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Find video protocols related to scientific articles indexed in Pubmed.
A time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) activity.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A novel time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) was developed. We used a straightforward strategy to modify a known ALK substrate into a peptide biosensor that can accommodate terbium luminescence sensitization upon its phosphorylation by ALK. Since this strategy is generalizable, this high-throughput screening compatible assay serves as an example for development of other kinase assays that employ terbium luminescence as a read-out.
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Baseline Factors Associated with Mortality within Six Months after Admission among Hospitalized HIV-1 Patients in Shenyang, China.
Intern. Med.
PUBLISHED: 11-01-2014
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Objective Short-term mortality rates remain high among critically ill human immunodeficiency virus-1 (HIV-1) patients though long-term mortality rates have dropped. Baseline risk factors for short-term mortality have not yet been determined in China. In this paper, we herein describe clinical characteristics, laboratory findings, causes of clinical deterioration, and risk factors associated with mortality among HIV-1 patients within six months after hospital admission. Methods We carried out a prospective study of hospitalized patients in advanced stages of HIV infection. These patients started antiretroviral therapy three or four weeks after admission. Follow-up was conducted for a period of six months. We used a multivariate logistic-regression analysis to identify risk factors associated with mortality. Results A total of 141 patients met our inclusion criteria. The mean age was 41 years. Fever and weight loss were the most common clinical manifestations of advanced HIV disease. Oral candidiasis, tuberculosis, cytomegaloviremia, and pneumocystis pneumonia were the most common opportunistic infections. Significantly decreased CD4+ T-cell counts, hypoalbuminemia, anemia, hyponatremia, as well as elevated C-reactive protein (CRP) and glutamic alanine transaminase levels were common laboratory test abnormalities. The mortality rate was 21.3%. The patients who died were more likely than the survivors to have low CD4+ T-cell counts as well as low creatinine, hemoglobin, albumin, and serum sodium levels while also having longer intervals of fever and higher CRP levels. A multivariate analysis demonstrated that the independent risk factors for mortality were active tuberculosis [odds ratio (OR): 2.681; 95% confidence interval (CI), 1.006-7.142; p=0.049], hyponatremia (OR: 3.027; 95% CI, 1.238-7.401; p=0.015), and being at clinical stage 4 (as defined by the World Health Organization) (OR: 9.492; 95% CI, 1.200-75.065; p=0.033) within the first six months of admission. Conclusion Special consideration should be given to patients who have active tuberculosis, are at clinical stage 4, and present with hyponatremia upon admission as these were found to be important factors associated with mortality within six months of hospital admission in HIV-1 patients.
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Homocysteine Accelerates Senescence of Endothelial Cells via DNA Hypomethylation of Human Telomerase Reverse Transcriptase.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-01-2014
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Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity.
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CD8 T Cells Are Involved in Skeletal Muscle Regeneration through Facilitating MCP-1 Secretion and Gr1high Macrophage Infiltration.
J. Immunol.
PUBLISHED: 10-22-2014
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Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8?-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8?-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8? deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8?-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8?-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.
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Evaluation of the immune response in Shitou geese (Anser anser domesticus) following immunization with GPV-VP1 DNA-based and live attenuated vaccines.
Vet Q
PUBLISHED: 10-15-2014
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Background: Goose parvovirus (GPV) is a highly contagious and deadly disease for goslings and Muscovy ducklings. Objectives: To compare the differences in immune response of geese immunized with GPV-VP1 DNA-based and live attenuated vaccines. Animals and methods: Shitou geese were immunized once with either 20 ?g pcDNA-GPV-VP1 DNA gene vaccine by gene gun bombardment via intramuscular injection, or 300 ?g by im injection, or 300 ?L live attenuated vaccine by im injection, whereas 300 ?g pcDNA3.1 (+) im or 300 ?L saline im were used as positive and negative controls, respectively. Each group comprised 28 animals. Peripheral blood samples were collected from 2-210 days after immunization and the proliferation of T lymphocytes, the number of CD4(+) and CD8(+) T cells and the level of IgG assessed. Statistical analysis was performed using a one-way analysis of variance with group multiple comparisons via Tukey's test. Results: The pcDNA-GPV-VP1 DNA and attenuated vaccine induced cellular and humoral responses, and there were no differences between the 20 and 300 ?g group in the responses of proliferation of T lymphocyte and the CD8(+) T-cell. However, as to CD4(+) T-cell response and humoral immunity, the 20 ?g group performed better than the 300 ?g group, which induced better cellular and humoral immunity than live attenuated vaccine. Conclusions: This study showed that it is possible to induce both cellular and humoral response using DNA-based vaccines and that the pcDNA-GPV-VP1 DNA gene vaccine induced better cellular and humoral immunity than live attenuated vaccine.
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Cardioprotective effects of single oral dose of nicorandil before selective percutaneous coronary intervention.
Anadolu Kardiyol Derg
PUBLISHED: 09-25-2014
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Nicorandil, an opener of ATP-sensitive K+ channels, was used to treat angina in patients with coronary artery disease. In this study, we aim to investigate the cardioprotective effects of single oral dose of nicorandil in patients undergoing selective percutaneous coronary intervention (PCI).
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The endocannabinoid system regulates synaptic transmission in nucleus accumbens by increasing DAGL-? expression following short-term morphine withdrawal.
Br. J. Pharmacol.
PUBLISHED: 09-23-2014
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The endocannabinoid (eCB) system is involved in pathways that regulate drug addiction, and eCB-mediated synaptic plasticity has been linked with addictive behaviors. Here, we investigated molecular mechanisms underlying changes in eCB-dependent synaptic plasticity in nucleus accumbens core (NAcc) following short-term withdrawal from repeated morphine treatment.
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Inhibiting ?-Amyloid-Associated Alzheimer's Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue.
J. Mol. Neurosci.
PUBLISHED: 09-01-2014
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Fibrillar aggregates of ?-amyloid protein (A?) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit the formation of A? fibrils and block A? fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China. In the current study, the inhibitory effect of B12H on the formation of A? fibrils and their associated toxicity was investigated both in vitro and in vivo. By using Thioflavin T fluorescence assay, we found that B12H (0.3-3 ?M) directly inhibited A? fibrils formation following co-incubation of B12H and A?1-40 at 37 °C for 6 days in vitro. However, huperzine A, at the same concentrations, did not show significant inhibitory effect on A?1-40 fibrils formation. Moreover, B12H markedly reduced A?1-40-induced cytotoxicity in cultured SH-SY5Y cells, as evidenced by the increase in cell viability, the decrease in lactate dehydrogenase release, and the reduction of apoptotic nuclei. Most importantly, B12H (0.2 and 0.4 mg/kg) reduced intracerebroventricular A?1-40 infusion-induced cognitive and memory impairments in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with increasing choline acetyltransferase activity and decreasing acetylcholinesterase activity. Collectively, our study provided novel sights into the potential application of B12H in AD treatment.
