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1.
ACS Appl Mater Interfaces ; 11(47): 44186-44195, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31692330

RESUMO

This work reports the synthesis of core-shell structured Au@C composite through a simple one-step laser ablation technique. The results demonstrate that the Au@C with a mean nanosphere size of ∼8.0 nm is composed of a spherical shaped Au core and 1-2 layered graphitic carbon shell with abundant defects. As a nitrogen reduction reaction (NRR) electrocatalyst, the Au@C gives a large NH3 yield rate of 241.9 µg h-1 mgcat.-1 with a high faradaic efficiency of 40.5% at -0.45 V versus reversible hydrogen electrode in a 0.1 M Na2SO4 electrolyte (pH = 6.3) under ambient conditions, surpassing the performances of most aqueous-based NRR electrocatalysts recently reported. The 15N labeling experimental results demonstrate that the produced NH3 is undoubtedly originated from the NRR process catalyzed by Au@C. The superior NRR performance of Au@C can be ascribed to the ultrathin carbon layer, effectively inhibiting the aggregation of Au nanospheres during the NRR, and the abundant defects such as carbon vacancies existed in the ultrathin carbon layer, providing additional NRR catalytic active sites. Our theoretical calculation results further confirm the role of carbon vacancies in the electrocatalytic NRR.

2.
Auris Nasus Larynx ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635898

RESUMO

OBJECTIVE: This study aimed to assess the possible role of hypoxia-inducible factor 1α (HIF-1α) in promoting neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. METHODS: We examined HIF-1α expression in sinonasal tissues from CRSwNP patients and healthy controls by using immunohistochemistry, qRT-PCR, and western blot. Next, the stimulatory effects of several cytokines (IFN-γ, IL-17A, IL-6, etc.) and reagents (dexamethasone (DEX), clarithromycin (CAM) and curcumin (CUM)) on HIF-1α expression in cultured normal nasal epithelial cells (NECs) were also evaluated. Moreover, the effects of CAM and glucocorticoid on nasal symptoms and signs of uncontrolled neutrophilic CRSwNP patients were evaluated. RESULTS: The mRNA and protein expression of HIF-1α were significantly increased in polyp tissues compared with healthy controls (P < 0.05), and the HIF-1α level in polyp tissues was positively associated with IL-17A production and tissue neutrophilia (P < 0.05). Moreover, in cultured NECs, HIF-1α expression was upregulated in the presence of IL-17A and IL-6 (P < 0.05). Both CAM and CUM showed an additive effect with DEX in inhibiting HIF-1α expression (P < 0.05). Moreover, combined glucocorticoid and CAM significantly improved nasal symptoms and signs compared with glucocorticoid alone in uncontrolled neutrophilic CRSwNP patients (P < 0.05). CONCLUSION: Our findings indicate that HIF-1α is associated with neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients.

3.
Chem Commun (Camb) ; 55(82): 12376-12379, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31559991

RESUMO

We report a pyrolysis-phosphorization approach to fabricate carbon nanotubes with embedded CoP nanoparticles (CoP/CNs) using ZIF-67 as a precursor for electrocatalytic nitrogen (N2) reduction to ammonia (NH3) under ambient conditions. The results demonstrate that the as-synthesized CoP/CNs as electrocatalysts exhibit high electrocatalytic activity toward the N2 reduction reaction (NRR), affording a large NH3 yield rate of 48.9 µg h-1 mgcat.-1 with a faradaic efficiency (FE) of 8.7% at -0.4 V (vs. RHE) in 0.1 M Na2SO4 electrolyte. The 15N isotopic labelling experiments confirm that the NH3 obtained is indeed from the CoP/CN catalyzed NRR process. Our theoretical calculation results reveal that the N2 molecules prefer to be adsorbed on the highly unsaturated three coordinated Co sites of the CoP(112) plane following an associative distal hydrogenation process.

4.
Phys Chem Chem Phys ; 21(11): 5950-5955, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30815666

RESUMO

It is highly attractive but challenging to develop earth-abundant electrocatalysts for nitrogen (N2) fixation. Here, by using density functional theory (DFT), we systematically investigate various single transition metal atom (Ti, V, Cr, Mn, Fe, Co, Ni, Ru, Rh and Pd) modified MoP surfaces as potential N2 reduction electrocatalysts for ammonia (NH3) synthesis. Through comparison of the stabilities of metal atom modified MoP, the adsorption energies and the bond lengths of N2 on different atom modified MoP, we select Mn and V as two candidates and study in detail the possible N2 reduction reaction (NRR) pathways for Mn-MoP and V-MoP. Our results revealed that Mn-MoP and V-MoP exhibit energy change values of 0.95 eV and 0.65 eV, respectively, with the first hydrogenation step being the potential-limiting step. Mn-MoP can efficiently suppress *H adsorption and reduce the competition of the hygrogen evolution reaction (HER) with the NRR; whereas, V-MoP cannot. Therefore, Mn-MoP is a better catalyst to realize the nitrogen reduction reaction. Overall, this work takes one step toward the NRR possibility of transition metal phosphides and provides some important insights and guidance to experiments.

