Common Signaling Pathways Involved in Alzheimer's Disease and Stroke: Two Faces of the Same Coin.

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-ß aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are the disruption of neuronal circuitry at different levels of cellular signaling, leading to the death of neurons and glial cells in the brain. Therefore, it is necessary to find out the common molecular mechanisms of these two diseases to understand their etiological connections. Here, we summarized the most common signaling cascades including autotoxicity, ApoE4, insulin signaling, inflammation, mTOR-autophagy, notch signaling, and microbiota-gut-brain axis, present in both AD and IS. These targeted signaling pathways reveal a better understanding of AD and IS and could provide a distinguished platform to develop improved therapeutics for these diseases.

Health Research and Education during and after the COVID-19 Pandemic: An Australian Clinician and Researcher Perspective.

Introduction: The COVID-19 pandemic had an unprecedented global effect on teaching and education. This review discusses research, education and diagnostics from the perspectives of four academic clinicians and researchers across different facilities in Australia. Materials and methods: The study adopted a literature review and an Australian researcher's perspective on the impact of the COVID-19 pandemic on health education, research and diagnostics. Results: At the start of the pandemic, medical facilities had to adhere urgently to major work restrictions, including social distancing, mask-wearing rules and/or the closure of facilities to protect staff, students and patients from the risk of COVID-19 infection. Telemedicine and telehealth services were rapidly implemented and adapted to meet the needs of medical education, the teaching of students, trainee doctors, nursing and allied health staff and became a widely accepted norm. The impact on clinical research and education saw the closure of clinical trials and the implementation of new methods in the conducting of trials, including electronic consents, remote patient assessments and the ability to commence fully virtual clinical trials. Academic teaching adapted augmented reality and competency-based teaching to become important new modes of education delivery. Diagnostic services also required new policies and procedures to ensure the safety of personnel. Conclusions: As a by-product of the COVID-19 pandemic, traditional, face-to-face learning and clinical research were converted into online formats. An hybrid environment of traditional methods and novel technological tools has emerged in readiness for future pandemics that allows for virtual learning with concurrent recognition of the need to provide for interpersonal interactions.

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases.

Nigella sativa (N. sativa) is an annual flowering plant that has been used as a traditional remedy for many centuries. The seed possesses a large variety of compounds with thymoquinone (TQ) considered its major but not sole bioactive constituent. Supercritical fluid extraction, geographical location, and oxidative status of N. sativa produces the highest yield of essential oil content including TQ. Thymoquinone is lipophilic, heat and light sensitive with low oral bioavailability and rapid elimination that have significantly inhibited its pharmacological development. Novel developments in nanoparticulate-based oral administration, nasal spray and transdermal delivery may allow the clinical development of N. sativa and TQ as therapeutic agents. Animal and human studies indicate a potential role of N. sativa seed oil and TQ for a diverse range of disease processes including hypertension, dyslipidaemia, type 2 diabetes mellitus, arthritis, asthma, bacterial and viral infections, neurological and dermatological disorders, as it belongs to the group of pan-assay interference compounds. This review outlines the pharmacological properties of N. sativa and TQ and their potential wide application for a large variety of human diseases. The paper will focus on recent studies of the anti-inflammatory and antiviral properties that make N. sativa and TQ promising therapeutic agents targeting contemporary inflammatory and infectious diseases including Covid 19.

Effect of D-serine on the serotonin receptors of human platelets.

Recent literature and our previous observations indicated the presence of both NMDA and serotonin type 3 receptors in human platelets with very similar ionic currents to that of cultured mammalian neuronal receptors. Baseline electrophysiological data shows similar profile for platelets from both normal and schizophrenic subjects, whereas serotonin receptor studies exhibited the presence of 5-hydroxytryptamine type-3 (5-HT3) currents in both normal and schizophrenic platelets significantly different from each other. The two major differences observed were: first, 5-HT3 receptors present in the platelets of schizophrenic patients were four times more sensitive to serotonin than those present in the platelets of normal subjects and, second, that D: -serine in micro molar concentrations dampens this effect in platelets from schizophrenic patients but increases the sensitivity of serotonin for platelet 5-HT3 receptors of normal subjects. Patch clamp technique was used to measure the whole cell currents passing through serotonin receptors in these two types of human platelets. The currents were found to be 5-HT3 receptor currents as they were abolished by 10 microM D-tubocurarine. Similarly, micromolar concentrations of D: -serine increased the sensitivity of 5HT3 receptor currents in the normal human platelets but decreased it in the platelets of the schizophrenic patients. This effect was reversed when D-amino acid oxidase (0.3 microM) was co applied with 100 microM of D-serine, raising the possibility that D-serine by itself may act as a modulator for platelet 5-HT3 receptor channel currents. These observations raised exciting new questions about the role of platelet serotonin receptors and their regulation by D-serine.