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Find video protocols related to scientific articles indexed in Pubmed.
Spontaneous calf hematoma in a patient with diabetic nephropathy receiving maintenance hemodialysis: A case report and review of the literature.
Hemodial Int
PUBLISHED: 11-19-2014
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We report the outcome of a 52-year-old patient with diabetic nephropathy and receiving maintenance hemodialysis (HD) using low molecular weight heparin (LMWH) as an anticoagulant for 2 years. He presented right lower limb pain accompanied with difficulty in walking for 2 months, and had no history of bleeding tendency or trauma. Physical examination revealed marked swelling and tenderness on his right lower limb. By ultrasound and magnetic resonance imaging (MRI) diagnoses, the calf hematoma was diagnosed and identified with venous thrombosis. Following treatment with heparin-free HD, the swelling regressed and pain subsided, and a follow-up MRI showed complete dissolution of hematoma. However, similar symptoms recurred in the right upper limb after 2 months without any predisposition, he was just placed on HD with LMWH, and symptoms regressed following the aforementioned therapy. This suggests that HD patients, especially with diabetic nephropathy having extremity hematoma, should be watched for the development of spontaneous hemorrhage that can be differentially diagnosed by imaging tests, such as MRI, and can be effectively treated with heparin-free HD.
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CYCLIN-DEPENDENT KINASE8 Differentially Regulates Plant Immunity to Fungal Pathogens through Kinase-Dependent and -Independent Functions in Arabidopsis.
Plant Cell
PUBLISHED: 10-03-2014
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CYCLIN-DEPENDENT KINASE8 (CDK8) is a widely studied component of eukaryotic Mediator complexes. However, the biological and molecular functions of plant CDK8 are not well understood. Here, we provide evidence for regulatory functions of Arabidopsis thaliana CDK8 in defense and demonstrate its functional and molecular interactions with other Mediator and non-Mediator subunits. The cdk8 mutant exhibits enhanced resistance to Botrytis cinerea but susceptibility to Alternaria brassicicola. The contributions of CDK8 to the transcriptional activation of defensin gene PDF1.2 and its interaction with MEDIATOR COMPLEX SUBUNIT25 (MED25) implicate CDK8 in jasmonate-mediated defense. Moreover, CDK8 associates with the promoter of AGMATINE COUMAROYLTRANSFERASE to promote its transcription and regulate the biosynthesis of the defense-active secondary metabolites hydroxycinnamic acid amides. CDK8 also interacts with the transcription factor WAX INDUCER1, implying its additional role in cuticle development. In addition, overlapping functions of CDK8 with MED12 and MED13 and interactions between CDK8 and C-type cyclins suggest the conserved configuration of the plant Mediator kinase module. In summary, while CDK8's positive transcriptional regulation of target genes and its phosphorylation activities underpin its defense functions, the impaired defense responses in the mutant are masked by its altered cuticle, resulting in specific resistance to B. cinerea.
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Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin-lightening cream.
Ann Saudi Med
PUBLISHED: 10-01-2014
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A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.
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Estimation of left ventricular stroke volume based on pressure waves measured at the wrist: a method aimed at home-based use.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Continuous monitoring of stroke volume (SV) or cardiac output (CO) has long been the subject of numerous studies. The majority of existing methods are calibration-dependent, requiring invasive measurements of CO to initialize the estimation algorithms, thus limiting their application to the clinical setting. In the present study, a new calibration-free method aimed at home-based use has been developed, which allows noninvasive estimation of SV from oscillometric signals measured at the wrist. The estimation equation was constructed based on the PRAM method, with significant modifications to incorporate more patient-specific information. Furthermore, the estimation equation was optimized based on the clinical data acquired from 96 patients (the 'Training' group) to obtain the best comparison of estimated SV with echocardiographic SV. The resulting estimation equation was then applied directly to another patient group (the 'Testing' group) to examine its validity. Obtained results demonstrate that our estimations correlated closely with the measurements in both patient groups. In addition to being noninvasive and calibration-free, the proposed method can be fully automated, which may be valuable for the future development of home-based cardiac monitoring systems.
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Effect of dialysis dose and membrane flux on hemoglobin cycling in hemodialysis patients.
Hemodial Int
PUBLISHED: 09-13-2014
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Many studies found that hemoglobin (Hb) fluctuation was closely related to the prognosis of the maintenance hemodialysis patients. We investigated the association of factors relating dialysis dose and dialyzer membrane with Hb levels. We undertook a randomized clinical trial in 140 patients undergoing thrice-weekly dialysis and assigned patients randomly to a standard or high dose of dialysis; Hb level was measured every month for 12 months. In the standard-dose group, the mean (±SD) urea reduction ratio was 65.1%?±?7.3%, the single-pool Kt/V was 1.26?±?0.11, and the equilibrated Kt/V was 1.05?±?0.09; in the high-dose group, the values were 73.5%?±?8.7%, 1.68?±?0.15, and 1.47?±?0.11, respectively. The standard deviation (SD) and residual SD (liner regression of Hb) values of Hb were significantly higher in the standard-dose group and low-flux group. The percentage achievement of target Hb in the high-dose dialysis group and high-flux dialyzer group was significantly higher than the standard-dose group and low-flux group, respectively. Patients undergoing hemodialysis thrice weekly appear to have benefit from a higher dialysis dose than that recommended by current KDQQI (Kidney Disease Qutcome Quality Initiative) guidelines or from the use of a high-flux membrane, which is in favor of maintaining stable Hb levels.
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RISK FACTORS FOR MORTALITY IN CHINESE PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIALYSIS.
Perit Dial Int
PUBLISHED: 09-02-2014
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? Objective: The intent of this study was to evaluate the clinical outcome and risk factors affecting mortality of the continuous ambulatory peritoneal dialysis (CAPD) patients in a single peritoneal dialysis (PD) center over a period of 10years. ? Patients and methods: We retrospectively analyzed patients on PD from June 2001 to June 2011. The clinical and biochemical data were collected from the medical records. Clinical variables included gender, age at the start of PD, smoking status, body mass index (BMI), cause of end-stage renal disease (ESRD), presence of diabetes mellitus and blood pressure. Biochemical variables included hemoglobin, urine volume, residual renal function (RRF), serum albumin, blood urea nitrogen (BUN), creatinine, total cholesterol, triglyceride, comorbidities, and outcomes. Survival curves were made by the Kaplan-Meier method. Univariate and multivariate analyses to identify mortality risk factors were performed using the Cox proportional hazard regression model. ? Results: A total of 421 patients were enrolled, 269 of whom were male (63.9%). The mean age at the start of PD was 57.9 ± 14.8 years. Chronic glomerulonephritis was the most common cause of ESRD (39.4%). Estimation of patient survival by Kaplan-Meier was 92.5%, 80.2%, 74.4%, and 55.7% at 1, 3, 5, and 10 years, respectively. Patient survival was associated with age (hazard ratio [HR]: 1.641 [1.027 - 2.622], p = 0.038), cardiovascular disease (HR: 1.731 [1.08 - 2.774], p = 0.023), hypertriglyceridemia (HR: 1.782 [1.11 - 2.858], p = 0.017) in the Cox proportional hazards model analysis. Estimation of technique survival by Kaplan-Meier was 86.7%, 68.8%, 55.7%, and 37.4% at 1, 3, 5, and 10 years, respectively. In the Cox proportional hazards model analysis, age (HR: 1.672 [1.176-2.377], p=0.004) and hypertriglyceridemia (HR: 1.511 [1.050-2.174], p = 0.026) predicted technique failure. ? Conclusion: The PD patients in our center exhibited comparable or even superior patient survival and technical survival rates, compared with reports from other centers in China and other countries.
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High glucose-induced Galectin-1 in human podocytes implicates the involvement of Galectin-1 in diabetic nephropathy.
Cell Biol. Int.
PUBLISHED: 09-02-2014
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The diabetic milieu is believed to change the activity, or result in damage of podocytes-a key component of the glomerular filtration barrier and known to secrete matrix for glomerular basement membrane. This in turn contributes to diabetic nephropathy. However, how podocyte dysfunction is triggered in diabetic nephropathy remains ambiguous. Galectin-1 belongs to Galectin family that bind to ?-galactoside residues of glycosylated proteins. We explored whether Galectin-1 is dysregulated in diabetic nephropathy using three different techniques, namely real-time polymerase chain reaction, western blotting, and immunofluorescent staining, to follow the expression of Galectin-1 under high glucose levels in podocytes. High glucose consistently induced Galectin-1 expression. Immunohistochemistry using a Galectin-1-specific antibody also showed elevated Galectin-1 in renal tissues of diabetic patients with manifestation of nephropathy, indicating a correlation of Galectin-1 overexpression with diabetic nephropathy. Upregulation of Galectin-1 is associated with loss of podocin, which is important for the physiological function of podocytes and decreases in the renal tissues of diabetic nephropathy. Increased Galectin-1 is a causal event for the high glucose-induced loss of podocin, since silencing Galectin-1 in podocytes increased podocin expression in the presence of 25?mM glucose. Thus expression of Galectin-1 in diabetic nephropathy may serve as a marker and contribute to disease progression by interfering with podocin expression.
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The biosafety of lanthanide upconversion nanomaterials.
