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Understanding, perspective and employ of advance care organizing among nursing interns: Any mixed-methods strategy.
Pulmonary arterial hypertension (PAH) is a rare, chronic disease of the pulmonary vasculature that is associated with poor outcomes. Its pathogenesis is multifactorial and includes micro-RNA (miRNA) deregulation. The understanding of the role of miRNAs in PAH is expanding quickly, and it is increasingly difficult to identify which miRNAs have the highest translational potential. This review summarizes the current knowledge of miRNA expression in PAH, discusses the challenges in miRNA analysis and interpretation, and highlights 4 promising miRNAs in this field (miR-29, miR-124, miR-140, and miR-204).Mesenchymal stromal cell (MSC) transplantation is a form of the stem-cell therapy that has shown beneficial effects for many diseases. The use of stem-cell therapy, including MSC transplantation, however, has limitations such as the tumorigenic potential of stem cells and the lack of efficacy of aged autologous cells. An ideal therapeutic approach would keep the beneficial effects of MSC transplantation while circumventing the limitations associated with the use of intact stem cells. This study provides proof-of-concept evidence that MSC-derived extracellular vesicles represent a promising platform to develop an acellular therapeutic approach that would just do that. Extracellular vesicles are membranous vesicles secreted by MSCs and contain bioactive molecules to mediate communication between different cells. Extracellular vesicles can be taken up by recipient cells, and once inside the recipient cells, the bioactive molecules are released to exert the beneficial effects on the recipient cells. This study, for the first time to our knowledge, shows that extracellular vesicles secreted by MSCs recapitulate the beneficial effects of MSCs on vascular repair and promote blood vessel regeneration after ischemic events. Furthermore, MSCs from aged donors can be engineered to produce extracellular vesicles with improved regenerative potential, comparable to MSCs from young donors, thus eliminating the need for allogenic young donors for elderly patients.As the next step in the translation of vascular tissue engineering, this study uniquely combines transcatheter delivery and in situ tissue regeneration using a novel bioresorbable electrospun polymer graft that can be implanted minimally invasively. Once delivered inside a small-diameter vessel, the electrospun microstructure supports the vessel wall, facilitates cellular infiltration, and guides organized tissue formation.Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. S63845 nmr Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.The treatment of pediatric heart failure is a long-standing unmet medical need. Angiotensin II supports mammalian perinatal circulation by activating cardiac L-type Ca2+ channels through angiotensin type 1 receptor (AT1R) and β-arrestin. TRV027, a β-arrestin-biased AT1R agonist, that has been reported to be safe but not effective for adult patients with heart failure, activates the AT1R/β-arrestin pathway. We found that TRV027 evokes a long-acting positive inotropic effect specifically on immature cardiac myocytes through the AT1R/β-arrestin/L-type Ca2+ channel pathway with minimum effect on heart rate, oxygen consumption, reactive oxygen species production, and aldosterone secretion. Thus, TRV027 could be utilized as a valuable drug specific for pediatric heart failure.Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection.The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge. Here, we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo. The multifunctional nanomatrix was composed of polypyrrole@polydopamine (PPy@PDA, 342 ± 5.6 nm) nanoparticles-crosslinked Pluronic F-127 (F127)-polycitrate matrix (FPCP). The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior, muscle-adhesive feature, injectable ability, electronic conductivity (0.48 ± 0.03 S/m) and antioxidant activity and photothermal function. The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation, which could provide the photo-controlled release of protein (91% ± 2.6% of BSA was released after irradiated 3 times). Additionally, FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells (C2C12) by promoting the expressions of myogenic genes (MyoD and MyoG) and myosin heavy chain (MHC) protein with negligible cytotoxicity.
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