bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of Ultraviolet‐B Radiation Damage by Resveratrol in Mouse Skin Is Mediated via Modulation in Survivin¶
Authors: Aziz Moammir Hasan , Afaq Farrukh , Ahmad Nihal 
Published: July 2010

ABSTRACTNonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV‐B component, 290–320 nm) is its major cause. “Chemoprevention”by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans‐3,5,4‐trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV‐B–mediated cutaneous damages in SKH‐1 hairless mice. Understanding the mechanism of resveratrol‐mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV‐exposure–mediated modulations in (1) cki‐cyclin‐cdk network and (2) mitogen activated protein kinase (MAPK)‐pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family protein Survivin during resveratrol‐mediated protection from multiple exposures of UV‐B (180 mJ/cm2; on alternate days; for a total of seven exposures) radiations in the SKH‐1 hairless mouse skin. Our data demonstrated that topical pretreatment of resveratrol (10 μmol in 200 μL acetone/mouse) resulted in significant inhibition of UV‐B exposure‐mediated increases in (1) cellular proliferations (Ki‐67 immunostaining), (2) protein levels of epidermal cyclooxygenase‐2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH‐1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV‐B–mediated decrease of Smac/DIABLO and (2) enhancement of UV‐B–mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV‐B exposure–mediated damages in SKH‐1 hairless mouse skin via inhibiting Survivin and the associated events.
Protective Effect of the Isoflavonoid Equol Against Hairless Mouse Skin Carcinogenesis Induced by UV Radiation Alone or with a Chemical Cocarcinogen¶
Authors: Widyarini Sitarina , Husband Alan J. , Reeve Vivienne E. 
Published: July 2010

ABSTRACTIsoflavones derived from many edible plants, such as genistein from the soybean, have well‐documented antioxidant and estrogenic activity but may also be anticarcinogenic. In this study, we examined the potential of the isoflavone equol [(S)‐4′,7‐dihydroxyisoflavane] to protect from skin carcinogenesis in the hairless mouse. Daily topical applications of equol lotions significantly protected against skin carcinogenesis induced by chronic exposure to solar‐simulated UV radiation (SSUV) or by topical treatment with the chemical carcinogen 7,12‐dimethylbenz(a)anthracene (DMBA) or by the combined cocarcinogenic treatment of DMBA followed by chronic SSUV. Monitoring of tumor development for 40 weeks showed significantly delayed tumor appearance and reduced tumor multiplicity in all equol‐treated groups. In mice treated with either SSUV or DMBA + SSUV, equol significantly reduced the proportion of tumors progressing from benign papillomas to malignant squamous cell carcinoma (SCC) by 33–58% and reduced the average diameter of SCC by 71–82%. In a short‐term study, equol dose dependently inhibited the SSUV induction of the tumor promotion biomarker enzyme, ornithine decarboxylase, in the skin, suggesting the anticarcinogenic activity of equol may be attributed to its inhibition of the tumor promotion phase of carcinogenesis.
Pomegranate Fruit Extract Modulates UV‐B–mediated Phosphorylation of Mitogen‐activated Protein Kinases and Activation of Nuclear Factor Kappa B in Normal Human Epidermal Keratinocytes¶
Authors: Afaq Farrukh , Malik Arshi , Syed Deeba , Maes Daniel , Matsui Mary S. , Mukhtar Hasan 
Published: July 2010

