Low-level laser activates Wnt/ß-catenin signaling pathway-promoting hair follicle stem cell regeneration and wound healing: Upregulate the expression of key downstream gene Lef 1.

BACKGROUND: The objective of this study is to investigate the mechanism by which low-level laser stimulation promotes the proliferation of intraepithelial hair follicle stem cells (HFSCs) in wounds. This research aims to expand the applications of laser treatment, enhance wound repair methods, and establish a theoretical and experimental foundation for achieving accelerated wound healing. METHODS: The experimental approach involved irradiating a cell model with low-level laser to assess the proliferation of HFSCs and examine alterations in the expression of proteins related to the Wnt/ß-catenin signaling pathway. A mouse back wound model was established to investigate the effects of low-level laser irradiation on wound healing rate, wound microenvironment, and the proliferation of HFSCs in relation to the Wnt/ß-catenin signaling pathway. RESULTS: The research findings indicate that low-level laser light effectively activates the Wnt signaling pathway, leading to the increased accumulation of core protein ß-catenin and the upregulation of key downstream gene Lef 1. Consequently, this regulatory mechanism facilitates various downstream biological effects, including the notable promotion of HFSC proliferation and differentiation into skin appendages and epithelial tissues. As a result, the process of wound healing is significantly accelerated. CONCLUSION: Low levels of laser activates the Wnt signalling pathway, promotes the regeneration of hair follicle stem cells and accelerates wound healing.

Blue light inhibits cell viability and proliferation in hair follicle stem cells and dermal papilla cells.

Hair loss is a prevalent issue worldwide, which, though not life-threatening, can result in psychological problems, low self-esteem, and social anxiety. Previous studies have shown that ultraviolet radiation can have negative effects on hair follicle cells, leading to hair loss, while the impact of blue light on hair and hair follicle has largely been overlooked. This study aimed to examine the effects of blue light on hair follicle stem cells (HFSCs) and primary dermal papilla cells (DPCs), which are essential components of hair follicles. Human HFSCs and primary DPCs were exposed to blue light (457 nm) at various intensities (1, 4, 8, and 16 mW/cm2) for 3 days. Subsequently, cell viability, cell proliferation, and intracellular reactive oxygen species (ROS) were assessed. The results showed that blue light (457 nm) significantly reduced the cell viability and proliferation of HFSCs and DPCs in vitro, with the inhibition being intensity-dependent. Additionally, blue light triggered the overproduction of ROS in the DPCs. While the exact mechanisms by which blue light affects hair follicle cells remain unclear, these findings suggest that blue light could impede the growth of these cells. This insight may offer a new approach to protecting hair by avoiding exposure to high-intensity blue light.

Carbon Dioxide Fractional Laser Treatment Induces Lgr5+ Stem Cell Activation and Hair Regrowth Through the Canonical Wnt/ß-Catenin Pathway.

BACKGROUND: Different types of alopecia have negative impacts on patients. Recently, some kinds of laser or light therapies have been reported to effectively alleviate hair loss. Carbon dioxide fractional laser (CO2FL) treatment is one of the most effective laser treatments, but its beneficial effects and exact mechanism in hair regrowth have not been reported in detail. The purpose of this study was to investigate the effect and molecular mechanism further. METHODS: C57 and Lgr5-Cre: Rosa-mTmG mouse models of hair regrowth were established by CO2FL treatment, and the parameters that induced the best effect were determined. Tissues were harvested on the day prior to the treatment day and on days 3, 5, 7, 10 and 14 after CO2FL. H&E and immunofluorescence staining, RNA sequencing (RNA-seq), quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and related inhibitor were used to determine the molecular mechanism underlying the effect of CO2FL treatment on the hair cycle and hair regrowth. In clinical trial, five participants were treated three sessions at 1-month intervals to obverse the effects. RESULTS: Hair regrew and covered the treatment area on the tenth day after CO2FL treatment with the best parameters, while the control group showed signs of hair growth on the 14th day. H&E and immunofluorescence staining showed that the transition of hair follicles (HFs) from telogen to anagen was accelerated, and the rapid activation and proliferation of Lgr5+ hair follicle stem cells (HFSCs) were observed in the treatment group. The RNA-seq, qPCR and WB results indicated that the Wnt pathway was significantly activated after CO2FL treatment. Improvement achieved with CO2FL treatment in clinical trial. CONCLUSIONS: The results of this study suggest that CO2FL treatment can promote hair regrowth by activating Lgr5+ HFSCs and upregulating the Wnt/ß-catenin pathway. Clinical trial results demonstrated that CO2FL treatment will be a promising therapeutic regimen for alopecia. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cryptochrome 1 is modulated by blue light in human keratinocytes and exerts positive impact on human hair growth.