Chem Soc Rev
PUBLISHED: 08-12-2014
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Lanthanide upconversion nanophosphors (UCNPs) show unique upconversion luminescence where lower-energy photons (such as near-infrared (NIR) excitation) are converted into higher-energy photons covering the NIR to the UV region, and are considered to have a bright future in clinical translation. As UCNPs are used in a significant number of potential bio-applications, their biosafety is important and has attracted significant attention. In this critical review, recent reports regarding the cellular internalization, biodistribution, excretion, cytotoxicity and in vivo toxic effects of UCNPs are reviewed. In particular, the studies which evaluated the association between the chemical and physical properties of UCNPs and their biodistribution, excretion, and toxic effects are presented in detail. Finally, we also discuss the challenges of ensuring the biosafety of UCNPs in vivo.
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Hemodynamic performance of the Fontan circulation compared with a normal biventricular circulation: a computational model study.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 07-25-2014
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The physiological limitations of the Fontan circulation have been extensively addressed in the literature. Many studies emphasized the importance of pulmonary vascular resistance in determining cardiac output (CO) but gave little attention to other cardiovascular properties that may play considerable roles as well. The present study was aimed to systemically investigate the effects of various cardiovascular properties on clinically relevant hemodynamic variables (e.g., CO and central venous pressure). To this aim, a computational modeling method was employed. The constructed models provided a useful tool for quantifying the hemodynamic effects of any cardiovascular property of interest by varying the corresponding model parameters in model-based simulations. Herein, the Fontan circulation was studied compared with a normal biventricular circulation so as to highlight the unique characteristics of the Fontan circulation. Based on a series of numerical experiments, it was found that 1) pulmonary vascular resistance, ventricular diastolic function, and systemic vascular compliance play a major role, while heart rate, ventricular contractility, and systemic vascular resistance play a secondary role in the regulation of CO in the Fontan circulation; 2) CO is nonlinearly related to any single cardiovascular property, with their relationship being simultaneously influenced by other cardiovascular properties; and 3) the stability of central venous pressure is significantly reduced in the Fontan circulation. The findings suggest that the hemodynamic performance of the Fontan circulation is codetermined by various cardiovascular properties and hence a full understanding of patient-specific cardiovascular conditions is necessary to optimize the treatment of Fontan patients.
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DNA gated photochromism and fluorescent switch in a thiazole orange modified diarylethene.
Chem. Commun. (Camb.)
PUBLISHED: 07-04-2014
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Thiazole orange-modified diarylethene (1) shows weak fluorescence but no photochromism in aqueous solution. When binding with DNA, the fluorescence of 1 is enhanced drastically and the photochromic reactivity is unlocked. This kind of DNA-responsive photoswitchable system can be used for imaging nucleic acids within cells.
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Numerical validation of a suprasystolic brachial cuff-based method for estimating aortic pressure.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Central aortic pressures are better predictors of cardiovascular events than peripheral pressures. However, central aortic blood pressures cannot be measured noninvasively; for this reason, estimating aortic pressures from noninvasive measurements of peripheral pressures has been the subject of numerous studies. In the present study, a novel method was proposed to noninvasively estimate aortic pressures from the oscillometric wave of a suprasystolic brachial cuff. The errors of estimation were evaluated in relation to various cardiovascular properties using an integrated cardiovascular-cuff model. Obtained results demonstrated that the estimation errors are affected mainly by aortic stiffness. The estimation errors for aortic systolic pressure, diastolic pressure, pulse pressure and wave shape under the assumed cardiovascular conditions were 5.84 ± 1.58 mmHg, -0.28 ± 0.41 mmHg, 6.12 ± 1.42 mmHg and 1.72 ± 0.57 mmHg, respectively, all of which fell within the error ranges established by existing devices. Since the method is easy to be automated and bases the estimation fully on patient-specific information, its clinical application is promising, although further clinical studies are awaited to validate the method in vivo.
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Aptamer-functionalized solid phase microextraction-liquid chromatography/tandem mass spectrometry for selective enrichment and determination of thrombin.
Anal. Chim. Acta
PUBLISHED: 06-05-2014
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In this publication, a novel solid phase microextraction (SPME) coating functionalized with a DNA aptamer for selective enrichment of a low abundance protein from diluted human plasma is described. This approach is based on the covalent immobilization of an aptamer ligand on electrospun microfibers made with the hydrophilic polymer poly(acrylonitrile-co-maleic acid) (PANCMA) on stainless steel rods. A plasma protein, human ?-thrombin, was employed as a model protein for selective extraction by the developed Apt-SPME probe, and the detection was carried out with liquid chromatography/tandem mass spectrometry (LC-MS/MS). The SPME probe exhibited highly selective capture, good binding capacity, high stability and good repeatability for the extraction of thrombin. The protein selective probe was employed for direct extraction of thrombin from 20-fold diluted human plasma samples without any other purification. The Apt-SPME method coupled with LC-MS/MS provided a good linear dynamic range of 0.5-50 nM in diluted human plasma with a good correlation coefficient (R(2)=0.9923), and the detection limit of the proposed method was found to be 0.30 nM. Finally, the Apt-SPME coupled with LC-MS/MS method was successfully utilized for the determination of thrombin in clinical human plasma samples. One shortcoming of the method is its reduced efficiency in undiluted human plasma compared to the standard solution. Nevertheless, this new aptamer affinity-based SPME probe opens up the possibility of selective enrichment of a given targeted protein from complex sample either in vivo or ex vivo.
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[Research progress of three-dimensional printing technique in joint surgery].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 05-22-2014
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To summarize the application status of three-dimensional (3-D) printing technique in joint surgery and look forward to the future research directions.
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New insights into the pathogenesis of IgA nephropathy: do toll like receptor 9-B cell activation factor-IgA class switching recombination signaling axis induce IgA hyper-production?
Ren Fail
PUBLISHED: 05-15-2014
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IgA nephropathy (IgAN) has become the most common form of primary glomerular disease worldwide. So far, it is still not very clear about the exact pathogenesis of IgAN, thus has no specific therapy. Generally mesangial deposition of IgA, especially polymeric IgA1 (pIgA1), suggests to be the initiating event in the pathogenesis of IgAN. In addition to decreased IgA clearance, IgA over production may also participate in the pathogenesis of IgAN. IgA class switching recombination (CSR) played key role during the process of IgA production. Stimulated with hemolytic streptococcus, tonsillar mononuclear cells (TMCs) of patients with IgAN presented with increased levels of Ia-Ca and activation-induced cytidine deaminase (AID), which are significant for IgA CSR. Human B cells and plasmacytoid dendritic cells express Toll-like receptor (TLR)-9, whose natural ligands are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of bacterial DNA (CpG-DNA). Unmethylated deoxycytidylic-deoxyguanosine oligodeoxynucleotide (CpG-ODN) is able to mimic the immunostimulatory activity of microbial DNA. Study found a significant increase in B cell activation factor (BAFF) production when tonsillar mononuclear cells stimulated with CpG-ODN in patients with IgAN. BAFF can induce germline C? gene expression, AID expression, and IgA class switching in a CD40-independent manner. Therefore, it could be hypothesized that in IgAN there may exist TLR9-BAFF-IgA CSR axis, which induces excessive IgA production. If the hypothesis is correct, it could be of great significance for pathogenesis of IgAN elucidate and IgAN treatment.
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A phosphorescent iridium(III) solvent complex for multiplex assays of cell death.
Biomaterials
PUBLISHED: 05-14-2014
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Cell death involves loss of transport function and physical integrity of the plasma membrane, and plays a critical role in many human diseases. At present, the development of an effective visualization tool to monitor cell death remains a significant challenge. Here, a cyclometalated iridium(III) solvent complex [Ir(pdz)2(H2O)2](+)[OTf](-) (IrC1) was designed and synthesized as a phosphorescent indicator of cell death. IrC1 specifically stained the nuclei of dead cells over living cells rapidly (<10 min) and at low concentrations (10 ?M), as observed using confocal luminescence microscopy. Moreover, the IrC1 uptake behavior leads to its further application in quantifying the population of early apoptotic cells using flow cytometry. In particular, successful application in time-gated fluorescence microscopy by virtue of its microsecond lifetime rendered IrC1 attractive as a luminescent probe. IrC1 additionally exhibited excellent long-term photostability, in contrast to traditional dyes. We conclude that in combination with luminescent microscopy and flow cytometry, IrC1 provides an effective, straightforward alternative to cell death assays.
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PKC? Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc.
Oxid Med Cell Longev
PUBLISHED: 05-11-2014
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Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKC? and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKC?, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKC? during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKC? was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKC?. Moreover, PKC? siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKC? promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient.
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Yolk-shell upconversion nanocomposites for LRET sensing of cysteine/homocysteine.
ACS Appl Mater Interfaces
PUBLISHED: 04-24-2014
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The fabrication of lanthanide upconversion nanocomposites as probes has become a new research hotspot due to its special advantages via utilizing upconversion luminescence (UCL) as a detection signal. Herein, a hybrid organic dye modified upconversion nanophosphor is successfully developed as a nanoprobe for cysteine/homocysteine. Yolk-shell structured upconversion nanoparticles (YSUCNP) with lanthanide upconversion nanophosphor as moveable core and silica as mesoporous shell are synthesized, and a colorimetric chemodosimeter for cysteine/homocysteine is accommodated in the hollow cavities. Thus, cysteine/homocysteine can be quantitatively detected on the basis of luminescent resonance energy transfer (LRET) in a UCL turn-off pattern. The dye-loaded YSUCNP possess good dispersibility in aqueous solution; thus detection of the targeted molecule can be achieved in pure water. Cellular experiments carried out with laser-scanning upconversion luminescence microscopy further demonstrate that the dye-loaded YSUCNP can serve as an intracellular nanoprobe to detect cysteine/homocysteine. Moreover, this dye-loading protocol can be developed as a common approach to construct other chemodosimeter-modified UCNP hybrid nanoprobes, as proved by a UCL turn-on style sensor for cyanide.
