Nanotechnology is playing a major role in the field of medical diagnosis, in particular with the biosensor and bioimaging. It improves the performance of the desired system dramatically by displaying higher selectivity and sensitivity. Carbon nanomaterial, gold nanostructure, magnetite nanoparticle, and silica substrate are the most popular nanomaterials greatly contributed to make the affordable and effective biosensor at low-cost. This research work is introducing a new sensing strategy with graphene oxide-constructed triangular electrodes to diagnose Alzheimer's disease (AD). MicroRNA-137 (miRNA-137) was found as a suitable biomarker for AD, and the sensing method was established here to detect miRNA-137 on the complementary sequence. To enhance the immobilization of capture miRNA-137, gold nanostar (GNS) was conjugated with capture miRNA and immobilized on the GO-modified surface through an amine linker. This immobilization process enhanced the hybridization of the target and reaches the detection limit at 10 fM with the sensitivity of 1 fM on the linear curve with a regression coefficient of 0.9038. Further control sequences of miRNA-21 and single and triple base mismatched miRNA-137 did not show a significant response in current changes, indicating the specific miRNA-137 detection for diagnosing AD.
Highly sensitive and easy detection method for Alzheimer's disease (AD) with a suitable biomarker is mandatory for preventing the factors resulting from AD. This research reports a modified ELISA with graphene for the detection of AD biomarker amyloid beta (Aβ) oligomer. Gold nanoparticle (AuNP) conjugated aptamer was used as the capture probe and attached on ELISA-graphene oxide surface through the amine linker. Antibody was used as the detection molecule to reach the maximum detection of Aβ oligomer. Suitable level of APTMS (2%), size of AuNP (30 nm) and aptamer concentration (2 μM) were optimized. This sandwich pattern of aptamer-Aβ oligomer-antibody helps to reach the detection at 50 pM on the optimized ELISA surface and the control experiments in the absence of Aβ oligomer or anti-Aβ oligomer antibody did not show the significant optical detection at 492 nm, indicting the specific detection. Further, Aβ oligomer spiked artificial cerebrospinal fluid did not interfere the detection of Aβ oligomer, confirming the selective detection. This new and modified ELISA surface helps to reach the lower detection of Aβ oligomer and diagnose AD.
Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
Periconceptional folic acid reduces neural tube defect (NTD) risk. Red blood cell folate concentration is inversely associated with NTD risk. In many countries there is a lack of information on NTD rates. Red cell folate status in women of childbearing age may be a surrogate for NTD rates and may be helpful in identifying countries or regions most likely to benefit from improved folate status.