Extracellular vesicle signalling in atherosclerosis

Atherosclerosis is a major cardiovascular disease and in 2016, the World Health Organisation (WHO) estimated 17.5 million global deaths, corresponding to 31% of all global deaths, were driven by inflammation and deposition of lipids into the arterial wall. This leads to the development of plaques which narrow the vessel lumen, particularly in the coronary and carotid arteries. Atherosclerotic plaques can become unstable and rupture, leading to myocardial infarction or stroke. Extracellular vesicles (EVs) are a heterogeneous population of vesicles secreted from cells with a wide range of biological functions. EVs participate in cell-cell communication and signalling via transport of cargo including enzymes, DNA, RNA and microRNA in both physiological and patholophysiological settings. EVs are present in atherosclerotic plaques and have been implicated in cellular signalling processes in atherosclerosis development, including immune responses, inflammation, cell proliferation and migration, cell death and vascular remodeling during progression of the disease. In this review, we summarise the current knowledge regarding EV signalling in atherosclerosis progression and the potential of utilising EV signatures as biomarkers of disease

Sobrevivência de Bacillus thurigiensis, antagonista a Hemileia vastatrix, no filoplano de cafeeiros.

O isolado B157 de Bacillus thurigiensis foi eficiente no biocontrole da ferrugem do cafeeiro em casa-de-vegetação e em cultivos orgânicos no campo. Para definir estratégias de uso do biocontrole, estudaram-se a dinâmica de sobrevivência do isolado B157 no filoplano de cafeeiro e a influência de diferentes fungicidas a base de cobre na sobrevivência do isolado, em casa-de-vegetação e campo. Para verificar o efeito de fungicidas cúpricos na sobrevivência de B157, pulverizou-se hidróxido de cobre em mudas ou sulfato de cobre em cafeeiros, em casa de vegetação e campo. Após a avaliação da densidade populacional de B157, verificou-se que em ambas as condições experimentais, a aplicação de fungicida, independente da fonte de cobre utilizada, reduziu a população da bactéria ao longo do tempo e o período de sobrevivência de B157. Em casa de vegetação, na primeira semana, a população de B157 reduziu-se, em média, 10 e 52% nas parcelas sem e com fungicida, respectivamente. A pulverização dos fungicidas reduziu o tempo de sobrevivência da bactéria, em casa de vegetação e no campo. Para controle da ferrugem no campo, poder-se-iam adotar duas estratégias: (i) pulverizar apenas o isolado B157 ou (ii) aplicar o isolado nas primeiras pulverizações e fungicidas cúpricos, posteriormente

Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries

<p><b>Objective:</b> We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.</p> <p><b>Methods and Results:</b> One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 micromol/L) reduced tumor necrosis factor-alpha (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.</p> <p><b>Conclusion:</b> Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.</p&gt

Comparison between Eight-Axis Articulated Robot and Five-Axis CNC Gantry Laser Metal Deposition Machines for Fabricating Large Components

Featured Application: Laser metal deposition of large axisymmetric components. Laser metal deposition (LMD) is an additive manufacturing (AM) process capable of producing large components for the aerospace and oil and gas industries. This is achieved by mounting the deposition head on a motion system, such as an articulated robot or a gantry computer numerical control (CNC) machine, which can scan large volumes. Articulated robots are more flexible and less expensive than CNC machines, which on the other hand, are more accurate. This study compares two LMD systems with different motion architectures (i.e., an eight-axis articulated robot and a five-axis CNC gantry machine) in producing a large gas turbine axisymmetric component. The same process parameters were applied to both machines. The deposited components show no significant differences in geometry, indicating that the different performances in terms of accuracy of the two machines do not influence the outcome. The findings indicate that LMD can consistently produce large-scale axisymmetric metal components with both types of equipment. For such an application, the user has the option of using an articulated robot when flexibility and cost are essential, such as in a research context, or a CNC machine where ease of programming and process standardization are important elements, such as in an industrial environment

Enhancing productivity and efficiency in conventional laser metal deposition process for Inconel 718 – Part II: advancing the process performance

