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Find video protocols related to scientific articles indexed in Pubmed.
Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis.
Clin. Cancer Res.
PUBLISHED: 10-27-2014
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Purpose: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival. Experimental Design: We searched PUBMED and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression free survival (PFS). Results: From 1201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and non-carriers in ovarian or breast cancer patients. Fourteen studies examined ovarian cancer survival and 13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2 mutation carriers had better OS (HR: 0.76, 95% CI: 0.70-0.83 for BRCA1 mutation carriers; HR: 0.58, 95% CI: 0.50-0.66 for BRCA2 mutation carriers) and PFS (HR: 0.65, 95% CI: 0.52-0.81 for BRCA1 mutation carriers; HR: 0.61, 95% CI: 0.47-0.80 for BRCA2 mutation carriers) compared to non-carriers, regardless of tumor stage, grade, or histologic subtype. Among breast cancer patients, BRCA1 mutation carriers had worse OS (HR: 1.50, 95%CI: 1.11-2.04) than non-carriers, but were not significantly different from non-carriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis. Conclusions: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancer and these mutations should be taken into account when devising appropriate therapeutic strategies.
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Association of Microtubule associated protein tau/Saitohin (MAPT/STH) MAPT_238bp/STH Q7R polymorphisms and Parkinson's disease: A meta-analysis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-27-2014
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The association between the extended tau haplotype (H1) and susceptibility to Parkinson's disease (PD) was controversial in previous studies. Therefore, we performed this meta-analysis to determine whether the additional polymorphisms in MAPT_238bp and STH Q7R which both included in H1 are associated with PD.
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Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons.
Eur Arch Otorhinolaryngol
PUBLISHED: 08-31-2014
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Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca(2+)-activated K(+) channel attributes to the medial vestibular nucleus (MVN) neural activity in VBI. To address this issue, we performed whole-cell patch clamp and quantitative polymerase chain reaction (qPCR) to examine the effects of hypoxia on neural activity and the changes of the large conductance Ca(2+) activated K(+) channels (BKCa channels) in the MVN neurons in brain slices of male C57BL/6 mice. Brief hypoxic stimuli of the brain slices containing MVN were administrated by switching the normoxic artificial cerebrospinal fluid (ACSF) equilibrated with 21 % O2/5 % CO2 to hypoxic ACSF equilibrated with 5 % O2/5 % CO2 (balance N2). 3-min hypoxia caused a depolarization in the resting membrane potential (RM) in 8/11 non-spontaneous firing MVN neurons. 60/72 spontaneous firing MVN neurons showed a dramatic increase in firing frequency and a depolarization in the RM following brief hypoxia. The amplitude of the afterhyperpolarization (AHPA) was significantly decreased in both type A and type B spontaneous firing MVN neurons. Hypoxia-induced firing response was alleviated by pretreatment with NS1619, a selective BKCa activator. Furthermore, brief hypoxia caused a decrease in the amplitude of iberiotoxin-sensitive outward currents and mRNA level of BKCa in MVN neurons. These results suggest that BKCa channels protect against abnormal MVN neuronal activity induced by hypoxia, and might be a key target for treatment of vertigo and hearing loss in VBI.
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Tamoxifen represses alcohol-induced transcription of RNA polymerase III-dependent genes in breast cancer cells.
Oncotarget
PUBLISHED: 08-23-2014
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Alcohol consumption in women has been associated with an increased risk of breast cancer, particular in estrogen receptor positive (ER+) cases. Deregulation of RNA polymerase III-dependent (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, leading to an increase in translational capacity to promote cell transformation and tumor formation. Our recent studies demonstrated that alcohol induces Brf1 expression and Pol III gene transcription via ER. Here, we report that Tamoxifen (Tam) inhibits the induction of Brf1 and Pol III genes in ER+ breast cancer cells. Further analysis indicates that alcohol increases c-Jun expression to upregulate the transcription of Brf1 and Pol III genes, whereas Tam reduces c-Jun expression to repress the transcription of Brf1. Repression of cJun decreases cellular levels of ER? and Brf1. Alcohol-dependent increased occupancy of Brf1 in Pol III gene promoters is reduced by Tam. The repression of Brf1 and Pol III genes by Tam reduces alcohol-induced cell proliferation and colony formation. Together, these results indicate that Tam inhibits alcohol-induced Brf1 expression through c-Jun and ER? to downregulate Pol III gene transcription. Our studies uncover a new mechanism of Tam-treated ER+ breast cancer, by which Tam inhibits tumor growth through repressing Pol III gene transcription.
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Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer's Disease?
Front Aging Neurosci
PUBLISHED: 08-19-2014
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA) is a natural inhibitor of acetylcholinesterase (AChE) derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta). It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has "non-cholinergic" effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-d-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.
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Prognostic value of red blood cell distribution width for patients with heart failure: a systematic review and meta-analysis of cohort studies.
PLoS ONE
PUBLISHED: 08-18-2014
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Multiple studies have investigated the prognostic role of red blood cell distribution width (RDW) for patients with heart failure (HF), but the results have been inconsistent. The aim of the present study was to estimate the impact of RDW on the prognosis of HF by performing a systematic review and meta-analysis.
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Congenital duodenal obstruction in neonates: a decade's experience from one center.
World J Pediatr
PUBLISHED: 08-15-2014
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Congenital duodenal obstruction (CDO) is one of the most common anomalies in newborns, and accounting for nearly half of all cases of neonatal intestinal obstruction. This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes.
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Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats.
Mol. Neurobiol.
PUBLISHED: 08-13-2014
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Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad-hepcidin emerges as a new pharmacological treatment and prevention for iron-associated neurodegenerative disorders.
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Arsenite promotes intestinal tumor cell proliferation and invasion by stimulating epithelial-to-mesenchymal transition.
Cancer Biol. Ther.
PUBLISHED: 07-10-2014
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Arsenite (AS) is a ubiquitous environmental element that is widely present in food, soil, and water. Environmental exposure to AS represents a major global health concern, because AS is a well-established human carcinogen. We hypothesize that low concentration of AS could enhance metastasis and proliferation of transformed cancer cells by promoting EMT. To test this hypothesis, we treated human colorectal cancer cells with low concentration of AS, and then measured the multiple readouts of cell viability, proliferation, migration, and adhesion in vitro and in vivo. Collectively, our data indeed strongly support our hypothesis and shed novel light into this important pathophysiological process. These novel insights are not only of high interests to basic cancer research, but may also have direct implications in cancer prevention and treatment.
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Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjögren's syndrome.
Clin. Biochem.
PUBLISHED: 06-24-2014
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The red blood cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) are increased in various inflammation related diseases, but their clinical significance in primary Sjögren's syndrome (pSS) has not been reported. The aim of the present study was to investigate the clinical significance of RDW and NLR in pSS patients.
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Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-?B signaling in activated HMC-1 human mast cells.
Pharm Biol
PUBLISHED: 06-13-2014
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Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.
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Removal of Cu(II) and Cr(VI) from wastewater by an amphoteric sorbent based on cellulose-rich biomass.