Photoactivation of cryptochrome-family proteins by blue light is a well-established reaction regulating physiology of plants, fungi, bacteria, insects and birds, while impact of blue light on cryptochrome synthesis and/or activity in human non-visual cells remains unknown. Here, we show that 453 nm blue light induces cryptochrome 1 (CRY1) accumulation in human keratinocytes and the hair follicle. CRY1 is prominently expressed in the human anagen hair follicle, including epithelial stem cells. Specific silencing of CRY1 promotes catagen, while stimulation of CRY1 by KL001 prolongs anagen ex vivo by altering the expression of genes involved in apoptosis and proliferation. Together, our study identifies a role for CRY1 in sustaining human hair growth. Previously, we demonstrated positive effects of 453 nm blue light on hair growth ex vivo. Taken all together, our study suggests that CRY1 might mediate blue light-dependent positive effects on hair growth.

Low-frequency electromagnetic fields promote hair follicles regeneration by injection a mixture of epidermal stem cells and dermal papilla cells.

The bioeffects of low-frequency electromagnetic fields (EMF) on a bio-engineered hair follicle generation had not been fully elucidated. This present study was designed to evaluat the therapeutically effective of low frequency EMF on hair follicles regeneration. In this experiment, epidermal stem cells (ESCs) and dermal papilla (DP) cells were isolated and culture-expanded. Then the mixture containing of ESCs and DP cells was implanted into the epidermal layer or corium layer of nude mice. Those mice were  divided at random into the control group and EMF group, 7 days or 14 days later, the skin specimens were harvested to assess for hair regeneration or a bio-engineered skin formation using H&E staining. After injection of the mixture into the epidermal layer of nude mice for 14 days, H&E staining showed that the new hair formed the correct structure comprising hair matrix, hair shaft, and inner root sheath, outer root sheath, and DP. Comparing to the control, the hair follicles erupted at a higher density in the EMF group. When the mixture was implanted into the corium layer for 7 days, comparing with the characteristics of new hair follicles in the control group, H&E staining also showed the mixture induced to form 4 ~ 6 epidermal layers with a higher density of hair follicle like-structures in the bioengineered epithelial layers after EMF exposure. Our results suggested that the injection of a mixture of ESCs and DP cells in combination with EMF exposure facilitated the induction of hair follicle regeneration and a bioengineered skin formation with hair follicle-like structures.

Establishment and characterization of a radiation-induced dermatitis rat model.

Radiation-induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of post-irradiation dermatitis, which remains a significant clinical problem. Resolving this challenge requires gaining a better understanding of the precise pathophysiology, which in turn requires establishment of a suitable animal model that mimics the clinical condition, and can also be used to investigate the mechanism and explore effective treatment options. In this study, a single dose of 90 Gy irradiation to rats resulted in ulceration, dermal thickening, inflammation, hair follicle loss, and sebaceous glands loss, indicating successful establishment of the model. Few hair follicle cells migrated to form epidermal cells, and both the severity of skin fibrosis and hydroxyproline levels increased with time post-irradiation. Radiation damaged the mitochondria and induced both apoptosis and autophagy of the skin cells. Therefore, irradiation of 90 Gy can be used to successfully establish a rat model of radiation-induced dermatitis. This model will be helpful for developing new treatments and gaining a better understanding of the pathological mechanism of radiation-induced dermatitis. Specifically, our results suggest autophagy regulation as a potentially effective therapeutic target.

UVB-induced depletion of donor-derived dendritic cells prevents allograft rejection of immune-privileged hair follicles in humanized mice.