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Contribution of PTHrP to mechanical strain-induced fibrochondrogenic differentiation in entheses of Achilles tendon of miniature pigs.
J Biomech
PUBLISHED: 04-09-2014
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Fibrochondrocytes are involved in entheses repair, but their response to mechanical strain (MS) is ill known.
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[Effectiveness of arthroscopic bipolar radiofrequency energy for lateral meniscus tear and cartilage injury].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 04-04-2014
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To investigate the effectiveness of arthroscopic bipolar radiofrequency energy (bRFE) and lateral partial meniscectomy for lateral meniscus tear and cartilage lesion.
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Construction of a CTGF and RFP-coexpressed renal tubular epithelial cell and its application on evaluation of CTGF-specific siRNAs on epithelial-mesenchymal transition.
Urology
PUBLISHED: 04-03-2014
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To construct a connective tissue growth factor (CTGF) and red fluorescent protein (RFP)-coexpressed renal tubular epithelial cell that can be used to quantitatively evaluate the CTGF-induced epithelial-mesenchymal transition (EMT).
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Tubular p53 regulates multiple genes to mediate AKI.
J. Am. Soc. Nephrol.
PUBLISHED: 04-03-2014
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A pathogenic role of p53 in AKI was suggested a decade ago but remains controversial. Indeed, recent work indicates that inhibition of p53 protects against ischemic AKI in rats but exacerbates AKI in mice. One intriguing possibility is that p53 has cell type-specific roles in AKI. To determine the role of tubular p53, we generated two conditional gene knockout mouse models, in which p53 is specifically ablated from proximal tubules or other tubular segments, including distal tubules, loops of Henle, and medullary collecting ducts. Proximal tubule p53 knockout (PT-p53-KO) mice were resistant to ischemic and cisplatin nephrotoxic AKI, which was indicated by the analysis of renal function, histology, apoptosis, and inflammation. However, other tubular p53 knockout (OT-p53-KO) mice were sensitive to AKI. Mechanistically, AKI associated with the upregulation of several known p53 target genes, including Bax, p53-upregulated modulator of apoptosis-?, p21, and Siva, and this association was attenuated in PT-p53-KO mice. In global expression analysis, ischemic AKI induced 371 genes in wild-type kidney cortical tissues, but the induction of 31 of these genes was abrogated in PT-p53-KO tissues. These 31 genes included regulators of cell death, metabolism, signal transduction, oxidative stress, and mitochondria. These results suggest that p53 in proximal tubular cells promotes AKI, whereas p53 in other tubular cells does not.
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Combination of chemotherapy and photodynamic therapy using graphene oxide as drug delivery system.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 03-27-2014
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Previous research indicated that graphene oxide (GO) can be used to deliver photosensitive anticancer drug, Hypocrellin A (HA), in photodynamic therapy (PDT). However, the anticancer activity of HA was obviously decreased after been loaded on GO. To solve this problem, a chemotherapy drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was co-loaded on the HA loaded GO (HA/SN-38/GO) as a multimodal carrier for the synergistic combination of PDT and chemotherapy for cancer. In vitro results showed that the combination therapy exhibited a synergistic antiproliferative effect compared with PDT and chemotherapy alone. Therefore, HA/SN-38/GO delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer.
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Patient-specific assessment of cardiovascular function by combination of clinical data and computational model with applications to patients undergoing Fontan operation.
Int J Numer Method Biomed Eng
PUBLISHED: 03-22-2014
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The assessment of cardiovascular function is becoming increasingly important for the care of patients with single-ventricle defects. However, most measurement methods available in the clinical setting cannot provide a separate measure of cardiac function and loading conditions. In the present study, a numerical method has been proposed to compensate for the limitations of clinical measurements. The main idea was to estimate the parameters of a cardiovascular model by fitting model simulations to patient-specific clinical data via parameter optimization. Several strategies have been taken to establish a well-posed parameter optimization problem, including clinical data-matched model development, parameter selection based on an extensive sensitivity analysis, and proper choice of parameter optimization algorithm. The numerical experiments confirmed the ability of the proposed parameter optimization method to uniquely determine the model parameters given an arbitrary set of clinical data. The method was further tested in four patients undergoing the Fontan operation. Obtained results revealed a prevalence of ventricular abnormalities in the patient cohort and at the same time demonstrated the presence of marked inter-patient differences and preoperative to postoperative changes in cardiovascular function. Because the method allows a quick assessment and makes use of clinical data available in clinical practice, its clinical application is promising.
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Scavenger receptor-recognized and enzyme-responsive nanoprobe for fluorescent labeling of lysosomes in live cells.
Biomaterials
PUBLISHED: 03-19-2014
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Lysosomal imaging represents a potent tool for investigating the organization of related cellular events and their modulation via diagnostic and therapeutic approaches. However, specific labeling of the lysosome in live cells is a significant challenge. Taking advantage of the inherent lysosomal entry of nanoparticles and unique digestive inclusions in the lysosome, we developed a nanoparticle-based, enzyme-switchable fluorescence OFF-ON strategy for specific labeling of the lysosome and further imaging of extracellular acidification-induced lysosome trafficking in living cells. The nanoprobe comprised a 16 nm spherical gold nanoparticle as the core and an enzyme-responsive oligomer of fluorescein-conjugated oligo(4-vinyl-phenyl phosphate) as the shell. Due to quenching of the core gold nanoparticle, the nanoprobe was non-fluorescent. After incubation with cancer cells, the nanoprobe was rapidly internalized via scavenger receptor-mediated endocytosis and significantly shuffled into the lysosome. The nanoprobe specifically lighted up the lysosome owing to lysosome-induced fluorescence enhancement. Specifically, digestive inclusions in the lysosome hydrolyzed and released gold-quenched fluorescein molecules, leading to significant augmentation of fluorescence. On account of specific lysosomal labeling, the nanoprobe effectively facilitated imaging of a 4-6 ?m anterograde trafficking event of the lysosome from the perinuclear region to the cell surface when an acidic extracellular environment developed. Our findings collectively highlight the use of nanoprobes for lysosomal imaging.
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Combination of dynamic pH junction with capillary electrophoresis-mass spectrometry for the determination of systemins in plant samples.
Electrophoresis
PUBLISHED: 03-17-2014
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Systemin is an important group of plant peptide hormones participating in the regulation of plant defensive responses. An improved method, based on dynamic pH junction and capillary electrophoresis-quadrupole time-of-flight mass spectrometry, was developed for online enrichment and sensitive determination of trace systemins in plants. After optimization, the online enrichment factors for six target systemins ranged from 90- to 127-fold. The detection limits reached lower than 0.5 nM, which were comparable with the sensitivity of LC-MS method. Satisfactory quantitative results were obtained in terms of linearity (R(2) ? 0.993), dynamic range (3-120 ng/mL), and reproducibility (?6.7%). For the analysis of real plant samples, a rapid sample preparation method was developed, using two steps of SPE purification with different retention and separation mechanisms. Finally, this method realized the successful detection of tomato systemin and tobacco hydroxyproline-rich systemin I from plant leaves with shorter analysis time.
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Mitochondrial dysregulation and protection in cisplatin nephrotoxicity.
Arch. Toxicol.
PUBLISHED: 03-13-2014
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Nephrotoxicity is a major side effect of cisplatin in chemotherapy. Pathologically, cisplatin nephrotoxicity is characterized by cell injury and death in renal tubules. The research in the past decade has gained significant understanding of the cellular and molecular mechanisms of tubular cell death, revealing a central role of mitochondrial dysregulation. The pathological changes in mitochondria in cisplatin nephrotoxicity are mainly triggered by DNA damage response, pro-apoptotic protein attack, disruption of mitochondrial dynamics, and oxidative stress. As such, inhibitory strategies targeting these cytotoxic events may provide renal protection. Nonetheless, ideal approaches for renoprotection should not only protect kidneys but also enhance the anticancer efficacy of cisplatin in chemotherapy.
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Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cells through phosphorylation of GSK?3?.
Mol Med Rep
PUBLISHED: 03-11-2014
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Emerging evidence has suggested that human peritoneal mesothelial cells (HPMCs) undergo epithelial?mesenchymal transition (EMT) in peritoneal fibrosis. The molecular mechanisms underlying peritoneal fibrosis and the key molecules involved are not yet fully elucidated. In order to enhance the understanding of peritoneal fibrosis, the present study investigated the roles of integrin?linked kinase (ILK) and glycogen synthase kinase 3? (GSK?3?) in high glucose?induced phenotypic alterations of HPMCs. It was observed that HPMCs exhibited a cobblestone morphology under normal glucose conditions, whereas under high glucose conditions they had a spindle morphology. Additionally, under high glucose conditions it was found that E?cadherin expression was decreased and vimentin expression was increased in HPMCs, suggesting HPMCs underwent EMT. ILK expression in high glucose conditions was also increased in a dose? and time?dependent manner. The role of ILK in the induction of EMT in HPMCs was further investigated using small interfering RNA (siRNA). Following knockdown of ILK gene expression by siRNA, low vimentin expression as well as high E?cadherin expression were observed, suggesting that EMT was inhibited. ILK?knockdown also inhibited phosphorylation of GSK?3?. These results indicate that ILK?knockdown inhibits EMT of HPMCs through inhibition of GSK?3? phosphorylation. These findings suggest that ILK may be used as a novel diagnostic and therapeutic target for HPMC fibrosis in the future.
