucleotide sequence as well as physical location in the LTR. DS3 was found to be well represented in other subtypes as well. Interestingly, DS3 overlaps with a previously identified region that bind members of the nuclear factor of activated T cells (NFAT) family of proteins. NFATc2 exhibited a higher relative affinity for DS3 as compared with members of the C/EBP family (C/EBP ? and ?). DS3 was able to compete efficiently with the low-affinity upstream C/EBP binding site I with respect to C/EBP binding, suggesting utilization of both NFAT and C/EBP. Moreover, cyclosporine A treatment, which has been shown to prevent dephosphorylation and nuclear translocation of NFAT isoforms, resulted in enhanced C/EBP? binding. The interactions at DS3 were also validated in an integrated HIV-1 LTR in chronically infected U1 cells. A binding knockout of DS3 demonstrated reduced HIV-1 LTR-directed transcription under both basal and interleukin-6-stimulated conditions only in cells of the monocyte-macrophage lineage cells and not in cells of T-cell origin. Thus, the events at DS3 positively regulate the HIV-1 promoter in cells of the monocyte-macrophage lineage.
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Flock house virus RNA polymerase initiates RNA synthesis de novo and possesses a terminal nucleotidyl transferase activity.
PLoS ONE
PUBLISHED: 01-01-2014
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Flock House virus (FHV) is a positive-stranded RNA virus with a bipartite genome of RNAs, RNA1 and RNA2, and belongs to the family Nodaviridae. As the most extensively studied nodavirus, FHV has become a well-recognized model for studying various aspects of RNA virology, particularly viral RNA replication and antiviral innate immunity. FHV RNA1 encodes protein A, which is an RNA-dependent RNA polymerase (RdRP) and functions as the sole viral replicase protein responsible for RNA replication. Although the RNA replication of FHV has been studied in considerable detail, the mechanism employed by FHV protein A to initiate RNA synthesis has not been determined. In this study, we characterized the RdRP activity of FHV protein A in detail and revealed that it can initiate RNA synthesis via a de novo (primer-independent) mechanism. Moreover, we found that FHV protein A also possesses a terminal nucleotidyl transferase (TNTase) activity, which was able to restore the nucleotide loss at the 3'-end initiation site of RNA template to rescue RNA synthesis initiation in vitro, and may function as a rescue and protection mechanism to protect the 3' initiation site, and ensure the efficiency and accuracy of viral RNA synthesis. Altogether, our study establishes the de novo initiation mechanism of RdRP and the terminal rescue mechanism of TNTase for FHV protein A, and represents an important advance toward understanding FHV RNA replication.
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PIWI: visually exploring graphs based on their community structure.
IEEE Trans Vis Comput Graph
PUBLISHED: 09-14-2013
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Community structure is an important characteristic of many real networks, which shows high concentrations of edges within special groups of vertices and low concentrations between these groups. Community related graph analysis, such as discovering relationships among communities, identifying attribute-structure relationships, and selecting a large number of vertices with desired structural features and attributes, are common tasks in knowledge discovery in such networks. The clutter and the lack of interactivity often hinder efforts to apply traditional graph visualization techniques in these tasks. In this paper, we propose PIWI, a novel graph visual analytics approach to these tasks. Instead of using Node-Link Diagrams (NLDs), PIWI provides coordinated, uncluttered visualizations, and novel interactions based on graph community structure. The novel features, applicability, and limitations of this new technique have been discussed in detail. A set of case studies and preliminary user studies have been conducted with real graphs containing thousands of vertices, which provide supportive evidence about the usefulness of PIWI in community related tasks.
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Mbd2 promotes foxp3 demethylation and T-regulatory-cell function.
Mol. Cell. Biol.
PUBLISHED: 08-26-2013
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Use of Foxp3-positive (Foxp3(+)) T-regulatory (Treg) cells as potential cellular therapy in patients with autoimmunity, or post-stem cell or -organ transplantation, requires a sound understanding of the transcriptional regulation of Foxp3. Conserved CpG dinucleotides in the Treg-specific demethylation region (TSDR) upstream of Foxp3 are demethylated only in stable, thymus-derived Foxp3(+) Treg cells. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, we tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. Surprisingly, while chromatin immunoprecipitation (ChIP) analysis showed Mbd2 binding to the Foxp3-associated TSDR site in Treg cells, Mbd2 targeting by homologous recombination, or small interfering RNA (siRNA), decreased Treg numbers and impaired Treg-suppressive function in vitro and in vivo. Moreover, we found complete TSDR demethylation in wild-type (WT) Treg cells but >75% methylation in Mbd2(-/-) Treg cells, whereas reintroduction of Mbd2 into Mbd2-null Treg cells restored TSDR demethylation, Foxp3 gene expression, and Treg-suppressive function. Lastly, thymic Treg cells from Mbd2(-/-) mice had normal TSDR demethylation, but compared to WT Treg cells, peripheral Mbd2(-/-) Treg cells had a marked impairment of binding of Tet2, the DNA demethylase enzyme, at the TSDR site. These data show that Mbd2 has a key role in promoting TSDR demethylation, Foxp3 expression, and Treg-suppressive function.