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Expressions of heparanase and upstream stimulatory factor in hepatocellular carcinoma.
Eur. J. Med. Res.
PUBLISHED: 08-23-2014
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The expression of heparanase (HPSE) was associated with postoperative metastatic recurrence in patients with hepatocellular carcinoma (HCC). The six E-box binding sites in the core promoter of the HPSE gene suggested that transcription factors of E-box such as upstream stimulatory factor (USF) might regulate the transcription of the HPSE gene. The aim of our study is to measure the levels of HPSE and USF expression and investigate the relationship between USF expression and clinicopathological parameters in patients with HCC.
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Empyema, acute respiratory failure, and septic shock after aspiration of a soft-shelled turtle (Pelodiscus sinensis) bone by an adult.
Springerplus
PUBLISHED: 08-20-2014
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The common late complications of foreign body aspiration include granulation formation, obstructive pneumonia, and atelectasis. However, a foreign body-induced pleural infection is very rare, and especially when it is not iatrogenic.
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Botanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process.
CNS Neurosci Ther
PUBLISHED: 08-19-2014
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Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process.
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Intra-day and inter-day biological variations of peripheral blood lymphocytes.
Clin. Chim. Acta
PUBLISHED: 08-17-2014
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The proportion and absolute numbers of lymphocyte subsets are important indices that reflect the immunological status of the body. Few studies on biological variations of absolute lymphocyte subset counts and no study in Asian population are currently available. Furthermore, there have been few reports on the biological variation of these indices in the short term.
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Significance of low peak Doppler velocity in the proximal sano conduit in hypoplastic left heart syndrome.
Ann. Thorac. Surg.
PUBLISHED: 08-16-2014
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The Sano modification of the Norwood operation is a well-established first step palliation for hypoplastic left heart syndrome (HLHS). Theoretically, the first point of resistance to pulmonary flow should be in the proximal Sano, generating high Doppler flow velocity. Paradoxically, however, some patients have low gradients in the proximal Sano conduit. The objective of this study was to determine the hemodynamic and anatomic significance of low proximal Sano Doppler flow velocity and its clinical implications.
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Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets.
Nanoscale
PUBLISHED: 08-16-2014
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Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.
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Novel mechanism of intra?renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats.
Mol Med Rep
PUBLISHED: 08-14-2014
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The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar?kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30 mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid?inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the Ang II?SGK1?NHE3 of intra?renal tissue.
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The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice.
Inflammation
PUBLISHED: 08-12-2014
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Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways.
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A strong integrated strength and toughness artificial nacre based on dopamine cross-linked graphene oxide.
ACS Nano
PUBLISHED: 08-12-2014
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Demands of the strong integrated materials have substantially increased across various industries. Inspired by the relationship of excellent integration of mechanical properties and hierarchical nano/microscale structure of the natural nacre, we have developed a strategy for fabricating the strong integrated artificial nacre based on graphene oxide (GO) sheets by dopamine cross-linking via evaporation-induced assembly process. The tensile strength and toughness simultaneously show 1.5 and 2 times higher than that of natural nacre. Meanwhile, the artificial nacre shows high electrical conductivity. This type of strong integrated artificial nacre has great potential applications in aerospace, flexible supercapacitor electrodes, artificial muscle, and tissue engineering.
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Palladium-catalyzed remote C(sp3)-H arylation of 3-pinanamine.
Org. Lett.
PUBLISHED: 08-04-2014
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3-Pinanamine is a prevalent motif in medicinal chemistry and asymmetric synthesis. In line with the pursuit of novel 3-pinanamine based anti-influenza virus A agent, the direct functionalization of 3-pinanamine was achieved by using Pd-catalyzed C(sp(3))-H activation logic. Good substrate scope and functional group tolerance were observed. The reaction represents a rare example of a direct functionalization of an aliphatic amine at the remote ? position.
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Efficient planar heterojunction perovskite solar cells employing graphene oxide as hole conductor.
Nanoscale
PUBLISHED: 08-01-2014
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Graphene oxide (GO) is employed as a hole conductor in inverted planar heterojunction perovskite solar cells, and the devices with CH?NH?PbI?-xClx as absorber achieve an efficiency of over 12%. The perovskite film grown on GO exhibits enhanced crystallization, high surface coverage ratio as well as preferred in-plane orientation of the (110) plane. Efficient hole extraction from the perovskite to GO is demonstrated.
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Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury.
Chin J Integr Med
PUBLISHED: 07-31-2014
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To investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury.
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[Effectiveness of digital three-dimensional titanium mesh in repairing skull defect under temporalis and reconstructing temporal muscle attachment points].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 07-31-2014
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To investigate the technique and the effectiveness of digital three-dimensional (3-D) titanium mesh in repairing skull defect under the temporalis and reconstructing temporal muscle attachment points.
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5' isomiR variation is of functional and evolutionary importance.
Nucleic Acids Res.
PUBLISHED: 07-23-2014
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We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.
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Acute fluctuation in blood glucose has no effect on platelet aggregation rate.
Clin. Lab.
PUBLISHED: 07-15-2014
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Short-term acute blood glucose fluctuations are often found among patients with high risk of thrombosis. Influence of the phenomenon on platelet aggregation rate is of clinical importance and should be clearly evaluated.
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Inhibition of TNF-? in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats.
Toxicol. Appl. Pharmacol.
PUBLISHED: 07-12-2014
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We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-?) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-?B (NF-?B) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-? blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (?-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-?B p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-? in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-?B p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy.
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To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.
Asian Pac J Trop Med
PUBLISHED: 07-10-2014
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To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.
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Activated carbon nanotubes: a highly-active metal-free electrocatalyst for hydrogen evolution reaction.
Chem. Commun. (Camb.)
PUBLISHED: 07-09-2014
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In this communication, for the first time, we report on the development and utilization of activated carbon nanotubes (CNTs) as a highly-active metal-free electrocatalyst for the hydrogen evolution reaction (HER) with good durability in acidic electrolytes. This catalyst shows an onset overpotential and an exchange current density of 100 mV and 16.0 × 10(-3) mA cm(-2), respectively. The possible catalytic mechanism for the HER is also proposed.
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Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages.
Pharmacol. Ther.
