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Molecular Medicine (Cambridge, Mass.) 2011Sepsis and ischemia-reperfusion (I/R) injury are among the leading causes of death in critically ill patients at the surgical intensive care unit setting. Both... (Review)
Review
Sepsis and ischemia-reperfusion (I/R) injury are among the leading causes of death in critically ill patients at the surgical intensive care unit setting. Both conditions are marked by the excessive inflammatory response which leads to a lethal disease complex such as acute lung injury, systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Despite the advances in the understanding of the pathophysiology of those conditions, very little progress has been made toward therapeutic interventions. One of the key aspects of these conditions is the accumulation of apoptotic cells that have the potential to release toxic and proinflammatory contents due to secondary necrosis without appropriate clearance by phagocytes. Along with the prevention of apoptosis, that is reported to be beneficial in sepsis and I/R injury, thwarting the development of secondary necrosis through the active removal of apoptotic cells via phagocytosis may offer a novel therapy. Milk fat globule-EGF factor VIII (MFG-E8), which is mainly produced by macrophages and dendritic cells, is an opsonin for apoptotic cells and acts as a bridging protein between apoptotic cells and phagocytes. Recently, we have shown that MFG-E8 expression is decreased in experimental sepsis and I/R injury models. Exogenous administration of MFG-E8 attenuated the inflammatory response as well as tissue injury and mortality through the promotion of phagocytosis of apoptotic cells. In this review, we describe novel information available about the involvement of MFG-E8 in the pathophysiology of sepsis and I/R injury, and the therapeutic potential of exogenous MFG-E8 treatment for those conditions.
Topics: Antigens, Surface; Humans; Inflammation; Milk Proteins; Reperfusion Injury; Sepsis
PubMed: 20882259
DOI: 10.2119/molmed.2010.00135 -
Journal of Biomolecular Structure &... Jul 2020Protein structures are highly dynamic macromolecules. This dynamics is often analysed through experimental and/or computational methods only for an isolated or a limited...
Protein structures are highly dynamic macromolecules. This dynamics is often analysed through experimental and/or computational methods only for an isolated or a limited number of proteins. Here, we explore large-scale protein dynamics simulation to observe dynamics of local protein conformations using different perspectives. We analysed molecular dynamics to investigate protein flexibility locally, using classical approaches such as RMSf, solvent accessibility, but also innovative approaches such as local entropy. First, we focussed on classical secondary structures and analysed specifically how β-strand, β-turns, and bends evolve during molecular simulations. We underlined interesting specific bias between β-turns and bends, which are considered as the same category, while their dynamics show differences. Second, we used a structural alphabet that is able to approximate every part of the protein structures conformations, namely protein blocks (PBs) to analyse (i) how each initial local protein conformations evolve during dynamics and (ii) if some exchange can exist among these PBs. Interestingly, the results are largely complex than simple regular/rigid and coil/flexible exchange. Abbreviationsnumber of equivalentPBProtein BlocksPDBProtein DataBankRMSfroot mean square fluctuationsCommunicated by Ramaswamy H. Sarma.
Topics: Entropy; Molecular Dynamics Simulation; Protein Conformation; Protein Structure, Secondary; Proteins
PubMed: 31361191
DOI: 10.1080/07391102.2019.1650112 -
Frontiers in Genetics 2018Exosomes are biomolecular nanostructures released from cells. They carry specific biomolecular information and are mainly researched for their exquisite properties as a... (Review)
Review
Exosomes are biomolecular nanostructures released from cells. They carry specific biomolecular information and are mainly researched for their exquisite properties as a biomarker source and delivery system. We introduce exosomes in the context of other extracellular vesicles, describe their biophysical isolation and characterisation and discuss their biochemical profiling. Motivated by our interest in early-life nutrition and health, and corresponding studies enrolling lactating mothers and their infants, we zoom into exosomes derived from human breast milk. We argue that these should be more extensively studied at proteomic and micronutrient profiling level, because breast milk exosomes provide a more specific window into breast milk quality from an immunological (proteomics) and nutritional (micronutrient) perspective. Such enhanced breast milk exosome profiling would thereby complement and enrich the more classical whole breast milk analysis and is expected to deliver more functional insights than the rather descriptive analysis of human milk, or larger fractions thereof, such as milk fat globule membrane. We substantiate our arguments by a bioinformatic analysis of two published proteomic data sets of human breast milk exosomes.
PubMed: 29636770
DOI: 10.3389/fgene.2018.00092 -
American Journal of Hematology Mar 2022The aim of this study was to (1) analyze blood viscosity, red blood cell (RBC) deformability, and aggregation in hospitalized patients with Coronavirus disease 19...
