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Carbon materials with elusive 0D, 1D, 2D, and 3D nanostructures and high surface area provide certain emerging applications in electrocatalytic and photocatalytic CO2 utilization. Since carbon possesses high electrical conductivity, it expels the photogenerated electrons from the catalytic surface and can tune the photocatalytic activity in the visible-light region. However, the photocatalytic efficiency of pristine carbon is comparatively low due to the high recombination of photogenerated carriers. Thus, supporting carbon materials, such as graphene, CNTs (Carbon nanotubes), g-C3N4, MWCNs (Multiwall carbon nanotubes), conducting polymers, and its other simpler forms like activated carbon, nanofibers, nanosheets, and nanoparticles, are usually combined with other metal and non-metal nanocomposites to increase the CO2 absorption and conversion. In addition, carbon-based materials with transition metals and organometallic complexes are also commonly used as photocatalysts for CO2 reduction. This review focuses on developing efficient carbon-based nanomaterials for the photoconversion of CO2 into solar fuels. It is concluded that MWCNs are one of the most used materials as supporting materials for CO2 reduction. Due to the multi-layered morphology, multiple reflections will occur within the layers, thus enhancing light harvesting. In particular, stacked nanostructured hollow sphere morphologies can also help the metal doping from corroding.
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Contaminants of Emerging Concern (CECs), a new category of contaminants currently in the limelight, are a major issue of global concern. The pervasive nature of CECs and their harmful effects, such as cancer, reproductive disorders, neurotoxicity, etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentrations of CECs can cause great impacts on living beings. They also have a nature of bioaccumulation. Thus, there is a great need to have efficient sensors for the detection of CECs to ensure a safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of the analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in the literature under each category for the detection of major CECs.
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Plaguicidas , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Plaguicidas/análisis , Monitoreo del AmbienteRESUMEN
BACKGROUND Wogonin (5,7-dihydroxy-8-methoxyflavone), one of flavonoids isolated from the Scutellaria baicalensis, has been regarded as an anticancer candidate because of its maximal efficacy in cancer cells. This study aimed to explore the possible mechanism that wogonin uses to enhance the sensitivity of ovarian cancer cells to cisplatin chemotherapy. MATERIAL AND METHODS The growth inhibition rates of ovarian cancer cells SKOV3/DDP and C13* were assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis was assessed under a fluorescence microscope following staining with Hoechst. We further analyzed the expression of Bcl-2, cleaved caspases-3, cleaved-PARP, and phospho-Akt by western blotting. RESULTS In the present study, we found that wogonin reduced proliferation of ovarian cancer cells SKOV3, SKOV3/DDP, OV2008, and C13* in dose- and time-dependent manners and it sensitized cisplatin-induced cytotoxicity. Moreover, treatment with wogonin also increased cisplatin-resistant SKOV3/DDP and C13* cells to low dose cisplatin-induced cell apoptosis. Additionally, such treatment resulted in a significant decrease in phosphorylated Akt. CONCLUSIONS Wogonin could significantly increase the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin by downregulating the PI3K/Akt pathway.
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Flavanonas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Ovario/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
BACKGROUND: Staphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus. RESULTS: In this study, we developed three human monoclonal antibodies against all F-components of leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo. CONCLUSIONS: Our findings revealed that neutralizing bicomponent leukocidins may be a promising strategy to combat infections caused by S. aureus.