5.
Molecules ; 24(5)2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30857341

RESUMO

The effects of amino acid-involved Maillard reactions (MRs) on the structure and activities of longan pulp polysaccharides (LPs), which were heteropolysaccharides mainly composed of glucose, galactose, mannose, rhamnose, glucuronic acid, ribose, and galacturonic acid, were investigated. The changes of browning degree and molecular weight (Mw) distribution in the MR systems containing LPs and amino acids (lysine, proline, or glycine) indicated that lysine was more active in conjugating with LPs. The MR-modified LPs (MLPs) obtained via a 4 h MR between LPs and lysine showed obvious structural differences from LPs. Specifically, particle-like LPs contained 94% fractions with a Mw less than 7.07 kDa, by contrast, network-like MLPs contained 45% fractions with a Mw larger than 264.1 kDa. Moreover, MLPs showed stronger radical scavenging abilities and macrophage immunostimulating effects, but weaker cancer cell growth-inhibitory abilities. The results indicate that the amino acid-involved MR is a promising method to modify native polysaccharides for better biological properties.


Assuntos
Lisina/química , Polissacarídeos/química , Antioxidantes/química , Reação de Maillard , Peso Molecular
6.
Chemistry ; 25(23): 5904-5911, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30767346

RESUMO

Electrosynthesis of NH3 through the N2 reduction reaction (NRR) under ambient conditions is regarded as promising technology to replace the industrial energy- and capital-intensive Haber-Bosch process. Herein, a room-temperature spontaneous redox approach to fabricate a core-shell-structured Au@CeO2 composite, with Au nanoparticle sizes below about 10 nm and a loading amount of 3.6 wt %, is reported for the NRR. The results demonstrate that as-synthesized Au@CeO2 possesses a surface area of 40.7 m2 g-1 and a porous structure. As an electrocatalyst, it exhibits high NRR activity, with an NH3 yield rate of 28.2 µg h-1 cm-2 (10.6 µg h-1 mg-1 cat. , 293.8 µg h-1 mg-1 Au ) and a faradaic efficiency of 9.50 % at -0.4 V versus a reversible hydrogen electrode in 0.01 m H2 SO4 electrolyte. The characterization results reveal the presence of rich oxygen vacancies in the CeO2 nanoparticle shell of Au@CeO2 ; these are favorable for N2 adsorption and activation for the NRR. This has been further verified by theoretical calculations. The abundant oxygen vacancies in the CeO2 nanoparticle shell, combined with the Au nanoparticle core of Au@CeO2 , are electrocatalytically active sites for the NRR, and thus, synergistically enhance the conversion of N2 into NH3 .

7.
Chem Commun (Camb) ; 55(16): 2344-2347, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30724313

RESUMO

Commercial carbon fiber cloth treated at 450 °C in air (CFC-450) possesses low C[double bond, length as m-dash]O content, exhibiting outstanding oxygen evolution activity in 1.0 M KOH electrolyte with an overpotential of 224 mV at current density of 10 mA cm-2. Meanwhile, we observed an electrochemical corrosion phenomenon associated with the carbon fiber cloth electrocatalyst during the OER tests, especially under high static potentials.

8.
Toxicol In Vitro ; 55: 43-50, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30496793

RESUMO

Lead (Pb) has long been known as a metallic toxin to exert detrimental effects on human health, particularly on the central nervous system (CNS). Misregulated autophagy was regularly associated with multiple cellular dysfunctions and human diseases. However, the role of autophagy underlying Pb-induced neurotoxicity remains to be elucidated. In this study, we demonstrated that Pb promoted the accumulation of autophagosomes in PC12 cells, and subsequent findings revealed that this autophagosome accumulation was primarily caused by the inhibition of autophagic flux. Moreover, the results showed that Pb affected autophagy course through increasing Beclin 1 and ATG5 expression levels. Specifically, by double labeling with LC3-II (a marker of autophagosome) and LAMP-1 (a marker of lysosome), Pb impaired fusion between autophagosomes and lysosomes. Additionally, Pb exposure significantly reduced the number or size of lysosomes via decreasing the level of LAMP1, which is confirmed by the LysoTracker Red staining. Furthermore, the impairment of lysosomal activity was also signaled by the altered pH value of this acidic organelle. Overall, Pb exposure led to injuries of autophagy of neural cells through inhibiting the genesis and activity of lysosomes. The data provides insight with the neurotoxicity of Pb in a novel perspective, autophagy.


