ABSTRACT
The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αß+GP38+SCA-1- cells prevailed in the embryonic thymus and declined thereafter, CD140αß+GP38+SCA-1+ cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αß+GP38+SCA-1+ cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αß+GP38+SCA-1+ maintained their phenotype in thymic organoids. Strikingly, CD140αß+GP38+SCA-1- generated CD140αß+GP38+SCA-1+, inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αß+GP38+SCA-1+ fibroblasts was gradually reduced in Rag2-/- and Rag2-/-Il2rg-/- thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αß+GP38+SCA-1- as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation.
Subject(s)
Stem Cells , T-Lymphocytes , Animals , Cell Differentiation , Epithelial Cells , Fibroblasts , Mice , Thymus GlandABSTRACT
The blood-brain barrier (BBB) is a barrier that separates the blood from the brain tissue and possesses unique characteristics that make the delivery of drugs to the brain a great challenge. To achieve this purpose, it is necessary to design strategies to allow BBB passage, in order to reach the brain and target the desired anatomic region. The use of nanomedicine has great potential to overcome this problem, since one can modify nanoparticles with strategic molecules that can interact with the BBB and induce uptake through the brain endothelial cells and consequently reach the brain tissue. This review addresses the potential of nanomedicines to treat neurological diseases by using nanoparticles specially developed to cross the BBB.
Subject(s)
Brain/metabolism , Drug Carriers/metabolism , Drug Delivery Systems , Nanoparticles/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Brain/drug effects , Drug Carriers/chemistry , Drug Delivery Systems/methods , Humans , Nanoparticles/chemistry , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Pharmaceutical Preparations/administration & dosage , PharmacokineticsABSTRACT
Quercetin is a flavonol present in many vegetables and fruits. Generally, quercetin can be found in aglycone and glycoside forms, mainly in leaves. The absorption of this compound occurs in the large and small intestine, where it suffers glucuronidation, sulfidation, and methylation to improve hydrophilicity. After metabolization, which occurs mainly in the gut, it is distributed throughout the whole organism and is excreted by feces, urine, and exhalation of carbon dioxide. Despite its in vitro cytotoxicity effects, in vivo studies with animal models ensure its safety. This compound can protect against cancer, cardiovascular diseases, chronic inflammation, oxidative stress, and neurodegenerative diseases due to its radical scavenging and anti-inflammatory properties. However, its poor bioavailability dampens the potential beneficial effects of this flavonoid. In that sense, many types of nanocarriers have been developed to improve quercetin solubility, as well as to design tissue-specific delivery systems. All these studies manage to improve the bioavailability of quercetin, allowing it to increase its concentration in the desired places. Collectively, quercetin can become a promising compound if nanotechnology is employed as a tool to enhance its therapeutic efficacy.
ABSTRACT
The microenvironments formed by cortical (c) and medullary (m) thymic epithelial cells (TECs) play a non-redundant role in the generation of functionally diverse and self-tolerant T cells. The role of TECs during the first weeks of the murine postnatal life is particularly challenging due to the significant augment in T cell production. Here, we critically review recent studies centered on the timely coordination between the expansion and maturation of TECs during this period and their specialized role in T cell development and selection. We further discuss how aging impacts on the pool of TEC progenitors and maintenance of functionally thymic epithelial microenvironments, and the implications of these chances in the capacity of the thymus to sustain regular thymopoiesis throughout life.
