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5-(3’,4’-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a colonic microbial metabolite derived from cacao. In the previous study, we found that cacao powder modulates DNA methylation and inhibits UVB-induced AP-1 activation and MMP-1 expression. To further investigate whether major metabolite of cacao, DHPV, has UV protective effect as cacao, we evaluated the regulatory role of DHPV on DNA methylation in keratinocytes after UVB irradiation. In this study, we found that UVB irradiation altered methylation profiles in HaCaT cells and these changes were ameliorated by DHPV.
Vitamin D and its receptor, VDR, together and independently, have been associated with DNA repair, though the mechanism by which they act is unclear. Upon ultraviolet irradiation through 3 mm pores in otherwise opaque filters to create focal spots of DNA damage, epidermal keratinocytes from both VDR-null mice and human keratinocytes depleted of VDR with siRNA exhibited slower removal of 6-4 photoproducts than normal control cells over 90 minutes. Co-staining with antibodies to XPC, the initial UV-induced DNA damage recognition sensor, revealed that XPC rapidly accumulated at DNA damage foci and gradually faded over 90 minutes as nucleotide excision repair proceeded in control human keratinocytes.
Hypochlorous acid (HOCl) is the active oxidizing principle released by standard swimming pool disinfectants used on a global scale, but the cutaneous consequences of human exposure to HOCl remain largely unknown, posing a major public health concern relevant to populations around the world. Here, for the first time, we have profiled the HOCl-induced cutaneous stress response in reconstructed human epidermis and SKH1 hairless mouse skin. In addition, we have investigated the molecular consequences of co-exposure to solar simulated ultraviolet (UV) radiation and HOCl, a procedure mimicking environmental exposure experienced by recreational swimmers.
Damage incurred by exposure to ultraviolet (UV) radiation stimulates multiple stress-responsive signaling pathways in the skin. There is mounting evidence that Toll-like receptor 4 (TLR4) mediates key inflammatory responses in skin cells, including keratinocytes. Pharmacological blockade of TLR4 using resatorvid (TAK-242) inhibits not only acute UV-induced signaling in vitro and in vivo, but blocks UV-induced skin carcinogenesis in mouse models. In order to better characterize the UV-induced responses linked to TLR4, we have recently utilized CRISPR/Cas9 techniques to delete TLR4 from the genome of human HaCaT keratinocyte cells in culture.
For many patients with Atopic Dermatitis (AD), first-line interventions fail to alleviate symptoms. UVA, PUVA, and UVB phototherapy have been utilized as a safe and cost-effective therapeutic options for a variety of inflammatory skin conditions including AD. We conducted a retrospective cohort study to examine the efficacy of phototherapy in the management of AD and to identify patient characteristics associated with treatment compliance and outcomes. We conducted a chart review of 145 AD patients treated at the Johns Hopkins Phototherapy Unit from 2009-2017 to characterize the demographics, comorbidities, concomitant medications, number of treatments, and UV irradiation dosing, as well as the post-treatment outcomes.
Non-melanoma skin cancers are more prevalent in people prone to repeated solar UVB expose. Though UVB is required for Vitamin-D3 production, yet it manifests tumorigenesis. 1,25(OH)2D3 protects from several autoimmune disorders and malignancies, however, due to its calcemic effects, therapeutic uses at pharmacological doses are limited. Previously, our lab reported that CYP11A1 produces 20(OH)D3 and is non-calcemic in mice and rats at pharmacological doses (60 μg/kg). Loss of PTCH gene function activates Sonic hedgehog (SHH) signaling, which drives BCC and perhaps SCC.
Several studies have indicated that UV-induced DNA photoproducts are removed from epidermal genomic DNA at a slower rate in geriatric skin than in young adult skin. Such a situation may result in a greater need for the translesion synthesis (TLS) pathway of DNA replication, in which specialized DNA polymerases are recruited to sites of DNA damage to replicate across DNA adducts in either an error-free or error-prone manner. Here we show that skin epidermis from geriatric individuals (>65 years of age) exhibits higher levels of mono-ubiquitinated PCNA, a biochemical marker of TLS pathway activation, than the skin of young adults (aged 21-29) following exposure to 700 J/m2 of UVB light.
In contrast to systemic agents, phototherapy is administered intermittently in the treatment of psoriasis. At least for systemic agents (such as biologics), there is a concern that after treatment interruption, restarting treatment may lead to a weaker therapeutic response compared to that of after initial treatment (e.g. due to formation of neutralizing antibodies). In this study, we analyzed the efficacy of narrowband UVB (311nm) phototherapy (NB-UVB) under daily life conditions in patients who had received one or more phototherapy cycles.
Several studies have shown that the ultraviolet (UVB/A) from terrestrial solar radiation are strongly implicated in the etiology of most skin cancers via the generation of DNA lesions and reactive oxygen species (ROS). Moreover, skin is also exposed to solar near infra-red (NIR) radiation which are responsible of oxidative stress generation. Therefore, it is important to protect the most sensitized skins (actinic keratosis or atopic dermatitis) in all circumstances/all day long. Thus, the aim of this project was to develop a SPF50+ sunfilter product in stick form to provide a nomad protection for sensitized skins.