ABSTRACTExcessive exposure of solar ultraviolet (UV) radiation, particularly its UV‐B component, to humans causes many adverse effects that include erythema, hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In recent years, there is increasing use of botanical agents in skin care products. Pomegranate derived from the tree Punica granatum contains anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) and possesses strong antioxidant and anti‐inflammatory properties. Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor promoting effects in a mouse model of chemical carcinogenesis. To begin to establish the effect of PFE for humans in this study, we determined its effect on UV‐B–induced adverse effects in normal human epidermal keratinocytes (NHEK). We first assessed the effect of PFE on UV‐B–mediated phosphorylation of mitogen‐activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis demonstrated that the treatment of NHEK with PFE (10–40 μg/mL) for 24 h before UV‐B (40 mJ/cm2) exposure dose dependently inhibited UV‐B–mediated phosphorylation of ERK1/2, JNK1/2 and p38 protein. We also observed that PFE (20 μg/mL) inhibited UV‐B–mediated phosphorylation of MAPK in a time‐dependent manner. Furthermore, in dose‐and time‐dependent studies, we evaluated the effect of PFE on UV‐B–mediated activation of nuclear factor kappa B (NF‐κB) pathway. Using Western blot analysis, we found that PFE treatment of NHEK resulted in a dose‐ and time‐dependent inhibition of UV‐B–mediated degradation and phosphorylation of IκBα and activation of IKKα. Using immunoblot analysis, enzyme‐linked immunosorbent assay and electrophoretic mobility shift assay, we found that PFE treatment to NHEK resulted in a dose‐ and time‐dependent inhibition of UV‐B–mediated nuclear translocation and phosphorylation of NF‐κB/p65 at Ser536. Taken together, our data shows that PFE protects against the adverse effects of UV‐B radiation by inhibiting UV‐B–induced modulations of NF‐κB and MAPK pathways and provides a molecular basis for the photochemopreventive effects of PFE.
Phioxine B Phototoxicity: A Mechanistic Study Using HaCaT Keratinocytes¶
Authors: Inbaraj Johnson J. , Kukielczak Barbara M. , Chignell Colin F. 
Published: July 2010

ABSTRACTPhloxine B (PhB) (2′,4′,5′,7′‐tetrabromo‐4,5,6,7‐tetrachloro‐fluorescein; D&C Red No. 28) is a red dye found in drugs, cosmetics and foods; it is also currently being evaluated as a phototoxin for the potential control of fruit flies. Previous studies have shown that PhB is an efficient photosensitizer of damage to cellular membranes; thus, exposure of the skin to the dye and sunlight or artificial light may result in phototoxicity. Therefore, we have studied the phototoxicity of PhB and its structural analogue 2′,7′‐dichlorofluorescein (DCF) to HaCaT keratinocytes. Anaerobic visible irradiation (>400 nm) of PhB generated a semiquinone type radical, as detected by direct electron paramagnetic resonance. Aerobic visible irradiation of a reaction mixture containing PhB, the spin trap 5,5‐di methyl‐1‐pyrroline N‐oxide (DMPO) and nicotinamide adenine dinucleotide (reduced) generated a superoxide dismutase–sensitive DMPO/O2•− adduct. Irradiation of PhB and DCF in D2O generated singlet oxygen with quantum yields of 0.59 and 0.06, respectively. PhB was much more phototoxic than DCF when cell viability was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium assay. Visible irradiation of HaCaT keratinocytes in the presence of PhB (5 μM) resulted in a 90% decrease in cell viability. 3β‐Hydroxy‐5α‐cholest‐6‐ene‐5‐hydroperoxide, a singlet oxygen photoproduct of cholesterol, was isolated from HaCaT keratinocytes irradiated in the presence of PhB. Furthermore, PhB phototoxicity was inhibited by histidine and cysteine, quenchers of singlet oxygen. PhB (0.5 μM) and light irradiation also resulted in DNA damage, as measured by the Comet assay. The phototoxicity mechanism of PhB most probably initially involves a Type‐II reaction with free radicals playing a minor role. However, secondary oxidative species such as radicals generated as a result of lipid peroxidation may serve to further promote oxidative damage. Our findings suggest that concern is warranted about the use of this dye in cosmetic products, as a food additive and in insecticidal sprays.
Optical Properties of Human Prostate at 732 nm Measured In Vivo During Motexafin Lutetium–mediated Photodynamic Therapy¶
Authors: Zhu Timothy C. , Dimofte Andreea , Finlay Jarod C. , Stripp Diana , Busch Theresa , Miles Jeremy , Whittington Richard , Malkowicz S. Bruce , Tochner Zellg , Glatstein Eli , Hahn Stephen M. 
Published: July 2010

