Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological ...activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.
The fundamental importance of correct protein glycosylation is abundantly clear in a group of diseases known as congenital disorders of glycosylation (CDGs). In these diseases, many biological ...functions are compromised, giving rise to a wide range of severe clinical conditions. By performing detailed analyses of the total serum glycoproteins as well as isolated transferrin and IgG, we have directly correlated aberrant glycosylation with a faulty glycosylation processing step. In one patient the complete absence of complex type sugars was consistent with ablation of GlcNAcTase II activity. In another CDG type II patient, the identification of specific hybrid sugars suggested that the defective processing step was cell type–specific and involved the mannosidase III pathway. In each case, complementary serum proteome analyses revealed significant changes in some 31 glycoproteins, including components of the complement system. This biochemical approach to charting diseases that involve alterations in glycan processing provides a rapid indicator of the nature, severity, and cell type specificity of the suboptimal glycan processing steps; allows links to genetic mutations; indicates the expression levels of proteins; and gives insight into the pathways affected in the disease process.
Despite intensive research on peroxisome biochemistry, the role of glutathione in peroxisomal redox homeostasis has remained a matter of speculation for many years, and only recently has this issue ...started to be experimentally addressed. Here, we summarize and compare data from several organisms on the peroxisome-glutathione topic. It is clear from this comparison that the repertoire of glutathione-utilizing enzymes in peroxisomes of different organisms varies widely. In addition, the available data suggest that the kinetic connectivity between the cytosolic and peroxisomal pools of glutathione may also be different in different organisms, with some possessing a peroxisomal membrane that is promptly permeable to glutathione whereas in others this may not be the case. However, regardless of the differences, the picture that emerges from all these data is that glutathione is a crucial component of the antioxidative system that operates inside peroxisomes in all organisms.
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•The protein repertoire of GSH-dependent peroxisomal enzymes in different organisms varies widely.•Different organisms may use different strategies to maintain a reduced pool of GSH inside peroxisomes.•Despite all the differences, GSH is a crucial component of the peroxisomal antioxidant system in all organisms.
Phyllosilicates have interesting properties, such as high capacity of ion exchange, adsorption, physicochemical stability and low/null toxicity, and thus, they are a promising material in ...pharmaceutical studies. Olanzapine (OLZ), used in the treatment of schizophrenia, is a drug of high cost and low water solubility, which are an obstacle to its use. In this work, an oral delivery system was developed using phyllosilicate (PHY-NT) and OLZ together to increase its solubility. PHY-NT was synthesized by sol–gel method, and then, OLZ was adsorbed creating the system called PHY-NT:OLZ. Thermal analysis was performed to investigate possible interactions between olanzapine and phyllosilicate. a sharp endothermic peak at 468 K was observed, which corresponds to the melting process of OLZ. When OLZ was added to PHY-NT, this peak was absent, suggesting an efficient denaturation of its crystal lattice. FTIR spectroscopy and X-ray powder diffraction were performed as complementary techniques to adequately support thermal analysis results. The created system caused a considerable increase in OLZ dissolution efficiency, and more than 80 % of the drug was released from PHY-NT:OLZ after 20 min. Drug release was evaluated in vitro and showed a Fickian diffusion-based pattern. Thus, results suggest that PHY-NT can be used as an alternative to increase drug dissolution rate of OLZ, expanding applications of these materials.
Newborn screening (NBS) is an important part of public healthcare systems in many countries. The provision of information to parents about NBS is now recognised as an integral part of the screening ...process. Informing parents on all aspects of screening helps to achieve the benefits, promote trust and foster support for NBS. Therefore, policies and guidelines should exist to govern how the information about NBS is provided to parents, taking into account evidence-based best practices. The purpose of our survey was to explore whether any legally binding provisions, guidelines or recommendations existed pertaining to the provision of information about NBS to parents across Europe. Questions were designed to determine the regulatory process of when, by whom and how parents should be informed about screening. Twenty-seven countries participated in the survey. The results indicated that most countries had some sort of legal framework or guidelines for the provision of information to parents. However, only 37% indicated that the provision of information was required prenatally. The majority of countries were verbally informing parents with the aid of written materials postnatally, just prior to sample collection. Information was provided by a neonatologist, midwife or nurse. A website dedicated to NBS was available for 67% of countries and 89% had written materials about NBS for parents. The survey showed that there is a lack of harmonisation among European countries in the provision of information about NBS and emphasised the need for more comprehensive guidelines at the European level.
