Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics.

Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients' saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects ( p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity

Metabolomic analysis of human oral cancer cells with adenylate kinase 2 or phosphorylate glycerol kinase 1 inhibition.

The purpose of this study was to use liquid chromatography-mass spectrometry (LC-MS) with XCMS for a quantitative metabolomic analysis of UM1 and UM2 oral cancer cells after knockdown of metabolic enzyme adenylate kinase 2 (AK2) or phosphorylate glycerol kinase 1 (PGK1). UM1 and UM2 cells were initially transfected with AK2 siRNA, PGK1 siRNA or scrambled control siRNA, and then analyzed with LC-MS for metabolic profiles. XCMS analysis of the untargeted metabolomics data revealed a total of 3200-4700 metabolite features from the transfected UM1 or UM2 cancer cells and 369-585 significantly changed metabolites due to AK2 or PGK1 suppression. In addition, cluster analysis showed that a common group of metabolites were altered by AK2 knockdown or by PGK1 knockdown between the UM1 and UM2 cells. However, the set of significantly changed metabolites due to AK2 knockdown was found to be distinct from those significantly changed by PGK1 knockdown. Our study has demonstrated that LC-MS with XCMS is an efficient tool for metabolomic analysis of oral cancer cells, and knockdown of different genes results in distinct changes in metabolic phenotypes in oral cancer cells

Characterization of Electronic Cigarette Aerosol and Its Induction of Oxidative Stress Response in Oral Keratinocytes.

In this study, we have generated and characterized Electronic Cigarette (EC) aerosols using a combination of advanced technologies. In the gas phase, the particle number concentration (PNC) of EC aerosols was found to be positively correlated with puff duration whereas the PNC and size distribution may vary with different flavors and nicotine strength. In the liquid phase (water or cell culture media), the size of EC nanoparticles appeared to be significantly larger than those in the gas phase, which might be due to aggregation of nanoparticles in the liquid phase. By using in vitro high-throughput cytotoxicity assays, we have demonstrated that EC aerosols significantly decrease intracellular levels of glutathione in NHOKs in a dose-dependent fashion resulting in cytotoxicity. These findings suggest that EC aerosols cause cytotoxicity to oral epithelial cells in vitro, and the underlying molecular mechanisms may be or at least partially due to oxidative stress induced by toxic substances (e.g., nanoparticles and chemicals) present in EC aerosols

E-cigarette aerosols induce unfolded protein response in normal human oral keratinocytes.

Objective: Since the introduction in 2004, global usage of e-cigarettes (ECs) has risen exponentially. However, the risks of ECs on oral health are uncertain. The purpose of this study is to understand if EC aerosol exposure impacts the gene pathways of normal human oral keratinocytes (NHOKs), particularly the unfolded protein response (UPR) pathway. Materials and methods: EC aerosols were generated reproducibly with a home-made puffing device and impinged into the culture medium for NHOKs. DNA microarrays were used to profile the gene expression changes in NHOKs treated with EC aerosols, and the Ingenuity Pathway Analysis (IPA) was used to reveal signaling pathways altered by the EC aerosols. Quantitative PCR was used to validate the expression changes of significantly altered genes. Results: DNA microarray profiling followed by IPA revealed a number of signaling pathways, such as UPR, cell cycle regulation, TGF-β signaling, NRF2-mediated oxidative stress response, PI3K/AKT signaling, NF-κB signaling, and HGF signaling, activated by EC aerosols in NHOKs. The UPR pathway genes, C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), X box binding protein 1 (XBP1), and inositol-requiring enzyme 1 alpha (IRE1α) were all significantly up-regulated in EC aerosol-treated NHOKs whereas immunoglobulin heavy-chain binding protein (BIP) and PRKR-like ER kinase (PERK) were slightly up-regulated. qPCR analysis results were found to be well correlated with those from the DNA microarray analysis. The most significantly changed genes in EC aerosol-treated NHOKs versus untreated NHOKs were CHOP, ATF4, XBP1, IRE1α and BIP. Meanwhile, Western blot analysis confirmed that CHOP, GRP78 (BIP), ATF4, IRE1α and XBP1s (spliced XBP1) were significantly up-regulated in NHOKs treated with EC aerosols. Conclusion: Our results indicate that EC aerosols up-regulate the UPR pathway genes in NHOKs, and the induction of UPR response is mediated by the PERK - EIF2α - ATF4 and IRE1α - XBP1 pathways

Association of sildenafil use with age-related macular degeneration:a retrospective cohort study

