MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression.

Background: MBL-associated serine proteases (MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19) are key factors in the activation of the lectin pathway of complement. Serum levels of these components have been associated with recurrence and poor survival of some types of cancer, such as colorectal and ovarian cancer. In this investigation, we determined the serum levels of MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods:A total of 351 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba-Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: n = 52; CIN-II: n = 73; CIN-III: n = 141; and invasive cancer: n = 78. All the serum protein levels were determined by time-resolved immunofluorometric assay (TRIFMA). Results:Patients with invasive cancer presented significantly higher MASP-2, MASP-1, and MAp-19 serum levels than other groups (p < 0.0001; p = 0.012; p = 0.025 respectively). No statistically significant differences in MASP-3 and MAp-44 serum levels were found between the four studied groups. In addition, high MASP-2, MASP-1, and MAp-19 serum levels were significantly associated with poor survival in patients with invasive cancer and relapse (p = 0.002, p = 0.0035 and p = 0.025, respectively). Conclusion:High MASP-2, MASP-1, and MAp-19 serum levels were associated with cervical cancer progression and worse disease prognosis. These novel findings demonstrate the involvement of the serine proteases of the lectin pathway in the pathogenesis of cervical cancer and future investigations should clarify their role in the disease process.

Nanosilver as a disinfectant in dental unit waterlines: Assessment of the physicochemical transformations of the AgNPs.

Dental unit water lines (DUWL) are susceptible to biofilm development and bacterial growth leading to water contamination, causing health and ecological effects. This study monitors the interactions between a commonly used nanosilver disinfectant (ASAP-AGX-32, an antimicrobial cleaner for dental units, 0.0032% Ag) and biofilm development in DUWL. To simulate the disinfection scenario, an in-house DUWL model was assembled and biofilm accumulation was allowed. Subsequent to biofilm development, the disinfection process was performed according to the manufacturer's instructions. The pristine nanosilver particles in the cleaner measured between 3 and 5 nm in diameter and were surrounded by a stabilizing polymer. However, the polymeric stabilizing agent diminished over the disinfection process, initiating partial AgNPs aggregation. Furthermore, surface speciation of the pristine AgNPs were identified as primarily AgO, and after the disinfection process, transformations to AgCl were observed. The physicochemical characteristics of AgNPs are known to govern their fate, transport and environmental implications. Hence, knowledge of the AgNPs characteristics after the disinfection process (usage scenario) is of significance. This study demonstrates the adsorption of AgNPs onto biofilm surfaces and, therefore, will assist in illustration of the toxicity mechanisms of AgNPs to bacteria and biofilms. This work can be an initial step in better understanding how AgNPs transform depending on the conditions they are exposed to during their lifetime. Until this date, most research has been focused on assessing the impacts of pristine (lab synthesized) nanomaterials on various systems. However, it is our belief that nanoparticles may undergo transformations during usage, which must be taken into consideration. Furthermore, this experiment is unique as it was conducted with a commonly used, commercially available nanosilver suspension leading to more realistic and applicable findings.

Anaerobic toxicity of cationic silver nanoparticles.

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag(+) under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10-15nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5mgL(-1), the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100mgL(-1) as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag(+). Both citrate and PVP-AgNPs did not exhibit toxicity at the 100mgL(-1) as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles.

The impact of silver nanoparticles on the composting of municipal solid waste.

The study evaluates the impact of polyvinylpyrrolidone (PVP) coated silver nanoparticles (PVP-AgNPs) on the composting of municipal solid waste. The results suggest that there was no statistically significant difference in the leachate, gas, and solid quality parameters and overall composting performance between the treatments containing the AgNPs, Ag(+), and negative control. Nonetheless, taxonomical analyses of 25 Illumina 16S rDNA barcoded libraries containing 2 393 504 sequences indicated that the bacterial communities in composted samples were highly diverse and primarily dominated by Clostridia (48.5%), Bacilli (27.9%), and beta-Proteobacteria (13.4%). Bacterial diversity studies showed that the overall bacterial community structure in the composters changed in response to the Ag-based treatments. However, the data suggest that functional performance was not significantly affected due to potential bacterial functional redundancy within the compost samples. The data also indicate that while the surface transformation of AgNPs to AgCl and Ag2S can reduce the toxicity, complexation with organic matter may also play a major role. The results of this study further suggest that at relatively low concentrations, the organically rich waste management systems' functionality may not be influenced by the presence of AgNPs.

Energetics of protein adsorption on amine-functionalized mesostructured cellular foam silica.

