Exploring the Efficacy of Anti-amyloid-β Therapeutics in Treating Alzheimer Disease

Alzheimer Disease (AD) is the most prevalent cause of dementia, characterized by initial memory impairment and progressive cognitive decline. The exact cause of AD is not yet completely understood. However, the presence of neurotoxic amyloid-beta (Aβ) peptides in the brain is often cited as the main causative agent in AD pathogenesis. In accordance with the amyloid hypothesis, Aβ accumulation initially occurs 15-20 years prior to the development of clinical symptoms. Current therapies focus on the prodromal and preclinical stages of AD due to past treatment failures involving patients with mild to moderate AD. Passive immunization via exogenous monoclonal antibodies (mAbs) administration has emerged as a promising anti-Aβ treatment in AD. This is reinforced by the recent approval of the mAb, aducanumab. mAbs have differential selectivity in their epitopes, each recognising different conformations of Aβ. In this way, various Aβ accumulative species can be targeted. mAbs directed against Aβ oligomers, the most neurotoxic species, are producing encouraging clinical results. Through understanding the process by which mAbs target the amyloid cascade, therapeutics could be developed to clear Aβ, prevent its aggregation, or reduce its production. This review examines the clinical efficacy evidence from previous clinical trials with anti-Aβ therapeutics, in particular, the mAbs. Future therapies are expected to involve a combined-targeted approach to the multiple mechanisms of the amyloid cascade in a particular stage or disease phenotype. Additional studies of presymptomatic AD will likely join ongoing prevention trials, in which mAbs will continue to serve as the focal point.

Cyclo.Plas 2: A Dual Focus Development as Alternative Materials to Plastic by Upcycling Fish Scale Waste Components

Using the biomimicry of fish scale composition, calcium salts and collagen, Cyclo.Plas 2 (CP2) is a dual-focus materials development addressing plastic degradability and waste accumulation. The biomineralisation concept was applied to valorise 3D-printed polylactic acid (PLA) waste with a fish scale-inspired mineral, hydroxyapatite (HAp), to form composites. It was found that the composites exhibited greater flexural strength compared to 3D-printed PLA waste and had faster degradation in hydrolysis, home composting and acidic environments. Following the sclerotisation concept, the physicochemical properties of intact collagenous matrix of fish scale waste were enhanced to form a thin, plastic-like material. These thin films were comparable to low-density polyethylene (LDPE), with high transparency and shrinkage performance. Samples biodegraded after 8 weeks with no phytotoxicity and enhanced plant growth. Trials showed improved thermal stability and water resistance, yet the samples degraded with low total dissolved solids. Cyclo.Plas 2 serves as a preventative and practical disposal solution to promoting a circular economy through home composting.

Comparing In Vitro and In Vivo Models as Part of Pre-Clinical Studies for COVID-19 Medicines

The emergence of SARS-CoV-2 (the aetiological agent of COVID-19) has called for the need to develop robust in vitro and in vivo models as part of the pre-clinical testing of novel therapeutics and treatments. In vitro studies used to study SARS-CoV-2 have included use of cell lines and organoids, which have the advantage of being manipulated to retain high viral loads using the ACE2 receptor. However, despite some drugs having similar data readouts during in vitro studies, as demonstrated by the conflicting approvals of remdesivir and hydroxychloroquine, these studies alone are not entirely reflective of the physiology of human tissue. Therefore, in vivo studies have been used small and large mammals to better understand how COVID-19 interact systematically in the body. This review compares different models of COVID-19 pathogenesis, considering their advantages and limitations to developing candidate drugs or testing existing drugs. Whilst both in vitro and in vivo methods have their advantages and disadvantages, together they allow for the expedition of therapies through clinical trials and reduce the risk of clinical failure. As highlighted during the COVID-19 pandemic, reflective and meaningful models have been crucial in tackling one of the biggest healthcare challenges in recent history.

SOX2 and BRN2 as Key Transcription Factors in Neural Rosette Formation In Vitro

Although neurogenesis has been well studied, its molecular mechanisms remain largely unknown due to the challenges posed by the complexity of the underlying processes. Whilst in vivo studies can be used to study neurogenesis, the inability to control confounding variables complicate findings. Therefore, the purpose of this study was to identify the markers of in vitro neural rosette formation and describe the formation of neural rosettes from pluripotent stem cells using immunofluorescence analysis. The protocol of stem cell cultivation and induction of neural rosette formation was tested. Following, two transcription factors, BRN2 and SOX2, were fluorescently labelled and cells were imaged over a period of eight days. It was identified that SOX2 and BRN2 are expressed during in vitro neural rosette formation. These results are concurrent with in vivo neurogenesis, which suggests that neural rosettes could be a suitable in vitro model for researching neural development. Given that mistakes can arise during neurogenesis, such as neural tube defects, developing robust models to understand the formation of the nervous system is important. Moving forward, a detailed molecular understanding of neural rosette formation has the potential to be used for targeting specific transcription factors to treat or prevent problematic neurogenesis.