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Find video protocols related to scientific articles indexed in Pubmed.
Long-term thiol monitoring in living cells using bioorthogonal chemistry.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Intracellular thiols play vital roles in living systems, and their in situ monitoring is of great importance. Here, we report on a bioorthogonal chemistry based fluorescent probe, which is capable of monitoring intracellular thiols in living cells for up to 36 hours with an obvious blue-to-green fluorescence change.
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[Molluscicidal effect comparison between TDS and MNSC in field].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 10-28-2014
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To compare the molluscicidal effects between "Luo-wei" (TDS), a plant molluscicide in 4 percent, and metaldehyde and niclosamide (MNSC) in the field.
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[Economic burden and economic risk of five major chronic diseases among Chinese urban residents].
Beijing Da Xue Xue Bao
PUBLISHED: 10-22-2014
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To provide scientific evidence for medical insurance and health policies allocating the limited health resources in China.
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Selective neuropsychological impairments and related clinical factors in children with moyamoya disease of the transient ischemic attack type.
Childs Nerv Syst
PUBLISHED: 10-22-2014
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Moyamoya disease is characterized by progressive narrowing of bilateral internal carotid arteries. Neuropsychological impairments are suspected due to frequent involvement of the frontotemporal areas. The present study thus aimed to investigate the pattern of neuropsychological function in children diagnosed with moyamoya disease.
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2-(1-Aryliminoethyl)-9-arylimino-5,6,7,8-tetrahydrocycloheptapyridyl iron(ii) dichloride: synthesis, characterization, and the highly active and tunable active species in ethylene polymerization.
Dalton Trans
PUBLISHED: 10-09-2014
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A series of 2-(1-arylimino)ethyl-9-arylimino-5,6,7,8-tetrahydrocycloheptapyridine derivatives was synthesized and fully characterized, and thereafter reacted with iron dichloride to form their corresponding iron(ii) complexes. The single crystals of representative organic and iron complex compounds were obtained and analyzed by the X-ray diffraction analysis, indicating the distorted bipyramidal geometry around the iron core. Moreover, DFT calculations were performed on selected species to determine their structural features. On treatment with either MAO or MMAO, all iron complex pre-catalysts showed high activities (up to 1.56 × 10(7) gPE mol(-1)(Fe) h(-1)) toward ethylene polymerization. Regarding the nature of the ligands and reaction parameters, their catalytic activities and the characters of the obtained polyethylenes have been carefully investigated. The ring strain of the fused-cycloheptane of the ligands within iron complexes was considered to affect their catalytic performance in ethylene polymerization. The active species were activated and controlled by using a co-catalyst of MMAO preferred over MAO, and the obtained polyethylenes with MMAO showed narrower molecular polydispersity than the corresponding polyethylenes with MAO.
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Medical intervention in parent-reported infant gastro-oesophageal reflux: A population-based study.
J Paediatr Child Health
PUBLISHED: 09-21-2014
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To report the cumulative incidence, health-seeking behaviour and medical intervention of infants with gastro-oesophageal reflux (GOR) in the first year of life.
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Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China.
Eur. Respir. J.
PUBLISHED: 09-20-2014
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Linezolid may be effective in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We conducted a prospective, multicentre, randomised study to further evaluate the efficacy, safety and tolerability of linezolid in patients with extensively drug-resistant tuberculosis in China. 65 patients who had culture-positive sputum for extensively drug-resistant tuberculosis were randomly assigned to a linezolid therapy group or a control group. Patients in the two groups adopted a 2-year individually based chemotherapy regimen. The linezolid therapy group was given linezolid at a start dose of 1200 mg per day for a period of 4-6 weeks and this was then followed by a dose of 300-600 mg per day. The proportion of sputum culture conversions in the linezolid therapy group was 78.8% by 24 months, significantly higher than that in the control group (37.6%, p<0.001). The treatment success rate in linezolid therapy group was 69.7%, significantly higher than that in the control group (34.4%, p = 0.004). 27 (81.8%) patients had clinically significant adverse events in the linezolid group, of whom 25 (93%) patients had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid. Linezolid containing chemotherapy for treatment of extensively drug-resistant tuberculosis may significantly promote cavity closure, increase sputum culture-conversion rate and improve treatment success rate.
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Glucuronidation of capsaicin by liver microsomes and expressed UGT enzymes: reaction kinetics, contribution of individual enzymes and marked species differences.
Expert Opin Drug Metab Toxicol
PUBLISHED: 09-16-2014
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The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin.
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Prospective Memory in Subjective Cognitive Decline: A Preliminary Study on the Role of Early Cognitive Marker in Dementia.
Alzheimer Dis Assoc Disord
PUBLISHED: 09-01-2014
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Accumulating evidence shows that subjective cognitive decline (SCD) without impairment on conventional neuropsychological tests may indicate increased risk for Alzheimer disease. Previous studies of mild cognitive impairment have demonstrated the potential role of prospective memory (PM) in the early detection of cognitive decline. We thus aimed to investigate the performance of people with SCD on PM tasks relative to their healthy controls (HCs). Forty-one participants with SCD and demographically matched HCs received regular cognitive testing as well as 2 single-trial naturalistic time-based and event-based PM tasks. Statistical analyses showed that the individuals with SCD performed worse on the time-based PM task, especially on the prospective component, when compared with their HCs. Our findings suggest that PM, especially the time-based one on the prospective component, may be an early cognitive marker of dementia. This implies an underlying difficulty among subjects with SCD in self-initiation that exacerbates their memory difficulties. Further investigation on a large scale is needed.
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Distinct Patterns and Clinical Implications of Semantic Memory Deterioration Among Patients With MCI.
Alzheimer Dis Assoc Disord
PUBLISHED: 09-01-2014
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Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.
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Warfarin is an Effective Modifier of Multiple UDP-Glucuronosyltransferase Enzymes: Evaluation of its Potential to Alter the Pharmacokinetics of Zidovudine.
J Pharm Sci
PUBLISHED: 08-28-2014
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In this study, we aimed to determine the modulatory effects of warfarin (an extensively used anticoagulant drug) and its metabolites on UDP-glucuronosyltransferase (UGT) activity and to assess the potential of warfarin to alter the pharmacokinetics of zidovudine (AZT). The effects of warfarin and its metabolites on glucuronidation were determined using human and rat liver microsomes (HLM and RLM) as well as expressed UGTs. The mechanisms of warfarin-UGT interactions were explored through kinetic characterization and modeling. Pharmacokinetic studies with rats were performed to evaluate the potential of warfarin to alter the pharmacokinetics of AZT. We found that warfarin was an effective modifier of a panel of UGT enzymes. The effects of warfarin on glucuronidation were inhibitory for UGT1A1, 2B7, and 2B17, but activating for UGT1A3. Mixed effects were observed for UGT1A7 and 1A9. Consistent with its inhibitory effects on UGT2B7 activity, warfarin inhibited AZT glucuronidation in HLM (Ki = 74.9-96.3 ?M) and RLM (Ki = 190-230 ?M). Inhibition of AZT glucuronidation by UGT2B7, HLM, and RLM was also observed with several hydroxylated metabolites of warfarin. Moreover, the systemic exposure (AUC) of AZT in rats was increased by a 1.5- to 2.1-fold upon warfarin coadministration. The elevated AUC was associated with suppressed glucuronidation that was probably attained through a combined action of warfarin and its hydroxylated metabolites. In conclusion, the activities of multiple UGT enzymes can be modulated by warfarin and the nature of modulation was isoform dependent. Also, pharmacokinetic interactions of zidovudine with warfarin were highly possible through inhibition of UGT metabolism. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
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Protective effects of astragaloside IV against ovalbumin-induced lung inflammation are regulated/mediated by T-bet/GATA-3.
