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2.
BMC Biotechnol ; 23(1): 2, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694155

RESUMO

BACKGROUND: Rhamnolipids are a group of the extracellular microbial surface-active molecules produced by certain Pseudomonas species with various environmental and industrial applications. The goal of the present research was to identify and optimize key process parameters for Pseudomonas aeruginosa PTCC 1074s synthesis of rhamnolipids utilizing soybean meal in solid state fermentation. A fractional factorial design was used to screen the key nutritional and environmental parameters to achieve the high rhamnolipid production. Response surface methodology was used to optimize the levels of four significant factors. RESULTS: The characterization of biosurfactant by TLC, FT-IR and H-NMR showed the rhamnolipids presence. In the optimum conditions (temperature 34.5 °C, humidity 80%, inoculum size 1.4 mL, and glycerol 5%), the experimental value of rhamnolipid production was 19.68 g/kg dry substrate. The obtained rhamnolipid biosurfactant decreased water's surface tension from 71.8 ± 0.4 to 32.2 ± 0.2 mN/m with a critical micelle concentration of nearly 70 mg/L. Additionally, analysis of the emulsification activity revealed that the generated biosurfactant was stable throughout a broad pH, temperature, and NaCl concentration range. CONCLUSIONS: The current study confirmed the considerable potential of agro-industrial residues in the production of rhamnolipid and enhanced the production yield by screening and optimizing the significant process parameters.


Assuntos
Pseudomonas aeruginosa , Tensoativos , Fermentação , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Glicolipídeos/química
3.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677779

RESUMO

The roles of medium- and long-chain triacylglycerols (MLCT) on health benefits under high fat diet (HFD) conditions remain in dispute. This study was conducted to investigate the effects of novel LaPLa-rich MLCT on the glycolipid metabolism and gut microbiota in HFD-fed mice when pork fat is half replaced with MLCT and palm stearin (PS). The results showed that although MLCT could increase the body weight in the mouse model, it can improve the energy utilization, regulate the glucose and lipid metabolism, and inhibit the occurrence of inflammation. Furthermore, 16S rRNA gene sequencing of gut microbiota indicated that PS and MLCT affected the overall structure of the gut microbiota to a varying extent and specifically changed the abundance of some operational taxonomic units (OTUs). Moreover, several OTUs belonging to the genera Dorea, Streptococcus, and g_Eryipelotrichaceae had a high correlation with obesity and obesity-related metabolic disorders of the host. Therefore, it can be seen that this new MLCT has different properties and functions from the previous traditional MLCT, and it can better combine the advantages of MLCT, lauric acid, and sn-2 palmitate, as well as the advantages of health function and metabolism. In summary, this study explored the effects of LaPLa-enriched lipids on glycolipid metabolism in mice, providing theoretical support for future studies on the efficacy of different types of conjugated lipids, intending to apply them to industrial production and subsequent development of related products.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Peso Corporal , Obesidade/etiologia , Obesidade/metabolismo , Triglicerídeos/química , Metabolismo dos Lipídeos , Glicolipídeos/farmacologia
4.
J Nanobiotechnology ; 21(1): 16, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647125

RESUMO

BACKGROUND: Oral administration offered a painless way and improved compliance for diabetics. However, the emerging GLP-1 analog peptide drugs for diabetes primarily rely on the injection route, and the development of oral dosage forms was hampered by the low oral bioavailability due to the structural vulnerability to digestive enzymes and molecule impermeability in the gastrointestinal tract. RESULTS: In this study, the non-covalent interaction between cholic acid (CA) and liraglutide (LIRA) was found and theoretically explained by molecular docking simulation. Formation of this physical complex of liraglutide and cholic acid (LIRA/CA Complex) reduced the self-aggregation of LIRA and accelerated intestinal epithelium penetration. By the anti-solvent method, LIRA/CA Complex was loaded into zein/rhamnolipids nanoparticles (LIRA/CA@Zein/RLs) with a loading efficiency of 76.8%. LIRA was protected from fast enzymatic degradation by the hydrophobic zein component. Meanwhile, Rhamnolipids, a glycolipid with surface activity, promoted endocytosis while also stabilizing the nanoparticles. The two components worked synergistically to ensure the delivery of LIRA/CA Complex to intestinal villi and improved oral absorption without disrupting tight junctions. LIRA/CA@Zein/RLs demonstrated a considerable intestinal epithelium absorption in mouse gastrointestinal section and a retention in vivo over 24 h, resulting in a significant and long-lasting hypoglycemic effect in Type 2 diabetes mice. CONCLUSION: This study provided a promising oral delivery approach for LIRA and exhibited the potential for further translation into clinical application.


