Hsin-Su Yu

Kaohsiung Medical University, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (118)384.04 Total impact

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    ABSTRACT: Previous epidemiological studies showed that chronic arsenic exposure is related to increased cardiovascular disease incidence. The detailed biochemical mechanisms by which arsenic exerts its effects remain unknown. Vascular disease progression is characterized by smooth muscle cell (SMC) phenotypic switching, vessel wall reorganization, and platelet-derived growth factor (PDGF) production. The objective of this study was to examine early biochemical and structural changes in the aortas of ICR mice systemically exposed to arsenic. Animals were fed sodium arsenite (20 mg/kg) via gavage 5 days/week or Milli-Q water only (control) for 8 weeks. Aortic proteins were subjected to two-dimensional (2-D) differential gel electrophoresis and proteomic studies. Two 2-D gel protein spots were identified as the same protein, smooth muscle (SM)22α, using proteomics. SM22α and Rho kinase 2 gene and protein expression were significantly decreased in the aortic tissue of arsenic-exposed mice compared with that of control mice. No atherosclerotic lesion formation or tissue injury was detected in the aortic wall of either the arsenic-fed or the control group. However, the percent (%) SMC area of the aortic wall was significantly decreased in arsenic-fed mice compared with that in control mice. Additionally, the expression levels of PDGF-BB and early growth response-1 (Egr-1) were significantly higher in the arsenic group than that in the control group. These findings reveal biochemical alterations of SM22α, PDGF, and Egr-1 in conjunction with decreased SMC area in the aortic wall of arsenic-fed mice. Arsenic may initiate aortic SMC alterations that subsequently lead to vascular dysfunction.
    Heart and Vessels 07/2015; DOI:10.1007/s00380-015-0708-7 · 2.11 Impact Factor
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    ABSTRACT: Syndecan-1 is a member of the transmembrane heparan sulfate proteoglycan family, whose membrane-bound and soluble forms are involved in wound healing, inflammation and vascular biology. Because these physiological events are implicated in the pathogenesis of systemic sclerosis (SSc), we investigated the clinical association of serum syndecan-1 levels in this disease. Serum syndecan-1 levels were significantly higher in SSc patients, both in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), than in healthy individuals, while comparable between dcSSc and lcSSc groups. In late stage dcSSc patients (disease duration of >6 years), but not non-late stage dcSSc patients (≤6 years), serum syndecan-1 levels were significantly higher than in normal controls. More importantly, SSc patients with elevated serum syndecan-1 levels had higher prevalence of telangiectasia, elevated right ventricular systolic pressure and decreased diffuse capacity of the lung for carbon monoxide than those with normal levels. Therefore, soluble syndecan-1 may be related to the development of proliferative vasculopathy in SSc patients. © 2015 Japanese Dermatological Association.
    The Journal of Dermatology 06/2015; DOI:10.1111/1346-8138.12986 · 2.35 Impact Factor
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    ABSTRACT: IL-9 and its receptor play important roles in the pathogenesis of asthma. Its role in atopic dermatitis (AD) was examined in just a few studies, including nucleotide polymorphisms, increased transcriptional levels of IL-9 and IL-9R in diseased skin, and an association of blood IL-9 levels with clinical severity. Little was known about the pathophysiological regulation of IL-9/IL-9R in AD skin. We asked whether IL-9R was expressed in epidermal keratinocytes; if so, what the functional outcome, cytokine production, and signaling pathway of IL-9/IL-9R in keratinocytes are. We measured and compared the expression of IL-9R in skin from AD patients and controls by immunofluorescence. We also performed in vitro studies on the IL-9-treated primary keratinocytes, including flow cytometry for IL-9R expressions, Western blotting for mTOR, S6K, ERK, p38, and STAT3 activations, ELISA for cytokine levels, and immunofluorescence