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Visible-light-excited and europium-emissive nanoparticles for highly-luminescent bioimaging in vivo.
Biomaterials
PUBLISHED: 03-01-2014
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Europium(III)-based material showing special milliseconds photoluminescence lifetime has been considered as an ideal time-gated luminescence probe for bioimaging, but is still limited in application in luminescent small-animal bioimaging in vivo. Here, a water-soluble, stable, highly-luminescent nanosystem, Ir-Eu-MSN (MSN = mesoporous silica nanoparticles, Ir-Eu = [Ir(dfppy)2(pic-OH)]3Eu·2H2O, dfppy = 2-(2,4-difluorophenyl)pyridine, pic-OH = 3-hydroxy-2-carboxypyridine), was developed by an in situ coordination reaction to form an insoluble dinuclear iridium(III) complex-sensitized-europium(III) emissive complex within mesoporous silica nanoparticles (MSNs) which had high loading efficiency. Compared with the usual approach of physical adsorption, this in-situ reaction strategy provided 20-fold the loading efficiency (43.2%) of the insoluble Ir-Eu complex in MSNs. These nanoparticles in solid state showed bright red luminescence with high quantum yield of 55.2%, and the excitation window extended up to 470 nm. These Ir-Eu-MSN nanoparticles were used for luminescence imaging in living cells under excitation at 458 nm with confocal microscopy, which was confirmed by flow cytometry. Furthermore, the Ir-Eu-MSN nanoparticles were successfully applied into high-contrast luminescent lymphatic imaging in vivo under low power density excitation of 5 mW cm(-2). This synthetic method provides a universal strategy of combining hydrophobic complexes with hydrophilic MSNs for in vivo bioimaging.
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TLR9 and BAFF: their expression in patients with IgA nephropathy.
Mol Med Rep
PUBLISHED: 02-21-2014
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Since it was first described in 1968, immunoglobulin (Ig)A nephropathy (IgAN) has become the most commonly diagnosed form of primary glomerular disease worldwide. A number of reports have shown that toll?like receptor 9 (TLR9) and B?cell activating factor (BAFF) may be associated with IgAN; however, sufficient evidence has not yet to be delivered. In the present study, serum levels of BAFF as well as TLR9 mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were assessed. Expression of TLR9 mRNA in PBMCs was examined by quantitative polymerase chain reaction and the TLR9 protein was determined by western blot analysis. The levels of serum BAFF and IgA1 were determined by specific ELISA. Serum levels of BAFF and IgA1 as well as levels of TLR9 mRNA and protein in PMBCs were significantly higher in patients with IgAN compared with patients with minimal glomerular abnormalities (P<0.05, P<0.01, P<0.01 and P<0.01, respectively) and normal controls (P<0.01, P<0.01, P<0.05 and P<0.01, respectively). A correlation and regression analysis was performed to determine the pathogenesis of IgAN. In patients with IgAN, serum levels of BAFF were positively correlated with IgA1 levels (rp, 0.515; P<0.01) and mesangial IgA deposition density (rp, 0.746; P<0.01). Expression levels of TLR9 protein in PBMCs of IgAN patients were positively correlated with levels of serum BAFF (rp, 0.444; P<0.05) and IgA1 (rp, 0.633; P<0.01). These results suggested that overexpression of TLR9 mRNA and protein in PBMCs and elevated levels of serum BAFF may be associated with overexpression of serum IgA1, and, furthermore, may have a role in the development of IgAN.
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Aggregation-induced emissive copper(I) complexes for living cell imaging.
Inorg Chem
PUBLISHED: 02-21-2014
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Phosphorescent binuclear copper(I) complexes [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2 with different conformations are obtained by reaction of [Cu(NCCH3)4]ClO4, 3,8-dibromo-1,10-phenanthroline (BrphenBr), and corresponding diphosphine ligands, where n = 1, 4, 5, and 6 in complexes Cu-1, Cu-2, Cu-3, and Cu-4, respectively. Complex Cu-4 exhibits both the eclipsed and the staggered conformations of 18-membered Cu2C12P4 metallacycles in a 1:1 ratio in the crystal structure. All complexes are very stable to air and moisture in the solid state because of the high level of protection of all the Cu(I) centers, N and P atom centers resulting from the close contact of BrphenBr and diphosphine ligands, and what is more important is that there exist very soft P donors and the chelating effect of aromatic N atoms. The ESI-MS result through changing the collision cell energy from 0 to 20 eV suggests that the corresponding [Cu2(Ph2P(CH2)nPPh2)2](2+) cations are the thermodynamically stable species, while [Cu2(BrphenBr)2(Ph2P(CH2)nPPh2)2](ClO4)2 are stable products in crystallization kinetics in solutions. All complexes Cu-1-Cu-4 display good aggregation-induced phosphorescence emission (AIPE) behavior in CH2Cl2/hexane mixed solvents, which are suggested to arise from restriction of intramolecular rotation. Aggregation-induced emission (AIE) of complexes Cu-1-Cu-4 in PBS/DMSO (99:1, v:v) is used for living HeLa cell imaging successfully with green intracellular emission image.
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Expression and correlation analysis of IL-4, IFN-? and Fc?RI in tonsillar mononuclear cells in patients with IgA nephropathy.
Cell. Immunol.
PUBLISHED: 02-18-2014
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Clinical deterioration of IgA nephropathy (IgAN) is frequently preceded by episodes of upper respiratory tract infection such as tonsillitis. The aim of this study was attempt to investigate the expression and correlation of IL-4, IFN-? and Fc?RI in tonsillar mononuclear cells under stimulations of ?-hemolytic streptococcus (HS) or lipopolysaccharide (LPS) in patients with IgA nephropathy.
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Novel regenerative large-volume immobilized enzyme reactor: preparation, characterization and application.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 02-14-2014
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A novel large-volume immobilized enzyme reactor (IMER) on small column was prepared with organic-inorganic hybrid silica particles and applied for fast (10 min) and oriented digestion of protein. At first, a thin enzyme support layer was formed in the bottom of the small column by polymerization with ?-methacrylic acid and dimethacrylate. After that, amino SiO2 particles was prepared by the sol-gel method with tetraethoxysilane and 3-aminopropyltriethoxysilane. Subsequently, the amino SiO2 particles were activated by glutaraldehyde for covalent immobilization of trypsin. Digestive capability of large-volume IMER for proteins was investigated by using bovine serum albumin (BSA), cytochrome c (Cyt-c) as model proteins. Results showed that although the sequence coverage of the BSA (20%) and Cyt-c (19%) was low, the large-volume IMER could produce peptides with stable specific sequence at 101-105, 156-160, 205-209, 212-218, 229-232, 257-263 and 473-451 of the amino sequence of BSA when digesting 1mg/mL BSA. Eight of common peptides were observed during each of the ten runs of large-volume IMER. Besides, the IMER could be easily regenerated by reactivating with GA and cross-linking with trypsin after breaking the -C=N- bond by 0.01 M HCl. The sequence coverage of BSA from regenerated IMER increased to 25% comparing the non-regenerated IMER (17%). 14 common peptides. accounting for 87.5% of first use of IMER, were produced both with IMER and regenerated IMER. When the IMER was applied for ginkgo albumin digestion, the sequence coverage of two main proteins of ginkgo, ginnacin and legumin, was 56% and 55%, respectively. (Reviewer 2) Above all, the fast and selective digestion property of the large-volume IMER indicated that the regenerative IMER could be tentatively used for the production of potential bioactive peptides and the study of oriented protein digestion.
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Lanthanide-based nanocrystals as dual-modal probes for SPECT and X-ray CT imaging.
Biomaterials
PUBLISHED: 01-29-2014
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Applications of lanthanide-based nanoparticles for bioimaging have attracted increasing attention. Herein, small size PEG-EuOF:(153)Sm nanocrystals (?5 nm) (PEG = poly(ethylene glycol)bis(carboxymethyl)ether) combined with the radioactive and X-ray absorption properties were synthesized. The distribution of the PEG-EuOF nanocrystals in living animals was studied by ex vivo radioassay, inductively coupled plasma-atomic emission spectrum (ICP-AES) analysis and in vivo SPECT imaging, which indicated that the small size PEG-EuOF:(153)Sm had long blood retention time (blood half-life (t1/2) reach to 4.65 h) and were eliminated significantly through biliary/gastrointestinal pathway in vivo. Meanwhile, benefiting from the high attenuation ability of Eu, the small size PEG-EuOF was successfully applied for lymph node CT imaging, extending the bio-applications of these small nanocrystals. The results of cytotoxicity and in vivo toxicity also showed that the PEG-EuOF nanocrystals have relatively low toxicity, which suggest their safety for in vivo imaging. The studies provide preliminary validation for the use of PEG-EuOF nanocrystals for in vivo bioimaging applications.