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Anticuerpos Monoclonales/administración & dosificación , Proteínas Hemolisinas/inmunología , Leucocidinas/inmunología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/fisiología , Animales , Anticuerpos Monoclonales/inmunología , Progresión de la Enfermedad , Eritrocitos/efectos de los fármacos , Femenino , Proteínas Hemolisinas/toxicidad , Hemólisis/efectos de los fármacos , Humanos , Leucocidinas/toxicidad , Ratones Endogámicos BALB C , Pruebas de Neutralización , Conejos , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genéticaRESUMEN
The presence of antibiotics in agroecosystems raises concerns about the proliferation of antibiotic-resistant bacteria and adverse effects to human health. Soil amendment with biochars pyrolized from manures may be a win-win strategy for novel manure management and antibiotics abatement. In this study, lincomycin sorption by manure-derived biochars was examined using batch sorption experiments. Lincomycin sorption was characterized by two-stage kinetics with fast sorption reaching quasi-equilibrium in the first 2 d, followed by slow sorption over 180 d. The fast sorption was primarily attributed to surface adsorption, whereas the long-term slow sorption was controlled by slow diffusion of lincomycin into biochar pore structures. Two-day sorption experiments were performed to explore effects of biochar particle size, solid/water ratio, solution pH, and ionic strength. Lincomycin sorption to biochars was greater at solution pH 6.0 to 7.5 below the dissociation constant of lincomycin (7.6) than at pH 9.9 to 10.4 above its dissociation constant. The enhanced lincomycin sorption at lower pH likely resulted from electrostatic attraction between the positively charged lincomycin and the negatively charged biochar surfaces. This was corroborated by the observation that lincomycin sorption decreased with increasing ionic strength at lower pH (6.7) but remained constant at higher pH (10). The long-term lincomycin sequestration by biochars was largely due to pore diffusion plausibly independent of solution pH and ionic composition. Therefore, manure-derived biochars had lasting lincomycin sequestration capacity, implying that biochar soil amendment could significantly affect the distribution, transport, and bioavailability of lincomycin in agroecosystems.
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Carbón Orgánico , Lincomicina/química , Estiércol , Adsorción , Suelo , AguaRESUMEN
Removal of arsenic (As) from water supplies is needed to reduce As exposure through drinking water and food consumption in many regions of the world. Magnetite nanoparticles (MNPs) are promising and novel adsorbents for As removal because of their great adsorption capacity for As and easy separation. This study aimed to investigate the adsorption mechanism of arsenate, As(V), and arsenite, As(III), on MNPs by macroscopic adsorption experiments in combination with thermodynamic calculation and microspectroscopic characterization using synchrotron-radiation-based X-ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS). Adsorption reactions are favorable endothermic processes as evidenced by increased adsorption with increasing temperatures, and high positive enthalpy change. EXAFS spectra suggested predominant formation of bidentate binuclear corner-sharing complexes ((2)C) for As(V), and tridentate hexanuclear corner-sharing ((3)C) complexes for As(III) on MNP surfaces. The macroscopic and microscopic data conclusively identified the formation of inner-sphere complexes between As and MNP surfaces. More intriguingly, XANES and XPS results revealed complex redox transformation of the adsorbed As on MNPs exposed to air: Concomitant with the oxidation of MNPs, the oxidation of As(III) and MNPs was expected, but the observed As(V) reduction was surprising because of the role played by the reactive Fe(II).
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Arsénico/aislamiento & purificación , Nanopartículas de Magnetita/química , Agua/química , Adsorción , Concentración de Iones de Hidrógeno , Punto Isoeléctrico , Concentración Osmolar , Oxidación-Reducción , Espectroscopía de Fotoelectrones , Termodinámica , Abastecimiento de Agua , Espectroscopía de Absorción de Rayos XRESUMEN
IMPORTANCE: Staphylococcus aureus is a Gram-positive opportunistic bacterium that is responsible for the majority of skin infections in humans. Our study provides important molecular insights into the pathogenesis of S. aureus skin infections and identifies a potential therapeutic target for the treatment of these infections. Our findings also indicate that ß-hemolysin (Hlb) secreted by colonized S. aureus is a risk factor for epidermal growth factor receptor (EGFR)-related diseases by acting as an agonist of EGFR. The neutralized monoclonal antibody we have developed for the first time will provide a functional inhibitor of Hlb. This study provides important insights to better understand the relationship between the skin colonization of S. aureus and inflammatory skin diseases.