for STIM1. We found that IL-9R was indeed expressed in keratinocytes but not in fibroblasts. Its expression in keratinocytes was enhanced by IL-4 but not by TGF-beta1. IL-9 induced a moderate production of IL-8 but not CXCL16, CCL22, TSLP, nor IL-33. IL-9 induced formation of STIM1-puncta. IL-9 induced ERK phosphorylation both dose- and time-dependently, but not mTOR, S6K, p38, or STAT3. Pretreatment with U0126 (ERK inhibitor) but not rapamycin (mTOR inhibitor) abrogated the IL-9-mediated IL-8 production. Blockage of STIM1 with BTP2 or SKF96265 abrogated ERK phosphorylation and IL-8 production induced by IL-9. This study represents the first to show the regulation of the IL-9-STIM1-ERK-IL-8 axis in keratinocyte, and how the axis might play an important role in the pathophysiology of AD. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
    Journal of dermatological science 03/2015; 78(3). DOI:10.1016/j.jdermsci.2015.03.004 · 3.34 Impact Factor
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    ABSTRACT: Light at visible spectrum has been associated with anti-inflammatory and anti-aging effects. Ultraviolet A (UVA) radiation is the most important environmental factor associated with exogenous aging via induction of reactive oxygen species (ROS). In this study, we focused on elucidating the molecular mechanisms involved in biological effects associated with 590nm light delivered from light emitting diode (LED). UVA-induced metalloproteinase-1 (MMP-1) expression in dermal fibroblast was used as a model system for investigation. Pretreating cultured human fibroblasts with 590nm light attenuated UVA-induced ROS, phosphorylated Jun N-terminal kinases, and MMP-1 expressions in a sequential manner. Pretreatment with potent antioxidant N-acetylcysteine produced similar effect, suggesting enhanced antioxidant capacity induced by 590nm photomodulation. Further experiments demonstrated that 590nm photomodulation attenuated UVA-induced ROS and MMP-1 expressions via mitochondrial retrograde signaling that augments the antioxidant enzyme expression in a peroxisome proliferators-activated receptor γ coactivator-1α-dependent manner. Our results provided possible mechanistic insights explaining the effect of visible light on treating clinical conditions associated with ROS-mediated dysfunctions. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Journal of dermatological science 03/2015; 78(2). DOI:10.1016/j.jdermsci.2015.02.018 · 3.34 Impact Factor
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    ABSTRACT: Arsenic remains an important environmental hazard that causes several human cancers. Arsenic-induced Bowen’s disease (As-BD), a skin carcinoma in situ, is the most common arsenical cancer. While great strides have been made in our understanding of arsenic carcinogenesis, how host immunity contributes to this process remains unknown. Patients with As-BD have an impaired contact hypersensitivity response. Although impaired T cell activation has been well-documented in arsenical cancers, how dendritic cell (DC), the key cell regulating innate immunity, regulates the immune response in arsenical cancers remains unclear. Using myeloid derived DC (MDDC) from patients with As-BD and normal controls as well as bone marrow derived DC (BMDC) from mice fed with or without arsenic, we measured the migration of DC. As-BD patients showed an impaired CCL21-mediated MDDC migration in vitro. Arsenic-fed mice had defective DC migration toward popliteal lymph nodes when injected with allogenic BMDCs via foot pad. Using skin from As-BD and normal controls, we found an increased expression of STAT3, a transcriptional factor contributing to impaired DC activation. Arsenic induced STAT3 activation and the production of VEGF in keratinocytes. The increase in VEGF was blocked by inhibiting STAT3 with RNA interference or pharmaceutically with JSI-124. While VEGF by itself minimally induced the expression of CD86 and MHC-II in MDDC, arsenic induced-MDDC activation was abolished by VEGF pretreatment. We concluded that the STAT3-VEGF axis in keratinocytes inhibits DC migration in the microenvironment of As-BD, indicating that cellular interactions play an important role in regulating the disease course of arsenical cancers.
