Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it is currently the seventh leading cause of death worldwide. It is characterized by the extracellular aggregation of the amyloid beta-peptide (A beta) into oligomers and fibrils that cause synaptotoxicity and neuronal death. A beta exhibits a dual role in promoting oxidative stress and inflammation. This review aims to unravel the intricate connection between these processes and their contribution to AD progression. The review delves into oxidative stress in AD, focusing on the involvement of metals, mitochondrial dysfunction, and biomolecule oxidation. The distinct yet overlapping concept of nitro-oxidative stress is also discussed, detailing the roles of nitric oxide, mitochondrial perturbations, and their cumulative impact on A beta production and neurotoxicity. Inflammation is examined through astroglia and microglia function, elucidating their response to A beta and their contribution to oxidative stress within the AD brain. The blood-brain barrier and oligodendrocytes are also considered in the context of AD pathophysiology. We also review current diagnostic methodologies and emerging therapeutic strategies aimed at mitigating oxidative stress and inflammation, thereby offering potential treatments for halting or slowing AD progression. This comprehensive synthesis underscores the pivotal role of A beta in bridging oxidative stress and inflammation, advancing our understanding of AD and informing future research and treatment paradigms.

JTD Keywords: A-beta, Alzheimer's disease, Amyloid beta-peptide, Bace, Blood-brain-barrier, Central-nervous-system, Genome-wide association, Mitochondrial dysfunctio, Mouse model, Neurodegeneration, Nitric-oxide, Nitro-oxidative stress, Precursor protein, Reactive oxygen, Receptor-related protein-1

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions. Subsequently, it is emphasized that to overcome the challenges of blood compatibility an endothelium-mimicking system is needed, proposing a synergy of bottom-up synthetic biology, particularly synthetic cells, with passive- and bioactive surface coatings. Such integration holds promise for developing advanced biomaterials capable of recapitulating endothelial functions, thereby enhancing the hemocompatibility and performance of blood-contacting medical devices. The activation of coagulation on the surface of blood-contacting medical devices often leads to thromboembolic complications. A concept for the next generation of hemocompatbile surfaces inspired by endothelium is proposed. This concept not only contribute to the fundamental understanding of hemocompatibility but also offer practical implications for the design and development of biomedical devices with enhanced biocompatibility and functionality. image

JTD Keywords: Antifouling coatings, Antifouling polymer brushes, Coagulation-factor-xii, Endothelium-inspired, Hemocompatibility, Hemocompatible surface coatings, Heparin-induced thrombocytopenia, Nitric-oxide release, Of-the-art, Peptide macrocycle inhibitor, Plasma contact system, Protein-adsorption, Self-assembled monolayers, Surface modificatio, Synthetic endotheliu

Microglia are very sensitive to changes in the environment and respond through morphological, functional and metabolic adaptations. To depict the modifications microglia undergo under healthy and pathological conditions, we developed free access image analysis scripts to quantify microglia morphologies and phagocytosis. Neuron-glia cultures, in which microglia express the reporter tdTomato, were exposed to excitotoxicity or excitotoxicity + inflammation and analysed 8 h later. Neuronal death was assessed by SYTOX staining of nucleus debris and phagocytosis was measured through the engulfment of SYTOX+ particles in microglia. We identified seven morphologies: round, hypertrophic, fried egg, bipolar and three 'inflamed' morphologies. We generated a classifier able to separate them and assign one of the seven classes to each microglia in sample images. In control cultures, round and hypertrophic morphologies were predominant. Excitotoxicity had a limited effect on the composition of the populations. By contrast, excitotoxicity + inflammation promoted an enrichment in inflamed morphologies and increased the percentage of phagocytosing microglia. Our data suggest that inflammation is critical to promote phenotypical changes in microglia. We also validated our tools for the segmentation of microglia in brain slices and performed morphometry with the obtained mask. Our method is versatile and useful to correlate microglia sub-populations and behaviour with environmental changes.

JTD Keywords: classification, identification, image analysis, injury, morphometry, neuroinflammation, neurotoxicity, phagocytosis, Classification, Image analysis, Microglia, Morphometry, Neuroinflammation, Nitric-oxide, Phagocytosis