BACKGROUND: High-intensity visible light (HEV), also referred to as blue light, has a wavelength of 400-500 nm and accounts for approximately one-third of the visible light. Blue light is also emitted from electronic devices and artificial indoor lighting. Studies have shown that exposure of human skin cells to light emitted from electronic devices, even as short as 1 h, can cause an increase in reactive oxygen species (ROS), apoptosis and necrosis. Despite comprising a significant portion of the light spectrum, the effects of HEV light have not been studied as extensively. This is in part due to a lack of suitable in vitro testing methods. This work was conducted in order to develop a reproducible testing method for assessing the effects of blue light on the skin.
METHODS: Testing was performed using a full thickness, 3D in vitro skin tissue model. Different exposure protocols were tested to (1) determine the biological effects of blue light on the skin and (2) to identify an appropriate exposure for routine testing of cosmetic materials that may protect the skin from blue light damage. Gene expression and protein biomarkers were measured using qPCR, ELISA and immunohistochemical (IHC) methods.
RESULTS: Our work demonstrates that daily exposure to blue light produced dose-and-time-dependent changes in biomarkers associated with skin damage. Exposure to blue light for 6 h for 5 consecutive days (total intensity of 30 J/cm2 ) increased the expression of genes that regulate inflammation and oxidative stress pathways and decreased the expression of genes that maintain skin barrier and tissue integrity. Exposure to blue light significantly increased protein biomarkers associated with ageing, inflammation and tissue damage. IHC staining confirmed changes in collagen, filaggrin and NQO1 protein expression. Treatment with ascorbic acid inhibited the effects of blue light, demonstrating a role in protection from blue light.
CONCLUSIONS: Our results showed that consistent blue light exposure produced skin damage via alterations in biological pathways that are associated with skin ageing. This work provides a new, reproducible in vitro testing method for assessing the effects of blue light on human skin using gene expression, protein ELISA and IHC staining.
BACKGROUND: La lumière visible à haute énergie (VHE), également appelée lumière bleue, a une longueur d’onde de 400 à 500 nm et représente environ un tiers de la lumière visible. La lumière bleue est également émise par les appareils électroniques et l’éclairage intérieur artificiel. Des études ont montré que l’exposition des cellules cutanées humaines à la lumière émise par les appareils électroniques, même pour une période de seulement 1 h, peut entraîner une augmentation des dérivés réactifs de l’oxygène (DRO), de l’apoptose et de la nécrose. Bien qu’ils représentent une partie importante du spectre lumineux, les effets de la lumière VHE n’ont pas été étudiés aussi largement. Cela est en partie dû à un manque de méthodes de test in vitro appropriées. Ces travaux ont été réalisé afin de développer une méthode de test reproductible pour évaluer les effets de la lumière bleue sur la peau. MÉTHODES: Les tests ont été réalisés à l’aide d’un modèle de tissu cutané 3D in vitro de pleine épaisseur. Différents protocoles d’exposition ont été testés pour (1) déterminer les effets biologiques de la lumière bleue sur la peau et (2) identifier une exposition appropriée pour les tests de routine des produits cosmétiques susceptibles de protéger la peau des dommages causés par la lumière bleue. L’expression génique et les biomarqueurs protéiques ont été mesurés à l’aide des méthodes de PCR quantitative, de dosage par la méthode immuno-enzymatique ELISA et immunohistochimiques (IHC). RÉSULTATS: Nos travaux démontrent que l’exposition quotidienne à la lumière bleue a produit des modifications dépendantes de la dose et du temps dans les biomarqueurs associés aux lésions cutanées. L’exposition à la lumière bleue pendant 6 h au cours de 5 jours consécutifs (intensité totale de 30 J/cm2) a augmenté l’expression des gènes qui régulent l’inflammation et les voies du stress oxydatif, et a diminué l’expression des gènes qui maintiennent la barrière cutanée et l’intégrité tissulaire. L’exposition à la lumière bleue a significativement augmenté les biomarqueurs protéiques associés au vieillissement, à l’inflammation et aux lésions tissulaires. La coloration par IHC a confirmé les modifications de l’expression du collagène, de la filaggrine et de la protéine NQO1. Le traitement par acide ascorbique a inhibé les effets de la lumière bleue, démontrant un rôle dans la protection contre la lumière bleue.
CONCLUSIONS: Nos résultats ont montré qu’une exposition continue à la lumière bleue produisait des lésions cutanées par le biais d’altérations des voies biologiques associées au vieillissement de la peau. Ces travaux fournissent une nouvelle méthode de test in vitro reproductible pour évaluer les effets de la lumière bleue sur la peau humaine à l’aide de l’expression des gènes, du test ELISA de détection de protéines et de la coloration IHC.

