The Effect of A2E On The Levels of ROS and The Distribution of A2E in RPE Cells Exposed to Blue Light

AimsTo establish the N-retinylidene-N-retinylethanolamine(A2E) and blue light induced RPE cells damage model to explore the regularity of distribution of A2E and the levels of reactive oxygen species(ROS).MethodsThe fourth to sixth generation of human RPE cells in vitro were divided into five groups randomly: control group, blue light group, A2E-loaded group, A2E-loaed+blue light group and A2E-loaded+blue light +nifedipine group. The levels of ROS in cytoplasm by DCFH-DA staining was assayed by flow cytometry. The concentration of A2E in cytoplasm and lysosomes were assayed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The fluorescence intensity of A2E in lysosomes by Lysotracker redDND-99 staining was assayed by confocal laser scanning microscope. ResultsExposure to blue light and/or A2E could increase the levels of ROS in RPE cells, and nifedipine could inhibit oxidative stress response and reduce ROS levels. By HPLC-MS, it was found that A2E was not detected in the groups without load A2E, and A2E levels in cytoplasm and lysosomes decreased after light exposure. The green fluorescence produced by A2E loaded on RPE cells was mostly coincident with the red fluorescence labeled by lysosomes.ConclusionBlue light and A2E can increase the ROS levels of RPE cells and both have a synergistic effect. A2E is mainly concentrated in lysosomes, which is reduced by oxidation under blue light irradiation, damages lysosomal membrane with oxidized species of A2E, and leaks out from lysosomes.

Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment

This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression. Measured sizes of LCP EGFR siRNA NPs and LCP Pyro-PA NPs were 34.9 ± 3.0 and 20 nm respectively, and their zeta potentials were 51.8 ± 1.8 and 52.0 ± 7.6 mV respectively. In vitro studies showed that EGFR siRNA was effectively knocked down after photodynamic therapy (PDT) with significant inhibition of cancer growth. SCC4 or SAS xenografted nude mice were used to verify therapeutic efficacy. The LCP Control siRNA+PDT group of SCC4 and SAS showed significantly reduced tumor volume compared to the phosphate buffered saline (PBS) group. In the LCP-EGFR siRNA+LCP Pyro PA without light group and LCP EGFR siRNA + PBS with light group, SCC4 and SAS tumor volumes were reduced by ~140% and ~150%, respectively, compared to the PBS group. The LCP EGFR siRNA+PDT group of SCC4 and SAS tumor volumes were reduced by ~205% and ~220%, respectively, compared to the PBS group. Combined therapy showed significant tumor volume reduction compared to PBS, control siRNA, or PDT alone. QPCR results showed EGFR expression was significantly reduced after treatment with EGFR siRNA with PDT in SCC4 and SAS compared to control siRNA or PDT alone. Western blot results confirmed decreased EGFR protein expression in the combined therapy group. No toxic results were found in serum biomarkers. No inflammatory factors were found in heart, liver and kidney tissues. Results suggest that the novel LCP Pyro PA mediated PDT combined with LCP siEGFR NPs could be developed in clinical modalities for treating human head and neck cancer in the future.

Comparison of efficacy & safety of Blue Light vs topical application of 1% Clindamycin solution in the treatment of mild to moderate inflammatory Acne Vulgaris

Aim: To compare the efficacy & safety of blue light vs topical application of 1% clindamycin solution in the treatment of mild to moderate inflammatory acne vulgaris. Study Design: Comparative interventional study done in Dermatology Outpatient Department Unit-II, KEMU/ Mayo Hospital, Lahore six months i.e. 1-06-2014 – 30-11-2014 Methodology: After an informed and written consent, 130 patients fulfilling the selection criteria were enrolled in the study and divided in two study groups A & B by balloting method. At first visit, a detailed history and clinical examination was recorded on a specially designed proforma. The acne was graded according to the acne grading scale of American Academy of Dermatology.4,13 Group A was exposed to blue light for twenty minutes twice weekly for eight weeks. Group B was given 1% clindamycin to apply twice daily for a period of eight weeks. Post- treatment follow up was done for next four weeks. Patients were assessed at 2nd, 4th, 6th, 8th, 10th, and 12th week. All findings and side effects were recorded on a predesigned proforma. To determine the efficacy of treatment, Acne Severity Index (ASI) was used.5 Result: Efficacy of treatment [≥ 50% improvement in ASI score] was seen in 39(60%) patients in blue light group while in clindamycin group it was achieved in 8 (12.3%) patients only. Blue light group had significantly less number of side effects observed in 35 (37.23%) patients while clindamycin group had a higher number of side effects observed in 59 (62.77%) patients, p-value= 0.013. Conclusion: Blue light is more efficacious and safer than topical 1% clindamycin in the treatment of mild to moderate inflammatory acne vulgaris. Keywords: Blue light, 1% Clindamycin, Acne vulgaris