ABSTRACTCharacterization of the tissue light penetration in prostate photodynamic therapy (PDT) is important to plan the arrangement and weighting of light sources so that sufficient light fluence is delivered to the treatment volume. The optical properties (absorption [μa], transport scattering [μ′s] and effective attenuation [μeff] coefficients) of 13 patients with locally recurrent prostate cancer were measured in situ using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu)–mediated PDT in four quadrants. Optical properties were derived by applying the diffusion theory to the fluence rates measured at several distances (0.5–5 cm) from a point source. μa and μ′s varied between 0.07 and 1.62 cm−1 (mean 0.37 ± 0.24 cm−1) and 1.1 and 44 cm−1 (mean 14 ± 11 cm−1), respectively. μa was proportional to the concentration of MLu measured by an ex vivo fluorescence assay. We have observed, on average, a reduction of the MLu concentration after PDT, presumably due to the PDT consumption of MLu. μeff varied between 0.91 and 6.7 cm−1 (mean 2.9 ± 0.7 cm−1), corresponding to an optical penetration depth (δ= 1/μeff) of 0.1–1.1 cm (mean 0.4 ± 0.1 cm). The mean penetration depth at 732 nm in human prostate is at least two times smaller than that found in normal canine prostates, which can be explained by a four times increase of the mean value of μ′s in human prostates. The mean light fluence rate per unit source strength at 0.5 cm from a point source was 1.5 ± 1.1 cm−2, excluding situations when bleeding occurs. The total number of measurements was N= 121 for all mean quantities listed above. This study showed significant inter‐ and intraprostatic differences in the optical properties, suggesting that a real‐time dosimetry measurement and feedback system for monitoring light fluences during treatment should be considered for future PDT studies.
Endogenous Fluorescence Spectroscopy of Cell Suspensions for Chemopreventive Drug Monitoring¶
Authors: Kirkpatrick Nathaniel D. , Zou Changping , Brewer Molly A. , Brands William R. , Drezek Rebekah A. , Utzinger Urs 
Published: July 2010

ABSTRACTCancer chemopreventive agents such asN‐4‐(hydroxyphenyl)‐retinamide (4HPR) are thought to prevent cancers by suppressing growth or inducing apoptosis in precancerous cells. Mechanisms by which these drugs affect cells are often not known, and the means to monitor their effects is not available. In this study endogenous fluorescence spectroscopy was used to measure metabolic changes in response to treatment with 4HPR in ovarian and bladder cancer cell lines. Fluorescence signals consistent with nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and tryptophan were measured to monitor cellular activity through redox status and protein content. Cells were treated with varying concentrations of 4HPR and measured in a stable environment with a sensitive fluorescence spectrometer. Results suggest that redox signal of all cells changed in a similar dose‐dependant manner but started at different baseline levels. Redox signal changes depended primarily on changes consistent with NADH fluorescence, whereas the FAD fluorescence remained relatively constant. Similarly, tryptophan fluorescence decreased with increased drug treatment, suggesting a decrease in protein production. Given that each cell line has been shown to have a different apoptotic response to 4HPR, fluorescence redox values along with changes in tryptophan fluorescence may be a response as well as an endpoint marker for chemopreventive drugs.
Global Forecast Model to Predict the Daily Dose of the Solar Erythemally Effective UV Radiation¶
Authors: Schmalwieser Alois W. , Schauberger Günther , Janouch Michal , Nunez Manuel , Koskela Tapani , Berger Daniel , Karamanian Gabriel 
Published: July 2010

ABSTRACTA worldwide forecast of the erythemally effective ultraviolet (UV) radiation is presented. The forecast was established to inform the public about the expected amount of erythemally effective UV radiation for the next day. Besides the irradiance, the daily dose is forecasted to enable people to choose the appropriate sun protection tools. Following the UV Index as the measure of global erythemally effective irradiance, the daily dose is expressed in units of UV Index hours. In this study, we have validated the model and the forecast against measurements from broadband UV radiometers of the Robertson–Berger type. The measurements were made at four continents ranging from the northern polar circle (67.4°N) to the Antarctic coast (61.1°S). As additional quality criteria the frequency of underestimation was taken into account because the forecast is a tool of radiation protection and made to avoid overexposure. A value closer than one minimal erythemal dose for the most sensitive skin type 1 to the observed value was counted as hit and greater deviations as underestimation or overestimation. The Austrian forecast model underestimates the daily dose in 3.7% of all cases, whereas 1.7% results from the model and 2.0% from the assumed total ozone content. The hit rate could be found in the order of 40%.
Enhancement of Riboflavin‐mediated Photo‐Oxidation of Glucose 6‐phosphate Dehydrogenase by Urocanic Acid¶
Authors: Silva Eduardo , Herrera Leonardo , Edwards Ana María , de la Fuente Julio , Lissi Eduardo 
Published: July 2010

