Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues

Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanopartides within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues

Use Of Different Doses Of Ovaprim To Induced Lelan (Osteochilus Pleurotaenia Blkr)

This research was conducted from May 23 to December 6 2015. The aim of this research was to determine the effect of ovaprim doses on spawning success of lelan fish (Osteochilus pleurotaenia Blkr). The method used in this research was an experimental method with Completely Randomized Design (CRD) with one factor, four treatments and three replications. The treatment used in this research was an injection of ovaprim with different doses i.e : P0 (0,2 mL NaCl physiology 0,9 %/kg of body weight), P1 (0,5 mL/kg of body weight), P2 (0,6 mL/kg of body weight) and P3 (0,7 mL/kg of body weight). The results showed that ovaprim dose of 0,6 mL/kg of body weight was the bestin turn of latencytime (6.08 hours), total eggs stripping (30.024 eggs/g gonads), egg diameter (0,827 mm), egg maturity (84,443%), Ovi Somatic Index (20,15%), fertility rate (20,01%), hatching rate (19,43 %), and survival rate (29,93 %)

Concrete design optimization by LCA: a critical analysis

In today’s societies, concrete is ever more frequently used, but its production demands a large amount of power that creates environmental pollution. The main material composing concrete is cement which is made from clinker. The necessary high production temperatures cause emissions of CO2. Simultaneously, very significant amounts of demolished concrete produced from deteriorated and obsolete structures create severe ecological and environmental issues. One of the ways to solve these problems is to use this ‘waste’ concrete as an aggregate. Various authors have studied the effects of mixing a portion of recycled aggregates with concrete and they found that this solution has a positive effect on environmental impacts reduction. Preservation of the environment and conservation of the rapidly diminishing natural resources should be the essence of sustainable development

Lymphatic vessels are present in human saccular intracranial aneurysms

Saccular intracranial aneurysm (sIA) rupture leads to subarachnoid haemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the sIA wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in sIAs has remained unexplored. Here we studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for lymphatic endothelial cell (LEC) markers. Of these LEC-markers, both extracellular and intracellular LYVE-1-, podoplanin-, VEGFR-3-, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and alpha-smooth muscle actin (alpha SMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and alpha SMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the pathogenesis of sIA.Peer reviewe

Small oligonucleotides detection in three-dimensional polymer network of dna-peg hydrogels

The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecule detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combines both molecular filtering and molecular capture capabilities for biosensing applications. Along this line, short oligonucleotide detection in a displacement assay is set within PEGDA hydrogels synthetized by UV radical photopolymerization. To provide insights on the molecular filter capability, diffusion studies of several probes (sulforho-damine G and dextrans) with different hydrodynamic radii were carried out using NMR technique. Moreover, fluorometric analyses of hybridization of DNA oligonucleotides inside PEGDA hydrogels shed light on the mechanisms of recognition in 3D, highlighting that mesh size and crowding effect greatly impact the hybridization mechanism on a polymer network. Finally, we found the best probe density and diffusion transport conditions to allow the specific oligonucleotide capture and detection inside PEGDA hydrogels for oligonucleotide detection and the filtering out of higher molecular weight molecules

Rockfall Hazard Analysis at Small Scale: A Numerical Study for the Estimation of Representative Slope Parameters

The identification of rockfall-affected areas depends on a large number of stochastic variables influencing both triggering and propagation phases. Therefore, rockfall hazard assessment presents huge uncertainties linked to the various scales of analysis. At the small scale (e.g. valley scale), a quick evaluation of rockfall hazard zones is generally required in order to highlight the most critical situations where more detailed analyses should be carried out. The Cone Method (Jaboyedoff and Labiouse 2011), recently implemented in the QPROTO plugin for QGIS, allows to reach this goal with simplified geometrical considerations. In a 3D analysis, the energy line angle and the lateral spreading angle α define a cone of propagation whose apex is located in the rockfall source point. The most significant issue in using the plugin is the evaluation of these angles, which must be defined by the users to consider all the rockfall dissipative processes included in the energy line method (Evans and Hungr 1993). In this paper a study concerning the influence of slope properties (forest coverage and slope inclination) and block characteristics (shape and volume) is proposed, in order to provide to the users of the plugin a preliminary dataset of calibrated angles