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Short-term effects of radiofrequency shrinkage treatment for anterior cruciate ligament relaxation on proprioception.
J. Int. Med. Res.
PUBLISHED: 08-23-2013
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Radiofrequency (RF) shrinkage is used in anterior cruciate ligament (ACL) reconstruction. The present study investigated the therapeutic effects of RF on ACL relaxation and the probable influencing factors.
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[Repair of severe nail bed defects with radial dorsal fasciocutaneous flap of thumb].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 07-25-2013
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To summarize the effectiveness of radial dorsal fasciocutaneous flap of thumb for repairing severe nail bed defects.
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Single rice growth period was prolonged by cultivars shifts, but yield was damaged by climate change during 1981-2009 in China, and late rice was just opposite.
Glob Chang Biol
PUBLISHED: 04-29-2013
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Based on the crop trial data during 1981-2009 at 57 agricultural experimental stations across the North Eastern China Plain (NECP) and the middle and lower reaches of Yangtze River (MLRYR), we investigated how major climate variables had changed and how the climate change had affected crop growth and yield in a setting in which agronomic management practices were taken based on actual weather. We found a significant warming trend during rice growing season, and a general decreasing trend in solar radiation (SRD) in the MLRYR during 1981-2009. Rice transplanting, heading, and maturity dates were generally advanced, but the heading and maturity dates of single rice in the MLRYR (YZ_SR) and NECP (NE_SR) were delayed. Climate warming had a negative impact on growth period lengths at about 80% of the investigated stations. Nevertheless, the actual growth period lengths of YZ_SR and NE_SR, as well as the actual length of reproductive growth period (RGP) of early rice in the MLRYR (YZ_ER), were generally prolonged due to adoption of cultivars with longer growth period to obtain higher yield. In contrast, the actual growth period length of late rice in the MLRYR (YZ_LR) was shortened by both climate warming and adoption of early mature cultivars to prevent cold damage and obtain higher yield. During 1981-2009, climate warming and decrease in SRD changed the yield of YZ_ER by -0.59 to 2.4%; climate warming during RGP increased the yield of YZ_LR by 8.38-9.56%; climate warming and decrease in SRD jointly reduced yield of YZ_SR by 7.14-9.68%; climate warming and increase in SRD jointly increased the yield of NE_SR by 1.01-3.29%. Our study suggests that rice production in China has been affected by climate change, yet at the same time changes in varieties continue to be the major factor driving yield and growing period trends.
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Inhibition of p300 impairs Foxp3? T regulatory cell function and promotes antitumor immunity.
Nat. Med.
PUBLISHED: 04-13-2013
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Forkhead box P3 (Foxp3)(+) T regulatory (T(reg)) cells maintain immune homeostasis and limit autoimmunity but can also curtail host immune responses to various types of tumors. Foxp3(+) T(reg) cells are therefore considered promising targets to enhance antitumor immunity, and approaches for their therapeutic modulation are being developed. However, although studies showing that experimentally depleting Foxp3(+) T(reg) cells can enhance antitumor responses provide proof of principle, these studies lack clear translational potential and have various shortcomings. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and nonhistone proteins. We now report that conditional deletion or pharmacologic inhibition of one HAT, p300 (also known as Ep300 or KAT3B), in Foxp3(+) T(reg) cells increased T cell receptor-induced apoptosis in T(reg) cells, impaired T(reg) cell suppressive function and peripheral T(reg) cell induction, and limited tumor growth in immunocompetent but not in immunodeficient mice. Our data thereby demonstrate that p300 is important for Foxp3(+) T(reg) cell function and homeostasis in vivo and in vitro, and identify mechanisms by which appropriate small-molecule inhibitors can diminish T(reg) cell function without overtly impairing T effector cell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy.
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Down-regulated lysosomal processing improved pegylated lipopolyplex-mediated gene transfection.
