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1.
J Hazard Mater ; 402: 123498, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712366

RESUMO

N-doped nanoporous carbon (NC) with two-dimensional structure derived from Zn-ZIF-L via KCl exfoliation and carbonization at different temperature were prepared for adsorptive removal of tetracycline (TC). Characterizations revealed the effective dopant of N atoms and low degree of graphitization with more defects related to the enhanced adsorption capacity of the NC materials. Benefiting from the huge surface area (2195.57 m2 g-1), high porosity (1.34 cm3 g-1) and accessible sheeting structure, the NC-800 exhibited its fast and efficient adsorption of TC in 60 min. Meantime, the maximum adsorption of TC could reach 347.06 mg g-1. Effects of pH, humic acid (HA) and ionic strength (Na+, Ca2+) were studied along with the interactions among influencing factors investigated by response surface model (RSM). By optimizing experimental conditions from RSM, the adsorption capacity could increase to 427.41 mg g-1. Additionally, electrostatic interaction and hydrogen bond interaction might play a dominating role in adsorption reaction. The NC-800 could maintain a high adsorption level after four cycles. Therefore, the NC-800 with great adsorptive property and reusability could be considered as an effective adsorbent with promising potential in applications for water treatment.

2.
J Colloid Interface Sci ; 581(Pt A): 195-204, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771731

RESUMO

Compared with the transition metal induced homogeneous catalytic system, the heterogeneous catalytic system based on transition metal-doped metal organic frameworks (MOFs) were stable for the efficient utilization of transition metal and avoiding the metal leaching. The aim of this work is to synthesize Co-doped MIL-53(Al) by one-step solvent thermal method and use it to activate peroxymonosulfate (PMS) to remove tetracycline (TC) in water. The successful synthesis of Co-MIL-53(Al) samples was demonstrated by XDR, SEM and FTIR characterizations. The 25% Co-MIL-53(Al)/PMS system showed the optimal TC removal effect compared to the PMS alone and MIL-53(Al)/PMS system. The catalytic performances of Co-MIL-53(Al)/PMS system in conditions of different pH, co-existing substances and water bodies were investigated. Quenching experiment and electron paramagnetic resonance (EPR) showed that the degradation mechanism by Co-MIL-53(Al) activation PMS was mainly attributed to sulfate radical (SO4•-) and singlet oxygen (1O2) non-radical. The degradation intermediates of TC were also identified and the possible degradation pathways were proposed. Co-MIL-53(Al) showed good activity after four cycles. These findings demonstrated that Co-MIL-53(Al) can be a promising heterogeneous catalyst for activating PMS to degrade TC.

3.
Aging (Albany NY) ; 122020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159013

RESUMO

XL388 is a highly efficient and orally-available ATP-competitive PI3K-mTOR dual inhibitor. Its activity against glioma cells was studied here. In established and primary human glioma cells, XL388 potently inhibited cell survival and proliferation as well as cell migration, invasion and cell cycle progression. The dual inhibitor induced significant apoptosis activation in glioma cells. In A172 cells and primary human glioma cells, XL388 inhibited Akt-mTORC1/2 activation by blocking phosphorylation of Akt and S6K1. XL388-induced glioma cell death was only partially attenuated by a constitutively-active mutant Akt1. Furthermore, it was cytotoxic against Akt1-knockout A172 glioma cells. XL388 downregulated MAF bZIP transcription factor G (MAFG) and inhibited Nrf2 signaling, causing oxidative injury in glioma cells. Conversely, antioxidants, n-acetylcysteine, pyrrolidine dithiocarbamate and AGI-106, alleviated XL388-induced cytotoxicity and apoptosis in glioma cells. Oral administration of XL388 inhibited subcutaneous A172 xenograft growth in severe combined immunodeficient mice. Akt-S6K1 inhibition and MAFG downregulation were detected in XL388-treated A172 xenograft tissues. Collectively, XL388 efficiently inhibits human glioma cell growth, through Akt-mTOR-dependent and -independent mechanisms.