Assuntos
Diabetes Mellitus Tipo 2 , Nanocompostos , Zeína , Camundongos , Animais , Liraglutida/farmacologia , Zeína/química , Ácido Cólico , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Glicolipídeos , Mucosa Intestinal
5.
Nature ; 613(7943): 324-331, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36599989

RESUMO

Pathogens generate ubiquitous selective pressures and host-pathogen interactions alter social behaviours in many animals1-4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal5-13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.


Assuntos
Caenorhabditis elegans , Feromônios , Pseudomonas aeruginosa , Reprodução , Comportamento Sexual Animal , Animais , Feminino , Masculino , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Glicolipídeos/metabolismo , Organismos Hermafroditas/fisiologia , Feromônios/metabolismo , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Receptores de Feromônios/metabolismo , Reprodução/fisiologia , Células Receptoras Sensoriais/metabolismo
6.
Adv Neurobiol ; 29: 419-448, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255683

RESUMO

Patients with nervous system disorders suffer from impaired cognitive, sensory and motor functions that greatly inconvenience their daily life and usually burdens their family and society. It is difficult to achieve functional recovery for the damaged central nervous system (CNS) because of its limited ability to regenerate. Glycosphingolipids (GSLs) are abundant in the CNS and are known to play essential roles in cell-cell recognition, adhesion, signal transduction, and cellular migration, that are crucial in all phases of neurogenesis. Despite intense investigation of CNS regeneration, the roles of GSLs in neural regeneration remain unclear. Here we focus on the respective potentials of glycolipids to promote regeneration and repair of the CNS. Mice lacking glucosylceramide, lactosylceramide or gangliosides show lethal phenotypes. More importantly, patients with ganglioside deficiencies exhibit severe clinical phenotypes. Further, neurodegenerative diseases and mental health disorders are associated with altered GSL expression. Accumulating studies demonstrate that GSLs not only delimit physical regions but also play central roles in the maintenance of the biological functions of neurons and glia. We anticipate that the ability of GSLs to modulate behavior of a variety of molecules will enable them to ameliorate biochemical and neurobiological defects in patients. The use of GSLs to treat such defects in the human CNS will be a paradigm-shift in approach since GSL-replacement therapy has not yet been achieved in this manner clinically.


Assuntos
Glicolipídeos , Lactosilceramidas , Animais , Humanos , Camundongos , Glucosilceramidas , Gangliosídeos/química , Gangliosídeos/metabolismo , Neurônios/metabolismo
7.
Methods Mol Biol ; 2613: 23-31, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587068

RESUMO

The cell envelopes of pathogens comprise a wealth of unique glycolipids, which are important modulators of the host immune responses during infection and in some cases have been used as adjuvants. Despite this abundant basic knowledge, the identities of the host immune receptors for mycobacterial lipids have long been elusive (Ishikawa et al., Trends Immunol 38:66-76, 2017). We describe the method of how to isolate glycolipids from microorganisms and how to analyze the glycolipids' potential to activate reporter cells and bone marrow-derived dendritic cells (BMDCs), such as surface marker expression and reactive oxygen species (ROS) production. Additionally, we outline an in vitro BMDC/T cell coculture model to investigate functional consequences of leukocyte activation, such as cytokine production. In this chapter, we provide a guide for extracting glycolipids from microorganisms and how to use them to activate leukocytes. We also present methods on how to generate and activate reporter cells, as well as BMDCs and how to set up BMDC/T cell cocultures. We further outline how to generate samples and how to analyze the immunomodulatory effect glycolipid exposure has on these cells, via flow cytometry, ROS production assays and ELISA.