Pharmacology
PUBLISHED: 08-28-2014
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Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness, and airway remodelling. Astragaloside IV (3-O-?-D-xylopyranosyl-6-O-?-D-glucopyranosyl-cycloastragenol, AST), the primary pure saponin isolated from the root of Astragalus membranaceus, is an effective compound with distinct pharmacological effects including anti-inflammation, immunoregulation, and antifibrosis. However, the effect of AST on asthma remains unclear. In the present study, in the murine model of asthma, the airway hyperresponsiveness was relieved after treatment with AST, accompanied by a reduction of inflammatory cells. In addition, the levels of IL-4 and IL-5 decreased, while the IFN-? level increased, in bronchoalveolar lavage fluid. The compound also significantly inhibited the synthesis of GATA-3-encoding mRNA and protein in addition to increasing the synthesis of T-bet-encoding mRNA and protein in both lung tissues and CD4+ T cells. Our findings indicate that AST treatment inhibits ovalbumin-induced airway inflammation by modulating the key master switches GATA-3 and T-bet, which results in committing T helper cells to a Th1 phenotype.
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Scavenger receptor on astrocytes and its relationship with neuroinflammation.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 07-07-2014
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Neuroinflammation in central nervous system,featured by glial cells activation,can always be found during the development of neurodegenerative diseases. Astrocytes,the most abundant glial cells in the brain,can release both pro-inflammatory and anti-inflammatory factors,thus playing a crucial role in the neuroinflammation. A variety of pattern-recognition receptors on astrocytes are involved in the inflammatory response,particularly the scavenger receptor. Scavenger receptor is a cell surface glycoprotein and can identify diverse ligands. With a variety of biological functions,it may activate many signal pathways related to neuroinflammation,regulate the host defense and the development of neuroinflammation,and eventually regulate the process of neuroinflammation. Thus,it play a key role in the development of neurodegenerative diseases and many other conditions. This review summarizes the scavenger receptor expressed on astrocytes and how it regulates signal transduction pathways associated with neuroinflammation and thus participates in regulating neuroinflammation.
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[The basic functions of inosine 5'-monophosphate dehydrogenase and its application in drug discovery].
Yao Xue Xue Bao
PUBLISHED: 06-26-2014
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Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.
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Reduced structural integrity and functional lateralization of the dorsal language pathway correlate with hallucinations in schizophrenia: A combined diffusion spectrum imaging and functional magnetic resonance imaging study.
Psychiatry Res
PUBLISHED: 06-15-2014
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Recent studies suggest that structural and functional alterations of the language network are associated with auditory verbal hallucinations (AVHs) in schizophrenia. However, the ways in which the underlying structure and function of the network are altered and how these alterations are related to each other remain unclear. To elucidate this, we used diffusion spectrum imaging (DSI) to reconstruct the dorsal and ventral pathways and employed functional magnetic resonance imaging (fMRI) in a semantic task to obtain information about the functional activation in the corresponding regions in 18 patients with schizophrenia and 18 matched controls. The results demonstrated decreased structural integrity in the left ventral, right ventral and right dorsal tracts, and decreased functional lateralization of the dorsal pathway in schizophrenia. There was a positive correlation between the microstructural integrity of the right dorsal pathway and the functional lateralization of the dorsal pathway in patients with schizophrenia. Additionally, both functional lateralization of the dorsal pathway and microstructural integrity of the right dorsal pathway were negatively correlated with the scores of the delusion/hallucination symptom dimension. Our results suggest that impaired structural integrity of the right dorsal pathway is related to the reduction of functional lateralization of the dorsal pathway, and these alterations may aggravate AVHs in schizophrenia.
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Comparative analysis of glucuronidation of ethanol in treeshrews, rats and humans.
Xenobiotica
PUBLISHED: 06-06-2014
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Abstract 1. The treeshrews consume food-derived alcohol (ethanol) at a dose that would intoxicate humans, highlighting a marked difference in detoxification of ethanol between the animal species and humans. 2. In this study, we reported that the treeshrews and rats exhibited considerably high glucuronidation capacity for ethanol. Ethanol glucuronidation was 7.1-fold (for the liver microsomes) or 29.2-fold (for the intestine microsomes) more efficient in treeshrews than in humans. Similar to treeshrews, rats also showed a high efficiency in glucuronidating ethanol. 3. In the single-pass perfused intestinal model, significant amount of ethyl glucuronide (EtG) was excreted into the perfusate (for both treeshrews and rats) and bile (for rats). Biliary excretion of EtG was 8.8-13.4 times of intestinal excretion of EtG, suggesting that the liver played a determinant role in glucuronidation of ethanol. In vivo pharmacokinetics showed that EtG production was rapid in the animals with a Tmax value of ?1.75?h. The excreted EtG into urine was 0.11-0.13% of dosed ethanol, a value increased by a 5.5- to 6.6-fold compared to that in humans. 4. This was the first report that the glucuronidation activity toward ethanol was much higher in treeshrews and rats than that in humans, revealing a marked species difference in ethanol glucuronidation.
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Cross-species cloning: influence of cytoplasmic factors on development.
J. Physiol. (Lond.)
PUBLISHED: 06-03-2014
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It is widely accepted that the crosstalk between naive nucleus and maternal factors deposited in the egg cytoplasm before zygotic genome activation is crucial for early development. This crosstalk may also exert some influence on later development. It is interesting to clarify the relative roles of the zygotic genome and the cytoplasmic factors in development. Cross-species nuclear transfer (NT) between two distantly related species provides a unique system to study the relative role and crosstalk between egg cytoplasm and zygotic nucleus in development. In this review, we will summarize the recent progress of cross-species NT, with emphasis on the cross-species NT in fish and the influence of cytoplasmic factors on development. Finally, we conclude that the developmental process and its evolution should be interpreted in a systemic way, rather than in a way that solely focuses on the role of the nuclear genome.
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MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1?.
J. Mol. Cell. Cardiol.
PUBLISHED: 05-28-2014
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It is well known that menopause could worsen age-related ventricular concentric remodeling following estrogen (E2) deficiency. However the underlying mechanisms of such phenomena are not fully understood. Mitochondria, as the 'cellular power station' of hearts, play an important role in maintaining normal cardiac function and structure. Therefore, the present study aims to investigate whether mitochondrial compromise is responsible for E2 deficiency associated concentric remodeling and, if so, what is its underlying molecular mechanism. We found evident concentric remodeling pattern in both postmenopausal and ovariectomized (OVX) mice, which could be attenuated by E2 replacement. Further study showed mitochondrial structural damages and respiratory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mitochondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the heart. Then, peroxisome proliferator-activated receptor-? co-activator 1-? (PGC-1?), a key mitochondrial function and biology regulator, was found significantly reduced in both postmenopausal and OVX mice. The reduction of PGC-1? protein level in OVX mice could be rescued by E2 delivery, indicating that E2 could positively regulate PGC-1? expression. Next, we found that microRNA-23a (miR-23a) could be negatively regulated by E2 in both myocardium and cultured cardiomyocytes. Moreover, miR-23a could directly downregulate PGC-1? expression in cardiomyocytes via binding to its 3'UTR which implied that miR-23a could be critical for the downregulation of PGC-1? under E2 deficiency. Overexpression of miR-23a was also found to damage mitochondria in cultured cardiomyocytes, ascribed to PGC-1? downregulation. Taken together, E2 deficiency may cause mitochondrial compromise through miR-23a-mediated PGC-1? downregulation, which may subsequently lead to the menopause-associated concentric remodeling.
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[A cohort study on the outcome of multidrug-resistant tuberculosis in elderly patients].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 05-10-2014
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To investigate the clinical curative effect and outcomes of multidrug-resistant tuberculosis (MDR-TB) in elderly patients.