J Gene Med
PUBLISHED: 04-06-2013
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Nonviral lipid-based gene delivery vectors have been shown to possess better stability and a longer circulation time after surface poly(ethylene glycol) PEG modification. However, surface PEGylation may decrease the transfection efficiency dramatically. In the present study, we addressed the hypothesis that down-regulating lysosomal processing with a clinical available proton pump inhibitor omeprazole might decrease the sequestration of PEGylated Lipid-Mu-DNA (LMD) in intracellular organelles, thereby increasing their transfection efficiencies.
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Foxp3+ T-regulatory cells require DNA methyltransferase 1 expression to prevent development of lethal autoimmunity.
Blood
PUBLISHED: 02-26-2013
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Protocols to use Foxp3+ T-regulatory (Treg) cells for cellular therapy, especially postallogeneic stem cell transplantation, are currently being developed and tested by various groups. Inhibitors of DNA methyltransferase (Dnmt) enzymes have been advocated as a means to promote and stabilize Foxp3 expression in Tregs undergoing expansion in vitro before their injection in vivo. We investigated the effects of conditionally deleting two Dnmt enzymes that co-immunoprecipitated with Foxp3 in Treg isolates. Deletion of Dnmt1, but not Dnmt3a, decreased the numbers and function of peripheral Tregs and impaired conversion of conventional T cells into Foxp3+ Tregs under polarizing conditions. Importantly, mice with conditional deletion of Dnmt1 in their Tregs died of autoimmunity by 3 to 4 weeks of age unless they were rescued by perinatal transfer of wild-type Tregs. Conditional Dnmt1 deletion did not affect methylation of CpG sites within Foxp3 but decreased global DNA methylation and altered Treg expression of several hundred pro-inflammatory and other genes. Hence, Dnmt1 is necessary for maintenance of the core gene program underlying Treg development and function, and its deletion within the Treg lineage leads to lethal autoimmunity. These data suggest that caution may be warranted when considering the use of DNMT inhibitors in development of Treg-based cellular therapies.
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Dephosphorylation of intact glycoprotein to greatly improve digestion efficiency coupled with matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometric analysis.
Anal. Chim. Acta
PUBLISHED: 02-13-2013
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Sialylation is essential for a variety of cellular functions. Herein, we used bovine fetuin with three potential N-linked glycosylation sites containing complex-type glycan structures, four potential O-linked glycosylation sites and six potential phosphorylation sites as a model compound to develop a highly-efficient digestion strategy for sialylated glycoproteins and efficient enrichment strategy for sialylated glycopeptides using titanium dioxide. The former according to the process of alkaline phosphatase digestion followed by tryptic digestion and then proteinase K digestion could greatly improve the enzymatic efficiency on fetuin, and the latter could obviously enhance the enrichment efficiency for multisialylated glycopeptides using phosphoric acid solution as elution buffer. The mass spectra of the enriched glycopeptides derived from fetuin reveal that several series of the ion clusters with mass difference of 291 Da correspond to the presence of multisialylated glycopeptides. In addition, the approach was applied to characterize the sialylated status of ?2-macroglobulin and transferrin, respectively, from the sera of healthy subjects and sex- and age-matched patients with thyroid cancer, and their spectra indicate that the change in the amount of the glycoforms containing different number of sialic acid (SA) residues from one glycosylation site may be used to differentiate between healthy subjects and cancer cases.
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Increased thymosin ?4 levels in the serum and SF of knee osteoarthritis patients correlate with disease severity.
Regul. Pept.
PUBLISHED: 01-26-2013
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Thymosin ?4, a member of a large family of thymic proteins, plays an important role in the process of articular cartilage degeneration which is a common cause of osteoarthritis (OA). This study aims to determine thymosin ?4 levels in the serum and synovial fluid (SF) of patients with knee OA and analyze the correlation of thymosin ?4 levels with the radiographic severity of OA.
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Expression of miRNAs in Papillary Thyroid Carcinomas Is Associated with BRAF Mutation and Clinicopathological Features in Chinese Patients.
