The biological properties of functionalized SBA-type mesoporous silica nanoparticles

Badania wykonano we współpracy z: Euromed Research Institute, Engineering Division, Euro-Mediterranean University of Fes (UEMF) Fez, Maroko Prof. Abdelkrim El Kadib; Přírodovědecká fakulta Univerzity J. E. Purkyně Uście nad Łabą, Czechy Dr Jan MalyMezoporowate nanocząsteczki krzemionkowe są stosunkowo nowymi związkami. Od momentu pierwszej syntezy ich potencjalne zastosowanie upatrywano w unikatowych właściwościach, które wynikają z ich struktury. Krzemionki posiadają mezopory o jednolitej i regularnej wielkości oraz bardzo dużej objętości. Ponadto nanocząsteczki te charakteryzują się regularną wielkością oraz bardzo dużą powierzchnią zewnętrzną. Ich silną bioaktywność wynika z obecności licznych grup funkcyjnych na zewnętrznej i wewnętrznej powierzchni. Krzemionki mogą być w łatwy sposób modyfikowane. Umożliwia to dołączanie organicznych i nieorganicznych grup, łączników czy całych cząsteczek, które pozwalają osiągnąć pożądane właściwości krzemionek. Szeroka charakterystyka materiałów mezoporowatych przyczynia się do ich lepszego poznania, określenia ich potencjalnego użycia w naukach biomedycznych i wyselekcjonowania najlepszych materiałów do poszczególnych zastosowań. Niniejsza praca jest charakterystyką czterech typów mezoporowatych nanocząsteczek krzemionkowych: SBA-OH, SBA-SH, SBA-NH2 oraz SBA-COOH. Nanocząsteczki te różnią się miedzy sobą grupami powierzchniowymi oraz modyfikacjami organicznymi, a także wielkością porów. Krzemionki te zostały także porównane z krzemionką amorficzną. Celem niniejszej rozprawy było określenie czy i w jakim stopniu modyfikacje organiczne oraz grupy funkcyjne wpływają na właściwości krzemionek. Badano wpływ mezoporowatych nanocząsteczek na czerwone komórki krwi poprzez ocenę stopnia hemolizy w próbkach erytrocytów oraz erytrocytów w obecności albuminy surowicy człowieka (HSA). Określono zdolność krzemionek do adsorbowania hemoglobiny (Hb). Badano również cytotoksyczność krzemionek względem linii komórkowej prawidłowej (B14) oraz linii nowotworowych (HL60, 1301 i BRL) wykorzystując testy MTT oraz AlamarBlue. Kolejnym etapem były badania oddziaływania mezoporowatych krzemionek z białkiem – albuminą surowicy ludzkiej z wykorzystaniem dichroizmu kołowego, gaszenia fluorescencji HSA oraz wolnego L-tryptofanu, a także oznaczenia adsorpcji albuminy. Ostatnim etapem było poznanie właściwości powierzchni krzemionek poprzez badanie rozmiaru porów, ich objętości oraz powierzchni właściwej nanocząsteczek. Ponadto zbadano potencjał zeta oraz za pomocą mikroskopu sił atomowych AFM oraz transmisyjnego mikroskopu elektronowego TEM obserwowano morfologię krzemionek. Wszystkie badania oraz porównanie krzemionek mezoporowatych i krzemionki amorficznej pozwoliły stwierdzić, iż zarówno struktura, jak i modyfikacje organiczne oraz przyłączanie grup powierzchniowych wpływają na właściwości tych materiałów. Znacznie niższa hemo- i cytotoksyczność, a także oddziaływanie z białkiem ukazują przewagę mezoporowatych krzemionek nad krzemionką amorficzną.Mesoporous silica nanoparticles are relatively new compounds. Since their first synthesis in 1992, their potential use in biomedical science was sought due to their unique properties associated with their structure. Silicates have numerous mesopores of uniform and regular size, as well as a large volume. In addition, these nanoparticles are characterized by a regular particle size and a very large outer surface area. It is worth noting that they exhibit strong bioactivity, which is related to the presence of numerous functional groups on both the external and internal surfaces. Significant is the fact that the silica can be easily modified during or after theirsynthesis. This enables the attaching of organic and inorganic groups, linkers, or whole particles, which can grant the mesoporous silica nanoparticle various desired properties. A wide characterisation of the different mesoporous materials will contribute to their better knowledge, determine their potential use in biomedical sciences and will aid in selecting the best materials for specific applications. This work characterises four types of mesoporous silica nanoparticles: SBA-OH, SBA-SH, SBA-NH2, and SBA-COOH. These nanoparticles vary in surface groups, organic modifications and mesopore size. The SBA-type (mesoporous) silicates were also compared with the amorphous silica. The aim of this work was to determine how modifications and addition of organic functional groups affect the properties of the silicates. The effect of mesoporous nanoparticles on red blood cells by evaluating the haemolytic activity in samples of pure erythrocytes and erythrocytes in the presence of human serum albumin (HSA) was investigated. Moreover, the ability of the silicates to adsorb haemoglobin (Hb) was determined. In this study the cytotoxicity of silica nanoparticles relative to the normal cell line (B14 - Chinese hamster fibroblast) and tumour lines (HL60 – human promyelocytic leukaemia cells, 1301 – T cell lymphoblastic leukaemia, and BRL – Buffalo rat liver cells) were investigated using the MTT and AlamarBlue assays. The next step was to study the interactions between mesoporous silica nanoparticles and protein (human serum albumin) using circular dichroism, 89 fluorescence quenching of free HSA and L-tryptophan and the adsorption of albumin. The final step of the presented work was to determine the surface properties of the silicates: the pore size, their volume and surface area. Furthermore, the zeta potential was measured and the atomic force microscope (AFM) and transmission electron microscope (TEM) were used to observe the morphology of silica. All four types of the tested nanoparticles affect the red blood cells, but at different levels: the silicates with amino groups cause the strongest haemolysis. However, the most harmful was amorphous silica, which even in the lowest concentrations caused high haemolysis. The presence of albumin decreased of haemolysis to the control level (erythrocytes untreated by silicates). The SBA-type silica nanoparticles were toxic to all tested cell lines, but they much less decreased cell viability than the amorphous silica. For mesoporous nanoparticles, it was possible to determine the concentration for which there was no haemo- and cytotoxic effect. This concentration is 100 µg/ml. All mesoporous silica interacted slightly with albumin and adsorbed up to 25% of HSA. The completed investigations have shown that the reduction of haemolytic activity occurs due to the protein corona which is formed on the surface of the silica nanoparticles. For the formation of the protein corona only a certain amount of adsorbed protein (25%) is needed. Covering the surface of the silica nanoparticles by proteins makes that they gain new – better properties. Microscopic observation revealed that the silica nanoparticles had a rod-like shape with clearly visible mesocanals. The silicates aggregated easily. The zeta potential of the mesoporous silica ranged from -5.6 mV for SBA-NH2 to -15 mV for unmodified SBA-OH. This means that any surface modifications contribute to an increase in the zeta potential. The zeta potential of amorphous silica was the lowest and amounted to -17.8 mV. The examination of silica nanoparticles surface evaluated surface area, total pore volume and its diameter. These results were consistent with the values obtained by the team of El Kadib straight after synthesis. This means that the tested silicates are stable and the dissolution process in a buffered saline solution (PBS) or the use of ultrasounds do not affect the surface of the nanoparticles. 90 All the studies and the comparison of mesoporous silica with amorphous silica allow for the conclusion that structure, organic modifications and attachment of surface groups affect the properties of these materials. Significantly lower haemo- and cytotoxicity, as well as slightly increased interaction with the protein show the advantage of mesoporous silica nanoparticles over the amorphous one