    Chemico-Biological Interactions 01/2015; 227. DOI:10.1016/j.cbi.2014.12.030 · 2.98 Impact Factor
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    ABSTRACT: Background To assess the severity and duration of herpes zoster (HZ)-associated pain (ZAP) and its impact on quality of life (QoL) and healthcare utilization (HCRU) from a patient perspective in routine care in Taiwan.MethodsA prospective, observational, single-cohort study was conducted in five centers across Taiwan. Patients were recruited at different time points during their HZ episode and were followed for ≤180 days. ZAP was assessed with the Initial Zoster Impact Questionnaire and the Zoster Brief Pain Inventory, QoL with the EQ-5D, and HCRU with a simple questionnaire.ResultsA total of 150 patients were included with a mean age of 64.9 years and mean time since rash onset of 18.8 days. Prodromal pain was experienced by 64.7% of patients, of whom 91.8% reported moderate-to-severe pain. At enrollment, 98.0% of patients experienced ZAP. Mean ± SD worst pain score decreased from 5.95 ± 3.09 at enrollment to 2.65 ± 2.98 at 30 days and 0.28 ± 0.83 at 180 days. Postherpetic neuralgia was observed in 20.7% of patients. Mean ± SD EQ-5D score significantly decreased (P < 0.001) from 0.91 ± 0.16 before rash onset to 0.67 ± 0.18 after rash onset, showing significant QoL deterioration up to 60 days. The impact of HZ on QoL and pain severity was similar across age groups. Significant HCRU was observed including visits to the doctor (83.3% of patients), specialist (30.7%), emergency department (24.7%), physiotherapist (23.3%), and hospitalizations (20.7%).Conclusion Severe morbidity and significant HCRU are associated with HZ in Taiwan, supporting the need for early intervention and preventive strategies to reduce the HZ-associated burden of illness.
    International journal of dermatology 09/2014; 54(5). DOI:10.1111/ijd.12484 · 1.23 Impact Factor
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    ABSTRACT: Arsenic is a class I human carcinogen (such as inducing skin cancer) by its prominent chemical interaction with protein thio (-SH) group. Therefore, arsenic may compromise protein S-nitrosylation by competing the -SH binding activity. In the present study, we aimed to understand the influence of arsenic on protein S-nitrosylation and the following proteomic changes. By using primary human skin keratinocyte, we found that arsenic treatment decreased the level of protein S-nitrosylation. This was coincident to the decent expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). By using LC-MS/MS, around twenty S-nitrosoproteins were detected in the biotin-switched eluent. With the interest that arsenic not only regulates posttranslational S-nitrosylation but also separately affects protein's translation expression, we performed two-dimensional gel electrophoresis and found that 8 proteins were significantly decreased during arsenic treatment. Whether these decreased proteins are the consequence of protein S-nitrosylation will be further investigated. Taken together, these results provide a finding that arsenic can deplete the binding activity of NO and therefore reduce protein S-nitrosylation.
    07/2014; 2014:360153. DOI:10.1155/2014/360153
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    ABSTRACT: Previous studies suggest that tazarotene, a new member of the acetylenic class of RARβ/γ selective retinoids which is approved to treat a variety of skin diseases, exhibits an anti-proliferative effect in human basal cell carcinoma (BCC) by triggering caspase-dependent apoptosis. However, the detailed molecular mechanisms underlying the anti-tumor activity of tazarotene are poorly understood. This study aims at investigating the molecular mechanisms of tazarotene-induced apoptosis in human BCC cells. Our results are the first to demonstrate that tazarotene induces mitochondria-dependent cleavage of caspase-9 and -3 and PARP in BCC cells by producing reactive oxygen species (ROS) and activating caspase-8 through both ROS and death receptor signaling. These events are accompanied by a decrease in BCL-2 and BCL-xl anti-apoptotic proteins as well as by survivin and XIAP, two IAP family members. Furthermore, our results presented for the first time that tazarotene triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the caspase-8-truncated Bid signaling pathway. Collectively, these data provide insights into the molecular mechanisms underlying tazarotene-induced apoptosis in human BCC cells, suggesting that this compound is a potential anti-skin cancer drug.
    DNA and Cell Biology 06/2014; 33(10). DOI:10.1089/dna.2014.2366 · 1.99 Impact Factor
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    ABSTRACT: The molecular pathogenesis of mycosis fungoides (MF) is currently poorly understood. The chemokine receptor CCR7 has been demonstrated to be involved in the development and progression of certain cancers, but its role in MF has rarely been investigated. We seek to determine whether CCR7 is expressed in MF skin lesions. In addition, we evaluate whether CCR7 plays a role in MF cell proliferation and migration, and which signaling pathways are involved. Immunohistochemical staining of 21 cases of MF pathology specimens with CCR7 was performed. Medical charts and pathology slides of these cases were reviewed. Surface expression of CCR7 on MyLa cells (MF cell line) and peripheral blood mononuclear cells (PBMCs) was assessed by flow cytometry. Cell proliferation and migration were evaluated with the Alamar Blue assay and transwell chemotaxis assay, respectively. CCR7 was found to be expressed in 62% (13 out of 21) of MF pathology specimens, and its expression correlated with subcutaneous extension of lymphoma cells. CCR7 expression was increased on the surface of MyLa cells compared to that on PBMCs. Addition of CCL21 (CCR7 agonist) enhanced MyLa cell migration but not proliferation. The CCL21-induced MyLa cell migration was found to be mediated by the mTOR pathway. CCR7 is more likely to be expressed in MF skin lesions with subcutaneous involvement. Activation of CCR7 promotes migration of MyLa cells (MF cell line) through the mTOR pathway. These findings provide new insights into the significance of CCR7 in the pathophysiology of MF.