Int J Endocrinol
PUBLISHED: 01-23-2013
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MicroRNAs (miRNAs) dysregulation has been shown to play a critical regulatory role in papillary thyroid carcinomas (PTCs). BRAF mutation is associated with poor clinicopathological outcomes in PTC. In order to identify a possible association between dysregulated miRNA expression and BRAF mutation as well as clinicopathological features in Chinese patients with PTC, we examined the expression levels of five reported dysregulated miRNAs (miRNA-221, miRNA-222, miRNA-146b, miRNA-181, and miRNA-21) and determined BRAF mutation status in 52 patients with PTC and 52 patients with benign thyroid nodules (BTNs). The expression levels of all five miRNAs were significantly increased in PTC when compared to BTN. The BRAF mutation occurred more frequently in PTC cases with advanced TNM stage. Importantly, miRNA-221, miRNA-222, miRNA-146b, and miRNA-181 expression levels were significantly higher in PTC patients with BRAF mutation. In addition, enhanced expression of miRNA-221 and miRNA-222 was found in patients with cervical lymph node metastasis and advanced TNM stage. Increased expression of miRNA-221 and miR-181 was evidenced in patients with larger tumors. These findings showed a potential role of this distinct profile of miRNAs in differentiating PTC from BTN. BRAF mutation might regulate or interact with miRNA in the pathogenesis and progression of PTC.
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WNT3A modulates chondrogenesis via canonical and non-canonical Wnt pathways in MSCs.
Front Biosci (Landmark Ed)
PUBLISHED: 01-02-2013
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The multilineage commitment of mesenchymal stem cells (MSCs) is controlled via unknown mechanisms. In this study, we investigated the regulation of the differentiation of MSCs into chondrocytes via the Wnt signaling pathway. Overexpression of WNT3A in MSCs activated both the canonical and non-canonical Wnt pathways, which were responsible for different WNT3A-induced outcomes. WNT3A promoted MSC proliferation via the ß-catenin-mediated canonical Wnt pathway, and inhibited chondrogenesis of MSCs via the calcium/calmodulin-dependent kinase II (CaMKII)-mediated non-canonical Wnt pathway. Interestingly, blockade of the canonical Wnt pathway by Dickkopf-related protein 1 exerted a synergistic effect on the inhibition of chondrogenesis of MSCs, while blockade of the non-canonical Wnt pathway by KN93 also exerted a synergistic effect on MSCs proliferation. These results suggest that the WNT3A-activated canonical and non-canonical pathways counteract each other in the setting of MSCs. This study provides evidence for the delicate regulation of the Wnt signaling cascade during chondrogenesis of MSCs, and suggests that genetic manipulation of the Wnt pathway may offer a powerful vehicle for modulating MSC differentiation in stem-cell-based cartilage repair.
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Lin28 Induces Epithelial-to-Mesenchymal Transition and Stemness via Downregulation of Let-7a in Breast Cancer Cells.
PLoS ONE
PUBLISHED: 01-01-2013
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The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.
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MicroRNA 34c gene down-regulation via DNA methylation promotes self-renewal and epithelial-mesenchymal transition in breast tumor-initiating cells.
J. Biol. Chem.
PUBLISHED: 11-10-2011
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Tumor-initiating cells (T-ICs), a subpopulation of cancer cells with stem cell-like properties, are related to tumor relapse and metastasis. Our previous studies identified a distinct profile of microRNA (miRNA) expression in breast T-ICs (BT-ICs), and the dysregulated miRNAs contribute to the self-renewal and tumorigenesis of these cells. However, the underlying mechanisms for miRNA dysregulation in BT-ICs remain obscure. In the present study, we demonstrated that the expression and function of miR-34c were reduced in the BT-ICs of MCF-7 and SK-3rd cells, a breast cancer cell line enriched for BT-ICs. Ectopic expression of miR-34c reduced the self-renewal of BT-ICs, inhibited epithelial-mesenchymal transition, and suppressed migration of the tumor cells via silencing target gene Notch4. Furthermore, we identified a single hypermethylated CpG site in the promoter region of miR-34c gene that contributed to transcriptional repression of miR-34c in BT-ICs by reducing DNA binding activities of Sp1. Therefore, miR-34c reduction in BT-ICs induced by a single hypermethylated CpG site in the promoter region promotes self-renewal and epithelial-mesenchymal transition of BT-ICs.
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[Arthroscopic reduction and fixation of tibial intercondylar eminence avulsion fractures using nonabsorbable suture with neck wear knot loop ligature].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 09-20-2011
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To investigate the effectiveness of percutaneous reduction by leverage and fixation using nonabsorbable suture with neck wear knot loop ligature to treat tibial intercondylar eminence avulsion fractures under the arthroscope.
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[Simultaneous determination of acteoside, oleanolic acid and ursolic acid in flower of Campsis grandiflora by HPLC].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-04-2011
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To develop an HPLC method for the determination of acteoside, oleanolic acid and ursolic acid in flowers of Campsis grandiflora.