Dendritic cells (DCs) are key targets for immunity and tolerance induction; they present donor antigens to recipient T cells by donor- and recipient-derived pathways. Donor-derived DCs, which are critical during the acute posttransplant period, can be depleted in graft tissue by forced migration via ultraviolet B light (UVB) irradiation. Here, we investigated the tolerogenic potential of donor-derived DC depletion through in vivo and ex vivo UVB preirradiation (UV) combined with the injection of anti-CD154 antibody (Ab) into recipients in an MHC-mismatched hair follicle (HF) allograft model in humanized mice. Surprisingly, human HF allografts achieved long-term survival with newly growing pigmented hair shafts in both Ab-treated groups (Ab-only and UV plus Ab) and in the UV-only group, whereas the control mice rejected all HF allografts with no hair regrowth. Perifollicular human CD3+ T cell and MHC class II+ cell infiltration was significantly diminished in the presence of UV and/or Ab treatment. HF allografts in the UV-only group showed stable maintenance of the immune privilege in the HF epithelium without evidence of antigen-specific T cell tolerance, which is likely promoted by normal HFs in vivo. This immunomodulatory strategy targeting the donor tissue exhibited novel biological relevance for clinical allogeneic transplantation without generalized immunosuppression.

How chemotherapy and radiotherapy damage the tissue: Comparative biology lessons from feather and hair models.

Chemotherapy and radiotherapy are common modalities for cancer treatment. While targeting rapidly growing cancer cells, they also damage normal tissues and cause adverse effects. From the initial insult such as DNA double-strand break, production of reactive oxygen species (ROS) and a general stress response, there are complex regulatory mechanisms that control the actual tissue damage process. Besides apoptosis, a range of outcomes for the damaged cells are possible including cell cycle arrest, senescence, mitotic catastrophe, and inflammatory responses and fibrosis at the tissue level. Feather and hair are among the most actively proliferating (mini-)organs and are highly susceptible to both chemotherapy and radiotherapy damage, thus provide excellent, experimentally tractable model systems for dissecting how normal tissues respond to such injuries. Taking a comparative biology approach to investigate this has turned out to be particularly productive. Started in chicken feather and then extended to murine hair follicles, it was revealed that in addition to p53-mediated apoptosis, several other previously overlooked mechanisms are involved. Specifically, Shh, Wnt, mTOR, cytokine signalling and ROS-mediated degradation of adherens junctions have been implicated in the damage and/or reparative regeneration process. Moreover, we show here that inflammatory responses, which can be prominent upon histological examination of chemo- or radiotherapy-damaged hair follicle, may not be essential for the hair loss phenotype. These studies point to fundamental, evolutionarily conserved mechanisms in controlling tissue responses in vivo, and suggest novel strategies for the prevention and management of adverse effects that arise from chemo- or radiotherapy.

Dose-response of human follicles during laser-based hair removal: Ex vivo photoepilation model with classification system embracing morphological and histological features.

OBJECTIVES: Photoepilation is a commonly used technology in home-use devices (HUDs) and in professional systems to remove unwanted body hair using pulses of laser or intense pulsed light (IPL). Albeit HUDs and professional systems operate at different fluences and treatment regimes, both demonstrate high hair reduction. The underlying mechanisms, however, remain unknown partly due to high divergence of the existing literature data. The objective of this study was to develop an ex vivo photoepilation model with a set of criteria evaluating response to light pulses; and to investigate dose-response behavior of hair follicles (HFs) subjected to a range of fluences. METHODS: After ex vivo treatment (single pulse, 810 nm, 1.7-26.4 J/cm2 , 4-64 ms pulse) human anagen HFs were isolated and maintained in culture for 7-10 days. Response to light was evaluated based on gross-morphology and histological examination (H&E and TUNEL stainings). RESULTS: HFs treated ex vivo demonstrated a dose-dependent response to light with five distinct classes defined by macroscopic and microscopic criteria. Fluences below 13.2 J/cm2 provoked catagen-like transition, higher fluences resulted in coagulation in HF compartments. CONCLUSION: Observed changes in the HF organ culture model were reflected by clinical efficacy. The developed photoepilation model provides an easy and fast method to predict clinical efficacy and permanency of light-based hair removal devices. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Pseudofolliculitis Barbae: A Review of Current Treatment Options

The purpose of this review is to discuss the disease process and wide variety of treatment options for psuedofolliculitis barbae (PFB), or razor bumps. PFB is caused by hair follicles penetrating the skin and causing an inflammatory response. PFB can occur to anyone who shaves, and is more likely in those with curly hair. PFB can cause significant hyperpigmentation and scarring, more noticeable in darker skin types. PFB can be treated with a variety of topical, systemic, or light/laser therapies. Minimal progress has been made in treating PFB in recent years, partially due to the success of well-established current treatments discussed in this review. The most effective treatments involve a multifaceted approach including behavioral changes in shaving habits as well as the use of topical therapies. J Drugs Dermatol. 2019;18(3):246-250.

