Photodynamic therapy is widely used in the clinical treatment of tumors, especially skin cancers. It has been reported that the photosensitizer curcumin, in combination with ultraviolet radiation B, induces HaCaT cell apoptosis, and this effect may be due to the activation of caspase pathways. In this study, we examined the photodynamic effects of demethoxycurcumin, a more stable analogue of curcumin, to determine whether it could induce apoptosis in skin cancer cells. We investigated the effects of a combination of ultraviolet radiation B and demethoxycurcumin on apoptotic cell death in A431 and HaCaT cells and determined the molecular mechanism of action. Our results showed increased apoptosis with a combination of ultraviolet radiation B with demethoxycurcumin, as compared to ultraviolet radiation B or demethoxycurcumin alone. The combination of ultraviolet radiation B irradiation with demethoxycurcumin synergistically induced apoptotic cell death in A431 and HaCaT cells through activation of p53 and caspase pathways, as well as through upregulation of Bax and p-p65 expression and downregulation of Bcl-2, Mcl-1, and nuclear factor-κB expression. In addition, we found that reactive oxygen species significantly increased with treatment, and mitochondrial membrane potential depolarization was remarkably enhanced. In conclusion, our data indicate that demethoxycurcumin may be a promising photosensitizer for use in photodynamic therapy to induce apoptosis in skin cancer cells.

Photodynamic therapy is widely used in the clinical treatment of tumors, especially skin cancers. It has been reported that the photosensitizer curcumin, in combination with ultraviolet radiation B, induces HaCaT cell apoptosis, and this effect may be due to the activation of caspase pathways. In this study, we examined the photodynamic effects of demethoxycurcumin, a more stable analogue of curcumin, to determine whether it could induce apoptosis in skin cancer cells. We investigated the effects of a combination of ultraviolet radiation B and demethoxycurcumin on apoptotic cell death in A431 and HaCaT cells and determined the molecular mechanism of action. Our results showed increased apoptosis with a combination of ultraviolet radiation B with demethoxycurcumin, as compared to ultraviolet radiation B or demethoxycurcumin alone. The combination of ultraviolet radiation B irradiation with demethoxycurcumin synergistically induced apoptotic cell death in A431 and HaCaT cells through activation of p53 and caspase pathways, as well as through upregulation of Bax and p-p65 expression and downregulation of Bcl-2, Mcl-1, and nuclear factor-κB expression. In addition, we found that reactive oxygen species significantly increased with treatment, and mitochondrial membrane potential depolarization was remarkably enhanced. In conclusion, our data indicate that demethoxycurcumin may be a promising photosensitizer for use in photodynamic therapy to induce apoptosis in skin cancer cells.

In sighted humans, light intensity, timing, exposure duration, and spectral composition of light are important to entrain the endogenous circadian pacemaker to the 24-h day-night cycle. We tested the impact of two realistic office lighting conditions during the afternoon on subjective sleepiness, hormonal secretion, and cognitive performance in the early evening hours. Twenty-nine young subjects came twice and spent 8 h (12:00-20:00) in our laboratory, where they were exposed for 6 h to either artificial light (AL) or to mainly daylight (DL). In the early evening, we assessed their salivary cortisol and melatonin secretion, subjective sleepiness, and cognitive performance (n-back test) under dim light conditions. Subjects felt significantly more alert at the beginning of the evening after the DL condition, and they became sleepier at the end of the evening after the AL condition. For cognitive performance we found a significant interaction between light conditions, mental load (2- or 3-back task) and the order of light administration. On their first evening, subjects performed with similar accuracy after both light conditions, but on their second evening, subjects performed significantly more accurately after the DL in both n-back versions and committed fewer false alarms in the 2-back task compared to the AL group. Lower sleepiness in the evening was significantly correlated with better cognitive performance (p<.05). In summary, even short-term lighting conditions during the afternoon had an impact on cognitive task performance in the evening. This rapid effect was only distinguishable on the second day of training, when a difficult task had been sufficiently practiced.

In sighted humans, light intensity, timing, exposure duration, and spectral composition of light are important to entrain the endogenous circadian pacemaker to the 24-h day-night cycle. We tested the impact of two realistic office lighting conditions during the afternoon on subjective sleepiness, hormonal secretion, and cognitive performance in the early evening hours. Twenty-nine young subjects came twice and spent 8 h (12:00-20:00) in our laboratory, where they were exposed for 6 h to either artificial light (AL) or to mainly daylight (DL). In the early evening, we assessed their salivary cortisol and melatonin secretion, subjective sleepiness, and cognitive performance (n-back test) under dim light conditions. Subjects felt significantly more alert at the beginning of the evening after the DL condition, and they became sleepier at the end of the evening after the AL condition. For cognitive performance we found a significant interaction between light conditions, mental load (2- or 3-back task) and the order of light administration. On their first evening, subjects performed with similar accuracy after both light conditions, but on their second evening, subjects performed significantly more accurately after the DL in both n-back versions and committed fewer false alarms in the 2-back task compared to the AL group. Lower sleepiness in the evening was significantly correlated with better cognitive performance (p<.05). In summary, even short-term lighting conditions during the afternoon had an impact on cognitive task performance in the evening. This rapid effect was only distinguishable on the second day of training, when a difficult task had been sufficiently practiced.