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[Study on purification of strictosamide from Nauclea officinalis by macroporous resin].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-04-2011
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To study on the purification of strictosamide from Nauclea officinalis by macroporous resin to provide reference for production.
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Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells.
Curr. Opin. Immunol.
PUBLISHED: 06-22-2011
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Lysine ?-acetylation is a post-translational modification that alters the biochemical properties of many proteins. The reaction is catalyzed by histone/protein acetyltransferases (HATs), and is reversed by histone/protein deacetylases (HDACs). As a result, HATs and HDACs constitute an important, though little recognized, set of proteins that control the functions of T-regulatory (Treg) cells. Targeting certain HDACs, especially HDAC6, HDAC9, and Sirtuin-1 (Sirt1), can augment Treg suppressive potency by several distinct and potentially additive mechanisms. These involve promoting Forkhead box p3 (Foxp3) gene expression and preserving Foxp3 lysine ?-acetylation, which infers resistance to ubiquitination and proteasomal degradation, and increases DNA binding. Moreover, depleting certain HDAC can enhance the heat shock response, which increases the tenacity of Treg to survive under stress, and helps preserve a suppressive phenotype. As a result, HDAC inhibitor therapy can be used to enhance Treg functions in vivo and have beneficial effects on allograft survival and autoimmune diseases.
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[Arthroscopic treatment for tibial eminence avulsion fracture using absorbable double suture anchors].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 03-25-2011
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To investigate the outcomes of arthroscopic reduction and internal fixation of tibial eminence avulsion fracture using absorbable double suture anchors.
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Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells.
Mol. Cancer
PUBLISHED: 02-24-2011
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Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.
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Vascular protective potential of the total flavanol glycosides from Abacopteris penangiana via modulating nuclear transcription factor-?B signaling pathway and oxidative stress.
J Ethnopharmacol
PUBLISHED: 01-08-2011
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"Sanxuelian", the rhizome of Abacopteris penangiana (AP), is traditionally used in Chinese medicine for the treatment of blood circulation stasis, hemorheology barriers, edema and inflammation for patients of metabolic syndrome. This study was to investigate the protective effect of the total flavanol glycosides from AP (FAP) on diabetic vascular impairments by measuring the extents of oxidative stress and inflammatory response in mice.
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Stimulation of A(?a) adenosine receptor abolishes the inhibitory effect of arachidonic acid on the basolateral 50-pS K channel in the thick ascending limb.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 01-05-2011
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The basolateral 50-pS K channels are stimulated by a cAMP-dependent pathway and inhibited by cytochrome P-450-omega-hydroxylase-dependent metabolism of arachidonic acid (AA) in the rat thick ascending limb (TAL). We now used the patch-clamp technique to examine whether stimulation of adenosine A(?a) receptor modulates the inhibitory effect of AA on the basolateral 50-pS K channels in the medullary TAL. Stimulation of adenosine A(?a) receptor with CGS-21680 or inhibition of phospholipase A? (PLA?) with AACOCF3 increased the 50-pS K channel activity in the TAL. Western blot demonstrated that application of CGS-21680 decreased the phosphorylation of PLA(2) at serine residue 505, an indication of inhibiting PLA? activity. In the presence of CGS-21680, inhibition of PLA? had no further effect on the basolateral 50-pS K channels. The possibility that CGS-21680-induced stimulation of the basolateral 50-pS K channels was partially achieved by inhibition of PLA? in the TAL was also supported by the observation that CGS-21680 had no additional effect in the presence of AACOCF3. Moreover, stimulation of adenosine A(?a) receptor with CGS-21680 also abolished the inhibitory effect of AA and 20-hydroxyeicosatetraenoic acid (20-HETE) on the 50-pS K channels. The effect of CGS-21680 on AA and 20-HETE-mediated inhibition of the 50-pS K channels was mediated by cAMP because application of membrane-permeable cAMP analog, dibutyryl-cAMP, not only increased the 50-pS K channel activity but also abolished the inhibitory effect of AA and 20-HETE. We conclude that stimulation of adenosine A(?a) receptor increased the 50-pS K channel activity in the TAL, an effect that is achieved by suppression of PLA? activity and 20-HETE-induced inhibition.
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Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs allograft survival.
Mol. Cell. Biol.
