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Identification of Master Regulator Genes of UV Response and Their Implications for Skin Carcinogenesis
摘要： Solar UV radiation is a major environmental risk factor for skin cancer. Despite decades of robust and meritorious investigation, our understanding of the mechanisms underlying UV-induced skin carcinogenesis remain incomplete. We previously performed comprehensive transcriptomic profiling in human keratinocytes following exposure to different UV radiation conditions to generate UV-specific gene expression signatures. In this study, we utilized VIPER, a robust systems biology tool, on UV-specific skin cell gene signatures to identify master regulators (MRs) of UV-induced transcriptomic changes. We identified multiple prominent candidate UV MRs, including forkhead box M1 (FOXM1), thyroid hormone receptor interactor 13, and DNA isomerase II alpha, which play important roles in cell cycle regulation and genome stability. MR protein activity was either activated or suppressed by UV in normal keratinocytes. Intriguingly, many of the UV-suppressed MRs were activated in human skin squamous cell carcinomas (SCCs), highlighting their importance in skin cancer development. We further demonstrated that selective inhibition of FOXM1, whose activity was elevated in SCC cells, was detrimental to SCC cell survival. Taken together, our study uncovered novel UV master regulators that can be explored as new therapeutic targets for future skin cancer treatment.
关键词： Keratinocyte,UV signature,skin cancer,master regulator
更新于2025-09-23 15:21:01
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585a??nm light-emitting diodes inhibit melanogenesis through upregulating H19/miR-675 axis in LEDs-irradiated keratinocytes by paracrine effect
摘要： 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. Objective: To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. Methods: NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. Results: Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. Conclusions: This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.
关键词： exosomes,H19/miR-675,melanogenesis,Light-emitting diode (LEDs),keratinocyte
更新于2025-09-19 17:13:59
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893 Low-level laser therapy for the treatment of male and female-pattern hair loss: A review of literature
摘要： Gain-of-function mutations in TRPV3 can result in Olmsted syndrome, characterized by palmoplantar and periorificial keratoderma, itch, and hair loss. The mechanisms underlying these phenotypes are unclear. Here, we engineered the first knock-in mouse model of Trpv3 by introducing a point mutation analogous to that (G568V) found in Olmsted syndrome patients. Homozygous Trpv3 knock-in (Trpv3G568V/G568V) mice exhibit sparse hair within two weeks after birth. Histologically, hair shafts in Trpv3G568V/G568V mice are twisted in the infundibulum, unable to penetrate the skin. Immunofluorescence demonstrated impaired inner root sheath cell differentiation as trichohyalin and KRT71 were diminished in mutant hair follicles. These abnormalities are consistent with the expression pattern of Trpv3, which is predominantly in the proximal region of inner root sheath as demonstrated by in situ hybridization and in a Trpv3 reporter mouse model we engineered. The hair loss phenotype is progressive, and is associated with the lack of typical telogen. After three hair cycles, Trpv3G568V/G568V mice became completely bald. Aberrantly increased proliferation and ectopic expression of epidermal markers, including KRT1 and loricrin, are characteristic of degenerating hair follicles in Trpv3G568V/G568V mice, which gradually lose stem cells, as marked by CD34, NFATc1 and KRT15, and the typical structure of a hair follicle. Findings from this study suggest that Trpv3 is an important regulator of inner root sheath keratinocyte differentiation, whereas hair loss associated with gain-of-function mutations in Trpv3 is caused by impaired proliferation and differentiation programs, leading to the exhaustion of follicular keratinocyte stem cells, and permanent disruption of the hair follicles.
关键词： keratinocyte differentiation,TRPV3,Olmsted syndrome,stem cells,hair loss
更新于2025-09-16 10:30:52
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ToF-SIMS and TIRF microscopy investigation on the effects of HEMA copolymer surface chemistry on spatial localization, surface intensity, and release of fluorescently labeled keratinocyte growth factor
摘要： The need for direct biomaterial-based delivery of growth factors to wound surfaces to aid in wound healing emphasizes the importance of interfacial interactions between the biomaterial and the wound surface. These interactions include the spatial localization of growth factor, the surface intensity of growth factor in contact with the wound, and the release profile of growth factor to the wound surface. The authors report the use of time-of-flight secondary ion mass spectrometry to determine the relationship between biomaterial surface chemistry and the spatial localization of growth factor. They have implemented a novel application of total internal reflectance fluorescence (TIRF) microscopy to measure the surface intensity and release of growth factor in contact with a glass substrate that has been used to model a wound surface. Detailed information regarding TIRF experiments has been included to aid in future studies regarding the biomaterial delivery to interfaces. The authors have evaluated the effects of (hydroxyethyl)methacrylate (HEMA) homopolymer, 5.89% methyl methacrylate/HEMA, and 5.89% methacrylic acid/HEMA surface chemistry on the spatial localization of AlexaFluor 488-labeled keratinocyte growth factor (AF488-KGF), AF488-KGF surface intensity at the copolymer surface, and release to a glass substrate. KGF is known to promote re-epithelialization in wound healing. The results show that the two copolymers allow for increased surface coverage, surface intensity, and release of AF488-KGF in comparison to the homopolymer. It is likely that differences in these three aspects could have a profound effect on the wound healing response.