4.
Phytomedicine ; 79: 153346, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33002828

RESUMO

BACKGROUND: Immunoglobulin E (IgE)-mediated mast cell (MC) activation is crucial in multiple allergic diseases. Parkinson disease protein 7 (DJ-1) and Lyn kinase were reported as the receptor-proximal events in IgE receptor (FcεRI) signals in human MC. Kaempferol, a natural flavonol mainly derived from the rhizome of traditional Chinese herb Kaempferia galanga L. (Zingiberaceae), has been known to inhibit allergic reactions, but it was limited to the receptor-distal signals on rat basophilic leukemia cells. A thorough investigation of the inhibitory effects of kaempferol on human MC has not been done. PURPOSE: To investigate the inhibitory effects of kaempferol on IgE-mediated anaphylaxis in vivo and in human MCs, as well as the mechanism underlying its effects, especially the receptor-proximal signals. METHODS: IgE-mediated passive cutaneous anaphylaxis and systemic anaphylaxis model were applied to elucidate the antiallergic activity of kaempferol in vivo. The degranulation assay, calcium imaging, the release of cytokines and chemokines on the laboratory of allergic disease 2 (LAD2) cells were used to evaluate the antiallergic effect of kaempferol in vitro. Western blot analysis was performed to investigate the DJ-1/Lyn signaling pathway and downstream molecules. Kinase activity assay, immunofluorescence, and molecular docking were conducted to confirm the influence of kaempferol on DJ-1/Lyn molecules. RESULTS: Kaempferol dose-dependently attenuated ovalbumin/IgE-induced mice paw swelling, primary MC activation from paw skin, as well as rehabilitated the hypothermia, and reduced the serum concentrations of histamine, tumor necrosis factor-alpha, interleukin-8, and monocyte chemo-attractant protein-1. Additionally, kaempferol suppressed IgE-mediated LAD2 cell degranulation and calcium fluctuation. Remarkably, kaempferol was found to bind with DJ-1 protein, and initially prevented DJ-1 from translocating to the plasma membrane, thereby inhibited full activation of Lyn, and eventually restrained those receptor-distal signaling molecules, involved Syk, Btk, PLCγ, IP3R, PKC, MAPKs, Akt and NF-κB. CONCLUSION: Kaempferol could be used as a DJ-1 modulator for preventing MC-mediated allergic disorders through attenuating Lyn activation.

6.
J Colloid Interface Sci ; 580: 470-479, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32711198

RESUMO

Herein, Mn-doped MIL-53(Fe) were fabricated via one-pot solvothermal method and used for peroxymonosulfate (PMS) activation towards tetracycline (TC) degradation from aqueous solution. The characterizations of SEM, FTIR and XRD were utilized to reveal the morphology and structure of the materials. The results showed that Mn-MIL-53(Fe)-0.3 displayed the optimal catalytic performance, the removal efficiency of TC could reach 93.2%. Moreover, the catalytic activity of Mn-MIL-53(Fe) towards TC under different initial pH values, co-existing anions (Cl-,CO32- and SO42-) and humic acid (HA) were investigated. The results of thermodynamic experiment suggested that the catalytic process was endothermic. In addition, integrated with capture experiments results and the characterization results of electron paramagnetic resonance (EPR), which revealed that SO4·- and HO- were the reactive radicals involving in the reaction. More importantly, the possible activation mechanism was discussed in detail based on the X-ray photoelectron spectroscopy results. The active species were generated by the active sites of Fe(II) and Mn(II) on Mn-MIL-53(Fe) effectively activated PMS. Furthermore, the degradation intermediates and possible degradation pathway were investigated by LC-MS. Finally, the catalyst also showed good performance in actual wastewater and demonstrated good recyclability. The Mn-MIL-53(Fe)/PMS system exhibited a promising application prospect for antibiotic-containing waste water treatment.