PUBLISHED: 01-03-2011
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Sirtuin 1 (Sirt1), a class III histone/protein deacetylase, is central to cellular metabolism, stress responses, and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation, and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4(+) T cells or Foxp3(+) Treg cells exhibited prolonged survival of major histocompatibility complex (MHC)-mismatched cardiac allografts. Allografts in Sirt1-targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3(+) Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions, and its targeting may have therapeutic value in autoimmunity and transplantation.
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Photodegradation mechanism of deltamethrin and fenvalerate.
J Environ Sci (China)
PUBLISHED: 12-24-2010
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To understand the degradation and environmental fate of pyrethroids, the process of their photodegradation under simulated natural conditions was investigated. The results showed that the degradation process follows first-order kinetics. The degradation intermediates were identified with gas chromatography-mass spectrometry. A plausible mechanism was discussed to explain the process. Several influences on degradation process were investigated and reported such as the effects of initial concentration of pyrethroids, total time of light irradiation, solvents, and light source, as well as the effect of a few substances that exist in the environment. This study could be a good reference for the degradation of pyrethroids in practical circumstances.
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[Arthroscopic reconstruction of anterior cruciate ligament for single bundle rupture with hamstring autograft].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 12-20-2010
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To investigate the effectiveness of anterior cruciate ligament (ACL) reconstruction for single bundle rupture using hamstring autograft with preservation of the left bundle.
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Loss of enigma homolog protein results in dilated cardiomyopathy.
Circ. Res.
PUBLISHED: 06-10-2010
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The Z-line, alternatively termed the Z-band or Z-disc, is a highly ordered structure at the border between 2 sarcomeres. Enigma subfamily proteins (Enigma, Enigma homolog protein, and Cypher) of the PDZ-LIM domain protein family are Z-line proteins. Among the Enigma subfamily, Cypher has been demonstrated to play a pivotal role in the structure and function of striated muscle, whereas the role of Enigma homolog protein (ENH) in muscle remains largely unknown.
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Structural and functional studies of CCAAT/enhancer binding sites within the human immunodeficiency virus type 1 subtype C LTR.
Biomed. Pharmacother.
PUBLISHED: 04-15-2010
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Human immunodeficiency virus type 1 (HIV-1) subtype C, which is most predominant in sub-Saharan Africa as well as in Asia and India, is the most prevalent subtype worldwide. A large number of transcription factor families have been shown to be involved in regulating HIV-1 gene expression in T lymphocytes and cells of the monocyte-macrophage lineage. Among these, proteins of the CCAAT/enhancer binding protein (C/EBP) family are of particular importance in regulating HIV-1 gene expression within cells of the monocytic lineage during the course of hematologic development and cellular activation. Few studies have examined the role of C/EBPs in long terminal repeat (LTR)-directed viral gene expression of HIV-1 subtypes other than subtype B. Within subtype B viruses, two functional C/EBP sites located upstream of the TATA box are required for efficient viral replication in cells of the monocyte-macrophage lineage. We report the identification of three putative subtype C C/EBP sites, upstream site 1 and 2 (C-US1 and C-US2) and downstream site 1 (C-DS1). C-US1 and C-DS1 were shown to form specific DNA-protein complexes with members of the C/EBP family (C/EBP?, ?, and ?). Functionally, within the U-937 monocytic cell line, subtype B and C LTRs were shown to be equally responsive to C/EBP?-2, although the basal activity of subtype C LTRs appeared to be higher. Furthermore, the synergistic interaction between C/EBP?-2 and Tat with the subtype C LTR was also observed in U-937 cells as previously demonstrated with the subtype B LTR.
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Nesprin 1 is critical for nuclear positioning and anchorage.
Hum. Mol. Genet.
PUBLISHED: 10-28-2009
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Nesprin 1 is an outer nuclear membrane protein that is thought to link the nucleus to the actin cytoskeleton. Recent data suggest that mutations in Nesprin 1 may also be involved in the pathogenesis of Emery-Dreifuss muscular dystrophy. To investigate the function of Nesprin 1 in vivo, we generated a mouse model in which all isoforms of Nesprin 1 containing the C-terminal spectrin-repeat region with or without KASH domain were ablated. Nesprin 1 knockout mice are marked by decreased survival rates, growth retardation and increased variability in body weight. Additionally, nuclear positioning and anchorage are dysfunctional in skeletal muscle from knockout mice. Physiological testing demonstrated no significant reduction in stress production in Nesprin 1-deficient skeletal muscle in either neonatal or adult mice, but a significantly lower exercise capacity in knockout mice. Nuclear deformation testing revealed ineffective strain transmission to nuclei in muscle fibers lacking Nesprin 1. Overall, our data show that Nesprin 1 is essential for normal positioning and anchorage of nuclei in skeletal muscle.