The aim of this study was to (1) analyze blood viscosity, red blood cell (RBC) deformability, and aggregation in hospitalized patients with Coronavirus disease 19 (COVID-19); (2) test the associations between impaired blood rheology and blood coagulation; and (3) test the associations between impaired blood rheology and several indicators of clinical severity. A total of 172 patients with COVID-19, hospitalized in COVID-unit of the Internal Medicine Department (Lyon, France) participated in this study between January and May 2021. Clinical parameters were collected for each patient. Routine hematological/biochemical parameters, blood viscosity, RBC deformability and aggregation, and RBC senescence markers were measured on the first day of hospitalization. A control group of 38 healthy individuals was constituted to compare the blood rheological and RBC profile. Rotational thromboelastography was performed in 76 patients to study clot formation dynamics. Our study demonstrated that patients with COVID-19 had increased blood viscosity despite lower hematocrit than healthy individuals, as well as increased RBC aggregation. In-vitro experiments demonstrated a strong contribution of plasma fibrinogen in this RBC hyper-aggregation. RBC aggregation correlated positively with clot firmness, negatively with clot formation time, and positively with the length of hospitalization. Patients with oxygen supplementation had higher RBC aggregation and blood viscosity than those without, and patients with pulmonary lesions had higher RBC aggregation and enhanced coagulation than those without. This study is the first to demonstrate blood hyper-viscosity and RBC hyper-aggregation in a large cohort of patients with COVID-19 and describe associations with enhanced coagulation and clinical outcomes.
Topics: Adult; Aged; Blood Coagulation; Blood Viscosity; COVID-19; Erythrocyte Aggregation; Erythrocyte Deformability; Erythrocytes; Humans; Middle Aged; SARS-CoV-2
PubMed: 34939698
DOI: 10.1002/ajh.26440 -
Food Chemistry Mar 2024Horse's milk, with a high nutritional value and few allergenic proteins, could substitute cow's milk for infant consumption. Herein, a label-free, proteomic method was...
Horse's milk, with a high nutritional value and few allergenic proteins, could substitute cow's milk for infant consumption. Herein, a label-free, proteomic method was used to identify and compare milk fat globule membrane (MFGM) and whey proteins from three different horse breeds: Selle Français (SF), Welsh pony (WP), and Tieling Draft Horse (TDH). In MFGMs, 16 (SF), 66 (WP), and 45 (TDH) unique proteins were identified, which are involved in the endocytosis, ribosome, and staphylococcus aureus infection pathways, respectively. In whey, 31 (SF), 75 (WP), and 23 (TDH) unique proteins were identified, which are involved in the autophagy-animal, phenylalanine metabolism, and Vasopressin-regulated water reabsorption pathways, respectively. SF contained the lowest concentration of β-lactoglobulin, which can cause allergic reactions in humans. Our findings describe the nutritional differences and functional diversities of MFGM and whey proteins in different horse breeds, which could support developing formula more suitable for human infants.
Topics: Infant; Cattle; Horses; Animals; Female; Humans; Whey Proteins; Proteomics; Milk Proteins; Glycolipids; Glycoproteins; Lipid Droplets; Allergens
PubMed: 37931453
DOI: 10.1016/j.foodchem.2023.137915 -
Haematologica May 2019
Topics: Anemia, Sickle Cell; Complement Factor H; Endothelium, Vascular; Erythrocytes; Erythrocytes, Abnormal; Humans
PubMed: 31040228
DOI: 10.3324/haematol.2018.214668 -
Microbiology Spectrum Dec 2022The folding and dynamics of three-dimensional (3D) genome organization are fundamental for eukaryotes executing genome functions but have been largely unexplored in...