    Journal of dermatological science 12/2013; DOI:10.1016/j.jdermsci.2013.12.003 · 3.34 Impact Factor
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    ABSTRACT: Endemic contamination of artesian water for drinking by arsenic is known to cause several human cancers, including cancers of the skin, bladder, and lungs. In skin, multiple arsenic-induced Bowen's disease (As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.
    Journal of Asian Earth Sciences 11/2013; 77:342-348. DOI:10.1016/j.jseaes.2013.07.007 · 2.83 Impact Factor
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    ABSTRACT: Alkylphenols, such as nonylphenol (NP) and 4-octylphenol (4-OP), have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. Plasmacytoid dendritic cells (PDCs) can secrete large amounts of type I IFNs and are critical in immune regulation. However, there has been limited study about the influence of alkylphenols on the function of pDCs. The aim of this study was to examine the effect of alkylphenols on pDC functions in vitro and in vivo and then further explored the involved signaling pathways and epigenetic changes. Circulating pDCs from human peripheral blood mononuclear cells were treated with alkylphenols with or without CpG stimulation. Alkylphenol-associated cytokine responses, signaling events, histone modifications and viral activity were further examined. In NP-exposed mice, the effect of NP on splenic pDC function and allergic lung inflammation were also assessed. The results showed that NP increased the expression of TNF-α, but suppressed IL-10 production in the range of physiological doses, concomitant with activation of the MKK3/6-p38 signaling pathway and enhanced levels of acetylated histone 3 as well as histone 4 at the TNFA gene locus. Further, in CpG-stimulated pDCs, NP suppressed type I IFNs production, associated with down-regulation of IRF-7 and MKK1/2-ERK-Elk-1 pathways and led to the impaired anti-enterovirus 71 activity in vitro. Additionally, splenic pDCs from NP-exposed mice showed similar cytokine changes upon CpG stimulation under conditions relevant to route and level of exposure in humans. NP treatment also enhanced allergic lung inflammation in vivo. Alkylphenols may influence pDCs' functions via their abilities to induce expression of a pro-inflammatory cytokine, TNF-α, and to suppress regulatory cytokines, including IL-10, IFN-α and IFN-β, suggesting the potential impact of endocrine disrupting chemicals on immune regulation.
    PLoS ONE 09/2013; 8(9):e73534. DOI:10.1371/journal.pone.0073534 · 3.53 Impact Factor
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    ABSTRACT: Sun exposure is an important environmental factor affecting human beings. Most knowledge regarding solar aging focused on light radiation (photoaging), and little emphasis has been placed on heat, a factor that is also closely associated with sun exposure. This study was launched to evaluate the effects of simulated solar radiation (SSR) and environmental heat on skin fibroblasts in terms of dermal aging. Cultured human dermal fibroblasts were treated with moderate amount of SSR (200J/cm(2)) and heat (+2°C). The metalloproteinase-1 (MMP-1) expression was used as a surrogate marker for dermal aging and the involved regulatory mechanisms were explored. Both treatment conditions did not affect viability but significantly increased the expressions of MMP-1. In parallel, both treatments increased the intracellular levels of reactive oxygen species (ROS), but the increase induced by SSR is much greater than heat. In contrast, transient receptor potential vanilloid 1 (TRPV-1), the sensor of environmental heat, was upregulated by heat but not SSR treatment. Pretreating fibroblasts with antioxidant abrogated the SSR-induced MMP-1 but has limited effect on heat-induced MMP-1. On the other hand, TRPV-1 antagonist pretreatment reduced heat-induced MMP-1 in fibroblasts but not their SSR-treated counterparts. Both SSR and heat induced MMP-1 expression in dermal fibroblasts but through different pathways. As current strategies for reducing sun-related aging focused on filtering of light and use of antioxidants, future strategies design to reduce solar aging should also incorporate heat-induced aging into consideration.