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Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Staphylococcus aureus/metabolismo , Proteínas Hemolisinas/metabolismo , Piel/microbiología , Receptores ErbB/metabolismo , Infecciones Estafilocócicas/microbiología , Inflamación/patologíaRESUMEN
Influenza A viruses (IAVs) continue to pose a huge threat to public health, and their prevention and treatment remain major international issues. Neuraminidase (NA) is the second most abundant surface glycoprotein on influenza viruses, and antibodies to NA have been shown to be effective against influenza infection. In this study, we generated a monoclonal antibody (mAb), named FNA1, directed toward N1 NAs. FNA1 reacted with H1N1 and H5N1 NA, but failed to react with the NA proteins of H3N2 and H7N9. In vitro, FNA1 displayed potent antiviral activity that mediated both NA inhibition (NI) and blocking of pseudovirus release. Moreover, residues 219, 254, 358, and 388 in the NA protein were critical for FNA1 binding to H1N1 NA. However, further validation is necessary to confirm whether FNA1 mAb is indeed a good inhibitor against NA for application against H1N1 and H5N1 viruses.
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Anticuerpos Monoclonales , Subtipo H1N1 del Virus de la Influenza A , Neuraminidasa , Neuraminidasa/inmunología , Neuraminidasa/metabolismo , Neuraminidasa/antagonistas & inhibidores , Anticuerpos Monoclonales/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Humanos , Animales , Anticuerpos Antivirales/inmunología , Ratones , Subtipo H5N1 del Virus de la Influenza A/inmunología , Ratones Endogámicos BALB C , Antivirales/farmacología , Proteínas Virales/inmunología , Proteínas Virales/metabolismo , Subtipo H3N2 del Virus de la Influenza A/inmunología , Subtipo H7N9 del Virus de la Influenza A/inmunologíaRESUMEN
The cytokine interleukin-6 (IL-6) plays a crucial role in autoimmune and inflammatory diseases. Understanding the precise mechanism of IL-6 interaction at the amino acid level is essential to develop IL-6-inhibiting compounds. In this study, we employed computer-guided drug design tools to predict the key residues that are involved in the interaction between IL-6 and its receptor IL-6R. Subsequently, we generated IL-6 mutants and evaluated their binding affinity to IL-6R and the IL-6R - gp130 complex, as well as monitoring their biological activities. Our findings revealed that the R167A mutant exhibited increased affinity for IL-6R, leading to enhanced binding to IL-6R - gp130 complex and subsequently elevated intracellular phosphorylation of STAT3 in effector cells. On the other hand, although E171A reduced its affinity for IL-6R, it displayed stronger binding to the IL-6R - gp130 complex, thereby enhancing its biological activity. Furthermore, we identified the importance of R178 and R181 for the precise recognition of IL-6 by IL-6R. Mutants R181A/V failed to bind to IL-6R, while maintaining an affinity for the IL-6 - gp130 complex. Additionally, deletion of the D helix resulted in complete loss of IL-6 binding affinity for IL-6R. Overall, this study provides valuable insights into the binding mechanism of IL-6 and establishes a solid foundation for future design of novel IL-6 inhibitors.
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Interleucina-6 , Simulación del Acoplamiento Molecular , Unión Proteica , Receptores de Interleucina-6 , Interleucina-6/metabolismo , Interleucina-6/genética , Humanos , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/química , Receptor gp130 de Citocinas/metabolismo , Receptor gp130 de Citocinas/genética , Receptor gp130 de Citocinas/química , Mutagénesis Sitio-Dirigida , Sitios de Unión , Factor de Transcripción STAT3/metabolismo , Fosforilación , MutaciónRESUMEN
Super-sensitive malathion detection was achieved using a nonenzymatic electrochemical sensor based on a CuO/ZnO-modified glassy carbon electrode (GCE). Due to the high affinity between the Cu element and the sulfur groups in malathion, the developed CuO-ZnO/GCE sensor may bond malathion with ease, inhibiting the redox signal of the Cu element when malathion is present. In addition to significantly increasing the ability of electron transfer, the addition of 3D-flower-like ZnO enhances active sites of the sensor interface for the high affinity of malathion, giving the CuO-ZnO/GCE composite an exceptional level of sensitivity and selectivity. This enzyme-free CuO-ZnO/GCE malathion sensor demonstrates outstanding stability and excellent detection performance under optimal operating conditions with a wide linear range of malathion from 0 to 200 nM and a low detection limit of 1.367 nM. A promising alternative technique for organophosphorus pesticide (OP) determination is offered by the analytical performance of the proposed sensor, and this method can be quickly and sensitively applied to samples that have been contaminated with these pesticides.