Activation of Wnt/ß-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in in vitro culture model.

Activation of the Wnt/ß-catenin signaling pathway plays an important role in hair follicle morphogenesis and hair growth. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth in numerous clinical studies, in which 655-nm red light was found to be most effective and practical for stimulating hair growth. We evaluated whether 655-nm red light + light-emitting diode (LED) could promote human hair growth by activating Wnt/ß-catenin signaling. An in vitro culture of human hair follicles (HFs) was irradiated with different intensities of 655-nm red light + LED, 21 h7 (an inhibitor of ß-catenin), or both. Immunofluorescence staining was performed to assess the expression of ß-catenin, GSK3ß, p-GSK3ß, and Lef1 in the Wnt/ß-catenin signaling. The 655-nm red light + LED not only enhanced hair shaft elongation, but also reduced catagen transition in human hair follicle organ culture, with the greatest effectiveness observed at 5 min (0.839 J/cm2). Additionally, 655-nm red light + LED enhanced the expression of ß-catenin, p-GSK3ß, and Lef1, signaling molecules of the Wnt/ß-catenin pathway, in the hair matrix. Activation of Wnt/ß-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in vitro and therefore may serve as an alternative therapeutic option for alopecia.

Exposure to non-ionizing electromagnetic fields emitted from mobile phones induced DNA damage in human ear canal hair follicle cells.

The aim of this study was to investigate effect of radiofrequency radiation (RFR) emitted from mobile phones on DNA damage in follicle cells of hair in the ear canal. The study was carried out on 56 men (age range: 30-60 years old)in four treatment groups with n = 14 in each group. The groups were defined as follows: people who did not use a mobile phone (Control), people use mobile phones for 0-30 min/day (second group), people use mobile phones for 30-60 min/day (third group) and people use mobile phones for more than 60 min/day (fourth group). Ear canal hair follicle cells taken from the subjects were analyzed by the Comet Assay to determine DNA damages. The Comet Assay parameters measured were head length, tail length, comet length, percentage of head DNA, tail DNA percentage, tail moment, and Olive tail moment. Results of the study showed that DNA damage indicators were higher in the RFR exposure groups than in the control subjects. In addition, DNA damage increased with the daily duration of exposure. In conclusion, RFR emitted from mobile phones has a potential to produce DNA damage in follicle cells of hair in the ear canal. Therefore, mobile phone users have to pay more attention when using wireless phones.

Wnt/ß-catenin and ERK pathway activation: A possible mechanism of photobiomodulation therapy with light-emitting diodes that regulate the proliferation of human outer root sheath cells.