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[An experimental study on anterior cruciate ligament reconstruction with remnants and remaining bundle preservation].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 04-16-2009
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To investigate whether anterior cruciate ligament (ACL) reconstruction with the remnants and the remaining bundle preservation is beneficial for the revascularization of the graft or not.
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CCAAT/enhancer-binding proteins and the pathogenesis of retrovirus infection.
Future Microbiol
PUBLISHED: 03-31-2009
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Previous studies indicate that two upstream CCAAT/enhancer-binding protein (C/EBP) sites and C/EBPbeta are required for subtype B HIV-1 gene expression in cells of the monocyte-macrophage lineage. The mechanisms of C/EBP regulation of HIV-1 transcription and replication remain unclear. This review focuses on studies concerning the role of C/EBP factors in HIV-1, human T-cell leukemia virus type 1, and SIV transcription in various cell types and tissues cultured in vitro, animal models and during human infection. The structure and function of the C/EBPbeta gene and the related protein isoforms are discussed along with the transcription factors, coactivators, viral proteins, cytokines and chemokines that affect C/EBP function.
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Fractionation of 50kGy electron beam irradiation: effects on biomechanics of human flexor digitorum superficialis tendons treated with ascorbate.
J Biomech
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The electron beam (Ebeam) irradiation has begun to be considered as an efficient alternative to gamma irradiation in the sterilization of allografts in the reconstruction of anterior cruciate ligament. The purpose of this study was to evaluate the biomechanical properties of human tendons after exposure to electron beam and free radical scavenger ascorbate. Forty human flexor digitorum superficialis tendons were prepared from five fresh cadavers and divided randomly into four groups: A, fresh (0kGy); B, 50kGy Ebeam irradiation; C, fractionated 50kGy Ebeam irradiation; D, fractionated 50kGy Ebeam on ascorbate-treated tendons. The fractionation of 50kGy was achieved by repeated irradiation of 2.5kGy for 20 repetitions. Biomechanical properties were analyzed during load-to-failure testing. The fresh tendons were found to be significant different in ultimate load, ultimate elongation relative to tendons in group B. Statistical differences were found between group B and C in ultimate load. No differences were detected between group A and C in all the parameters. Compare tendons in group C and D, significant differences were found in ultimate load and ultimate stress. It is recommended that fractionated 50kGy electron beam irradiation and free radical scavenger ascorbate should be applied in the sterilization of allografts tendons.
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[Effectiveness comparison between arthroscopic and nonsurgical treatments for ankle degenerative osteoarthropathy].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
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To evaluate the effectiveness of arthroscopic treatment and nonsurgical treatment on ankle degenerative osteoarthropathy.
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Lymph node metastasis in sinonasal squamous cell carcinoma treated with IMRT/3D-CRT.
Oral Oncol.
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To analyze the patterns of neck and retropharyngeal lymph nodes (RPLNs) metastases with magnetic resonance imaging (MRI) in patients with sinonasal squamous cell carcinoma (SCC), and to explore the patterns of treatment failure treated with intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). We also attempt to discuss the role of elective neck irradiation (ENI) in the treatment of cervical negative patients.
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Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function.
Cell Rep
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FOXP3 is a key transcription factor for regulatory T cell function. We report the crystal structure of the FOXP3 coiled-coil domain, through which a loose or transient dimeric association is formed and modulated, accounting for the activity variations introduced by disease-causing mutations or posttranslational modifications. Structure-guided mutagenesis revealed that FOXP3 coiled-coil-mediated homodimerization is essential for Treg function in vitro and in vivo. In particular, we identified human FOXP3 K250 and K252 as key residues for the conformational change and stability of the FOXP3 dimer, which can be regulated by protein posttranslational modifications such as reversible lysine acetylation. These studies provide structural and mechanistic explanations for certain disease-causing mutations in the coiled-coil domain of FOXP3 that are commonly found in IPEX syndrome. Overall, the regulatory machinery involving homooligomerization, acetylation, and heteroassociation has been dissected, defining atomic insights into the biological and pathological characteristics of the FOXP3 complex.
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Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms.