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Smallpox is an infectious disease caused by the variola virus, and it has a high mortality rate. Historically it has broken out in many countries and it was a great threat to human health. Smallpox was declared eradicated in 1980, and Many countries stopped nation-wide smallpox vaccinations at that time. In recent years the potential threat of bioterrorism using smallpox has led to resumed research on the treatment and prevention of smallpox. Effective ways of preventing and treating smallpox infection have been reported, including vaccination, chemical drugs, neutralizing antibodies, and clinical symptomatic therapies. Antibody treatments include anti-sera, murine monoclonal antibodies, and engineered humanized or human antibodies. Engineered antibodies are homologous, safe, and effective. The development of humanized and genetically engineered antibodies against variola virus via molecular biology and bioinformatics is therefore a potentially fruitful prospect with respect to field application. Natural smallpox virus is inaccessible, therefore most research about prevention and/or treatment of smallpox were done using vaccinia virus, which is much safer and highly homologous to smallpox. Herein we summarize vaccinia virus epitope information reported to date, and discuss neutralizing antibodies with potential value for field application.
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Castor cake is a major by-product generated after castor oil extraction and has been widely used as an organic fertilizer. Once applied to soil, a toxic alkaloid ricinine in castor cake may be released into soils and subsequently taken up by crops, which poses a potential threat to food safety and human health. However, the environmental fate of castor cake derived ricinine in agroecosystems remains unclear. In this study, the release and metabolism of ricinine in soils were conducted using soil pot experiments with different castor cake application rates. The analytical methodology of ricinine quantification in soil pore water was first established using solid phase extraction (SPE) coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A non-target screening workflow associated with LC-QTOF/MS and SIRIUS platform was further developed to identify ricinine metabolites in soil pore water. After castor cake application, the ricinine concentrations in soil pore water significantly increased to 297-7990 µg L-1 at 1 day and then gradually decreased to 62.1-3460 µg L-1 at 7 days and 1.70-279 µg L-1 at 14 days for the selected two tested soils with castor cake application rates of 2, 10, and 20 g castor cake/kg soil. In addition, two ricinine metabolites R-194 and R-180 were tentatively identified and one ricinine metabolite N-demethyl-ricinin was confirmed through authentic reference standard for the first time by the developed non-target screening workflow. This study highlights the release and metabolism of toxic alkaloid ricinine in soils once applied castor cake as an organic fertilizer. Ricinine could be released into soil pore water in a short-term after castor cake application and then undergo demethylation, hydroxylation, and hydroxylation followed by methylation metabolisms over time in agroecosystems.
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Alcaloides , Fertilizantes , Humanos , Fertilizantes/análisis , Suelo , Aceite de Ricino , Flujo de Trabajo , Cromatografía Liquida , Alcaloides/análisis , Espectrometría de Masas , Agua/análisisRESUMEN
Heavy metals are one of the most important classes of environmental pollutants which are toxic to living beings. Many efforts are made by scientists to fabricate better sensors for the identification and quantification of heavy metal ions (HMI) in water and food samples to ensure good health. Electrocatalysts have been demonstrated to play an important role in enhancing the sensitivity and selectivity of HMI detection in electrochemical sensors. In this review, we presented morphologically well-tuned nanomaterials used as efficient sensor materials. Based on the molecular dimensions, shapes, and orientation, nanomaterials can be classified into 0-D, 1-D, 2-D, and 3-D nanomaterials. Active surface areas with significant exposure of active sites and adsorption-desorption abilities are extensively varied with dimensionality, which in turn ultimately influence the sensing performance for HMI.
