Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

\ua9 2024 Author(s).Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 7 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle\u27s trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 μg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death

Cold Jupiters and improved masses in 38 Kepler and K2 small planet systems from 3661 HARPS-N radial velocities. No excess of cold Jupiters in small planet systems

The exoplanet population characterized by relatively short orbital periods ($P<100$ d) around solar-type stars is dominated by super-Earths and sub-Neptunes. However, these planets are missing in our Solar System and the reason behind this absence is still unknown. Two theoretical scenarios invoke the role of Jupiter as the possible culprit: Jupiter may have acted as a dynamical barrier to the inward migration of sub-Neptunes from beyond the water iceline; alternatively, Jupiter may have reduced considerably the inward flux of material (pebbles) required to form super-Earths inside that iceline. Both scenarios predict an anti-correlation between the presence of small planets (SPs) and that of cold Jupiters (CJs) in exoplanetary systems. To test that prediction, we homogeneously analyzed the radial-velocity (RV) measurements of 38 Kepler and K2 transiting SP systems gathered over almost 10 years with the HARPS-N spectrograph, as well as publicly available RVs collected with other facilities. We detected five CJs in three systems, two in Kepler-68, two in Kepler-454, and a very eccentric one in K2-312. We derived an occurrence rate of $9.3^{+7.7}_{-2.9}\%$ for CJs with $0.3-13~M_{Jup}$ and 1-10 AU, which is lower but still compatible at $1.3\sigma$ with that measured from RV surveys for solar-type stars, regardless of the presence or absence of SPs. The sample is not large enough to draw a firm conclusion about the predicted anti-correlation between SPs and CJs; nevertheless, we found no evidence of previous claims of an excess of CJs in SP systems. As an important by-product of our analyses, we homogeneously determined the masses of 64 Kepler and K2 small planets, reaching a precision better than 5, 7.5 and 10$\sigma$ for 25, 13 and 8 planets, respectively. Finally, we release the 3661 HARPS-N radial velocities used in this work to the scientific community. [Abridged]Comment: 21 pages, 10 figures, 10 tables, published in Astronomy and Astrophysics. The updated version of the article takes into account the A&A language editing and guidelines. Tables 1, A.1 and full Table 2 are available at the CDS via anonymous ftp to cdsarc.cds.unistra.fr (130.79.128.5) or via https://cdsarc.cds.unistra.fr/viz-bin/cat/J/A+A/677/A3

Cold Jupiters and improved masses in 38 Kepler and K2 small-planet systems from 3661 high-precision HARPS-N radial velocities. No excess of cold Jupiters in small-planet systems

The exoplanet population characterized by relatively short orbital periods ($P<100$ d) around solar-type stars is dominated by super-Earths and sub-Neptunes. However, these planets are missing in our Solar System and the reason behind this absence is still unknown. Two theoretical scenarios invoke the role of Jupiter as the possible culprit: Jupiter may have acted as a dynamical barrier to the inward migration of sub-Neptunes from beyond the water iceline; alternatively, Jupiter may have reduced considerably the inward flux of material (pebbles) required to form super-Earths inside that iceline. Both scenarios predict an anti-correlation between the presence of small planets (SPs) and that of cold Jupiters (CJs) in exoplanetary systems. To test that prediction, we homogeneously analyzed the radial-velocity (RV) measurements of 38 Kepler and K2 transiting SP systems gathered over almost 10 years with the HARPS-N spectrograph, as well as publicly available RVs collected with other facilities. We detected five CJs in three systems, two in Kepler-68, two in Kepler-454, and a very eccentric one in K2-312. We derived an occurrence rate of $9.3^{+7.7}_{-2.9}\%$ for CJs with $0.3-13~M_{Jup}$ and 1-10 AU, which is lower but still compatible at $1.3\sigma$ with that measured from RV surveys for solar-type stars, regardless of the presence or absence of SPs. The sample is not large enough to draw a firm conclusion about the predicted anti-correlation between SPs and CJs; nevertheless, we found no evidence of previous claims of an excess of CJs in SP systems. As an important by-product of our analyses, we homogeneously determined the masses of 64 Kepler and K2 small planets, reaching a precision better than 5, 7.5 and 10$\sigma$ for 25, 13 and 8 planets, respectively. Finally, we release the 3661 HARPS-N radial velocities used in this work to the scientific community. [Abridged]Comment: 21 pages, 10 figures, 10 tables, published in Astronomy and Astrophysics. The updated version of the article takes into account the A&A language editing and guidelines. Tables 1, A.1 and full Table 2 are available at the CDS via anonymous ftp to cdsarc.cds.unistra.fr (130.79.128.5) or via https://cdsarc.cds.unistra.fr/viz-bin/cat/J/A+A/677/A3

Bone marrow derived stem cells for the treatment of end-stage liver disease

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell (BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups

Bone marrow derived stem cells for the treatment of end-stage liver disease.

