The Skin Epilipidome in Stress, Aging, and Inflammation

Lipids are highly diverse biomolecules crucial for the formation and function of cellular membranes, for metabolism, and for cellular signaling. In the mammalian skin, lipids additionally serve for the formation of the epidermal barrier and as surface lipids, together regulating permeability, physical properties, acidification and the antimicrobial defense. Recent advances in accuracy and specificity of mass spectrometry have allowed studying enzymatic and non-enzymatic modifications of lipids—the epilipidome—multiplying the known diversity of molecules in this class. As the skin is an organ that is frequently exposed to oxidative-, chemical- and thermal stress, and to injury and inflammation, it is an ideal organ to study epilipidome dynamics, their causes, and their biological consequences. Recent studies uncover loss or gain in biological function resulting from either specific modifications or the sum of the modifications of lipids. These studies suggest an important role for the epilipidome in stress responses and immune regulation in the skin. In this minireview we provide a short survey of the recent developments on causes and consequences of epilipidomic changes in the skin or in cell types that reside in the skin.

Neurotoxic peptides from the venom of the giant Australian stinging tree

Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. We show here that the venoms of Australian Dendrocnide species contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are miniproteins of 4 kDa, whose 3D structure is stabilized in an inhibitory cystine knot motif, a characteristic shared with neurotoxins found in spider and cone snail venoms. Our results provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure, and pharmacology.

Far UV-C lights and fiber optics induced and selective far UV-C treatment against COVID-19 for fatality-survival tradeoff

<p>This work focuses on the usability of Ultraviolet (UV) on humans as an economical way of contesting against COVID-19. Specifically, far-UVC is presented as a promising candidate against COVID-19 since it can inactivate pathogens including viruses and bacteria without harming mammalian skin or eyes. Furthermore, the work also points out the applicability of far-UVC lights for public spaces and treatment of selective region in COVID-19 patients by using fiberoptic as the medium for high-risk cases where chances of survival are low and such treatment may avoid fatality due to the COVID-19.</p>

Far UV-C lights and fiber optics induced and selective far UV-C treatment against COVID-19 for fatality-survival tradeoff

<p>This work focuses on the usability of Ultraviolet (UV) on humans as an economical way of contesting against COVID-19. Specifically, far-UVC is presented as a promising candidate against COVID-19 since it can inactivate pathogens including viruses and bacteria without harming mammalian skin or eyes. Furthermore, the work also points out the applicability of far-UVC lights for public spaces and treatment of selective region in COVID-19 patients by using fiberoptic as the medium for high-risk cases where chances of survival are low and such treatment may avoid fatality due to the COVID-19.</p>

Coexistence of lipid phases stabilizes interstitial water in the outer layer of mammalian skin

ABSTRACTThe lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques, aimed at identifying hydrophilic and lipophilic pathways of permeation. While consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using molecular dynamics simulations of a model mixture of skin lipids, the self-assembly of the lipid matrix lamellae has been studied. At higher humidity, the resulting lamellar phase is maintained by partitioning excess water into isolated droplets of controlled size and spatial distribution. The droplets may fuse together to form intra-lamellar water channels, thereby providing a pathway for the permeation of hydrophilic species. These results reconcile competing data on the outer skin’s structure and broaden the scope of molecular-based methods to improve the safety of topical products and to advance transdermal drug delivery.

Regulated spindle orientation buffers tissue growth in the epidermis

Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.