Carbohydr Polym
PUBLISHED: 05-13-2014
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A cellulose-rich biomass was modified as a new amphoteric sorbent to eliminate toxic Cu(II) and Cr(VI) from wastewater. The product (WSCA, which stands for modified wheat straw containing both cationic and anionic characters) presents high sorption capacities for the two ions which was evidenced by the comparison with unmodified wheat and other similar samples. Kinetic data and sorption equilibrium isotherms were conducted in batch process. The sorption kinetic analysis revealed that sorption of Cu(II) and Cr(VI) followed the pseudo second-order model well during the whole sorption process. The linear Langmuir isotherm model could perfectly describe the equilibrium data for Cu(II), while the sorption data of Cr(VI) were well fitted by the Freundlich. Results of the static test illustrated the complicated interactions between Cr(VI)/Cu(II) and WSCA including complexation and/or electrostatic attraction mechanisms.
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Cytochrome P450 1A1 (CYP1A1) polymorphism and susceptibility to esophageal cancer: an updated meta-analysis of 27 studies.
Tumour Biol.
PUBLISHED: 04-29-2014
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Cytochrome P450 1A1 (CYP1A1) polymorphisms are known to play a crucial role in the development and metastasis of malignant diseases including esophageal cancer. However, the results of previous studies investigating the association between CYP1A1 polymorphisms and esophageal cancer risk have been inconsistent. This meta-analysis of 27 eligible studies, encompassing 4,215 esophageal cancer cases and 6,339 control subjects, pooled the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CI) to assess this association. The effects of ethnicity (Caucasian and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) were considered in subgroup analyses. A significant association was observed between the CYP1A1 Ile/Val gene polymorphism and esophageal cancer in all of the genetic models (Ile/Val vs. Ile/Ile, OR?=?1.41, 95 % CI?=?1.25-1.58; Val/Val vs. Ile/Ile, OR?=?1.94, 95 % CI?=?1.34-2.82; Ile/Val?+?Val/Val vs. Ile/Ile, OR?=?1.49, 95 % CI?=?1.33-1.66). The subgroup analysis based on ethnicity showed that the association between the CYP1A1 Ile/Val polymorphism and esophageal cancer existed in Asian and Caucasian populations. However, no association was observed between the CYP1A1 MspI polymorphism and esophageal cancer in either subgroup or in the overall population. These results suggested that the CYP1A1 Ile/Val polymorphism was associated with an increased risk of esophageal cancer, whereas the CYP1A1 MspI polymorphism may not have increased susceptibility to esophageal cancer. Further studies are required to confirm these findings.
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Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.
J Neural Transm
PUBLISHED: 04-21-2014
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Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95 % confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95 % CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95 % CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95 % CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.
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SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide.
J Control Release
PUBLISHED: 04-10-2014
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Breast cancer is the most common malignant cancer and is the leading cause of cancer death among females. Molecular imaging is a promising approach for the early detection and staging of breast cancer as well as for assessing therapeutic responses. Tumor-targeting peptides are effective targeting vehicles for molecular imaging. Here, we identified a breast cancer-targeting peptide CLKADKAKC (CK3) contains a cryptic C-end rule motif that may mediate its binding to neuropilin-1 (NRP-1), an attractive therapeutic target which expression was associated with poor outcome of the patients with breast cancer. Phage CK3 bound to NRP-1-positive breast cancer cells, which could be inhibited by peptide CK3 in a dose-dependent manner or by knock-down NRP-1 expression. Consistently, NRP-1 overexpression in cells increased the binding of phage CK3. Furthermore, peptide CK3 co-localized with NRP-1. Importantly, unlike previously reported NRP-1-targeting peptides with exposed C-end rule motifs, peptide CK3 did not penetrate into lungs and heart in vivo, which could make it more clinically applicable. Single-photon emission CT (SPECT) and near-infrared fluorescence (NIRF) imaging showed enrichment of peptide CK3 to the xenograft tumors in nude mice. In conclusion, as a novel NRP-1-targeting peptide, peptide CK3 could be used for breast cancer molecular imaging, which may represent a new avenue for breast cancer diagnostics, staging and assessments of therapeutic response.
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Angiotensin II inhibits iron uptake and release in cultured neurons.
Neurochem. Res.
PUBLISHED: 03-13-2014
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Based on the well-confirmed roles of angiotensin II (ANGII) in iron transport of peripheral organs and cells, the causative link of excess brain iron with and the involvement of ANGII in neurodegenerative disorders, we speculated that ANGII might also have an effect on expression of iron transport proteins in the brain. In the present study, we investigated effects of ANGII on iron uptake and release using the radio-isotope methods as well as expression of cell iron transport proteins by Western blot analysis in cultured neurons. Our findings demonstrated for the first time that ANGII significantly reduced transferrin-bound iron and non-transferrin bound iron uptake and iron release as well as expression of two major iron uptake proteins transferrin receptor 1 and divalent metal transporter 1 and the key iron exporter ferroportin 1 in cultured neurons. The findings suggested that endogenous ANGII might have a physiological significance in brain iron metabolism.
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Ochrovirga pacifica gen. nov., sp. nov., a novel agar-lytic marine bacterium of the family Flavobacteriaceae isolated from a seaweed.
Curr. Microbiol.
PUBLISHED: 03-10-2014
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A strain designated as S85(T) was isolated from a seaweed collected from coastal area of Chuuk State in Micronesia. The strain was gram-negative, rod-shaped, and non-motile and formed yellow colonies on the SWY agar (0.2 % yeast extract and 1.5 % agar in seawater) and Marine agar 2216. The strain grew at pH 5-9 (optimum, pH 8), at 15-40 °C (optimum, 25-28 °C), and with 1-9 % (w/v) NaCl (optimum, 3 %). The phylogenetic analysis based on 16S rRNA gene sequence showed that strain S85(T) was related to Lutibacter litoralis CL-TF09(T) and Maritimimonas rapanae A31(T) with 91.4 % and with 90.5 % similarity, respectively. The dominant fatty acids were iso-C15:0, iso-C15:0 3-OH and iso-C17:0 3-OH, C16:0 3-OH and summed feature 3 (C16:1 ?7c and/or iso-C15:0 2-OH). The major isoprenoid quinone was MK-6. The DNA G+C content of the type strain was 34.6 mol %. The major polar lipids were phosphatidylethanolamine, an unknown glycolipid and two unknown polar lipids. Based on this polyphasic taxonomic data, strain S85(T) stands for a novel species of a new genus, and we propose the name Ochrovirga pacifica gen. nov., sp. nov. The type strain of O. pacifica is S85(T) (=KCCM 90106 =JCM 18327(T)).
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Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals.
Balkan Med J
PUBLISHED: 03-01-2014
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Recent studies have reported contrasting results regarding the association of polymorphisms in two integrin genes, ITGA2 and ITGB3, with ischemic stroke.
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Lipopolysaccharides Upregulate Hepcidin in Neuron via Microglia and the IL-6/STAT3 Signaling Pathway.
Mol. Neurobiol.
PUBLISHED: 02-28-2014
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Neuroinflammation is closely related to brain iron homeostasis. Our previous study demonstrated that lipopolysaccharides (LPS) can regulate expression of iron-regulatory peptide hepcidin; however, the mechanism is undefined. Here, we demonstrated that intracerebroventricular injection of LPS in rat brain upregulated hepcidin and downregulated ferroportin 1 in the cortex and substantia nigra. LPS increased hepcidin expression in neurons only when they were co-cultured with BV-2 microglia, and the upregulation was suppressed by IL-6 neutralizing antibody in vitro. In addition, IL-6 but not IL-1?, IL-1?, or tumor necrosis factor-alpha increased hepcidin expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cortical neurons and MES23.5 dopaminergic neurons. These effects were blocked by the STAT3 inhibitor, stattic. Our results show that neurons are the major source of increased hepcidin expression in response to LPS challenge but microglia play a key mediator role by releasing IL-6 and recruiting the STAT3 pathway. We conclude that LPS upregulates hepcidin expression in neurons via microglia and the IL-6/STAT3 signaling pathway.
