Clathrin-dependent endocytosis is believed to be involved in TGFβ-stimulated cellular responses, but the subcellular locus at which TGFβ induces signaling remains unclear. Here, we demonstrate that inhibitors of clathrin-dependent endocytosis, which are known to arrest the progression of endocytosis at coated-pit stages, inhibit internalization of cell-surface-bound TGFβ and promote colocalization and accumulation of TβR-I and SARA at the plasma membrane. These inhibitors enhance TGFβ-induced signaling and cellular responses (Smad2 phosphorylation/nuclear localization and expression of PAI-1). Dynasore, a newly identified inhibitor of dynamin GTPase activity, is one of the most potent inhibitors among those tested and, furthermore, is a potent enhancer of TGFβ. Dynasore ameliorates atherosclerosis in the aortic endothelium of hypercholesterolemic ApoE-null mice by counteracting the suppressed TGFβ responsiveness caused by the hypercholesterolemia, presumably acting through its effect on TGFβ endocytosis and signaling in vascular cells.

The authors' findings support the inclusion of walking exercise into the multimodal approaches to managing sleep in people with cancer. Healthcare providers must convey the benefits of walking exercise to individuals with cancer who are suffering from sleep problems.

Cell-surface retention sequence (CRS) binding protein (CRSBP-1) is a membrane glycoprotein identified by its ability to bind PDGF-BB and VEGF-A via their CRS motifs (clusters of basic amino acid residues). CRSBP-1 is identical to LYVE-1 and exhibits dual ligand (CRS-containing proteins and hyaluronic acid) binding activity, suggesting the importance of CRSBP-1 ligands in lymphatic function. Here, we show that CRSBP-1 ligands induce disruption of VE-cadherin-mediated intercellular adhesion and opening of intercellular junctions in lymphatic endothelial cell (LEC) monolayers as determined by immunofluorescence microscopy and Transwell permeability assay. This occurs by interaction with CRSBP-1 in the CRSBP-1–PDGFβR–β-catenin complex, resulting in tyrosine phosphorylation of the complex, dissociation of β-catenin and p120-catenin from VE-cadherin, and internalization of VE-cadherin. Pretreatment of LECs with a PDGFβR kinase inhibitor abolishes ligand-stimulated tyrosine phosphorylation of VE-cadherin, halts the ligand-induced disruption of VE-cadherin intercellular adhesion and blocks the ligand-induced opening of intercellular junctions. These CRSBP-1 ligands also induce opening of lymphatic intercellular junctions that respond to PDGFβR kinase inhibitor in wild-type mice (but not in Crsbp1-null mice) as evidenced by increased transit of injected FITC–dextran and induced edema fluid from the interstitial space into lymphatic vessels. These results disclose a novel mechanism involved in the opening of lymphatic intercellular junctions.

BackgroundDeveloping a stroke health-education mobile app (SHEMA) and examining its effectiveness on improvement of knowledge of stroke risk factors and health-related quality of life (HRQOL) in patients with stroke.MethodsWe recruited 76 stroke patients and randomly assigned them to either the SHEMA intervention (n = 38) or usual care where a stroke health-education booklet was provided (n = 38). Knowledge of stroke risk factors and HRQOL were assessed using the stroke-knowledge questionnaire and European Quality of Life–Five Dimensions (EQ-5D) questionnaire, respectively.ResultsSixty-three patients completed a post-test survey (the SHEMA intervention, n = 30; traditional stroke health-education, n = 33). Our trial found that patients’ mean knowledge score of stroke risk factors was improved after the SHEMA intervention (Mean difference = 2.83; t = 3.44; p = .002), and patients’ knowledge was also improved in the after traditional stroke health-education (Mean difference = 2.79; t = 3.68; p = .001). However, patients after the SHEMA intervention did not have significantly higher changes of the stroke knowledge or HRQOL than those after traditional stroke health-education.ConclusionsBoth the SHEMA intervention and traditional stroke health-education can improve patients’ knowledge of stroke risk factors, but the SHEMA was not superior to traditional stroke health-education.Trial registrationNCT02591511 Verification Date 2015-10-01.

The adapted Taiwan Chinese version of the FFI is reliable and valid and can be applied among traumatic and non-traumatic foot disorders. Nevertheless, its clinical application may be limited by a relatively high proportion of non-applicable answers and significant floor effect in some items.