The energetics of lysozyme adsorption on aminopropyl-grafted MCF silica (MCF-NH2) are compared to the trends observed during lysozyme adsorption on native MCF silica using flow microcalorimetry (FMC). Surface modification on MCF silica affects adsorption energetics significantly. All thermograms consist of two initial exothermic peaks and one later endothermic peak, but the heat signal trends of MCF-NH2 are opposite from those observed for adsorption onto native MCF silica in salt solutions of sodium acetate and sodium sulfate. At low ionic strength (0.01 M), LYS adsorption onto MCF-NH2 was accompanied by a large exotherm followed by a desorption endotherm. With increasing ionic strength (0.1 and 3.01 M), the magnitude of the thermal signal decreased and the total process became less exothermic. Also a higher protein loading of 14 µmol g(-1) was obtained at low ionic strength in batch adsorption isotherm measurements. Taken together, the FMC thermograms and batch adsorption isotherms reveal that MCF-NH2 has the nature of an ion exchange adsorbent, even though lysozyme and the aminopropyl ligands have like net charges at the adsorption pH. Reduced electrostatic interaction, reduced Debye length, and increased adsorption-site competition attenuate exothermicity at higher ionic strengths. Thermograms from flow microcalorimetry (FMC) give rich insight into the mechanisms of protein adsorption. A two-step adsorption mechanism is proposed in which negatively charged surface amino acid side chains on the lysozyme surface make an initial attachment to surface aminopropyl ligands by electrostatic interaction (low ionic strength) or van der Waals interaction (high ionic strength). Secondary attachments take place between protruding amino acid side chains and silanol groups on the silica surface. The reduced secondary adsorption heat is attributed to the inhibitory effect of the enhanced steric barrier of aminopropyl group on MCF silica.

Energetics of lysozyme adsorption on mesostructured cellular foam silica: effect of salt concentration.

The heat of lysozyme adsorption on mesostructured cellular foam (MCF) silica was measured using flow microcalorimetry (FMC) to investigate the influence of a neutral salt, sodium sulfate. At concentrations up to 0.5 M sodium sulfate, a complex initial exotherm was followed by an endotherm. Protein surface coverage, the magnitudes of the exothermic heat signals and the magnitudes of the net heat of adsorption increased with sodium sulfate concentration. These observations suggest that electrostatic interactions are the principal driving force at low ionic strengths; van der Waals interactions become dominant at higher salt concentrations. Each exotherm could be deconvoluted into two exotherms, indicating multiple modes of lysozyme attachment to the silica surface. The endothermic peak, associated with protein desorption, disappeared at the highest sodium sulfate concentration (1.0 M), indicating irreversible adsorption of the protein on the MCF silica surface. The data are consistent with an adsorption mechanism in which the initial attachment of lysozyme to the surface is followed by a reorientation and formation of a secondary or stronger attachment to the surface.

Investigation of the mechanism of protein adsorption on ordered mesoporous silica using flow microcalorimetry.

The adsorption of bovine serum albumin (BSA) and lysozyme (LYS) on siliceous SBA-15 with 24 nm pores was studied using flow microcalorimetry; this is the first attempt to understand the thermodynamics of protein adsorption on SBA-15 using flow microcalorimetry. The adsorption mechanism is a strong function of protein structure. Exothermic events were observed when protein-surface interactions were attractive. Entropy-driven endothermic events were also observed in some cases, resulting from lateral protein-protein interactions and conformational changes in the adsorbed protein. The magnitudes of the enthalpies of adsorption for primary protein-surface interactions decrease with increased surface coverage, indicating the possibility of increased repulsion between adsorbed protein molecules. Secondary exothermic events were observed for BSA adsorption, presumably due to secondary adsorption made possible by conformational changes in the soft BSA protein. These secondary adsorption events were not observed for lysozyme, which is structurally robust. The results of this study emphasize the influence of solution conditions and protein structure on conformational changes of the adsorbed protein and the value of calorimetry in understanding protein-surface interactions.

Comparative thermodynamic and spectroscopic properties of water interaction with human stratum corneum.

BACKGROUND/PURPOSE: The water content of skin has a significant impact on skin properties; sufficient hydration is necessary to keep the skin supple, flexible, and smooth. To understand more completely the water retention properties of the human skin barrier, physical macroscopic properties must be related to the structural organization of the stratum corneum (SC). Water, lipids, and natural moisturizing factor (NMF) influence the molecular structures that affect the properties of SC, including water sorption and binding enthalpy. In the research reported here, isothermal microcalorimetry was used to study the interaction of water vapor with isolated human SC in intact, delipidized, and water-washed delipidized forms to identify the influences of the principal components of SC on water sorption. The calorimetric data are interpreted in conjunction with spectroscopic results to identify the conformational changes in keratins induced by lipid and NMF removal and to assess the influence of these changes on water binding in SC. METHODS: Isothermal calorimetry was used to measure the integral heat of water vapor sorption on intact, delipidized, and water-washed delipidized human SC at 32 degrees C as a function of relative humidity using back and thigh skin from three donors. Calorimetric measurements were combined with water vapor sorption measurements to determine the differential thermodynamic properties of these systems. Attenuated total reflection-Fourier transform infrared spectroscopy was used to investigate effects of extraction on protein secondary structure. RESULTS: The magnitudes of the differential enthalpy, entropy, and free energy were greatest for intact SC and least for water-washed delipidized SC. Water sorption followed a similar trend. Delipidization led to a significantly reduced binding enthalpy at low water content; water washing the delipidized SC had only a small additional effect on binding enthalpy. Delipidization converts a fraction of keratin alpha-helixes to turns and random coils, while water sorption converts a fraction of keratin alpha-helixes to beta-sheets, turns, and random coils. CONCLUSIONS: The results of this study are consistent with a water sorption model in which keratin-keratin hydrogen bonds are replaced by keratin-water hydrogen bonds. Delipidization reduces the fraction of dry keratin that is in the alpha-helix conformation, suggesting that lipids hold the keratins in a conformation conducive to optimal hydration.