The calcium ion (Ca2+) is a diverse secondary messenger with a near-ubiquitous role in a vast array of cellular processes. Cilia are present on nearly every cell type in either a motile or non-motile form; motile cilia generate fluid flow needed for a variety of biological processes, such as left–right body patterning during development, while non-motile cilia serve as the signaling powerhouses of the cell, with vital singling receptors localized to their ciliary membranes. Much of the research currently available on Ca2+-dependent cellular actions and primary cilia are tissue-specific processes. However, basic stimuli-sensing pathways, such as mechanosensation, chemosensation, and electrical sensation (electrosensation), are complex processes entangled in many intersecting pathways; an overview of proposed functions involving cilia and Ca2+ interplay will be briefly summarized here. Next, we will focus on summarizing the evidence for their interactions in basic cellular activities, including the cell cycle, cell polarity and migration, neuronal pattering, glucose-mediated insulin secretion, biliary regulation, and bone formation. Literature investigating the role of cilia and Ca2+-dependent processes at a single-cellular level appears to be scarce, though overlapping signaling pathways imply that cilia and Ca2+ interact with each other on this level in widespread and varied ways on a perpetual basis. Vastly different cellular functions across many different cell types depend on context-specific Ca2+ and cilia interactions to trigger the correct physiological responses, and abnormalities in these interactions, whether at the tissue or the single-cell level, can result in diseases known as ciliopathies; due to their clinical relevance, pathological alterations of cilia function and Ca2+ signaling will also be briefly touched upon throughout this review.
A world-wide coronavirus pandemic is in full swing and, at the time of writing, there are only few treatments that have been successful in clinical trials, but no effective anti-viral treatment has been approved. Because of its lethality, it is important to understand the current strain's effects and mechanisms not only in the respiratory system, but in other affected organ systems as well. Past coronavirus outbreaks caused by SARS-CoV and MERS-CoV inflicted life-threatening acute kidney injuries (AKI) on their hosts leading to significant mortality rates, which went somewhat overlooked in the face of the severe respiratory effects. Recent evidence has emphasized renal involvement in SARS-CoV-2, stressing that kidneys are damaged in COVID-19 patients. The mechanism by which this virus inflicts AKI is still unclear, but evidence from other coronavirus strains may hold some clues. Two theories exist for the proposed mechanism of AKI: 1) the AKI is a secondary effect to reduced blood and oxygen levels causing hyperinflammation and 2) the AKI is due to cytotoxic effects. Kidneys express angiotensin-converting enzyme-2 (ACE2), the confirmed SARS-CoV-2 target receptor as well as collectrin, an ACE2 homologue, that localizes to the primary cilium, an organelle historically targeted by coronaviruses. While the available literature suggests that kidney damage is leading to higher mortality rates in COVID-19 patients, especially in those with pre-existing kidney and cardiovascular diseases, the pathogenesis of COVID-19 is still being investigated. Here, we present brief literature review supporting our proposed hypothesis of a possible link between SARS-CoV-2 cellular infection and cilia.
Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Because factors such as antigenic drift allow influenza strains to avoid being fully suppressed by seasonal vaccines, public interest has led to increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of sufficient clinical trials, as well as a lack of toxicity data; this is especially true of umifenovir (Arbidol), a popularly used drug for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid, widespread cross-resistance, and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when coadministered with other antiviral drugs. Indeed, the low genetic barriers to resistance faced by influenza antivirals may be surmounted by coadministration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and current data on their susceptibility to resistance and efficacy at this time.
Antigenic drift in influenza strains allows viruses to avoid being fully suppressed by seasonal vaccines. As a result, public interest has led to increased scrutiny and reevaluation of anti-influenza antiviral drugs as possible solutions. Unfortunately, many anti-influenza drugs developed around the globe suffer from a lack of sufficient clinical trials, as well as a lack of toxicity data. This is especially true of Arbidol, a popularly used drug for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, which were developed in the United States, also fall victim to inconclusive clinical trials and adverse effects. Adamantanes, while proven to be effective in treating influenza A, are encountering rapid, widespread cross-resistance. Baloxavir marboxil, a newer anti-influenza medication, shows promise in treating acute uncomplicated influenza, and may avoid the development of resistance when coadministered with other antiviral drugs. This review explores the antivirals available for influenzas treatment at this time.
Primary cilia are sensory organelles present on the surface of most polarized cells. Primary cilia have been demonstrated to play many sensory cell roles, including mechanosensory and chemosensory functions. We demonstrated previously that primary cilia of vascular endothelial cells will bend in response to fluid shear stress, which leads to the biochemical production and release of nitric oxide. This process is impaired in endothelial cells that lack primary cilia function or structure. In this chapter, we will provide an overview of ciliogenesis and the differences between primary cilia and multicilia, as well as an overview of our published work on primary cilia and nitric oxide, and a brief perspective on their implications in health and disease.
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