The Co-oligomers of Aß42 and Human Islet Amyloid Polypeptide Exacerbate Neurotoxicity and Alzheimer-like Pathology at Cellular Level.

The Aß hypothesis has long been central to Alzheimer's disease (AD) theory, with a recent surge in attention following drug approvals targeting Aß plaque clearance. Aß42 oligomers (AßO) are key neurotoxins. While ß-amyloid (Aß) buildup is a hallmark of AD, postmortem brain analyses have unveiled human islet amyloid polypeptide (hIAPP) deposition in AD patients, suggesting a potential role in Alzheimer's pathology. This study investigates the neurotoxic effects of co-aggregates of Aß42 and hIAPP, specifically focusing on their impact on cell survival, apoptosis, and AD-like pathology. We analyzed and compared the impact of AßO and Aß42-hIAPP on cell survival in SH-SY5Y cells, apoptosis and inducing AD-like pathology in glutamatergic neurons. Aß42-hIAPP co-oligomers exhibited significantly greater toxicity, causing 2.3-3.5 times higher cell death compared to AßO alone. Furthermore, apoptosis rates were significantly exacerbated in glutamatergic neurons when exposed to Aß42-hIAPP co-oligomers. The study also revealed that Aß42-hIAPP co-oligomers induced typical AD-like pathology in glutamatergic neurons, including the presence of Aß deposits (detected by 6E10 and 4G8 immunofluorescence) and alterations in tau protein (changes in total tau HT7, phosphorylated tau AT8, AT180). Notably, Aß42-hIAPP co-oligomers induced a more severe AD pathology compared to AßO alone. These findings provide compelling evidence for the heightened toxicity of Aß42-hIAPP co-oligomers on neurons and their role in exacerbating AD pathology. The study contributes novel insights into the pathogenesis of Alzheimer's disease, highlighting the potential involvement of hIAPP in AD pathology. Together, these findings offer novel insights into AD pathogenesis and routes for constructing animal models.

The JMJD family of histone demethylase and their intimate links to cardiovascular disease.

The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.

The synergistic effect of a graphene nanoplate/Fe3O4@BaTiO3 hybrid and MWCNTs on enhancing broadband electromagnetic interference shielding performance.

In this work, methyl vinyl silicone rubber (VMQ) nanocomposites were prepared by solution blending VMQ, a graphene nanoplate/Fe3O4@BaTiO3 hybrid (GFBT) and MWCNTs, aiming to improve the electromagnetic interference (EMI) shielding performance of VMQ. Using the low defect graphene nanoplates (GNPs) as a carrier of Fe3O4@BaTiO3 nanoparticles, the GFBT hybrid was synthesized using a two-step solvothermal method. The micro morphology observed by scanning and transmission electron microscopy (SEM and TEM) showed that Fe3O4 (∼200 nm) and BaTiO3 (∼20 nm) were successfully loaded over GNPs. The GFBT hybrid and MWCNTs had good dispersion in the as-prepared VMQ/GFBT/MWCNTs (VGFBTM) nanocomposite. With a loading of 16.1 wt% total filler (GFBT : MWCNTs = 5 : 1), the shielding effectiveness (SE) of the VGFBTM composite ranged from 26.7 to 33.3 dB (>99.8% attenuation) in a wide frequency range of 1.0-20.0 GHz. A synergistic effect between the GFBT hybrid and MWCNTs provided good dielectric loss and magnetic loss, which played a significant role in improving the electromagnetic interference shielding effectiveness of VMQ. Besides, the electrical conductivity of the VGFBTM nanocomposite was improved compared with VMQ owing to the conducting network structure which was built from two-dimensional GNPs and one-dimensional MWCNTs.