The folding and dynamics of three-dimensional (3D) genome organization are fundamental for eukaryotes executing genome functions but have been largely unexplored in nonmodel fungi. Using high-throughput sequencing coupled with chromosome conformation capture (Hi-C) data, we generated two chromosome-level assemblies for Puccinia striiformis f. sp. , a fungus causing stripe rust disease on wheat, for studying 3D genome architectures of plant pathogenic fungi. The chromatin organization of the fungus followed a combination of the fractal globule model and the equilibrium globule model. Surprisingly, chromosome compartmentalization was not detected. Dynamics of 3D genome organization during two developmental stages of P. striiformis f. sp. indicated that regulation of gene activities might be independent of the changes of genome organization. In addition, chromatin conformation conservation was found to be independent of genome sequence synteny conservation among different fungi. These results highlighted the distinct folding principles of fungal 3D genomes. Our findings should be an important step toward a holistic understanding of the principles and functions of genome architecture across different eukaryotic kingdoms. Previously, our understanding of 3D genome architecture has mainly come from model mammals, insects, and plants. However, the organization and regulatory functions of 3D genomes in fungi are largely unknown. In this study, we comprehensively investigated P. striiformis f. sp. , a plant fungal pathogen, and revealed distinct features of the 3D genome, comparing it with the universal folding feature of 3D genomes in higher eukaryotic organisms. We further suggested that there might be distinct regulatory mechanisms of gene expression that are independent of chromatin organization changes during the developmental stages of this rust fungus. Moreover, we showed that the evolutionary pattern of 3D genomes in this fungus is also different from the cases in mammalian genomes. In addition, the genome assembly pipeline and the generated two chromosome-level genomes will be valuable resources. These results highlighted the unexplored distinct features of 3D genome organization in fungi. Therefore, our study provided complementary knowledge to holistically understand the organization and functions of 3D genomes across different eukaryotes.
Topics: Basidiomycota; Genome, Fungal; Synteny; Plant Diseases
PubMed: 36250889
DOI: 10.1128/spectrum.02608-22 -
Acta Dermato-venereologica Jul 2015In order to determine dermoscopic parameters, a case-control test set of naevus-associated melanomas vs de novo melanomas paired by Breslow thickness and...
In order to determine dermoscopic parameters, a case-control test set of naevus-associated melanomas vs de novo melanomas paired by Breslow thickness and histopathological subtype was analysed by 2 blinded experienced dermoscopists, according to presence of naevus, pattern analysis and ABCD dermoscopy score. The ability to identify naevus-associated melanomas by pattern analysis was low for both blinded dermoscopists (κ < 0.2). Dermoscopy features associated with naevus-associated melanomas were: presence of negative pigment network (OR 9.915, CI 95% 2.182-45.049), globules (OR 2.383, CI 95% 1.15-4.95) and streaks (OR 2.439, CI 95% 1.271-4.680). In contrast, the presence of blue-white veil was related to absence of associated naevus (OR 0.520, CI 95% 0.273-0.991). With the results obtained, 2 different algorithms were proposed. The use of the proposed algorithms could help raise awareness of naevus-associated melanomas and avoid the possibility of incorrectly diagnosing a naevus-associated melanoma if partial biopsies are performed.
Topics: Algorithms; Case-Control Studies; Dermoscopy; Humans; Melanoma; Neoplasms, Multiple Primary; Nevus, Pigmented; Random Allocation; Sensitivity and Specificity; Single-Blind Method; Skin Neoplasms
PubMed: 25394499
DOI: 10.2340/00015555-2009 -
Biomolecules Dec 2023Lipids from milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for cognitive development and human health. Milk-derived whey...
Lipids from milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for cognitive development and human health. Milk-derived whey concentrates rich in these lipids are therefore used as ingredients in infant formulas to mimic human milk and in medical nutrition products to improve the metabolic fitness of adults and elderly people. In spite of this, there is no consensus resource detailing the multitude of lipid molecules in whey concentrates. To bridge this knowledge gap, we report a comprehensive and quantitative lipidomic resource of different whey concentrates. In-depth lipidomic analysis of acid, sweet, and buttermilk whey concentrates identified 5714 lipid molecules belonging to 23 lipid classes. The data show that the buttermilk whey concentrate has the highest level of fat globule-derived triacylglycerols and that the acid and sweet whey concentrates have the highest proportions of MFGM- and EV-derived membrane lipids. Interestingly, the acid whey concentrate has a higher level of cholesterol whereas sweet whey concentrate has higher levels of lactosylceramides. Altogether, we report a detailed lipid molecular compendium of whey concentrates and lay the groundwork for using in-depth lipidomic technology to profile the nutritional value of milk products and functional foods containing dairy-based concentrates.
Topics: Adult; Aged; Infant; Humans; Whey; Lipidomics; Whey Proteins; Glycolipids; Extracellular Vesicles; Milk, Human; Glycoproteins; Lipid Droplets
PubMed: 38254655
DOI: 10.3390/biom14010055 -
Blood Nov 2021
Topics: Adolescent; Adult; Anemia, Sickle Cell; Clonal Hematopoiesis; Female; Humans; Male; Middle Aged; Mutation; Polymorphism, Single Nucleotide; Young Adult
PubMed: 34521115
DOI: 10.1182/blood.2021011121