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Complement C5a is detrimental to histological and functional locomotor recovery after spinal cord injury in mice.
Neurobiol. Dis.
PUBLISHED: 02-23-2014
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Based on the studies on the role of complements C3, C1q and factor B, we hypothesized that complement C5a is detrimental to locomotor recovery at the early stage of secondary injury after spinal cord injury (SCI). To test this hypothesis, we investigated the effect of inhibition of complement C5a receptor (C5aR) by using C5aR antagonist PMX53 (C5aRA) and deficiency of complement C5a receptor (C5aR-/- mice) on histological and locomotor recovery after SCI in mice. We demonstrated that the Basso Mouse Scale scores in the mice injected with C5aRA (C5aRA-mice) at 45min before and 24h after SCI and the C5aR-/- mice were markedly higher than those in the mice treated with saline (Saline-mice) and the C5aR+/+ mice respectively between 7 and 28days after SCI. Also, expression of TNF-? and IL-1? in C5aRA-mice was significantly lower than that in Saline-mice from 1 to 24h after SCI. In addition, the percentage of microglia/macrophage in C5aRA mice and C5aR-/- mice was significantly lower than those in their corresponding control groups from 1 to 14days after SCI. Furthermore, C5aRA mice and C5aR-/- mice had less GFAP expression in the injured spinal cord epicenter as compared to Saline mice and C5aR+/+ mice at day 28 after SCI. These findings provided evidence that inhibition or deficiency of C5aR could significantly improve histological and functional locomotor recovery after SCI in mice.
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Drosophila models for studying iron-related neurodegenerative diseases.
Sheng Li Xue Bao
PUBLISHED: 02-21-2014
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In recent years, iron has been regarded as a common pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Friedreich's ataxia (FRDA). A number of genes involved in iron transport, storage and regulation have been found associated with initiation and progression of neurodegeneration. However, whether iron abnormalities represent a primary or secondary event still remains unknown. Due to the limitation in transgenic rodent model construction and transfection systems, the progress in unraveling the pathogenic role of different iron-related proteins in neurodegenerative diseases has been slow. Drosophila melanogaster, a simple organism which has a shorter lifespan and smaller genome with many conserved genes, and captures many features of human nervous system and neurodegeneration, may help speed up the progress. The characteristics that spatial- and temporal-specific transgenic Drosophila can be easily constructed and raised in large quantity with phenotype easily determined turn Drosophila into an excellent in vivo genetic system for screening iron-related modifiers in different neurodegenerative conditions and hence provide a better picture about the pathogenic contribution of different iron-related protein abnormalities. It is believed that identification of important iron-related genes that can largely stop or even reverse degenerative process in Drosophila models may lead to development of novel therapeutic strategies against neurodegenerative diseases.
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Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma.
BMC Cancer
PUBLISHED: 02-16-2014
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Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).
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Subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy.
Eur Arch Otorhinolaryngol
PUBLISHED: 01-28-2014
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The objective of the study is to document the role of subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy. Twenty-two cases with idiopathic recurrent facial palsy, which had over 95 % degeneration of facial nerve on electroneurography, were included in the study, among which 12 accepting subtotal facial nerve decompression were involved in surgery group, and 10 who refused surgery and received prednisolone were classified into control group. The recurrence of facial palsy and facial nerve recovery was compared. The patients were followed up for 5.3 years (range 3-8 years) and 5.2 years (range 3-7 years) in surgery group and control group, respectively. Further recurrence of facial palsy occurred in none of 12 patients (0 %) in surgery group in contrast to 4 of 10 cases (40 %) in control group, with statistical difference (p < 0.05). 11 of 12 cases (91.7 %) in surgery group recovered to Grade I or Grade II compared to 3 of 10 cases (30.0 %) in control group, with significant difference (p < 0.05). Subtotal facial nerve decompression is effective to prevent further recurrence of facial palsy and promote facial nerve recovery of severe idiopathic recurrent facial palsy.
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Angiotensin II inhibits uptake of transferrin-bound iron but not non-transferrin-bound iron by cultured astrocytes.
Neuropeptides
PUBLISHED: 01-25-2014
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The existence of all components of the renin-angiotensin system (RAS) and the iron metabolism system, and the recent findings on the functions of angiotensin II (ANGII) in peripheral iron metabolism imply that ANGII might play a role in iron homeostasis by regulating expression of iron transport proteins in the brain. Here, we investigated effects of ANGII on uptake and release of iron as well as expression of cell iron transport proteins in cultured astrocytes. We demonstrated that ANGII could significantly inhibit transferrin-bound iron (Tf-Fe) uptake and iron release as well as the expression of transferrin receptor 1 (TfR1) and the iron exporter ferroportin 1 (Fpn1) in cultured astrocytes. This indicated that the inhibitory role of ANGII on Tf-Fe uptake and iron release is mediated by its negative effect on the expression of TfR1 and Fpn1. We also provided evidence that ANGII had no effect on divalent metal transporter 1 (DMT1) expression as well as non-transferrin-bound iron (NTBI) uptake in the cells. Our findings showed that ANGII has a role to affect expression of iron transport proteins in astrocytes in vitro and also suggested that ANGII might have a physiological function in brain iron homeostasis.
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Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.
Rheumatology (Oxford)
PUBLISHED: 11-05-2013
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Objectives. Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA.Methods. Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-?, IFN-? and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined.Results. The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-?, IFN-? and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies.Conclusion. Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.
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Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells.
Mar Drugs
PUBLISHED: 10-08-2013
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Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death.
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[Abnormal expression of miR-let-7b in primary biliary cirrhosis and its clinical significance].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 10-01-2013
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To evaluate the expression of microRNA (miR)-let-7b in peripheral blood cells of patients with primary biliary cirrhosis (PBC) and investigate its relationship to clinical disease parameters.
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Iron and Intracerebral Hemorrhage: From Mechanism to Translation.
Transl Stroke Res
PUBLISHED: 09-17-2013
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Intracerebral hemorrhage (ICH) is a leading cause of morbidity and mortality around the world. Currently, there is no effective medical treatment available to improve functional outcomes in patients with ICH due to its unknown mechanisms of damage. Increasing evidence has shown that the metabolic products of erythrocytes are the key contributor of ICH-induced secondary brain injury. Iron, an important metabolic product that accumulates in the brain parenchyma, has a detrimental effect on secondary injury following ICH. Because the damage mechanism of iron during ICH-induced secondary injury is clear, iron removal therapy research on animal models is effective. Although many animal and clinical studies have been conducted, the exact metabolic pathways of iron and the mechanisms of iron removal treatments are still not clear. This review summarizes recent progress concerning the iron metabolism mechanisms underlying ICH-induced injury. We focus on iron, brain iron metabolism, the role of iron in oxidative injury, and iron removal therapy following ICH, and we suggest that further studies focus on brain iron metabolism after ICH and the mechanism for iron removal therapy.
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[Clinical evaluation on aesthetic effect of custom pressable metal ceramic abutment for dental implant restoration in anterior zone].