BACKGROUND: Outer root sheath cells (ORSCs) play important roles in maintaining hair follicle structure and provide support for the bulge area. The hair growth promoting effects of photobiomodulation therapy (PBMT) have been reported, but the mechanisms for this in human ORCs (hORSCs) have rarely been studied. OBJECTIVE: The aim of this study was to investigate the effect of various wavelengths of light-emitting diode (LED) irradiation on human ORSCs (hORSCs). METHODS: LED irradiation effects on hORSC proliferation and migration were examined with MTT assay, BrdU incorporation assay and migration assays. hORSCs were irradiated using four LED wavelengths (415, 525, 660, and 830 nm) with different low energy levels. LED irradiation effects on the expression of molecules associated with the Wnt/ß-catenin signaling and ERK pathway, hair stem cell markers, and various growth factors and cytokines in hORSCs were examined with real-time PCR and Western blot assay. The effect of the LED-irradiated hORSCs on cell proliferation of human dermal papilla cells (hDPCs) was examined with co-culture and MTT assay. RESULTS: PBMT with LED light variably promoted hORSC proliferation and suppressed cell apoptosis depending on energy level. LED irradiation induced Wnt5a, Axin2, and Lef1 mRNA expression and ß-catenin protein expression in hORSCs. Phosphorylation of ERK, c-Jun, and p38 in hORSCs was observed after LED light irradiation, and ERK inhibitor treatment before irradiation reduced ERK and c-Jun phosphorylation. Red light-treated hORSCs showed substantial increase in IL-6, IL-8, TNF-a, IGF-1, TGF-ß1, and VEGF mRNA. Light irradiation at 660 and 830 nm projected onto hORSCs accelerated in vitro migration. LED-irradiated hORSCs increased hDPCs proliferation when they were co-cultured. The conditioned medium from LED-irradiated hORSCs was sufficient to stimulate hDPCs proliferation. CONCLUSION: These results demonstrate that LED light irradiation induced hORSC proliferation and migration and inhibited apoptosis in vitro. The growth-promoting effects of LEDs on hORSCs appear to be associated with direct stimulation of the Wnt5a/ß-catenin and ERK signaling pathway. Lasers Surg. Med. 49:940-947, 2017. © 2017 Wiley Periodicals, Inc.

A review on laser and light-based therapies for alopecia areata.

Alopecia areata is a form of non-scarring alopecia that results from a hyperactive immune response of T cells against hair follicles. Many patients with visible hair loss experience psychological and emotional distress, as a result of their cosmetic disfigurement, and frequently seek treatment. However, existing treatment methods, such as corticosteroids, topical irritants, sensitizing agents, immunosuppressants, and psoralen plus ultraviolet light A, may result in various adverse effects and often lack efficacy. Laser and light treatments offer a safe and effective alternative. This review aims to provide clinicians with a comprehensive summary of laser and light-based modalities used for the treatment of alopecia areata. Currently, the excimer laser is the most widely studied device and has shown positive results thus far. However, the development of future randomized controlled clinical trials will help determine the appropriate treatment protocols necessary, in order to achieve superior clinical outcomes.

Low-level laser treatment stimulates hair growth via upregulating Wnt10b and ß-catenin expression in C3H/HeJ mice.

This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and ß-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and ß-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/ß-catenin pathway.

Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion.

Photobiomodulation is reported to positively influence hair regrowth, wound healing, skin rejuvenation and psoriasis. Despite rapid translation of this science to commercial therapeutic solutions, significant gaps in our understanding of the underlying processes remain. The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and wound healing. Our investigation of 90 reports published between 1985 and 2015 revealed major inconsistencies in optical parameters selected for clinical applications. Moreover, poorly understood photoreceptors expressed in skin such as cytochrome c oxidase, cryptochromes, opsins etc. may trigger different molecular mechanisms. All this could explain the plethora of reported physiological effects of light. To derive parameters for optimal clinical efficacy of photobiomodulation, we recommend a more rational approach to underpin clinical studies, with research on molecular targets and pathways using well-defined biological model systems to enable translation of optical parameters from in vitro to in vivo. Furthermore, special attention needs to be paid when conducting studies for hair regrowth, aiming for double-blind, placebo-controlled randomized clinical trials as the gold standard for quantifying hair growth.

Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma Irradiation.

To determine whether the effects of low-dose-rate gamma (γ) irradiation are identifiable in the regeneration of murine hair follicles, we irradiated whole bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with 137Cs γ-rays. The mice were examined for effects on hair follicles, including number, morphology, and pigmentation in the second anagen phase. Effects of γ-radiation on melanocyte stem cells were also investigated by the indirect immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a decrease in hair follicle density and the induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs. There was a small, but not significant, change in the number of TRP2-positive melanocyte stem cells in the hair bulge region of the irradiated skin. These results suggest that low-dose rate γ-irradiation does not deplete melanocyte stem cells, but can damage stem cells and progenitors for both keratinocytes and melanocytes, thereby affecting the structure and pigmentation of regenerated hair follicles in the 2nd anagen phase.

Clinical Evaluation of Hair Removal Using an 810 nm Diode Laser With a Novel Scanning Device.

