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Skin -- Genetic aspects

Fibroblasts have long been recognized as important stromal cells, playing key roles in synthesizing and maintaining the extracellular matrix, but historically were treated as a relatively uniform cell type. Studies in recent years have revealed a surprising level of heterogeneity of fibroblasts across tissues, and even within organs such as the skin and heart. This heterogeneity may have functional consequences, including during stress and disease. While the field has moved forward quickly to begin to address the scientific import of this heterogeneity, the descriptive language used for these cells has not kept pace, particularly when considering the phenotype changes that occur as fibroblasts convert to myofibroblasts in response to injury. We discuss here the nature and sources of the heterogeneity of fibroblasts, and review how our understanding of the complexity of the fibroblast to myofibroblast phenotype conversion has changed with increasing scrutiny. We propose that the time is opportune to reevaluate how we name and describe these cells, particularly as they transition to myofibroblasts through discrete stages. A standardized nomenclature is essential to address the confusion that currently exists in the literature as to the usage of terms like myofibroblast and the description of fibroblast phenotype changes in disease. Key words: fibroblast, myofibroblast, phenotype conversion, heart, dermis, pressure overload, infarction, scar. Les fibroblastes sont depuis longtemps reconnus comme etant des cellules stromales importantes, qui jouent des roles cles dans la synthese et le maintien de la matrice extracellulaire, mais qui ont historiquement ete traitees comme constituant un type cellulaire relativement uniforme. Les etudes des dernieres annees ont revele la presence d'un degre etonnamment eleve d'heterogeneite entre les fibroblastes de differents tissus, et meme au sein d'un meme organe, comme la peau et le creur. Cette heterogeneite pourrait avoir des consequences fonctionnelles, notamment en situation de stress ou au cours de processus pathologiques. Alors que le domaine a progresse rapidement pour commencer a aborder l'importance scientifique de cette heterogeneite, le langage descriptif utilise dans le cas de ces cellules n'a pas maintenu le rythme, en particulier quant aux modifications du phenotype qui surviennent lors de la conversion des fibroblastes en myofibroblastes au cours de reactions lesionnelles. Nous discutons ici de la nature et des sources de l'heterogeneite des fibroblastes, et nous proposons une synthese de l'evolution de notre comprehension de la complexite de la conversion du phenotype de fibroblaste a myofibroblaste avec l'intensification de la surveillance de cette transition. Nous proposons que soit venu le temps de reevaluer notre maniere de nommer et de decrire ces cellules, particulierement lors de leur transition vers le myofibroblaste par l'intermediaire de stades distincts. L'adoption d'une nomenclature standardisee est essentielle en vue de mettre fin a la confusion qui prevaut actuellement dans la litterature quant a l'utilisation de termes comme celui de myofibroblaste, ainsi que pour aborder la description des modifications du phenotype des fibroblastes au cours des processus pathologiques. [Traduit par la Redaction] Mots-cles: fibroblaste, myofibroblaste, conversion du phenotype, creur, derme, surcharge de pression, infarctus, cicatrice.

Fibrosis -- Physiological aspects, Fibrosis -- Care and treatment, Heart diseases -- Physiological aspects, Heart diseases -- Care and treatment, and Cardiac patients -- Physiological aspects

Cardiac fibrosis is a significant global health problem that is closely associated with multiple forms of cardiovascular disease, including myocardial infarction, dilated cardiomyopathy, and diabetes. Fibrosis increases myocardial wall stiffness due to excessive extracellular matrix deposition, causing impaired systolic and diastolic function, and facilitating arrhythmogenesis. As a result, patient morbidity and mortality are often dramatically elevated compared with those with cardiovascular disease but without overt fibrosis, demonstrating that fibrosis itself is both a pathologic response to existing disease and a significant risk factor for exacerbation of the underlying condition. The lack of any specific treatment for cardiac fibrosis in patients suffering from cardiovascular disease is a critical gap in our ability to care for these individuals. Here we provide an overview of the development of cardiac fibrosis, and discuss new research directions that have recently emerged and that may lead to the creation of novel treatments for patients with cardiovascular diseases. Such treatments would, ideally, complement existing therapy by specifically focusing on amelioration of fibrosis. Key words: cardiac fibrosis, extracellular matrix, fibrosis therapy, fibroblast, myofibroblast. A l'echelle mondiale, la fibrose cardiaque est un important probleme de sante etroitement lie a diverses formes de maladies cardiaques, y compris l'infarctus du myocarde, la cardiomyopathie dilatee et le diabete. La fibrose entraine une augmentation de la rigidite de la paroi myocardique en raison du depot d'un exces de matrice extracellulaire, ce qui affecte les fonctions systolique et diastolique et qui favorise l'arythmogenese. En consequence, les taux de morbidite et de mortalite des patients sont souvent considerablement plus eleves qu'en absence de fibrose manifeste, ce qui montre que la fibrose elle-meme est a la fois une reaction pathologique a une maladie existante et un important facteur de risque de l'exacerbation de l'affection sous-jacente. Le manque de tout traitement specifique de la fibrose cardiaque chez les patients atteints de maladie cardiovasculaire constitue une lacune cruciale dans notre capacite de soigner ces personnes. Nous presentons ici un apercu de la formation de fibrose cardiaque, et nous discutons de nouvelles avenues de recherche emergentes qui pourraient mener au developpement de nouveaux traitements pour les patients atteints de maladies cardiovasculaires. Idealement, de tels traitements pourraient apporter un complement aux traitements existants en se centrant specifiquement sur des ameliorations en matiere de fibrose. [Traduit par la Redaction] Mots-cles: fibrose cardiaque, matrice extracellulaire, traitement de la fibrose, fibroblaste, myofibroblaste.

Organic compounds -- Research, Cancer -- Care and treatment, and Cancer -- Research

Background The quinazoline are an important class of medicinal compounds that possess a number of biological activities like anticancer, anticonvulsant and antioxidant etc. Results We evaluated the previously synthesized quinazoline derivatives 1-3 for their anticancer activities against three cancer cell lines (HepG2, MCF-7, and HCT-116). Among the tested compounds, quinazolines 1 and 3 were found to be more potent than the standard drug Vinblastine against HepG2 and MCF-7 cell lines. All the tested compounds had less antioxidant activity and did not exhibit any anticonvulsant activity. Also, molecular docking studies were performed to get an insight into the binding modes of the compounds with human cyclin-dependent kinase 2, butyrylcholinesterase enzyme, human gamma-aminobutyric acid receptor. These compounds showed better docking properties with the CDK2 as compared to the other two enzymes. Conclusions The overall study showed that thioxoquinazolines are suitable antitumor agents and they should be explored for other biological activities. Modification in the available lot of quinazoline and synthesis of its novel derivatives is essential to explore the potential of this class of compounds. The increase in the threat and with the emergence of drug resistance, it is important to explore and develop more efficacious drugs. Keywords: Thioxoquinazolin-4(3H)-one, Anticancer activity, Antioxidant activity, Anticonvulsant activity, Molecular docking

Social networks -- Research and Big data -- Research

Author(s): Matthew Zook 1,*, Solon Barocas 2, danah boyd 2,3, Kate Crawford 2,4, Emily Keller 3, Seeta Pena Gangadharan 5, Alyssa Goodman 6, Rachelle Hollander 7, Barbara A. Koenig 8, [...]