Physiology in Perspective.

Abstract

EditorialPhysiology in PerspectiveNikki ForresterNikki ForresterAmerican Physiological Society, Rockville, MarylandPublished Online:07 Oct 2022https://doi.org/10.1152/physiol.00025.2022MoreSectionsPDF (80 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat This issue of Physiology features five excellent review articles that summarize current evidence and identify key areas for future research across a range of topics in physiology. First, we examine clinical outcomes of COVID-19 and response to COVID-19 vaccines in patients with inborn errors of immunity. Next, we discuss peripheral nerve physiology as it relates to injury and recent advancements in treatments. Third, we evaluate mechanistic links between free fatty acid receptor 4 and the attenuation of cardiometabolic disease. Next, we describe the diverse roles of granule-secreted enzymes beyond lymphocyte-mediated target cell death. Finally, we summarize the physiology of the glymphatic waste clearance system and how it is affected by the wake/sleep cycle.COVID-19 has infected more than 600 million people and caused more than 6 million deaths, as of September 2022. Individuals with inborn errors of immunity (IEI), a heterogeneous group of disorders that affect immune host defense and immunoregulation, may be more susceptible to infection and have worse clinical outcomes from the virus than others. For instance, COVID-19 patients with IEI often experience respiratory symptoms, pneumonia, fever, headaches, and gastrointestinal symptoms. However, the risk of developing severe COVID-19 differs depending on the form of IEI. In this review, Delmonte et al. (1) summarize clinical outcomes of SARS-CoV-2 infection and responses to COVID-19 vaccines in patients with IEI.Acute trauma accounts for more than 5,000 nerve injuries in the United States each year. Some of these injuries occur in the peripheral nervous system, leading to life-altering functional deficiencies. Although the peripheral nervous system has the ability to regenerate lost axons, irreversible target atrophy prevents the full restoration of function in patients with peripheral nerve injury, even when their injuries are optimally managed. Over the past 20 years, a better understanding of nerve physiology has paved the way for improved treatments for peripheral nerve injuries. In this review, O’Brien et al. (2) describe nerve regeneration physiology in regard to injury, current treatment options, and recent advances in electrical stimulation, gene therapy, and surgical techniques.In the United States, cardiometabolic diseases, such as heart failure, coronary heart disease, myocardial infarction, and stroke, are increasing in prevalence with the widespread occurrence of metabolic syndrome, which is primarily driven by obesity and type 2 diabetes. Free fatty acid receptor 4 (Ffar4) is a nutrient sensor for endogenous long-chain fatty acids, including ω3-polyunsaturated fatty acids (ω3-PUFAs), that can attenuate metabolic syndrome and resolve inflammation. Ffar4 is also cardioprotective. In this review, O’Connell et al. (3) discuss the physiological function of Ffar4 as well as the mechanistic links between Ffar4, ω3-PUFAs, and the attenuation of cardiometabolic disease.Granule-secreted enzymes (granzymes) are a family of serine proteases. There are five granzymes in the human genome that differ in substrate binding clefts, resulting in unique substrate specificities and various physiological and pathological consequences. In the past, granzymes were thought to play redundant roles in lymphocyte-mediated target cell death. However, recent studies revealed that granzymes function in inflammation, extracellular matrix degradation, impaired wound healing, autoimmunity, and a variety of other roles. In this review, Richardson et al. (4) highlight the noncytotoxic functions of granzymes within a health and disease framework.Cerebral homeostasis requires the constant maintenance of cellular metabolism, fluid homeostasis, and waste elimination. Waste elimination from the brain occurs through cellular metabolism, the blood-brain barrier, and a dedicated perivascular channel network called the glymphatic system. The functionality and efficiency of waste clearance via the glymphatic system vary with the wake/sleep cycle and decline in the aging brain, which may contribute to neurodegenerative diseases, such as Alzheimer’s disease. In this review, Zhao et al. (5) explore the physiology of the glymphatic waste clearance system and the mechanisms driving an increase in waste clearance during sleep.No conflicts of interest, financial or otherwise, are declared by the author.