012 Overnight light exposure acutely increases heart rate during sleep and decreases insulin sensitivity the following day

Introduction Prior reports indicate that exposure to light at night negatively impacts sleep quality, autonomic and metabolic function, but the interaction between these physiologically interconnected systems is not fully elucidated. We examined the acute effects of nighttime light exposure on sleep macro and microarchitecture, heart rate (HR) and response to oral glucose tolerance test (OGTT), and the relationship between these measures. Methods Twenty healthy adults (18 - 40 years) were randomized into Light or Dark groups and run in parallel for a three-day and two-night laboratory stay. The Light group (n=10) slept in the dark (< 3 lux) on Night 1 and slept with overhead room lights on (100 lux) on Night 2, while the Dark group (n=10) slept in the dark (< 3 lux) on both Nights 1 and 2. Overnight polysomnography (PSG) was used to assess sleep macro and microstructure (slow wave activity: SWA: 0.5–4 Hz, and slow oscillatory (SO) activity: 0.5–1 Hz), and beat-to-beat measurement of HR. A two-hour OGTT was completed each morning. The between groups change in PSG-derived measures and metabolic parameters from Night/Day 2 to Night/Day 1, was calculated. Results While a greater percentage of time was spent in stage 2 (p= 0.003) and a smaller percentage of time was spent in stage 3 (p= 0.04), there were no between group differences in SWA and SO activity. Time series analysis of HR changes across the night from Night 1 to Night 2 showed higher HR in the Light vs the Dark group (p< 0.001). The change from Day 1 to Day 2 of the initial insulin response (60-min. area under the curve, AUC) showed a higher insulin response in the Light vs the Dark group (p= 0.029). The change in HR was positively correlated with the change in the 60-min. AUC of insulin (R= 0.46, p= 0.049). Conclusion A single overnight light exposure acutely increases heart rate during sleep and decreases insulin sensitivity the following day and these responses appear to be associated, suggesting that elevated autonomic activity in response to light at night impacts next day metabolic responses. Support (if any) Center for Circadian and Sleep Medicine, UL1TR001422

Hopfer-etal-HopsPerception-preprint

Hops, the flowers of the Humulus lupus plant, is almost exclusively used in beer production, where they add important flavor qualities, such as bitter taste and a variety of aromas, to the finished product. Depending on concentration, variety, and time of addition, different beer styles are created, appealing to a broad range of consumer needs. Consumers of different beer styles both state and reveal a strong preference for their respective preferred style, presumably due to the unique aromas and flavors experienced with different styles. Here we use several rapid profiling methods – free sorting (FS) in combination with check-all-that-apply (CATA) – to perceptually characterize nine samples of hops (7 varieties; 2 blind duplicates) with naïve participants who had been segmented by their typical beer consumption habits (craft versus light beer consumers). The ‘light’ group (n=30) exclusively consumed light, American lager beer styles while the ‘craft’ group (n=32) exclusively consumed what they considered ‘craft’ or ‘micro-brew’ beers. All participants were asked to first sort the hop samples into groups based solely on perceptual similarity; they were then asked to endorse a list of 24 common hops aroma descriptors in a CATA task. Sorting data were used to generate perceptual maps via DISTATIS. Inspection of the perceptual maps indicate participants successfully differentiated between hop samples, and no differences in the number of groups formed between the two consumer groups were found; however, the two cohorts grouped hops samples differently, and resulting maps showed little agreement. Further, light-style beer drinkers checked significantly fewer attributes in the CATA task to describe their hops groups and were also less discriminating between the hops samples relative to the craft-style beer consumers. These data suggest free sorting can be used to profile hops, and observed differences between types of beer drinkers are both perceptual and linguistic in nature.