PUBLISHED: 07-03-2014
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Alcohol abuse can result in significant alterations to the structure of the brain and ultimately to behavioral dysfunctions. Epidemiological studies have shown that alcoholism is closely associated with impaired memory and judgment. However, the degree of deficit (brain injury) depends on factors such as the age of onset, duration of heavy drinking, continuous versus periodic (binge) drinking and the typical amount consumed per session. In recent years, neuroinflammation has been proposed as one of the alcoholism-induced neuropathological mechanisms, since increased levels of microglial markers are observed in the brains of both post-mortem human alcoholics and various alcohol-treated animals, from newborn or adolescent rodents to adult rodents. Many studies have investigated how microglia modulate alcohol-induced behavioral changes such as cognitive deficits, abnormal locomotor activity, motor impairment and mood disturbance. Importantly, we try to characterize and compare the distinct features in different ethanol (EtOH)-induced neurodegenerative disease (NDD) models. Moreover, mounting evidence indicates that in response to certain environmental toxins, microglia can become over-activated under oxidative stress, releasing pro-inflammatory mediators that cause central nervous system (CNS) disease. The molecular mechanisms involve free radical formation and the release of pro-inflammatory cytokines that are detrimental to neighboring neurons and interfere with the molecules regulating cell-cell interactions. The identification and understanding of the cellular and molecular mechanisms of microglial activation are described, as well as multiple downstream targets, in different alcohol-treated animal models. This review might contribute to the development of treatments and/or therapeutic agents that can reduce or eliminate the deleterious effects of alcohol-induced NDD.
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Molecular cloning and characterization of pseudorabies virus EP0 gene.
Indian J. Biochem. Biophys.
PUBLISHED: 07-02-2014
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The pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the exact function of EP0 is not clear. In this study, using polymerase chain reaction, a 1,104 base-pair sequence of the EP0 gene was amplified from the PRV Becker strain genome and identification of the EP0gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV EP0 gene encoded a putative polypeptide with 367 amino acids. The encoded protein, designated as EP0 contained a conserved RING-finger superfamily domain and was found to be closely related with the herpes virus RING-finger superfamily and was highly conserved among the counterparts encoded by RING-finger genes. Multiple nucleic acid sequence and amino-acid sequence alignments suggested that PRV EP0 showed a relatively higher similarity with EP0-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV EP0 had a close evolutionary relationship with members of genus Varicellovirus, especially bovine herpesvirus 1 (BoHV-1) and BoHV-5. Antigen prediction indicated that several potential B-cell epitopes were located in EP0. Also, subcellular localization analysis demonstrated that EP0 was predominantly localized in the nucleus, suggesting that it might function as a nuclear-targeted protein.
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Identification and characterization of long intergenic non-coding RNAs related to mouse liver development.
Mol. Genet. Genomics
PUBLISHED: 06-20-2014
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Long non-coding RNAs (lncRNAs) have been studied extensively over the last few years. Liver is an important organ that plays a crucial role in glucose metabolism and homeostasis; however, there are few reports of the identification and functional characterization of lncRNAs with important roles in liver development. Therefore, it is necessary to systematically identify lncRNAs that are involved in liver development. In this paper, we assembled the transcriptome using published RNA-seq data across three mouse liver developmental stages and identified 4,882 putative long intergenic non-coding RNAs (lincRNAs) expressed in at least one of the investigated stages. Combining these with Ensembl lincRNAs, we established a reference catalog of 6,602 transcribed lincRNAs in the mouse liver. We then analyzed all the lincRNAs in this reference catalog systematically and revealed that liver lincRNAs carry different genomic signatures from protein-coding genes, while the putative lincRNAs are generally comparable with known Ensembl lincRNAs. In addition, putative lincRNAs are functionally associated with essential biological processes, including RNA splicing, protein localization and fatty acid metabolic process, implying that they may play an important role in regulating liver development. The validation of selected lincRNAs that are specifically expressed in developing liver tissues further suggested the effectiveness of our approach. Our study shows that lincRNAs that are differentially expressed during three liver developmental stages could have important regulatory roles in liver development. The identified putative lincRNAs are a valuable resource for further functional studies.
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DNA methylation of human telomerase reverse transcriptase associated with leukocyte telomere length shortening in hyperhomocysteinemia-type hypertension in humans and in a rat model.
Circ. J.
PUBLISHED: 05-30-2014
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Elevated homocysteine (Hcy) levels might play a role in the development of essential hypertension (EH). Telomere dynamics provide valuable insight into the pathogenesis of age-related diseases. The contribution of Hcy to leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was examined.
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??T Cell-derived interleukin-17A via an interleukin-1?-dependent mechanism mediates cardiac injury and fibrosis in hypertension.
Hypertension
PUBLISHED: 05-29-2014
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Inflammation is implicated in the initiation of hypertension and end-organ injury. Interleukin-17A (IL-17A) is a key pathogenic factor in a variety of inflammatory diseases and hypertension. However, the mechanisms underlying IL-17A production, and its role in mediating inflammation and early cardiovascular injury in hypertensive heart, remain unknown. Angiotensin II (Ang II) infusion increased cardiac IL-17A mRNA expression and IL-17A+CD3+ cell infiltration in a time-dependent manner. IL-17A in the hypertensive heart was derived mostly from infiltrating ??T cells rather than from CD4 T cells. Genetic knockdown of ??T cells or specific anti-??T antibody abolished IL-17A production in Ang II–infused heart. Moreover, monocyte-secreted IL-1?, not cardiac fibroblast–secreted IL-6 or transforming growth factor-?, was required for IL-17A production from ??T cell. IL-17A accelerated differentiation of myofibroblast through promoting IL-6 production from cardiac fibroblast. Finally, inflammatory cell infiltration, proinflammatory or profibrotic cytokine expression, and fibrotic lesion induced by Ang II were attenuated in IL-17A–deficient mice. Moreover, the deletion of ??T cell was protected from Ang II–induced cardiac injury. Thus, a triangular positive feedback loop exists among monocytic-secreted IL-1?, ??T-cell–derived IL-17A, and cardiac fibroblast–produced IL-6, which triggers the cardiac injury in hypertension.
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The effect of dalteparin versus unfractionated heparin on the levels of troponin I and creatine kinase isoenzyme MB in elective percutaneous coronary intervention: a multicenter study.
Coron. Artery Dis.
PUBLISHED: 05-27-2014
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The aim of this study was to investigate the safety and efficacy of dalteparin during an elective percutaneous coronary intervention (PCI) procedure in a large cohort.
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[Horizontal transmission of Streptococcus mutans in caries-active preschool children].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 05-23-2014
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To analyze horizontal transmission patterns of Streptococcus mutans among caries-active preschool children for early interventions of dental caries.
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Catheter-related Candida bloodstream infection in intensive care unit patients: a subgroup analysis of the China-SCAN study.