Objective: Despite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)—a major cause of global blindness—lacks effective treatment to prevent the irreversible degeneration of photoreceptors leading to central vision loss. Limited studies suggest phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may prevent AMD by increasing retinal blood flow. This study explores the potential association between sildenafil use and AMD risk in men with erectile dysfunction using UK data. Methods and analysis: Using the UK’s IQVIA Medical Research Data, the study analysed 31 575 men prescribed sildenafil for erectile dysfunction and no AMD history from 2007 to 2015, matched with a comparator group of 62 155 non-sildenafil users in a 1:2 ratio, over a median follow-up of approximately three years. Results: The primary outcome was the incidence of AMD in the two groups. The study found no significant difference in AMD incidence between the sildenafil users and the non-users, with an adjusted hazard ratio (HR) of 0.99 (95% CI 0.84 to 1.16), after accounting for confounders such as age, ethnicity, Townsend deprivation quintile, body mass index category, and diagnosis of hypertension and type 2 diabetes. Conclusion: The study results indicated no significant association between sildenafil use and AMD prevention in UK men with erectile dysfunction, suggesting sildenafil’s protective effect on AMD is likely insignificant

New Frontiers for Terrestrial-sized to Neptune-sized Exoplanets In the Era of Extremely Large Telescopes

Surveys reveal that terrestrial- to Neptune-sized planets (1 $< R <$ 4 R$_{\rm{Earth}}$) are the most common type of planets in our galaxy. Detecting and characterizing such small planets around nearby stars holds the key to understanding the diversity of exoplanets and will ultimately address the ubiquitousness of life in the universe. The following fundamental questions will drive research in the next decade and beyond: (1) how common are terrestrial to Neptune-sized planets within a few AU of their host star, as a function of stellar mass? (2) How does planet composition depend on planet mass, orbital radius, and host star properties? (3) What are the energy budgets, atmospheric dynamics, and climates of the nearest worlds? Addressing these questions requires: a) diffraction-limited spatial resolution; b) stability and achievable contrast delivered by adaptive optics; and c) the light-gathering power of extremely large telescopes (ELTs), as well as multi-wavelength observations and all-sky coverage enabled by a comprehensive US ELT Program. Here we provide an overview of the challenge, and promise of success, in detecting and comprehensively characterizing small worlds around the very nearest stars to the Sun with ELTs. This white paper extends and complements the material presented in the findings and recommendations published in the National Academy reports on Exoplanet Science Strategy and Astrobiology Strategy for the Search for Life in the Universe.Comment: Astro2020 Science White Pape

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Copyright © 2014 Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Hybrid type-I InAs/GaAs and type-II GaSb/GaAs quantum dot structure with enhanced photoluminescence

We investigate the photoluminescence (PL) properties of a hybrid type-I InAs/GaAs and type-II GaSb/GaAs quantum dot (QD) structure grown in a GaAs matrix by molecular beam epitaxy. This hybrid QD structure exhibits more intense PL with a broader spectral range, compared with control samples that contain only InAs or GaSb QDs. This enhanced PL performance is attributed to additional electron and hole injection from the type-I InAs QDs into the adjacent type-II GaSb QDs. We confirm this mechanism using time-resolved and power-dependent PL. These hybrid QD structures show potential for high efficiency QD solar cell applications

Controlled Dephasing of Electrons by Non-Gaussian Shot Noise

In a 'controlled dephasing' experiment [1-3], an interferometer loses its coherence due to entanglement with a controlled quantum system ('which path' detector). In experiments that were conducted thus far in mesoscopic systems only partial dephasing was achieved. This was due to weak interactions between many detector electrons and the interfering electron, resulting in a Gaussian phase randomizing process [4-10]. Here, we report the opposite extreme: a complete destruction of the interference via strong phase randomization only by a few electrons in the detector. The realization was based on interfering edge channels (in the integer quantum Hall effect regime, filling factor 2) in a Mach-Zehnder electronic interferometer, with an inner edge channel serving as a detector. Unexpectedly, the visibility quenched in a periodic lobe-type form as the detector current increased; namely, it periodically decreased as the detector current, and thus the detector's efficiency, increased. Moreover, the visibility had a V-shape dependence on the partitioning of the detector current, and not the expected dependence on the second moment of the shot noise, T(1-T), with T the partitioning. We ascribe these unexpected features to the strong detector-interferometer coupling, allowing only 1-3 electrons in the detector to fully dephase the interfering electron. Consequently, in this work we explored the non-Gaussian nature of noise [11], namely, the direct effect of the shot noise full counting statistics [12-15].Comment: 14 pages, 4 figure