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HLA Disparity is not crucial for the survival rate and severity of chronic health conditions in adult recipients following family donor hematopoietic stem cell transplantation.
Int. J. Hematol.
PUBLISHED: 05-05-2014
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The shortage of HLA-identical siblings or unrelated donors has restricted the application of hematopoietic stem cell transplantation (HSCT). Few studies have systematically assessed survival and chronic health conditions (CHCs) in the same cohort of patients after HLA-mismatched/haploidentical (mismatched) family donor transplantation. In the present study, we retrospectively analyzed the survival of 127 adult patients receiving either HLA-matched (71 cases) or HLA-mismatched (56 cases) family donor transplantation. Of 127 patients, 81 patients survived at least 2 years after HSCT and were still alive until the present investigation. We evaluated the CHCs in 76 survivors (41 matched and 35 mismatched). CHC-related information was scored according to the Bone Marrow Transplant Survivor Study questionnaire. There was no significant difference in overall survival or disease-free survival between HLA-matched and -mismatched transplant recipients. The CHCs were less severe in HLA-mismatched recipients than in matched cohorts. Multivariate analysis identified that age over 40 years at transplantation and presence of chronic graft-versus-host disease were independent risk factors for CHCs, while anti-thymocyte globulin-containing conditioning regimens might be protective. However, HLA disparity was not crucial for either the survival rate or CHCs. In conclusion, HLA-mismatched family donor transplantation can achieve comparable therapeutic effects to HLA-identical sibling transplantation.
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An in vivo microdialysis study of FLZ penetration through the blood-brain barrier in normal and 6-hydroxydopamine induced Parkinson's disease model rats.
Biomed Res Int
PUBLISHED: 04-03-2014
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FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson's disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats. In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances.
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Electroacupuncture treatment improves neurological function associated with regulation of tight junction proteins in rats with cerebral ischemia reperfusion injury.
Evid Based Complement Alternat Med
PUBLISHED: 04-02-2014
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Strategies to develop effective neuroprotective therapy to reduce brain damage and related behavioral deficits in stroke patients are of great significance. Electroacupuncture (EA), which derives from traditional Chinese medicine, may be effective as a complementary and alternative method for promoting recovery of neurological function and quality of life. Adult Sprague-Dawley rats were randomly divided into 3 groups: (1) sham, (2) middle cerebral artery occlusion (MCAO) model groups of 2?h MCAO followed by 1, 3, 5, or 7?d of reperfusion, and (3) EA groups of 2?h MCAO followed by 1, 3, 5, or 7?d of reperfusion. EA groups received EA therapy by needling at GV20 and left ST36. The results show that EA therapy improved the neurological function and reduced infarct volume, confirmed by modified neurological severity scores and TTC staining. Real-time PCR, immunohistochemistry, and western blot assay verified that EA upregulated the expression of tight junction (TJ) claudin-5, occludin, and zonula occluding-1 from 1 to 7?d after reperfusion. Our findings suggest that EA reduces brain damage and related behavioral deficits via upregulation of the TJ proteins.
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Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/?-catenin pathway.
Nat Commun
PUBLISHED: 03-21-2014
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Upon stimulation by Wnt ligands, the canonical Wnt/?-catenin signalling pathway results in the stabilization of ?-catenin and its translocation into the nucleus to form transcriptionally active complexes with sequence-specific DNA-binding T-cell factor/lymphoid enhancer factor (TCF/LEF) family proteins. In the absence of nuclear ?-catenin, TCF proteins act as transcriptional repressors by binding to Groucho/Transducin-Like Enhancer of split (TLE) proteins that function as co-repressors by interacting with histone deacetylases whose activity leads to the generation of transcriptionally silent chromatin. Here we show that the transcription factor Ladybird homeobox 2 (Lbx2) positively controls the Wnt/?-catenin signalling pathway in the posterior lateral and ventral mesoderm of the zebrafish embryo at the gastrula stage, by directly interfering with the binding of Groucho/TLE to TCF, thereby preventing formation of transcription repressor complexes. These findings reveal a novel level of regulation of the canonical Wnt/?-catenin signalling pathway occurring in the nucleus and involving tissue-specific derepression of TCF by Lbx2.
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Comparison of the efficacy of a distal clavicular locking plate versus a clavicular hook plate in the treatment of unstable distal clavicle fractures and a systematic literature review.
Int Orthop
PUBLISHED: 03-12-2014
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The purpose of this study was to retrospectively compare and review the clinical outcomes between the distal clavicular locking plate and clavicular hook plates in the treatment of unstable distal clavicle fractures; moreover, the relevant literature of the two fixation methods was reviewed systematically to identify the non-union, complications, or functional scores, according to the treatment methods and determine which treatment method is better.
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Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway.
Mol Med Rep
PUBLISHED: 03-11-2014
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Octamer?binding transcription factor 4 (OCT4) is one of the factors associated with self?renewal and differentiation in cancer stem cells, and is crucial for the progression of various types of human malignancy. However, the expression and function of OCT4 in human pancreatic cancer has not been fully elucidated. The purpose of the present study was to investigate the function and molecular mechanisms of OCT4 in pancreatic cancer cells. The clinical significance of OCT4 expression was assessed by an immunohistochemical assay using a tissue microarray procedure in pancreatic cancer tissues and cells with different degrees of differentiation. A loss?of?function approach was used to examine the effects of a lentivirus?mediated OCT4 small hairpin RNA vector on biological behaviors, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of OCT4 protein in cancer tissues were significantly elevated compared with those in adjacent non?cancerous tissues (65.0 vs. 42.5%; P=0.005), which was correlated with tumor differentiation (P=0.008). The knockdown of OCT4 inhibited the proliferation and invasion of pancreatic cancer cells (Panc?1) expressing high levels of OCT4, accompanied with decreased expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase?2 (MMP?2). In conclusion, the present study reveals that the increased expression of OCT4 is correlated with the differentiation of pancreatic cancer, while knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of AKT pathway?mediated PCNA and MMP?2 expression, suggesting that OCT4 might serve as a potential therapeutic target for the treatment of pancreatic cancer.
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Effects of acupuncture at Baihui (DU20) and Zusanli (ST36) on the expression of heat shock protein 70 and tumor necrosis factor ? in the peripheral serum of cerebral ischemia-reperfusion-injured rats.
Chin J Integr Med
PUBLISHED: 03-07-2014
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To explore the effects of acupuncture on the peripheral serum expression of heat shock protein 70 (HSP70) and tumor necrosis factor ? (TNF-?) in rats with cerebral ischemia-reperfusion injury (CIRI).
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[Clinical and pathological analysis of 236 patients with primary extranodal lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 03-07-2014
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This study was aimed to analyze the clinical and pathological characteristics of patients with primary extranodal lymphoma (PENL). A total of 236 patients with PENL were enrolled to evaluate the clinical and pathological features. The clinical data of 236 patients with PENL confirmed by pathological and immunohistochemical methods between January 2001 and March 2012 were analyzed retrospectively. The results indicated that: (1)236 patients with PENL accounted for 40.7% of lymphoma over the same period. Median age was 55 years old (from 16 to 91 years old) . There were 153 males and 83 females(ratio 1.8: 1). (2)The common sites of involvement were gastrointestinal tract, nasal cavity, tonsil, mediastinum, skin, spleen, testis, bone and soft tissue, central nervous system, which accounted for 30.1% (71/236), 10.6% (25/236), 8.9% (21/236), 5.9% (14/236), 5.1% (12/236), 4.7% (11/236), 4.2% (10/236) , 4.2% (10/236) , 3.0% (7/236) respectively. (3)Symptoms of PENL did not have special characteristics, however its signs usually manifested with the enlargement or mass of organs, which accounted for 66.9% (158/236) in this study. (4)According to WHO classification of tumours of haematopoietic and lymphoid tissues in 2008, the common pathological type of gastrointestinal lymphoma was diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma; the common pathological type of nasal lymphoma was extranodal NK/T cell lymphoma; the common pathological type of tonsillar lymphoma, testicular lymphoma, CNS lymphoma was diffuse large B-cell lymphoma. It is concluded that the primary extranodal lymphoma is not rare, it is alert to PENL while organs enlarge or mass forms, so that clinical physician should pay attention to tissue biopsy.