Hua Xi Kou Qiang Yi Xue Za Zhi
PUBLISHED: 09-03-2013
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OBJECTIVE To evaluate the aesthetic effect of restorations with custom pressable metal ceramic abutments for defective soft and hard tissue in the maxillary anterior zone.
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Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging of early acute pancreatitis.
Biomaterials
PUBLISHED: 08-14-2013
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Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly dependent on serum enzyme analysis and imaging techniques that are too low in sensitivity and specificity to accurately and promptly diagnose AP. The lack of early diagnostic tools highlights the need to search for a highly effective and specific diagnostic method. In this study, we synthesized a conditionally activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a diagnostic tool for the early identification of AP. Gadolinium diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA exhibited low cytotoxicity and excellent biocompatibility when characterized in vitro and in vivo studies. L-arginine induced a gradual increase in the intensity of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to detect early AP.
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[Oxidative damage effect of the serum of severe preeclamptic patients on human umbilical vein endothelial cell].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 07-16-2013
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To investigate oxidative damage effect of the serum of severe preeclamptic patients on human umbilical vein endothelial cells (HUVEC).
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The effect of regions flanking target site on siRNA potency.
Genomics
PUBLISHED: 07-14-2013
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For a successful RNA interference (RNAi) experiment, selecting the small interference RNA (siRNA) candidates which maximize the knock down effect of the given gene is the critical step. Although various computational approaches have been attempted, the design of efficient siRNA candidates is far from satisfactory yet. In this study, we proposed a novel feature selection algorithm of combined random forest and support vector machine to predict active siRNAs. Using a publically available dataset, we demonstrated that the predictive accuracy would be markedly improved when the context sequence features outside the target site were included. The Pearson correlation coefficient for regression is as high as 0.721, compared to 0.671, 0.668, 0.680, and 0.645, for Biopredsi, i-score, ThermoComposition21 and DSIR, respectively. It revealed that siRNA-target interaction requires appropriate sequence context not only in the target site but also in a broad region flanking the target site.
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Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 07-12-2013
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Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimers disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimers disease.
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Risk factors of hospital mortality after re-laparotomy for post-hepatectomy hemorrhage.
World J Surg
PUBLISHED: 07-02-2013
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Post-hepatectomy hemorrhage (PHH) requiring re-laparotomy is a life-threatening situation and is associated with a considerably high hospital mortality rate. However, risk factors of hospital mortality in patients with this condition have not yet been investigated.
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Assessment of heavy metal contamination and bioaccumulation in soybean plants from mining and smelting areas of southern Hunan Province, China.
Environ. Toxicol. Chem.
PUBLISHED: 06-25-2013
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Soybean is one of most important dicotyledonous food crops and is widely planted in Hunan Province, China. However, mining activity causes contamination of the soil in which soybean grows. To assess the impact of mining-induced soil contamination on soybean plants, a geoaccumulation index (I(geo)) was used to evaluate 20 soil samples from the mining and smelting areas of southern Hunan Province. The results indicated that Zn ranged from uncontaminated to a moderately contaminated level (I(geo)<1), Pb was at a strongly contaminated level (I(geo)>3), and Cd was at an extremely contaminated level (I(geo)>5) across the whole study area. All of the studied soybean plants were affected by heavy metal Pb and Cd contamination, and the mean concentrations in seeds were 13.9 mg/kg and 2.95 mg/kg, respectively. The estimated bioconcentration factor and translocation factor showed that the soybean roots had a strong Cd bioconcentration capability and the stems had a strong translocation capability in terms of Pb, Cd, and Zn, with preferential transference of metals to the soybean leaves. The bioavailable fraction in the soil was characterized by the exchangeable fraction of heavy metals. In the present study, the bioavailable fractions of Pb, Cd, and Zn were significantly positively correlated with the concentration of these metals in soybean tissues (roots, stems, leaves, husks, and seeds).
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Role of phosphorylated histone H3 serine 10 in DEN-induced deregulation of Pol III genes and cell proliferation and transformation.
Carcinogenesis
PUBLISHED: 06-17-2013
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The products of Pol III genes (RNA polymerase III-dependent genes), such as tRNAs and 5S rRNA, are elevated in both transformed and tumor cells suggesting that they play a crucial role in tumorigenesis. An increase in Brf1 (TFIIIB-related factor 1), a subunit of TFIIIB, augments Pol III gene transcription and is sufficient for cell transformation and tumor formation. We have demonstrated that enhancement of Brf1 and Pol III gene expression is associated with the occurrences of hepatocellular carcinoma (HCC) in mice. This suggests that Brf1 may be a key molecule during HCC development. Diethylnitrosamine (DEN), a chemical carcinogen, has been used to induce HCC in rodents. To determine the role of Brf1 and the epigenetic-regulating events in cell proliferation and transformation, hepatocytes were treated with DEN. The results indicate that DEN increases proliferation and transformation of AML-12 cells. DEN enhanced Brf1 expression and tRNA(Leu) and 5S rRNA transcription, as well as H3S10ph (phosphorylation of histone H3 serine 10). Interestingly, DEN-induced Pol III gene transcription and H3S10ph in tumor cells of liver are significantly higher than in non-tumor cells. Inhibition of H3S10ph by H3S10A attenuates the induction of Brf1 and Pol III genes. Further analysis indicates that H3S10ph occupies the promoters of Brf1 and Pol III genes to modulate their expression. Blocking H3S10ph represses cell proliferation and transformation. These results demonstrate that DEN induces H3S10ph, which mediate Brf1 expression, including but not limited Brf1-dependent genes, to upregulate Pol III gene transcription, resulting in an increase in cell proliferation and transformation.
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Expression of beclin 1 in bladder cancer and its clinical significance.
Int. J. Biol. Markers
PUBLISHED: 06-01-2013
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The aim of this study is to explore the expression of beclin 1, an autophagy gene, in bladder cancer and to evaluate its clinical and prognostic significance in patients with bladder cancer.
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[Species study on Chinese medicine leech and discussion on its resource sustainable utilization].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 05-31-2013
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Through systemically sorting and studying literature of Chinese medicine, this article pointed out that leech used by the traditional Chinese medicine in ancient time has the features of small, living in water, able to suck blood of animal and people. The species of leeches having these features were Hirudo nipponia Whitman, H. pulchra Song, Poecilobdella nanjingensis sp. Nov. , P. manillensis (Lesson) and P. hubeiensis Yang, which were not fully coincidence with the species recorded in Chinese Pharmacopeia of 2010 edition. We suggests that species of leech in Chinese Pharmacopeia be revised: H. nipponica Whitman should be kept, P. manillensis (Lesson) should be added in, Whitmania pigra Whitman and W. acranulata Whitma should be temporarily reserved, and H. pulchra Song, P. nanjingensis sp. Nov. , and P. hubeiensis Yang should be considered.
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[Principles for molecular identification of traditional Chinese materia medica using DNA barcoding].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 05-16-2013
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Since the research of molecular identification of Chinese Materia Medica (CMM) using DNA barcode is rapidly developing and popularizing, the principle of this method is approved to be listed in the Supplement of the Pharmacopoeia of the Peoples Republic of China. Based on the study on comprehensive samples, the DNA barcoding systems have been established to identify CMM, i.e. ITS2 as a core barcode and psbA-trnH as a complementary locus for identification of planta medica, and COI as a core barcode and ITS2 as a complementary locus for identification of animal medica. This article introduced the principle of molecular identification of CMM using DNA barcoding and its drafting instructions. Furthermore, its application perspective was discussed.