    Journal of dermatological science 08/2013; 72(3). DOI:10.1016/j.jdermsci.2013.07.015 · 3.34 Impact Factor
  • Journal of dermatological science 06/2013; 37. DOI:10.1016/j.jdermsci.2013.05.005 · 3.34 Impact Factor
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    ABSTRACT: Ecological studies in Taiwan, Chile, Argentina, Bangladesh, and Mexico have confirmed significant dose-dependent associations between ingestion of arsenic-contaminated drinking water and the risk of various human malignancies. The FHIT and WWOX genes are active in common fragile sites FRA3B and FRA16D, respectively. Reduced expression of FHIT or WWOX is known to be an early indicator of carcinogen-induced cancers. However, the effect of arsenite on the expressions and molecular mechanisms of these markers is still unclear. The aims of this study were (i) to observe the expression of ATR, WWOX and FHIT proteins in urothelial carcinoma (UC) between endemic and non-endemic areas of blackfoot disease (BFD) by immunohistochemical analyses; (ii) to compare expression of these genes between arsenite-treated SV-HUC-1 human epithelial cells and rat uroepithelial cells and (iii) to determine the role of DNMT and MEK inhibitors on expressions of WWOX and FHIT in response to arsenite in SV-HUC-1. The experiments revealed that expressions of ATR, WWOX and FHIT in UC significantly differed between BFD areas and non-BFD areas (p=0.003, 0.009 and 0.021, respectively). In fact, the results for the arsenite-treated groups showed that ATR, WWOX and FHIT are downregulated by arsenite in SV-HUC-1. However, the inhibitors suppressed the effects of arsenite on WWOX and FHIT proteins and mRNA expression. In conclusion, arsenite decreased expressions of ATR, WWOX and FHIT via ERK1/2 activation in SV-HUC-1 cells. These findings confirm that dysregulations of these markers may contribute to arsenite-induced carcinogenesis.
    Toxicology Letters 04/2013; DOI:10.1016/j.toxlet.2013.04.007 · 3.36 Impact Factor
  • 04/2013; 23(2). DOI:10.1684/ejd.2013.1965
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    ABSTRACT: Abstract is missing (Letter).
    Acta Dermato-Venereologica 03/2013; 93(6). DOI:10.2340/00015555-1584 · 4.24 Impact Factor
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    ABSTRACT: Arsenic causes several human cancers. Arsenic-induced Bowen's disease (As-BD), the most common arsenical cancers, is characterized by increased proliferation, dysplasia, and individual cell apoptosis, all of which involve mitochondria. We reported arsenic causes aberrant keratinocyte proliferation through mtTFA-mediated mitochondrial biogenesis in As-BD. Increasing mitochondrial biogenesis render cells undergo oxidative stresses. However, how arsenic induces oxidative stress and causes mitochondrial DNA (mtDNA) damage in arsenical cancers remains largely unknown. Using tissues from As-BD patients and arsenic-treated keratinocytes, we determined the oxidative stress, antioxidant enzymes, DNA repair enzymes, and 8-OHdG level in mtDNA by immunofluorescence, real-time PCR, and Western blot. The results showed that oxidative stress was enhanced in both As-BD and arsenic-treated keratinocytes. Antioxidant enzymes including Mn-SOD and Cu/Zn-SOD and DNA repair enzymes were upregulated concomitantly in tissues and cells. In arsenic-treated keratinocytes, increased mitochondrial oxidative stress and the 8-OHdG level in mtDNA was attenuated by pretreatment with ascorbic acid, a potent antioxidant. Further, we found several somatic mutations in the ND4, ND5 and ND6 genes of mtDNA in lesional but not in perilesional skin from As-BD patients. Taken together, the results suggest oxidative damage and mutations to mtDNA might be involved in the arsenical skin cancers in the context of mitochondrial biogenesis.
