Pulmonary surfactant is a complex of lipids and proteins assembled and secreted by the alveolar epithelium into the thin layer of fluid coating the respiratory surface of lungs. There, surfactant ...forms interfacial films at the air-water interface, reducing dramatically surface tension and thus stabilizing the air-exposed interface to prevent alveolar collapse along respiratory mechanics. The absence or deficiency of surfactant produces severe lung pathologies. This review describes some of the most important surfactant-related pathologies, which are a cause of high morbidity and mortality in neonates and adults. The review also updates current therapeutic approaches pursuing restoration of surfactant operative films in diseased lungs, mainly through supplementation with exogenous clinical surfactant preparations. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
Display omitted
•Exogenous surfactant supplementation has saved thousands of lives of preterm neonates.•Development of humanized clinical surfactants is a main motivation for current research.•Meconium aspiration syndrome associates with inactivation of surfactant at different levels.•Surfactant therapy in MAS or ARDS depends on production of enhanced inhibition-resistant surfactants.
Mollusk shell is composed of two CaCO3 polymorphs (calcite and aragonite) and an organic matrix that consists of acetic acid- or ethylenediaminetetraacetic acid (EDTA)-soluble and insoluble proteins ...and other biomolecules (polysaccharides, β-chitin). However, the shell matrix proteins involved in nacre formation are not fully known. Thus, the aim of this study was to identify and characterize a novel protein from the acetic acid-insoluble fraction from the shell of Pteria sterna, named in this study as Ps19, to have a better understanding of the biomineralization process. Ps19 biochemical characterization showed that it is a glycoprotein that exhibits calcium- and chitin-binding capabilities. Additionally, it is capable of inducing aragonite plate crystallization in vitro. Ps19 partial peptide sequence showed similarity with other known shell matrix proteins, but it displayed similarity with proteins from Crassostrea gigas, Mizuhopecten yessoensis, Biomphalaria glabrata, Alpysia californica, Lottia gigantea and Elysia chlorotica. The results obtained indicated that Ps19 might play an important role in nacre growth of mollusk shells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious ...pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The European LIFE Project, Repolyuse – “REcovery of POLYurethane for reUSE in eco-efficient materials” seeks to solve the environmental challenge of resource scarcity and waste management in order to ...mitigate the effects of climate change. The material is a prefabricated gypsum mortar in the form of a removable roofing plate to which residues of rigid polyurethane foam have been added. That system reduces the weight of the plates about 30%. The investigation has consisted of the final design of the mixtures of plaster mortar with residues of rigid polyurethane foam, mineral fibers, additives and water to achieve the adequate industrial manufacturing system of “Plaster mortar plates lightened with polyurethane foam waste” to put in roofs detachable. In the industry’s own production chain, the plasticity, moulding and drying of the plates can be similar to the process of the standard plates. The final result of the plates shows that the Flexural strength, Flatness, Angular deviation, Thermal conductivity, Superficial hardness, Reaction to the fire and Resistance to humidity have been similar to the results obtained in the laboratory. In the end, the plates were placed in two buildings in Spain. Consequently these results have enough been to achieve the CE marking
The adoption of sustainable building policies and the society’s increasing emphasis on sustainability underscore the urgent need to evaluate the environmental and economic impact of construction ...materials. This study examines the effects of incorporating polyurethane foam waste into gypsum-based ceiling tiles. It compares its economic performance and eco-efficiency with conventional alternatives. Methodologically, Life Cycle Cost Analysis (LCCA) quantifies total life cycle costs, followed by Eco-Efficiency Assessment (EE), considering results from both Life Cycle Assessment (LCA) and LCCA. Our findings reveal a compelling 5.91% cost advantage for the novel precast, driven by enhanced production capacity resulting from shorter drying times. The economic benefits of this approach are underscored by a detailed breakdown of cost savings in production phases. Furthermore, the EE remarks a substantial 7.5% boost, emphasizing the positive environmental impact achieved through reduced resource consumption and lower emissions combined with lower life-cycle costs. These results highlight the economic viability and eco-efficiency of polymeric waste-integrated gypsum ceiling tiles for environmental sustainability. The specific percentage improvements in cost and eco-efficiency provide a quantitative basis for understanding the advantages of adopting these innovative materials.
•Economic Gains: PW-gypsum tile cuts costs 5.91%, ensuring financial viability.•Cost: Manufacturing is 60% of total expenses for both materials.•Energy Savings: 20% less drying time, lowering energy consumption.•Green Innovation: Novel tech is 7.5% more eco-efficient (enviro-economic ratio).