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Thermal stability of glucokinases in Thermoanaerobacter tengcongensis.
Biomed Res Int
PUBLISHED: 04-29-2013
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In the genome of Thermoanaerobacter tengcongensis, three genes belonging to ROK (Repressor, ORF, and Kinase) family are annotated as glucokinases (GLKs). Using enzyme assays, the three GLKs were identified as ATP-dependent GLK (ATP-GLK), ADP-dependent GLK (ADP-GLK), and N-acetyl-glucosamine/mannosamine kinase (glu/man-NacK). The kinetic properties of the three GLKs such as K(m), V(max), optimal pH, and temperature were characterized, demonstrating that these enzymes performed the specific functions against varied substrates and under different temperatures. The abundance of ATP-GLK was attenuated when culture temperature was elevated and was almost undetectable at 80°C, whereas the ADP-GLK abundance was insensitive to temperature changes. Using degradation assays, ATP-GLK was found to have significantly faster degradation than ADP-GLK at 80°C. Co-immunoprecipitation results revealed that heat shock protein 60 (HSP60) could interact with ATP-GLK and ADP-GLK at 60 and 75°C, whereas at 80°C, the interaction was only effectively with ADP-GLK but not ATP-GLK. The functions of GLKs in T. tengcongensis are temperature dependent, likely regulated through interactions with HSP60.
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Discriminating bioluminescent proteins by incorporating average chemical shift and evolutionary information into the general form of Chous pseudo amino acid composition.
J. Theor. Biol.
PUBLISHED: 04-24-2013
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Bioluminescent proteins are highly sensitive optical reporters for imaging in live animals; they have been extensively used in analytical applications in intracellular monitoring, genetic regulation and detection, and immune and binding assays. In this work, we systematically analyzed the sequence and structure information of 199 bioluminescent and nonbioluminescent proteins, respectively. Based on the results, we presented a novel method called auto covariance of averaged chemical shift (acACS) for extracting structure features from a sequence. A classifier of support vector machine (SVM) fusing increment of diversity (ID) was used to distinguish bioluminescent proteins from nonbioluminescent proteins by combining dipeptide composition, reduced amino acid composition, evolutionary information, and acACS. The overall prediction accuracy evaluated by jackknife validation reached 82.16%. This result was better than that obtained by other existing methods. Improvement of the overall prediction accuracy reached up to 5.33% higher than those of the SVM and auto covariance of sequential evolution information by 10-fold cross-validation. The acACS algorithm also outperformed other feature extraction methods, indicating that our approach is better than other existing methods in the literature.
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Correlation between interleukin-18 promoter -607C/A polymorphism and susceptibility to ischemic stroke.
Braz. J. Med. Biol. Res.
PUBLISHED: 03-18-2013
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Single nucleotide polymorphisms in the promoter region of interleukin-18 (IL-18), an inflammatory cytokine, have been linked to susceptibility to many diseases, including cancer and immune dysfunction. Here, we explored the potential association between the IL-18 -607C/A (rs1946518) promoter region polymorphism and susceptibility to ischemic stroke (IS). This locus was amplified from peripheral blood samples of 386 IS patients (cases) and 364 healthy individuals (controls) by the polymerase chain reaction with sequence-specific primers. Significant differences were observed by the ?2 test in the -607C/A (rs1946518) genotype and allele frequencies between cases and controls (P < 0.05). Furthermore, after excluding for age, gender, smoking status, and hypertension, logistic regression indicated that IS susceptibility of -607C carriers increased 1.6 times (OR = 1.601, 95%CI = 1.148-2.233, P = 0.006) compared to -607A carriers. Additionally, similar increases in IS risk were noted for male patients or patients less than 65 years old. In conclusion, IL-18 -607C/A (rs1946518) promoter polymorphism is associated with IS susceptibility, and the C allele may confer increased IS risk.
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Low expression of PTK6/Brk predicts poor prognosis in patients with laryngeal squamous cell carcinoma.
J Transl Med
PUBLISHED: 03-03-2013
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Protein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (Brk), was a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. The deregulated expression of PTK6 was observed in various human cancers. However, little was known about PTK6 expression and its clinicopathological significance in human laryngeal squamous cell carcinoma (LSCC).
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Open kyphoplasty in the treatment of a painful vertebral lytic lesion with spinal cord compression caused by multiple myeloma: A case report.
Oncol Lett
PUBLISHED: 02-13-2013
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Multiple myeloma is a fatal hematological malignancy, with the most common localization being the spine. A 72-year-old male patient presented with progressive back pain and dysfunction of ambulation. Spinal computed tomography (CT) and magnetic resonance imaging (MRI) showed spinal cord compression at the T9-T10 level due to an extensive epidural mass in the spinal canal, a large lytic mass of T7-T12 with extraosseous extension and involvement of T9 and T10 vertebral pedicle and posterior wall. The patient underwent posterior spinal decompression and kyphoplasty of T9 and T10 with pedicle screw fixation in T7, T8, T11 and T12. Pain and neural function were improved significantly postoperatively. To our knowledge, such methods have rarely been used to treat a patient with intractable back pain and neurological compromise with multiple myeloma or spinal metastases.
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The role of Siglec-1 and SR-BI interaction in the phagocytosis of oxidized low density lipoprotein by macrophages.
PLoS ONE
PUBLISHED: 02-07-2013
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Macrophages play a proatherosclerotic role in atherosclerosis via oxLDL uptake. As an adhesion molecular of I-type lectins, Siglec-1 is highly expressed on circulating monocytes and plaque macrophages of atherosclerotic patients, but the exact role of Siglec-1 has not been elucidated.
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Elk1 and AP-1 sites in the TBP promoter mediate alcohol-induced deregulation of Pol III-dependent genes.
Gene
PUBLISHED: 02-05-2013
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The major risk factors for hepatocellular carcinoma (HCC) are chronic liver diseases that include hepatitis B, hepatitis C, alcoholic liver disease and non-alcoholic steatohepatitis. However, the mechanisms of alcohol-associated HCC remain to be elucidated. The products of RNA Pol III (RNA polymerase III) dependent genes are elevated in both transformation cells and tumor cells. TBP (TATA-box binding protein) is a central transcription factor, which regulates Pol I, Pol II and Pol III gene activity. Our studies have demonstrated that alcohol increases TBP expression and Pol III gene transcription to promote liver tumor formation. We continue to investigate how ethanol mediates TBP expression. Here, we report that ethanol induces TBP promoter activity and the induction is ethanol dose dependent. Blocking the JNK1 pathway by a chemical inhibitor and siRNA reduces this ethanol-induced activity. Furthermore, mutating G>A at a -46 bp Elk1 binding site of the TBP promoter or mutating AP-1 binding site at -37 bp (A>G) and -38 bp (C>T) reduces the TBP promoter activity. Mutation of both Elk1 and AP-1 binding sites dramatically represses this induction. Together, these studies demonstrate that, for the first time, alcohol increases Pol III gene transcription through a response element, which is composed of the overlapping Elk1 and AP-1 binding sites of the TBP promoter and affected by alcohol. It suggests that these binding sites may play a critical role in alcohol-induced deregulation of Pol III genes in liver tumor development.
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The road for nanomaterials industry: a review of carbon nanotube production, post-treatment, and bulk applications for composites and energy storage.