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Development of continuous microwave-assisted protein digestion with immobilized enzyme.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-26-2014
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In this study, an easy and efficiency protein digestion method called continuous microwave-assisted protein digestion (cMAED) with immobilized enzyme was developed and applied for proteome analysis by LC-MS(n). Continuous microwave power outputting was specially designed and applied. Trypsin and bromelain were immobilized onto magnetic micropheres. To evaluate the method of cMAED, bovine serum albumin (BSA) and protein extracted from ginkgo nuts were used as model and real protein sample to verify the digestion efficiency of cMAED. Several conditions including continuous microwave power, the ratio of immobilized trypsin/BSA were optimized according to the analysis of peptide fragments by Tricine SDS-PAGE and LC-MS(n). Subsequently, the ginkgo protein was digested with the protocols of cMAED, MAED and conventional heating enzymatic digestion (HED) respectively and the LC-MS(n) profiles of the hydrolysate was compared. Results showed that cMAED combined with immobilized enzyme was a fast and efficient digestion method for protein digestion and microwave power tentatively affected the peptide producing. The cMAED method will be expanded for large-scale preparation of bioactive peptides and peptide analysis in biological and clinical research.
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Long-term biodistribution in vivo and toxicity of radioactive/magnetic hydroxyapatite nanorods.
Biomaterials
PUBLISHED: 01-15-2014
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Although nanoscale hydroxyapatite [Ca10(PO4)6(OH)2; HA] has been widely investigated as a carrier in the delivery of drugs, genes, or siRNA, the in vivo toxicity of nanoscale HA is not clear and the long-term dynamic distribution in vivo has not hitherto been visualized. In this work, gadolinium-doped HA nanorods (HA:Gd) with an r1 value of 5.49 s(-1) (mm)(-1) have been prepared by a hydrothermal method. Samarium-153 ((153)Sm) was then effectively post-labeled onto the HA:Gd ((153)Sm-HA:Gd) with a labeling rate of ?100% and a radio-labeling stability in vitro of ?100% over 48 h. The product could serve as a new dual-modality probe for SPECT and MR imaging in vivo. By means of SPECT and MRI, the HA:Gd nanorods were found to be quickly taken up by the mononuclear phagocyte system, especially the liver and spleen. The nanorods in the liver and lung tended to be eliminated within 24 h, but nanorods in the spleen behaved differently and proved difficult to excrete. In vitro studies by cell transmission electron microscopy (TEM) and methyl thiazolyl tetrazolium (MTT) assay showed good biocompatibility of the HA:Gd nanorods with HeLa cells, even at a high concentration. The indicators of body weight, histology, and serology demonstrated that the HA:Gd nanorods exhibited excellent biocompatibility in vivo for at least 61 days. Therefore, (153)Sm-HA:Gd nanorods with excellent relaxivity, ?-emission, and biosafety offer clear advantages and potential for bioapplications.
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Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder: a case report and review of literature.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder (EBV + LPD) has predominantly been observed among pediatric patients as a life-threatening condition. The present study presents a rare case of EBV + LPD in an adult with good outcome. This patient's history is more than 2 years and her condition was stable. She received 6 cycles of chemotherapy cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP). The evaluation was complete remission. The low levels of EBV-DNA in the peripheral blood may have potential benefit factor for the sensitivity to the chemotherapy and good outcome.
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Wnt/?-catenin signaling regulates the proliferation and differentiation of mesenchymal progenitor cells through the p53 pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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Mesenchymal progenitor cells (MPCs) are found in articular cartilage from normal controls and patients with osteoarthritis (OA). Nevertheless, the molecular mechanisms of the proliferation and differentiation of these cells remain unclear. In this study, we aimed to determine the involvement of Wnt/?-catenin signaling in regulating the proliferation and differentiation of MPCs.
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Study on anti-osteosarcoma activity of ethanol extract of Venenum bufonis in vitro.
Afr J Tradit Complement Altern Med
PUBLISHED: 01-01-2014
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Venenum bufonis is the dried white secretion of the auricular and skin glands of Bufo gargarizans Cantor, or Bufo melanostictus Schneider, Bufonidae. It is used in the treatment of deep-rooted carbuncle, boils and swelling; pain in the throat, heart stroke, coma, abdominal pain, vomiting and diarrhea. The objective of this paper is to preliminarily observe the effects of ethanol extract of Venenum bufonis on growth, and proliferation of human osteosarcoma U2OS cell lines, and to provide a theoretical basis for an in-depth study of the clinical application of Venenum bufonis for osteosarcoma inhibition, with its mechanism of action.
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[RIFLE and AKIN criteria for mortality and risk factors of acute kidney injury in hospitalized patients.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-31-2013
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Objective: To evaluate the mortality and risk factors for acute kidney injury (AKI) in hospitalized patients by the risk, injury, failure, loss, end stage kidney disease (RIFLE) and acute kidney injury network (AKIN). Methods: We constructed a retrospective study of all AKI patients in the Second Xiangya Hospital of Central South University between February 2006 and January 2011. The diagnosis and classification of AKI were reconfirmed and categorized by RIFLE and AKIN criteria. To compare the clinical characteristics, mortality and associated risk factors in AKI patients by the RIFLE and AKIN stage, univariate analysis and multivariate logistic regression analysis were performed. Results: The patients were diagnosed as AKI by AKIN (n=1027) or by RIFLE criteria (n=1020). There was no significant difference in the hospital mortality, hospital length stay (days), or the proportion of complete recovery in each stage of AKI patients by RIFLE and AKIN (P>0.05). In the univariate analysis, age, pre-renal causes, proportion of hospital acquired AKI, mechanical ventilation, hypotension, the number of failed organs, acute tubular necrosis-index severity score (ATN-ISS), and the peak of serum potassium ion concentration were significantly higher in the non-survivors than in the survivors (P<0.05). Logistic regression analysis revealed that age older than 65, hospital acquired AKI, hypotension, number of failed organs, ATN-ISS scores, and the peak of serum potassium ion concentration were independent risk factors for hospital mortality. Conclusion: Both RIFLE and AKIN criteria have similar scientific value in assessing hospital mortality. AKI stage is associated with the recent prognosis of AKI patients.
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[Role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney diseases.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-31-2013
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Objective: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney disease (DKD). Methods: Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin, ?-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin, ?-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. Results: Tranilast can inhibit the infiltration of mast cells in the kidneys of DKD rats. The expression of ?-SMA in the kidneys of DKD rats inereased significantly (P<0.05), while the expression of E-cadherin decreased (P<0.05). Tranilast increased the expression of E-cadherin and decreased the expression of ?-SMA in the prophase of DKD dose dependently. The expressions of FN and Col I were increased in the tubulointerstitial fields in DKD model rats (P<0.05). After the tranilast treatment, these changes were relieved to a certein degree (P<0.05). The expression of SCF and c-kit in the tubular and interstitial tissue was slight. The increased expressions of SCF and c-kit protein and mRNA in DKD model rats were downregulated by tranilat (P<0.05). The expressions of SCF and c-kit were positively correlated with the infiltration degree of mast cells and the expressions of FN, Col I. Conclusion: Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the infiltration of mast cells induced by SCF/c-kit pathway.
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Rap1 ameliorates renal tubular injury in diabetic nephropathy.
Diabetes
PUBLISHED: 12-18-2013
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Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular cells. However, its role and precise mechanism in diabetic nephropathy (DN) in vivo remains unclear. We hypothesize that Rap1 plays a protective role in tubular damage of DN by modulating primarily the mitochondria-derived oxidative stress.The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of tubular cells in DN was examined in rats with Streptozotocin (STZ)-induced diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated technique as well as in renal proximal epithelial tubular cell line (HK-2) exposed to HG ambiance. The results showed that Rap1b expression decreased significantly in tubules of renal biopsies from patients with DN. Over-expression of a constitutively active Rap1b G12V notably ameliorated renal tubular mitochondrial dysfunction, oxidative stress, apoptosis in the kidneys of STZ-induced rats, which was accompanied with increased expression of transcription factor C/EBP-? and PGC-1?. Furthermore, Rap1b G12V also decreased phosphorylation of Drp1, a key mitochondrial fission protein, while boosting the expression of genes related to mitochondrial biogenesis and antioxidants in HK-2 cells induced treated with HG. These effects were imitated by transfection with C/EBP-? or PGC-1? siRNA. In addition, Rap1b could modulate C/EBP-? binding to the endogenous PGC-1? promoter and the interaction between PGC-1? and Catalase or mitochondrial superoxide dismutase. Indicating that Rap1b ameliorates tubular injury and slows the progression of DN by modulation of mitochondrial dysfunction via C/EBP-?:PGC-1? signaling.
