Modulation of macrophage differentiation and activation by paracrine signals from cardiac progenitor cells

Myocardial infarction (MI) triggers an inflammatory response that contributes to cardiac remodelling in adult mice. In contrast, the heart of the post-MI neonatal mouse regenerates without scarring due to an anti-inflammatory macrophage-dependent process. Previously, Noseda and colleagues demonstrated that intramyocardial injection of Lin-Sca1+CD31-PDGFRalpha+SP+ cardiac progenitor/stem cells (CSCs) improved cardiac function. However, despite the lack of long-term engraftment, the cardiac improvement could be explained by paracrine factors released by CSCs. The paracrine effects of CSCs could affect several cell types in the heart, including macrophages. Therefore, this PhD thesis hypothesises that CSCs release paracrine factors that promote a subtype of anti-inflammatory macrophage phenotype to support cardiac regeneration. After flow sorting, single F4/80+CD11b+ macrophages were analysed by single qRT PCR. GM-CSF+LPS+IFNγ-driven M, identified as CX3CR1+CD11b+F4/80loCD206-, co-expressed pro-inflammatory genes, Nos2, Cxcl9, Cxcl10 and Il-6. On the other hand, M-CSF+IL-4+IL-13-driven Mf identified as CX3CR1+CD11b+F4/80+CD206+, upregulated anti-inflammatory genes, Arg1, Angpt2, and Igf1. Notably, CSCs conditioned media (CSC CondM)-driven macrophages were indistinguishable from M-CSF+IL-4+IL-13-Mf. Lastly, CSC CondM+IL4+IL13-driven M group was identified as CX3CR1+CD11b+F4/80+CD206+, expressing Arg1, Angptl2, Igf1, Il1rl1, and Mrc1, and showing a distinct subtype of anti-inflammatory macrophage phenotype compared to all prior reports of anti-inflammatory/M2-like macrophages. After confirming that CSCs secrete M-CSF (20pg/mL) as the potential protective factor, the M-CSF/CSF1R pathway was inhibited by using first the pharmacological inhibitor BLZ945 and then a monoclonal antibody against CSF1R. These inhibitory experiments demonstrated that the inhibition of M-CSF activity reduced cell viability, the percentage of F4/80+CD11b+CX3CR1+CD206+ macrophages, expression of anti-inflammatory and pro-fibrotic genes (Arg1, Angpt2, Igf1, Il1rl1, Mrc1 and Gdf15), and phagocytosis activity. Multiplex bead-based flow immunoassays also showed that CSC CondM+LPS+IFN-Mf secrete IL-10 depending upon the M-CSF/CSF1R pathway. In conclusion, CSC-secreted M-CSF is the indispensable paracrine factor that induces macrophages with an anti-inflammatory phenotype. In conclusion, CSC-secreted M-CSF is the indispensable paracrine factor that induces macrophages with an anti-inflammatory phenotype.Open Acces

Estado de ansiedad previo a la cita odontológica en adolescentes

Introducción: la ansiedad dental, es un fenómeno que influye en los cuidados y estados de la salud bucal y no deja que el paciente tenga un tratamiento bucal optimo, según datos estudiados la ansiedad dental tiene tasas de prevalencia del 4% al 23%, este es un factor importante para trabajar puesto que de lo contrario no se podría llegar a tener una mejora en la calidad de vida oral del paciente Objetivo: describir la ansiedad en adolescentes en la cita odontológica en la “UNIDAD EDUCATIVA ALLURIQUÍN” Método: se realizó un estudio descriptivo y de corte transversal en adolescentes pertenecientes a La Unidad Educativa Alluriquín ubicada en la parroquia de Alluriquín “Santo Domingo” en el año 2022, se trabajó con 37 adolescentes Resultados: se determinó que 25 adolescentes para un 69 % de los encuestados si han sufrido de alguna mala experiencia odontológica al momento de los procedimientos o consultas, los jóvenes no se sienten intranquilos en los días previos de su cita odontológica con 22 adolescentes para un 59 %, 18 adolescentes para un 49 % se sentían relajados antes de un tratamiento odontológico Conclusiones: se determinó que la mayoría de los adolescentes no presentan un alto nivel de ansiedad o temerosidad previo a un día antes de la cita o mientras se encuentran en la sala de espera, en cambio se presentan ansiosos cuando se muestra el instrumental odontológico o tienen desconocimiento del procedimiento que se le va a realizar

Single Cell Gene Expression to Understand the Dynamic Architecture of the Heart.

