Search results for "DISEASES"
showing 10 items of 20537 documents
Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications
2021
Cholesterol, an essential component of the brain, and its local metabolism are involved in many neurodegenerative diseases. The blood-brain barrier is impermeable to cholesterol; hence, cholesterol homeostasis in the central nervous system represents a balance betweenin situbiosynthesis and elimination. Cytochrome P450 46A1 (CYP46A1), a central nervous system-specific enzyme, converts cholesterol to 24-hydroxycholesterol, which can freely cross the blood-brain barrier and be degraded in the liver. By the dual action of initiating cholesterol efflux and activating the cholesterol synthesis pathway, CYP46A1 is the key enzyme that ensures brain cholesterol turnover. In humans and mouse models,…
Cellular and molecular basis of the imbalance between vascular damage and repair in ageing and age-related diseases: As biomarkers and targets for ne…
2016
Preclinical and clinical studies suggest that specific subsets of cells isolated from the peripheral blood, play an essential role in the imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous regeneration of the vessel wall involves cells of the vascular wall, inflammatory cells, circulating precursors, and mature endothelial cells, which are capable to restore the endothelium in a concerted interaction. Early detection of such imbalances with specific biomarkers may reduce age-associated diseases and subsequent cardiovascular events. Likewise, new strategies have …
Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing
2018
Cardiovascular diseases are a worldwide health problem and are the leading cause of mortality in developed countries. Together with experimental data, the lower incidence of cardiovascular diseases in women than in men of reproductive age points to the influence of sex hormones at the cardiovascular level and suggests that estrogens play a protective role against cardiovascular disease and that this role is also modified by ageing. Estrogens affect cardiovascular function via their specific estrogen receptors to trigger gene expression changes at the transcriptional level. In addition, emerging studies have proposed a role for microRNAs in the vascular effects mediated by estrogens. miRNAs …
Cardiac Nonmyocyte Cell Functions and Crosstalks in Response to Cardiotoxic Drugs
2017
The discovery of the molecular mechanisms involved in the cardiac responses to anticancer drugs represents the current goal of cardio-oncology research. The oxidative stress has a pivotal role in cardiotoxic responses, affecting the function of all types of cardiac cells, and their functional crosstalks. Generally, cardiomyocytes are the main target of research studies on cardiotoxicity, but recently the contribution of the other nonmyocyte cardiac cells is becoming of growing interest. This review deals with the role of oxidative stress, induced by anticancer drugs, in cardiac nonmyocyte cells (fibroblasts, vascular cells, and immune cells). The alterations of functional interplays among t…
The close link between the fetal programming imprinting and neurodegeneration in adulthood: The key role of “hemogenic endothelium” programming
2021
The research on neurodegenerative diseases (NeuroDegD) has been traditionally focused on later life stages. There is now an increasing evidence, that they may be programmed during early development. Here, we propose that NeuroDegD are the result of the complex process of imprinting on fetal hemogenic endothelium, from which the microglial cells make to origin. The central role of placenta and epigenetic mechanisms (methylation of DNA, histone modifications and regulation by non-coding RNAs) in mediating the short and long-term effects has been also described. Precisely, it reports their role in impacting plasticity and memory of microglial cells. In addition, we also underline the necessity…
The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases
2016
Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until …
Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases
2016
Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic stra…
Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus
2017
Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8) and GDM (n=8) pregnancies. S-Nitrosylation was measured using the biotin-switch …
Effects of Study Population, Labeling and Training on Glaucoma Detection Using Deep Learning Algorithms
2020
Author(s): Christopher, Mark; Nakahara, Kenichi; Bowd, Christopher; Proudfoot, James A; Belghith, Akram; Goldbaum, Michael H; Rezapour, Jasmin; Weinreb, Robert N; Fazio, Massimo A; Girkin, Christopher A; Liebmann, Jeffrey M; De Moraes, Gustavo; Murata, Hiroshi; Tokumo, Kana; Shibata, Naoto; Fujino, Yuri; Matsuura, Masato; Kiuchi, Yoshiaki; Tanito, Masaki; Asaoka, Ryo; Zangwill, Linda M | Abstract: PurposeTo compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models.MethodsTwo fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent…
Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size i…
2017
ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI). In the animal model, a sharp drop in circulating T lymphocytes occurred within the first hours after reper…