Immunosensor incorporating half-antibody fragment for electrochemical monitoring of amyloid-β fibrils in artificial blood plasma.
- 作者列表："Palla G","Malecka K","Dehaen W","Radecki J","Radecka H
:In this report, an electrochemical immunosensor for the selective and sensitive monitoring of Aβ1-42 fibrils is presented. The sensing platform was prepared by the formation of a 4,4'-thiobisbenzenethiol (TBBT) self-assembled monolayer on a clean gold surface followed by the covalent entrapment of gold nanoparticles (AuNPs). The half-antibody fragments of the Anti-Amyloid Fibrils antibody were immobilized on AuNPs via S-Au covalent bonds. Each step of immunosensor fabrication was characterized with cyclic voltammetry and electrochemical impedance spectroscopy. The biosensor was successfully used for the sensing of Aβ1-42 fibrils in both phosphate saline buffer (PBS) and artificial blood plasma (ABP). The immunosensor sensitivity estimated based on calibration slopes was better in the presence of APP in the comparison to PBS. The LOD values obtained for both measuring media were of 0.6 pM level. The moderate response towards Aβ1-42 oligomers demonstrated the immunosensor selectivity.
: 在本报告中，介绍了一种用于选择性和灵敏监测Aβ1-42原纤维的电化学免疫传感器。通过在干净的金表面上形成4,4 '-硫代双苯并硫醇 (TBBT) 自组装单层，然后共价截留金纳米颗粒 (AuNPs) 来制备传感平台。抗淀粉样原纤维抗体的半抗体片段通过S-Au共价键固定在aunp上。用循环伏安法和电化学阻抗谱对免疫传感器制备的各个步骤进行了表征。该生物传感器成功地用于感测磷酸盐盐水缓冲液 (PBS) 和人工血浆 (ABP) 中的Aβ1-42原纤维。与PBS相比，基于校准斜率估计的免疫传感器灵敏度在APP存在的情况下更好。两种测量培养基获得的LOD值均为0.6 pM水平。对Aβ1-42寡聚体的中等响应证明了免疫传感器的选择性。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.