Barium titanate (BT) nanoparticles were prepared using both microwave- and conventional oven-assisted hydrothermal syntheses with varying reaction times (1 h, 3 h, and 6 h). In the case of the ...conventional oven-assisted hydrothermal syntheses, 16 h, 24 h, 48 h and 72 h reaction times were also studied. Structural and morphological evolution of BT particles were investigated. Microwave-assisted hydrothermal synthesis allowed for the rapid formation of nearly pure barium titanate (BT) phase in just 1 h at 200 °C. On the other hand, using a conventional oven as the heat source required at least 6 h of synthesis to achieve a similar material. When the different BT powders were pelletized and sintered at 1300 °C, ceramics with over 95 % density were obtained. The room-temperature (RT) dielectric permittivity exceeded 1750 for BT particles prepared over 6 h using both heating methods. However, a significant distinction emerged when comparing the piezoelectric coefficient (d33) values. The BT pellet obtained through the sintering of BT synthesized in the conventional oven for 6 h exhibited a notably higher d33 value, approximately 171 pC/N, as opposed to the 146 pC/N value observed in BT ceramics resulting from the microwave synthesized powders. Among the ceramic BT variations, the one derived from the best-crystallized tetragonal BT particles (CON_72h) displayed the lowest d33 value at 79 pC/N. These findings underscore the immense potential of microwave- and conventional oven-assisted hydrothermal syntheses in the sustainable production of BT nanomaterials, which can then be sintered to enable the preparation of ceramics with enhanced ferroelectric and piezoelectric properties.
Abstract
A previously unreported tetragonal phase has been discovered in a epitaxially strained GdMnO
3
thin films deposited on (001)-oriented SrTiO
3
substrates by radio frequency (RF) magnetron ...sputtering. The tetragonal axis of the films grown up to a 35 nm thickness is perpendicular to the film surface and the basal lattice parameters are imposed by the cubic structure of the substrate. Furthermore, the emergence of a spontaneous electric polarization below ~32 K points to the stabilization of an improper ferroelectric phase at low temperatures, which is not observed in bulk GdMnO
3
. This work shows how strain engineering can be used to tailor the structure and properties of strongly correlated oxides.
Objectives: We devised liposome-entrapped antimony with the negatively charged lipid phosphatidylserine—liposome-entrapped antimony (Sb-LP)—in order to improve their targeting to infected macrophages ...through the interaction with scavenger receptors (SRs). Methods: SR production was indirectly evaluated by its mRNA synthesis in infected and uninfected peritoneal macrophages using RT–PCR. The interaction and cytotoxicity of Sb-LP with SRs and their metabolism were determined by incubation with macrophages in the presence of cytochalasin B, chloroquine or different competitive ligands, with determination of the 50% inhibitory concentration (IC50) in vitro in infected macrophages. The intracellular trafficking of Sb-LP was evaluated by confocal microscopy using trapped fluorescent dyes. Results: Our results showed an up-regulation of macrophage SR mRNA during the initial steps of Leishmania (L.) chagasi infection. By competitive ligand assays, we demonstrated the preferential uptake of Sb-LP by macrophage SRs. Sb-LP was 16-fold more effective (IC50=14.11 μM) than the free drug (IC50=225.9 μM) against L. (L.) chagasi-infected macrophages. The binding and uptake of Sb-LP in macrophages were shown to be energy-dependent and were reduced in the presence of cytochalasin B, showing the dependency of the cell microfilament system. Confocal analysis using trapped fluorescent dyes showed fluorescence of parasites or in their close proximity, compatible with the localized delivery of the liposomes. Conclusions: The uptake of Sb-LP was reduced in infected macrophages, despite their effectiveness and targeting ability, suggesting a low metabolic rate in infected macrophages that could be overcome by the higher efficiency of the liposomal formulation. These in vitro results suggest that liposomes could improve the therapeutic index of old drugs, such as pentavalent antimony, via targeted delivery to Leishmania-infected cells.
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•PLA/CNC and PLA/CNC/GTE films prepared by direct melt processing.•PLA/2%CNC/1%GTE nanocomposite film, showed good dispersion level of CNC and GTE.•PLA/2%CNC/1%GTE nanocomposite film ...presents an efficient barrier effect.•PLA/2%CNC/1%GTE nanocomposite film presents a good macroscopic mechanical behavior.•The active films effectiveness on retarding lipid oxidation was evaluated in a model food.
Eco-friendly and antioxidant bioactive films based on polylactic acid (PLA), loaded with cellulose nanocrystals (CNC) and green tea extract (GTE) were prepared by direct melt processing. GTE was chemically characterized by using high performance liquid chromatography (HPLC), coupled with tandem mass spectrometry. The antioxidant, physical, thermal, mechanical and microstructural properties of the produced films were investigated. The efficiency of the active films on retarding the lipid oxidation of the salami, was evaluated by the thiobarbituric acid reactive substances (TBARS) and p-anisidine value. Experimental results highlight that the PLA/2%CNC/1%GTE nanocomposite film (film containing 2 wt% of CNC and 1 wt% of GTE) shows the highest reduction in terms of oxygen transmission ratio and water vapor permeability (60 % and 33 % respectively) and the optimal macroscopic mechanical behavior. However, it shows a slight antioxidant activity only at short storage time, namely 7 and 15 days. Overall, PLA/2CNC nanocomposite film exhibits the best compromise in terms of improvement of material properties and of effectiveness in retarding lipid oxidation at short and long storage time, mainly related to its enhanced barrier properties.
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