Alzheimer's disease diagnosis based on detection of autoantibodies against Aß using Aß40 peptide in liposomes.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and affect more than 50 million people worldwide. Thus, there is a high demand by non-invasive methods for an early diagnosis. This work explores the AD diagnostic using the amyloid beta 1-40 (Aß40) peptide encapsulated into dipalmitoyl phosphatidyl glycerol (DPPG) liposomes and immobilized on polyethylene imine previously deposited on screen-printed carbon electrodes to detect autoantibodies against Aß40, a potential biomarker found in plasma samples. METHODS: The immunosensor assembly was accompanied by atomic force microscopy (AFM) images that showed globular aggregates from 20 to 200 nm corresponding liposomes and by cyclic voltammetry (CV) through increase of the voltammogram area each material deposited. After building the immunosensor, when it was exposed to antibody anti-Aß40, there was an increase in film roughness of approximately 9 nm, indicating the formation of the immunocomplex. RESULTS: In the detection by CV, the presence of specific antibody, in the range of 0.1 to 10 µg/ml, resulted in an increase in the voltammograms area and current in 0.45 V reaching 3.2 µA.V and 5.7 µA, respectively, in comparison with the control system, which remained almost unchanged from 0.1 µg/ml. In patient samples, both cerebrospinal fluid (CSF) and plasma, was possible separated among positive and negative samples for AD using CV profile and area, with a difference of 0.1 µA.V from the upper error bar of healthy samples for CSF sample and 0.6 µA.V for plasma sample. CONCLUSIONS: These results showed the feasibility of the method employed for the non-invasive diagnostic of Alzheimer's disease detecting natural autoantibodies that circulate in plasma through a simple and easy-to-interpret method.

Sonic hedgehog drives layered double hydroxides-induced acute inflammatory landscape.

Although layered double hydroxides (LDH) have been listed as promising nanomaterials in human healthcare, very little has been achieved on osteoblast inflammatory signaling. Thus, osteoblasts were challenged with two LDHs (Mg2Al-Cl and Zn2Al-Cl, at 0.002 mg/mL) up to 24 h, establishing an acute inflammatory mechanism, as well as identifying whether Sonic hedgehog (Shh) signaling has an influence. Functional experiments were performed by previously treating (2 h) semiconfluent osteoblast cultures with cyclopamine molecule (cyc), a widely used Shh inhibitor. Considering inflammasome complex, the asc1 gene was significantly up-expressed in response to Zn2Al-Cl - LDHs, as well as the nrlp3 gene. By treating the osteoblast with cyc, the asc1 gene presented an even higher profile. Our results found a down-modulation of major pro-inflammatory cytokines-related genes, when tnfα and il1ß were significantly down-modulated in response to LDHs. Conversely, anti-inflammatory cytokines were up-modulated considering the same experimental procedures. Except the il6, the other il13, il10, and tgfß genes were up modulated. Additionally, Shh signaling seems to modulate this repertory as both the il13 and il10 genes were significantly up-modulated when the Shh signaling was inhibited. Altogether, our results reveal for the first time the exigency of Shh-dependent anti-inflammatory signals in LDH-induced osteoblast responses.

Canine Adipose-Derived Mesenchymal Stromal Cells Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury.

Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham ( n = 8); Crush+PBS ( n = 8); Crush+MSC ( n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group ( p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality ( p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group ( p < 0.04). There were no statistical differences in muscle weight between the groups ( p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2-4 weeks in the rat model of sciatic nerve crush injury.