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Background: Bladder cancer (BC) is the most common malignancy of the urinary tract in China, and the extent of tumor invasion negatively correlates with prognosis. The mechanism of tumor invasion in BC has been unclear until recent studies revealed the critical role of long noncoding RNAs (lncRNAs) in the proliferation and invasion of tumors. Several lncRNAs have been reported to be associated with pathogenesis in BC, but not specifically. Methods: We used a microarray to screen the candidate lncRNAs with different expressions in BC. The expression of the lncRNAs in BC tissues or cells was identified by reverse transcription polymerase chain reaction (RT-PCR) or quantitative real-time PCR (qRT-PCR), and their ectopic expressions were measured via transfection experiment. The function of the lncRNAs was investigated by flow cytometry, caspase-3 enzyme linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8), wound healing, transwell and colony formation experiments in vitro and xenograft experiments in vivo. Results: We identified a novel sense lncRNA, NONHSAT070806, that was downregulated in BC tissues and cells and negatively correlated with level of tumor invasion in patients. Furthermore, overexpression of NONHSAT070806 induced apoptosis of T24 and 5637 cells, inhibited the proliferation, migration and invasion of BC cells, and attenuated the tumorigenesis of BC cells both in vitro and in vivo. Conclusions: NONHSAT070806 may act as a suppressor of BC and is a potential indicator of the invasiveness of BC.
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The electron transport behavior in chemically reduced graphene oxide (rGO) sheets with different thicknesses of 2, 3, and 5 nm was investigated. The four-probe method for the sheet resistance (R(S)) measurement on the intensively reduced graphene oxide samples indicates an Arrhenius characteristic of the electron transport at zero magnetic field B = 0, consistent with previous experimental results on well-reduced GO samples. The anticipated variable range hopping (VRH) transport of electrons in a two-dimensional electron system at low temperatures was not observed. The measured R(S) of the rGO samples are below 52 kΩ/square at room temperature. With the application of a magnetic field up to 4 T, negative magnetoresistance in the Mott VRH regime was observed. The magnetotransport features support a model based on the spin-coupling effect from the vacancy-induced midgap states that facilitate the Mott VRH conduction in the presence of an external magnetic field.
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IFN-γ is produced upon stimulation with S. aureus and may play a detrimental role during infection. However, whether hemolysins play a role in the mechanism of IFN-γ production has not been fully characterized. In this study, we demonstrated that Hlb, one of the major hemolysins of S. aureus, upregulated IFN-γ production by CD56bright NK cells from human peripheral blood mononuclear cells (PBMCs). Further investigation showed that Hlb increased calcium influx and induced phosphorylation of ERK1/2. Either blocking calcium or specifically inhibiting phosphorylation of ERK1/2 decreased the production of IFN-γ induced by Hlb. Moreover, we found that this process was dependent on the sphingomyelinase activity of Hlb. Our findings revealed a novel mechanism of IFN-γ production in NK cells induced by Hlb, which may be involved in the pathogenesis of S. aureus.
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Leucocitos Mononucleares , Staphylococcus aureus , Antígeno CD56 , Proteínas Hemolisinas , Humanos , Interferón gamma , Células Asesinas Naturales , Esfingomielina FosfodiesterasaRESUMEN
Polymers are highly promising materials for capturing carbon dioxide (CO2), a greenhouse gas. Hence in this work, we prepared phyllosilicate supported mesoporous polymer via reversible addition-fragmentation chain transfer (RAFT) polymerisation, which is the one among the controlled radical polymerisation. The mesoporous material anchored on dodecanethiol trithiocarbonate acts as a chain transfer agent (CTA) for the polymerisation of chloromethyl styrene and further conversion to quaternary ammonium compound which is effective to trap CO2 using tertiary amine. The synthesised porous phyllosilicate/polymer nanocomposites have been characterised by using various analytical tools. The CO2 sorption experiments were carried out by passing CO2 onto the synthesised porous phyllosilicate/polymer nanocomposites. The sorption kinetics was monitored by X-Ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) spectra in the presence of carbonate were obtained by reaction of quaternary ammonium hydroxide and CO2. The phyllosilicate anchored macromolecular CTA (macro-CTA) and the surface-initiated polymer nanocomposites encompassed apparent surface areas of 94.5 and 26.8 m2 g-1, respectively. In addition, the total pore volumes calculated for the macro-CTA and polymer were found to be 0.27 and 0.095 cm3g-1, while the average pore sizes were 14.24 and 11.46 nm, respectively. The CO2 sorption capacity of the phyllosilicate/polymer nanocomposites, monitored at different temperatures, is the fastest for 25°C but slower for the sample treated at 50°C which may due to the dipole and quadrupole interaction.