9.
J Pharm Pharmacol ; 72(9): 1221-1231, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557699

RESUMO

OBJECTIVES: To investigate the inhibitory effects of Kaempferol, a natural flavonol active compound, on pseudo-allergic reactions (in vivo and in vitro), particularly on the mechanism underlying its effect in human mast cells. METHODS: Compound 48/80 (C48/80)-induced immunoglobulin E (IgE)-independent passive cutaneous anaphylaxis (PCA) model and systemic anaphylaxis were applied to investigate the anti-allergic activity of Kaempferol. The degranulation assay, calcium imaging and the secretion of cytokines and chemokines were used to evaluate the inhibitory effect on mast cell activation. Western blot analysis was performed to investigate intracellular calcium fluctuation-related signalling pathways. KEY FINDINGS: Kaempferol dose-dependently attenuated C48/80-induced mice hind paw swelling, dye extravasation and skin mast cell degranulation, and rehabilitated the hypothermia, as well as reduced the serum concentrations of histamine, tryptase, tumour necrosis factor-alpha (TNF-α), interleukin-8 (IL-8) and monocyte chemo-attractant protein-1 (MCP-1). Furthermore, Kaempferol suppressed C48/80-triggered human MC degranulation and calcium fluctuations by inhibiting phospholipase Cγ (PLCγ) phosphorylation and subsequent cytokines synthesis pathways. CONCLUSIONS: The inhibition of the process of PLCγ phosphorylation to Ca2+ mobilization represents a major strategy in Kaempferol-suppressed pseudo-allergic reactions. Thus, Kaempferol could be considered as a therapeutic drug candidate for non-IgE-mediated allergic reactions or inflammations.

10.
ACS Sens ; 5(7): 2198-2204, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32551563

RESUMO

Conventional ion current-based nanopore techniques that identify single molecules are hampered by limitations of providing only the ionic current information. Here, we introduce a silver nanotriangle-based nanopore (diameter < 50 nm) system for detecting molecule translocation using surface-enhanced Raman scattering. Rhodamine 6G is used as a model molecule to study the effect of an electric field (-1 V) on the mass transport. The four DNA bases also show significantly different SERS signals when they are transported into the plasmonic nanopore. The observations suggest that in the electric field, analyte molecules are driven into the nanopipette through the hot spot of the silver nanopore. The plasmonic nanopore shows great potential as a highly sensitive SERS platform for detecting molecule transport and paves the way for single molecule probing.

11.
Int J Med Inform ; 139: 104141, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32325369

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease related to inflammation affected by harmful gas and particulate matter in the air. Mathematical prediction models between COPD and air pollutants are helpful for early identification, individualized interventions to slow disease progression, and for reduction of medical expenditures. The aim was to build a regression prediction model for the occurrence of COPD acute exacerbation. We collected hospital admissions for COPD in 2015-2018 from ten hospitals in Chongqing, China, used the increment per week as response, and the local sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and particulate matter 2.5 (PM2.5) concentrations as predictor variables to build a multiple prediction model. The Mean Absolute Percentage Error (MAPE) was used to evaluate the efficiency. We found that PM2.5 and SO2 are the most important factors contributing to the improvement of prediction accuracy. Multiple locally weighted linear regression (LWLR) Model based on integrated kernel framework with the K-means algorithm demonstrated minimum prediction error of 9.03 %(k=11).


Assuntos
Poluentes Atmosféricos/efeitos adversos , Modelos Estatísticos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Monóxido de Carbono/análise , China/epidemiologia , Humanos , Incidência , Modelos Lineares , Morbidade , Dióxido de Nitrogênio/análise , Material Particulado/análise , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Dióxido de Enxofre/análise
12.
Sci Total Environ ; 724: 138248, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32247117