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P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats.
Xenobiotica
PUBLISHED: 02-20-2014
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1.?The promising anticancer agent SNX-2112 (a novel Hsp90 inhibitor) is poorly bioavailable after oral administration. Here, we aim to determine the role of P-glycoprotein (P-gp) in the intestinal absorption of SNX-2112. 2.?We found that SNX-2112 significantly stimulated P-gp ATPase activity in in vitro ATPase assay with a small EC50 (the half-maximal effective concentration) value of 0.32?µM. 3.?In the single-pass perfused rat intestine model, absorption of SNX-2112 was not favored in the small intestine with a [Formula: see text] (the wall permeability) value of 0.38-0.64. By contrast, the compound was well absorbed in the colon with a [Formula: see text] value of 1.19. The P-gp inhibitors cyclosporine and elacridar (i.e. GF120918A) markedly enhanced SNX-2112 absorption in all four intestinal segments (i.e. duodenum, jejunum, ileum and colon) and the fold change ranged from 3.1 to 14.1. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of SNX-2112 by a 2.5-fold after oral administration. 4.?This is the first report that P-gp-mediated efflux is a limiting factor for intestinal absorption of SNX-2112 in rats.
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Identification of glucuronidation and biliary excretion as the main mechanisms for gossypol clearance: in vivo and in vitro evidence.
Xenobiotica
PUBLISHED: 02-20-2014
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1.?The natural polyphenol gossypol possesses many therapeutic benefits. Here we aim to determine the elimination pathways of gossypol in vivo and in vitro. 2.?Metabolite elucidation of gossypol was performed using UPLC-QTOF/MS coupled with Metabolynx analysis. Clearance of gossypol was evaluated in bile duct cannulated rats and in the single-pass perfused rat intestine model. In vitro glucuronidation of gossypol was characterized using liver and intestine microsomes as well as recombinant UDP-glucuronosyltransferase (UGT) enzymes. 3.?Analysis of rat plasma, urine, and feces revealed glucuronidation as the only metabolic pathway for gossypol. In bile duct cannulated rats, considerable amounts of glucuronides (G1, G2 and G3; 58.8-83.2% of dose) and parent compound (5.0-20%) were excreted into bile after IV administration. In the perfused rat intestine model, gossypol was well absorbed with a [Formula: see text] (the dimensionless effective permeability) value of 4.4. Significant amounts of glucuronides (G1, G2 and G3) were excreted into the gut lumen (2.5%) and into the bile (4.8%). Biliary excretion of unchanged gossypol (6.0%) was comparable to that of glucuronides. Further, gossypol was subjected to rapid glucuronidation by liver and intestine microsomes. Reaction phenotyping showed that multiple UGT1A enzymes (including UGT1A1, 1A3, 1A7 and 1A8) are mainly responsible for gossypol metabolism. 4.?In conclusion, glucuronidation was the only metabolic pathway for gossypol in rats. Excretion of unchanged gossypol into bile was also an important clearance mechanism.
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Double transgenesis of humanized fat1 and fat2 genes promotes omega-3 polyunsaturated fatty acids synthesis in a zebrafish model.
Mar. Biotechnol.
PUBLISHED: 02-13-2014
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Omega-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients for human health. However, vertebrates, including humans, have lost the abilities to synthesize EPA and DHA de novo, majorly due to the genetic absence of delta-12 desaturase and omega-3 desaturase genes. Fishes, especially those naturally growing marine fish, are major dietary source of EPA and DHA. Because of the severe decline of marine fishery and the decrease in n-3 LC-PUFA content of farmed fishes, it is highly necessary to develop alternative sources of n-3 LC-PUFA. In the present study, we utilized transgenic technology to generate n-3 LC-PUFA-rich fish by using zebrafish as an animal model. Firstly, fat1 was proved to function efficiently in fish culture cells, which showed an effective conversion of n-6 PUFA to n-3 PUFA with the n-6/n-3 ratio that decreased from 7.7 to 1.1. Secondly, expression of fat1 in transgenic zebrafish increased the 20:5n-3 and 22:6n-3 contents to 1.8- and 2.4-fold, respectively. Third, co-expression of fat2, a fish codon-optimized delta-12 desaturase gene, and fat1 in fish culture cell significantly promoted n-3 PUFA synthesis with the decreased n-6/n-3 ratio from 7.7 to 0.7. Finally, co-expression of fat1 and fat2 in double transgenic zebrafish increased the 20:5n-3 and 22:6n-3 contents to 1.7- and 2.8-fold, respectively. Overall, we generated two types of transgenic zebrafish rich in endogenous n-3 LC-PUFA, fat1 transgenic zebrafish and fat1/fat2 double transgenic zebrafish. Our results demonstrate that application of transgenic technology of humanized fat1 and fat2 in farmed fishes can largely improve the n-3 LC-PUFA production.
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Transcriptional factors smad1 and smad9 act redundantly to mediate zebrafish ventral specification downstream of smad5.
J. Biol. Chem.
PUBLISHED: 01-31-2014
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Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play crucial roles during embryonic development and cell fate determination. Nuclear transduction of BMP signals requires the receptor type Smad proteins, Smad1, Smad5, and Smad9. However, how these Smad proteins cooperate in vivo to regulate various developmental processes is largely unknown. In zebrafish, it was widely believed that the maternally expressed smad5 is essential for dorso-ventral (DV) patterning, and the zygotically transcribed smad1 is not required for normal DV axis establishment. In the present study, we have identified zygotically expressed smad9, which cooperates with smad1 downstream of smad5, to mediate zebrafish early DV patterning in a functional redundant manner. Although knockdown of smad1 or smad9 alone does not lead to visible dorsalization, double knockdown strongly dorsalizes zebrafish embryos, which cannot be efficiently rescued by smad5 overexpression, whereas the dorsalization induced by smad5 knockdown can be fully rescued by overexpression of smad1 or smad9. We have further revealed that the transcription initiations of smad1 and smad9 are repressed by each other, that they are direct transcriptional targets of Smad5, and that smad9, like smad1, is required for myelopoiesis. In conclusion, our study uncovers that smad1 and smad9 act redundantly to each other downstream of smad5 to mediate ventral specification and to regulate embryonic myelopoiesis.
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Photovoltaic enhancement due to surface-plasmon assisted visible-light absorption at the inartificial surface of lead zirconate-titanate film.
Nanoscale
PUBLISHED: 01-30-2014
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PZT film of 300 nm thickness was deposited on tin indium oxide (ITO) coated quartz by a sol-gel method. Four metal electrodes, such as Pt, Au, Cu and Ag, were used as top electrodes deposited on the same PZT film by sputtering at room temperature. In ITO-PZT-Ag and ITO-PZT-Au structures, the visible light (400-700 nm) can be absorbed partially by a PZT film, and the maximum efficiency of photoelectric conversion of the ITO-PZT-Ag structure was enhanced to 0.42% (100 mW cm(-2), AM 1.5G), which is about 15 times higher than that of the ITO-PZT-Pt structure. Numerical simulations show that the natural random roughness of polycrystalline-PZT-metal interface can offer a possibility of coupling between the incident photons and SPs at the metal surface. The coincidence between the calculated SP properties and the measured EQE spectra reveals the SP origin of the photovoltaic enhancement in these ITO-PZT-metal structures, and the improved photocurrent output is caused by the enhanced optical absorption in the PZT region near the metal surface, rather than by the direct charge-transfer process between two materials.
