- Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system. [Journal Article]
- BLBiotechnol Lett 2018 Feb 20
- CONCLUSIONS: 3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.
- Determination of glycated albumin using boronic acid-derived agarose beads on paper-based devices. [Journal Article]
- BBiomicrofluidics 2018; 12(1):014111
- Self-monitoring of glycated albumin (GA), a useful glycemic marker, is an established method for preventing diabetes complications. Here, the paper-based lateral flow assay devices were developed for...
Self-monitoring of glycated albumin (GA), a useful glycemic marker, is an established method for preventing diabetes complications. Here, the paper-based lateral flow assay devices were developed for the sensitive detection of GA and the total human serum albumin (tHSA) in self-monitoring diabetes patients. Boronic acid-derived agarose beads were packed into a hole on a lateral flow channel. These well-coordinated agarose beads were used to capture GA through specific cis-diol interactions and to enhance the colorimetric signals by concentrating the target molecules. The devices exhibited large dynamic ranges (from 10 μg/ml to 10 mg/ml for GA and from 10 mg/ml to 50 mg/ml for tHSA) and low detection limits (7.1 μg/ml for GA and 4.7 mg/ml for tHSA), which cover the range of GA concentration in healthy plasma, which is 0.21-1.65 mg/ml (0.6%-3%). In determining the unknown GA concentrations in two commercial human plasma samples, the relative percentage difference between the values found by a standard ELISA kit and those found by our developed devices was 2.62% and 8.80%, which are within an acceptable range. The measurements of GA and tHSA were completed within 20 min for the total sample-to-answer diagnosis, fulfilling the demand for rapid analysis. Furthermore, the recovery values ranged from 99.4% to 110% in device accuracy tests. These results indicate that the developed paper-based device with boronic acid-derived agarose beads is a promising platform for GA and tHSA detection as applied to self-monitoring systems.
- O2-generating MnO2nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia. [Journal Article]
- TTheranostics 2018; 8(4):990-1004
- Photodynamic therapy (PDT) is an emerging effective treatment for cancer. However, the great promise of PDT for bladder cancer therapy has not yet been realized because of tumor hypoxia. To address t...
Photodynamic therapy (PDT) is an emerging effective treatment for cancer. However, the great promise of PDT for bladder cancer therapy has not yet been realized because of tumor hypoxia. To address this challenge, we fabricated O2-generating HSA-MnO2-Ce6 NPs (HSA for human serum albumin, Ce6 for chlorin e6, and NPs for nanoparticles) to overcome tumor hypoxia and thus enhance the photodynamic effect for bladder cancer therapy.Methods: The HSA-MnO2-Ce6 NPs were prepared. We investigated the O2generation of NPsin vitroandin vivo. The orthotopic bladder cancer model in C57BL/6 mice was established forin vivostudy, and dual-modal imaging of NPs were demonstrated. Therapeutic efficacy of NPs for bladder cancer was evaluated.Results: HSA-MnO2-Ce6 NPs had an excellent performance in generating O2in vitroupon reaction with H2O2at endogenous levels. Moreover,1O2generation was increased two-fold by using HSA-MnO2-Ce6 NPs instead of HSA-Ce6 NPs in the presence of H2O2under 660 nm laser irradiation.In vitrocell viability assays showed that HSA-MnO2-Ce6 NPs themselves were non-toxic but greatly enhanced PDT effects on bladder cancer cells under laser irradiation.In vivonear-infrared (NIR) fluorescence and magnetic resonance (MR) imaging suggested the excellent bladder tumor-targeting property of HSA-MnO2-Ce6 NPs. O2content in orthotopic bladder cancer was increased 3.5-fold after injection of HSA-MnO2-Ce6 NPs as compared with pre-injection. Given the excellent tumor-targeting ability and negligible toxicity, HSA-MnO2-Ce6 NPs were then used to treat orthotopic bladder cancer by PDT. The PDT with HSA-MnO2-Ce6 NPs showed remarkably improved therapeutic efficacy and significantly prolonged lifetime of mice as compared with controls.Conclusion: This study not only demonstrated the great potential of HSA-MnO2-Ce6 NPs for bladder cancer photodynamic ablation but also provided a new therapeutic strategy to overcoming tumor hypoxia.
- All-in-One Theranostic Nanoplatform Based on Hollow MoSxfor Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy. [Journal Article]
- TTheranostics 2018; 8(4):955-971
- CONCLUSIONS: O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel multifunctional theranostic nanoagent for triple-modal imaging as well as single wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.
- Generation and Characterization of a Novel Small Biologic Alternative to PCSK9 Antibodies, DS-9001a, Albumin Binding Domain-Fused Anticalin Protein. [Journal Article]
- JPJ Pharmacol Exp Ther 2018 Feb 20
- Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduced the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought ...
Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduced the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought to be an attractive therapy for dyslipidemia. In the present study, we created a novel small biologic alternative to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be produced by a microbial production system. DS-9001a strongly interfered with PCSK9 binding to low-density-lipoprotein receptor (LDL-R) and PCSK9-mediated degradation of LDL-R. In cynomolgus monkeys, single administration of DS-9001a reduced the serum LDL-C level by about 62.4% for more than 21 days. Moreover, DS-9001a reduced plasma non-high-density-lipoprotein cholesterol and oxidized LDL levels, and their further reductions were observed when atorvastatin and DS-9001a were administered in combination in human CETP/ApoB double transgenic mice. Additionally, their reductions upon the combination of atorvastatin and DS-9001a were more pronounced than those upon the combination of atorvastatin and anacetrapib. Besides its favorable pharmacological profile, DS-9001a has a lower molecular weight (about 22 kDa), yielding a high stoichiometric drug concentration that might result in a smaller administration volume than that in existing antibody therapy. Since bacterial production systems are viewed as more suited to mass production at low cost, DS-9001a may provide a new therapeutic option to treat a large number of patients with dyslipidemia. In addition, considering the growing demand for antibody-like drugs, ABD-fused Anticalin proteins could represent a promising new class of small biological molecules.
- The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation. [Journal Article]
- CPCell Physiol Biochem 2018 Feb 15; 45(4):1399-1409
- CONCLUSIONS: NAC used intravenously or in the presence of blood increases bacterial biofilm formation rather than inhibits it.
- A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products. [Journal Article]
- FRFree Radic Biol Med 2018 Feb 17
- There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired ph...
There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting.
- Thermo-sensitive Metal Chelation Dual-template Epitope Imprinting Polymer using Distillation-precipitation Polymerization for Simultaneous Recognition of Human Serum Albumin and Transferrin. [Journal Article]
- AAACS Appl Mater Interfaces 2018 Feb 20
- A new type of thermo-sensitive dual-template epitope molecular imprinting polymer was prepared coated on magnetic carbon nanotubes (MCNTs@D-EMIP) for simultaneous recognition of human serum albumin (...
A new type of thermo-sensitive dual-template epitope molecular imprinting polymer was prepared coated on magnetic carbon nanotubes (MCNTs@D-EMIP) for simultaneous recognition of human serum albumin (HSA) and transferrin (Trf) via the strategies of dual-template epitope imprinting, metal chelation imprinting and distillation-precipitation polymerization (DPP). C-terminal peptides of HSA and C-terminal peptides of Trf were selected as templates, zinc acrylate and N-isopropylacrylamide (NIPAM) were used as functional monomers, and MCNTs@D-EMIP was prepared by the method of DPP. The two types of template epitopes were immobilized by metal chelation and six-membered ring formed with zinc acylate. MCNTs@D-EMIP was prepared only in 30 min which was much shorter than other polymerization methods. The resultant MCNTs@D-EMIP showed excellent specific recognition ability towards HSA and Trf. The adsorption amounts of MCNTs@D-EMIP for HSA and Trf were 103.67 mg g-1 and 68.48 mg g-1 and imprinting factors were 2.57 and 2.17, respectively. In addition, MCNTs@D-EMIP displayed thermo-sensitive property to realize temperature controlled recognition and release of target proteins. Furthermore, the results of HPLC analysis proved that MCNTs@D-EMIP could be applied to specifically recognize two types of targets simultaneously in bio-sample. The proposed strategy provided a preparation method for thermo-sensitive dual-template epitope imprinting polymer via dual-template imprinting, metal chelation imprinting and DPP.
- Effects of goal-directed fluid therapy on enhanced postoperative recovery: An interventional comparative observational study with a historical control group on oesophagectomy combined with ERAS program. [Journal Article]
- CNClin Nutr ESPEN 2018; 23:184-193
- CONCLUSIONS: The GDT-ERAS program enhanced postoperative gastrointestinal recovery and mobilisation, as well as postoperative nutritional status and protein synthesis. The program did not affect either postoperative LOS or the incidence of complications.
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- Fabrication of Calixarene Based Protein Scaffold by Electrospin Coating for Tissue Engineering. [Journal Article]
- JNJ Nanosci Nanotechnol 2018 Aug 01; 18(8):5292-5298
- In this study, calixarene was synthesized by using different functional groups as p-tert-butyl-Calixarene ester and amides. Calixarene nanofibers were produced by electrospin coating. Protein immo...
In this study, calixarene was synthesized by using different functional groups as p-tert-butyl-Calixarene ester and amides. Calixarene nanofibers were produced by electrospin coating. Protein immobilization onto the calixarene nanofibers was carried out with human serum albumin (HSA). The maximum amount of binding on produced three different calixarene nanofibers (DE, 2-AMP and 3-AMP) was compared by using a fluorescence technique for protein analysis. Result showed that maximum binding amount was found to be as 177.85 mg cm-2 for 3-AMP surface. The protein binding was also characterized by using SEM, TEM, AFM and FT-IR. From obtained results, calixarene-albumin nanofiber was also fabricated by spin coating using 3-AMP which has ability max binding of protein.