Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Diagnostic accuracy of myocardial perfusion imaging with czt technology. Systemic review and meta-analysis of comparison with invasive coronary angiography

OBJECTIVES: This study sought to summarize the evidence on stress myocardial perfusion imaging (MPI) using cadmium-zinc-telluride (CZT) technology for the diagnosis of obstructive coronary artery disease (CAD). The CZT cameras are newly introduced, and comparative data with the conventional Anger technology (Anger-MPI) are lacking. BACKGROUND: The diagnostic accuracy of Anger-MPI for detection of angiographically significant CAD is well established; however, less evidence is available on the diagnostic accuracy of CZT-MPI. METHODS: Clinical studies comparing CZT-MPI and invasive coronary angiography were systematically searched and abstracted. Calculations of diagnostic accuracy, including sensitivity, specificity, likelihood ratios, and diagnostic odds ratio, were obtained with fixed and random effects, reporting point estimates and 95% confidence intervals. RESULTS: Based on our search, a total of 16 studies (N = 2,092) were included. The sensitivity of CZT-MPI was 0.84 (95% confidence interval [CI]: 0.78 to 0.89), whereas the specificity of 0.69 (95% CI: 0.62 to 0.76) was significantly reduced. The positive likelihood ratio was 2.73 (95% CI: 2.21 to 3.39), the negative likelihood ratio was 0.24 (95% CI: 0.17 to 0.31), and the diagnostic odds ratio was 11.93 (95% CI: 7.84 to 17.42). At subgroup and meta-regression analyses, the diagnostic accuracy between D-SPECT and Discovery cameras was similar (p = 0.711) and not impacted upon by smaller sample size studies (p = 0.573). CONCLUSIONS: CZT-MPI has satisfactory sensitivity for angiographically significant CAD, but its suboptimal specificity warrants further development and research

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Morphochemical age-related changes in the nematode Caenorhabditis elegans: immunoperoxidase localization of cytokine- and growth factor-like molecules

Morphochemical age-related features in the hermaphrodite Caenorhabditis elegans are reported. The study of worms of different ages shows a gradual decline in response to the various histochemical reactions and a disorganization of the components of the gonad during ageing. Using an immunocytochemical procedure, we show for the first time the presence of immunoreactive IL-1alpha and PDGF-AB molecules in neurons from young adult C. elegans. Moreover, TNF-alpha- and PDGF-AB-like molecules are also present in the secretory cells of the pharyngeal terminal bulb. The number of positive cells to anti-cytokine and anti-growth factor antibodies decreases in older worms, suggesting that these molecules may play an important role in worm ageing. The present investigation therefore supports the findings in the literature obtained with different approaches on the crucial role of the nervous and reproductive systems in the life span of C. elegans

Nuclear functions of the tyrosine kinase Src

Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors

Aortic regurgitation in athletes. Pieces of the puzzle we have so far omitted

The prevalence of valvular heart disease (VHD) rises with age, reaching 11.7% in individuals older than 75 years.1 In young individuals, VHD is usually related to the presence of a congenital valve abnormality, as bicuspid aortic valve (BAV) or mitral valve prolapse. This is also the case for athletes, where in the presence of these abnormalities few restrictions exist in eligibility for competitive sports participation, even if a strict follow-up would be desirable. BAV is the most common congenital valve abnormality (1%) found in the general population and in athletes. BAV is more prevalent in males and it can lead to aortic regurgitation (AR), aortic stenosis and/or aortic root dilation. At present, no definitive studies have proved that intensive sports participation could worsen the progression of BAV and limited data are available on athletes

Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA

In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation. We hypothesized that endotracheal tube-induced sore throat pain is linked to mitochondrial DNA-mediated neutrophil inflammation. A nonrandomized prospective survey for sore throat pain was conducted in 31 patients who required short-term intubation and had no evidence of upper airway infection. Patterns of neutrophil abundance, activation, and mitochondrial DNA levels were analyzed in tracheal lavage fluid following intubation and prior to extubation. Thirteen of 31 patients reported sore throat pain. Sore throat patients had high neutrophilia with elevated adhesion molecule and TLR9 expression and constitutive reactive oxygen species generation. Tracheal lavage fluid from sore throat patients accumulated mitochondrial DNA and stimulated neutrophils to release mediators associated with pain in a TLR9- and DNAse-dependent fashion. Endotracheal tube-induced sore throat is linked to the release of mitochondrial DNA and can drive TLR9-mediated inflammatory responses by neutrophils reported to cause pain. Mitigating the effects of cell-free mitochondrial DNA may prove beneficial for the prevention of endotracheal tube-mediated sore throat pain

Heavy metal distribution in a sediment phytoremediation system at pilot scale

The continuous stream of polluted sediments, dredged from harbors and water bodies in order to maintain the navigation, is a common practice, but the fate of these sediments is an issue recognized worldwide. This pilot case study evaluated the application of phytoremediation as sustainable management strategy for the decontamination of polluted dredged marine sediments. The synergic action of different plant species (Paspalum vaginatum; P. vaginatum + Spartium junceum and P. vaginatum + Tamarix gallica) and organic matter (compost) in removing both heavy metals (Cd, Ni, Zn, Pb and Cu) and total petroleum hydrocarbons, and in recovering the nutritive and biological sediment properties were evaluated. In addition to the detection of total metal removal efficiency, the chemical distribution of metals in the sediment phases (exchangeable, manganese and iron oxides, organic matter and residual minerals) was also measured in order to make a more realistic estimation of the phytoremediation efficiency for the sediment decontamination. Finally, a complete picture of the metal flux was obtained by investigating the metal mass-balance in the treated sediments. The results of metal content in the sediment phases showed that metal distribution was not uniform and each metal predominated in different fractions; the solubility of metals in the sediment in the decreasing order was: Cd>Zn>Cu>Pb>Ni. The higher proportion of Ni and Pb in the residual phase can be the reason of the lower translocation of these metals in the plant tissues. On the other hand, Cd, Zn and Cu were the metals most easily translocated in plant tissues, both aboveground and roots, confirming their higher availability for the plants. The results of mass balance indicated that, at the end of the experimentation, a high content of metals were still found in the sediment. The greatest contribution in metal removal was attributed to a phytostabilization process at rhizosphere level followed by gravel and sand absorption. The capacity of rhizophere to precipitate heavy metals, could be considered as an alternative option for reducing the metal availability and, consequently, the toxicity in contaminated sediments

Taxa endemic to Campania (southern Italy): Nomenclatural and taxonomic notes

The authors briefly discuss about the list of the taxa endemic to Campania (southern Italy) and the typification of their names. The names Santolina neapolitana and Seseli polyphyllum (and other linked names) are lectotypified on herbarium specimens kept at LY and BOLO. A new combination at subspecific rank is proposed for Globularia neapolitana, validating both a previous invalid proposal and an unpublished lectotypification