BACKGROUND AND PURPOSE Several studies have demonstrated anti‐proliferative and pro‐apoptotic actions of cannabinoids on various tumours, together with their anti‐angiogenic properties. The ...non‐psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down‐regulates some pro‐angiogenic signals produced by glioma cells. As its anti‐angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis.
EXPERIMENTAL APPROACH Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability – through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and FACS analysis – and in vitro motility – both in a classical Boyden chamber test and in a wound‐healing assay. We next investigated CBD effects on different angiogenesis‐related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice.
KEY RESULTS CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down‐modulation of several angiogenesis‐related molecules.
CONCLUSIONS AND IMPLICATIONS This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy.
Introduction In this systematic review, we assessed the literature to determine which evidence level supports the association of orthodontic force system and root resorption. Methods PubMed, ...Cochrane, and Embase databases were searched with no restrictions on year, publication status, or language. Selection criteria included human studies conducted with fixed orthodontic appliances or aligners, with at least 10 patients and the force system well described. Results A total of 259 articles were retrieved in the initial search. After the review process, 21 full-text articles met the inclusion criteria. Sample sizes ranged from 10 to 73 patients. Most articles were classified as having high evidence levels and low risks of bias. Conclusions Although a meta-analysis was not performed, from the available literature, it seems that positive correlations exist between increased force levels and increased root resorption, as well as between increased treatment time and increased root resorption. Moreover, a pause in tooth movement seems to be beneficial in reducing root resorption because it allows the resorbed cementum to heal. The absence of a control group, selection criteria of patients, and adequate examinations before and after treatment are the most common methodology flaws.
Summary
Background
Ticagrelor, a P2Y12 antagonist, is an antiplatelet agent approved for the treatment of acute coronary syndromes; it also inhibits adenosine uptake by erythrocytes and other cells.
...Objective
To test whether ticagrelor inhibits platelet aggregation (PA) in whole blood (WB) by increasing the extracellular levels of adenosine, which inhibits PA via the A2A receptor.
Methods
Collagen‐induced PA was measured in WB or platelet‐rich plasma (PRP) from 50 healthy subjects and two patients with inherited P2Y12 deficiency, in presence/absence of adenosine concentrations that by themselves marginally affected PA in WB, and ZM241385 (A2A antagonist). The effects of ticagrelor, the active metabolite of prasugrel (PAM) (P2Y12 antagonist), and dipyridamole (adenosine uptake inhibitor) on PA and on adenosine clearance in WB were compared.
Results
For PA in WB, adenosine contributed to drug‐induced inhibition of PA; the adenosine contribution was similar for dipyridamole and ticagrelor but was significantly greater for ticagrelor than for PAM (P < 0.01). For PA in PRP (no adenosine uptake by erythrocytes), adenosine contributed to inhibition of PA in the presence/absence of all tested drugs. ZM241385 reversed the inhibition by adenosine in WB and PRP. Similar results were obtained with WB and PRP from P2Y12‐deficient patients. Adenosine (7.1 μmol L–1) added to WB, was detectable for 0.5 min in the presence of vehicle or PAM, for 3–6 min in the presence of ticagrelor, and for > 60 min in the presence of dipyridamole.
Conclusion
This study provides the first evidence of an additional antiplatelet mechanism by ticagrelor, mediated by the induced increase of adenosine levels.
Orthodontic tooth movement is achieved by (re)modeling processes of the alveolar bone, which are triggered by changes in the stress/strain distribution in the periodontium. In the past, the finite ...element (FE) method has been used to describe the stressed situation within the periodontal ligament (PDL) and surrounding alveolar bone. The present study sought to determine the impact of the modeling process on the outcome from FE analyses and to relate these findings to the current theories on orthodontic tooth movement. In a series of FE analyses simulating teeth subjected to orthodontic loading, the influence of geometry/morphology, material properties, and boundary conditions was evaluated. The accurate description of alveolar bone morphology and the assignment of non-linear mechanical properties for the PDF elements demonstrate that loading of the periodontium cannot be explained in simple terms of compression and tension along the loading direction. Tension in the alveolar bone was far more predominant than compression.
Proteomics and metabolomics are analytic tools used in combination with bioinformatics to study proteins and metabolites which contribute to describing complex biological systems. The growing ...interest in research concerning the resolution of these systems has stimulated the development of sophisticated procedures and new applications. This paper introduces the evolution of statistical techniques for the treatment of data, suggesting the possibility to successfully characterize the milk-whey syneresis process by applying two-dimensional correlation analysis (2DCOR) to a series of CE electropherograms referring to milk-whey samples collected during cheese manufacturing. Two cheese-making processes to produce hard cheese (Grana type) and fresh cheese (Crescenza) were taken as models. The applied chemometric tools were shown to be useful for the treatment of data acquired in a systematically perturbed chemical system as a function of time.
