• Flores Hurst posted an update 6 months, 2 weeks ago

    Virus-like particles (VLPs) are non-genetic multimeric nanoparticles synthesized through in vitro or in vivo self-assembly of one or more viral structural proteins. Immunogenicity and safety of VLPs make them ideal candidates for vaccine development and efficient nanocarriers for foreign antigens or adjuvants to activate the immune system.

    The present study aimed to design and synthesize a chimeric VLP vaccine of the phage Qbeta (Qβ) coat protein presenting the universal epitope of the coronavirus.

    The RNA phage Qβ coat protein was designed and synthesized, denoted as Qbeta. The CoV epitope, a universal epitope of coronavirus, was inserted into the C-terminal of Qbeta using genetic recombination, which was designated as Qbeta-CoV. The N-terminal of Qbeta-CoV was successively inserted into the TEV restriction site using mCherry red fluorescent label and modified affinity-purified histidine label 6xHE, which was denoted as HE-Qbeta-CoV. Isopropyl β-D-1-thiogalactopyranoside (IPTG) assessment revealed the nstruction of the chimeric VLPs of the phage Qβ coat protein presenting the universal epitope of coronavirus provides a vaccine form with potential clinical applications for the treatment of coronavirus disease.

    The successful construction of the chimeric VLPs of the phage Qβ coat protein presenting the universal epitope of coronavirus provides a vaccine form with potential clinical applications for the treatment of coronavirus disease.

    1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving the diffusion and bioavailability of NQs into the skin.

    We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application.

    Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as a non-polar solvent and span 65 as organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz cell” in vitro permeation model.

    Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds to LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50 2.6 and 9.8 µM) y. The M1 release from bigels was faster and more efficient than that of M2.

    M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

    M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

    Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post-cardiotomy cardiac failure, and refractory cardiac arrest. However, VA-ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA-ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA-ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA-ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support.

    WEANILEVO is a randomized, prospective, multicentre, double-blind, parallel-group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA-ECMO and for whom weaning is expected within 48h. The study drugs are either levosimendan (0.2μg/kg/min for 24h) or a placebo. The primary endpoint of the trial is the absence of VA-ECMO weaning, recourse to another VA-ECMO, or other temporary circulatory assistance or death within 7days of VA-ECMO weaning.

    Levosimendan use in VA-ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA-ECMO weaning.

    Levosimendan use in VA-ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA-ECMO weaning.Omecamtiv mecarbil (OM) is a cardiac myosin activator under development for the treatment of heart failure. The effect of CYP3A4 and CYP2D6 inhibition on OM pharmacokinetics and the potential for OM to induce CYP3A4 was assessed in 2 studies. Study 1, part A, assessed the effect of ketoconazole 200 mg on the pharmacokinetics of OM 10 mg in CYP2D6 extensive metabolizers (EMs; n = 8) or poor metabolizers (PMs; n = 8). Study 1, part B, assessed the effect of diltiazem 240 mg on the pharmacokinetics of OM 10 mg (EM; n = 8). Study 2 assessed the effect of OM 25 mg on the pharmacokinetics of midazolam 5 mg (n = 14). Coadministration with ketoconazole led to 51% and 31% increases in OM AUCinf in EM and PM subjects, respectively, whereas OM Cmax remained similar (3% higher and 14% lower for EM and PM subjects, respectively). No changes in OM pharmacokinetics were observed in EM subjects following coadministration with diltiazem. read more Midazolam AUCinf and Cmax decreased by 18% and 10%, respectively, when coadministered with OM.

All content contained on CatsWannaBeCats.Com, unless otherwise acknowledged,is the property of CatsWannaBeCats.Com and subject to copyright.

CONTACT US

We're not around right now. But you can send us an email and we'll get back to you, asap.

Sending

Log in with your credentials

or    

Forgot your details?

Create Account