Sci Signal
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Therapeutic inhibition of the histone deacetylases HDAC6, HDAC9, or sirtuin-1 (Sirt1) augments the suppressive functions of regulatory T cells (T(regs)) that contain the transcription factor Foxp3 (Forkhead box P3) and is useful in organ transplant patients or patients with autoimmune diseases. However, it is unclear whether distinct mechanisms are involved for each HDAC or whether combined inhibition of HDACs would be more effective. We compared the suppressive functions of T(regs) from wild-type C57BL/6 mice with those from mice with either complete or cell-specific deletion of various HDACs, as well as with those of T(regs) treated with isoform-selective HDAC inhibitors. The improvement of T(reg) suppressive function mediated by inhibition of HDAC6, but not Sirt1, required an intact heat shock response. Although HDAC6, HDAC9, and Sirt1 all deacetylated Foxp3, each protein had different effects on transcription factors that control expression of the gene encoding Foxp3. For example, loss of HDAC9, but not other HDACs, was associated with stabilization of the acetylated form of signal transducer and activator of transcription 5 (STAT5) and promoted its transcriptional activity. Thus, targeting different HDACs increased T(reg) function through multiple and additive mechanisms, which suggests the therapeutic potential for using combinations of HDAC inhibitors in the management of autoimmunity and organ transplantation.
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Observed changes in winter wheat phenology in the North China Plain for 1981-2009.
Int J Biometeorol
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Climate change in the last three decades could have major impacts on crop phenological development and subsequently on crop productivity. In this study, trends in winter wheat phenology are investigated in 36 agro-meteorological stations in the North China Plain (NCP) for the period 1981-2009. The study shows that the dates of sowing (BBCH 00), emergence (BBCH 10) and dormancy (start of dormancy) are delayed on the average by 1.5, 1.7 and 1.5 days/decade, respectively. On the contrary, the dates of greenup (end of dormancy), anthesis (BBCH 61) and maturity (BBCH 89) occur early on the average by 1.1, 2.7 and 1.4 days/decade, respectively. In most of the investigated stations, GP2 (dormancy to greenup), GP3 (greenup to anthesis) and GP0 (entire period from emergence to maturity) of winter wheat shortened during the period 1981-2009. Due, however, to early anthesis, grain-filling stage occurs at lower temperatures than before. This, along with shifts in cultivars, slightly prolongs GP4 (anthesis to maturity). Comparison of field-observed CERES (Crop Environment Resource Synthesis)-wheat model-simulated dates of anthesis and maturity suggests that climate warming is the main driver of the changes in winter wheat phenology in the NCP. The findings of this study further suggest that climate change impact studies should be strengthened to adequately account for the complex responses and adaptations of field crops to this global phenomenon.
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[Correlation analysis between recurrent anterior shoulder dislocation and secondary intra-articular injuries].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
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To explore the effect of recurrent anterior shoulder dislocation on the secondary intra-articular injuries through analyzing the correlation between the number of dislocation, disease duration, and the secondary intraarticular injuries.
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HDAC inhibitor therapy in autoimmunity and transplantation.
Ann. Rheum. Dis.
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Pharmacological inhibitors of histone/protein deacetylases (HDACi) have considerable therapeutic potential as anti-inflammatory and immunosuppressive drugs. The utility of HDACi as anti-inflammatory agents is dependent upon their proving safe and effective in experimental models. Current pan-HDACi compounds are ill-suited to this role, given the broad distribution of target HDACs and their complex and multifaceted mechanisms of action. By contrast, the development of isoform-selective HDACi may provide important new tools for treatment in autoimmunity and transplantation. This review discusses which HDACs are worthwhile targets in inflammation, and the progress made towards their therapeutic inhibition, including the use of HDAC subclass and isoform-selective HDACi to promote the functions of Foxp3+ T-regulatory cells.
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[Arthroscopic poking reduction and internal fixation of radial head fractures].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
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To investigate the methods and effectiveness of arthroscopic poking reduction and percutaneous fixation of radial head fractures.
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Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma.
Mol. Cell. Biochem.
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Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.
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Two lysines in the forkhead domain of foxp3 are key to T regulatory cell function.
PLoS ONE
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The forkhead box transcription factor, Foxp3, is master regulator of the development and function of CD4+CD25+ T regulatory (Treg) cells that limit autoimmunity and maintain immune homeostasis. The carboxyl-terminal forkhead (FKH) domain is required for the nuclear localization and DNA binding of Foxp3. We assessed how individual FKH lysines contribute to the functions of Foxp3 in Treg cells.
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Histone/protein deacetylases and T-cell immune responses.
Blood
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Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3(+) T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.
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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.