BMC Infect. Dis.
PUBLISHED: 05-19-2014
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BackgroundIn patients hospitalized in intensive care units (ICU), Candida infections are associated with increased morbidity, mortality and costs. However, previous studies reported confused risk factors for catheter-related Candida bloodstream infection (CRCBSI). The objective was to describe the risk factors, microbiology, management and outcomes of CRCBSI in the China-SCAN population.MethodsPatients with ¿1 Candida-positive peripheral blood culture were selected from the China-SCAN study. Peripheral and catheter blood samples were collected for Candida isolation. Patients with the same strain of Candida in peripheral and catheter blood samples were considered as being with CRCBSI, while patients with Candida-positive peripheral blood cultures only or different strains were considered as non-CRCBSI. Data were collected from the China-SCAN study.ResultsCRCBSI incidence in ICU was 0.03% (29/96,060), accounting for 9.86% of all candidemia observed in ICU (29/294). The proportion of CRCBSI due to Candida parapsilosis reached 33.3%, more than that of Candida albicans (28.6%). In univariate analyses, older age (P¿=¿0.028) and lower body weight (P¿=¿0.037) were associated with CRCBSI. Multivariate analysis showed that the sequential organ failure assessment (SOFA) score was independently associated with CRCBSI (odds ratio (OR)¿=¿1.142, 95% confidence interval¿=¿1.049-1.244, P¿=¿0.002). Catheter removal and immune enhancement therapy were often used for CRCBSI treatment.ConclusionsIn China, CRCBSI was more likely to occur in old patients with low body weight. SOFA score was independently associated with CRCBSI. Candida parapsilosis accounted for a high proportion of CRCBSI, but the difference from non-CRCBSI was not significant.
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Multiplex microfluidic paper-based immunoassay for the diagnosis of hepatitis C virus infection.
Anal. Chem.
PUBLISHED: 05-13-2014
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Hepatitis C virus (HCV) infection is a serious and rising global healthcare problem. One critical challenge to tackle this disease is the lack of adequate diagnosis. Here, we develop a multiplex microfluidic paper-based immunoassay, as a novel diagnostic approach, to detect human IgG antibody against HCV (anti-HCV). The paper substrate, highly flammable nitrocellulose (NC), is patterned under ambient temperature by craft punch patterning (CPP) to generate multiple test zones. On the basis of superior merits of patterned paper, this new diagnostic approach demonstrates the key novelty to unprecedentedly combine segmented diagnostic assays into a single multiplex test. The generated diagnostic results are not only informative but can be rapidly and cost-effectively delivered. It would significantly transform the clinical pathway for unwitting individuals with HCV infection. This work highlights the promising role of microfluidic paper-based immunoassays in tackling the diagnostic challenge for the HCV pandemic as well as other diseases.
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[Application of high-content screening and flow cytometry analysis techniques to evaluation of myocardial fibroblasts proliferation].
Sheng Li Xue Bao
PUBLISHED: 04-30-2014
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The proliferation of cardiac fibroblasts (CFs) is a key pathological process in the cardiac remodeling. To establish an objective, quantitative method for the analysis of cell proliferation and cell cycle, we applied the high-content screening (HCS) and flow cytometry (FCM) techniques. CFs, isolated by enzyme digestion from newborn C57BL/6J mice, were serum starved for 12 h and then given 10% fetal bovine serum (FBS) for 24 h. Followed by BrdU and DAPI (or 7-AAD) staining, CFs proliferation and cell cycle were analyzed by HCS and FCM, respectively. Discoidin domain receptor 2 (DDR2) staining indicated that the purity of isolated CFs was over 95%. (1) HCS analysis showed that the ratio of BrdU-positive cells was significantly increased in 10% FBS treated group compared with that in serum-free control group [(12.96 ± 0.67)% vs (2.77 ± 0.33)%; P < 0.05]. Cell cycle analysis showed that CFs in G0/G1 phase were diploid, and CFs in S phase were companied with proliferation, DNA replication and enlarged nuclei; CFs in G2 phase were tetraploid, and CFs in M phase produced two identical cells (2N). (2) FCM analysis showed that the ratio of BrdU-positive cells was increased in 10% FBS treated group compared with that in the control group [(11.10 ± 0.42)% vs (2.22 ± 0.31)%; P < 0.05]; DNA content histogram of cell cycle analysis indicated that the platform of S phase elevated in 10% FBS group compared with control group. (3) There were no differences between the two methods in the results of proliferation and cell cycle analysis. In conclusion, HCS and FCM methods are reliable, stable and consistent in assessment of the proliferation and cell cycle in CFs.
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Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy.
J. Hepatol.
PUBLISHED: 04-27-2014
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Autophagy is an intracellular lysosomal degradation process that plays an important role in regulating normal physiological functions of the liver. The purpose of the present study was to investigate the mechanism(s) by which the loss of hepatic autophagy leads to liver inflammation, fibrosis and tumorigenesis.
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Complement 5a receptor mediates angiotensin II-induced cardiac inflammation and remodeling.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 04-17-2014
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Inflammation contributes to hypertension-induced cardiac damage and fibrotic remodeling. Complement activation produces anaphylatoxins, which are major inflammatory effectors. Here, we investigated the role of complement anaphylatoxins in angiotensin II (Ang II)-induced cardiac remodeling.
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Person-to-person asymptomatic infection of severe fever with thrombocytopenia syndrome virus through blood contact.
Intern. Med.
PUBLISHED: 04-15-2014
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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently discovered in northeastern and central China that is caused by a novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). Humans are primarily infected through tick bites. Four previous reports have discussed SFTS infection from person to person, all cases of which were symptomatic. In this report, we analysed the epidemiological and clinical data for a cluster of cases, including one case of secondary-asymptomatic infection, and review the literature regarding SFTSV transmission from person to person. We conclude that SFTSV caused the asymptomatic infections via person-to-person contact with infected blood.
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Carbon nanotubes decorated with CoP nanocrystals: a highly active non-noble-metal nanohybrid electrocatalyst for hydrogen evolution.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 04-10-2014
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The development of effective and inexpensive hydrogen evolution reaction (HER) electrocatalysts for future renewable energy systems is highly desired. The strongly acidic conditions in proton exchange membranes create a need for acid-stable HER catalysts. A nanohybrid that consists of carbon nanotubes decorated with CoP nanocrystals (CoP/CNT) was prepared by the low-temperature phosphidation of a Co3O4/CNT precursor. As a novel non-noble-metal HER catalyst operating in acidic electrolytes, the nanohybrid exhibits an onset overpotential of as low as 40?mV, a Tafel slope of 54?mV?dec(-1), an exchange current density of 0.13?mA?cm(-2), and a Faradaic efficiency of nearly 100?%. This catalyst maintains its catalytic activity for at least 18?hours and only requires overpotentials of 70 and 122?mV to attain current densities of 2 and 10?mA?cm(-2), respectively.