Purpose: This study was designed to measure vitamin D metabolites in the aqueous and vitreous humor and in tear fluid, and to determine if dietary vitamin D3 supplementation affects these levels. We also determined if the corneal epithelium can synthesize vitamin D following UV-B exposure. Methods: Rabbits were fed a control or vitamin D3 supplemented diet. Pilocarpine-stimulated tear fluid was collected and aqueous and vitreous humor were drawn from enucleated eyes. Plasma vitamin D was also measured. To test for epithelial vitamin D synthesis, a human corneal limbal epithelial cell line was irradiated with two doses of UV-B (10 and 20 mJ/cm(2)/day for 3 days) and vitamin D was measured in control or 7-dehydrocholesterol treated culture medium. Measurements were made using mass spectroscopy. Results: 25(OH)-vitamin D3 and 24,25(OH)(2)-vitamin D3 increased significantly following D3 supplementation in all samples except vitreous humor. Tear fluid and aqueous humor had small but detectable 1,25(OH)(2)-vitamin D3 levels. Vitamin D2 metabolites were observed in all samples. Vitamin D3 levels were below the detection limit for all samples. Minimal vitamin D3 metabolites were observed in control and UV-B-irradiated epithelial culture medium except following 7-dehydrocholesterol treatment, which resulted in a UV-B-dose dependent increase in vitamin D3, 25(OH)-vitamin D3 and 24,25(OH)(2)-vitamin D3. Conclusions: There are measurable concentrations of vitamin D metabolites in tear fluid and aqueous and vitreous humor, and oral vitamin D supplementation affects vitamin D metabolite concentrations in the anterior segment of the eye. In addition, the UV exposure results lead us to conclude that corneal epithelial cells are likely capable of synthesizing vitamin D3 metabolites in the presence of 7-dehydrocholesterol following UV-B exposure.

BACKGROUND:Middle East respiratory syndrome coronavirus (MERS-CoV) has been identified as a potential threat to the safety of blood products. The Mirasol Pathogen Reduction Technology System uses riboflavin and ultraviolet (UV) light to render blood-borne pathogens noninfectious while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against MERS-CoV when tested in human plasma.

STUDY DESIGN AND METHODS:MERS-CoV (EMC strain) was used to inoculate plasma units that then underwent treatment with riboflavin and UV light. The infectious titers of MERS-CoV in the samples before and after treatment were determined by plaque assay on Vero cells. The treatments were initially performed in triplicate using pooled plasma (n = 3) and then repeated using individual plasma units (n = 6).

RESULTS:In both studies, riboflavin and UV light reduced the infectious titer of MERS-CoV below the limit of detection. The mean log reductions in the viral titers were≥4.07 and ≥4.42 for the pooled and individual donor plasma, respectively.

CONCLUSION:Riboflavin and UV light effectively reduced the titer of MERS-CoV in human plasma products to below the limit of detection, suggesting that the treatment process may reduce the risk of transfusion transmission of MERS-CoV.

OBJECTIVE:The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied.

METHODS:Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection.

RESULTS:The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level.

CONCLUSION:The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.

The relationship between human skin pigmentation and protection from ultraviolet (UV) radiation is an important element underlying differences in skin carcinogenesis rates. The association between UV damage and the risk of skin cancer is clear, yet a strategic balance in exposure to UV needs to be met. Dark skin is protected from UV-induced DNA damage significantly more than light skin owing to the constitutively higher pigmentation, but an as yet unresolved and important question is what photoprotective benefit, if any, is afforded by facultative pigmentation (i.e. a tan induced by UV exposure). To address that and to compare the effects of various wavelengths of UV, we repetitively exposed human skin to suberythemal doses of UVA and/or UVB over 2 weeks after which a challenge dose of UVA and UVB was given. Although visual skin pigmentation (tanning) elicited by different UV exposure protocols was similar, the melanin content and UV-protective effects against DNA damage in UVB-tanned skin (but not in UVA-tanned skin) were significantly higher. UVA-induced tans seem to result from the photooxidation of existing melanin and its precursors with some redistribution of pigment granules, while UVB stimulates melanocytes to up-regulate melanin synthesis and increases pigmentation coverage, effects that are synergistically stimulated in UVA and UVB-exposed skin. Thus, UVA tanning contributes essentially no photoprotection, although all types of UV-induced tanning result in DNA and cellular damage, which can eventually lead to photocarcinogenesis.

BACKGROUND:Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (AAA) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental AAA.

METHODS AND RESULTS:We used an angiotensin II-induced AAA model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/mUVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of AAA formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed AAA, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of AAA (=0.004 and=0.006, respectively). UVB-irradiated mice had significantly smaller diameter AAA (=0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4Foxp3regulatory T cells and decreased effector CD4CD44CD62LT cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells.

CONCLUSIONS:Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental AAA and may provide a novel strategy for the treatment of AAA.