Small
PUBLISHED: 02-04-2013
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The innovation on the low dimensional nanomaterials brings the rapid growth of nano community. Developing the controllable production and commercial applications of nanomaterials for sustainable society is highly concerned. Herein, carbon nanotubes (CNTs) with sp(2) carbon bonding, excellent mechanical, electrical, thermal, as well as transport properties are selected as model nanomaterials to demonstrate the road of nanomaterials towards industry. The engineering principles of the mass production and recent progress in the area of CNT purification and dispersion are described, as well as its bulk application for nanocomposites and energy storage. The environmental, health, and safety considerations of CNTs, and recent progress in CNT commercialization are also included. With the effort from the CNT industry during the past 10 years, the price of multi-walled CNTs have decreased from 45 000 to 100 $ kg(-1) and the productivity increased to several hundred tons per year for commercial applications in Li ion battery and nanocomposites. When the prices of CNTs decrease to 10 $ kg(-1) , their applications as composites and conductive fillers at a million ton scale can be anticipated, replacing conventional carbon black fillers. Compared with traditional bulk chemicals, the controllable synthesis and applications of CNTs on a million ton scale are still far from being achieved due to the challenges in production, purification, dispersion, and commercial application. The basic knowledge of growth mechanisms, efficient and controllable routes for CNT production, the environmental and safety issues, and the commercialization models are still inadequate. The gap between the basic scientific research and industrial development should be bridged by multidisciplinary research for the rapid growth of CNT nano-industry.
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Protein tyrosine kinase 6 is associated with nasopharyngeal carcinoma poor prognosis and metastasis.
J Transl Med
PUBLISHED: 01-25-2013
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The aim of this study was to analyze the expression of protein tyrosine kinase 6 (PTK6) in nasopharyngeal carcinoma (NPC) samples, and to identify whether PTK6 can serve as a biomarker for the diagnosis and prognosis of NPC.
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Matrix metalloproteinases (MMPs) inhibitory effects of an octameric oligopeptide isolated from abalone Haliotis discus hannai.
Food Chem
PUBLISHED: 01-23-2013
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Abalone (Haliotis discus hannai) is a marine gastropod, and an important fishery and food industrial resource that is massively maricultured in Asia, Africa, Australia and America. However, its health benefits have rarely been studied for nutraceutical and pharmaceutical application. In this study, the purified abalone oligopeptide (AOP) with anti-matrix metalloproteinases (anti-MMPs) effects was isolated from the digests of abalone intestine using recycle HPLC with a JAI W253 column and an OHpak SB-803 HQ column. The AOP was identified as Ala-Glu-Leu-Pro-Ser-Leu-Pro-Gly (MW=782.4 Da) with a de novo peptide sequencing technique using a tandem mass spectrometer. The AOP exhibited a specific inhibitory effect against MMP-2/-9 activity and attenuated protein expression of p50 and p65 in the human fibrosarcoma (HT1080) cells, dose-dependently. The results presented illustrate that the AOP could inhibit MMP-2/-9 expression in HT1080 cells via the nuclear factor-kappaB (NF-?B)-mediated pathway. This data suggest that the AOP from H. discus hannai intestine may possess therapeutic and preventive potential for the treatment of MMPs-related disorders such as angiogenesis and cardiovascular diseases.
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PreDNA: accurate prediction of DNA-binding sites in proteins by integrating sequence and geometric structure information.
Bioinformatics
PUBLISHED: 01-17-2013
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Protein-DNA interactions often take part in various crucial processes, which are essential for cellular function. The identification of DNA-binding sites in proteins is important for understanding the molecular mechanisms of protein-DNA interaction. Thus, we have developed an improved method to predict DNA-binding sites by integrating structural alignment algorithm and support vector machine-based methods.
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Value of baseline platelet count for prediction of complications in primary biliary cirrhosis patients treated with ursodeoxycholic acid.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 01-07-2013
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Decreased platelet count has been observed in various liver diseases, but its significance in primary biliary cirrhosis (PBC) remains unknown. The present study aimed to evaluate the predictive value of the platelet count at diagnosis for PBC-related complications in patients newly diagnosed with PBC and treated with ursodeoxycholic acid (UDCA).
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Establishment and characterization of a novel nasopharyngeal carcinoma cell line (SUNE2) from a Cantonese patient.
Chin J Cancer
PUBLISHED: 12-16-2011
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The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage-independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.
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Statistical optimization of microalgae Pavlova lutheri cultivation conditions and its fermentation conditions by yeast, Candida rugopelliculosa.
Bioresour. Technol.
PUBLISHED: 09-05-2011
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In this study, sequential strategy based design was applied to optimize the microalgae, Pavlova lutheri mass culture conditions and fermentation conditions of the cultured algae by proteolytic yeast Candidia rugopelliculosa to obtain small peptide chains. This optimization of culture and fermentation conditions by response surface methodology (RSM) finally leads to effective purification of a bioactive peptide MPGPLSPL (793.01 Da) with hydroxyl radical scavenging activity. Collectively, these results indicated that microalgae P. lutheri can enhance the hydroxyl radical inhibiting effect through protein hydrolysis process under RSM optimal condition.
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Live-attenuated measles virus vaccine confers cell contact loss and apoptosis of ovarian cancer cells via ROS-induced silencing of E-cadherin by methylation.
Cancer Lett.
PUBLISHED: 07-27-2011
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Herein we present a novel molecular mechanism of the antitumor effects of live-attenuated measles virus (MV) vaccine in ovarian cancer. Using a 2-DE/MS-based comparative proteomics strategy, we identified 17 proteins differentially expressed in live-attenuated MV vaccine-treated SKOV-3 ovarian cancer cells, including oxidative stress-associated enzymes and cell contact-related proteins, which indicated that live-attenuated MV vaccine could induce aberrant ROS activation. It further mediated epigenetic silencing of E-cadherin via upregulating DNMT3a that conferred both cell-cell and cell-matrix contact loss and apoptosis of ovarian cancer cells. This process could be reversed through ROS inhibition. Our study lays the theoretical foundation for the clinical application of live-attenuated MV vaccine as a potential oncotherapeutic agent for ovarian cancer treatment.
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Predicting protein submitochondria locations by combining different descriptors into the general form of Chous pseudo amino acid composition.
Amino Acids
PUBLISHED: 06-28-2011
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Knowledge of the submitochondria location of protein is integral to understanding its function and a necessity in the proteomics era. In this work, a new submitochondria data set is constructed, and an approach for predicting protein submitochondria locations is proposed by combining the amino acid composition, dipeptide composition, reduced physicochemical properties, gene ontology, evolutionary information, and pseudo-average chemical shift. The overall prediction accuracy is 93.57% for the submitochondria location and 97.79% for the three membrane protein types in the mitochondria inner membrane using the algorithm of the increment of diversity combined with the support vector machine. The performance of the pseudo-average chemical shift is excellent. For contrast, the method is also used to predict submitochondria locations in the data set constructed by Du and Li; an accuracy of 94.95% is obtained by our method, which is better than that of other existing methods.
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Divalent metal transporter 1 is a hypoxia-inducible gene.