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Sox2, a key factor in the regulation of pluripotency and neural differentiation.
World J Stem Cells
PUBLISHED: 04-07-2014
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Sex determining region Y-box 2 (Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells (PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogramming, reversing the epigenetic configuration of differentiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mechanisms underlying these roles.
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S100a8/a9 released by CD11b+Gr1+ neutrophils activates cardiac fibroblasts to initiate angiotensin II-Induced cardiac inflammation and injury.
Hypertension
PUBLISHED: 04-07-2014
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Angiotensin II induces cardiovascular injury, in part, by activating inflammatory response; however, the initial factors that trigger the inflammatory cascade remain unclear. Microarray analysis of cardiac tissue exposed to systemic angiotensin II infusion revealed that extracellular heterodimeric proteins S100a8/a9 were highly upregulated. The increase in S100a8/a9 mRNA of CD11b(+)Gr1(+) neutrophils isolated from both the peripheral blood and heart was highest on day 1 of angiotensin II infusion and decreased to baseline at day 7. Immunostaining showed that S100a8/a9 was primarily present in infiltrating CD11b(+)Gr1(+) neutrophils in the heart. The receptor for advanced glycation end products, an S100a8/a9 receptor, was expressed in cardiac fibroblasts (CFs). Microarray analysis and Bio-Plex protein array showed that treatment of CFs with recombinant S100a8/a9 activated multiple chemokine and cytokines released. Luciferase reporter assay indicated S100a8/a9-activated nuclear factor-? B pathway in CFs. Consequently, recombinant S100a8/a9-treated CFs promoted migration of monocytes and CFs, whereas neutralizing S100a9 antibody blocked S100a9 or receptor for advanced glycation end products-suppressed cellular migration. Finally, administration of a neutralizing S100a9 antibody prevented angiotensin II infusion-induced nuclear factor-? B activation, inflammatory cell infiltration, cytokine production, subsequent perivascular and interstitial fibrosis, and hypertrophy in heart. Our findings identify neutrophil-produced S100a8/a9 as an initial proinflammatory factor needed to trigger inflammation and cardiac injury during acute hypertension.
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Cloning, expression, purification, antiserum preparation and its characteristics of the truncated UL6 protein of herpes simplex virus 1.
Mol. Biol. Rep.
PUBLISHED: 04-06-2014
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The herpes simplex virus 1 (HSV-1) portal protein UL6 is important for HSV-1 replication, however, its precise functions in the virus life cycle are poorly understood. As we known, a relatively important tool for disclosing these functions is the antiserum specifically detecting UL6 in the HSV-1-infected cell. To this end, a recombinant protein consisting of C-terminal 297-676 amino acids of UL6 fused to His-tag was expressed in E. coli and purified from inclusion body by the Ni(2+)-NTA affinity chromatography under denaturing conditions, which was then refolded and used for the preparation of antiserum in rabbit. As results, western blot and immunofluorescence assay showed that this antiserum could specifically detect the purified truncated UL6 as well as native UL6 in the HSV-1 infected cells, indicating that the prepared antiserum could serve as a valuable tool for further exploring the functions of UL6.
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Finite-key analysis for measurement-device-independent quantum key distribution.
Nat Commun
PUBLISHED: 03-27-2014
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Quantum key distribution promises unconditionally secure communications. However, as practical devices tend to deviate from their specifications, the security of some practical systems is no longer valid. In particular, an adversary can exploit imperfect detectors to learn a large part of the secret key, even though the security proof claims otherwise. Recently, a practical approach--measurement-device-independent quantum key distribution--has been proposed to solve this problem. However, so far its security has only been fully proven under the assumption that the legitimate users of the system have unlimited resources. Here we fill this gap and provide a rigorous security proof against general attacks in the finite-key regime. This is obtained by applying large deviation theory, specifically the Chernoff bound, to perform parameter estimation. For the first time we demonstrate the feasibility of long-distance implementations of measurement-device-independent quantum key distribution within a reasonable time frame of signal transmission.
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17?-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts.
Lab. Invest.
PUBLISHED: 03-20-2014
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Although many studies have suggested that estrogen prevents postmenopausal bone loss partially due to its anti-apoptosis effects in osteoblasts, the underlying mechanism has not been fully elucidated. In the present study, we found that 17?-estradiol (17?-E?), one of the primary estrogens, inhibited endoplasmic reticulum (ER) stress-induced apoptosis in MC3T3-E1 cells and primary osteoblasts. Interestingly, 17?-E?-promoted Grp78 induction, but not CHOP induction in response to ER stress. We further confirmed that Grp78-specific siRNA reversed the inhibition of 17?-E? on ER stress-induced apoptosis by activating caspase-12 and caspase-3. Moreover, we found that 17?-E? markedly increased the phosphorylated TFII-I levels and nuclear localization of TFII-I in ER stress conditions. 17?-E? stimulated Grp78 promoter activity in a dose-dependent manner in the presence of TFII-I and enhanced the binding of TFII-I to the Grp78 promoter. In addition, 17?-E? notably increased phosphorylated ERK1/2 levels and Ras kinase activity in MC3T3-E1 cells. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked 17?-E?-induced TFII-I phosphorylation and Grp78 expression in response to ER stress. Together, 17?-E? protected MC3T3-E1 cells against ER stress-induced apoptosis by promoting Ras-ERK1/2-TFII-I signaling pathway-dependent Grp78 induction.
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TRF2-mediated stabilization of hREST4 is critical for the differentiation and maintenance of neural progenitors.
Stem Cells
PUBLISHED: 03-08-2014
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Telomere repeat binding factor 2 (TRF2) is a component of the shelterin complex that is known to bind and protect telomeric DNA, yet the detection of TRF2 in extra-telomeric regions of chromosomes suggests other roles for TRF2 besides telomere protection. Here, we demonstrate that TRF2 plays a critical role in antagonizing the repressive function of neuron-restrictive silencer factor, also known as repressor element-1 silencing transcription factor (REST), during the neural differentiation of human embryonic stem cells (hESCs) by enhancing the expression of a truncated REST splice isoform we term human REST4 (hREST4) due to its similarity to rodent REST4. We show that TRF2 is specifically upregulated during hESC neural differentiation concordantly with an increase in the expression of hREST4 and that both proteins are highly expressed in NPCs. Overexpression of TRF2 in hESCs increases hREST4 levels and induces their neural differentiation, whereas TRF2 knockdown in hESCs and NPCs reduces hREST4 expression, hindering their ability to differentiate to the neural lineage. Concurrently, we show that TRF2 directly interacts with the C-terminal of hREST4 through its TRF2 core binding motif [F/Y]xL, protecting hREST4 from ubiquitin-mediated proteasomal degradation and consequently furthering neural induction. Thus, the TRF2-mediated counterbalance between hREST4 and REST is vital for both the generation and maintenance of NPCs, suggesting an important role for TRF2 in both neurogenesis and function of the central nervous system.
