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Elastin is a long-lived extracellular matrix protein that is organized into elastic fibers that provide elasticity to the arterial wall, allowing stretch and recoil with each cardiac cycle. By forming lamellar units with smooth muscle cells, elastic fibers transduce tissue-level mechanics to cell-level changes through mechanobiological signaling. Altered amounts or assembly of elastic fibers leads to changes in arterial structure and mechanical behavior that compromise cardiovascular function. In particular, genetic mutations in the elastin gene (ELN) that reduce elastin protein levels are associated with focal arterial stenosis, or narrowing of the arterial lumen, such as that seen in supravalvular aortic stenosis and Williams-Beuren syndrome. Global reduction of Eln levels in mice allows investigation of the tissue- and cell-level arterial mechanical changes and associated alterations in smooth muscle cell phenotype that may contribute to stenosis formation. A loxP-floxed Eln allele in mice highlights cell type- and developmental origin-specific mechanobiological effects of reduced elastin amounts. Eln production is required in distinct cell types for elastic layer formation in different parts of the mouse vasculature. Eln deletion in smooth muscle cells from different developmental origins in the ascending aorta leads to characteristic patterns of vascular stenosis and neointima. Dissecting the mechanobiological signaling associated with local Eln depletion and subsequent smooth muscle cell response may help develop new therapeutic interventions for elastin-related diseases.The carbohydrate hyaluronan (or hyaluronic acid, HA) is found in all human tissues and biofluids where it has wide-ranging functions in health and disease that are dictated by both its abundance and size. Consequently, hyaluronan evaluation in physiological samples has significant translational potential. Although the analytical tools and techniques for probing other biomolecules such as proteins and nucleic acids have become standard approaches in biochemistry, those available for investigating hyaluronan are less well established. In this review, we survey methods related to the assessment of native hyaluronan in biological specimens, including protocols for separating it from biological matrices and technologies for determining its concentration and molecular weight.Primary airway epithelial cells (pAECs) cultivated at air-liquid interface (ALI) conditions are widely used as surrogates for human in vivo epithelia. To extend the proliferative capacity and to enable serially passaging of pAECs, conditional reprogramming (cr) has been employed in recent years. However, ALI epithelia derived from cr cells often display functional changes with increasing passages. This highlights the need for thorough validation of the ALI cultures for the respective application. In our study, we evaluated the use of serially passaged cr nasal epithelial cells (crNECs) as a model to study SARS-CoV-2 infection and effects on ion and water transport. NECs were obtained from healthy individuals and cultivated as ALI epithelia derived from passages 1, 2, 3, and 5. We compared epithelial differentiation, ion and water transport, and infection with SARS-CoV-2 between passages. Our results show that epithelia maintained major differentiation characteristics and physiological ion and water transport properties through all passages. However, the frequency of ciliated cells, short circuit currents reflecting epithelial Na+ channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) activity and expression of aquaporin 3 and 5 decreased gradually over passages. crNECs also expressed SARS-CoV-2 receptors angiotensin converting enzyme 2 (ACE2) and transmembrane serin2 protease 2 (TMPRSS2) across all passages and allowed SARS-CoV-2 replication in all passages. In summary, we provide evidence that passaged crNECs provide an appropriate model to study SARS-CoV-2 infection and also epithelial transport function when considering some limitations that we defined herein.Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and are the target of approximately one-third of all Food and Drug Administration (FDA)-approved pharmaceutical drugs. GPCRs interact with many transducers, such as heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. Recent experiments have demonstrated that some ligands can activate distinct effector proteins over others, a phenomenon termed "biased agonism." These discoveries have raised the potential of developing drugs which preferentially activate therapeutic signaling pathways over those that lead to deleterious side effects. However, to date, only one biased GPCR therapeutic has received FDA approval and many others have either failed to meet their specified primary end points and or demonstrate superiority over currently available treatments. In addition, there is a lack of understanding regarding how biased agonism measured at a GPCR leads to specific downstream physiological responses. Here, we briefly summarize the history and current status of biased agonism at GPCRs and suggest adoption of a "systems pharmacology" approach upon which to develop GPCR-targeted drugs that demonstrate heightened therapeutic efficacy with improved side effect profiles.The matricellular glycoprotein thrombospondin-1 (TSP1) has complex roles in the extracellular matrix (ECM) and at cell surfaces, but relatively