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Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo.
Kidney Int.
PUBLISHED: 01-22-2014
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Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. We expressed enhanced green fluorescent protein-tagged to ribosomal protein L10a in podocytes under the control of the collagen-1?1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1?1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression data sets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and defines novel biomarkers and therapeutic targets for human glomerular disease.Kidney International advance online publication, 18 June 2014; doi:10.1038/ki.2014.204.
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Two xanthones from Swertia punicea with hepatoprotective activities in vitro and in vivo.
J Ethnopharmacol
PUBLISHED: 01-22-2014
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Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice.
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Toxicity of multi-walled carbon nanotubes, graphene oxide, and reduced graphene oxide to zebrafish embryos.
Biomed. Environ. Sci.
PUBLISHED: 01-09-2014
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This study was aimed to investigate the toxic effects of 3 nanomaterials, i.e. multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO), and reduced graphene oxide (RGO), on zebrafish embryos.
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Enhancement of oral bioavailability of tripterine through lipid nanospheres: preparation, characterization, and absorption evaluation.
J Pharm Sci
PUBLISHED: 01-09-2014
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Oral delivery of anticancer drugs remains challenging because of limited water-solubility and/or poor permeability. Here, we aimed to enhance the oral bioavailability of tripterine (TRI, a plant-derived anticancer compound) using lipid nanospheres (LNs) and to determine the mechanisms of oral absorption. TRI-loaded LNs (TRI-LNs) were prepared by rapid dispersion of an ethanol mixture of TRI, lecithin, sodium oleate, and soybean oil into water. The obtained LNs were 150 nm in size with a high value of entrapment efficiency (99.95%). TRI-LNs were fairly stable and the drug release was negligible (<0.2%) in simulated physiological fluid. The pharmacokinetic results showed that LNs significantly enhanced the oral bioavailability of TRI with a relative bioavailability of 224.88% (TRI suspensions was used as a reference). The mechanistic studies demonstrated that improved intestinal permeability and post-enterocyte lymphatic transport were mainly responsible for the enhanced oral absorption. Our findings suggested that LNs may be a viable oral carrier for poorly bioavailable drugs.
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Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo.
Immunity
PUBLISHED: 01-09-2014
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Patients with systemic autoimmune diseases show increased incidence of atherosclerosis. However, the contribution of proatherogenic factors to autoimmunity remains unclear. We found that atherogenic mice (herein referred to as LDb mice) exhibited increased serum interleukin-17, which was associated with increased numbers of T helper 17 (Th17) cells in secondary lymphoid organs. The environment within LDb mice was substantially favorable for Th17 cell polarization of autoreactive T cells during homeostatic proliferation, which was considerably inhibited by antibodies directed against oxidized low-density lipoprotein (oxLDL). Moreover, the uptake of oxLDL induced dendritic-cell-mediated Th17 cell polarization by triggering IL-6 production in a process dependent on TLR4, CD36, and MyD88. Furthermore, self-reactive CD4(+) T cells that expanded in the presence of oxLDL induced more profound experimental autoimmune encephalomyelitis. These findings demonstrate that proatherogenic factors promote the polarization and inflammatory function of autoimmune Th17 cells, which could be critical for the pathogenesis of atherosclerosis and other related autoimmune diseases.
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Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat.
Cell. Physiol. Biochem.
PUBLISHED: 01-02-2014
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Background: Aging is associated with the gradual cognitive decline and shows the typical senile plaque formation in the brain, which results from the aggregation of beta amyloid (A?) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by ?-secretase (BACE1) and ?-secretase. Accumulating evidence indicates that several microRNAs (miRNAs) are involved in the Alzheimer's disease (AD) by regulating the expression of APP and BACE1 proteins. However, the cognitive ability and the expression profile of the APP- and BACE1-associated miRNAs in the middle-aged population are largely unknown. Methods: The learning and memory ability in rats were determined by Morris Water Maze test. The protein levels of APP and BACE1 were detected by western blotting. The quantitative polymerase chain reaction was used to identify the miRNAs levels in forebrain cortex and the hippocampus. Results: Middle-aged rats have declined learning ability without changes in the memory ability, and increased APP and BACE1 protein expression in the forebrain cortex. Computational analysis using Targetscan and Pictar databases reveals that totally 4 predicted miRNAs have conserved binding site with APP, namely miR-106b, -17-5p, -153, -101. All of them showed decreased expression in both the forebrain cortex and hippocampus. Among the 10 predicted miRNAs targeting BACE1, different expression profiles were identified in the forebrain cortex (decreased: miR-9, -19a, -135a, -15b, -16, -195, -29c, -214; increased: miR-124; no change: miR-141) and the hippocampus (decreased: miR-9, -15b, -16, -195, -29c, -124; increased: miR-19a, -135a, -214, -141) in the middle-aged rats compared with the young rats. Conclusion: Our results provided the first evidence that middle-aged rats have begun displaying cognitive disability with abnormal expression of APP- and BACE1-related miRNAs in the hippocampus and forebrain cortex. © 2014 S. Karger AG, Basel.
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The clinical utility of informants' appraisals on prospective and retrospective memory in patients with early Alzheimer's disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Increasing studies suggest the importance of including prospective memory measures in clinical evaluation of dementia due to its sensitivity and functional relevance. The Prospective and Retrospective Memory Questionnaire (PRQM) is originally a self-rated memory inventory that offers a direct comparison between prospective and episodic memory. However, the informant's report has been recognized as a more valid source of cognitive complaints. We thus aimed to examine the validity of the informant-rated form of the PRMQ in assessing memory function of the patients and in detecting individuals with early dementia. The informants of 140 neurological outpatients with memory complaints completed the Taiwan version of the PRMQ. Tests of prospective memory, short-term memory, and general cognitive ability were also administered to non-demented participants and patients with early stages of Alzheimer's disease (AD). Results showed significant relationships between the PRMQ ratings and objective cognitive measures, and showed that higher ratings on the PRMQ were associated with increasing odds of greater dementia severity. Receiver operative characteristic (ROC) curves showed an adequate ability of the PRMQ to identify patients with dementia (93% sensitivity and 84% specificity). Hierarchical regression revealed that the PRMQ has additional explanatory power for dementia status after controlling for age, education and objective memory test results, and that the prospective memory subscale owns predictive value for dementia beyond the retrospective memory subscale. The present study demonstrated the external validity and diagnostic value of informants' evaluation of their respective patients' prospective and retrospective memory functioning, and highlighted the important role of prospective memory in early dementia detection. The proxy-version of the PRMQ is a useful tool that captures prospective and episodic memory problems in patients with early AD, in combination with standardized cognitive testing.
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P-glycoprotein mediated efflux limits the transport of the novel anti-Parkinson's disease candidate drug FLZ across the physiological and PD pathological in vitro BBB models.