RESUMO

In this work, we investigated the impact of iron nanoparticle, including magnetite nanoparticles (Fe3O4 NPs) and nanoscale zero-valent iron (nZVI), on the anaerobic digestion (AD) performance. Moreover, the evolutions of antibiotic resistance genes (ARGs), class 1 integrons-integrase (intI1) and potential hosts of ARGs were also investigated. The optimal addition of Fe3O4 NPs and nZVI to promote methane production was 0.5 g/L and 1 g/L, which led to 22.07% and 23.02% increase in methane yield, respectively. The degradation rate of organic matter was also enhanced with the addition of Fe3O4 NPs or nZVI. The results of high-throughput sequencing showed that the reactors with iron NPs exhibited significant differences in microbial community structure, compared to the reactors with the non­iron NPs. Iron NPs have caused the relative abundance of the dominant bacteria (Proteobacteria, Firmicutes and Actinobacteria) generally decreased, while the dominant archaea (Euryarchaeota) increased in AD sludge. Quantitative PCR results revealed that iron NPs accelerated the reductions in total absolute abundance of ARGs, especially a beta-lactamase resistance encoded gene (blaOXA). Network analysis displayed that the attenuation of ARGs was mainly attributed to the decline of potential hosts (Proteobacteria, Firmicutes and Actinobacteria). Meanwhile, environmental factors (such as pH, soluble chemical oxygen demand and heavy metals) were also strongly correlated with ARGs.


Assuntos
Integrons , Nanopartículas , Anaerobiose , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Genes Bacterianos/efeitos dos fármacos , Integrases/farmacologia , Ferro/farmacologia , Esgotos
13.
Toxicol Appl Pharmacol ; 392: 114921, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32061592

RESUMO

Angioedema may occur during local anesthetic (LA) injection in the perioperative period. Histaminergic angioedema is the most common form of angioedema. It has been reported that LA is a potential exogenous ligand for histamine receptor 1 (H1R). Whether H1R participates in LA-induced angioedema is still controversial. By using a constructed H1R high-expressed cell model, siRNA transfection, pharmacologic means, and genetically modified animal models, here we showed that H1R mediated LA-induced hyperpermeability. LA with uncycled N-methyl scaffold in the side chain (procaine, tetracaine and lidocaine) had a better strength of drug-H1R affinity than that for LA with cycled N atom (bupivacaine and ropivacaine) by the molecular docking assay and equilibrium dissociation constant (KD values) obtained from the cell membrane chromatography (CMC) relative standard method. Procaine, tetracaine, and lidocaine triggered big calcium mobilization in H1R-HEK293 cells and human umbilical vein endothelial cells (HUVECs) but much weaker in NC-HEK293 cells or H1R knockdown HUVECs. Besides, the results of transendothelial resistance measurement, paracellular flux assay and immunofluorescence showed that procaine induced H1R-dependent hyperpermeability, which involved in PLCγ/IP3R/PKC, ERK1/2, Akt signaling pathways, downstream vascular endothelial cadherin (VE-cad) destabilization. Furthermore, H1R gene knockout prevented paw swelling and vascular leakage caused by procaine, tetracaine, and lidocaine in vivo. This study supported a key role of H1R in LA-induced angioedema, and suggested that in the design of LA structure, the ring formation of the N-methyl scaffold on the side chain can properly avoid the angioedema.


Assuntos
Anestésicos Locais/farmacologia , Angioedema/patologia , Permeabilidade Capilar/efeitos dos fármacos , Receptores Histamínicos H1/metabolismo , Animais , Feminino , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Mastócitos , Camundongos , Camundongos Knockout , Distribuição Aleatória
14.
Bioresour Technol ; 304: 123016, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32078907

RESUMO

The effects of four conductive nanomaterials (nano-carbon powder, nano-Al2O3, nano-ZnO, nano-CuO) on sludge anaerobic digestion (AD) performance and microbial community were investigated through a 36-day fermentation experiment. Results showed that biogas production enhanced by 16.9% and 23.4% with nano-carbon powder and nano-Al2O3 added but decreased by 90.2% and 17.3% with nano-ZnO and nano-CuO. Total solids (TS) removal efficiency was increased by 38.73% and 27.11% with nano-carbon powder and nano-Al2O3 added but decreased by 70.67% and 43.70% with nano-ZnO and nano-CuO. Kinetic analysis indicated four conductive nanomaterials could shorten the lag phase of AD sludge with an average rate of 51.75%. 16S rRNA amplicon sequencing results demonstrated microbes such as Syntrophomonas and Methanosaeta were enriched in nano-carbon powder and nano-Al2O3 reactors. However, microbial community diversity and richness were both inhibited by adding nano-ZnO and nano-CuO. Redundancy analysis (RDA) revealed that genera belong to Firmicutes and Chloroflexi could conduce to methanogenesis process.