little is known about its intracellular associations prior to secretion. To search for novel intracellular interactions of TSP1 in situ, we carried out a biotin ligase-based TSP1 interactome screen and identified protein disulfide isomerase A3 (PDIA3/ERp57) as a novel candidate binding protein. In validation, TSP1 and PDIA3 were established to bind in vitro and to colocalize in the endoplasmic reticulum of human dermal fibroblasts (HDF). Loss of PDIA3 function, either by pharmacological inhibition in HDF or in Pdia3-/- mouse embryo fibroblasts (Pdia3-/- MEFs), led to alterations in the composition of cell-derived extracellular matrix, involving changed abundance of fibronectin and TSP1, was correlated with reduced cell spreading, altered organization of F-actin, and reduced focal adhesions. These cellular phenotypes of Pdia3-/- MEFs were normalized by exposure to conditioned medium (WTCM) or extracellular matrix (WTECM) from wild-type (WT)-MEFs. Rescue depended on PDIA3 activity in WT-MEFs and was not prevented by immunodepletion of fibronectin. Heparin-binding proteins in WTCM were found to be necessary for rescue. Comparative quantitative tandem-mass-tag proteomics and functional assays on the heparin-binding secretomes of WT-MEFs and Pdia3-/- MEFs identified multiple ECM and growth factor proteins to be downregulated in the CM of Pdia3-/- MEFs. Of these, cell communication network 2 (CCN2) was identified to be necessary for the adhesion-promoting activity of WTCM on Pdia3-/- MEFs and to bind TSP1. Thus, PDIA3 coordinates fibroblast production of an ECM-rich, proadhesive microenvironment, with implications for PDIA3 as a translational target.Paragangliomas of the trachea are rare neoplasms and can present to the clinician with acute airway problems. These neoplasms sometimes are misdiagnosed by general practitioners as asthmatic exacerbation. We present the case of a 66-year-old woman who presented to us with a history of dyspnoea at rest in the supine position and on exertion and a productive cough. This was diagnosed as bronchial asthma and she was treated with corticosteroid inhalers for four months by her GP. She was subsequently evaluated by computed tomography of the neck and thorax, which revealed an intratracheal enhancing lesion measuring around 11 mm in the lower cervical trachea. Fibreoptic bronchoscopy showed a mass lesion at the level of mid trachea. A low tracheostomy was followed by telescopic examination and the mass was resected using coablation. Histology of the mass was reported as paraganglioma. Difficulties encountered and literature review of various management options are presented in this report.<br /><br /> Although it is true that adolescence is a stage of evolutionary development in which there are innumerable windows of opportunity, it is also the peak age at which some psychiatric disorders may appear. On the other hand, music is an auditory stimulus that interests and motivates youngsters, as it is used for identity, social connection, and emotional regulation.<br /><br /> We conducted a strategic search by consulting scientific databases. The following search terms were employed Music Therapy AND Psychology AND Psychiatry AND Adolescents. The following international electronic databases were searched Medline, Ovid, and Cochrane Library.<br /><br /> A total of 142 sources were identified from which 9 papers on music therapy published exclusively in scientific journals specialized in psychology or child psychiatry were selected. The total number of participants was 651. The studies reported that music therapy interventions have the potential to improve self-esteem, social engagement, decrease social isolation, and depressive and anxiety symptoms in psychiatric adolescents (both in inpatient and outpatient settings).<br /><br /> Given the heterogeneity and methodological quality of the few studies included, it is complex to extrapolate and generalize results. More quality research is needed to expand music therapy interventions on youth mental health.<br /><br />Given the heterogeneity and methodological quality of the few studies included, it is complex to extrapolate and generalize results. More quality research is needed to expand music therapy interventions on youth mental health.Monocytes are one of the principal immune defense cells that encounter infectious agents. However, an essential role of monocytes has been shown in the spread of viruses throughout the human body. Considering this dilemma, this study aimed to evaluate monocyte subsets and Human Leukocyte Antigen-DR isotype (HLA-DR) expressions in clinical coronavirus disease 2019 (COVID-19) cases. [https://www.selleckchem.com/products/gi254023x.html GI254023X] This prospective, multicenter, case-control study was conducted with COVID-19 patients and healthy controls. The patient group was divided into two subgroups according to disease severity (severe and non-severe). Three monocyte subsets (classical, CL; intermediate, INT; non-classical, NC) were analyzed with flow cytometry upon the patients' hospital admission. A total of 42 patients with COVID-19 and 30 controls participated in this study. The patients' conditions were either severe (n = 23) or non-severe (n = 19). All patients' monocyte and HLA-DR expressions were decreased compared with the controls (p  less then  0.05). Per disease severity, all monocyte subsets were not significant with disease severity; however, the HLA-DR expressions of CL monocytes (p = 0.