A MW 6.3 earthquake struck on April 6, 2009 the Abruzzi region (central Italy) producing vast damage in the L'Aquila town and surroundings. In this paper we present the location and geometry of the ...fault system as obtained by the analysis of main shock and aftershocks recorded by permanent and temporary networks. The distribution of aftershocks, 712 selected events with ML ≥ 2.3 and 20 with ML ≥ 4.0, defines a complex, 40 km long, NW trending extensional structure. The main shock fault segment extends for 15–18 km and dips at 45° to the SW, between 10 and 2 km depth. The extent of aftershocks coincides with the surface trace of the Paganica fault, a poorly known normal fault that, after the event, has been quoted to accommodate the extension of the area. We observe a migration of seismicity to the north on an echelon fault that can rupture in future large earthquakes.
The consumption of ready-to-eat (RTE) leafy vegetables has increased rapidly due to changes in consumer diet. RTE products are perceived as fresh, high-quality, and health-promoting. The monitoring ...of the RTE quality is crucial in relation to safety issues. This study aimed to evaluate the maintenance of RTE rocket salad freshness packed under modified atmospheres. A portable E-nose, the electrolyte leakage test (which measures the index of leaf damage-I
), and NIR spectroscopy and Aquaphotomics were employed. Two trials were carried out, using the following gas mixtures: (A) atmospheric air (21% O
, 78% N
); (B) 30% O
, 70% N
; (C) 10% CO
, 5% O
, 85% N
. Samples were stored at 4 °C and analyzed at 0, 1, 4, 7, 11, and 13 days. ANOVA, PCA, PLS were applied for data processing. E-nose and I
results identified the B atmosphere as the best for maintaining product freshness. NIR spectroscopy was able to group the samples according to the storage time. Aquaphotomics proved to be able to detect changes in the water structure during storage. These preliminary data showed a good agreement NIR/I
suggesting the use of NIR for non-destructive monitoring of the damage to the plant membranes of RTE rocket salad.
Background: Light transmission aggregometry (LTA) is the most common method used in clinical and research laboratories to assess platelet function. However, the method has never been standardized. ...Objectives: As the first step towards development of methodological guidelines, the Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH) undertook a large, detailed, global survey of LTA practices. Methods: Members of ISTH and of External Quality Assurance in Thrombosis and Haemostasis organizations were invited to complete a 129 item, online questionnaire. Results were analyzed anonymously to participant identities. Results: The online supplement for this article (http://www.isth.org/Publications/OfficialCommunications/PlateletPhysiology/LightTransmissionAggregometry/tabid/201/Default.aspx) contains the full details of the study findings. 359 (244 clinical, 115 research) laboratories from 48 countries participated in the survey. LTA was widely used to assess inherited or acquired bleeding disorders. Common practices were identified in sample collection, processing and analysis and although some are generally considered acceptable, others are not ideal. The agonist concentrations used for LTA varied, and many laboratories used ADP, collagen, epinephrine and Ristocetin, at more than one concentration, in addition to arachidonic acid. The parameters commonly used to assess LTA responses were maximal amplitude or % aggregation, which was considered particularly important, in addition to the presence of a ‘secondary wave’, deaggregation, shape change and a measure of the lag phase. However, many laboratories did not have appropriate reference intervals. Conclusions: This is the largest and most detailed survey of LTA practices ever undertaken. It shows a very high variability in LTA practices worldwide, and, as a consequence, methodological standardization is necessary. The information gathered in this survey will be helpful in the development of ISTH methodological guidelines for LTA.
Summary
The activation of thromboxane prostanoid (TP) receptor on platelets, monocytes/macrophages, endothelial cells, and vascular smooth muscle cells (SMC) plays important roles in regulating ...platelet activation and vascular tone and in the pathogenesis of thrombosis and vascular inflammation. Oxidative stress and vascular inflammation increase the formation of TP receptor agonists, which promote initiation and progression of atherogenesis and thrombosis. Furthermore, TP receptor activation promotes angiogenesis and vessel wall constriction. Besides thromboxane A2 and its endoperoxide precursors, prostaglandin G2 and H2, isoprostanes, and 20‐hydroxyeicosatetraenoic acid also activate TP receptor as autocrine or paracrine ligands. These additional TP activators play a role in pathological conditions such as diabetes, obesity, and hypertension, and their biosynthesis is not inhibited by aspirin, at variance with that of thromboxane A2. The understanding of TP receptor function increased our current knowledge of the pathogenesis of atherosclerosis and thrombosis, highlighting the great impact that this receptor has in cardiovascular disorders.
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