RNA sequencing on muscle biopsy from a 5-week bed rest study reveals the effect of exercise and potential interactions with dorsal root ganglion neurons.

Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5-week bed-rest study with an exercise intervention arm.

Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain.

SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease.

A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction.

The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing.

A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction.

The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing.

In vitro cytotoxicity of montelukast in HAPI and SH-SY5Y cells.

Montelukast is a cysteinyl leukotriene (CysLT) receptor antagonist with efficacy against a variety of diseases, including asthma and inflammation-related conditions. However, various neuropsychiatric events (NEs) suspected to be related to montelukast have been reported recently, with limited understanding on their association and underlying mechanisms. This study aimed to investigate whether montelukast can induce neuroinflammation and neurotoxicity in microglial HAPI cells and neural SH-SY5Y cells.

Enhanced availability of serotonin increases activation of unfatigued muscle but exacerbates central fatigue during prolonged sustained contractions.

Key Points: Animal preparations have revealed that moderate synaptic release of serotonin (5-HT) onto motoneurones enhances motor activity via activation of 5-HT receptors, whereas intense release of 5-HT causes spillover of 5-HT to extrasynaptic 5-HT receptors on the axon initial segment to reduce motoneurone activity. We explored if increasing extracellular concentrations of endogenously released 5-HT (via the selective serotonin reuptake inhibitor paroxetine) influences the ability to perform unfatigued and fatigued maximal voluntary contractions in humans. Following the ingestion of paroxetine, voluntary muscle activation and torque generation increased during brief unfatigued maximal contractions.

Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure.

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 Ẇ) in a 30°C environment in 10 patients with HF (New York Heart Association Class I-II) and 10 healthy controls (CON).

Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes in vivo.

Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P. aeruginosa) that has been shown to have numerous toxic effects in both in vitro and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant mediated responses.

A pilot study assessing the value of 3D printed molecular modelling tools for pharmacy student education.

Background And Purpose: Medicinal chemistry and pharmacology are difficult topics to both teach and learn given the complex nature of drug mechanisms and drug-receptor interactions. This highlights the need for innovative teaching methods to deliver this information to students. One such method is through three-dimensional (3D) printing of enzymes and ligands in the teaching of molecular modelling concepts relating to drug-receptor and enzyme interactions be ligands.

Appraising the role of the virtual patient for therapeutics health education.

Background: Face-to-face instruction, paper-based case-studies and clinical placements remain the most commonly used teaching methods for therapeutics curricula. Presenting clinical content in a didactic manner presents challenges in engaging learners and developing their clinical reasoning skills which may be overcome by inclusion of the virtual patient (VP). Currently there is limited literature examining the use of the VP in therapeutics teaching and learning.

Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa.

Pyocyanin has recently emerged as an important virulence factor produced by Pseudomonas aeruginosa. The redox-active tricyclic zwitterion has been shown to have a number of potential effects on various organ systems in vitro, including the respiratory, cardiovascular, urological, and central nervous systems. It has been shown that a large number of the effects to these systems are via the formation of reactive oxygen species.

Paradoxical effects of the autophagy inhibitor 3-methyladenine on docetaxel-induced toxicity in PC-3 and LNCaP prostate cancer cells.

Docetaxel was the first chemotherapeutic agent to increase survival time in patients with androgen-resistant prostate cancer. However, it provides only a modest increase in survival and is associated with significant toxicity. Therefore, there is an urgent need to identify potential adjunct therapies.

Molecular mechanisms underlying the effects of statins in the central nervous system.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins' effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins' effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system.

ERK1/2 activation modulates pyocyanin-induced toxicity in A549 respiratory epithelial cells.

Pyocyanin (PCN), a virulence factor produced by Pseudomonas aeruginosa, has many damaging effects on mammalian cells. Several lines of evidence suggest that this damage is primarily mediated by its ability to generate oxidative stress. However mechanisms underlying PCN-induced oxidative injury remain unclear.

Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells.

The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 μmol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers.

Effects of Pseudomonas aeruginosa virulence factor pyocyanin on human urothelial cell function and viability.

Purpose: We determined the effects of Pseudomonas aeruginosa virulence factor pyocyanin on human urothelial cell viability and function in vitro.

Materials And Methods: RT4 urothelial cells were treated with pyocyanin (1 to 100 μM) for 24 hours. After exposure the treatment effects were measured according to certain end points, including changes in urothelial cell viability, reactive oxygen species formation, caspase-3 activity, basal and stimulated adenosine triphosphate release, SA-β-gal activity and detection of acidic vesicular organelles.

Inhibition of autophagy by 3-methyladenine protects 1321N1 astrocytoma cells against pyocyanin- and 1-hydroxyphenazine-induced toxicity.

Central nervous system (CNS) infections due to Pseudomonas aeruginosa are difficult to treat and have a high mortality rate. Pyocyanin, a virulence factor produced by P. aeruginosa, has been shown to be responsible for the majority of P.