This paper is the second part of a work focused on optimizing the performance of conventional Laser Metal Deposition (C-LMD) process for Inconel 718 (IN718). In Part I, through an extensive experimental campaign on single tracks, the interplay between process parameters and their impact on the deposition rate, powder catchment efficiency, and clad geometry is examined. The parameters investigated include laser power, scan speed, powder feed rate, and standoff distance. By systematically adjusting these parameters, the aim is to identify optimal conditions that maximize productivity while maintaining a favorable clad shape for multi-pass multi-layer depositions. Part II starts from the findings and results of Part I by continuing the optimization on thick wall structures. These are utilized to assess the effect of 3D geometrical process parameters, specifically hatch spacing and Z-step, on process performance and stability. Based on the findings, further optimization procedure is presented, pushing the boundaries of the C-LMD process for IN718. By fine-tuning the process parameters, the capability of the C-LMD process to deposit fully dense IN718 with a productivity of 1500 g/h and a powder catchment efficiency of 70% is demonstrated. These results highlight the potential of C-LMD as a viable manufacturing technique for efficiently fabricating large components. Overall, this study contributes to a deeper understanding of the relationship between process parameters and performance in C-LMD for IN718. The insights gained from this research can guide the development of efficient and cost-effective LMD strategies, facilitating the practical implementation of this process in various industries

Enhancing productivity and efficiency in conventional laser metal deposition process for Inconel 718 - part I: the effects of the process parameters

The sustainable energy transition has spurred the development of technologies that minimize material and energy waste, such as additive manufacturing (AM). Laser metal deposition (LMD) is a promising AM technique, but its complexity and limited automation hinder its implementation in production chains. To enhance productivity, the high deposition rate LMD (HDR-LMD) technology has been developed, requiring advanced equipment and powerful laser sources. In contrast, the conventional LMD (C-LMD) process is simpler and less expensive to implement. This study aims to optimize the productivity and efficiency of C-LMD by adjusting laser power, scan speed, powder feed rate, and standoff distance on Inconel 718 single tracks. An innovative approach eliminates the need for cutting specimens to evaluate single tracks, allowing comprehensive geometric and performance characterization with limited operator involvement, making the analysis quicker and more robust. An extensive experimental campaign was conducted to examine the influence of process parameters on track geometry, productivity, and efficiency. A multi-objective optimization procedure identified parameter combinations maximizing productivity while maintaining high efficiency and desirable clad shape. The study attained deposition rates ranging from 700 to 800 g/h, with powder catchment efficiency ranging between 75 and 90%. These results were achieved using parameters including 1775 W of laser power, scan speeds ranging from 960 to 1140 mm/min, powder feed rates between 810 and 1080 g/h, and standoff distance of 9 mm. The study also clearly indicated that further potential for improving C-LMD process performance may be possible. The findings gathered in this paper are the base for the further optimization presented in the second part of the work, which is focused on multi-pass multi-layer and reaches deposition rates of 1500 g/h, promoting the implementation of C-LMD process at industrial level

Imaging interactions between the immune and cardiovascular systems in vivo by multiphoton microscopy

Several recent studies in immunology have used multiphoton laser-scanning microscopy to visualise the induction of an immune response in real time in vivo. These experiments are illuminating the cellular and molecular interactions involved in the induction, maintenance and regulation of immune responses. Similar approaches are being applied in cardiovascular research where there is an increasing body of evidence to support a significant role for the adaptive immune system in vascular disease. As such, we have begun to dissect the role of T lymphocytes in atherosclerosis in real time in vivo. Here, we provide step-by-step guides to the various stages involved in visualising the migration of T cells within a lymph node and their infiltration into inflamed tissues such as atherosclerotic arteries. These methods provide an insight into the mechanisms involved in the activation and function of immune cells in vivo

The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.<br></br> Methods and Results—In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-kB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 micromol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E-/-, mice in which the NBD peptide (150 microg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).<br></br> Conclusion—The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kB activation