Assuntos
Glicolipídeos , Linfócitos T , Glicolipídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adjuvantes Imunológicos , Apresentação de Antígeno , Células Dendríticas
8.
Methods Mol Biol ; 2613: 145-152, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587077

RESUMO

Lipid rafts are usually isolated from cells or tissues using sucrose gradient ultracentrifugation in the presence of detergents such as Triton X-100 at 4 °C. Although detergents should be removed for further structural characterization following fractionation, these compounds are often difficult to completely remove, especially from the glycolipids. In this chapter, we describe a novel method for the fast and convenient removal of detergents from lipid raft glycolipids following fraction and describe the application of this method.


Assuntos
Detergentes , Glicolipídeos , Glicolipídeos/análise , Detergentes/química , Centrifugação com Gradiente de Concentração , Octoxinol , Microdomínios da Membrana/química
9.
Methods Mol Biol ; 2613: 79-87, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587072

RESUMO

Glycolipids play important biological roles mainly in biological membranes, but their functions at the molecular level remain to be fully established. A chemical biology approach using exogenously added glycolipid probes would be promising, but the possibility of cleavage by cellular glycohydrolases complicates the interpretation of results. Thus, there is a need for non-hydolyzable analogues. In the present study, we designed and synthesized GM3 analogues resistant to GM3-degrading sialidase by replacing the O-sialoside linkage with a C-sialoside linkage. The bioactivity of the analogues was also investigated.


Assuntos
Gangliosídeo G(M3) , Neuraminidase , Membrana Celular , Glicolipídeos
10.
Methods Mol Biol ; 2613: 13-22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587067

RESUMO

CD1d is a non-classical major histocompatibility complex (MHC) protein, responsible for lipid antigen presentation, which presents lipids to natural killer T (NKT) cells. Various CD1d lipid ligands have been reported, including microbial and endogenous glycolipids/phospholipids. Among them, an α-galactosylceramide (α-GalCer), a representative CD1d ligand, is one of the most potent ligands and its derivatives have been developed. In this chapter, the chemistry of α-GalCer and its derivatives are described with an emphasis on their chemical syntheses and molecular interaction analysis with CD1d are described.


Assuntos
Galactosilceramidas , Glicolipídeos , Galactosilceramidas/química , Ligantes , Antígenos CD1d/metabolismo , Glicolipídeos/química , Apresentação de Antígeno
11.
Methods Mol Biol ; 2613: 181-188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587079

RESUMO

Mammalian glycolipids play a variety of roles, often coupled with interactions with endogenous and exogenous molecules. The interactions can induce intracellular signaling and are the means by which glycolipids express biological phenotypes. Insights into the structure-function relationships of glycolipids (both glycan and lipid moieties) provide the basis for gaining an understanding of the mechanisms at play, an important area for further study. Solution nuclear magnetic resonance (NMR) spectroscopy is a unique and powerful method employed to provide, at the atomic level, structural information on glycolipids and other biomolecules in solutions. This chapter briefly describes how we measure NMR spectra of glycolipids and the information gained from NMR spectral analysis.


Assuntos
Glicolipídeos , Imageamento por Ressonância Magnética , Animais , Glicolipídeos/análise , Espectroscopia de Ressonância Magnética , Polissacarídeos , Mamíferos
12.
Methods Mol Biol ; 2613: 189-202, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587080

RESUMO

Glycolipids are mainly distributed in the outer leaflet of the plasma membrane and are involved in cellular signaling by modulating the activity of cell surface receptor proteins. Glycolipids themselves also work as cell surface receptors of bacterial toxins. Anti-glycolipid antibodies are associated with various pathological conditions. The cellular distribution of glycolipids has been studied using specific toxins or antibodies. However, these proteins are multivalent and thus potentially induce the artificial aggregation of glycolipids. Since chemical fixative such as paraformaldehyde does not fix glycolipids, an alternative methodology is required to localize glycolipids with multivalent probes. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) physically fixes glycolipids on the cast after quick freezing. Thus, SDS-FRL provides the opportunity to observe the natural distribution of glycolipids using multivalent probes. Here, we describe the application of SDS-FRL on the cell surface distribution of phosphatidylglucoside.


