Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial.

INTRODUCTION: To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days. METHODS: Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258. RESULTS: The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR ≤ 3 hours = 0.78, 0.68 to 0.90; HR > 3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise. CONCLUSIONS: Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury

Synthesis and in vitro cytotoxicity of glycans-capped silver nanoparticles

Silver nanostructures were successfully synthesized through a simple and "green" method using saccharides as reducing and caping agent. Transmission electron microscopy (TEM) and UV-Vis absorption were used to certify the quality of the silver nanoparticles obtained: firstly, size and dispersion. In this work Silver NanoParticles (AgNPs) cytotoxicity related to saccharides capping (Glucose and (GlucoseSucrose) was explored in human epithelia cervix carcinoma cells (HeLa). The cells were incubated with increasing AgNPs number/cell and HeLa cells viability was monitored for a period of 48 h compared with the positive and negative controls. We observed that the toxicity increases with incubation time and with AgNPs number/cell. In particular, the different cytotoxic degree of the AgNPs, i.e. AgNP-G are more toxic than AgNP-GS, suggest that the cytotoxic effects are largely depended on the capping agent. The highest concentration of AgNP-G number/cell is able to induce extensive cell death of HeLa cells soon after 1hr of incubation; conversely the lowest concentration of AgNP-GS number/cell, surprisingly, is able to induce cell proliferation

Effect of temperature on the physical, optical and photocatalytic properties of TiO2 nanoparticles

In this paper we describe the effect of calcination temperature on the structural, morphological, optical and photocatalytic properties of TiO2 nanoparticles. The titanium dioxide powders were produced by the sol–gel method starting from titanium tetraisopropoxide (TTIP) in neutral aqueous medium (pH 5.5). After that, the TiO2 nanoparticles were treated at three different calcination temperatures for 4 h: 100, 450 and 800 °C. Then, the powders were characterized by XRD, Raman and photoluminescence techniques. We observed the anatase phase for the powders treated at 100 and 450 °C and rutile for that treated at 800 °C. The photocatalytic activity of the TiO2 powders was investigated using Methylene Blue test and showed a strong correlation with the temperature (i.e. TiO2 phase). The better photocatalysis exhibited by the nanoparticles treated at 100 and 450 °C compared to the powder at 800 °C was due to the higher recombination of photo-generated electrons and holes of rutile with respect to anatase

Green Silver Nanoparticles Promote Inflammation Shutdown in Human Leukemic Monocytes

The use of silver nanoparticles (Ag NPs) in the biomedical field deserves a mindful analysis of the possible inflammatory response which could limit their use in the clinic. Despite the anti-cancer properties of Ag NPs having been widely demonstrated, there are still few studies concerning their involvement in the activation of specific inflammatory pathways. The inflammatory outcome depends on the synthetic route used in the NPs production, in which toxic reagents are employed. In this work, we compared two types of Ag NPs, obtained by two different chemical routes: conventional synthesis using sodium citrate and a green protocol based on leaf extracts as a source of reduction and capping agents. A careful physicochemical characterization was carried out showing spherical and stable Ag NPs with an average size between 20 nm and 35 nm for conventional and green Ag NPs respectively. Then, we evaluated their ability to induce the activation of inflammation in Human Leukemic Monocytes (THP-1) differentiated into M0 macrophages using 1 µM and 2 µM NPs concentrations (corresponded to 0.1 µg/mL and 0.2 µg/mL respectively) and two-time points (24 h and 48 h). Our results showed a clear difference in Nuclear Factor ?B (NF-?b) activation, Interleukins 6–8 (IL-6, IL-8) secretion, Tumor Necrosis Factor-? (TNF-?) and Cyclooxygenase-2 (COX-2) expression exerted by the two kinds of Ag NPs. Green Ag NPs were definitely tolerated by macrophages compared to conventional Ag NPs which induced the activation of all the factors mentioned above. Subsequently, the exposure of breast cancer cell line (MCF-7) to the green Ag NPs showed that they exhibited antitumor activity like the conventional ones, but surprisingly, using the MCF-10A line (not tumoral breast cells) the green Ag NPs did not cause a significant decrease in cell viability. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

High Doses of Silica Nanoparticles Obtained by Microemulsion and Green Routes Compromise Human Alveolar Cells Morphology and Stiffness Differently