Vegetated roofs in boreal climate support mobile open habitat arthropods, with differentiation between meadow and succulent roofs

Vegetated roofs are hoped to benefit urban wildlife, yet there are few empirical results regarding the conservation potential of such roofs. In this paper, we focus on arthropods on vegetated roofs. We vacuum sampled 17 succulent, meadow or succulent-meadow roofs, in Helsinki, Finland, and used order to species level information together with trait data to describe the communities. We evaluated the importance of biophysical roof characteristics on shaping arthropod assemblages to provide information concerning roof designs that promote rich arthropod fauna. Arthropod communities differed between the three roof types and the influence of roof variables varied between and within arthropod orders. The main local drivers of arthropod abundance across the individually analysed taxa were roof height and vegetation, with mainly positive effects of height (up to 11 m) and litter cover, and mainly negative effects of grass cover. Based on trait data from true bugs, spiders and ants, the roofs consisted mainly of common dispersive species that are generalist feeders and associated with dry open habitats or have wide habitat tolerance. We found one true bug species new to the country and assume that it arrived with imported vegetation. Based on these findings, vegetated roofs of varying height and size benefit common generalists and fauna of open dry habitats, but seem to lack rare native specialists and may introduce non-natives if imported plant material is used. Because the responses to vegetation characteristics are taxon-specific, high diversity of roof vegetation types would benefit arthropod conservation.Peer reviewe

Minichromosome maintenance (MCM) and AgNOR proteins expression in desmoid tumours: a tissue microarray analysis.