Assuntos
Glicolipídeos , Dodecilsulfato de Sódio/metabolismo , Glicolipídeos/metabolismo , Membrana Celular/metabolismo , Técnica de Fratura por Congelamento , Imuno-Histoquímica
13.
Methods Mol Biol ; 2613: 257-270, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587084

RESUMO

Glycosphingolipids (GSLs) in the mammalian plasma membrane are essential for various biological events as they form glycolipid-rich membrane domains, such as lipid rafts. GSLs consist of a certain oligosaccharide head group and a ceramide tail with various lengths of acyl chains. The structure of the head group as well as the carbon number and degree of the unsaturation of the acyl chain are known to regulate the membrane distributions and interleaflet couplings of GSLs by altering physicochemical properties, such as dynamics, interactions, and cluster sizes. This chapter provides the detailed use of time-resolved fluorescence measurement for investigating the membrane properties of lactosylceramide (LacCer)-enriched domains in bilayer membranes. LacCer belongs to the neutral GSLs and is believed in forming a highly ordered phase in model membranes and biological membranes, while the details of the domain remain unclear. Here, we suggest using trans-parinaric acid (tPA) and tPA-LacCer fluorescent probes to reveal the dynamics and size of the GSL domains since they prefer to be distributed in the GSL-rich ordered phase. The fluorescence lifetime in the nanosecond timescale reveals the difference in the surrounding membrane environments, which relates to hydrocarbon chain ordering, membrane hydration, and submicrometer domain size. The fluorescence lifetime of these probes can thus provide important information on submicron- to nano-scale small GSL domains not only in model membranes but also in biological membranes.


Assuntos
Glicolipídeos , Lipossomos , Animais , Simulação de Dinâmica Molecular , Glicoesfingolipídeos/metabolismo , Membrana Celular/metabolismo , Lactosilceramidas , Mamíferos/metabolismo
14.
Methods Mol Biol ; 2613: 229-256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587083

RESUMO

Microbial glycosphingolipid (GSL)-degrading enzymes with unique specificity are useful tools for GSL research. On the other hand, some microbial glycolipids, not only GSLs but also steryl glucosides, are closely related to pathogenicity, and, thus, the metabolism of microbial glycolipids is attracting attention as a target for antibiotics. This chapter describes the assays and utilization of microbial enzymes useful for glycolipid research and those involved in pathogenicity or host immune reactions.


Assuntos
Glicolipídeos , Glicoesfingolipídeos , Glicolipídeos/metabolismo , Glicoesfingolipídeos/metabolismo , Fungos/metabolismo , Bactérias/metabolismo
15.
Biomacromolecules ; 24(1): 33-42, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36576429

RESUMO

Controlling the viscoelastic properties of hydrogels is a challenge for many applications. Low molecular weight gelators (LMWGs) like bile salts and glycolipids and biopolymers like chitosan and alginate are good candidates for developing fully biobased hybrid hydrogels that combine the advantages of both components. Biopolymers lead to enhanced mechanics, while LMWGs add functionality. In this work, hybrid hydrogels are composed of biopolymers (gelatin, chitosan, and alginate) and microbial glycolipid bioamphiphiles, known as biosurfactants. Besides their biocompatibility and natural origin, bioamphiphiles can present chameleonic behavior, as pH and ions control their phase diagram in water around neutrality under strongly diluted conditions (<5 wt%). The glycolipid used in this work behaves like a surfactant (micellar phase) at high pH or like a phospholipid (vesicle phase) at low pH. Moreover, at neutral-to-alkaline pH in the presence of calcium, it behaves like a gelator (fiber phase). The impact of each of these phases on the elastic properties of biopolymers is explored by means of oscillatory rheology, while the hybrid structure is studied by small angle X-ray scattering. The micellar and vesicular phases reduce the elastic properties of the hydrogels, while the fiber phase has the opposite effect; it enhances the hydrogel's strength by forming an interpenetrated biopolymer-LMWG network.