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Staphylococcus aureus is a major pathogenic bacterium that causes a variety of clinical infections. The emergence of multi-drug resistant mechanisms requires novel strategies to mitigate S. aureus infection. Alpha-hemolysin (Hla) is a key virulence factor that is believed to play a significant role in the pathogenesis of S. aureus infections. In this study, we screened a naïve human Fab library for identification of monoclonal antibodies targeting Hla by phage display technology. We found that the monoclonal antibody YG1 blocked the Hla-mediated lysis of rabbit red blood cells and inhibited Hla binding to A549 cells in a concentration-dependent manner. YG1 also provided protection against acute peritoneal infection, bacteremia, and pneumonia in murine models. We further characterized its epitope using different Hla variants and found that the amino acids N209 and F210 of Hla were functionally and structurally important for YG1 binding. Overall, these results indicated that targeting Hla with YG1 could serve as a promising protective strategy against S. aureus infection.
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple autoantibody production and often affects the kidneys, known as lupus nephritis. However, the mechanism underlying lupus nephritis development is unclear. Biofilms that protect bacteria from stress are ubiquitous in almost every environment. Here, we identified that a conserved peptide (HU1) derived from DNABII proteins, one of major bacterial biofilm components, was specifically recognized by sera from about 47% patients with SLE. Moreover, the serum anti-HU1 levels showed a significant positive correlation with lupus nephritis occurrence. Presence of antibodies against HU1 in pristane-induced mice aggravated lupus nephritis, although these antibodies also attenuated bacterial biofilm formation. We further identified that antibodies against HU1 cross-recognized protein disulfide isomerase (P4HB) located on the renal cell surface and inhibited the activities of this enzyme. Our findings reveal a novel mechanism underlying the development of lupus nephritis triggered by bacterial biofilms.
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Autoanticuerpos/inmunología , Bacterias/inmunología , Biopelículas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/etiología , Nefritis Lúpica/patología , Secuencia de Aminoácidos , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Autoanticuerpos/sangre , Autoantígenos/inmunología , Biomarcadores , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/sangre , Ratones , Ratones Transgénicos , Péptidos/química , Péptidos/inmunología , Terpenos/efectos adversosRESUMEN
Extracellular traps released by neutrophils (NETs) are essential for the clearance of Pseudomonas aeruginosa. Alkaline protease (AprA) secreted by P. aeruginosa negatively correlates with clinical improvement. Moreover, anti-AprA in patients with cystic fibrosis (CF) can help identify patients with aggressive forms of chronic infection. However, the mechanism underlying the clinical outcomes remains unclear. We demonstrated that aprA deficiency in P. aeruginosa decreased the bacterial burden and reduced lung infection. AprA degraded NET components in vitro and in vivo but did not affect NET formation. Importantly, antibodies induced by AprA acted as an agonist and directly enhanced the degrading activities of AprA. Moreover, antisera from patients with P. aeruginosa infection exhibited antibody-dependent enhancement (ADE) similar to that of the antibodies we prepared. Our further investigations showed that the interaction between AprA and the specific antibodies might make the enzyme active sites better exposed, and subsequently enhance the recognition of substrates and accelerate the degradation. Our findings revealed that AprA secreted by P. aeruginosa may aggravate infection by destroying formed NETs, an effect that was further enhanced by its antibodies.