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Effects of peroxisome proliferator-activated receptor ? in simvastatin antiplatelet activity: influences on cAMP and mitogen-activated protein kinases.
Thromb. Res.
PUBLISHED: 03-02-2014
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Statins are widely used as hypolipidemic drugs, and have beneficial effects in reducing cardiovascular events. In addition, recent studies on the pleiotropic effects of statins (i.e., simvastatin) reveal that these drugs have many additional anti-atherogenic effects, including antiplatelet activity. The mechanisms may be partly related to activation of peroxisome proliferator-activated receptors (PPARs), which are present in human platelets, and whose activation inhibits platelet aggregation. However, the details of the signaling pathway by which simvastatin inhibits platelet activation via PPARs have not yet been completely established. The aim of this study was to examine the mechanisms by which the PPAR-mediated pathways contribute to the antiplatelet activity of simvastatin. Simvastatin (3-50 ?M) induced PPAR? and PPAR? activation in a dose-dependent manner in washed platelets. Additionally, simvastatin inhibited collagen-induced platelet aggregation, expression of CD62 and PAC-1, and Ca(2+) mobilization. These effects of simvastatin on platelet responses were strongly reduced by adding a selective PPAR? antagonist (GW9662), but not PPAR? antagonist (GW6471). Moreover, in the presence of GW9662, simvastatin-mediated increase of cyclic adenosine monophosphate (cAMP) production, vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation and inhibition of Akt phosphorylation were markedly reversed. Furthermore, simvastatin was found to inhibit phosphorylation of mitogen-activated protein kinases (MAPKs, i.e., p38 MAPK, ERK) by increasing the association between PPAR? and the components of MAPKs after platelet activation. Taken together, the present results confirm that simvastatin inhibition of platelet activation is mediated by PPAR?-dependent processes, which involves mediating MAPKs signaling, increase of cAMP formation and VASP Ser(157) phosphorylation, inhibition of Akt phosphorylation and intracellular Ca(2+) mobilization.
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The intrinsically disordered structural platform of the plant defence hub protein RPM1-interacting protein 4 provides insights into its mode of action in the host-pathogen interface and evolution of the nitrate-induced domain protein family.
FEBS J.
PUBLISHED: 02-14-2014
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Arabidopsis thaliana (At) RPM1-interacting protein 4 (RIN4), targeted by many defence-suppressing bacterial type III effectors and monitored by several resistance proteins, regulates plant immune responses to pathogen-associated molecular patterns and type III effectors. Little is known about the overall protein structure of AtRIN4, especially in its unbound form, and the relevance of structure to its diverse biological functions. AtRIN4 contains two nitrate-induced (NOI) domains and is a member of the NOI family. Using experimental and bioinformatic approaches, we demonstrate that the unbound AtRIN4 is intrinsically disordered under physiological conditions. The intrinsically disordered polypeptide chain of AtRIN4 is interspersed with molecular recognition features (MoRFs) and anchor-identified long-binding regions, potentially allowing it to undergo disorder-to-order transitions upon binding to partner(s). A poly-l-proline II structure, often responsible for protein recognition, is also identified in AtRIN4. By performing bioinformatics analyses on RIN4 homologues from different plant species and the NOI proteins from Arabidopsis, we infer the conservation of intrinsic disorder, MoRFs and long-binding regions of AtRIN4 in other plant species and the NOI family. Intrinsic disorder and MoRFs could provide RIN4 proteins with the binding promiscuity and plasticity required to act as hubs in a pivotal position within plant defence signalling cascades.
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Synergistic inhibition on acetylcholinesterase by the combination of berberine and palmatine originally isolated from Chinese medicinal herbs.
J. Mol. Neurosci.
PUBLISHED: 02-12-2014
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Alzheimer's disease is a multi-factorial neurodegenerative disorder devastatingly affecting the aged population worldwide. Previous studies have shown that medicinal herbs used in traditional Chinese medicine might be benefit to Alzheimer's disease patients. Berberine and palmatine, two isoquinoline alkaloids found in several medicinal herbs, were used for memory enhancement in China. In this study, the inhibitory effects of combined berberine and palmatine on acetylcholinesteras were evaluated using recombinant human acetylcholinesterase. Our results showed that the combination of berberine and palmatine inhibited acetylcholinesterase in a mixed competitive pattern. By the median-effect principle, the calculated combination index of the combination was less than 1, suggesting that berberine and plamatine inhibited acetylcholinesterase synergistically. Furthermore, the drug-reducing index of berberine and palmatine were 2.98 and 2.66, respectively. Taken together, the results showed that the combination of the two alkaloids might potentially be developed as a more effective therapeutic strategy for Alzheimer's disease patients.
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Patterns of circulating tumor cells identified by CEP8, CK and CD45 in pancreatic cancer.
Int. J. Cancer
PUBLISHED: 02-11-2014
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To improve the identification for CTCs with weak or negative CK and diploid CTCs in pancreatic cancer, we combined immune-staining of CK, CD45, DAPI and fluorescence in situ hybridization with the centromere of chromosome 8 (CEP8) probe method. CTCs in 3.75 mL of blood were depleted for CD45 positive cells with anti-CD45 antibodies and identified by combining CK, CD45, DAPI and CEP8 in 61 cases including 22 pancreatic cancers, 3 borderline pancreatic solid pseudopapillary tumors, 6 pancreatic benign tumors, and 30 healthy individuals. We found that enriched cells could be classified into 5 patterns: CK+CD45-DAPI+CEP8=2 (2 hybridization signals), CK+CD45-DAPI+CEP8>2 (>2 hybridization signals), CK-CD45-DAPI+CEP8>2, CK-CD45-DAPI+CEP8=2, and CK+/-CD45+DAPI+CEP8=2 or >2. Among 22 pancreatic cancers, CK+CD45-DAPI+CEP8=2 and CK+CD45-DAPI+CEP8>2 patterns were identified in two cases, and CK-CD45- DAPI+CEP8>2 pattern was identified in 16 cases. CK-CD45-DAPI+CEP8=2 and CK+/-CD45+DAPI+CEP8=2 or >2 patterns were detected in pancreatic cancers, other pancreatic diseases and healthy individuals. Among the five patterns, CK+CD45-DAPI+CEP8=2, CK+CD45-DAPI+CEP8>2 and CK-CD45-DAPI+CEP8>2 were considered as CTCs, while CK-CD45-DAPI+CEP8=2 and CK+/-CD45+DAPI+CEP8=2 or >2 were considered as indeterminate cells. When the cutoff value was set as 2 cells/3.75 mL based on ROC curve, the sensitivity and specificity in the diagnosis of pancreatic cancer was 68.18 and 94.87%, respectively. Dynamically monitoring CTCs changes prior to and after surgery in pancreatic patients revealed that CTCs count decreased in 3 days after surgery, but increased in 10 days after surgery in most patients. During our one and a half year follow-up, CTCs positive patients showed metastasis and worse survival rate.