Among all the inorganic nanomaterials used in commercial products, industry, and medicine, the amorphous silica nanoparticles (SiO2 NPs) appeared to be often tolerated in living organisms. However, despite several toxicity studies, some concerns about the exposure to high doses of SiO2 NPs with different sizes were raised. Then, we used the microemulsion method to obtain stable SiO2 NPs having different sizes (110 nm, 50 nm, and 25 nm). In addition, a new one-pot green synthetic route using leaves extract of Laurus nobilis was performed, obtaining monodispersed ultrasmall SiO2 NPs without the use of dangerous chemicals. The NPs achieved by microemulsion were further functionalized with amino groups making the NPs surface positively charged. Then, high doses of SiO2 NPs (1 mg/mL and 3 mg/mL) achieved from the two routes, having different sizes and surface charges, were used to assess their impact on human alveolar cells (A549), being the best cell model mimicking the inhalation route. Cell viability and caspase-3 induction were analyzed as well as the cellular uptake, obtaining that the smallest (25 nm) and positive-charged NPs were more able to induce cytotoxicity, reaching values of about 60% of cell death. Surprisingly, cells incubated with green SiO2 NPs did not show strong toxicity, and 70% of them remained vital. This result was unusual for ultrasmall nanoobjects, generally highly toxic. The actin reorganization, nuclear morphology alteration, and cell membrane elasticity analyses confirmed the trend achieved from the biological assays. The obtained data demonstrate that the increase in cellular softness, i.e., the decrease in Young's modulus, could be associated with the smaller and positive NPs, recording values of about 3 kPa. On the contrary, green NPs triggered a slight decrease of stiffness values (c.a. 6 kPa) compared to the untreated cells (c.a. 8 kPa). As the softer cells were implicated in cancer progression and metastasization, this evidence strongly supported the idea of a link between the cell elasticity and physicochemical properties of NPs that, in turn, influenced the interaction with the cell membrane. Thus, the green SiO2 NPs compromised cells to a lesser extent than the other SiO2 NPs types. In this scenario, the elasticity evaluation could be an interesting tool to understand the toxicity of NPs with the aim of predicting some pathological phenomena associated with their exposure

Enhanced adsorption capacity of porous titanium dioxide nanoparticles synthetized in alkaline sol

Abstract In recent years, the exploitation of natural resources and industrial development have led to the production of harmful pollutants. Much of these contaminants end up in water resources, reducing the availability of drinking water. Therefore, it is necessary to find remedies to this situation. Solutions could be the adsorption or the degradation through photocatalysis of these compounds. A good candidate for this task is titanium dioxide (TiO2), due to its non-toxicity, stability and low cost. In this work, we propose a novel synthesis of TiO2 nanoparticles (NPs), with high adsorption capacity, produced at low temperature in alkaline environment. Adsorption tests were conducted using methylene blue and diclofenac as model pollutants. Moreover, the obtained NPs have been characterized through Raman spectroscopy, Scanning and Transmission electron microscopies and with thermogravimetric analysis. The results showed a porous structure with a high surface area, able to efficiently adsorb large amounts of dye from the aqueous solution. These properties make the obtained TiO2 powders suitable for applications devoted to the adsorption and recovery of harmful compounds. Graphic abstrac

Sustainable Synthesis of FITC Chitosan-Capped Gold Nanoparticles for Biomedical Applications

The quest for novel nanoscale materials for different applications necessitates that they are easy to obtain and have excellent physical properties and low toxicity. Moreover, considering the ongoing environmental impact of noxious chemical waste products, it is important to adopt eco-friendly approaches for nanoparticle synthesis. In this work, a natural polymer (medium molecular weight chitosan) derived from chitin was employed as a reducing agent to obtain gold nanoparticles (AuNPs) with a chitosan shell (AuNPs@CS) by a microwave oven. The chitosan is economically viable and cost-competitive in the market showing also nontoxic behavior in the environment and living organisms. The synthesized AuNPs@CS-FITC NPs were fully characterized by spectroscopic and microscopic characterization techniques. The size distribution of NPs was about 15 nm, which is a suitable dimension to use in biomedical applications due to their high tissue penetration, great circulation in blood, and optimal clearance as well as low toxicity. The prepared polymer-capped NPs were further functionalized with a fluorescent molecule, i.e., Fluorescein-5-isothiocyanate (FITC), to perform imaging in the cell. The results highlighted the goodness of the synthesis procedure, as well as the high internalization rate that resulted in an optimal fluorescence intensity. Thus, this work presents a good sustainable/green approach-mediated polymer nanocomposite for various applications in the field of diagnostic imaging