    Journal of Investigative Dermatology 03/2013; 133(7):1890-1900. DOI:10.1038/jid.2013.55 · 6.37 Impact Factor
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    ABSTRACT: The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS. When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis. Intriguingly, receptor activator of NF-κB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis. Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition, melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy that has been widely used in the treatment of many dermatological diseases.
    International Journal of Molecular Sciences 03/2013; 14(3):6414-35. DOI:10.3390/ijms14036414 · 2.46 Impact Factor
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    ABSTRACT: Light exposure modulates development of living organisms. In the field of medicine, light has frequently been used for regenerative purposes. Excimer light (308nm) has demonstrated superior efficacy in treating vitiligo, a condition requiring development of melanoblasts and a model for studying nerve cell regeneration, as compared to narrow-band UVB (NBUVB; 311nm). Using mouse-derived melanoblast cells to examine the pro-differentiation effects of these two light sources, we demonstrated that at equivalent fluence, excimer light induces melanoblast differentiation while NBUVB failed to so. Mechanistically, activation of arylhydrocarbon receptor pathway and nuclear translocation of epidermal growth factor receptor are involved in pro-differentiation effects of excimer light. Reduction of irradiance by filter abrogated the effects of excimer light in melanoblasts, even when equivalent fluence was delivered by the same light source. Since UVB irradiation is closely associated pigment cell development, future therapy employing UVB for pigmentation purposes should incorporate irradiance as a crucial specification. © 2013 John Wiley & Sons A/S.
    Pigment Cell & Melanoma Research 02/2013; 26(3). DOI:10.1111/pcmr.12077 · 5.64 Impact Factor
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    ABSTRACT: Abstract Purpose: Many studies have been conducted to elucidate the molecular consequences of ultraviolet irradiation, whereas little is known about the effect of infrared radiation on ocular disease. Heat is generated as a consequence of infrared irradiation, in addition to photons, and heat shock is widely considered to be an environmental stressor. Our previous study has demonstrated that heat shock (42 °C) induces apoptosis of Statens Seruminstitut Rabbit Cornea (SIRC) cells. However, the biological effect of mild heat shock (39 °C), which does not induce apoptosis, on SIRC cells has not been studied yet. Methods: The SIRC cells were treated with mild heat shock and the expression of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), in the mRNA and protein levels were then assayed with reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The levels of heat shock protein 90 (HSP90), phosphorylated AKT, phosphorylated IκBα and nuclear NF-κB were assessed with immunoblot assays; the involvement of these molecules in the signaling pathway were further assessed by using specific inhibitor for HSP90, AKT or NF-κB. Results: Mild heat shock increased the production of inflammatory cytokines, IL-1β and IL-6. Mild heat shock increased expression of HSP90, which increased the phosphorylation of AKT. The activated AKT then increased the phosphorylation of IκBα, resulting in nuclear translocation of NF-κB, which up-regulated the expression of IL-1β and IL-6 in SIRC cells. Conclusions: These findings suggest a critical role for the HSP90-AKT-NF-κB signaling pathway in mild heat shock-induced inflammatory response of cornea cells.
    Current eye research 01/2013; DOI:10.3109/02713683.2012.763103 · 1.66 Impact Factor

Publication Stats

2k Citations
384.04 Total Impact Points


  • 2000–2015
    • Kaohsiung Medical University
      • • College of Medicine
      • • Institute of Medicine
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2006–2013
    • National Yang Ming University
      • • Institute of Biochemistry and Molecular Biology
      • • Department of Dermatology
      T’ai-pei, Taipei, Taiwan
    • Buddhist Tzu Chi General Hospital
      • Department of Urology
      T’ai-pei, Taipei, Taiwan
  • 2011
    • Kaohsiung Municipal Ta-Tung Hospital, Taiwan
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2008
    • National Health Research Institutes
      Miao-li-chieh, Taiwan, Taiwan
  • 2007
    • National Sun Yat-sen University
      • Institute of Biomedical Science
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2004–2006
    • National Taiwan University
      • College of Medicine
      T’ai-pei, Taipei, Taiwan
  • 2005
    • National Taiwan University Hospital
      T’ai-pei, Taipei, Taiwan
  • 1998
    • Keio University
      Edo, Tōkyō, Japan