关键词： ToF-SIMS,TIRF microscopy,HEMA copolymer,keratinocyte growth factor,wound healing
更新于2025-09-16 10:30:52
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Performance evaluation of solar absorption-compression cascade refrigeration system with an integrated air-cooled compression cycle
摘要： Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disorder affecting apocrine gland-bearing areas of the body. Although the precise pathogenesis of HS is unclear, genetic mutation may one important factor. Recently, loss-of-function mutations of nicastrin (NCSTN), a subunit of γ-secretase, are detected in some familial HS patients. In 2016, we reported that the expression of both AKT and its activated form phosphorylated-AKT (p-AKT) is up-regulated in NCSTN-silencing HaCaT cells. But how defective NCSTN affected AKT is still unknown. MicroRNAs (miRNAs) are small noncoding RNAs functioning as biological regulators in some skin diseases. In previous study, we found that miR-100-5p was down-regulated in both familial HS and keratinocyte specific-NCSTN-knockout (NcstnΔKC) mice. As AKT-related pathway is one target of miR-100-5p, whether decreased miR-100-5p expression could affect skin cells through this pathway in familial HS with NCSTN mutation remains to be proved. Here, we investigated the effect of miR-100-5p on AKT to influence skin keratinocyte proliferation in the presence of NCSTN mutation.
关键词： miR-100-5p,AKT,keratinocyte proliferation,NCSTN mutation,Hidradenitis suppurativa
更新于2025-09-11 14:15:04
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Controllable Interlayer Charge and Energy Transfer in Perovskite Quantum Dots/ Transition Metal Dichalcogenide Heterostructures
摘要： Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) acts through its receptor fibroblast growth factor inducible 14 (Fn14), and participates in skin inflammation. Both TWEAK and Fn14 are highly expressed in skin lesions of patients with atopic dermatitis. The purpose of this study was to further explore the effect of Fn14 inhibition on experimental atopic dermatitis. Experimental atopic dermatitis was induced in the wild-type and Fn14 knock-out BALB/c mice. The effect of TWEAK/Fn14 interaction on keratinocytes was studied in an in-vitro model of atopic dermatitis. Fn14 deficiency ameliorates skin lesions in the mice model, accompanied by less infiltration of inflammatory cells and lower local levels of proinflammatory cytokines, including TWEAK, TNF-α and interleukin (IL)-17. Fn14 deficiency also attenuates the up-regulation of TNFR1 in skin lesions of atopic dermatitis. Moreover, topical TWEAK exacerbates skin lesion in the wild-type but not in the Fn14 knock-out mice. In vitro, TWEAK enhances the expressions of IL-17, IL-18 and IFN-γ in keratinocytes under atopic dermatitis-like inflammation. These results suggest that Fn14 deficiency protects mice from experimental atopic dermatitis, involving the attenuation of inflammatory responses and keratinocyte apoptosis. In the context of atopic dermatitis-like inflammation, TWEAK modulates keratinocytes via a TNFR1-mediated pathway.
关键词： keratinocyte,tumor necrosis factor receptor (TNFR),tumor necrosis factor-like weak inducer of apoptosis (TWEAK),atopic dermatitis,fibroblast growth factor-inducible 14 (Fn14)
更新于2025-09-11 14:15:04
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Daylight photodynamic therapy for prevention of new actinic keratosis and keratinocyte carcinomas in organ transplants. A cryotherapy‐controlled randomized clinical trial.
摘要： Background: Organ transplant recipients (OTR) have a higher risk of actinic keratosis (AK) and keratinocyte carcinomas (KC). There are no clinical trials assessing the effectiveness of daylight photodynamic therapy (DPDT) to prevent new AK and KC in OTR. Objectives: To determine whether repeated treatments of field cancerization with DPDT are effective in preventing new AK and KC in OTR. Methods: A randomized, intra-subject controlled, evaluator-blind, split-face and/or scalp trial, from April 2016 to October 2018. Participants were OTR older than 18 years, 1 year post-transplant, with at least 5 AK on each hemi-face/hemi-scalp. One side received 6 field-treatments with DPDT: two sessions 15 days apart at baseline, two at 3 months, and two at 9 months after baseline. Control side received lesion-directed treatment with cryotherapy (double freeze-thaw) at baseline, 3 and 9 months. Total number of lesions (AK and KC) at 21 months, number of new AK and KC at 3, 9, 15 and 21 months and treatment preferences were analysed. Results: Of 24 men included, 23 were analysed at 3 months; and 21, at 9, 15 and 21 months. Mean (SD) age was 69.8 years (9.2). Total number of lesions at 21 months were 4.7 (4.3) for DPDT and 5.8 (5.0) for control side; P= 0.09. DPDT showed significantly lower means [SD] of new lesions compared to control side at 3 months (4.2 [3.4] vs 6.8 [4.8]; P< 0.001), 9 months (3.0 [3.3] vs 4.3 [3.4]; P= 0.04) and 15 months (3.0 [4.6] vs 4.8 [5.0]; P= 0.02), and nonsignificant at 21 months (3.7 [3.5] vs 5.0 [4.5]; P= 0.06). Most participants preferred DPDT. Conclusion: DPDT showed potential effectiveness in preventing new AK and KC in OTR by consecutive treatments of field cancerization. The preference for DPDT could facilitate adherence to the long-term treatment necessary in these patients.
关键词： methyl aminolevulinate,daylight photodynamic therapy,keratinocyte carcinomas,actinic keratosis,organ transplant recipients
更新于2025-09-11 14:15:04