MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling.

Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis.

Analysis of debrided and non-debrided invasive squamous cell carcinoma skin lesions by in vivo reflectance confocal microscopy before and after therapy.

Hyperkeratosis hinders the application of reflectance confocal microscopy (RCM) to image squamous cell carcinoma (SCC). Not all lesions with SCC show hyperkeratosis, and these lesions can be directly imaged. However, lesions with hyperkeratosis can be treated by debriding the hyperkeratotic surface for further imaging.

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling.

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts.

An investigation of crosstalk between Wnt/β-catenin and transforming growth factor-β signaling in androgenetic alopecia.

Background: Wnt and transforming growth factor-β (TGF-β) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-β signaling is altered in patients with AGA and whether there exists a crosstalk between them in pathogenetic process of AGA remain unclear.

Objectives: To investigate the expression of Wnt and TGF-β signaling and the crosstalk between these 2 signaling pathways in AGA.

Real-time in vivo confocal laser scanning microscopy of melanin-containing cells: A promising diagnostic intervention.

The use of noninvasive imaging techniques to evaluate different types of skin lesions is increasing popular. In vivo confocal laser scanning microscopy (CLSM) is a new method for high resolution non-invasive imaging of intact skin in situ and in vivo. Although many studies have investigated melanin-containing cells in lesions by in vivo CLSM, few studies have systematically characterized melanin-containing cells based on their morphology, size, arrangement, density, borders, and brightness.

HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway.

In the present study, we examined the mechanisms of oxaliplatin-induced drug resistance in human colorectal cancer cell lines HT29 and HCT116. Our results demonstrate a significant autophagy expression in CRC cells after an oxaliplatin treatment. Administration of oxaliplatin to human CRC cells significantly enhanced the expression of HMGB1, which regulated the autophagy response and negatively regulate the cell apoptosis.

Astragaloside IV controls collagen reduction in photoaging skin by improving transforming growth factor-β/Smad signaling suppression and inhibiting matrix metalloproteinase-1.

Exposure to ultraviolet (UV) light reduces levels of type I collagen in the dermis and results in human skin damage and premature skin aging (photoaging). This leads to a wrinkled appearance through the inhibition of transforming growth factor‑β (TGF‑β)/Smad signaling. UV irradiation increases type I collagen degradation through upregulating matrix metalloproteinase (MMP) expression.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SIN1 association mediates ultraviolet B (UVB)-induced Akt Ser-473 phosphorylation and skin cell survival.

Background: The exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation.

Results: We found that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and mammalian target of rapamycin (mTOR) complex 2 (mTORC2) were both required for UVB-induced Akt Ser-473 phosphorylation in keratinocytes.

Deguelin induces both apoptosis and autophagy in cultured head and neck squamous cell carcinoma cells.

Head and neck squamous cell carcinoma (HNSCC) represents more than 5% of all cancers diagnosed annually in United States and around the world. Despite advances in the management of patients with this disease, the survival has not been significantly improved, and the search for potential alternative therapies is encouraging. Here we demonstrate that deguelin administration causes a significant HNSCC cell death.

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway.

UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H(2)O(2)) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC).

Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells.

Recent published studies suggest that increasing levels of ceramides enhance the chemo-sensitivity of curcumin. Using in vitro approaches, we analyzed the impact of sphingosine kinase-1 (SphK-1) inhibition on ceramide production, and evaluated SphK1 inhibitor II (SKI-II) as a potential curcumin chemo-sensitizer in ovarian cancer cells. We found that SphK1 is overexpressed in ovarian cancer patients' tumor tissues and in cultured ovarian cancer cell lines.

Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of skin cancer prevention?

We demonstrate here that a relative low dose of perifosine significantly enhanced UVB-induced apoptosis in skin cells (keratinocytes and fibroblasts), associated with a significant increase of reactive oxygen species (ROS) and ceramide production as well as multiple perturbations of diverse cell signaling pathways, shifting to a significant pro-apoptosis outcomes. Perifosine inhibited UVB-induced pro-survival Akt/mammalian target of rapamycin (mTOR) and ERK activation, while facilitating pro-apoptotic AMP-activated protein kinas (AMPK), c-Jun-NH(2)-kinase (JNK), and p53 activation; these signaling changes together promoted a striking increase in skin cell apoptosis and a significantly reduced amount of DNA damages. Our results suggest that perifosine may represent a novel skin cancer prevention strategy.

Increasing ceramides sensitizes genistein-induced melanoma cell apoptosis and growth inhibition.

The aim of the current study is to investigate the effect of ceramides on genistein-induced anti-melanoma effects in vitro. We found that exogenously added cell-permeable short-chain ceramides (C6) dramatically enhanced genistein-induced growth inhibition and apoptosis in cultured melanoma cells. Genistein treatment only induced a moderate intracellular ceramides accumulation in B16 melanoma cells.