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell (BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups

A new decoupled CFD and FEM methodology for the fatigue strength assessment of an engine head

A 2200 cc engine head for marine applications has been analysed and optimized by means of decoupled CFD and FEM simulations in order to assess the fatigue strength of the component. The fluid distribution within the cooling jacket was extensively analysed and improved in previous works, in order to enhance the performance of the coolant galleries.As a consequence of the many complex phenomena involved, an improved approach is presented in this paper, capable of a better characterization of the fatigue strength of the engine head under both high-cycle and low-cycle fatigue loadings. The improved methodology is once again based on a decoupled CFD and FEM analysis, with relevant improvements added to both simulation realms.From the CFD side, a new generation polyhedral grid is employed to combine high resolution surface spacing, computational demand, and numerical stability of the CFD simulations, with particular emphasis on the boundary layer representation. The local heat flux distribution is calculated by means of CFD analyses of the coolant galleries, now including the engine block portion, plus the engine head metal cast. In order to tune and improve the accuracy of the numerical forecasts, comparisons are carried out with experiments in terms of local metal cast temperature distribution for steady operation of the cooling circuit. Once again, particular care is devoted to the CFD representation of the boundary layer, both fluid and thermal. At the same time, great attention is paid to the thermal boundary conditions, i.e. the distribution of the heat fluxes among the many components facing the combustion process. In order to improve the accuracy of the CFD forecasts, effects of coolant boiling on the heat transfer forecast are investigated and included in the procedure.As a result, a pointwise heat transfer distribution on the fluid/solid interface is transferred as a boundary condition to a thermo-structural analysis for the evaluation of the fatigue strength of the component. An ad-hoc routine is used to map the CFD computed pointwise distribution of the heat flux on a FEM-optimized grid.From the FEM side, an energy based fatigue strength criterion is now implemented in order to create a design tool capable of predicting the fatigue strength of automotive parts subjected to different thermo-mechanical loadings. Both high-cycle fatigue and low-cycle fatigue regions are analysed, and the proposed methodology is successfully applied to predict the site of crack nucleation on an actual engine head and to improve the cooling jacket behaviour

Thermo-mechanical analysis of an engine head by means of integrated CFD and FEM

A 2200 cc engine head for marine applications has been analysed and optimized by means of both fluid-dynamic and thermo-structural simulations. First, the fluid distribution within the cooling jacket has been deeply investigated, in order to point out critical aspects of the current jacket layout and propose modified gaskets aiming at modifying the coolant path and increasing the cooling performance. A new generation polyhedral grid has been employed to combine high resolution surface spacing, computational demand, and numerical stability of the CFD simulations. Different turbulence models and near-wall approaches have been tested in order to accurately predict the boundary layer behaviour, which is fundamental for the subsequent thermal analysis. Comparisons have been carried out between the different gasket layouts in terms of both cylinder to cylinder flow balancing and cooling effectiveness in the critical regions of the engine head.At a second stage, the CFD model has been extended to the whole engine head, i.e. covering both the cooling jacket and the metal cast, and heat flux distribution on the fluid/solid interface has been computed and transferred as a boundary condition to a structural finite elements code for the analysis of the fatigue strength of the component. To this aim, an ad-hoc developed routine has been created to map the computed punctual distribution of the heat transfer coefficient on a FEM-optimized grid. Particular attention has been paid to the thermal boundary conditions, i.e. the distribution of the heat losses among the combustion chamber and pre-chamber components.Along with this coherent approach of thermo-mechanical loading, the mechanical constitutive law of the material, the damage parameters and an energy based fatigue strength criterion have been considered in order to create a design strategy capable of performing predictive calculations of automotive parts subjected to thermo-mechanical loading. The methodology favoured in this study has been successfully applied to predict the site of incipient crack on an actual engine head

CD133+ hematopoietic stem cells reinfusion in end-stage liver disease (ESLD): final results of a phase I clinical trial

none13nononeC. Margini, L. Brodosi, S. Lorenzini, L. Catani, V. Giudice, R. Giordano, A. Casadei, D. Sollazzo, F.G. Foschi, M. Baccarani, M. Bernardi, R. Lemoli, P. AndreoneC. Margini, L. Brodosi, S. Lorenzini, L. Catani, V. Giudice, R. Giordano, A. Casadei, D. Sollazzo, F.G. Foschi, M. Baccarani, M. Bernardi, R. Lemoli, P. Andreon