In the present study, nuclear proliferative proteins: MCM2, MCM5, MCM7, Ki-67 and AgNORs expression was assessed in paraffin sections from sporadic desmoid tumours using a tissue microarray (TMA)-based immuno- and histochemistry, respectively. Nuclear expression of MCM7, where the percentage of positive cells was 0.87% (Âą 1.64) (range 0-5%), was found in 4/20 (20.0%) cases. In 32/32 (100%) of the examined desmoid cases no expression of nuclear proteins MCM2 and MCM5 was detected. Nuclear expression of Ki-67 was observed in 4/21 (19%) cases. Paraffin sections from 30 cases of desmoid tumours were silver-stained to visualize AgNORs. The following AgNOR parameters were calculated: mean AgNOR number per nucleus (N), mean AgNOR area per nucleus, mean AgNOR dot area per nucleus (A), and mean AgNOR content (C = N/A). In the investigated group the mean values of AgNOR parameters were the following number: 4.34 (Âą 0.11); area: 0.74 Îźm2 (Âą 0.19); dot area: 0.18 m2 (Âą 0.01), and AgNOR content: 23.73 (Âą 1.85). The mean AgNOR number per nucleus and mean AgNOR content in desmoid tumours were statistically significantly higher as compared to the controls (tonsil tissue) (

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

The intestine of intrauterine growth retarded (IUGR) neonates showed different morphology compared to neonates born with normal body weight (NBW). The aim of the present study was to investigate the ultrastructure and proteomic profile of the gut epithelium in IUGR pig neonates with special attention to the digestive and absorptive function. Intestine tissue samples were investigated in 7-day-old IUGR and NBW littermate piglets using histometry, immunofluorescence, scanning electron microscopy (SEM), and mass spectrometry analysis. IUGR piglets have shown reduced mucosa and muscularis thickness and an enhanced number of foetal type enterocytes (FTE). SEM studies have shown the lack of the characteristic large-size vacuole in IUGR’s enterocytes. Delayed removal of FTE in IUGR neonates was probably due to the inhibited apoptosis in the apical part of villi and increased apoptosis and reduced mitosis in the crypt region. In the expression of proteins in the intestinal mucosa such as hexokinase I, histones, and prelamin A/C, carbamoyl phosphate was reduced in IUGR neonates. Finally, IUGR intestines showed higher expression of HSPA9 and HSPA5 as apoptosis markers. The data indicate modifications of gut mucosa in IUGRs that may result in slower gut mucosa maturation and reduced utilisation of nutrient as compared to NBW pig neonates

Vocational activity for patients with multiple sclerosis

Introduction. Multiple sclerosis (MS) usually occurs in young adults and, due to its long-lasting course and variety of symptoms, can affect their vocational activity. Our study aimed to evaluate employment status and working activity for persons with MS with regard to disease-related factors, quality of life, and depression. Material and methods. 250 subjects with MS (62 men, 188 women, aged 19–71 years, mean 42.2) responded to a survey into various aspects of their employment. Relationships were sought between work-related issues and disease-related variables [MS type and duration, major symptoms, disability level on the Expanded Disability Status Scale (EDSS)], quality of life (WHOQOL- -BREF, World Health Organisation Quality of Life brief questionnaire) and depression (BDI, Beck Depression Inventory). Statistical analysis included Mann-Whitney U, Student’s t, and Pearson’s chi-squared tests. Results. 71.2% of the patients were employed, and 49.1% perceived an impact of the disease upon their working activity (i.e. job loss, problems with finding a new one, and/or forced change of type and/or character of employment). Unemployed subjects had higher EDSS scores (4.05 vs. 2.34, p < 0.001) and longer disease durations (13.6 vs. 9.4, p < 0.001) than employed ones. They also scored higher on BDI (15.4 vs. 9.05, p < 0.001) and lower in all domains of WHOQOL-BREF (p < 0.001). Conclusions. The consequences of MS negatively influence many work-related factors. Unemployment is associated with a higher frequency of depression and a lower quality of life in MS patients

ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy

Rekomendacje Sekcji Hepatologicznej Polskiego Towarzystwa Gastroenterologii dotyczące cholestatycznych chorób wątroby — adaptacja wytycznych europejskich

Celem publikacji jest przybliżenie polskim lekarzom europejskich wytycznych dotyczących diagnostyki i leczenia chorób przebiegających z cholestazą. Wytyczne europejskie przedyskutowano na forum Sekcji Hepatologicznej Polskiego Towarzystwa Gastroenterologii pod kątem możliwości ich zastosowania w polskich realiach, a następnie poddano głosowaniu przez członków Sekcji. W opracowaniu przedstawiono ogólne zasady diagnostyki cholestazy oraz omówiono wytyczne rozpoznawania i leczenia najczęstszych chorób przebiegających z cholestazą — pierwotnej żółciowej marskości wątroby, pierwotnego stwardniającego zapalenia dróg żółciowych, zespołów nakładania, polekowych cholestatycznych uszkodzeń wątroby i zespołów cholestazy występujących u ciężarnych i dzieci. Omówiono również IgG4-zależne stwardniające zapalenie dróg żółciowych — niedawno poznaną i często sprawiającą trudności diagnostyczne jednostkę należącą do spektrum układowej choroby IgG4-zależnej. Po każdym rozdziale przedstawiono komentarz panelistów odnoszący się do rozbieżności w głosowaniu

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world