Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

The effect of Fluoxetine on Ouabain-induced toxicity in isolated atrium of guinea pig

History and Objectives: Fluoxetine is an anti-depressant drug that specifically inhibits serotonin re-uptake. Since fluoxetine can lead to bradycardia and may have pro-arrhythmic and anti-arrhythmic properties, this study was carried out to evaluate the effect of fluoxetine on ouabain-induced arrhythmia in isolated atrium of Guinea pig. Materials and Methods: In this study, Guinea pigs from both sexes (350-600 g) were used. The animal’s atrium was totally isolated from the ventricle. Thirty-two isolated atria were studied in 4 groups, that is, control, fluoxetine, ouabain and ouabain in combination with fluoxetine. The isolated atria were inserted into modified Oxygenated Krebs solution. Therefore, the mentioned drugs were added to the bath and 20 min later, ionic content of the tissue was measured. Results: Fluoxetine (2-16 µg) can produce a short increase in contractile force (4 min), but finally decrease force and rate of isolated atrium. Ouabain (1.2 µg/ml) can lead to atrial arrhythmic after 1.5 min and after 16 min leads to total toxicity, asystole and atrial cease. Fluoxetine pretreatment (4 µg/ml) can delay the occurrence of arrhythmia up to 5 min (P<0.05). Meanwhile, survival time for atrium increased to greater than 40 min (P<0.05). Ionic measurement of atrial tissue showed that ouabain by itself can increase the level of sodium, but no such effect on potassium and calcium levels. In addition, fluoxetine in itself can significantly increase potassium level (P<0.05). Administration of fluoxetine and therefore, ouabain can attenuate the toxic effect of ouabain on ionic changes and even return it to normal level. Conclusion and Recommendations: It is concluded that fluoxetine has a direct negative inotropic and chronotropic effect on isolated atrium as a possible result of inhibition of sodium and calcium channels and it can probably prevent ouabain-induced toxicity and arrhythmia in atrium of Guinea pig through stabilization of cell membrane and/or prevention of ionic changes that is a quinidine-like effect

The effect of various conductivity and viscosity models considering Brownian motion on nanofluids mixed convection flow and heat transfer

In this paper the effect of using various models for conductivity and viscosity considering Brownian motion of nanoparticles is investigated. This study is numerically conducted inside a cavity full of Water-Al2O3 nanofluid at the case of mixed convection heat transfer. The effect of some parameters such as the nanoparticle volume fraction, Rayleigh, Richardson and Reynolds numbers has been examined. The governing equations with specified boundary conditions has been solved using finite volume method. A computer code has been prepared for this purpose. The results are presented in form of stream functions, isotherms, Nusselt number and the flow power with and without the Brownian motion taken into consideration. The results show that for all the applied models the stream functions and isotherm have approximately same patterns and no considerable difference has been observed. In all the studied models when considering the Brownian motion, the average Nusselt number is higher than not taking this effect into account. The models of Koo-Kleinstreuer and Li-Kleinstreuer give almost same values for the maximum stream function and average Nusselt number. It is also true about the models of Vajjha-Das and Xiao et al

Large Extracellular Vesicle Characterization and Association with Circulating Tumor Cells in Metastatic Castrate Resistant Prostate Cancer

Liquid biopsies hold potential as minimally invasive sources of tumor biomarkers for diagnosis, prognosis, therapy prediction or disease monitoring. We present an approach for parallel single-object identification of circulating tumor cells (CTCs) and tumor-derived large extracellular vesicles (LEVs) based on automated high-resolution immunofluorescence followed by downstream multiplexed protein profiling. Identification of LEVs >6 µm in size and CTC enumeration was highly correlated, with LEVs being 1.9 times as frequent as CTCs, and additional LEVs were identified in 73% of CTC-negative liquid biopsy samples from metastatic castrate resistant prostate cancer. Imaging mass cytometry (IMC) revealed that 49% of cytokeratin (CK)-positive LEVs and CTCs were EpCAM-negative, while frequently carrying prostate cancer tumor markers including AR, PSA, and PSMA. HSPD1 was shown to be a specific biomarker for tumor derived circulating cells and LEVs. CTCs and LEVs could be discriminated based on size, morphology, DNA load and protein score but not by protein signatures. Protein profiles were overall heterogeneous, and clusters could be identified across object classes. Parallel analysis of CTCs and LEVs confers increased sensitivity for liquid biopsies and expanded specificity with downstream characterization. Combined, it raises the possibility of a more comprehensive assessment of the disease state for precise diagnosis and monitoring

Cross-Diagnosis Structural Correlates of Autistic-Like Social Communication Differences

Social communication differences are seen in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD), but the brain mechanisms contributing to these differences remain largely unknown. To address this gap, we used a data-driven and diagnosis-agnostic approach to discover brain correlates of social communication differences in ASD, ADHD, and OCD, and subgroups of individuals who share similar patterns of brain-behavior associations. A machine learning pipeline (regression clustering) was used to discover the pattern of association between structural brain measures (volume, surface area, and cortical thickness) and social communication abilities. Participants (n = 416) included children with a diagnosis of ASD (n = 192, age = 12.0[5.6], 19% female), ADHD (n = 109, age = 11.1[4.1], 18% female), or OCD (n = 50, age = 12.3[4.2], 42% female), and typically developing controls (n = 65, age = 11.6[7.1], 48% female). The analyses revealed (1) associations with social communication abilities in distributed cortical and subcortical networks implicated in social behaviors, language, attention, memory, and executive functions, and (2) three data-driven, diagnosis-agnostic subgroups based on the patterns of association in the above networks. Our results suggest that different brain networks may contribute to social communication differences in subgroups that are not diagnosis-specific