PLoS ONE
PUBLISHED: 01-01-2014
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FLZ, a novel anti-Parkinson's disease (PD) candidate drug, has shown poor blood-brain barrier (BBB) penetration based on the pharmacokinetic study using rat brain. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two important transporters obstructing substrates entry into the CNS as well as in relation to PD neuropathology. However, it is unclear whether P-gp and BCRP are involved in low BBB permeability of FLZ and what the differences of FLZ brain penetration are between normal and Parkinson's conditions. For this purpose, in vitro BBB models mimicking physiological and PD pathological-related BBB properties were constructed by C6 astroglial cells co-cultured with primary normal or PD rat cerebral microvessel endothelial cells (rCMECs) and in vitro permeability experiments of FLZ were carried out. High transepithelial electrical resistance (TEER) and low permeability for sodium fluorescein (NaF) confirmed the BBB functionality of the two models. Significantly greater expressions of P-gp and BCRP were detected in PD rCMECs associated with the lower in vitro BBB permeability of FLZ in pathological BBB model compared with physiological model. In transport studies only P-gp blocker effectively inhibited the efflux of FLZ, which was consistent with the in vivo permeability data. This result was also confirmed by ATPase assays, suggesting FLZ is a substrate for P-gp but not BCRP. The present study first established in vitro BBB models reproducing PD-related changes of BBB functions in vivo and demonstrated that poor brain penetration of FLZ and low BBB permeability were due to the P-gp transport.
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Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions.
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Fine physical and genetic mapping of powdery mildew resistance gene MlIW172 originating from wild emmer (Triticum dicoccoides).
PLoS ONE
PUBLISHED: 01-01-2014
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Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most important wheat diseases in the world. In this study, a single dominant powdery mildew resistance gene MlIW172 was identified in the IW172 wild emmer accession and mapped to the distal region of chromosome arm 7AL (bin7AL-16-0.86-0.90) via molecular marker analysis. MlIW172 was closely linked with the RFLP probe Xpsr680-derived STS marker Xmag2185 and the EST markers BE405531 and BE637476. This suggested that MlIW172 might be allelic to the Pm1 locus or a new locus closely linked to Pm1. By screening genomic BAC library of durum wheat cv. Langdon and 7AL-specific BAC library of hexaploid wheat cv. Chinese Spring, and after analyzing genome scaffolds of Triticum urartu containing the marker sequences, additional markers were developed to construct a fine genetic linkage map on the MlIW172 locus region and to delineate the resistance gene within a 0.48 cM interval. Comparative genetics analyses using ESTs and RFLP probe sequences flanking the MlIW172 region against other grass species revealed a general co-linearity in this region with the orthologous genomic regions of rice chromosome 6, Brachypodium chromosome 1, and sorghum chromosome 10. However, orthologous resistance gene-like RGA sequences were only present in wheat and Brachypodium. The BAC contigs and sequence scaffolds that we have developed provide a framework for the physical mapping and map-based cloning of MlIW172.
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Identification of a novel protein complex containing ASIC1a and GABAA receptors and their interregulation.
PLoS ONE
PUBLISHED: 01-01-2014
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Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are widely distributed within both the central and peripheral nervous systems. ASICs were modified by the activation of ?-aminobutyric acid receptors (GABAA), a ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity of GABAA receptors were also modulated by extracellular pH. However so far, the mechanisms underlying this intermodulation remain obscure. We hypothesized that these two receptors-GABAA receptors and ASICs channels might form a novel protein complex and functionally interact with each other. In the study reported here, we found that ASICs were modified by the activation of GABAA receptors either in HEK293 cells following transient co-transfection of GABAA and ASIC1a or in primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of ASIC1a also modifies the GABAA receptor-channel kinetics. Immunoassays showed that both GABAA and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABAA and ASIC1a or in primary cultured DRG neurons. Our results indicate that putative GABAA and ASIC1a channels functionally interact with each other, possibly via an inter-molecular association by forming a novel protein complex.
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Effects of acupuncture at GV20 and ST36 on the expression of matrix metalloproteinase 2, aquaporin 4, and aquaporin 9 in rats subjected to cerebral ischemia/reperfusion injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Ischemic stroke is characterized by high morbidity and mortality worldwide. Matrix metalloproteinase 2 (MMP2), aquaporin (AQP) 4, and AQP9 are linked to permeabilization of the blood-brain barrier (BBB) in cerebral ischemia/reperfusion injury (CIRI). BBB disruption, tissue inflammation, and MMP/AQP upregulation jointly provoke brain edema/swelling after CIRI, while acupuncture and electroacupuncture can alleviate CIRI symptoms. This study evaluated the hypothesis that acupuncture and electroacupuncture can similarly exert neuroprotective actions in a rat model of middle cerebral artery occlusion (MCAO) by modulating MMP2/AQP4/APQ9 expression and inflammatory cell infiltration.
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[The pulmonary function and respiratory muscle power in multiple systemic atrophy and Parkinsons disease].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 11-26-2013
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To investigate the characteristics of pulmonary function and respiratory muscle performance in patients with multiple system atrophy (MSA) and Parkinsons disease (PD).
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Metabolite elucidation of the Hsp90 inhibitor SNX-2112 using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS).
Xenobiotica
PUBLISHED: 11-05-2013
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Abstract 1.? The novel heat-shock protein 90 inhibitor SNX-2112 is a promising drug candidate for treating various types of cancers. Here we aim to determine the metabolic pathways of SNX-2112 in rats in vivo and in humans in vitro. 2.? Metabolite identification was performed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method. In vitro metabolism studies were performed using liver and intestine microsomes, as well as recombinant human cytochrome P450 (CYP) enzymes. 3.? Analysis of rat plasma, urine, and feces revealed a total of eight metabolites, one reductive metabolite (M1), one structurally unknown metabolite (M2), and six mono-oxidative metabolites (M3-1, M3-2, M3-3, M3-4, M3-5, and M3-6). The reduction, M2, and mono-oxidation pathways were responsible for 0.8?±?0.3 %, 18.3?±?9.1 %, and 39.4%?±?6.1 of SNX-2112 clearance from rats, respectively. 4.? SNX-2112 was subjected to the same types of metabolism in human liver and intestine microsomes. Reaction phenotyping showed that CYP3A4, 3A5, 2D6, and 1A1 were mainly responsible for SNX-2112 metabolism. 5.? In conclusion, we have elucidated the metabolic pathways of SNX-2112 and highlighted that metabolism was the predominant pathway for its clearance. Better understanding of SNX-2112 metabolism should facilitate the drug development of this promising anti-cancer agent.
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Squamosamide derivative FLZ protected dopaminergic neuron by activating Akt signaling pathway in 6-OHDA-induced in vivo and in vitro Parkinsons disease models.
Brain Res.
PUBLISHED: 11-01-2013
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Parkinsons disease (PD) is a neurodegenerative disease affecting up to 80% of dopaminergic neurons in the nigrostriatal pathway. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, has been shown to have neuroprotective effects in experimental PD models. In this study, we carried out a set of in vitro and in vivo experiments to address the neuroprotective effect of FLZ and related mechanism. The results showed that FLZ significantly improved motor dysfunction and dopaminergic neuronal loss of rats injured by 6-hydroxydopamine (6-OHDA). The beneficial effects of FLZ attributed to the elevation of dopaminergic neuron number, dopamine level and tyrosine hydroxylase (TH) activity. Mechanistic study showed that FLZ protected TH activity and dopaminergic neurons through decreasing ?-synuclein (?-Syn) expression and the interaction between ?-Syn and TH. Further studies indicated the involvement of phosphoinositide 3-kinases (PI3K)/Akt signaling pathway in the protective effect of FLZ since it showed that blocking PI3K/Akt signaling pathway prevented the expression of ?-Syn and attenuated the neuroprotection of FLZ. In addition, FLZ treatment reduced the expression of RTP801, an important protein involved in the pathogenesis of PD. Taken together, these results revealed that FLZ suppressed ?-Syn expression and elevated TH activity in dopaminergic neuron through activating Akt survival pathway in 6-OHDA-induced PD models. The data also provided evidence that FLZ had potent neuroprotecive effects and might become a new promising agent for PD treatment.