Blue light insertion at night is involved in sleep and arousal-promoting response delays and depressive-like emotion in mice

Light plays a direct crucial role in the switch between sleep and arousal and the regulation of physiology and behaviour, such as circadian rhythms and emotional change. Artificial lights, which are different from natural light sources with a continuous light spectrum, are composed of three single-colour lights and are increasingly applied in modern society. However, in vivo research on the mechanisms of blue light-regulated sleep and arousal is still insufficient. In this work, we detected the effects of inserting white or blue light for 1 h during the dark period on the wheel-running activity and sucrose preference of C57 mice. The results showed that blue light could induce delays in sleep and arousal-promoting responses. Furthermore, this lighting pattern, including blue light alone, induced depressive-like emotions. The c-fos expression in the blue light group was significantly higher in the arcuate hypothalamic nucleus (Arc) and significantly lower in the cingulate cortex (Cg) and anterior part of the paraventricular thalamic nucleus (PVA) than in the white light group. Compared with the white light group, the phospho-ERK expression in the paraventricular hypothalamic nucleus (PVN) and PVA was lower in the blue light group. These molecular changes indicated that certain brain regions are involved in blue light-induced response processes. This study may provide useful information to explore the specific mechanism of special light-regulated physiological function.

Environmental hazard of loparite ore dressing tailings

Mobilization of environmentally hazardous elements from loparite ore tailings when exposed to various leaching agents was studied in laboratory conditions. Leaching of pollutants from fresh tailings when exposed to atmospheric precipitation and the processes of interaction of mature tailings dust particles (-0.071 mm) with soil water were examined. It was found that in both cases, there is an intensive decomposition of the minerals making up the tailings and conversion of heavy metals (Zn, Mn, Sr) and rare earth elements of the light group (La - Sm) into a dissolved, and therefore bioavailable form. At the same time, the pollutant concentrations were many times higher than the maximum permissible concentrations for fishery water bodies. The results of the experiments indicate the environmental hazard associated with loparite ore concentration tailings due to the pollution of environment with heavy metals and rare earth elements released when the tailings interact with rainwater and soil water.

Transcriptome analysis of genes and pathways associated with metabolism in Scylla paramamosain under different light intensities during indoor overwintering

Background Scylla paramamosain is one of the commercially crucial marine crustaceans belonging to the genus Scylla, which is commonly distributed along the coasts of China, Vietnam, and Japan. Genomic and transcriptomic data are scarce for the mud crab. Light intensity is one of the ecological factors that affect S. paramamosain during indoor overwintering. To understand the energy metabolism mechanism adapted to light intensity, we analyzed the transcriptome of S. paramamosain hepatopancreas in response to different light intensities (0, 1.43, 40.31 μmol·m− 2·s− 1). Results A total of 5052 differentially expressed genes were identified in low light group (LL group, 3104 genes were up-regulated and 1948 genes were down-regulated). A total of 7403 differentially expressed genes were identified in high light group (HL group, 5262 genes were up-regulated and 2141 genes were down-regulated). S. paramamosain adapts to different light intensity environments through the regulation of amino acids, fatty acids, carbon and energy metabolism. Different light intensities had a strong impact on the energy generation of S. paramamosain by influencing oxygen consumption rate, aerobic respiration, glycolysis/gluconeogenesis pathway, the citrate cycle (TCA cycle) and fatty acid degradation. Conclusion Low light is more conducive to the survival of S. paramamosain, which needs to produce and consume relatively less energy to sustain physiological activities. In contrast, S. paramamosain produced more energy to adapt to the pressure of high light intensities. The findings of the study add to the knowledge of regulatory mechanisms related to S. paramamosain metabolism under different light intensities.

Factors Affecting Persistent Postoperative Pain in Patients with Hip Fractures

Osteoporotic fractures are common among older people, and hip fractures (HF) can be devastating. Surgery is indicated for most cases of HF, and chronic persistent postoperative pain is likely to occur. This study investigated the multifaceted factors related to persistent pain occurring during the acute phase and subacute phase of recovery after HF surgery. We conducted a prospective 8-week study of older HF patients after surgery. We evaluated pain intensity, depression symptoms, the fear of falling, pain catastrophizing, cognition and attention, the ability to perform activities of daily living, and the physical performance at 2 weeks (acute phase) and at 4 weeks (subacute phase) after surgery. Patients were divided into the light group (Verbal Rating Scale (VRS) score ≤1) and severe group (VRS score ≥2) according to pain intensity at 8 weeks (recovery phase) after surgery. Factors affecting persistent postoperative pain during recovery were examined using logistic regression analysis. Seventy-two patients were analyzed: 50 in the light group and 22 in the severe group. In the severe group, pain with movement and Pain Catastrophizing Scale scores were higher than those of the light group at 2 weeks and at 4 weeks after surgery. The regression analysis showed that pain with movement at 2 weeks and at 4 weeks after surgery and pain catastrophizing at 4 weeks after surgery were related to persistent postoperative pain. HF patients may have persistent pain if they continue to experience pain and catastrophize their pain during the acute phase and subacute phase after surgery.