INTRODUCTION: Diode lasers are often considered as the gold standard preference for hair removal due to the deep penetration and ef- fective targeting of the hair follicle. A wide variety of diode lasers are available, which can differ in terms of their parameters (such as fluence, pulse duration, repetition rate, scanner, and cooling). OBJECTIVE: The objective of the study was to evaluate the safety and ef cacy of hair removal with an 810 nm novel scanning diode laser, up to six months after last treatment. METHODS: A scanning 810 nm diode laser was used for axillary hair removal of 14 female patients who received 3 treatments, 4-6 weeks apart. Follow-up on hair count was conducted 3 and 6 months after last treatment and compared to baseline hair count. RESULTS: No unexpected or signi cant adverse events were recorded. An average hair count reduction of 72.8% after 3 months and 67.6% 6 months after the last treatment is demonstrated. CONCLUSIONS: The examined 810 nm diode laser was proven to be safe and effective for hair removal. Results were sustained for 6 months after last treatment. Longer follow-up data are followed for further substantiation of the clinical effect. Scanning technology can provide for potentially faster and safer treatments. J Drugs Dermatol. 2016;15(11):1330-1333..

Prospective Evaluation of the Safety and Efficacy of a 1060-nm Large Spot Size, Vacuum-Assisted Hair Removal Diode Laser System in Asian/Pacific Fitzpatrick's Skin Types IV-V Patients.

Laser-based photoepilation of dark skin types demands a delicate combination of appropriate light wavelengths and spot size to achieve optimal epidermal-to-follicular energy absorption ratios. This prospective study assessed the axillary, arm, thigh, and back hair clearing ef cacy of the LightSheer In nity 1060 nm diode laser in 10 Fitzpatrick skin type IV-V patients. Each area was treated up to ve times, at 4-6-week intervals, after which immediate skin responses and adverse events were recorded. Hair count, color and coarseness were assessed before each treatment session, as well as 1, 3, and 6 months following the last session. Both patients and the treating physician rated the degree of improvement with time, and patients also ranked their satisfaction with the treatment outcome. Percent hair reduction from baseline gradually increased with treatment and peaked at 74.6%, 68.4%, and 65.7% for axillary, arm and thigh regions, respectively, 6 months following the last treatment session. Baseline hair growth patterns precluded effective selection of a representative area for hair counting. Patients satisfaction was consistently higher for axillary hair clearance rates, followed by thigh and arm responses. Throughout the follow-up period, the investigator rated 50-67% of the treated axillae as presenting "good" or "very good" hair clearance, and provided similar ratings for 67% of the treated thigh regions at both the 1 and 6 month follow-up sessions. Immediate responses to treatment were mild to moderate and short-lived and no incidents of brosis or scarring were reported. Taken together, the LightSheer In nity 1060 HS Handpiece provided for an ideal ef cacy-safety balance in treating dark-skinned patients, providing for long-term hair clearance with minimal downtime. J Drugs Dermatol. 2016;15(11):1427-1434.

Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling.

Regenerative cycling of hair follicles offers an unique opportunity to explore the role of circadian clock in physiological tissue regeneration. We focused on the role of circadian clock in actively proliferating transient amplifying cells, as opposed to quiescent stem cells. We identified two key sites of peripheral circadian clock activity specific to regenerating anagen hair follicles, namely epithelial matrix and mesenchymal dermal papilla. We showed that peripheral circadian clock in epithelial matrix cells generates prominent daily mitotic rhythm. As a consequence of this mitotic rhythmicity, hairs grow faster in the morning than in the evening. Because cells are the most susceptible to DNA damage during mitosis, this cycle leads to a remarkable time-of-day-dependent sensitivity of growing hair follicles to genotoxic stress. Same doses of γ-radiation caused dramatic hair loss in wild-type mice when administered in the morning, during mitotic peak, compared with the evening, when hair loss is minimal. This diurnal radioprotective effect becomes lost in circadian mutants, consistent with asynchronous mitoses in their hair follicles. Clock coordinates cell cycle progression with genotoxic stress responses by synchronizing Cdc2/Cyclin B-mediated G2/M checkpoint. Our results uncover diurnal mitotic gating as the essential protective mechanism in highly proliferative hair follicles and offer strategies for minimizing or maximizing cytotoxicity of radiation therapies.