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2-(1-(2-Benzhydrylnaphthylimino)ethyl)pyridylnickel halides: synthesis, characterization, and ethylene polymerization behavior.
Dalton Trans
PUBLISHED: 10-14-2013
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A series of 2-(1-(2-benzhydrylnaphthylimino)ethyl)pyridine derivatives (L1-L3) was synthesized and fully characterized. The organic compounds acted as bi-dentate ligands on reacting with nickel halides to afford two kinds of nickel complexes, either mononuclear bis-ligated L2NiBr2 (Ni1-Ni3) or chloro-bridged dinuclear L2Ni2Cl4 (Ni4-Ni6) complexes. The nickel complexes were fully characterized, and the single crystal X-ray diffraction revealed for Ni2, a distorted square pyramidal geometry at nickel comprising four nitrogens of two ligands and one bromide; whereas for Ni4, a centrosymmetric dimer possessing a distorted octahedral geometry at nickel was formed by two nitrogens of one ligand, two bridging chlorides and one terminal chloride along with oxygen from methanol (solvent). When activated with diethylaluminium chloride (Et2AlCl), all nickel complexes performed with high activities (up to 1.22 × 10(7) g (PE) mol(-1) (Ni) h(-1)) towards ethylene polymerization; the obtained polyethylene possessed high branching, low molecular weight and narrow polydispersity, suggestive of a single-site active species. The effect of the polymerization parameters, including the nature of the ligands/halides on the catalytic performance is discussed.
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Variation of blood T lymphocyte subgroups in patients with non- small cell lung cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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To study variation in T lymphocyte subgoups and its clinical significance in non-small cell lung cancer (NSCLC).
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One-pot facile synthesis of a concentrated Si nanoparticle solution.
Chem. Commun. (Camb.)
PUBLISHED: 09-25-2013
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A silicon nanoparticle solution (size ? 50 nm) with the concentration of 100 mM, which is contamination free, was synthesized using a ball milling method and was stable for 4 months without aggregation. This stability was responsible for large negative zeta potential on the surface of Si-NPs, established by milling in 2-propanol solvent.
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PCAF impairs endometrial receptivity and embryo implantation by down-regulating ?3-integrin expression via HOXA10 acetylation.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-13-2013
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Homeobox A10 (HOXA10), a key transcription factor, plays a critical role in endometrial receptivity by regulating the expression of downstream target genes, such as ?3-integrin (ITGB3), but little is understood about the mechanisms of the posttranslational modification of HOXA10 during embryo implantation.
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[Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 09-04-2013
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This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.
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Clinical observations on the association between diagnosis of lung cancer and serum tumor markers in combination.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-03-2013
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To evaluate the association of a diagnosis of lung cancer and combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1).
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[Pathological and immunohistochemical analyses of 32 cases of nephrogenic adenoma].
Beijing Da Xue Xue Bao
PUBLISHED: 08-14-2013
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To observe clinical and pathological features of nephrogenic adenoma (NA), and to find some useful immunohistochemical markers for its diagnosis.
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Plasma tau as a window to the brain-negative associations with brain volume and memory function in mild cognitive impairment and early alzheimers disease.
Hum Brain Mapp
PUBLISHED: 07-26-2013
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Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimers disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders (HE). All received a 3D-brain MRI scan and a set of cognitive function test. We explored their relationships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the performance of logical memory, visual reproduction, and verbal fluency; also negatively associated with volume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions. Regression analyses indicated that logical memory explained 0.394 and hippocampus volume predicted .608 of the variance of plasma tau levels, both P < 0.001. Education years were negatively associated with the gray matter densities of the supramarginal (r = -0.407), middle temporal gyrus (r = -0.40) and precuneus (r = -0.377; all P < 0.05) in HE; and negatively associated with plasma tau levels in patients (r = -0.626). We propose that plasma tau may serve as a window to both structure and function of the brain. Higher education is a protective factor against AD and is associated with lower plasma tau levels in patients. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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Zinc 2-((2-(benzoimidazol-2-yl)quinolin-8-ylimino)methyl)phenolates: synthesis, characterization and photoluminescence behavior.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 07-12-2013
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A series of 2-(2-(1H-benzoimidazol-2-yl)quinolin-8-yliminomethyl)phenol derivatives and their zinc complexes (C1-C5) were synthesized and fully characterized. The molecular structure of the representative complex C2 was determined by single crystal X-ray diffraction, which revealed that the zinc was five-coordinated with the tetra-dentate ligand and a methanol bound to the metal to afford a distorted square-pyramidal geometry. The UV-Vis absorption and fluorescence spectra of the organic compounds and their zinc complexes were measured and investigated in various solvents such as methanol, THF, dichloromethane, and toluene; significant influences by solvents were observed on their luminescent properties; red-shifts for the zinc complexes were clearly observed in comparison to the free organic compounds.
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SKB1/PRMT5-mediated Histone H4R3 Dimethylation of Ib Subgroup bHLH Genes Negatively Regulates Iron Homeostasis in Arabidopsis thaliana.
Plant J.
PUBLISHED: 06-18-2013
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Histone modifications play critical roles in the perception of environmental cues by plants. Here, we report that Shk 1 binding protein 1 (SKB1/AtPRMT5), which catalyzes symmetric dimethylation of histone H4R3 (H4R3sme2), is involved in iron homeostasis in Arabidopsis. SKB1-lesion mutant exhibited higher iron accumulation in shoots and greater tolerance to iron deficiency than wild-type. The expression of SKB1 was not affected by iron, but the level of H4R3sme2 mediated by SKB1 was related to iron status in plants. We showed by chromatin immunoprecipitation (ChIP) and genome-wide ChIP-seq that SKB1 associated with the chromatin of the Ib subgroup bHLH genes (AtbHLH38, AtbHLH39, AtbHLH100, and AtbHLH101), and symmetrically dimethylated histone H4R3. The amount of SKB1 that associated with chromatin of the Ib subgroup bHLH genes and the level of H4R3sme2 corresponded to the iron status of plants (higher with increased iron supply and lower when iron was removed). We conclude that SKB1-mediated H4R3sme2 regulates iron homeostasis in Arabidopsis in the context of increasing or decreasing expression of Ib subgroup bHLH genes. Iron deficiency may cause an increase in disassociation of SKB1 from chromatin of the bHLH genes and a decrease in the level of H4R3sme2, thereby elevating their transcription and enhancing iron uptake. Our findings provide new insight into the molecular mechanisms of iron homeostasis in strategy I plants. This article is protected by copyright. All rights reserved.
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Vasorelaxant effects of the extracts and some flavonoids from the buds of Coreopsis tinctoria.
Pharm Biol
PUBLISHED: 06-13-2013
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The buds of Coreopsis tinctoria Nutt (Compositae) are used in the treatment of hypertension in the Uyghur folk medicine in China.
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Evident cognitive impairments in seemingly recovered patients after midazolam-based light sedation during diagnostic endoscopy.
J. Formos. Med. Assoc.
PUBLISHED: 06-11-2013
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Midazolam is a widely used sedative agent during colonoscopy, with cognitive toxicity. However, the potential cognitive hazard of midazolam-based light sedation has not been sufficiently examined. We aimed to examine the cognitive safety and vulnerability profile under midazolam light sedation, with a particular focus on individual variations.
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[Efficacy observation on knee osteoarthritis treated with electroacupuncture and its influence on articular cartilage with T2 mapping].
Zhongguo Zhen Jiu
PUBLISHED: 05-30-2013
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To observe therapeutic efficacy of osteoarthritis treated by electroacupuncture, and explore its function of promoting cartilage restoration.
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[Role of cyclic adenosine monophosphate(cAMP) in the regulation of intestinal epithelial barrier function under hypoxia].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 05-23-2013
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To investigate the role of cyclic adenosine monophosphate(cAMP) in the regulation of intestinal epithelial barrier function under hypoxia.