ABSTRACTWe have investigated the riboflavin (RF)‐sensitized inactivation of glucose 6‐phosphate dehydrogenase (G6PD) in the presence and absence of trans‐urocanic acid (UCA). The inactivation of the enzyme results from its direct oxidation by the excited triplet RF in a Type‐I–photosensitized reaction whose efficiency increases at low oxygen concentration. The addition of histidine to the system produced no change in the inactivation rate, discarding the participation of singlet oxygen in the reaction. On the other hand, the presence of UCA results in its bleaching, with a significant enhancement of RF‐mediated inactivation of G6PD. Both the consumption of UCA and G6PD are faster at low oxygen concentrations. UCA also produced a decrease in the sensitizer photodecomposition yield. These results indicate that the enhancement of the RF‐mediated G6PD inactivation observed in the presence of UCA is not a singlet oxygen–mediated process. It is proposed that UCA consumption and its effect on G6PD inactivation are due to a complex reaction sequence initiated by a direct oxidation of UCA by the excited sensitizer triplet. The oxidation of the semireduced flavin gives rise to reactive oxygen species (ROS) responsible for the increased rate of the process. This is supported by the protection afforded by several additives with ROS removal capacity: benzoate, superoxide dismutase and catalase.
Synthesis, Photophysical Studies and Anticancer Activity of a New Halogenated Water‐Soluble Porphyrin
Authors: Dąbrowski Janusz M. , Pereira Mariette M. , Arnaut Luis G. , Monteiro Carlos J. P. , Peixoto Andreia F. , Karocki Andrzej , Urbańska Krystyna , Stochel Grażyna 
Published: July 2010

ABSTRACTA water‐soluble halogenated porphyrin, namely 5,10,15,20‐tetrakis(2‐chloro‐3‐sulfophenyl)porphyrin (TCPPSO3H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO3H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO3H is non‐toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time‐dependent cellular uptake of TCPPSO3H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water‐soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents.
Chlorpromazine Binding to Na+, K+‐ATPase and Photolabeling: Involvement of the Ouabain Site Monitored by Fluorescence
Authors: Guevara Elmer A. C. , De Lourdes Barriviera Maria , Hassón‐Voloch Aída , Louro Sonia R. W. 
Published: July 2010

ABSTRACTThis work reports the results of ultraviolet irradiation on the interaction of the phototoxic antipsychotic drug chlorpromazine (CPZ) with the sodium pump Na+, K+‐ATPase. The study was performed by monitoring the fluorescence modifications of CPZ itself and of the specific probe anthroylouabain (AO). CPZ association with Na+, K+‐ATPase was found to modify the kinetics of CPZ‐photodegradation. It was demonstrated that UV irradiation produces a stable fluorescent photoproduct of CPZ covalently bound to Na+, K+‐ATPase. The fluorescent probe AO, which specifically binds to the extracellular ouabain site of the pump, was used to localize the CPZ binding site. UV‐irradiation of AO‐labeled Na+, K+‐ATPase treated with CPZ at concentration about 20 μMproduced dose‐dependent modifications of the AO fluorescence,e.g.increased quantum yield and blue shift. The results demonstrated that CPZ binds near the ouabain site. The photo‐induced reaction of CPZ with AO‐labeled Na+, K+‐ATPase protected the ouabain site from the aqueous environment. It was also found that UV irradiation of CPZ‐treated enzyme obstructs the binding of AO, which suggested occlusion of the ouabain site. This effect can be evaluated for a potential use of CPZ in photochemotherapy.
Polymeric Photosensitizer Prodrugs for Photodynamic Therapy
Authors: Campo Marino A. , Gabriel Doris , Kucera Pavel , Gurny Robert , Lange Norbert 
Published: July 2010