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[Effect of high glucose peritoneal dialysis solution on PGC-1? expression and mitochondria related oxidative injury in human peritoneal mesothelial cells].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-10-2013
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Objective: To investigate the mechanism of mitochondrial oxidative injury induced by high glucose peritoneal dialysis solution (PDS) and the protective effect of peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1?) in the mitochondria of human peritoneal mesothelial cells (HPMC) in the high glucose ambience. Methods: HPMC was cultured in a PDS containing 1.5%, 2.5% and 4.25% glucose for 24 hours. Western blot analysis was used to detect PGC-1? expression. MitoSOX? Red staining, respiratory chain complexes and antioxidant enzyme activities were determined. Results: The activities of respiratory chain complex III and antioxidant enzymes decreased significantly in a concentration- and time-dependent manner, along with the increased production of mitochondrial reactive oxygen species (ROS) and cellular apoptosis. In addition, protein expression of PGC-1? was also decreased in the high glucose PDS ambience. Conclusion: High glucose PDS might inhibit PGC-1? expression, resulting in the inhibition of mitochondrial function and increase of mitochondrial ROS and cellular apoptosis.
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Th1/Th2 polarization in tonsillar lymphocyte form patients with IgA nephropathy.
Ren Fail
PUBLISHED: 12-03-2013
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Abstract Imbalance of Th1/Th2 pro-inflammatory cytokines plays an important role in the development and progression of IgA nephropathy (IgAN). Clinical development and exacerbation of IgAN are frequently preceded by episodes of upper respiratory tract infection, and palatine tonsils represent the predominant immunocompetent tissue of the upper respiratory tract. This study examined tonsillar lymphocytes of IgAN who suffered from tonsillitis (n?=?22), and using tonsils derived from patients with chronic tonsillitis (n?=?24) but without renal disease as a control. We identified a polarization toward Th2 response in tonsils of IgAN patients. TH0 cells are differentially mobilized during contact sensitization and by adjuvants such as lipopolysaccharide (LPS) that induce T-helper type 1 (Th1) responses, or ?-hemolytic streptococcus (HS) that induces T-helper type 2 (Th2) responses. Th1:Th2 ratio is correlated with proteinuria and renal pathologic changes in IgAN group. Our study suggests that IgAN is associated with the change in Th1/Th2 balance in favor of Th2 lymphocytes.
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Core-shell lanthanide upconversion nanophosphors as four-modal probes for tumor angiogenesis imaging.
ACS Nano
PUBLISHED: 11-13-2013
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Multimodality imaging overcomes the shortage and incorporates the advantages of different imaging tools. Lanthanide-based nanoprobes are unique and have rich optical, magnetic, radioactive, and X-ray attenuation properties; however, simple doping of different lanthanide cations into one host can result in a material with multifunction but not the optimized properties. In this study, using NaLuF4:Yb,Tm as the core and 4 nm of (153)Sm(3+)-doped NaGdF4 (half-life of (153)Sm = 46.3 h) as the shell, we developed a lanthanide-based core-shell nanocomposite as an optimized multimodal imaging probe with enhanced imaging ability. The lifetime of upconversion luminescence (UCL) at 800 nm and relaxation rate (1/T1) were at 1044 ?s and 18.15 s(-1)·mM(-1), respectively; however, no significant decrease in the attenuation coefficient was observed, which preserved the excellent X-ray imaging ability. The nanomaterial NaLuF4:Yb,Tm@NaGdF4((153)Sm) was confirmed to be effective and applicable for UCL imaging, X-ray computed tomography (CT), magnetic resonance imaging, and single-photon emission computed tomography (SPECT) in vivo. Furthermore, the NaLuF4:Yb,Tm@NaGdF4((153)Sm) nanoparticles were applied in tumor angiogenesis analysis by combining multimodality imaging of CT, SPECT, and confocal UCL imaging, which shows its value of multifunctional nanoparticles NaLuF4:Yb,Tm@NaGdF4((153)Sm) in tumor angiogenesis imaging.
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Oxidative stress, a common molecular pathway for kidney disease: Role of the redox enzyme p66Shc.
Ren Fail
PUBLISHED: 11-04-2013
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Abstract Accumulation of oxidative stress is considered to be a causative mediator of kidney disease, and oxidative stress can affect some key regulators of kidney homeostasis and control a number of signaling pathways that are relevant to kidney disease. The p66Shc adaptor protein was discovered more than two decades ago as a pivotal regulator of oxidative stress. Given the importance of oxidative stress in kidney homeostasis, several molecular and cellular studies using a p66Shc antagonist have depicted a role for p66Shc in renal pathophysiology. The specificity of p66Shc functions may depend upon their intracellular localization and expression in the kidney. This review focuses on the biochemical functions of the p66Shc adaptor protein, as well as its potential implications in the pathophysiology of kidney disease. In addition, the concept that pharmacologic modulation of p66Shc expression and activity may serve as a novel and effective target for the treatment of kidney disease is discussed.
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Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of extracellular matrix molecules in cultured human renal proximal tubular cells.
Ren Fail
PUBLISHED: 10-29-2013
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Abstract Objective: In this study, we investigated the effect of small interfering RNA (siRNA) of connective tissue growth factor (CTGF) by pRetro-Super (PRS) retrovirus vector on the expression of CTGF and related extracellular matrix molecules in human renal proximal tubular cells (HKCs) induced by high glucose, to provide help for renal tubulointerstitial fibrosis therapy. Methods: HKCs were exposed to d-glucose to observe their dose and time effect, while the mannitol as osmotic control. Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect HKC. The expression of CTGF, fibronectin (FN) and collagen-type I (col1) were measured by semi-quantitative RT-PCR and Western blot. Results: In response to high glucose, CTGF expression in HKCs was increased in a dose- and time-dependent manner, whereas the increase did not occur in the osmotic control. Introduction of PRS-CTGF-siRNA resulted in the significant reduction of CTGF, FN, col1 mRNA (p??0.05). Conclusions: CTGF siRNA therapy can effectively reduce the levels of CTGF, FN and col1 induced by high glucose in cultured HKCs, which suggested that it may be a potential therapeutic strategy to prevent the renal interstitial fibrosis in the future.
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A bioprobe based on aggregation induced emission (AIE) for cell membrane tracking.
Chem. Commun. (Camb.)
PUBLISHED: 10-25-2013
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A new organic dye (FD-9) derived from 1,8-naphthalimide is synthesized and shows significant aggregation induced emission (AIE) characteristics. The FD-9 dye presents excellent photostability and low toxicity, which can specifically track a cell membrane for 4 days.
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Red-light-controllable liquid-crystal soft actuators via low-power excited upconversion based on triplet-triplet annihilation.
J. Am. Chem. Soc.
PUBLISHED: 10-24-2013
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A red-light-controllable soft actuator has been achieved, driven by low-power excited triplet-triplet annihilation-based upconversion luminescence (TTA-UCL). First, a red-to-blue TTA-based upconversion system with a high absolute quantum yield of 9.3 ± 0.5% was prepared by utilizing platinum(II) tetraphenyltetrabenzoporphyrin (PtTPBP) as the sensitizer and 9,10-bis(diphenylphosphoryl)anthracene (BDPPA) as the annihilator. In order to be employed as a highly effective phototrigger of photodeformable cross-linked liquid-crystal polymers (CLCPs), the PtTPBP&BDPPA system was incorporated into a rubbery polyurethane film and then assembled with an azotolane-containing CLCP film. The generating assembly film bent toward the light source when irradiated with a 635 nm laser at low power density of 200 mW cm(-2) because the TTA-UCL was effectively utilized by the azotolane moieties in the CLCP film, inducing their trans-cis photoisomerization and an alignment change of the mesogens via an emission-reabsorption process. It is the first example of a soft actuator in which the TTA-UCL is trapped and utilized to create photomechanical effect. Such advantages of using this novel red-light-controllable soft actuator in potential biological applications have also been demonstrated as negligible thermal effect and its excellent penetration ability into tissues. This work not only provides a novel photomanipulated soft actuation material system based on the TTA-UCL technology but also introduces a new technological application of the TTA-based upconversion system in photonic devices.
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Greater omentum folding in the open surgical placement of peritoneal dialysis catheters: a randomized controlled study and systemic review.
Nephrol. Dial. Transplant.
PUBLISHED: 09-30-2013
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Mechanical catheter dysfunction caused by omentum entrapment remains a major complication of peritoneal dialysis (PD) therapy. The purpose of this study was to determine the outcomes of omentum folding at the time of primary open catheter insertion.
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Upconversion luminescence imaging of cells and small animals.
Nat Protoc
PUBLISHED: 09-26-2013
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Upconversion luminescence (UCL) is an anti-Stokes process whereby low-energy photons are converted to higher-energy ones. UCL imaging for cells and animal tissues has attracted substantial attention in recent years because of the unique abilities of upconversion materials, which can minimize the background interference from the autofluorescence of biosamples and enhance tissue penetration. This protocol describes a step-by-step guide for the fabrication of UCL probes, including lanthanide-based upconversion nanoparticles (Ln-UCNPs) with a particle size of ?20 nm (NaYF4/NaLuF4: Yb, Er/Tm) and triplet-triplet annihilation-based UCNPs (TTA-UCNPs) with a particle size of ?10 nm (palladium octaethylporphyrin as sensitizer and 9,10-diphenylanthracene as annihilator). We also describe the characterization of the UCL nanoprobes (via transmission electron microscopy and UCL emission spectroscopy) and functionalization (via silica coating and ligand exchange), as well as applications for UCL bioimaging of living cells (HeLa cells) and small animals (nude mice and Kunming mice). The setup of a laser-scanning UCL microscope and a UCL imaging system is also presented. Compared with a normal imaging setup, we adopted longer-wavelength excitation lasers and short-pass filters. The synthesis of hydrophilic UCNP for application in UCL bioimaging requires ?15 d.
