• Mays Moss posted an update 1 day, 6 hours ago

    Human nasal septal chondrocytes (NC) are a promising minimally invasive derivable chondrogenic cell source for cartilage repair. However, the quality of NC-derived cartilage is variable between donors. Coculture of NC with mesenchymal stem cells (MSCs) mitigates the variability but with undesirable markers of chondrocyte hypertrophy, such as type X collagen, and the formation of unstable calcifying cartilage at ectopic sites. In contrast, monoculture NC forms non-calcifying stable cartilage. Formation of a stable NC-MSC coculture cartilage is crucial for clinical application. The aim of this study was to explore the utility of parathyroid hormone-related peptide (PTHrP) hormone to suppress chondrocyte hypertrophy in NC-MSC cocultures and form stable non-calcifying cartilage at ectopic sites.

    Human NC and bone marrow MSCs, and cocultures of NC and MSC (13 ratio) were aggregated in pellet form and subjected to

    chondrogenesis for 3 weeks in chondrogenic medium in the presence and absence of PTHrP. Following

    chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.

    Coculture of NC and MSC resulted in synergistic cartilage matrix production. PTHrP suppressed the expression of hypertrophy marker, type X collagen (

    ), in a dose-dependent fashion without affecting the synergism in cartilage matrix synthesis, and

    calcification was eradicated with PTHrP. In contrast, cocultured control (CC) pellets without PTHrP treatment expressed

    , calcified, and became vascularized

    .

    Coculture of NC and MSC resulted in synergistic cartilage matrix production. PTHrP suppressed the expression of hypertrophy marker, type X collagen (COL10A1), in a dose-dependent fashion without affecting the synergism in cartilage matrix synthesis, and in vivo calcification was eradicated with PTHrP. In contrast, cocultured control (CC) pellets without PTHrP treatment expressed COL10A1, calcified, and became vascularized in vivo.Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). As of October 21, 2020, more than 41.4 million confirmed cases and 1.1 million deaths have been reported. Thus, it is immensely important to develop drugs and vaccines to combat COVID-19. The spike protein present on the outer surface of the virion plays a major role in viral infection by binding to receptor proteins present on the outer membrane of host cells, triggering membrane fusion and internalization, which enables release of viral ssRNA into the host cell. Understanding the interactions between the SARS-CoV-2 trimeric spike protein and its host cell receptor protein, angiotensin converting enzyme 2 (ACE2), is important for developing drugs and vaccines to prevent and treat COVID-19. Several crystal structures of partial and mutant SARS-CoV-2 spike proteins have been reported; however, an atomistic structure of the wild-type SARS-CoV-2 trimeric spike protein complexed with ACE2 is not yet available.s to prevent SARS-CoV-2 infection and combat COVID-19.Lipase-catalyzed reactions offer many advantages among which a high degree of selectivity combined with the possibility to convert even non-natural substrates are of particular interest. A major drawback in the applicability of lipases in the conversion of synthetically interesting, non-natural substrates is the substantial insolubility of such substrates in water. The conversion of substrates, natural or non-natural, by lipases generally involves the presence of a water-oil interface. In the present paper, we exploit the fact that the presence of lipases, in particular the lipase from Candida antarctica B (CalB), changes the bending elastic properties of a surfactant monolayer in a bicontinuous microemulsion consisting of D2O/NaCl -n-(d)-octane-pentaethylene glycol monodecyl ether (C10E5) in a similar manner as previously observed for amphiphilic block-copolymers. To determine the bending elastic constant, we have used two approaches, small angle neutron scattering (SANS) and neutron spin echo (NSE) spectroscopy. The time-averaged structure from SANS showed a slight decrease in bending elasticity, while on nanosecond time scales as probed with NSE, a stiffening has been observed, which was attributed to adsorption/desorption mechanisms of CalB at the surfactant monolayer. The results allow to derive further information on the influence of CalB on the composition and bending elasticity of the surfactant monolayer itself as well as the underlying adsorption/desorption mechanism.Objective The aim of this study was to construct light and temperature dual-sensitive micellar carriers loaded with doxorubicin (DOX) and gold nanorods (DOX-GNRs-PNIPAM@PEG-PLA, DAPP) for melanoma therapy. Methods The DAPP self-assembled using fine-tuned physicochemical properties in water. The DAPP structure, temperature- and photo-sensitivity, drug-release, in-vitro serum stability, and cytotoxicity against melanoma B16F10 cells were evaluated in detail. The corresponding in-vitro and in-vivo therapeutic mechanisms were then evaluated using a B16F10-melanoma bearing BALB/c nude mouse model (B16F10). Results The light and temperature sensitive micellar drug-delivery system assembled from block copolymer and gold nanorods exhibited a narrow particle size and size distribution, good biocompatibility, well-designed photo-temperature conversion, controlled drug release, and high serum stability. check details Compared with the free DOX- and PBS-treated groups, the cell endocytosis-mediated cytotoxicity and intra-tumor accumulation of DAPP was markedly enhanced by the NIR-light exposure and induced potent in-vivo tumor inhibitory activity. Conclusion The design of DAPP, a dual-functional micellar drug-delivery system with temperature- and light-sensitive properties, offers a new strategy for skin-cancer therapy with a potent therapeutic index.Objectives Minimal invasive repair of pectus excavatum (MIRPE) described by Nuss is the most popular correction nowadays of this deformity. During the introduction of the bars, they can hurt or compress the internal mammary arteries (IMA). The aim of this study was to observe the prevalence of IMA compression in children after MIRPE. Also, we examined if IMA obstruction increases the risk of complications at bar removal, and if these vascular changes are reversible. Materials and Methods All patients operated on pectus excavatum in our tertiary pediatric surgical center between 2013 and 2019 were involved in the study. Data of age, sex, number of bars and characteristics of the deformity were examined. IMA flow was checked by Doppler ultrasound (DUS) after MIRPE and after bar removal, too. Results Among 41 patients with mean age of 15.2 years there were 18 asymmetrical deformities, 23 sternal rotations. Mean pectus index was 4.01. After the Nuss procedure 7(9%) stenoses and 10(12%) occlusions of IMA were found on DUS.