Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory ...activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from
venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 10
with ATXL and 5 × 10
with BATXH. TNF-α was identified in the supernatant of BATXH-or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC-MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4-5 × 10
) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in
envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways.
•An accessible and highly concentrated working standard specific for IgG against SARS-CoV-2 Spike-protein was prepared.•The serological SARS-CoV-2 WHO International Standard behaves differently from ...the working standard produced using sera from vaccinated subjects.•A single instrument-to-instrument conversion factors is not sufficient to harmonize different instruments readouts from single samples.•The devices tested performed well in predicting neutralization activity based on the antibody titer.
Vaccines, to limit SARS-CoV-2 infection, were produced and reliable assays are needed for their evaluation. The WHO produced an International-Standard (WHO-IS) to facilitate the standardization/comparison of serological methods. The WHO-IS, produced in limited amount, was never tested for reproducibility. This study aims at developing a reproducible and accessible working standard (WS) to complement the WHO-IS.
Sera from vaccinated individuals were used to produce the WSs. The WHO-IS, the WSs and single serum samples (n = 48) were tested on 6 quantitative serological devices. Neutralization assays were performed for the 48 samples and compared with their antibody titers.
The WS carry an antibody titer 20-fold higher than the WHO-IS. It was reproducible, showed both good linearity and insignificant intra- and inter-laboratory variability. However, the WSs behave differently from the WHO-IS. Analysis of the 48 samples showed that single correlation factors are not sufficient to harmonize results from different assays. Yet, all the devices predict neutralization activity based on the antibody titer.
A reproducible and highly concentrated WS, specific for IgG against SARS-CoV-2 Spike-glycoprotein was produced. Such characteristics make it particularly suited for the harmonization of commercially available assays and the consequent evaluation of post-vaccinated individuals.
Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a ...devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed <3 kDa type I collagen has been developed and is currently available on the market as an injectable medical device. The primary objective of this study was to investigate the in vitro and in vivo effects of ChondroGrid in treating knee osteoarthritis symptoms to assess its safety and performance. Viability and proliferation of ChondroGrid-exposed human chondrocytes derived from five donors were assessed through the Alamar Blue/CyQuant assays. Their expression of
/
and
/
was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4mg/2mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.
Sputter deposition of multiprincipal element alloys (MPEAs) is a relatively new field of research with high functional potential. The multicomponent design space is immense and practically ...unexplored. An important obstacle for academic research of such sputtered films is the availability of single‐alloy targets and technical difficulties in using cosputtering of multiple metal targets or powder targets. This article focuses on the development of a simple powder metallurgy route, including cold uniaxial pressing of powder mixtures followed by pressureless sintering, for the preparation of targets made of two common base alloys forming simple solid solutions, i.e., FeNiCrCo and FeNiCrMn. In addition, targets of the former one containing 10 at% Al are also prepared. The sintered pellets are composed of randomly oriented crystallites with face‐centered cubic structures and an optimum chemical homogeneity. Oxide inclusions and residual porosity, inherent to consolidation and sintering of metal precursors, are observed and possible solutions to overcome these challenging problems are discussed. Nevertheless, encouraging results from preliminary deposition tests of FeNiCrCoAl0.4 using both direct current magnetron sputtering (DCMS) and high‐power impulse magnetron sputtering (HiPIMS) are presented.
Powder metallurgy is promising for the synthesis of sputtering targets made of multiprincipal element alloys (MPEAs), as verified in this work through preliminary deposition tests using magneton sputtering techniques. Uniaxial compaction of mixes of elemental powders (FeNiCrCo, FeNiCrMn, FeNiCrMnAl0.4) followed by pressureless sintering leads to in situ formation of simple solid solution alloys (face‐centered cubic fcc structure) with good chemical homogeneity.
Rheumatic disease (RD) represents a broad spectrum of systemic conditions characterized by inflammation and pain in muscles or joints with a significant burden on quality of life. Increasing evidence ...suggests that diet could play a modulatory role in RD by influencing cardiovascular diseases (CVD) risk factors frequently present in these patients as well as inflammation and antioxidant defence.
This review aims to summarize the available evidence on the effect of nutrients, foods and dietary patterns on the most common autoimmune inflammatory RD including rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus and systemic sclerosis.