The effect of oxaprozin (OXP) on an experimental model of seizures in rats was investigated in this study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg). The anticonvulsant effect of OXP (100, 200, and 400 mg/kg, intraperitoneally) was evaluated in a seizure model. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for antioxidant assays (nitric oxide (NO) and glutathione (GSH)). The animals\' brains were also isolated to gauge the relative expression of genes in the oxidative stress pathway (sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)). Intraperitoneal injection of OXP increased the mean latency of myoclonic jerks and generalized tonic-clonic seizure (GTCS) and decreased the number of myoclonic jerks and GTCS duration compared with the PTZ group. Biochemical tests showed that pretreatment with OXP was able to restore GSH serum levels and reverse the augmented NO serum levels caused by PTZ induction to the normal level. The quantitative polymerase chain reaction results also revealed that OXP counteracts the negative effects of PTZ by affecting the expression of the Sirt1 and Pgc1α genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal, anti-inflammatory OXP drug in a model of neural impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Genomic reorganization, such as rearrangements and inversions, influences how genetic information is organized within the bacterial genomes. Inversions, in particular, facilitate genome evolution through gene gain and loss, and can alter gene expression. Previous studies have investigated the impact inversions have on gene expression induced inversions targeting specific genes or examine inversions between distantly related species. This fails to encompass a genome-wide perspective of naturally occurring inversions and their post-adaptation impact on gene expression. Here, we used bioinformatic techniques and multiple RNA-seq datasets to investigate the short- and long-range impact inversions have on genomic gene expression within Escherichia coli. We observed differences in gene expression between homologous inverted and non-inverted genes even after long-term exposure to adaptive selection. In 4% of inversions representing 33 genes, differential gene expression between inverted and non-inverted homologs was detected, with greater than two-thirds (71%) of differentially expressed inverted genes having 9.4-85.6-fold higher gene expression. The identified inversions had more overlap than expected with nucleoid-associated protein binding sites, which assist in the regulation of genomic gene expression. Some inversions can drastically impact gene expression, even between different strains of E. coli, and could provide a mechanism for the diversification of genetic content through controlled expression changes.

We are taking advantage of the launch of the latest version (v4.6) of our web-based data mining tool \"breast cancer gene-expression miner\" (bc-GenExMiner) to take stock of its position within the oncology research landscape and to present an activity report ten years after its establishment (http://bcgenex.ico.unicancer.fr). bc-GenExMiner is an open-access, user-friendly tool for statistical mining on breast tumor transcriptomes, annotated with more than 20 clinicopathologic and molecular characteristics. The database comprises more than 16,000 patients from 64 cohorts - including TCGA, METABRIC and SCAN-B - for whom several thousands of genes have been quantified by microarrays or RNA-seq. Correlation, expression and prognostic analyses are available for targeted, exhaustive or customized explorations of queried genes. bc-GenExMiner facilitates the validation, investigation, and prioritization of discoveries and hypotheses on genes of interest. It allows users to analyse large databases, create data visualizations, and obtain robust statistical analysis, thereby accelerating biomarker discovery. Ten years after its launch, judging by the number of visits, analyses, and scientific citations of bc-GenExMiner, we conclude that this web resource serves its purpose in the international scientific community working in breast cancer research, with a never-ending rise in its use.

The tall wheatgrass species Thinopyrum elongatum carries on the long arm of chromosome 7E, a locus that contributes strongly to resistance to fusarium head blight (FHB), a devastating fungal disease affecting wheat crops in all temperate areas of the world. Introgression of Th. elongatum 7E chromatin into chromosome 7D of wheat was induced by the ph1b mutant of CS. Recombinants between chromosome 7E and wheat chromosome 7D, induced by the ph1b mutation, were monitored by a combination of molecular markers and phenotyping for FHB resistance. Progeny of up to five subsequent generations derived from two lineages, 64-8 and 32-5, were phenotyped for FHB symptoms and genotyped using published and novel 7D- and 7E-specific markers. Fragments from the distal end of 7EL, still carrying FHB resistance and estimated to be less than 114 and 66 Mbp, were identified as introgressed into wheat chromosome arm 7DL of progeny derived from 64-8 and 32-5, respectively. Gene expression analysis revealed variation in the expression levels of genes from the distal ends of 7EL and 7DL in the introgressed progeny. The 7EL introgressed material will facilitate the use of the 7EL FHB resistance locus in wheat breeding programs.

