Click chemistry as a tool in biosensing systems for sensitive copper detection.

Copper detection for diagnostic purposes is an appealing field due to the important biological role copper plays as a trace metal. A convenient strategy for sensing copper is to utilize its catalytic ability. Therefore, this review summarizes approaches for copper determination by CuI-catalyzed azide/alkyne cycloaddition (CuAAC). The concept was introduced in 2006 and all contributions made up to the middle of 2020 are covered in this review. The issue is divided into three categories: electrochemical, visual, and fluorescence-based methods. The advantages, as well as the disadvantages, of every group, are discussed in detail. The methodology which allows for the determination of copper content in water and human biological samples from 5 s up to 48 h without complex instrumentation are discussed. The reported range of limit of detection (LOD) was 0.38 aM-20 µM, with 1-10 nM being the typical range. The most successful strategies involved using DNA chains or enzymes in the sensing systems.

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy.

OBJECTIVE: Here we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets. RESEARCH DESIGN AND METHODS: We compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs. RESULTS: Patients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vß/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures. CONCLUSIONS: T1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs. TRIAL REGISTRATION NUMBER: EudraCT 2014-004319-35.