Assuntos
Microbiota , Nanoestruturas , Anaerobiose , Reatores Biológicos , Cinética , Metano , RNA Ribossômico 16S , Esgotos
15.
Int Immunopharmacol ; 81: 106258, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32044660

RESUMO

While imiquimod (IMQ) has been widely used in dermatology, its side effect manifested as dermatitis couldn't be ignored. However, the underlying mechanism has not been fully understood. Considering the clinical features of IMQ-related dermatitis similar to pseudo-allergic reaction and the presence of large numbers of mast cell in tissues treated with IMQ, the possibility that IMQ-related dermatitis mediated by mast cell-specific Mas-related G protein-coupled receptor X2 (MRGPRX2) should be addressed. To investigate the role of MRGPRX2 in vivo, MrgprB2, the mice homology of human MRGPRX2, was detected in IMQ-induced dermatitis mouse model. Histopathological changes including mast cell degranulation and footpad swelling were assayed in wild-type and MrgprB2-/- mice. The results showed that IMQ application induced dermatitis and footpad swelling with inflammatory cells infiltration plus mast cell activation in the skin of wild-type mice but reduced significantly in MrgprB2-/- mice. Further, compared to wild-type mice, serum histamine and inflammatory cytokine levels were compromised in MrgprB2-/- mice treated with IMQ, while the serum IgE level didn't change significantly. In vitro studies, levels of mediators released from murine peritoneal mast cells (MPMCs) after IMQ treatment were increased in a dose-dependent manner, which were much mild in MPMCs from MrgprB2-/- mice. Intracellular Ca2+ concentration was increased in a dose dependent manner after IMQ treatment both in MrgprB2-HEK293 and MRGPRX2-HEK293 cells. Moreover, ß-hexosaminidase released after IMQ treatment was blocked by siRNA directed at the MRGPRX2 receptor in LAD2 cells. In summary, MrgprB2 /MRGPRX2 mediate mast cell activation and participate in IMQ-related dermatitis.

16.
Food Chem Toxicol ; 135: 110924, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672514

RESUMO

BACKGROUND: Allergic conjunctivitis (AC) resulting from conjunctival reactive inflammation is a common ocular surface disease. Quercetin is known for its anti-allergic properties but its effects on conjunctivitis are less well understood. PURPOSE: In this study, we evaluated the anti-allergic effects of quercetin in animal models of conjunctivitis, and explored its molecular mechanism(s) of action in cultured human mast cells (MCs). KEY RESULTS: Quercetin inhibited the ovalbumin (OVA) induced expression of IgE, HA, IL-4, TNF-α and substance-P in the peripheral blood of AC mouse models. Quercetin also attenuated OVA induced MC degranulation, eosinophil number, substance P concentrations, and mRNA IL-4/TNF-α expression in the conjunctival tissue of AC models. In vitro analysis showed that quercetin reduced DNP-HSA/IgE induced calcium (Ca2+) influx, and suppressed degranulation and chemokine release in LAD2 cells (human primary mast cell). Quercetin also inhibited DNP-HSA/IgE induced Lyn/PLCγ/IP3R-Ca2+ activation, Lyn/ERK1/2 signaling, and Lyn/NF-κB activation in LAD2 cells, all of which promote inflammation. When added alone, quercetin had no effect on PLCγ1 phosphorylation or expression, but potently inhibited Lyn and phosphorylation-Lyn. Quercetin (200 µM) and Lyn inhibitors (Bafetinib, 10 µM) inhibit the activity of Lyn kinase, and quercetin can reduce the activation of Lyn kinase by Lyn agonist (Tolimidone, 10 µM). These data can be preliminarily determined that quercetin can inhibit allergic conjunctivitis as a Lyn kinase inhibitor. CONCLUSIONS AND IMPLICATIONS: This study illustrated the use of quercetin for the treatment of allergic conjunctivitis, which might act through its ability to inhibit Lyn/PLCγ/IP3R-Ca2+, Lyn/ERK1/2, and Lyn/NF-κB signaling. The inhibition of Lyn likely represents a major mechanism by which quercetin dampens the inflammatory response in AC disease models.