The recent development of single cell gene expression technologies, and especially single cell transcriptomics, have revolutionized the way biologists and clinicians investigate organs and organisms, allowing an unprecedented level of resolution to the description of cell demographics in both healthy and diseased states. Single cell transcriptomics provide information on prevalence, heterogeneity, and gene co-expression at the individual cell level. This enables a cell-centric outlook to define intracellular gene regulatory networks and to bridge toward the definition of intercellular pathways otherwise masked in bulk analysis. The technologies have developed at a fast pace producing a multitude of different approaches, with several alternatives to choose from at any step, including single cell isolation and capturing, lysis, RNA reverse transcription and cDNA amplification, library preparation, sequencing, and computational analyses. Here, we provide guidelines for the experimental design of single cell RNA sequencing experiments, exploring the current options for the crucial steps. Furthermore, we provide a complete overview of the typical data analysis workflow, from handling the raw sequencing data to making biological inferences. Significantly, advancements in single cell transcriptomics have already contributed to outstanding exploratory and functional studies of cardiac development and disease models, as summarized in this review. In conclusion, we discuss achievable outcomes of single cell transcriptomics' applications in addressing unanswered questions and influencing future cardiac clinical applications

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Occupational Stress among Health Nurses Working in Health Services Centers in Gonbad Kavous - 2016

Introduction: Occupational consequences and their effects on health and healthcare workers have been examined in many studies. Occupational stress is recognized as an important risk factor in the creation of physical and chronic mental disorders and the quality of work performance. Therefore, this study was carried out with the aim of investigating the stress induced by the work and some social factors among the Health Nurses Working in town Gonbad Kavous in 2016. Methods: This cross-sectional descriptive-analytic study was performed on 147 health workers in Gonbad Kavous town. in order to collect data, the HSE questionnaire including 35 questions with seven fields, role, communication, support of  Authorities,  Fellow support, control, demand and change were used. data analyzed and evaluated by SPSS22 software Results: The mean and standard deviation Health Nurses of age were 43.29 ± 6.50 years. Approximately 40% of health nurses experienced as Intense up to very intense occupational stress. Also, there was a significant relationship between age group (P=0.023), gender (P=0.015), education level (P=0.043), number of children (P=0.046) and financial status (P=0.028) with job stress level of health care workers. Conclusion: The results indicate a high prevalence of occupational stress among health nurses. It seems that assessing work-related stresses of health nurses can lead to appropriate identification of occupational injury risk factors. Also, interventional studies are needed to Compilation a stress management program for health nurses and in order to Coping with work-related stress

Single Cell Gene Expression to Understand the Dynamic Architecture of the Heart.

The recent development of single cell gene expression technologies, and especially single cell transcriptomics, have revolutionized the way biologists and clinicians investigate organs and organisms, allowing an unprecedented level of resolution to the description of cell demographics in both healthy and diseased states. Single cell transcriptomics provide information on prevalence, heterogeneity, and gene co-expression at the individual cell level. This enables a cell-centric outlook to define intracellular gene regulatory networks and to bridge toward the definition of intercellular pathways otherwise masked in bulk analysis. The technologies have developed at a fast pace producing a multitude of different approaches, with several alternatives to choose from at any step, including single cell isolation and capturing, lysis, RNA reverse transcription and cDNA amplification, library preparation, sequencing, and computational analyses. Here, we provide guidelines for the experimental design of single cell RNA sequencing experiments, exploring the current options for the crucial steps. Furthermore, we provide a complete overview of the typical data analysis workflow, from handling the raw sequencing data to making biological inferences. Significantly, advancements in single cell transcriptomics have already contributed to outstanding exploratory and functional studies of cardiac development and disease models, as summarized in this review. In conclusion, we discuss achievable outcomes of single cell transcriptomics' applications in addressing unanswered questions and influencing future cardiac clinical applications

Centering Sexual and Reproductive Health and Justice in the Global COVID-19 Response

The Lancet 395, no. 10231 (April 11, 2020): 1175–77. Overview of sexual and reproductive health issues related to COVID-19

Cells of the adult human heart.

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies