As an essential and universal hydrolase, alkaline phosphatase (ALP) has been identified as a crucial indicator of various diseases. Herein, we, for the first time, expanded the application of fluorescent polydopamine (F-PDA) nanoparticles to nanoquencher-based biosensing system, as well as discovered the reversible quenching effect of manganese dioxide (MnO) nanosheets on the fluorescence of F-PDA nanoparticles and intensively confirmed the quenching mechanism of Förster resonance energy transfer by using transmission electron microscopy, UV-vis, Fourier transform infrared spectroscopy, and fluorescence lifetime experiments. By means of the ALP-triggered generation of ascorbic acid (AA) from the substrate ascorbic acid 2-phosphate, the AA-triggered reduction of MnO nanosheets to Mn, as well as the clear quenching mechanism of F-PDA nanoparticles by MnO nanosheets, we have developed a label-free, low-cost, visual, and facile synthetic fluorescent biosensor for convenient assay of ALP activity. The fluorescent bioassay shows a good linear relationship from 1 to 80 mU/mL (R = 0.999), with a low detection limit of 0.34 mU/mL, and the excellent applicability in human serum samples demonstrates potential applications in clinical diagnosis and biomedical research.
Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.
miRNA is a potentially sensitive biomarker for NSTEMI AMI patients for disease detection and treatment monitoring. The sensitivities were comparable to cTnT for diagnostic accuracy and patients with sustained or higher levels were correlated to secondary complications.
Alkaline
phosphatase (ALP) usually acts as a signal transmitter
in enzyme-linked immunosorbent assay (ELISA); therefore, developing
an attractive ALP activity assay, especially using a preferable substrate,
would help improve the efficiency and convenience of ELISA in practical
applications. Herein we have first prepared an original and creative
substrate, named m-hydroxyphenyl phosphate sodium
salt (m-HPP), with a desirable dephosphorylation
site for ALP. On the basis of the ALP-catalyzed hydrolysis of m-HPP to resorcinol and its subsequent specific nucleophilic
reaction with dopamine, we have exploited a fluorometric and colorimetric
dual-readout ALP activity assay and ALP-based ELISA system. Under
the employed experimental conditions, highly sensitive and specific
assay of ALP and cardiac troponin I (cTnI) has been accomplished in
a straightforward way. Furthermore, the commendable sensing performance
of our proposed ELISA in the determination of the cTnI level in diluted
human serum unambiguously illustrates great potential in the early
diagnosis of acute myocardial infarction.
IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague-Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200 μg/kg/d intragastrically) from 12 to 28 weeks. At Week 28, the rats was sacrificed, kidneys and blood samples were collected for further analysis. Our data shown that IgAN rat model showed marked deterioration of proteinuria together with higher levels of the urine protein:creatinine ratio compared to the normal control. Animals that underwent intermittent exposure to triptolide treatment exhibited significant improvements in the functional parameters without severe side effects. Rats developing IgAN had profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, while triptolide treatment significantly attenuated it. We also observed that treatment with triptolide significantly decreases serum levels of IL-1β and IL-18, and may exerted anti-inflammatory effects by down-regulating NLRP3 and TLR4 expression. Our study clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.
To develop a risk stratification model based on complete blood count (CBC) components in patients with acute coronary syndrome (ACS) using a classification and regression tree (CART) method. CBC variables and the Global Registry of Acute Coronary Events (GRACE) scores were determined in 2,693 patients with ACS. The CART analysis was performed to classify patients into different homogeneous risk groups and to determine predictors for major adverse cardiovascular events (MACEs) at 1-year follow-up. The CART algorithm identified the white blood cell count, hemoglobin, and mean platelet volume levels as the best combination to predict MACE risk. Patients were stratified into three categories with MACE rates ranging from 3.0% to 29.8%. Kaplan-Meier analysis demonstrated MACE risk increased with the ascending order of the CART risk categories. Multivariate Cox regression analysis showed that the CART risk categories independently predicted MACE risk. The predictive accuracy of the CART risk categories was tested by measuring discrimination and graphically assessing the calibration. Furthermore, the combined use of the CART risk categories and GRACE scores yielded a more accurate predictive value for MACEs. Patients with ACS can be readily stratified into distinct prognostic categories using the CART risk stratification tool on the basis of CBC components.
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