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[Nuclear transfer and reprogramming in fish].
Yi Chuan
PUBLISHED: 05-11-2013
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As an important sub-field in the study of animal cloning, fish nuclear transfer was first established in the early 1960s by Chinese embryologists. Due to its advantages, zebrafish has become a unique animal model to study the mystery of reprogramming in nuclear transfer. This article summarizes the history and current situation in fish nuclear transfer technology and discusses the factors that may influence the development of the cloned embryos. A comprehensive understand-ing of the mechanism for epigenetic modification following nuclear transfer, such as genomic DNA methylation and histone acetylation and/or methylation, will likely increase the success rate and eventually lead to the future freedom of cloning technique.
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Divergent manifestations of irritability in patients with mild and moderate-to-severe traumatic brain injury: perspectives of awareness and neurocognitive correlates.
Brain Inj
PUBLISHED: 05-10-2013
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To evaluate irritability in patients with mild traumatic brain injury (mTBI) and moderate-to-severe traumatic brain injury (msTBI), respectively.
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Effects of electroacupuncture on depression and the production of glial cell line-derived neurotrophic factor compared with fluoxetine: a randomized controlled pilot study.
J Altern Complement Med
PUBLISHED: 05-06-2013
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Postmortem studies indicate that the number and density of glial cells are reduced in different brain regions of patients with depression. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the pathogenesis of depressive disorder (DD) and might be a biomarker for damage to nerve cells. In this study, we compared the therapeutic effects of electroacupuncture (EA) and fluoxetine, a serotonin reuptake inhibitor, on DD patients, focusing on the serum level of GDNF.
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Molecular characterization, expression patterns, and association analysis with carcass traits of porcine USF1 gene.
Appl. Biochem. Biotechnol.
PUBLISHED: 05-01-2013
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The upstream stimulatory factor 1 (USF1) is a transcription factor controlling expression of several genes involved in lipid and glucose homeostasis. In this study, two isoforms of the porcine USF1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR), termed USF1 wild-type (wt) and USF1/CD, both of them contain a helix-loop-helix leucine zipper (HLH-LZ) conserved domain. Tissue distribution analysis showed that the two transcripts of porcine USF1 gene were ubiquitously expressed in all tested tissues, except for heart. Moreover, we found that a single nucleotide polymorphism (SNP, C/T) in intron 10 was significantly associated with ratio of lean to fat (P < 0.05), dress percentage (P < 0.05), average backfat thickness (P < 0.05), loin eye width (P < 0.05), lean meat percentage (P < 0.01), loin eye height (P < 0.01), and loin eye area (P < 0.01). This result suggests that porcine USF1 gene may be a candidate gene of meat production trait.
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[Clinical and prognostic analysis of 101 cases of primary gastrointestinal non-Hodgkins lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 05-01-2013
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This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkins lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkins lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P < 0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkins lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkins lymphoma, IPI score and pathological type are independent risk factors affecting OS.
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Inverted formin 2 regulates actin dynamics by antagonizing Rho/diaphanous-related formin signaling.
J. Am. Soc. Nephrol.
PUBLISHED: 04-25-2013
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Mutations in inverted formin 2 INF2 are a common cause of familial FSGS. INF2 interacts with diaphanous-related formins (mDia) and antagonizes mDia-mediated actin polymerization in response to active Rho signaling, suggesting that dysregulation of these pathways may mediate the development of INF2-related FSGS. However, the precise mechanisms by which INF2 regulates actin-dependent podocyte behavior remain largely unknown. Here, we investigated the possible role of INF2 in both lamellipodia-associated actin dynamics and actin-dependent slit diaphragm (SD) protein trafficking by manipulating the expression of INF2 and the activity of Rho/mDia signaling in cultured podocytes. Activation of mDia in the absence of INF2 led to defective formation of lamellipodia and abnormal SD trafficking. Effects of mutations disrupting the INF2-mDia interaction suggested the specificity of the mDia-antagonizing effect of INF2 in maintaining the lamellipodium. Furthermore, we found that SD trafficking requires INF2 interaction with lipid raft components. In summary, INF2 regulates lamellipodial actin dynamics and the trafficking of slit diaphragm proteins by opposing Rho/mDia-mediated actin polymerization. Thus, in podocytes, INF2 appears to be an important modulator of actin-dependent behaviors that are under the control of Rho/mDia signaling.
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Long-term Expression of Apolipoprotein B mRNA-specific Hammerhead Ribozyme via scAAV8.2 Vector Inhibits Atherosclerosis in Mice.
Mol Ther Nucleic Acids
PUBLISHED: 04-01-2013
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Target substrate-specific hammerhead ribozyme cleaves the specific mRNA efficiently and results in the inhibition of gene expression. In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. The goal of this study is to demonstrate that long-term reduction of apoB gene expression using hammerhead ribozyme would result in inhibition of atherosclerosis development. We designed two hammerhead ribozymes targeted at the nucleotides of apoB mRNA GUC(2326) (designated RB1) and GUA(6679) (designated RB15), and we used self-complementary adeno-associated virus 8.2 (scAAV8.2) vector to deliver these active ribozymes of RB1, RB15, combination of RB1/RB15, and an inactive hammerhead ribozyme RB15 mutant to atherosclerosis-prone LDb mice (Ldlr(-/-)Apobec1(-/-)). LDb mice lack both low density lipoproteins (LDL) receptor (Ldlr(-/-)) and apoB mRNA editing enzyme (Apobec1(-/-)) genes and develop atherosclerosis spontaneously. After the RB1, RB15, or combination of RB1/RB15 ribozymes treatment, the LDb mice had significantly decreased plasma triglyceride and apoB levels, resulting in markedly decreased of atherosclerotic lesions, Furthermore, the active ribozymes treatment decreased the levels of diacylglycerol acyltransferase 1 (Dgat1) mRNA and the levels of multiple diacylglycerol (DAG) molecular species. These results provide the first evidence that decreased apoB levels results to reduction of Dgat1 expression and triglyceride levels (TAG), which had a significant impact on the development of atherosclerosis.Molecular Therapy-Nucleic Acids (2013) 2, e125; doi:10.1038/mtna.2013.53; published online 1 October 2013.
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Z-ligustilide activates the Nrf2/HO-1 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro.
Brain Res.
PUBLISHED: 03-26-2013
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Z-ligustilide (LIG), the main lipophilic component of Radix Angelica sinensis, has been shown to protect against brain ischemic damage in rodents by oral and intra-peritoneal treatments. The present study aimed to confirm the therapeutic effect of LIG administered intravenously on 2h middle cerebral artery occlusion (MCAO) and 22 h reperfusion injury in rats since oral administration has low bioavailability, slow absorption and distribution. Moreover, whether LIG activated the NF-E2-related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway was also investigated in vivo and in vitro to further elucidate the precise protective mechanisms. In vivo, rats treated intravenously with LIG immediately after the surgery was finished had less neurological dysfunction and smaller infarct volume than that of the vehicle-treated rats. Additionally, LIG promoted Nrf2 nuclear translocation, and further remarkably increased Nrf2 and HO-1 protein expression. In vitro, LIG induced Nrf2 nuclear translocation and up-regulated HO-1 expression in a time-dependent and concentration-dependent manner. Furthermore, LIG treatment reduced cell death induced by OGD, however, the protective action was abolished while Nrf2/HO-1 expression was knockdown by RNA interference. These results noted that intravenous post-treatment with LIG exhibits noticeable neuroprotective properties against brain damage by ischemia-reperfusion and the ability of LIG to activate Nrf2/HO-1 pathway may be partly responsible for it.
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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.