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Premature skin aging evidenced by a rough skin texture and wrinkles is known to be driven by external factors, mainly by sunlight and in particular UV radiation including UVB (280-320 nm) and UVA (320-400 nm). However, recent advance highlighted the role of visible light and especially the blue light part (400-500nm) in skin aging. As the blue light is the highest energetic wavelength of the visible light, it penetrates deeper into the skin and damages the skin by inducing oxidative stress and production of proteases which degrade the extracellular matrix of the dermis.
Imatinib mesylate is a tyrosine kinase inhibitor (TKI) that regulates cell growth, thereby inhibiting cancer cell proliferation. It has been used to treat various neoplasms such as chronic myeloid leukemia (CML). The most common side effect in skin is hypopigmentation. However, hyperpigmentation has also been rarely reported. A 48-year-old woman diagnosed as chronic myeloid leukemia presented with bluish to grayish macules and patches on face, shoulder, and buttock. She had got a treatment of CML with imatinib mesylate for 9 years.
Skin is the largest organ of the human body and possesses a unique microbiome which is known to play a significant role in skin barrier function. Throughout life, both cutaneous cells and skin microorganisms are exposed to solar ultraviolet radiation (UVR). Although the effects of UVR on keratinocytes have been investigated in many studies, little is known about the effects of UVR on the skin microbiome, and the potential effect of the altered skin microbiome on skin cells. The aims of this study were to test the hypothesis that irradiation of fourspecific skin commensal bacteria (Staphylococcus epidermidis, Staphylococcus hominis,Staphylococcus capitis and Cutibacterium acnes) change their interactions with normal human epidermal keratinocytes (NHEKs).
Visible light between 400 to 500nm was identified as an additional contributor to cutaneous photo-aging. Clinical studies showing clear effects of blue light on photo-aging are, however, still scarce. While there is evidence for increased skin pigmentation, the underlying mechanisms of photo-aging in vivo are still not clear. Furthermore, there is still a lack of means to significantly protect from blue light induced signs of photo-aging in vivo. We conducted a randomized, double-blind and placebo controlled clinical study on 33 female Caucasian and Asian volunteers with skin phototype III and IV.
Wrinkling has been attributed to the cumulative effects of acute Ultraviolet Radiation (UVR) exposure on the dermis. Previous studies have shown that the collagenase MMP-1 is secreted by dermal fibroblasts and degrades collagen immediately after UV exposure. However, skin ages gradually, and not intermittently after sun exposure. In this study we sought to examine the mechanism underpinning the gradual appearance of wrinkles, and to determine whether this is a result of intrinsic changes in the biology of the dermis.
It is well known that solar radiation accelerates photoaging. To protect the skin especially from the early phase of ultraviolet (UV)-induced damage, we have focused on ultraweak photon emission (UPE), which is also called biophoton, to evaluate the photodamage in a quick and simple manner. Our previous research revealed that the amount of UV-induced long-lasting UPE predominantly from lipid peroxidation would be a valuable indicator to assess cutaneous photodamage even at a suberythemal dose, though it was only applied to acute UV damage.
To protect the human body against environmental stress, such as UVB, a multifunctional enzymatic and antioxidant defense system is expressed in the skin. A key regulator of this pathway is the transcription factor Nrf2. Thus, we have speculated that target activation of this pathway may provide therapeutic options against oxidative stress-related disorders. A novel pharmacological Nrf2 activator (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) was synthesis and evaluated on several in vitro skin models.
Poliosis circumscripta is the localized depigmentation of hair in a group of hair follicles, and is associated with several genetic or acquired medical conditions, trauma or stress. Rare cases of transient alopecia followed by poliosis have been previously reported, although the exact etiology remains unclear. Additionally, reported cases of the manifestation of trigeminal autonomic cephalalgia with poliosis in a matching dermatomal area implicate a possible pathogenic involvement of sensory nerves in the development of poliosis.
Ultraviolet B radiation (UVB) causes direct DNA damage by inducing the formation of cyclobutane pyrimidine dimers (CPDs). These photolesions lead to diverse cellular effects, but their involvement in the regulation of mitochondrial function is unexplored. Here, we characterized the impact of UVB-induced DNA damage on the mitochondria using our established model system, in which human keratinocytes are transfected with methylpseudouridine-modified mRNA encoding CPD-photolyase. Our results demonstrate that CPD removal by photoactivated CPD-photolyase in HaCaT cells reduces PARP activation and bulk autophagy after UVB exposure.
GPNMB is a highly glycosylated type I transmembrane protein, which is known to be expressed in many cell types with multiple functions including cell adhesion, stress protection, and stem cell maintenance. In the skin, melanocyte GPNMB is suggested to mediate pigmentation through melanosome formation, but details of its expression and function in epidermal keratinocytes are not well characterized. We previously confirmed the predominant expression of GPNMB at a lower calcium condition in cultured normal human epidermal keratinocytes (NHEK).
Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, searches for factors regulating this pathway are strongly desired. Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. In vitro assessment indicated that melatonin arrests cell viability in highly pigmented MNT-1 melanoma cells, amelanotic Sk-Mel-28 melanoma as well as normal human melanocytes.
Exposure of skin to UV irradiation causes oxidative stress, DNA damage and immune suppression associated with increased incidence of skin cancer. Therefore, protection against UV-induced damages may have a positive skin clinical impact. The efficacy of ectoine and mannitol (0.01% and 0.05% respectively) were tested on three parameters. First, using UV irradiated keratinocytes, quantification of intracellular reduced glutathione (GSH), an intracellular tripeptide that neutralises reactive oxygen species, was performed following full solar spectrum irradiation (200 J/cm2, 750 W/m2).
Macrophages, an essential component of immune system, play a critical role not only in inflammation but also in wound healing. There are two subtypes of macrophages, M1 macrophages which encourage inflammation and M2 macrophages which decrease inflammation and encourage tissue repair. Glycoprotein non-metastatic melanoma protein b (GPNMB) is a glycosylated transmembrane protein which is highly expressed in multiple cells, including macrophages. GPNMB is also reported to act as a negative regulator of macrophage inflammatory responses in Alzheimer diseases and Parkinson diseases.
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a Type I transmembrane glycoprotein which has important roles in cancer and amyotrophic lateral sclerosis (ALS). In skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in pigmentation. Previously, we showed that GPNMB was highly expressed in keratinocytes from healthy donors, but decreased in vitiligo lesions. The function of keratinocyte-derived GPNMB is yet to be known. Therefore, we first confirmed GPNMB expression in cultured normal human epidermal keratinocytes, and oxidative stress (H2O2) down-regulated both membrane GPNMB and soluble GPNMB (sGPNMB) expression.
Age related hair greying is due to exhaustion of the melanocyte stem cells (McSC) pool. This phenomenon can be accelerated by genetic and/or environmental factors inducing stress and the premature death and/or early differentiation of McSCs in the bulge. Since Dicer is downregulated by stress, we inactivated this gene in the melanocyte lineage to investigate its contribution to McSC survival. The absence of Dicer in McSC at birth led to a progressive hair greying due to mis-localization and migration of melanocytes, and exhaustion of the McSC pool.
Photoaging is a common skin condition characterized by wrinkles, dyspigmentation, and sagging skin. It is caused by chronic exposure to UVA (320-400nm) and UVB (280-320nm). UVA is more abundant in sunlight than UVB and penetrates deeper into the dermis and considered to be the major culprit of photoaging. Previous research done on lighter skin types established upregulated collagen breakdown by matrix metalloproteinases (MMP) with concurrent reduction in procollagen synthesis as surrogate markers for wrinkled skin.
Xeroderma Pigmentosum C (XPC) is a rare genodermatosis which manifests clinically as pronounced photosensitivity, abnormal pigmentation and numerous skin cancers. It is caused by mutations in XPC gene that initiates global-genome nucleotide excision repair (GG-NER), a repair system responsible for bulky DNA adducts removal. Interestingly, development of internal and skin cancers in non-photo-exposed areas in parallel to an increase in oxidative DNA damages are observed upon these mutations. Therefore, we propose in our work to study XPC role in the modulation of BER, a major route for repairing oxidative DNA damage, at transcriptomic and proteomic levels along with repair activity using normal and XPC-mutated primary fibroblasts.
Claudin-1 is a major barrier forming protein of tight junctions in the epidermal granular layer. The function of claudin-1 in other epidermal layers is poorly understood. However, claudin-1 is reduced in conditions induced by ultraviolet radiation (UVR) including polymorphic light eruption and photoageing.. The aim of this study was to investigate the mechanisms whereby UV could induce loss of claudin-1 from keratinocytes. Using western blotting for claudin-1 of primary human keratinocytes exposed to solar-simulated radiation (SSR) at 10 or 20J/cm2, we showed that claudin-1 abundance was reduced by 50% at 72h post irradiation.
Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining auto-immune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. Recent data point to an association between vascular involvement in SSc and skin pigmentation. CCN3 (NOV), a member of the CCN family of extra-cellular matrix proteins, is a pro-angiogenic factor and contributes to epidermal homeostasis. We performed skin biopsies on 26 SSc patients, both in fibrotic and non-fibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture.
Pityriasis versicolor (PV) is a common chronic superficial fungal infection of the skin caused by an unusual increased proliferation of Malassezia species in the stratum corneum layer of skin. Malassezia is a yeast that is part of the skin’s habitual flora and it acquires a pathogenic potential when assuming the mycelial form under the influence of trigger factors including, humidity, immunosuppression, and hyperhidrosis. Systemic therapies are recommended for severe or recalcitrant cases, but they could come with important side effects and drug interactions.