Introduction: The prevalence of skin cancer has increased in last decade and is mostly due to chronic sunlight exposure. Therefore, it is important to prevent sun-induced skin damage by using photoprotection strategies. Objective: To assess the photoprotective efficacy of an innovative emulsion containing specific sunfilters combination to protect the skin against UV-induced lesions. Materials and Methods: An ex vivo human skin model was developed to mimic chronic exposure of solar-simulated radiation (CSSR).
Low-level light therapy uses non-thermal irradiance to modulate cellular functions via laser or light emitting diodes (LEDs). Red light has been clinically shown to stimulate wound healing, improve hair growth, relieve pain and inflammation as well as reduce skin wrinkles. Recent studies suggest that the biological responses to continuous wave light treatment may decrease or desensitize over time, and therefore continuous wave light treatment may not provide optimum efficacy. Thus, we sought to characterize the cellular effects of non-continuous "pulsed" wave (PW) vs continuous wave (CW) lights on induction of extracellular matrix gene expression in skin cells.
Risk factors for non-melanoma skin cancer (NMSC) include UVB exposure, genetic mutations, immunosuppression, and chronic inflammation. Activation of Toll-Like-Receptor 3 (TLR3), which recognizes dsRNA, leads to downstream activation of NF-κB and an upregulation of inflammatory cytokines. TLR3 protein expression is higher in moderately differentiated squamous cell carcinomas (SCCs) and infiltrative basal cell carcinomas (BCCs) compared to well-differentiated SCCs by immunohistochemistry (n > 6) suggesting TLR3 expression correlates with more aggressive NMSCs.
UVB irradiation causes specific DNA damage to keratinocytes that can lead to cancer-causing mutations if they are allowed to persist in proliferating cells. Previously, we demonstrated that the activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to UVB exposure. Briefly, geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response consisting of basal keratinocytes proliferating while still harboring unrepaired DNA damage.
Microvesicle particles (MVP) are small membrane bound particles released from cells that have been demonstrated to act as signal transporters between cells via their abilities to transport bioactive molecules. Previously our laboratory has reported that environmental injuries such as ultraviolet B radiation (UVB) and thermal burn injury can generate MVP release via a novel pathway involving the Platelet-activating factor (PAF) receptor in epithelial cell lines and human skin. Our current studies using pharmacologic and genetic approaches demonstrate that MVPs released from keratinocytes in vitro and mice in vivo in response to UVB (UVB-MVP) are dependent upon PAF receptor and acid sphingomyelinase (aSMase).
To address the need for clinically relevant cutaneous squamous cell carcinoma (cSCC) mouse models, we exposed SKH-1, FVB/N, Balb/c and C57BL/6 mice to solar simulated light (SSL), the environmental etiologic factor in human disease. Outbred SKH-1 mice are highly susceptible to SSL-induced tumor formation. However, an outbred strain limits the ability to evaluate MHC-restricted, antigen-specific T cell responses and perform studies with genetic mutants. The susceptibility of inbred strains FVB/N, Balb/c and C57BL/6 is unknown.
Although light from light emitting diodes (LEDs) has become a very common and important environmental factor in our daily lives, there is limited research regarding LED light’s possible effects on biological functions on the skin and the brain. Herein, we investigated the long-term effects of white (WL), blue (BL), and red (RL) LED light on cognitive learning and memory recall by using a zebrafish animal model. Zebrafish that were 36 days post fertilization (dpf) were used for light exposure. Light intensity was 7.2 J/cm2 for 120 mins per day for 30 days.
We previously reported that Etanercept blocks UVB-induced recruitment of neutrophils and macrophages into the dermis in mice, but paradoxically, accelerates loss of dermal collagen by increasing breakdown of mature collagen and decreasing synthesis of procollagen. To examine the role of macrophages in dermal collagen preservation during UVB exposure, we performed macrophage depletion in mice. Macrophages increase inflammation and tissue remodeling in many conditions by producing MMPs and TGFβ. MMPs can degrade collagen and TGFβ can induce procollagen synthesis.
Pain during conventional photodynamic therapy (C-PDT) is the main limiting adverse effect in its use in dermatology. During the course of C-PDT, most patients experience sensations of burning and tingling pain that vary in intensity. In some cases, patients have to stop the treatment because of unbearable pain. It is generally believed that C-PDT pain is mediated by free radicals generated by PpIX; ROS can either stimulate nerve endings directly or mediate pain through inflammatory by-products. Pain remains the top obstacle that prevents C-PDT application to all patients.
Phototherapy is an important treatment modality used in dermatology practice, and UVB radiation is often used for treating inflammatory skin disorders due to its immune suppressive effects. Currently, several UVB emitting radiation with different irradiance (W/cm2) are available. Clinical reports have shown different response profiles from devices emitting similar wavelengths at different irradiance. We previously showed that at equivalent fluence (mJ/cm2), high irradiance (HI) UVB imparted more immune suppressive effect as compared to its low irradiance (LI) counterpart.
Topical ALA-mediated PDT, ALA-PDT, is a novel therapeutic modality widely used to treat actinic keratosis, Bowen’s Disease, superficial skin SCC, and other cancerous and precancerous skin diseases. Several studies have proved that ALA-PDT can inhibit SCC growth and reduce tumor volume. Subsequent research suggested that ALA-PDT not only directly induced tumor cells apoptosis, but also improve tumor microenvironment through regulation of immune cells. However, the anti-tumor immune function of ALA-PDT is still need to be elucidated.