Effects of anhydrous gel with TriHex peptides on healing after hybrid laser resurfacing.

BACKGROUND: Hybrid fractional laser skin resurfacing is a procedure that combines fractional nonablative and ablative wavelengths to improve photoaging. The postoperative period involves overt skin swelling, redness, and roughness. OBJECTIVE: A single-center, randomized trial was performed to compare the effect of a standard Skincare regimen, with and without an anhydrous gel with TriHex peptides (a proprietary tripeptide and hexapeptide blend), on recovery after hybrid laser resurfacing of the face. METHODS: Five subjects were assigned to a split-face protocol. Use of the skin regimen began approximately 2 weeks before the hybrid laser resurfacing and ended 7 days after. Subjects were evaluated by a physician for postprocedural healing. Additionally, the subjects were photographed and completed surveys to assess postprocedural healing and overall preference for Skincare regimen. RESULTS: Based on physician assessment, mean redness on postoperative days 1 and 4 and mean roughness on the postoperative days 3 and 4 were significantly (P < .05) improved on the side of the face using the anhydrous gel with TriHex peptides compared with the side using a standard skin regimen. Based on subject assessment, 4 out of 5 subjects thought that their skin and complexion appeared better on the anhydrous gel-treated side and preferred the Skincare regimen with the gel. CONCLUSIONS: These data suggest that using the anhydrous gel with TriHex peptides before and after hybrid fractional laser skin resurfacing can minimize the postoperative redness and roughness that are typical and expected for this procedure.

Camphor white oil induces tumor regression through cytotoxic T cell-dependent mechanisms.

Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora, are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products are not fully understood. We tested an essential-oil derivative, camphor white oil (CWO), for anti-tumor activity in a mouse model of keratinocyte-derived skin cancer. Daily topical treatment with CWO induced dramatic regression of pre-malignant skin tumors and a two-fold reduction in cutaneous squamous cell carcinomas. We next investigated underlying cellular and molecular mechanisms. In cultured keratinocytes, CWO stimulated calcium signaling, resulting in calcineurin-dependent activation of nuclear factor of activated T cells (NFAT). In vivo, CWO induced transcriptional changes in immune-related genes identified by RNA-sequencing, resulting in cytotoxic T cell-dependent tumor regression. Finally, we identified chemical constituents of CWO that recapitulated effects of the admixture. Together, these studies identify T cell-mediated tumor regression as a mechanism through which a plant-derived essential oil diminishes established tumor burden.

Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors.

Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.

The ion channel TRPA1 is required for chronic itch.

Chronic itch is a debilitating condition that affects one in 10 people. Little is known about the molecules that mediate chronic itch in primary sensory neurons and skin. We demonstrate that the ion channel TRPA1 is required for chronic itch. Using a mouse model of chronic itch, we show that scratching evoked by impaired skin barrier is abolished in TRPA1-deficient animals. This model recapitulates many of the pathophysiological hallmarks of chronic itch that are observed in prevalent human diseases such as atopic dermatitis and psoriasis, including robust scratching, extensive epidermal hyperplasia, and dramatic changes in gene expression in sensory neurons and skin. Remarkably, TRPA1 is required for both transduction of chronic itch signals to the CNS and for the dramatic skin changes triggered by dry-skin-evoked itch and scratching. These data suggest that TRPA1 regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch.

DEG/ENaCs lead by a nose: mechanotransduction in a polymodal sensory neuron.

Degenerin/epithelial sodium channels (DEG/ENaCs) are luminaries of gentle touch in Caenorhabditis elegans. In this issue of Neuron, Geffeney et al. demonstrate that eponymous DEG-1 channels carry mechanotransduction currents in a polymodal neuron, where they act upstream of transient receptor potential (TRP) channels.

The cell biology of touch.

The sense of touch detects forces that bombard the body's surface. In metazoans, an assortment of morphologically and functionally distinct mechanosensory cell types are tuned to selectively respond to diverse mechanical stimuli, such as vibration, stretch, and pressure. A comparative evolutionary approach across mechanosensory cell types and genetically tractable species is beginning to uncover the cellular logic of touch reception.

Merkel cells are essential for light-touch responses.

The peripheral nervous system detects different somatosensory stimuli, including pain, temperature, and touch. Merkel cell-neurite complexes are touch receptors composed of sensory afferents and Merkel cells. The role that Merkel cells play in light-touch responses has been the center of controversy for over 100 years. We used Cre-loxP technology to conditionally delete the transcription factor Atoh1 from the body skin and foot pads of mice. Merkel cells are absent from these areas in Atoh1(CKO) animals. Ex vivo skin/nerve preparations from Atoh1(CKO) animals demonstrate complete loss of the characteristic neurophysiologic responses normally mediated by Merkel cell-neurite complexes. Merkel cells are, therefore, required for the proper encoding of Merkel receptor responses, suggesting that these cells form an indispensible part of the somatosensory system.