Serum Amyloid A Is Present in Human Saccular Intracranial Aneurysm Walls and Associates With Aneurysm Rupture

Saccular intracranial aneurysm (sIA) rupture leads to a disabling subarachnoid hemorrhage. Chronic inflammation and lipid accumulation in the sIA wall contribute to wall degenerative remodeling that precedes its rupture. A better understanding of the pathobiological process is essential for improved future treatment of patients carrying sIAs. Serum amyloid A (SAA) is an acute-phase protein produced in response to acute and chronic inflammation and tissue damage. Here, we studied the presence and the potential role of SAA in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), that had previously been studied by histology and immunohistochemistry. SAA was present in all sIAs, but the extent of immunopositivity varied greatly. SAA immunopositivity correlated with wall degeneration (p=0.028) and rupture (p=0.004), with numbers of CD163-positive and CD68-positive macrophages and CD3-positive T lymphocytes (all pPeer reviewe

Optical signature of erythrocytes by light scattering in microfluidic flows

A camera-based light scattering approach coupled with a viscoelasticity-induced cell migration technique has been used to characterize the morphological properties of erythrocytes in microfluidic flows. We have obtained the light scattering profiles (LSPs) of individual living cells in microfluidic flows over a wide angular range and matched them with scattering simulations to characterize their morphological properties. The viscoelasticity-induced 3D cell alignment in microfluidic flows has been investigated by bright-field and holographic microscopy tracking, where the latter technique has been used to obtain precise cell alignment profiles in-flow. Such information allows variable cell probability control in microfluidic flows at very low viscoelastic polymer concentrations, obtaining cell measurements that are almost physiological. Our results confirm the possibility of precise, label-free analysis of individual living erythrocytes in microfluidic flows

Non-invasive and label-free identification of human natural killer cell subclasses by biophysical single-cell features in microfluidic flow

Natural killer (NK) cells are indicated as favorite candidates for innovative therapeutic treatment and are divided into two subclasses: immature regulatory NK CD56bright and mature cytotoxic NK CD56dim. Therefore, the ability to discriminate CD56dim from CD56bright could be very useful because of their higher cytotoxicity. Nowadays, NK cell classification is routinely performed by cytometric analysis based on surface receptor expression. Here, we present an in-flow, label-free and non-invasive biophysical analysis of NK cells through a combination of light scattering and machine learning (ML) for NK cell subclass classification. In this respect, to identify relevant biophysical cell features, we stimulated NK cells with interleukine-15 inducing a subclass transition from CD56bright to CD56dim. We trained our ML algorithm with sorted NK cell subclasses (≥86% accuracy). Next, we applied our NK cell classification algorithm to cells stimulated over time, to investigate the transition of CD56bright to CD56dim and their biophysical feature changes. Finally, we tested our approach on several proband samples, highlighting the potential of our measurement approach. We show a label-free way for the robust identification of NK cell subclasses based on biophysical features, which can be applied in both cell biology and cell therapy

Using Visual Cues to Enhance Haptic Feedback for Palpation on Virtual Model of Soft Tissue

This paper explores methods that make use of visual cues aimed at generating actual haptic sensation to the user, namely pseudo-haptics. We propose a new pseudo-haptic feedback based method capable of conveying 3D haptic information and combining visual haptics with force feedback to enhance the user’s haptic experience. We focused on an application related to tumor identification during palpation and evaluated the proposed method in an experimental study where users interacted with a haptic device and graphical interface while exploring a virtual model of soft tissue, which represented stiffness distribution of a silicone phantom tissue with embedded hard inclusions. The performance of hard inclusion detection using force feedback only, pseudo-haptic feedback only, and the combination of the two feedbacks were compared with the direct hand touch. The combination method and direct hand touch had no significant difference in the detection results. Compared with the force feedback alone, our method increased the sensitivity by 5%, the positive predictive value by 4%, and decreased detection time by 48.7%. The proposed methodology has great potential for robot-assisted minimally invasive surgery and in all applications where remote haptic feedback is needed