Engineering of NIR fluorescent PEGylated poly(RGD) proteinoid polymers and nanoparticles for drug delivery applications in chicken embryo and mouse models

Proteinoids are non-toxic biodegradable polymers based on thermal step-growth polymerization of natural or synthetic amino acids. Hollow proteinoid nanoparticles (NPs) may then be formed via a self-assembly process of the proteinoid polymers in an aqueous solution. In the present article polymers and NPs based on d-arginine, glycine and l-aspartic acid, poly(R^DGD), were synthesized for tumor targeting, particularly due to the high affinity of the RGD motif to areas of angiogenesis. Near IR fluorescent P(R^DGD) NPs were prepared by encapsulating the fluorescent NIR dye indocyanine green (ICG) within the formed P(R^DGD) NPs. Here, we investigate the effect of the covalent conjugation of polyethylene glycol (PEG), with different molecular weights, to the surface of the near IR encapsulated P(R^DGD) NPs on the release of the dye to human serum due to bio-degradation of the proteinoid NPs and on the uptake by tumors. This work illustrates that the release of the encapsulated ICG from the non-PEGylated NPs is significantly faster than for that observed for the PEGylated NPs, and that the higher molecular weight is the bound PEG spacer the slower is the dye release profile. In addition, in a chicken embryo model, the non-PEGylated ICG-encapsulated P(R^DGD) NPs exhibited a higher uptake in the tumor region in comparison to the PEGylated ICG-encapsulated P(R^DGD) NPs. However, in a tumor xenograft mouse model, which enables a prolonged experiment, the importance of the PEG is clearly noticeable, when a high concentration of PEGylated P(R^DGD) NPs was accumulated in the area of the tumor compared to the non-PEGylated P(R^DGD). Moreover, the length of the PEG chain plays a major role in the ability to target the tumor. Hence, we can conclude that selectivity towards the tumor area of non-PEGylated and the PEGylated ICG-encapsulated P(R^DGD) NPs can be utilized for targeting to areas of angiogenesis, such as in the cases of tumors, wounds or cuts, etc.

Synthesis of NIR/ICG PEGylated poly(R^DGD) proteinoid NPs and their drug delivery towards mCherry-labeled 4T1 tumor.     

Augmentation index predicts mortality in patients with aortic stenosis: an echo-tracking study

The International Journal of Cardiovascular Imaging - Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical...     

Bibliometric indexes,databases and impact factors in cardiology

Bibliometry is a quantitative statistical technique to measure levels of production and dissemination of knowledge, as well as a useful tool to track the development of an scientific area. The valuation of production required for recognition of researchers and magazines is accomplished through tools called bibliometricindexes, divided into quality indicators and scientific impact. Initially developed for monographs of statistical measures especially in libraries, today bibliometrics is mainly used to evaluate productivity of authors and citation repercussion. However, these tools have limitations and sometimes provoke controversies about indiscriminate application, leading to the development of newer indexes. It is important to know the most common search indexes and use it properly even acknowledging its limitations as it has a direct impact in their daily practice, reputation and funds achievement.     

Predicting Vertical Jump Height from Bar Velocity

The objective of the study was to assess the use of maximum (V_max) and final propulsive phase (FPV) bar velocity to predict jump height in the weighted jump squat. FPV was defined as the velocity reached just before bar acceleration was lower than gravity (-9.81 m·s^-2). Vertical jump height was calculated from the take-off velocity (V_take-off) provided by a force platform. Thirty swimmers belonging to the National Slovenian swimming team performed a jump squat incremental loading test, lifting 25%, 50%, 75% and 100% of body weight in a Smith machine. Jump performance was simultaneously monitored using an AMTI portable force platform and a linear velocity transducer attached to the barbell. Simple linear regression was used to estimate jump height from the V_max and FPV recorded by the linear velocity transducer. V_max (y = 16.577x - 16.384) was able to explain 93% of jump height variance with a standard error of the estimate of 1.47 cm. FPV (y = 12.828x - 6.504) was able to explain 91% of jump height variance with a standard error of the estimate of 1.66 cm. Despite that both variables resulted to be good predictors, heteroscedasticity in the differences between FPV and V_take-off was observed (r² = 0.307), while the differences between V_max and V_take-off were homogenously distributed (r² = 0.071). These results suggest that V_max is a valid tool for estimating vertical jump height in a loaded jump squat test performed in a Smith machine.

Key points

• Vertical jump height in the loaded jump squat can be estimated with acceptable precision from the maximum bar velocity recorded by a linear velocity transducer.
• The relationship between the point at which bar acceleration is less than -9.81 m·s^-2 and the real take-off is affected by the velocity of movement.
• Mean propulsive velocity recorded by a linear velocity transducer does not appear to be optimal to monitor ballistic exercise performance.

Key words: Linear velocity transducer, force platform, jump performance, swimming     

Cloning and functional expression of venom prothrombin activator protease from Pseudonaja textilis with whole blood procoagulant activity

The snake venom group C prothrombin activators contain a number of components that enhance the rate of prothrombin activation. The cloning and expression of full-length cDNA for one of these components, an activated factor X (factor Xa)-like protease from Pseudonaja textilis as well as the generation of functional chimeric constructs with procoagulant activity were described. The complete cDNA codes for a propeptide, light chain, activation peptide (AP) and heavy chain related in sequence to mammalian factor X. Efficient expression of the protease was achieved with constructs where the AP was deleted and the cleavage sites between the heavy and light chains modified, or where the AP was replaced with a peptide involved in insulin receptor processing. In human kidney cells (H293F) transfected with these constructs, up to 80% of the pro-form was processed to heavy and light chains. Binding of the protease to barium citrate and use of specific antibodies demonstrated that gamma-carboxylation of glutamic acid residues had occurred on the light chain in both cases, as observed in human factor Xa and the native P. textilis protease. The recombinant protease caused efficient coagulation of whole citrated blood and citrated plasma that was enhanced by the presence of Ca2+. This study identified the complete cDNA sequence of a factor Xa-like protease from P. textilis and demonstrated for the first time the expression of a recombinant form of P. textilis protease capable of blood coagulation.