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Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: involvement of Nrf2/HO-1 pathway.
CNS Neurosci Ther
PUBLISHED: 02-09-2014
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Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death.
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Low-grade B-cell lymphoma presenting primarily in the bone marrow.
Hum. Pathol.
PUBLISHED: 02-06-2014
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Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.
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Building a nano-crystalline ?-alumina layer at a liquid metal/sapphire interface by ultrasound.
Ultrason Sonochem
PUBLISHED: 01-19-2014
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Transitional layers at the metal/ceramic interface play an very important role in ceramic joining. In this study, sapphire blocks were ultrasonically dipped in liquid Sn-Zn-Al alloy. It is found that the ultrasound promoted rapid oxidation reaction of aluminum at the Sn-Zn-Al/sapphire interface at 230°C in the ambient atmosphere, resulting in the formation of a nano-crystalline ?-Al2O3 layer (NCAL). In a ?2nm boundary layer of the NCAL, the lattice matches the sapphire substrate well. Thus, a smooth transition of the lattice from sapphire to metal was formed through the NCAL. Ultrasonically soldered sapphire joints were made with Sn-Zn-Al as the filler alloy. Compressive shear strength of the joints reached 43-48MPa, which is relatively high comparing to other Al2O3 joints made of Sn alloys doped with Ti or Rear Earth elements. Thus, a new mechanism of ultrasonic soldering, i.e. building an oxide transitional layer on the surface of the solid, was revealed. We expect this sonochemical process to be applicable to other metal/oxide systems.
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High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis.
Cancer
PUBLISHED: 01-06-2014
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Telomere maintenance is crucial in carcinogenesis and tumor progression. The results of a previous study from the authors indicated that infection with high-risk human papillomavirus (HR-HPV) types 16, 18, and 58 was a risk factor for esophageal squamous cell carcinoma (ESCC) in the Shantou region of China. In the current study, the authors explored the association between HR-HPV infection, telomere length (TL), and DNA methylation and their significance in the prognosis of patients with ESCC.
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Interleukin-6 receptor blockade suppresses subretinal fibrosis in a mouse model.
Int J Ophthalmol
PUBLISHED: 01-01-2014
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To determine the involvement of the interleukin (IL)-6 with the development of experimental subretinal fibrosis in a mouse model.
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Role of Na+/Ca2+ exchanger (NCX) in modulating postovulatory aging of mouse and rat oocytes.
PLoS ONE
PUBLISHED: 01-01-2014
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We studied the role of the Na+/Ca2+ exchanger (NCX) in modulating oocyte postovulatory aging by observing changes in NCX contents and activities in aging mouse and rat oocytes. Whereas the NCX activity was measured by observing oocyte activation following culture with NCX inhibitor or activator, the NCX contents were determined by immunohistochemical quantification. Although NCX was active in freshly-ovulated rat oocytes recovered 13 h post hCG injection and in aged oocytes recovered 19 h post hCG in both species, it was not active in freshly-ovulated mouse oocytes. However, NCX became active when the freshly-ovulated mouse oocytes were activated with ethanol before culture. Measurement of cytoplasmic Ca2+ revealed Ca2+ increases always before NCX activation. Whereas levels of the reactive oxygen species (ROS) and the activation susceptibility increased, the density of NCX member 1 (NCX1) decreased significantly with oocyte aging in both species. While culture with H2O2 decreased the density of NCX1 significantly, culture with NaCl supplementation sustained the NCX1 density in mouse oocytes. It was concluded that (a) the NCX activity was involved in the modulation of oocyte aging and spontaneous activation; (b) ROS and Na+ regulated the NCX activity in aging oocytes by altering its density as well as functioning; and (c) cytoplasmic Ca2+ elevation was essential for NCX activation in the oocyte.
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Non-frozen preservation protocols for mature mouse oocytes dramatically extend their developmental competence by reducing oxidative stress.
Mol. Hum. Reprod.
PUBLISHED: 11-26-2013
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The objective of this study was to test whether aging induces oxidative stress (OS) during oocyte preservation at different temperatures and whether the oocyte competence can be extended by antioxidant supplementation. The increase in activation susceptibility was efficiently prevented when oocytes were preserved at 37°C for 9 h in HCZB medium with 10.27 mM pyruvate and 10 µM ?-tocopherol, at 25°C for 30 h with 20.27 mM pyruvate, and at 15°C for 96 h and at 5°C for 48 h with 10.27 mM pyruvate. Satisfactory blastocyst development was achieved after oocyte preservation at 37°C for 9 h, at 25°C for 30 h, at 15°C for 48 h and at 5°C for 24 h using the above protocols but with cysteamine/cystine supplementation. Transfer of blastocysts obtained from the above protocols showed no difference in pregnancy outcome between newly ovulated and preserved oocytes. Because oocytes preserved at 15°C for 48 h were fertilized after a 6-h recovery culture, aging of ovulated mouse oocytes has been successfully prevented for 54 h. Assays for ROS and glutathione indicated that in vitro preservation caused marked OS in oocytes. In conclusion, marked OS was observed following in vitro preservation of mature oocytes at different temperatures. Whereas any protocol that reduced OS could inhibit activation susceptibility, only those protocols that decreased OS while increasing glutathione synthesis could sustain oocyte competence.
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[Comparing hydroxyapatite coated versus non hydroxyapatite coated femoral stems in primary total hip arthroplasty: a meta analysis of randomized controlled trial].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 11-22-2013
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To evaluate the difference of clinical outcomes and radiological outcomes through meta-analysis on the total hip arthroplasty (THA) between hydroxyapatite(HA) coating and non-HA coating femoral stems.
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Inhibition of Toll-like receptor 2 reduces cardiac fibrosis by attenuating macrophage-mediated inflammation.
Cardiovasc. Res.