Assuntos
Quitosana , Hidrogéis , Hidrogéis/química , Quitosana/química , Fase S , Biopolímeros/química , Alginatos/química , Glicolipídeos/química
16.
Soft Matter ; 19(3): 378-393, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36562421

RESUMO

Low-molecular weight gelators (LMWGs) are small molecules (Mw < ∼1 kDa), which form self-assembled fibrillar network (SAFiN) hydrogels in water when triggered by an external stimulus. A great majority of SAFiN gels involve an entangled network of self-assembled fibers, in analogy to a polymer in a good solvent. In some rare cases, a combination of attractive van der Waals and repulsive electrostatic forces drives the formation of bundles with a suprafibrillar hexagonal order. In this work, an unexpected micelle-to-fiber transition is triggered by Ca2+ or Ag+ ions added to a micellar solution of a novel glycolipid surfactant, whereas salt-induced fibrillation is not common for surfactants. The resulting SAFiN, which forms a hydrogel above 0.5 wt%, has a "nano-fishnet" structure, characterized by a fibrous network of both entangled fibers and ß-sheet-like rafts, generally observed for silk fibroin, actin hydrogels or mineral imogolite nanotubes, but not known for SAFiNs. The ß-sheet-like raft domains are characterized by a combination of cryo-TEM and SAXS and seem to contribute to the stability of glycolipid gels. Furthermore, glycolipid is obtained by fermentation from natural resources (glucose, rapeseed oil), thus showing that naturally engineered compounds can have unprecedented properties, when compared to the wide range of chemically derived amphiphiles.


Assuntos
Hidrogéis , Tensoativos , Hidrogéis/química , Conformação Proteica em Folha beta , Peso Molecular , Espalhamento a Baixo Ângulo , Difração de Raios X , Micelas , Glicolipídeos
17.
Soft Matter ; 19(3): 366-377, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36508178

RESUMO

Low-molecular weight gelators (LMWGs) are small molecules (Mw < ∼1 kDa), which form self-assembled fibrillar network (SAFiN) hydrogels in water. A great majority of SAFiN gels are described by an entangled network of self-assembled fibers, in analogy to a polymer in a good solvent. Here, fibrillation of a biobased glycolipid bolaamphiphile is triggered by Ca2+ or Ag+ ions which are added to its diluted micellar phase. The resulting SAFiN, which forms a hydrogel above 0.5 wt%, has a "nano-fishnet" structure, characterized by a fibrous network of both entangled fibers and ß-sheet-like rafts, generally observed for silk fibroin, actin hydrogels or mineral imogolite nanotubes, but generally not known for SAFiN. This work focuses on the strength of the SAFIN gels, their fast recovery after applying a mechanical stimulus (strain) and their unusual resistance to temperature, studied by coupling rheology to small angle X-ray scattering (rheo-SAXS) using synchrotron radiation. The Ca2+-based hydrogel maintains its properties up to 55 °C, while the Ag+-based gel shows a constant elastic modulus up to 70 °C, without the appearance of any gel-to-sol transition temperature. Furthermore, the glycolipid is obtained by fermentation from natural resources (glucose and rapeseed oil), thus showing that naturally engineered compounds can have unprecedented properties, when compared to the wide range of chemically derived amphiphiles.


Assuntos
Glicolipídeos , Hidrogéis , Conformação Proteica em Folha beta , Espalhamento a Baixo Ângulo , Temperatura , Glicolipídeos/química , Difração de Raios X , Hidrogéis/química , Reologia
18.
Biomed Res Int ; 2022: 4293172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457344

RESUMO

Glycosphingolipids (GSLs) play numerous roles in cellular processes, including cell proliferation, apoptosis, inflammation, and cell signaling. Alteration of the GSLs metabolism leads to the accumulation of particular species of GSLs, which can lead to various pathologies, including carcinogenesis and metastasis; in essence, all neoplasms are characterized by the synthesis and aberrant organization of GSLs expressed on the cell surface. Secondary brain tumors make up the majority of intracranial cancers and generally present an unfavorable prognosis. In the present work, a native GSL mixture extracted and purified from a secondary brain tumor with primary pulmonary origin was obtained through extraction and purification and analyzed by MALDI TOF mass spectrometry. Research in the field of lipidomics could offer new data for the understanding of brain tropism and metastatic pathways, by studying the glycolipid molecules involved in the process of metastasis in general and in the production of brain metastases in particular. This could shed new light on the pattern of lipid glycosylation in secondary brain tumors, with a great impact on the effectiveness of cancer therapies, which could be adapted to the specific molecular pattern of the tumor.