SARS-CoV-2 infection of host cells is driven by binding of the SARS-CoV-2 spike-(S)-protein to lung type II pneumocytes, followed by virus replication. Surfactant protein SP-D, member of the ...front-line immune defense of the lungs, binds glycosylated structures on invading pathogens such as viruses to induce their clearance from the lungs. The objective of this study is to measure the pulmonary SP-D levels in COVID-19 patients and demonstrate the activity of SP-D against SARS-CoV-2, opening the possibility of using SP-D as potential therapy for COVID-19 patients. Pulmonary SP-D concentrations were measured in bronchoalveolar lavage samples from patients with corona virus disease 2019 (COVID-19) by anti-SP-D ELISA. Binding assays were performed by ELISAs. Protein bridge and aggregation assays were performed by gel electrophoresis followed by silver staining and band densitometry. Viral replication was evaluated in vitro using epithelial Caco-2 cells. Results indicate that COVID-19 patients (n = 12) show decreased pulmonary levels of SP-D (median = 68.9 ng/mL) when compared to levels reported for healthy controls in literature. Binding assays demonstrate that SP-D binds the SARS-CoV-2 glycosylated spike-(S)-protein of different emerging clinical variants. Binding induces the formation of protein bridges, the critical step of viral aggregation to facilitate its clearance. SP-D inhibits SARS-CoV-2 replication in Caco-2 cells (EC90 = 3.7 μg/mL). Therefore, SP-D recognizes and binds to the spike-(S)-protein of SARS-CoV-2 in vitro, initiates the aggregation, and inhibits viral replication in cells. Combined with the low levels of SP-D observed in COVID-19 patients, these results suggest that SP-D is important in the immune response to SARS-CoV-2 and that rhSP-D supplementation has the potential to be a novel class of anti-viral that will target SARS-CoV-2 infection.
This work is focused on the potential use of pulmonary surfactant to deliver full-length recombinant human surfactant protein SP-D (rhSP-D) using the respiratory air-liquid interface as a shuttle. ...Surfactant protein D (SP-D) is a collectin protein present in the pulmonary surfactant (PS) system, involved in innate immune defense and surfactant homeostasis. It has been recently suggested as a potential therapeutic to alleviate inflammatory responses and lung diseases in preterm infants suffering from respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD). However, none of the current clinical surfactants used for surfactant replacement therapy (SRT) to treat RDS contain SP-D. The interaction of SP-D with surfactant components, the potential of PS as a respiratory drug delivery system and the possibility to produce recombinant versions of human SP-D, brings the possibility of delivering clinical surfactants supplemented with SP-D. Here, we used an
setup that somehow emulates the respiratory air-liquid interface to explore this novel approach. It consists in two different compartments connected with a hydrated paper bridge forming a continuous interface. We firstly analyzed the adsorption and spreading of rhSP-D alone from one compartment to another over the air-liquid interface, observing low interfacial activity. Then, we studied the interfacial spreading of the protein co-administered with PS, both at different time periods or as a mixed formulation, and which oligomeric forms of rhSP-D better traveled associated with PS. The results presented here demonstrated that PS may transport rhSP-D long distances over air-liquid interfaces, either as a mixed formulation or separately in a close window time, opening the doors to empower the current clinical surfactants and SRT.
Insecticidal proteins from Bacillus thuringiensis (Bt) are used extensively in sprays and transgenic crops for pest control, but their efficacy is reduced when pests evolve resistance. Better ...understanding of the mode of action of Bt toxins and the mechanisms of insect resistance is needed to enhance the durability of these important alternatives to conventional insecticides. Mode of action models agree that binding of Bt toxins to midgut proteins such as cadherin is essential for toxicity, but some details remain unresolved, such as the role of toxin oligomers. In this study, we evaluated how Bt toxin Cry1Ac and its genetically engineered counterpart Cry1AcMod interact with brush border membrane vesicles (BBMV) from resistant and susceptible larvae of Pectinophora gossypiella (pink bollworm), a global pest of cotton. Compared with Cry1Ac, Cry1AcMod lacks 56 amino acids at the amino-terminus including helix α-1; previous work showed that Cry1AcMod formed oligomers in vitro without cadherin and killed P. gossypiella larvae harboring cadherin mutations linked with >1000-fold resistance to Cry1Ac. Here we found that resistance to Cry1Ac was associated with reduced oligomer formation and insertion. In contrast, Cry1AcMod formed oligomers in BBMV from resistant larvae. These results confirm the role of cadherin in oligomerization of Cry1Ac in susceptible larvae and imply that forming oligomers without cadherin promotes toxicity of Cry1AcMod against resistant P. gossypiella larvae that have cadherin mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Familial hypercholesterolaemia (FH) is an autosomal-dominant disorder associated with high low-density lipoprotein cholesterol (LDL-C). Left untreated, 50% of men with FH will develop coronary heart ...disease by the age of 50 and 30% of women by the age 60 1,2. It is estimated that the prevalence may be as high as one in 250 people, with most undiagnosed.
This article explores the development of advocacy in FH patient organisations, citing examples from Canada, the Netherlands, Spain, the US and the UK as well as the pan-European patient organisation, FH Europe. The article demonstrates that for patient advocacy, the link with medical and scientific expertise is essential to ensure that advocacy for familial hypercholesterolaemia is well-founded and credible and that patient associations are prepared to take a long-term view on achieving improvements in identification and treatment.
•Familial hypercholesterolaemia (FH) is mostly an unidentified disease that does not discriminate.•More awareness is required to increase the number of FH patients identified.•Patient empowerment and the patient voice is paramount in raising awareness and getting system change to identify and optimally treat all FH cases.•Patient organisations and healthcare professionals work together to find all FH patients worldwide, the earlier the better.•Networking by and between FH patient organisations is important to share information and learning.
Galloyl catechins, in particular (-)-epicatechin gallate (ECg), have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA); they also prevent ...biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (-)-epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