Assuntos
Antialérgicos/uso terapêutico , Conjuntivite Alérgica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quercetina/uso terapêutico , Quinases da Família src/antagonistas & inibidores , Animais , Linhagem Celular , Quimiocinas/metabolismo , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Humanos , Imunoglobulina E/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos Endogâmicos C57BL , Ovalbumina , Transdução de Sinais/efeitos dos fármacos , Pele/patologia
17.
Nat Commun ; 10(1): 5668, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827098

RESUMO

Biological nanopores are capable of resolving small analytes down to a monoatomic ion. In this research, tetrachloroaurate(III), a polyatomic ion, is discovered to bind to the methionine residue (M113) of a wild-type α-hemolysin by reversible Au(III)-thioether coordination. However, the cylindrical pore geometry of α-hemolysin generates shallow ionic binding events (~5-6 pA) and may have introduced other undesired interactions. Inspired by nanopore sequencing, a Mycobacterium smegmatis porin A (MspA) nanopore, which possesses a conical pore geometry, is mutated to bind tetrachloroaurate(III). Subsequently, further amplified blockage events (up to ~55 pA) are observed, which report the largest single ion binding event from a nanopore measurement. By taking the embedded Au(III) as an atomic bridge, the MspA nanopore is enabled to discriminate between different biothiols from single molecule readouts. These phenomena suggest that MspA is advantageous for single molecule chemistry investigations and has applications as a hybrid biological nanopore with atomic adaptors.


Assuntos
Cloretos/química , Compostos de Ouro/química , Mycobacterium smegmatis/metabolismo , Porinas/química , Motivos de Aminoácidos , Cloretos/metabolismo , Compostos de Ouro/metabolismo , Proteínas Hemolisinas/química , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Mycobacterium smegmatis/química , Mycobacterium smegmatis/genética , Nanoporos , Porinas/genética , Porinas/metabolismo , Ligação Proteica
18.
J Immunol ; 203(7): 1701-1714, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484729

RESUMO

Intrathecal morphine infusion is often applied to treat chronic pain related to cancer and other conditions. However, persistent pain can be caused by nerve compression because of granuloma formation. In this study, a mouse model of morphine-induced granuloma formation by intrathecal catheterization morphine infusion into the atlanto-occipital membrane of the foramen magnum was established in wild-type mice, MrgprB2 mutant (MrgprB2-/-) mice, and in mast cell-deficient W-sash c-kit mutant (KitW-sh/W-sh) mice. Heat-related pain after surgery was performed to investigate the antipain effect of morphine. H&E staining and immunofluorescence staining of the spinal cord were applied to analyze the mechanism of granuloma formation. Morphine-induced mast cell degranulation was assessed by measuring the Ca2+ influx and mediator release. Anaphylactoid reactions were measured after s.c. morphine infusion to the paws. Chemokine release by mast cells was determined by Human XL Cytokine Array. Experiments with wild-type, MrgprB2 mutant, and mast cell-deficient W-sash c-kit mutant mice demonstrated that morphine activated mast cells and inflammatory cell aggregation through MrgprB2 in intrathecal infusion sites. The chemokine production of human mast cells demonstrated that granuloma formation is correlated with chemokines release. In addition, morphine activated mouse primary mast cells and de novo chemokine synthesis via the MRGPRX2 in human LAD2 cells. We concluded that granuloma formation during intrathecal morphine infusion was associated with MrgprB2/X2. Reducing MRGPRX2 potentially blocks morphine-induced side effects, including granuloma formation.


