When nanoparticles come into contact with biological media, they are covered by a biomolecular 'corona', which confers a new identity to the particles. In all the studies reported so far ...nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let multicomponent liposomes interact with fetal bovine serum (FBS) both statically and dynamically, i.e. in contact with circulating FBS (≈40 cm s(-1)). The structure and composition of the liposome-protein corona, as determined by dynamic light scattering, electrophoretic light scattering and liquid chromatography tandem mass spectrometry, were found to be dependent on the incubation protocol. Specifically, following dynamic exposure to FBS, multicomponent liposomes were less enriched in complement proteins and appreciably more enriched in apolipoproteins and acute phase proteins (e.g. alpha-1-antitrypsin and inter-alpha-trypsin inhibitor heavy chain H3) that are involved in relevant interactions between nanoparticles and living systems. Supported by our results, we speculate that efficient predictive modeling of nanoparticle behavior in vivo will require accurate knowledge of nanoparticle-specific protein fingerprints in circulating biological media.
The importance of Diffusion Weighted Imaging (DWI) in prostate cancer (PCa) diagnosis have been widely handled in literature. In the last decade, due to the mono-exponential model limitations, ...several studies investigated non-Gaussian DWI models and their utility in PCa diagnosis. Since their results were often inconsistent and conflicting, we performed a systematic review of studies from 2012 examining the most commonly used Non-Gaussian DWI models for PCa detection and characterization. A meta-analysis was conducted to assess the ability of each Non-Gaussian model to detect PCa lesions and distinguish between low and intermediate/high grade lesions. Weighted mean differences and 95% confidence intervals were calculated and the heterogeneity was estimated using the I
statistic. 29 studies were selected for the systematic review, whose results showed inconsistence and an unclear idea about the actual usefulness and the added value of the Non-Gaussian model parameters. 12 studies were considered in the meta-analyses, which showed statistical significance for several non-Gaussian parameters for PCa detection, and to a lesser extent for PCa characterization. Our findings showed that Non-Gaussian model parameters may potentially play a role in the detection and characterization of PCa but further studies are required to identify a standardized DWI acquisition protocol for PCa diagnosis.
Although clinical examination still represents the gold standard for the differential diagnosis of prolonged disorders of consciousness (pDoC), the introduction of innovative markers is essential for ...diagnosis and prognosis, due to the problem of covert cognition. We evaluated the brain-derived neurotrophic factor protein (BDNF) and the soluble cell adhesion molecules proteins (CAMs) in a cohort of prolonged disorders of consciousness patients to identify a possible application in the clinical context. Furthermore, peripheral blood determinations were correlated with imaging parameters such as white matter hyperintensities (WMH), cranial standardized uptake value (cSUV), electroencephalography (EEG) data and clinical setting. Our results, although preliminary, identify BDNF as a possible blood marker for the diagnosis of pDoC (p value 0.001), the soluble CAMs proteins CD44, Vcam-1, E-selectin (p value < 0.01) and Icam-3 (p value < 0.05) showed a higher peripheral blood value in pDoC compared with control. Finally, soluble Ncam protein could find useful applications in the clinical evolution of the pDoC, showing high levels in the MCS and EMCS subgroups (p value < 0. 001) compared to VS/UWS.
When liposomes are exposed to biological fluids, a dynamic coating of proteins immediately covers them. Similarly to the aura of plasma surrounding the Sun, plasma proteins are thought of as ...establishing an aura that surrounds each liposome, hence the phenomenon was dubbed ‘protein corona’. This natural functionalization includes proteins engaged from the blood that can interact with receptors (over)expressed on the plasma membrane of target cells, thus targeting the liposomes to their final destination. Exploiting the liposome–protein corona for targeting has the potential to revolutionize the treatment of many disorders and requires a deep understanding of the factors shaping the corona. Following incubation with human plasma (HP), here we manipulated this corona by using six liposomal formulations with systematic changes in lipid composition. The lipids we employed are among the most frequently used lipid species for drug and gene delivery applications in vitro and in vivo . The six liposome–protein coronas were thoroughly characterized by synchrotron small angle X-ray scattering, dynamic light scattering, zeta-potential and nanoliquid-chromatography tandem mass spectrometry experiments. We identified general principles shaping the liposome–protein corona and established clear-cut relationships between lipid species and classes of plasma proteins. This knowledge sets the basis for a rational manipulation of the protein corona for targeted drug delivery by liposome design.
