1,721,009 research outputs found
Concise Review: Perspectives and Clinical Implications of Bone Marrow and Circulating Stem Cell Defects in Diabetes
No full textDiabetes mellitus is a complex systemic disease characterized by severe morbidity and excess mortality. The burden of its multiorgan complications relies on an imbalance between hyperglycemic cell damage and defective endogenous reparative mechanisms. Inflammation and abnormalities in several hematopoietic components are typically found in diabetes. The discovery that diabetes reduces circulating stem/progenitor cells and impairs their function has opened an entire new field of study where diabetology comes into contact with hematology and regenerative medicine. It is being progressively recognized that such rare circulating cell populations mirror finely regulated processes involved in hematopoiesis, immunosurveillance, and peripheral tissue homeostasis. From a clinical perspective, pauperization of circulating stem cells predicts adverse outcomes and death. Furthermore, studies in murine models and humans have identified the bone marrow (BM) as a previously neglected site of diabetic end-organ damage, characterized by microangiopathy, neuropathy, fat deposition, and inflammation. As a result, diabetes impairs the mobilization of BM stem/progenitor cells, a defect known as mobilopathy or myelokathexis, with negative consequences for physiologic hematopoiesis, immune regulation, and tissue regeneration. A better understanding of the molecular and cellular processes that govern the BM stem cell niche, cell mobilization, and kinetics in peripheral tissues may uncover new therapeutic strategies for patients with diabetes. This concise review summarizes the current knowledge on the interplay between the BM, circulating stem cells, and diabetes, and sets the stages for future developments in the field. Stem Cells 2017;35:106–116
Estrogen receptor functions and pathways at the vascular immune interface
Full text linkEstrogen receptor (ER) activity mediates multiple physiological processes in the cardiovascular system. ERα and ERβ are ligand-activated transcription factors of the nuclear hormone receptor superfamily, while the G protein-coupled estrogen receptor (GPER) mediates estrogenic signals by modulating non-nuclear second messengers, including activation of the MAP kinase signaling cascade. Membrane localizations of ERs are generally associated with rapid, non-genomic effects while nuclear localizations are associated with nuclear activities/transcriptional modulation of target genes. Gender dependence of endothelial biology, either through the action of sex hormones or sex chromosome-related factors, is becoming increasingly evident. Accordingly, cardiometabolic risk increases as women transition to menopause. Estrogen pathways control angiogenesis progression through complex mechanisms. The classic ERs have been acknowledged to function in mediat-ing estrogen effects on glucose metabolism, but 17β-estradiol also rapidly promotes endothelial glycolysis by increasing glucose transporter 1 (GLUT1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) levels through GPER-dependent mechanisms. Estrogens alter monocyte and macrophage phenotype(s), and induce effects on other estrogen-responsive cell lineages (e.g., secretion of cytokines/chemokines/growth factors) that impact macrophage function. The pharmacological modulation of ERs for therapeutic purposes, however, is particularly challenging due to the lack of ER subtype selectivity of currently used agents. Identifying the determinants of biological responses to estrogenic agents at the vascular immune interface and developing targeted pharmacological interventions may result in novel improved therapeutic solutions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Post-transcriptional and epigenetic regulation of estrogen signaling
Full text linkPost-translational and epigenetic regulation are important mechanisms controlling functions of genes and proteins. Although the "classic" estrogen receptors (ERs) have been acknowledged to function in mediating estrogen effects via transcriptional mechanisms, estrogenic agents modulate the turnover of several proteins via post-transcriptional and post-translational pathways including epigenetics. For instance, the metabolic and angiogenic action of G-protein coupled estrogen receptor (GPER) in vascular endothelial cells has been recently elucidated. By interacting with GPER, 17β-estradiol (E2) and the GPER agonist G1 enhance endothelial stability of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and capillary tube formation by increasing ubiquitin specific peptidase 19 (USP19) levels, thereby reducing PFKFB3 ubiquitination and proteasomal degradation. In addition to ligands, the functional expression and trafficking of ERs can be modulated by post-translational modification, including palmitoylation. MicroRNAs (miRNAs), the most abundant form of endogenous small RNAs in humans, regulate multiple target genes and are at the center of the multi-target regulatory network. This review discusses also the emerging evidence how miRNAs affect glycolytic metabolism in cancer, as well as their regulation by estrogens. Restoring dysregulated miRNA expression represents a promising strategy to counteract the progression of cancer and other disease conditions. Accordingly, estrogen posttranscriptional regulatory and epigenetic mechanisms represent novel targets for pharmacological and non-pharmacological intervention for the treatment and prevention of hormone-sensentive non-communicable diseases, including estrogen-sensitive cancers of the reproductive system in women
Diabetes pharmacotherapy and circulating stem/progenitor cells. State of the art and evidence gaps
No full textDiabetes is burdened with the development of several end-organ complications leading to excess mortality. Though the causes of such organ damage are far from being clarified, diabetes has been redefined as a disease of impaired damage control, wherein ongoing damage is not adequately compensated by activation of repair processes. Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) and their descendants endothelial progenitor cells (EPCs) have been extensively studied as major players in tissue homeostasis as well as biomarkers of diabetic complication risk. Thus, strategies to raise the levels of circulating HSPCs/EPCs have attracted interest for their potential to modify the future risk of complications. We herein discuss state-of-the-art of the effects exerted by diabetes pharmacotherapy on such cell populations. Further, we highlight which outstanding questions remain to be addressed for a more comprehensive understanding of this topic
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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