ABSTRACTA targeting strategy based on the selective enzyme‐mediated activation of polymeric photosensitizer prodrugs (PPP) within pathological tissue has led to the development of agents with the dual ability to detect and treat cancer. Herein, a detailed study of a simple model system for these prodrugs is described. We prepared “first‐generation” PPP by directly tethering the photosensitizer (PS) pheophorbide a to poly‐(l)‐lysine via epsilon amide links and observed that by increasing the number of PS on a polymer chain, energy transfer between PS units improved leading to better quenching efficiency. Fragmentation of the PPP backbone by trypsin digestion gave rise to a pronounced fluorescence increase and to more efficient generation of reactive oxygen species upon light irradiation. In vitro tests using the T‐24 bladder carcinoma cell line and ex vivo experiments using mouse intestines illustrated the remarkable and selective ability of these PPP to fluoresce and induce phototoxicity upon enzymatic activation. This work elucidated the basic physicochemical parameters, such as water solubility and quenching/activation behavior, required for the future elaboration of more adaptable “second‐generation” PPP, in which the PS is tethered to a proteolytically stable polymer backbone via enzyme‐specific peptide linkers. This polymer architecture offers great flexibility to tailor make the PPP to target any pathological tissue known to over‐express a specific enzyme.
Interaction of Fusarium solani Lectin with Monosaccharides and Oligosaccharides: A Fluorometric Study
Authors: Khan Feroz , Ahmad Absar , Khan M. Islam 
Published: July 2010

ABSTRACTThe intrinsic fluorescence intensity of Fusarium solani lectin was quenched upon binding to mono‐ and oligosaccharides without any change in the emission maximum and it was used to determine association constants for several sugars and glycans. The lectin interacted very poorly with monosaccharides but well with disaccharides (T‐antigen and LacNAc) with a distinction between β1→4 and β1→3 linkages. Among the monosaccharides, the interaction was observed only with Gal/GalNAc derivatives and not with Glc/Man derivatives. Thermodynamic studies revealed that the binding of the lectin with all the saccharides is enthalpically driven and exothermic in nature. Asialo‐triantennary N‐glycan and asialo‐biantennary N‐glycan showed higher affinity than monovalent LacNAc with significant increase in binding enthalpy, pointing towards the importance of multivalency in the lectin–ligand interactions. Time‐resolved fluorescence measurement indicated the lectin has two lifetimes for tryptophan and the shorter lifetime is affected on ligand binding.
Effects of Low Power Laser Irradiation on Intracellular Calcium and Histamine Release in RBL‐2H3 Mast Cells
Authors: Yang Wen‐Zhong , Chen Ji‐Yao , Yu Ji‐Tong , Zhou Lu‐Wei 
Published: July 2010

AbstractAlthough laser irradiation has been reported to promote skin wound healing, the mechanism is still unclear. As mast cells are found to accumulate at the site of skin wounds we hypothesized that mast cells might be involved in the biological effects of laser irradiation. In this work the mast cells, RBL‐2H3, were usedin vitroto investigate the effects of laser irradiation on cellular responses. After laser irradiation, the amount of intracellular calcium ([Ca2+]i) was increased, followed by histamine release, as measured by confocal fluorescence microscopy with Fluo‐3/AM staining and a fluorescence spectrometer witho‐phthalaldehyde staining, respectively. The histamine release was mediated by the increment of [Ca2+]ifrom the influx of the extracellular buffer solution through the cation channel protein, transient receptor potential vanilloid 4 (TRPV4). The TRPV4 inhibitor, Ruthenium Red (RR) can effectively block such histamine release, indicating that TRPV4 was the key factor responding to laser irradiation. These induced responses of mast cells may provide an explanation for the biological effects of laser irradiation on promoting wound healing, as histamine is known to have multi‐functions on accelerating wound healing.