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NIR photothermal therapy using polyaniline nanoparticles.
Biomaterials
PUBLISHED: 08-06-2013
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Developing a biocompatible and efficient photothermal coupling agent with appropriate size is a prerequisite for the development of near-infrared (NIR) light-induced photothermal therapy (PTT). In the present study, polyaniline nanoparticles (PANPs) with a size of 48.5 ± 1.5 nm were fabricated and exhibited excellent dispersibility in water by a hydrothermal method and further surface functionalization by capping with F127. The developed F127-modified PANPs (F-PANPs) had a high molar extinction coefficient of 8.95 × 10(8) m(-1) cm(-1), and high NIR photothermal conversion efficiency of 48.5%. Furthermore, combined with NIR irradiation at 808 nm and injection of F-PANP samples, in vivo photothermal ablation of tumor with excellent treatment efficacy was achieved. In vitro transmission electron microscopy (TEM) images of cells, methyl thiazolyl tetrazolium (MTT) assay, histology, and hematology studies revealed that the F-PANPs exhibit low toxicity to living systems. Therefore, F-PANPs could be used as PTT agents for ablating cancer, and the concept of developing polyaniline-based nanoparticles can serve as a platform technology for the next generation of in vivo PTT agents.
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[Monolithic molecularly imprinted column-high performance liquid chromatography for enrichment and determination of trace cytokinins in plant samples].
Se Pu
PUBLISHED: 08-01-2013
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A method based on monolithic molecularly imprinted polymer enrichment combining with high performance liquid chromatography (mMIP-HPLC) detection was developed for the selective determination of trace cytokinins (CTKs) in plant samples. Monolithic molecularly imprinted polymer (mMIP) column was prepared in stainless steel tube by using kinetin as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, and toluene-dodecanol as the porogenic solvents. Compared with non-imprinted polymer (NIP) monolith, the prepared mMIP exhibited selective separation ability, good reproducibility and reusability, and high extraction efficiency in the separation and enrichment of the four CTKs. Under the optimized experimental conditions, mean recoveries were 91.9%, 80.0%, 87.5% and 50.2% for kinetin (K), kinetin glucoside (KR) , trans-zeatin (tZ) and meta-topolin (mT), respectively, with the corresponding RSDs less than 11.8%. The proposed mMIP-HPLC method was successfully applied in the separation and determination of the four cytokinins in different plant samples
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Activation of the interleukin-4/signal transducer and activator of transcription 6 signaling pathway and homeodomain-interacting protein kinase 2 production by tonsillar mononuclear cells in IgA nephropathy.
Am. J. Nephrol.
PUBLISHED: 07-25-2013
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Clinical development and exacerbation of IgA nephropathy (IgAN) are frequently preceded by episodes of upper respiratory tract infection such as tonsillitis. This study aimed to determine the role of the interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) signaling pathway and homeodomain-interacting protein kinase 2 (HIPK2) in aberrant IgA1 O-glycosylation production, and identify potential therapeutic targets in IgAN.
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Study of tonsillectomy for IgA nephropathy patients: short- and longer-term observation.
Int Urol Nephrol
PUBLISHED: 07-06-2013
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We observed serum parameters and urinary findings of IgA nephropathy (IgAN) patients in the short and longer time after tonsillectomy, to provide evidences to clarify the role of tonsils in the pathogenesis of IgAN and the feasibility of tonsillectomy for IgAN patients.
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A cyanine-modified nanosystem for in vivo upconversion luminescence bioimaging of methylmercury.
J. Am. Chem. Soc.
PUBLISHED: 06-25-2013
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Methylmercury (MeHg(+)) is a strong liposoluble ion, which can be accumulated in the organs of animals and can cause prenatal nervous system and visceral damage. Therefore, the efficient and sensitive monitoring of MeHg(+) in organisms is of great importance. Upconversion luminescence (UCL) detection based on rare-earth upconversion nanophosphors (UCNPs) as probes has been proved to exhibit a large anti-Stokes shift, no autofluorescence from biological samples, a remarkably deep penetration depth, and no photobleaching. In this study, a hydrophobic heptamethine cyanine dye (hCy7) modified by two long alkyl moieties and amphiphilic polymer (P-PEG)-modified nanophosphors (hCy7-UCNPs) was fabricated as a highly sensitive water-soluble probe for UCL monitoring and bioimaging of MeHg(+). Further application of hCy7-UCNPs for sensing MeHg(+) was confirmed by an optical titration experiment and upconversion luminescence live cell imaging. Using the ratiometric upconversion luminescence as a detection signal, which provides a built-in correction for environmental effects, the detection limit of MeHg(+) for this nanosystem was as low as 0.18 ppb. Importantly, the hCy7-UCNPs nanosystem was shown to be capable of monitoring MeHg(+)ex vivo and in vivo by upconversion luminescence bioimaging.
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Blood flow dynamic improvement with aneurysm repair detected by a patient-specific model of multiple aortic aneurysms.
Heart Vessels
PUBLISHED: 06-07-2013
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Aortic aneurysms may cause the turbulence of blood flow and result in the energy loss of the blood flow, while grafting of the dilated aorta may ameliorate these hemodynamic disturbances, contributing to the alleviation of the energy efficiency of blood flow delivery. However, evaluating of the energy efficiency of blood flow in an aortic aneurysm has been technically difficult to estimate and not comprehensively understood yet. We devised a multiscale computational biomechanical model, introducing novel flow indices, to investigate a single male patient with multiple aortic aneurysms. Preoperative levels of wall shear stress and oscillatory shear index (OSI) were elevated but declined after staged grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and 0.221 (second operation). Graftings may strategically counter the loss of efficient blood delivery to improve hemodynamics of the aorta. The energy efficiency of blood flow also improved postoperatively. Novel indices of pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation), respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831. Graftings contributed not only to ameliorate wall shear stress or oscillatory shear index but also to improve efficient blood flow. This patient-specific modeling will help in analyzing the mechanism of aortic aneurysm formation and may play an important role in quantifying the energy efficiency or loss in blood delivery.
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Polyphosphoric acid capping radioactive/upconverting NaLuF4:Yb,Tm,153Sm nanoparticles for blood pool imaging in vivo.
Biomaterials
PUBLISHED: 05-28-2013
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Nanoparticles that circulate in the bloodstream for a prolonged period of time have important biomedicine applications. However, no example of lanthanide-based nanoparticles having a long-term circulation bloodstream has been reported to date. Herein, we report on difunctional radioactive and upconversion nanoparticles (UCNP) coated with polyphosphoric acid ligand, that is ethylenediamine tetramethylenephosphonic acid (EDTMP), for an application in single-photon emission computed tomography (SPECT) blood pool imaging. The structure, size and zeta-potential of the EDTMP-coated nanoparticles (EDTMP-UCNP) are verified using transmission electron microscopy and dynamic light scattering. Injection of radioisotope samarium-153-labeled EDTMP-UCNP (EDTMP-UCNP:(153)Sm) into mice reveal superior circulation time compared to control nanoparticles coated with citric acid (cit-UCNP:(153)Sm) and (153)Sm complex of EDTMP (EDTMP-(153)Sm). The mechanism for the extended circulation time may be attributed to the adhesion of EDTMP-UCNP on the membrane of red blood cells (RBCs). In vivo toxicity results show no toxicity of EDTMP-UCNP at the dose of 100 mg/kg, validating its safety as an agent for blood pool imaging. Our results provide a new strategy of nanoprobe for a long-term circulation bloodstream by introducing polyphosphoric acid as surface ligand.
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Differential accumulation of phenolic compounds and expression of related genes in black- and yellow-seeded Brassica napus.
J. Exp. Bot.
PUBLISHED: 05-22-2013
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Developing yellow-seeded Brassica napus (rapeseed) with improved qualities is a major breeding goal. The intermediate and final metabolites of the phenylpropanoid and flavonoid pathways affect not only oil quality but also seed coat colour of B. napus. Here, the accumulation of phenolic compounds was analysed in the seed coats of black-seeded (ZY821) and yellow-seeded (GH06) B. napus. Using toluidine blue O staining and liquid chromatography-mass spectrometry, histochemical and biochemical differences were identified in the accumulation of phenolic compounds between ZY821 and GH06. Two and 13 unique flavonol derivatives were detected in ZY821 and GH06, respectively. Quantitative real-time PCR analysis revealed significant differences between ZY821 and GH06 in the expression of common phenylpropanoid biosynthetic genes (BnPAL and BnC4H), common flavonoid biosynthetic genes (BnTT4 and BnTT6), anthocyanin- and proanthocyandin-specific genes (BnTT3 and BnTT18), proanthocyandin-specific genes (BnTT12, BnTT10, and BnUGT2) and three transcription factor genes (BnTTG1, BnTTG2, and BnTT8) that function in the flavonoid biosynthetic pathway. These data provide insight into pigment accumulation in B. napus, and serve as a useful resource for researchers analysing the formation of seed coat colour and the underlying regulatory mechanisms in B. napus.
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[Effects of TIMP-1 on PTEN expression on renal tubular epithelial cells].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 05-22-2013
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To investigate the role of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in regulating both angiogenesis and the expressions of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and vascular endothelial growth factor (VEGF)/Flk-1 expression in human proximal tubular epithelial cells (HKC).