We documented that MUFAs and PUFAs seem to have positive effects in modulating the inflammatory process. Regarding the dietary interventions, low-calorie diets, Mediterranean diet and fasting appear to be effective in reducing the symptoms of the most common RD. Positive results were also obtained in some cases with gluten-free, low-fat, vegan, elimination or anti-inflammatory diets.
Although further and specific studies are needed, the fact that people obtained an improvement in clinical outcomes after almost all these dietary patterns suggests that a healthy diet could play a pivotal role in the RD management.
Abstract
Snake venoms harbor a wide and diverse array of enzymatic and nonenzymatic toxic components, allowing them to exert myriad effects on their prey. However, they appear to trend toward a few ...optimal compositional scaffolds, dominated by four major toxin classes: SVMPs, SVSPs, 3FTxs, and PLA2s. Nevertheless, the latter appears to be restricted to vipers and elapids, as it has never been reported as a major venom component in rear-fanged species. Here, by investigating the original transcriptomes from 19 species distributed in eight genera from the Pseudoboini tribe (Dipsadidae: Xenodontinae) and screening among seven additional tribes of Dipsadidae and three additional families of advanced snakes, we discovered that a novel type of venom PLA2, resembling a PLA2-IIE, has been recruited to the venom of some species of the Pseudoboini tribe, where it is a major component. Proteomic and functional analyses of these venoms further indicate that these PLA2s play a relevant role in the venoms from this tribe. Moreover, we reconstructed the phylogeny of PLA2s across different snake groups and show that different types of these toxins have been recruited in at least five independent events in caenophidian snakes. Additionally, we present the first compositional profiling of Pseudoboini venoms. Our results demonstrate how relevant phenotypic traits are convergently recruited by different means and from homologous and nonhomologous genes in phylogenetically and ecologically divergent snake groups, possibly optimizing venom composition to overcome diverse adaptative landscapes.
A new approach was explored to purify proteins in a multi-step procedure for the characterisation of proteinaceous materials (casein, animal glue, and egg) in artwork samples by gas ...chromatography–mass spectrometry. High concentrations of inorganic salts, such as azurite, have been found to impair the determination of protein via amino acid analysis. The effect of varying concentrations of copper-based pigments on the quantification of amino acids was evaluated through the analysis of replica paintings prepared with the three types of proteinaceous materials. Glycine, aspartic and glutamic acids are the amino acids most affected by the presence of copper salts. In the case of high concentration of salts, this interference hampers the correct identification of the proteins. To eliminate the inorganic salts, a C18 pipette tip was used to clean-up the ammonia extracts before the acidic hydrolysis step. The clean-up procedure allows us to prevent the influence of the inorganic salts and thus allows correct protein identification, though the quantitative recovery of proteinaceous material is quite low. The effectiveness of the optimised procedure was evaluated by analysing samples from two Italian wall paintings from the 13th and the 14th centuries. Without the clean-up it would not have been possible to detect the presence of a mixture of egg and animal glue in one case, and that of egg in the other one.
The burial assemblage of Kha and Merit discovered in 1906 and now preserved at the Museo Egizio in Turin (Italy) constitutes the most abundant, complete, and well-preserved non-royal Egyptian burial ...assemblage ever found. The discoverer of the tomb and director of Museo Egizio, Ernesto Schiaparelli, limited investigations to a few non-unique items, leaving most of the assemblage untouched. His decision has enabled contemporary scholars to study such exceptional archaeological finding with non-invasive approaches that could not be foreseen at the time. Here we show that the volatile compounds emitted by organic materials contained in vessels can be analyzed and detected directly in museums by a transportable mass spectrometer (selected-ion flow-tube mass spectrometry, SIFT-MS). The interpretation of the mass spectrometric data, supported by statistical data analysis, shed new light on the chemical nature of the organic materials preserved in 50 vessels of the Museo Egizio in a completely non-destructive way.
Our study proves the reliability of SIFT-MS as a fast-screening method for archaeometric investigations directly in museum, providing the unique possibility to complement, confirm and extend the archaeological research on the use and purpose of archaeological vessels and jars.
•The content of vessels from the burial assemblage of Kha and Merit was investigated.•Volatile compounds emitted by organic materials were analyzed by mass spectrometry.•A transportable selected-ion flow-tube mass spectrometry (SIFT-MS) was used.•SIFT-MS acted as a screening method for archaeometric investigations directly in museum.•Information was obtained on most of the amorphous materials contained in the objects.
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