Assuntos
Granuloma/imunologia , Mastócitos/imunologia , Morfina/efeitos adversos , Dor/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Medula Espinal/imunologia , Animais , Quimiocinas/genética , Quimiocinas/imunologia , Forame Magno/imunologia , Forame Magno/patologia , Granuloma/patologia , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Injeções Espinhais , Masculino , Mastócitos/patologia , Camundongos , Camundongos Knockout , Morfina/farmacologia , Dor/tratamento farmacológico , Dor/patologia , Receptores Acoplados a Proteínas-G/genética , Medula Espinal/patologia
19.
Bioresour Technol ; 294: 122139, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525586

RESUMO

The effect of nanoscale zero-valent iron (NZVI) and magnetite nanoparticles (Fe3O4 NPs) on anaerobic digestion (AD) performance was investigated through a series of 100-day semi-continuous mesophilic anaerobic digestions. The results indicated that biogas production had increased by 24.44% and 21.66% with the addition of 0.5 g/L Fe3O4 NPs and 1.0 g/L NZVI, respectively. Besides, the abundance of five widespread antibiotic resistance genes (ARGs) (ermF, ermA, ermT, aac(6')-IB, blaOXA-1) was also studied. The decrease in abundance of aac(6')-IB and blaOXA-1 was observed during the AD process with an average removal rate of 95.69% and 44.82%, respectively. Most of the ARGs, especially ermA and ermT, were less abundant in NZVI group compared with control group. The overall results suggested that the addition of NZVI and Fe3O4 NPs contributed to a better sludge anaerobic digestion performance, and NZVI was beneficial to the removal of some ARGs.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Aminoglicosídeos , Anaerobiose , Ferro , Macrolídeos , Resistência beta-Lactâmica
20.
J Dermatol Sci ; 95(3): 99-106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31558225

RESUMO

BACKGROUND: Thimerosal has been used as a preservative in many products which may cause contact dermatitis. It is the second most common allergen in positive patch test reactions, though being a clinical irrelevant allergen. Thimerosal-induced contact dermatitis is generally considered to be a delayed-type hypersensitivity reaction, but it is difficult to explain the fact that most patients develop an allergic reaction upon first encounter with thimerosal. Recent studies have demonstrated the association between Mas-related G protein coupled receptor X2 (MRGPRX2) and pseudo-allergic reactions which occur at the first contact with stimulation. This suggests the possibility that thimerosal may cause contact dermatitis via MRGPRX2 mediated mechanism. OBJECTIVES: To investigate the role of Mas-related G-protein coupled receptor B2 (MrgprB2)/MRGPRX2 in contact dermatitis induced by thimerosal. METHODS: Thimerosal induced pseudo-allergic reactions via MrgprB2/ MRGPRX2 were investigated using a novel skin pseudo-allergic reaction mouse model, footpad swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. RESULTS: Thimerosal induced contact dermatitis in dorsal skin and footpad swelling in wild-type mice, but had no significant effect in MrgprB2-knockout mice. Thimerosal-induced dermatitis is characterized by infiltration of inflammatory cells and elevation of serum histamine and inflammatory cytokines, rather than elevation of serum IgE level. Thimerosal increased the intracellular Ca2+ concentration in HEK293 cells overexpressing MrgprB2/MRGPRX2. Downregulation of MRGPRX2 resulted in the reduced degranulation of LAD2 human mast cells. CONCLUSIONS: MrgprB2 mediates thimerosal-induced mast cell degranulation and pseudo-allergic reaction in mice. MRGPRX2 may be a key contributor to human contact dermatitis.


Assuntos
Dermatite de Contato/etiologia , Hipersensibilidade Tardia/etiologia , Mastócitos/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Conservantes Farmacêuticos/toxicidade , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Neuropeptídeos/metabolismo , Timerosal/efeitos adversos , Administração Cutânea , Animais , Degranulação Celular/efeitos dos fármacos , Dermatite de Contato/patologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Hipersensibilidade Tardia/patologia , Masculino , Mastócitos/patologia , Camundongos , Camundongos Knockout , Conservantes Farmacêuticos/administração & dosagem , Receptores Acoplados a Proteínas-G/genética , Timerosal/administração & dosagem
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