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Hollow silica nanoparticles loaded with hydrophobic phthalocyanine for near-infrared photodynamic and photothermal combination therapy.
Biomaterials
PUBLISHED: 05-16-2013
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Owing to the convenience and minimal invasiveness, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful technique for cancer treatment. To date, however, few examples of combination PDT and PTT have been reported. Phthalocyanine (Pc) is a class of traditional photosensitizer for PDT, but its bioapplication is limited by high hydrophobicity. In this present study, hollow silica nanospheres (HSNs) were employed to endow the hydrophobic phthalocyanine with water-dispersity, and the as-prepared hollow silica nanoparticles loaded with hydrophobic phthalocyanine (Pc@HSNs) exhibits highly efficient dual PDT and PTT effects. In vitro and in vivo experimental results clearly indicated that the dual phototherapeutic effect of Pc@HSNs can kill cancer cells or eradicate tumor tissues. This multifunctional nanomedicine may be useful for PTT/PDT treatment of cancer.
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[Research progress of Th17 cells and glomerulonephritis].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 05-07-2013
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T helper (Th) 17 cells are a kind of Th cell subset, and are distinct from the Th1 and Th2 cells and produce interleukin-17A (IL-17A, IL-17). Th17 cells have a mechanism of independent differentiation and developmental regulation. The differentiation and cytokine secretion of Th17 cells are regulated by TGF-?, IL-6, IL-23 and orphan nuclear receptor (ROR?t). IL-17A induces pro-inflammatory cytokines and chemokines, mediating neutrophil recruitment. Increasing evidence implicated involvement of Th17 cells in anti-glomerular basement membrane disease, lupus nephritis and pauciimmune glomerulonephritis. In this review, we discussed the discovery of Th17 subset, its properties, its relationship with other Th subsets and involvement of Th17 cells in glomerulonephritis.
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Changes in expression of four molecular marker proteins and one microRNA in mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis patients.
Exp Ther Med
PUBLISHED: 04-27-2013
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The aim of this study was to detect the expression of microRNA-200c and epithelial-mesenchymal transition (EMT) in the mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis (PD) patients, and to investigate the association between microRNA-200c and peritoneal mesothelial cell EMT. Twelve patients who had recently started continuous ambulatory peritoneal dialysis (PD start group) and 16 patients who had been undergoing peritoneal dialysis for >6 months (PD >6 months group) were randomly chosen for the isolation, culture and identification of effluent cells. qPCR and western blot analysis were used to detect the expression levels of microRNA-200c and the levels of four cellular marker proteins, E-cadherin, vimentin, fibronectin (FN) and COL-1, in effluent cells. The results showed that the effluent cells in peritoneal dialysis were peritoneal mesothelial cells. The level of E-cadherin protein expression was significantly lower in the PD >6 months group than in the PD start group, while vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. microRNA-200c in the PD >6 months group was significantly downregulated. The E-cadherin protein expression level was significantly decreased and vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. The level of microRNA-200c was significantly reduced in the PD > 6 months group, suggesting that microRNA-200c may be associated with EMT.
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Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in vitro photodynamic therapy of cancer.
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-19-2013
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Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2 complex, which exhibits enhanced (1)O2 generation quantum yield through the increased intersystem crossing efficiency mediated by internal heavy atom effect. Besides, the chelate process greatly improved the water solubility of HA. Comparative studies with HA and complexes have demonstrated that the heavy-atom effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT) efficacy.
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Upconversion-nanophosphor-based functional nanocomposites.
Adv. Mater. Weinheim
PUBLISHED: 04-13-2013
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Upconversion nanophosphors have the ability to generate visible or near-infrared (NIR) emissions under continuous-wave NIR excitation. Utilizing this special photoluminescent properties, upconversion nanophosphors can be used as key components in complex nanocomposites for a wide range of applications. This review summarizes the basic concept, fabrication strategy, and typical application of upconversion-nanophosphor-based functional nanocomposites. The motivation to design these structures comes from the potential applications in detection, multi-modality bioimaging, and NIR light-induced therapy, as well as the tuning of the upconversion luminescence emissions. This review will give a brief summary of this rapidly developing field, and provide guidance to design and to fabricate new nanocomposites based on upconversion nanophosphors.
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A glimpse of the glomerular milieu: from endothelial cell to thrombotic disease in nephrotic syndrome.
Microvasc. Res.
PUBLISHED: 04-12-2013
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Patients with nephrotic syndrome (NS) carry a high risk of venous thromboembolism (VTE) due to the abnormalities in coagulation and fibrinolysis. Although massive urine protein loss is considered to trigger the cascade of hypercoagulation, the exact nature of VTE in NS patients still remains obscure, especially in some cases when VTE occurs far before the presence of nephrotic proteinuria. Recent findings illustrate that loss of local glomerular homeostasis, like disturbance of cytokine profiles in endothelial cells or aberrant cellular crosstalks in glomerulus, is sufficient to initiate the development of thrombotic disease in glomerulonephropathy. Emerging data have highlighted the glomerular endothelial cell as a key regulator of local homeostasis, which might mediate the haemostatic derangement in the beginning of glomerular disease by expression of numerous prothrombotic factors and result in the subsequent predilection of VTE in NS. As the glomerulus-derived circulating factors are all collected and flushed into the renal vein directly, it is reasonable to suggest that increased release of glomerulus-derived thrombotic regulators, particularly from endothelial cells, may play a significant role in the highest proclivity for the renal vein as the site of thrombosis in NS. In this review, we thus discuss the current understandings of thromboembolism in NS with focus on how the glomerular endothelial cell involves in the pathogenesis of VTE, which may help to increase our understandings in the anti-thrombotic therapy for patients with NS.
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New insights into the pathogenesis and treatment of peritoneal fibrosis: a potential role of Wnt/?-catenin induced epithelial to mesenchymal transition and stem cells for therapy.
Med. Hypotheses
PUBLISHED: 03-28-2013
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Peritoneal fibrosis is a chronic, progressive progress, which is associated with ultrafiltration failure. In the development of peritoneal fibrosis, Epithelial to mesenchymal transition is an important cellular process whereby epithelial cells transform into mesenchymal cells under physiology and pathology conditions, along with change of cell morphology and expression of related genes. It plays an important role in embryogenesis and development of tissues and organs, as well as organ fibrosis and tumorigenesis. Several intracellular signal transduction pathways induce the process of Epithelial to mesenchymal transition. In recent researches, Wnt/?-catenin induced epithelial to mesenchymal transition was suggested to be an important reason for tissues and organs fibrosis. The following paper reviews the potential role of Wnt/?-catenin induced epithelial to mesenchymal transition in peritoneal fibrosis. New potential therapeutic interventions of peritoneal fibrosis are discussed.
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Type I collagen and polyvinyl alcohol blend fiber scaffold for anterior cruciate ligament reconstruction.
Biomed Mater
PUBLISHED: 03-26-2013
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The aim of this study was to perform an evaluation of a braided fiber scaffold for anterior cruciate ligament (ACL) reconstruction. The scaffold was composed of 50% type I collagen (Col-I) and 50% polyvinyl alcohol (PVA). First, the biocompatibility and in vitro weight loss of the scaffold were tested. Then, the scaffolds were used to reconstruct the ACL in China Bama mimi pigs. At 24 weeks post-operation, the mechanical properties and histology of the regenerated ACL were analyzed. The maximum load and tensile strength were 472.43± 15.2 N and 29.71± 0.96 MPa, respectively; both were ~75% of those of native ACL and ~90% of those of fiber scaffold. This indicated that the scaffold maintained a large portion of native ACLs mechanical properties, and tissue formation on the scaffold compensated most of the tensile strength loss caused by scaffold degradation. Histology and immunohistology analysis showed the morphology and major extracellular matrix components of the regenerated ligament resembled the native ACL. Thus, the Col-I/PVA blend fiber ACL scaffold showed good potential for clinical applications.
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Urine miRNAs: potential biomarkers for monitoring progression of early stages of diabetic nephropathy.
Med. Hypotheses
PUBLISHED: 03-19-2013
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With a steep increase in the incidence of type 1 and 2 diabetes globally, diabetic nephropathy (DN) has now become the leading cause of renal failure in the world. There are no suitable biomarkers for the diagnosis of early stages of DN. In recent years, tremendous efforts are being made worldwide to delineate the role of micro RNAs in the pathogenesis of DN. Circulating miRNAs in serum, plasma, urine and other body fluids, which reflect a response to various pathophysiological stresses, are being investigated in the context of diabetic nephropathy. Delineation of the changes in miRNA levels in patients with DN may lead to a better understanding of the progression of the disease. We present here an exhaustive survey of the miRNA literature, highlighting various studies performed over the last decade. The aim is to assess if changes in various miRNAs could correlate with the progression of diabetic nephropathy. Based on the survey, we found that miRNA-377, miRNA-192, miRNA-216/217 and miRNA-144 are increased in body fluids of patients with DN, while miRNA-21 and miRNA-375 are decreased. Overall, there are a very few miRNAs that are kidney specific, and although significant differences were observed in the urinary excretion of certain miRNAs, they were not correlative to their levels in the blood or plasma. Thus, it is completely plausible that urine-specific miRNAs could serve as novel biomarkers for the diagnosis of early stages of diabetic nephropathy.
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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.