PUBLISHED: 11-20-2013
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Toll-like receptor 2 (TLR2) is an important player in innate immunity, and recent studies have identified TLR2 as a critical mediator in cardiovascular diseases. Here, we investigated the involvement of TLR2 in angiotensin (Ang) II-induced cardiac fibrosis and the underlying mechanisms.
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Potential association of pulmonary tuberculosis with genetic polymorphisms of toll-like receptor 9 and interferon-gamma in a Chinese population.
BMC Infect. Dis.
PUBLISHED: 10-28-2013
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Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI).
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Numerical evidences for a free energy barrier in starlike polymer brushes.
J Chem Phys
PUBLISHED: 10-15-2013
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The existence of a free energy barrier, which prohibits the upward motion of retracted molecules into the surface region of starlike polymer brushes, is analyzed through molecular dynamics simulations in good solvent. This barrier emerges at moderate and high grafting densities, as a result of a density-discontinuity at the branching points of the highly stretched starlike molecules. The vertical force profiles of brushes of varying densities are taken with the help of a probe-particle that is gradually moved into the brush, and the results are compared with the density profiles and their negative gradients which generate the local osmotic pressures. Chain expulsion simulations, supported by scaling theory, are conducted to understand the dynamics of individual molecules inside the brushes. We prove that the flip-rates between retracted and extended states, being of relevance for the generation of efficiently switchable, environment-responsive brush layers, are determined by the elastic tension of the stretched molecules.
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Dynamic expression pattern of Pde4d and its relationship with CpG methylation in the promoter during mouse embryo development.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-12-2013
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Mouse Pde4d is located on chromosome 13 and serves many functions in important physiological processes involving cyclic adenosine monophosphate. In this study, imprinting analysis indicated that Pde4d exhibits a dynamic and specific allelic expression pattern during embryo development. This showed paternal-origin sex bias in embryonic day 9.5 (E9.5) whole embryos and placenta, and biallelic expression in the major embryonic organs and placenta at E15.5. In situ hybridization determined the spatiotemporal expression pattern of Pde4d in mouse embryos from the mid- to late-embryonic stages. This demonstrated that Pde4d was widely expressed in the neural tissues, including the forebrain, midbrain, hindbrain, and neural tube, at the mid-embryonic stage. By the late-embryonic stage, Pde4d was extensively detected throughout the developing organism, including in the liver, brain, lung, kidney, and tongue. In addition, methylation analyses indicated that tissue-specific CpG methylation of the Pde4d promoter was correlated with Pde4d mRNA expression in major E15.5 tissues. Furthermore, stage-specific CpG methylation of the Pde4d promoter was associated with gene expression in the liver at three developmental stages. Our results suggest that Pde4d might serve specific biological functions in regulating the development process of the mouse embryo, and that CpG methylation of the Pde4d promoter may play an important role in regulating Pde4d at a transcriptional level.
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Assembly of catalase-based bioconjugates for enhanced anticancer efficiency of photodynamic therapy in vitro.
Chem. Commun. (Camb.)
PUBLISHED: 10-10-2013
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An oxygen generation core-shell structure uploading rose bengal has been fabricated by covalent assembly of catalase and alginate dialdehyde via Schiffs base. The composite can catalyze the decomposition of intracellular H2O2 to increase the concentration of O2, which effectively enhances the anticancer efficiency of photodynamic therapy in vitro.
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[Primary culture and multiple differentiation potency of mesenchymal stem cells from human umbilical cord].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 10-10-2013
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To establish a reliable method of isolation, culture and characterization of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and study its multiple differentiation potency.
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[Effect of radix sophorae flavescentis (RSF) mixture on mast cells in jejunal mucosa of mice infected by Cryptosporidium].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
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To elucidate the role of mast cells (MC) activation in the jejunal mucous membrane in the pathogenesis of cryptosporidiosis (CPS) and explore the mechanism of prevention and treatment of radix sophorae flavescetis(RSF) mixture on CPS.
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Effect of 5- AZn-2 -deoxycytidine on proliferation of human lung adenocarcinoma cell line A549 in vitro.
Asian Pac J Trop Med
PUBLISHED: 09-10-2013
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To explore effect of 5-AZn-2 -deoxycytidine on proliferation of human lung adenocarcinoma cell line A549 in vitro.
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Invasive candidiasis in intensive care units in China: in vitro antifungal susceptibility in the China-SCAN study.
J. Antimicrob. Chemother.
PUBLISHED: 09-04-2013
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The objectives of this study were to determine species distribution and in vitro antifungal susceptibility of Candida isolates identified in the multicentre China-SCAN study of invasive Candida infection (ICI) in intensive care units (ICUs) across China.
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Methylomics of gene expression in human monocytes.
Hum. Mol. Genet.
PUBLISHED: 07-29-2013
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DNA methylation is one of several epigenetic mechanisms that contribute to the regulation of gene expression; however, the extent to which methylation of CpG dinucleotides correlates with gene expression at the genome-wide level is still largely unknown. Using purified primary monocytes from subjects in a large community-based cohort (n = 1264), we characterized methylation (>485 000 CpG sites) and mRNA expression (>48K transcripts) and carried out genome-wide association analyses of 8370 expression phenotypes. We identified 11 203 potential cis-acting CpG loci whose degree of methylation was associated with gene expression (eMS) at a false discovery rate threshold of 0.001. Most of the associations were consistent in effect size and direction of effect across sex and three ethnicities. Contrary to expectation, these eMS were not predominately enriched in promoter regions, or CpG islands, but rather in the 3 UTR, gene bodies, CpG shores or offshore sites, and both positive and negative correlations between methylation and expression were observed across all locations. eMS were enriched for regions predicted to be regulatory by ENCODE (Encyclopedia of DNA Elements) data in multiple cell types, particularly enhancers. One of the strongest association signals detected (P < 2.2 × 10(-308)) was a methylation probe (cg17005068) in the promoter/enhancer region of the glutathione S-transferase theta 1 gene (GSTT1, encoding the detoxification enzyme) with GSTT1 mRNA expression. Our study provides a detailed description of the epigenetic architecture in human monocytes and its relationship to gene expression. These data may help prioritize interrogation of biologically relevant methylation loci and provide new insights into the epigenetic basis of human health and diseases.
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Inhibition of platelet activation by clopidogrel prevents hypertension-induced cardiac inflammation and fibrosis.
Cardiovasc Drugs Ther
PUBLISHED: 07-27-2013
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Platelets are essential for primary hemostasis; however, platelet activation also plays an important proinflammatory role. Inflammation promotes the development of cardiac fibrosis and heart failure induced by hypertension. In this study, we aimed to determine whether inhibiting platelet activation using clopidogrel could inhibit hypertension-induced cardiac inflammation and fibrosis.
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What is Visualize?

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

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

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