J. Cell. Physiol.
PUBLISHED: 05-17-2011
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Our recent study revealed a high correlation between the expression of hypoxia-inducible factor-1 (HIF-1) alpha and divalent metal transporter 1 (DMT1) in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated that DMT1 might be one of the target genes of HIF-1. Here, we characterized the DMT1 exon1B promoter region and identified a functional hypoxia response element (HRE, 5-TCAGTACCTAACGTGGCGCCACGGC-3) harboring a binding site for HIF-1. We demonstrated that hypoxia-dependent activation of a luciferase reporter gene in transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter containing the putative HRE sequence. We also showed that the HIF-1 binding site (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5-ACGTG-3) at -327 to -323 relative to the transcription start site of the human DMT1 exon1B gene. The mutation of this sequence prevented stimulation of luciferase activity. Electrophoretic mobility shift assays revealed that the HRE sequence found in the DMT1 gene promoter was bound by HIF-1. In addition, we provide evidence that hypoxia could significantly increase ferrous uptake, while the silencing of total DMT1 by RNA interference down-regulates DMT1 expression and ferrous uptake in HepG2 cells. We conclude that DMT1 is a hypoxia-inducible gene.
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1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] suppresses pro-inflammatory responses by blocking NF-?B and MAPK signaling pathways in activated microglia.
Eur. J. Pharmacol.
PUBLISHED: 04-23-2011
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Unregulated activation of microglia is a key risk factor contributes to neurodegenerative diseases and suppression of this phenomenon is considered as a potential therapeutic target. The compound isolated from sea horse Hippocampus kuda Bleeler; 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] was characterized for its ability in suppressing LPS mediated activation of murine BV-2 cells. Despite the presence of various active molecular groups in the structure, SE1 has not well explored for its biological activities. The outcome of this study clearly indicated that SE1 inhibited the production of inflammatory mediators; nitric oxide, prostaglandin E(2) and pro-inflammatory cytokines. Furthermore, it inhibited the protein and gene expression levels of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-?, interleukin-1? and interleukin-6. The responsible signaling mechanisms leading to these inhibitions were identified as SE1 mediated blocking of phosphorylation of mitogen activate protein kinase (MAPK) molecules; C-jun-N-terminal kinase (JNK), p38 and nuclear translocation of nuclear factor-?B (NF-?B) p65 and p50 subunits. These results suggest that SE1 has the potential to be further developed as therapeutic against neuro-inflammation.
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Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells.
Int J Nanomedicine
PUBLISHED: 04-20-2011
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Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification.
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A comparative study of thermal calcination and an alkaline hydrolysis method in the isolation of hydroxyapatite from Thunnus obesus bone.
Biomed Mater
PUBLISHED: 04-13-2011
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In the present study, hydroxyapatite (HAp) was isolated from Thunnus obesus bone using alkaline hydrolysis and thermal calcination methods. The obtained ceramic has been characterized by thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), powder x-ray diffraction analysis (XRD), field-emission scanning electron microscopy, energy-dispersive x-ray analysis, transmission electron microscopy (TEM), selected area diffraction analysis, cytotoxic analysis and cell proliferation analysis. The results indicate that there are significant differences between the ceramics and T. obesus bone. FT-IR and TGA results affirmed that the collagen and organic moieties have been eliminated by both the proposed methods. XRD results were in agreement with JCPDS data. TEM and selective area diffraction images have signified that the thermal calcination method produces good crystallinity with dimensions 0.3-1.0 µm, whereas the alkaline hydrolysis method produces nanostructured HAp crystals with 17-71 nm length and 5-10 nm width. Biocompatibility of HAp crystals was evaluated by cytotoxicity and cell proliferation with human osteoblast-like cell MG-63.
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Carbon nanotube mass production: principles and processes.
ChemSusChem
PUBLISHED: 04-05-2011
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Our society requires new materials for a sustainable future, and carbon nanotubes (CNTs) are among the most important advanced materials. This Review describes the state-of-the-art of CNT synthesis, with a focus on their mass-production in industry. At the nanoscale, the production of CNTs involves the self-assembly of carbon atoms into a one-dimensional tubular structure. We describe how this synthesis can be achieved on the macroscopic scale in processes akin to the continuous tonne-scale mass production of chemical products in the modern chemical industry. Our overview includes discussions on processing methods for high-purity CNTs, and the handling of heat and mass transfer problems. Manufacturing strategies for agglomerated and aligned single-/multiwalled CNTs are used as examples of the engineering science of CNT production, which includes an understanding of their growth mechanism, agglomeration mechanism, reactor design, and process intensification. We aim to provide guidelines for the production and commercialization of CNTs. Although CNTs can now be produced on the tonne scale, knowledge of the growth mechanism at the atomic scale, the relationship between CNT structure and application, and scale-up of the production of CNTs with specific chirality are still inadequate. A multidisciplinary approach is a prerequisite for the sustainable development of the CNT industry.
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Antitumor activity of monomethoxy poly(ethylene glycol)-poly (?-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma.
Oncol. Rep.
PUBLISHED: 03-31-2011
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Doxorubicin (Dox) is one of the most commonly used and highly effective antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the therapeutic effect and decrease the systematic toxicity for the administration of doxorubicin. In our study, doxorubicin was incorporated into monomethoxy poly(ethylene glycol)-poly(?-caprolactone) (MPEG-PCL) micelle by a self-assembly method. The cytotoxicity and cellular uptake efficiency of Dox-loaded MPEG-PCL (Dox/MPEG-PCL) micelle against B16-F10 murine melanoma cells was examined by the methylthiazoltetrazolium (MTT) test and flow cytometry. The antitumor activity of Dox/MPEG-PCL was evaluated in C57BL/6 mice injected subcutaneously with B16-F10 cells. Toxicity was evaluated in tumor-free mice. Meanwhile, tumor proliferation, intratumoal angiogenesis and apoptotic cells were evaluated by PCNA, CD31 staining and TUNEL assay, respectively. Encapsulation of doxorubicin in MPEG-PCL micelle improved the cytotoxicity of doxorubicin and enhanced its cellular uptake on B16-F10 cell in vitro. Administration of Dox/MPEG-PCL micelle resulted in significant inhibition (75% maximum inhibition relative to controls) in the growth of B16-F10 tumor xenografts and prolonged the survival of the treated mice (P<0.05). These anti-tumor responses were associated with marked increase of tumor apoptosis and notable reduction of cell proliferation and intratumoral microvessel density (P<0.05). The system toxicity also decreased in the Dox/MPEG-PCL group compared with free doxorubicin group. Our data indicate that the encapsulation of doxorubicin in MPEG-PCL micelle improved the anti-tumor activity in vivo without conspicuous systemic toxic effects.
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Neuroprotective effect of ligustilide against ischaemia-reperfusion injury via up-regulation of erythropoietin and down-regulation of RTP801.
Br. J. Pharmacol.
PUBLISHED: 03-18-2011
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Ligustilide, the main lipophilic component of Danggui, has been reported to protect the brain against ischaemic injury. However, the mechanisms are unknown. Here, we investigated the roles of erythropoietin (EPO) and the stress-induced protein RTP801 in neuroprotection provided by ligustilide against ischaemia-reperfusion (I/R) damage to the brain.
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Dieckol from Ecklonia cava Regulates Invasion of Human Fibrosarcoma Cells and Modulates MMP-2 and MMP-9 Expression via NF-?B Pathway.