Assuntos
Neoplasias Encefálicas , Glicolipídeos , Humanos , Encéfalo , Carcinogênese , Tropismo
19.
Sci Rep ; 12(1): 20916, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463380

RESUMO

Sepsis remains a significant clinical challenge. Ferroptosis is involved in the pathogenesis of sepsis. Ferroptosis is associated with oxidative stress, and excessive oxidative stress is suppressed by milk fat globule epidermal growth factor 8 (MFG-E8) under various conditions. However, the role of MFG-E8 in sepsis-induced ferroptosis and oxidative stress is still unclear. First, we collected blood samples from patients with sepsis and detected the expression of serum MFG-E8. Then, the relationship between serum concentrations of MFG-E8 and disease severity was detected. Finally, the effects of MFG-E8 treatment on ferroptosis and oxidative stress in the livers of septic mice were determined. The expression of serum MFG-E8 in healthy subjects was notably higher than that in septic patients. In addition, when nonsurvivors and survivors of sepsis were compared, MFG-E8 levels were considerably lower in the former. The ROC curve for MFG-E8 was also generated. The area under the curve for MFG-E8 was 0.768 (95% confidence interval [CI] 0.627-0.909, p = 0.003). The patients were separated into two groups based on the MFG-E8 cut-off value of 3.86 ng/mL. According to the Kaplan‒Meier survival analysis, patients with low MFG-E8 levels had a significantly decreased 28-day survival rate compared with patients with high MFG-E8 levels. High MFG-E8 levels were substantially related to a decreased risk of death, as demonstrated by the Cox proportional hazard model that we utilized. In addition, compared with sham mice, septic mice exhibited liver and kidney damage, and MFG-E8 may have protective effects. The survival study indicated that MFG-E8 could effectively improve the survival rate of septic mice. Treatment with MFG-E8 suppresses oxidative stress and ferroptosis in the livers of septic mice. Serum MFG-E8 levels are lower in septic patients and are negatively related to disease severity. Treatment with MFG-E8 suppresses oxidative stress and ferroptosis in the livers of septic mice, contributing to significantly improved survival in septic mice. These findings showed that MFG-E8 could be a new sepsis predictive biomarker. MFG-E8 may have therapeutic potential in the treatment of sepsis.


Assuntos
Fator VIII , Sepse , Camundongos , Animais , Prognóstico , Glicolipídeos
20.
Curr Microbiol ; 80(1): 16, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459236

RESUMO

Streptococcus agalactiae (group B Streptococcus, GBS) is a gram-positive bacterium that is an asymptomatic colonizer commonly found in the gastrointestinal and genitourinary tract of healthy adults. GBS is also the most common cause of life-threatening bacterial infections in newborns and is emerging as a pathogen in immunocompromised and diabetic adults. The GBS cell wall and covalently linked capsular polysaccharides (CPS) are vital to the protection of the bacterial cell and act as virulence factors. GBS-CPS have been successfully used to produce conjugate vaccines for all currently identified GBS serotypes. However, the mechanisms of biosynthesis and assembly of CPS and the other cell wall components remain poorly defined due to their complex surface structures. In this biosynthetic study of the GBS cell wall-CPS complex, glycolipids with varying lengths of glycosyl-chains were discovered. Among those, one of the smallest glycolipids (named GBS Lipid-α) was structurally characterized. Lipid-α is involved in GBS saccharide metabolism and presumably acts as a glycosyl acceptor to elongate the glycosyl chain. GBS Lipid-α was determined to be a 3-monosaccharide 1,2 acyl glycerol with a molecular mass in the range of m/z = 724-808. GBS Lipid-α is highly heterogenic with various acyl groups and glycosyl moieties. This knowledge will pave the way for future studies to elucidate the entire metabolic pathway and genes involved. The Lipid-α pathway may also exist in other bacterial species and has the potential to be a biomarker for future drug development.


Assuntos
Parede Celular , Streptococcus agalactiae , Recém-Nascido , Humanos , Adulto , Sorogrupo , Glicerol , Glicolipídeos
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