Protective effect of astragaloside IV against matrix metalloproteinase-1 expression in ultraviolet-irradiated human dermal fibroblasts.

Ultraviolet (UV) irradiation induces skin photoaging associated with up-regulated matrix metalloproteinase (MMP) expression. Inhibition of MMP expression is suggested to alleviate photoaging induced by UV irradiation. Astragaloside IV (As-IV), one of the main active ingredients of Astragalus membranaceus (Fisch) Bge, has been reported to have various biological activities.

Regiodivergent annulation of alkynyl indoles to construct spiro-pseudoindoxyl and tetrahydro-β-carbolines.

Regiodivergent annulations of 3-phenoxy alkynyl indoles have been developed and tuned by protective groups through gold catalysis. With electron-donating protective groups, the substrate followed a C3-selective annulation and gave structurally interesting tetrahydro-β-carboline derivatives possessing potential bioactivity. Using electron-withdrawing protective groups, the substrate underwent a C2-selective annulation and afforded the structurally useful spiro-pseudoindoxyl found in natural indole alkaloids.

Increased MAPK and NF-κB expression of Langerhans cells is dependent on TLR2 and TLR4, and increased IRF-3 expression is partially dependent on TLR4 following UV exposure.

Toll-like receptors (TLRs) and epidermal Langerhans cells (LCs) play a crucial role in innate and adaptive immunity. To date, the pattern of TLR expression has not been fully analyzed. The effects of ultraviolet (UV) light on TLR expression and the downstream signaling cascades of human LC have not been examined.

IPL irradiation rejuvenates skin collagen via the bidirectional regulation of MMP-1 and TGF-β1 mediated by MAPKs in fibroblasts.

The efficacy of intense pulsed light (IPL) in remodeling the extracellular matrix of aged skin had been proven by an increasing number of clinical trials. However, because of the lack of research about the underlying molecular and signaling mechanisms, its efficiency had not been accepted universally. A potential mechanism of IPL rejuvenation effects is due to its different effects on diverse cytokines, the impact of IPL on them may determine the phenotype and prognosis of the aged skin.

Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes.

Solar ultraviolet (UV) irradiation is one of the most significant extrinsic factors contributing to skin photoaging. One major characteristic of photoaging induced by UV is water loss of the skin. Water movement across the plasma membrane can occur via two pathways: by diffusion through the lipid bilayer and by membrane-inserted water channels (aquaporins).

In vivo confocal laser scanning microscopy of hypopigmented macules: a preliminary comparison of confocal images in vitiligo, nevus depigmentosus and postinflammatory hypopigmentation.

The use of confocal laser scanning microscopy (CLSM) may be an eligible alternative for confirmation of the diagnosis of hypopigmented macules. Our purpose was to evaluate CLSM features for non-invasive imaging of vitiligo, nevus depigmentosus and postinflammatory hypopigmentation in vivo. A total of 68 patients with a clinical diagnosis of the aforementioned diseases were included in this study.

[Construction and immunogenicity evaluation of chimerical DNA vaccine of human papillomavirus type 11].

Objective: To construct chimerical DNA vaccine plasmid of human papillomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity.

Methods: Molecular cloning techniques were used to construct recombinant plasmid pcDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection.

In vitro preparation and characterization of the human CD3 epsilon epsilon homodimer and CD3 epsilon gamma and CD3 epsilon delta heterodimers.

The CD3 molecule is a critical component of both humoral and cellular immune responses, and yet while the structure and molecular assembly of other key mediators such as CD4 and CD8 have been reported, individual CD3 subunits have not been well characterized. Our understanding of the manner in which they interact remains limited, and the question of how many subunits are required for a functional CD3 molecular complex is yet to be addressed. It has been suggested that CD3 epsilon pairs with CD3 gamma or with CD3 delta, forming CD3 epsilon gamma and CD3 epsilon delta heterodimers that associate with alpha/beta T cell receptors (TCRs) and CD3 zeta 2 dimers.

MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells.

Aquaporins (AQPs) are a family of 13 small ( approximately 30 kDa/monomer), hydrophobic, integral membrane proteins. AQPs are expressed in various epithelial and endothelial cells involved in fluid transport. Here, we demonstrated for the first time that AQP1 is expressed in cultured human retinal pigment epithelial (RPE) cells (ARPE-19 cell line).

Trans-Zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts.

Ultraviolet (UV) irradiation induces the expression of matrix metalloproteinases (MMPs), disturbing the metabolism of extracellular matrix (ECM), and causes the characteristic changes of photoaging in skin. Inhibition of induction of MMPs is suggested to alleviate photoaging induced by UV irradiation. Zeatin, purified from Zea mays, is a member of the cytokinin group of plant growth factors, the activity of which is attributed to its more stable trans form.