Evid Based Complement Alternat Med
PUBLISHED: 03-17-2011
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The matrix metalloproteinase (MMP) family is involved in the breakdown of extracellular matrix in normal physiological processes, as well as in the disease processes such as arthritis and cancer metastasis. In the present study, dieckol was obtained with high yield from marine brown alga Ecklonia cava (EC), and its effect was assessed on the expression of MMP-2 and -9 and morphological changes in human fibrosarcoma cell line (HT1080). Dieckol inhibited the expression of MMP-2 and -9 in a dose-dependent manner and also suppressed the cell invasion and the cytomorphology in 3D culture system on HT1080 cells. Moreover, dieckol may influence nuclear factor kappa B (NF-?B) pathway without obvious influence on activator protein-1 (AP-1) pathway and tissue inhibitor of metalloproteinases (TIMPs). In conclusion, dieckol could significantly suppress MMP-2 and -9 expression and alter cytomorphology of HT1080 cell line via NF-?B pathway.
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Long, cold, early r process? Neutrino-induced nucleosynthesis in He shells revisited.
Phys. Rev. Lett.
PUBLISHED: 03-07-2011
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We revisit a ?-driven r-process mechanism in the He shell of a core-collapse supernova, finding that it could succeed in early stars of metallicity Z ? 10?³ Z(?), at relatively low temperatures and neutron densities, producing A ~ 130 and 195 abundance peaks over ~10-20 s. The mechanism is sensitive to the ? emission model and to ? oscillations. We discuss the implications of an r process that could alter interpretations of abundance data from metal-poor stars, and point out the need for further calculations that include effects of the supernova shock.
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Quantitative determination of 10 phenylpropanoid and lignan compounds in Lancea tibetica by high-performance liquid chromatography with UV detection.
Planta Med.
PUBLISHED: 02-23-2011
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An HPLC method was developed for simultaneous determination of one phenylpropanoid glycoside, verbascoside (1), and nine lignans, including lantibeside (2), phillyrin (3), lantibeside B (4), lantibeside C (5), tibeticoside A (6), styraxjaponoside C (7), sylvatesmin (8), (+)-piperitol (9), and horsfieldin (10), from the Tibetan medicinal plant Lancea tibetica Hook. F. et Thoms. The analysis was performed within 45?min. The extraction method was optimized with different solvent systems. The HPLC method was validated for linearity, repeatability, accuracy, limits of detection, and limits of quantification. The limits of detection and limits of quantification of 10 analytes were found to be less than 0.1 and 0.5?µg/mL, respectively. The RSD for intra- and inter-day analyses was less than 4.2?%, and the recovery efficiency was 90-105?%. The method was used to analyze different populations of L. tibetica collected in China. HPLC profiles showed that the concentrations of analytes were different in samples collected from different areas of China. Verbascoside was the dominant component in three out of five plant samples; compounds 2, 3, 6, and 8 accounted for over 62?% yields in total lignan contents. The method is useful for identification, quality assurance, and quality control of L. tibetica and its related products.
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Evaluation of cell tracking effects for transplanted mesenchymal stem cells with jetPEI/Gd-DTPA complexes in animal models of hemorrhagic spinal cord injury.
Brain Res.
PUBLISHED: 02-20-2011
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Cell tracking using iron oxide nanoparticles has been well established in MRI. However, in experimental rat models, the intrinsic iron signal derived from erythrocytes masks the labeled cells. The research evaluated a clinically applied Gd-DTPA for T1-weighted positive enhancement for cell tracking in spinal cord injury (SCI) rat models. MSCs were labeled with jetPEI/Gd-DTPA particles to evaluate the transfection efficiency by MRI in vitro. Differentiation assays were carried out to evaluate the differentiation ability of Gd-DTPA-labeled MSCs. The Gd-DTPA-labeled MSCs were transplanted to rat SCI model and monitored by MRI in vivo. Fluorescence images were taken to confirm the MRI results. Behavior test was assessed with Basso, Beattie, and Bresnahan (BBB) scoring in 6weeks after cell transplantation. The Gd-labeled MSCs showed a significant increase in signal intensity in T1-weighted images. After local transplantation, Gd-DTPA-labeled MSCs could be detected in SCI rat models by the persistent T1-weighted positive enhancement from 3 to 14days. Under electronic microscope, Gd-DTPA/jetPEI complexes were mostly observed in cytoplasm. Fluorescence microscopy examination showed that the Gd-labeled MSCs survived and distributed within the injured spinal cord until 2weeks. The Gd-labeled MSCs were identified and tracked with MRI by cross and sagittal sections. The BBB scores of the rats with labeled MSCs transplantation were significantly higher than those of control rats. Our results demonstrated that Gd-DTPA is appropriate for cell tracking in rat model of SCI, indicating that an efficient and nontoxic label method with Gd-DTPA could properly track MSCs in hemorrhage animal models.
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Characteristics of cellulosic amine-crosslinked copolymer and its sorption properties for Cr(VI) from aqueous solutions.
J. Hazard. Mater.
PUBLISHED: 02-14-2011
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A new cellulosic amine-crosslinked copolymer was prepared after the amination reaction with cotton stalk peel (CSP). The physicochemical characteristics of amine-crosslinked cotton stalk peel (AC-CSP) and raw CSP were determined after the surface analysis (including specific surface area, micropore volume and SEM), zeta potential analysis and spectrum analysis (FTIR and Raman spectrum). The sorption properties of AC-CSP for Cr(VI) were evaluated in the static, column sorption and desorption tests. The surface characteristics indicated the absence of porous adsorption in the potential Cr(VI) sorption mechanism. Zeta potential and spectrum analysis of AC-CSP illustrated the involvement of amine groups in the Cr(VI) sorption process. The sorption capacity of AC-CSP for Cr(VI) was 129.0mg/g as comparison with 14.8 mg/g of raw CSP. Flow rate and influent Cr(VI) concentration were demonstrated as two influencial factors in the column sorption tests. NaCl was used as the eluent, and the desorption efficiencies during three successive cycles were 75.9%, 69.8% and 64.3%, respectively. In addition, the results of the static, column sorption and desorption tests illustrated the complicated interactions between Cr(VI) and AC-CSP including complexation and ion exchange mechanisms.
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Hepcidin directly inhibits transferrin receptor 1 expression in astrocytes via a cyclic AMP-protein kinase A pathway.
Glia
PUBLISHED: 02-10-2011
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Hepcidin, an iron-regulatory hormone, plays a central role in iron homeostasis in peripheral tissues. The widespread distribution of hepcidin in the brain implies that the hormone may be essential for brain iron homeostasis. Here, we investigated the effects of hepcidin on the expression of iron uptake proteins, including transferrin receptor 1 (TfR1) and divalent metal transporter1 (DMT1) and the release protein ferroportin1 (Fpn1) in the cultured astrocytes. The effects of hepcidin on iron uptake, including transferrin-bound iron (Tf-Fe) and non-transferrin-bound iron (NTBI), and iron release were also studied. Our results demonstrated that astrocytes, when treated with hepcidin peptide or infected with hepcidin expression adenovirus (ad-hepcidin), showed a significant ability in reducing iron uptake (both Tf-Fe and NTBI), and iron release, which were accompanied by decreased expressions of TfR1, DMT1, and Fpn1. Moreover, we found that the effect of hepcidin in reducing TfR1 expression, which is dependent on the cyclic AMP-protein kinase A pathway, was the primary and dominant event. In conclusion, our results demonstrated that hepcidin controlled iron uptake and release by regulating expression of iron transport proteins. The findings also implied the existence of a novel hepcidin-receptor on the membrane of astrocytes.
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Hierarchical organization of brain functional networks during visual tasks.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 01-24-2011
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The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.
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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.