A laboratory experimental model of an incident ocean wave interacting with an ice floe is used to validate the canonical, solitary floe version of contemporary theoretical models of wave attenuation ...in the ice‐covered ocean. Amplitudes of waves transmitted by the floe are presented as functions of incident wave steepness for different incident wavelengths. The model is shown to predict the transmitted amplitudes accurately for low incident steepness but to overpredict the amplitudes by an increasing amount, as the incident wave becomes steeper. The proportion of incident wave energy dissipated by the floe in the experiments is shown to correlate with the agreement between the theoretical model and the experimental data, thus implying that wave‐floe interactions increasingly dissipate wave energy as the incident wave becomes steeper.
Key Points
Wave scattering theory alone is not sufficient to predict attenuation of waves
Wave energy is not conserved during wave‐ice interactions
Turbulent bores at the floes front and rear edges induce dissipation
As soon as nanomaterials, such as nanoparticles (NPs), are injected into a physiological environment a rich coating of biomolecules known as the "protein corona" rapidly covers them. This protein ...dress is the main factor, which affects the interaction of NPs with living systems. While the relationship between NP features and the biomolecule corona has been extensively investigated, whether and how changes in the physiological environment affect the NP-protein corona remains under-investigated. This is one of the most important steps in translating results in animal models to the clinic. Here we investigated thoroughly the biological identity of lipid NPs (size, charge, aggregation state and composition of the corona) after incubation with human plasma (HP) and mouse plasma (MP) by dynamic light scattering, micro-electrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC/MS-MS). Specifically, we used two different liposomal formulations: the first one was made of polyethyleneglycol (PEG)-coated 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), while the second one was made of 30% of DOTAP, 50% of neutral saturated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 20% cholesterol. The temporal evolution and complexity of the NP-protein corona was found to be strongly dependent on the biological environment. In MP, liposomes were more negatively charged, less enriched in opsonins and appreciably more enriched in apolipoproteins than their counterparts in HP. Collectively, our results suggest that the biological identities of NPs in mice and humans can be markedly different from each other. Relevance of results to in vivo applications is discussed.
Allergic rhinitis Incorvaia, C; Cavaliere, C; Frati, F ...
Journal of biological regulators and homeostatic agents,
2018 Jan-Feb, Letnik:
32, Številka:
1 Suppl. 1
Journal Article
Recenzirano
Allergic rhinitis (AR) was long considered a quite trivial disease, but the advance in epidemiological and clinical knowledge, with a major role for Allergic rhinitis and its Impact on Asthma (ARIA) ...initiative, substantially changed the scene. Now we know that AR has significant effects on patients quality of life and also has a relevant economic burden. The ARIA phenotypes related to the duration of symptoms and to the severity of AR are very useful in establishing the optimal strategy in each patient with AR, also according to the kind of allergens that cause rhinitis. When traditional allergy testing, including skin prick tests and in vitro of specific IgE antibodies are not sufficient for the diagnosis, modern techniques such as molecular diagnostics may be used. Also the management of AR may be tailored to single patients according to the clinical expression of AR, that may vary from mild to moderate-severe stage, with the aim of achieving the best possible control of the disease.
Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large ...population of severe asthmatics.
340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab.
Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.1141.509–6.424, p = 0.002), for a disease partial/no control (OR:2.6651.064–6.680, p = 0.036), for excessive SABA use (OR:4.4481.837–10.768, p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (β = −6.981,p = 0.04), FVC (β = −11.689,p = 0.014) and ACT (β = −2.585, p = 0.027) and was associated with a higher FENO level (β = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.3831.128–1.697, p = 0.008) and for an ACT <20 (OR:2.4101.071–3.690, p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response.
Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.
•A fair proportion of severe asthmatics may have a reduced Omalizumab response.•Several factors may reduce Omalizumab effectiveness in these patients.•They are: age, obesity, comorbidities, smoking, nasal polyps, polysensitization.•These factors act independently of many asthma-influencing variables.•When managing these patients, we should consider multidisciplinary interventions.
Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein ...among Italian cypress pollen-allergic patients.
A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7.
Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP.
Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.
Highlights • Simultaneous PET/MRI is a suitable tool for head/neck T-staging. • No significant differences have been found for PET measures get by both PET/CT and PET/MRI. • SUV 2D and 3D measures in ...HN lesion offer comparable estimations. • Multiparametric evaluation allows a complete characterization of HN lesions.
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