WUSCHEL-related homeobox (WOX) proteins are plant-specific transcription factors that are profoundly involved in regulation of plant development and stress responses. In this study, we totally identified 11 WOX transcription factor family members in cucumber (Cucumis sativus, CsWOX) genome and classified them into three clades with nine subclades based on phylogenetic analysis results. Alignment of amino acid sequences revealed that all WOX members in cucumber contained the typical homeodomain, which consists of 60-66 amino acids and is folded into a helix-turn-helix structure. Gene duplication event analysis indicated that CsWOX1a and CsWOX1b were a segment duplication pair, which might affect the number of WOX members in cucumber genome. The expression profiles of CsWOX genes in different tissues demonstrated that the members sorted into the ancient clade (CsWOX13a and CsWOX13b) were constitutively expressed at higher levels in comparison to the others. Cis-element analysis in promoter regions suggested that the expression of CsWOX genes was associated with phytohormone pathways and stress responses, which was further supported by RNA-seq data. Taken together, our results provide new insights into the evolution of cucumber WOX genes and improve our understanding about the biological functions of the CsWOX gene family.

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

Chronic endurance exercise is a therapeutic strategy in the treatment of many chronic diseases in humans, including the prevention and treatment of metabolic diseases such as diabetes mellitus. Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified. In the liver, however, the cellular and molecular pathways that are modified by exercise and have preventive or therapeutic relevance to metabolic disease need to be elucidated. The mouse model used in the current study allows for the quantification of a human-relevant exercise \"dosage\". In this study we show hepatic gene expression differences between sedentary female and sedentary male mice and that chronic exercise modifies the transcription of hepatic genes related to metabolic disease and steatosis in both male and female mice. Chronic exercise induces molecular pathways involved in glucose tolerance, glycolysis, and gluconeogenesis while producing a decrease in pathways related to insulin resistance, steatosis, fibrosis, and inflammation. Given these findings, this mouse exercise model has potential to dissect the cellular and molecular hepatic changes following chronic exercise with application to understanding the role that chronic exercise plays in preventing human diseases. Novelty: Exercise modifies the hepatic gene expression and hepatic pathways related to metabolic disease in male and female mice. Sex differences were seen in hepatic gene expression between sedentary and exercised mice. The mouse exercise model used in this study allows for application and evaluation of exercise effects in human disease.

Chloroplast ribonucleoproteins (cpRNPs) are implicated in splicing, editing, and stability control of chloroplast RNAs as well as in regulating development and stress tolerance. To facilitate a comprehensive understanding of their functions, we carried out a genome-wide identification, curation, and phylogenetic analysis of cpRNP genes in Oryza sativa (rice) and Arabidopsis thaliana (Arabidopsis). Ten cpRNP genes were identified in each of Arabidopsis and rice genomes based on the presence of two RRM (RNA-recognition motif) domains and an N-terminal chloroplast targeting signal peptide in the predicted proteins. These proteins are localized to chloroplasts. Gene expression analysis revealed that cpRNP genes have differential tissue expression patterns and some cpRNP genes are induced by abiotic stresses such as cold, heat, and drought. Taken together, our study provides a comprehensive annotation of the cpRNP gene family and their expression patterns in Arabidopsis and rice which will facilitate further studies on their roles in plant growth and stress responses.

Candidiasis caused by multidrug-resistant Candida species continues to be difficult to eradicate. The use of live probiotic bacteria has gained a lot of interest in the treatment of candidiasis; however, whole-cell probiotic use can often be associated with a high risk of sepsis. Strategies manipulating cell-free methods using probiotic strains could lead to the development of novel antifungal solutions. Therefore, we evaluated the effect of three probiotic cell-free extracts (CFEs) on the growth, virulence traits, and drug efflux pumps in C. albicans. On the basis of its minimum inhibitory concentration, Lactobacillus rhamnosus was selected and assessed against various virulence traits and drug resistance mechanisms. The results showed that L. rhamnosus CFE significantly inhibited hyphae formation and reduced secretion of proteinases and phospholipases. Moreover, L. rhamnosus inhibited the drug efflux proteins in resistant C. albicans strains thus reversing drug resistance. Gene expression data confirmed downregulation of genes associated with microbial virulence and drug resistance following treatment of C. albicans with L. rhamnosus CFE. Through gas chromatography - mass spectrometry chemical characterization, high contents of oleic acid (24.82%) and myristic acid (13.11%) were observed in this CFE. Collectively, our findings indicate that L. rhamnosus may potentially be used for therapeutic purposes to inhibit C. albicans infections.