Assuntos
Chumbo/toxicidade , Lisossomos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Células PC12 , Ratos
9.
Allergy Asthma Immunol Res ; 10(6): 698-715, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30306751

RESUMO

PURPOSE: Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and protein expression in nasal tissue extracts. Cells isolated from nasal tissues and peripheral blood mononuclear cells were characterized by flow cytometry. Local antibody production was measured in tissue extracts with a Bio-Plex assay. Additionally, changes in Hrd1 expression in response to specific inflammatory stimuli were measured in cultured dispersed polyp cells. RESULTS: Nasal polyps (NPs) from patients with eosinophilic CRSwNP (ECRS) had increased levels of Hrd1, B-cells and plasma cells compared with NPs from patients with non-eosinophilic CRSwNP (non-ECRS) or other control subjects (P < 0.05). The average Hrd1 levels in B-cells in NPs from ECRS patients were significantly higher than those from non-ECRS patients and control subjects (P < 0.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal controls (P < 0.05). Interestingly, Hrd1 expression in cultured polyp cells from ECRS patients, but not non-ECRS patients, was significantly increased by interleukin-1ß, lipopolysaccharide and Poly(I:C) stimulation, and inhibited by dexamethasone treatment (P < 0.05). CONCLUSIONS: Differential Hrd1 expression and B-cell accumulation between the ECRS and non-ECRS subsets suggests that they can exhibit distinct pathogenic mechanisms and play important roles in NP.

10.
ACS Appl Mater Interfaces ; 10(37): 31394-31403, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30141620

RESUMO

We present the self-assembly synthesis of core-shell structure Au/CeO2 composites with different Au loadings through a spontaneous chemical redox approach at an ambient temperature utilizing HAuCl4 and Ce(NO3)3 as reaction substrates in an alkaline environment. The results demonstrate that the as-synthesized Au/CeO2 composites exhibit spherical shape morphologies with porous structures, composed of Au nanoparticle (∼10 nm) cores and CeO2 nanoparticle shells with abundant oxygen vacancies. The introduction of Au nanoparticles in CeO2 not only effectively improves the visible light utilization efficiency but also provides rich surface catalytic active sites for highly efficient visible light photocatalysis. As visible light photocatalysts (λ > 400 nm), the as-synthesized Au/CeO2 composites with the Au loading amount ≥4.0 wt % exhibit high conversion and selectivity (∼100%) of benzyl alcohol to benzaldehyde under the given experimental conditions. Moreover, Au/CeO2 also shows a general applicability as a visible light photocatalyst for the selective oxidation of other alcohols to corresponding aldehydes or ketones. The photocatalytic mechanism studies indicate that the photoelectrons/holes produced from the photoexcited Au and the formed superoxide radicals in the oxygen vacancies of CeO2 synergistically contribute to the high performance of the selective photocatalytic oxidation of alcohols to aldehydes or ketones.

11.
Int J Biol Macromol ; 119: 617-623, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30036620

RESUMO

This paper studied the extraction of polysaccharide from Portulaca oleracea L. (POP) by hot water extraction and ethanol precipitation. Structural properties of the extracted polymers were determined. POP was composed of rhamnose, arabinose and galactose in ratios of 1: 2.34: 3.07 with a molecular weight of 1.55 × 107 Da. The neuroprotective effect of POP on Pb-induced neuronal toxicity was then evaluated in vitro and in vivo test. Treatment with POP markedly increased the survival of PC12 cells and repressed the generation of reactive oxygen species following Pb exposure. In Morris water maze analysis, Pb exposure led to an increase in escape latency and a decrease in platform crossing times of rats in the probe test, which could be attenuated by POP treatment. Additionally, the Pb-induced loss of dendritic spine was recovered after feeding rats with POP at 600 mg/kg/day. These results indicated that Pb-induced cognitive impairments could be inhibited by POP.


Assuntos
Chumbo/efeitos adversos , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Polissacarídeos/farmacologia , Portulaca/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
12.
Small ; 14(36): e1801953, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30058300

RESUMO

Highly dispersed copper nanoparticles (Cu NPs) supported on activated carbon (AC) are effectively synthesized by one-pot carbothermal method at temperature range of 400-700 °C. The X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller analysis reveal that Cu NPs with diameters of 20-30 nm are evenly anchored in carbon matrix. The 15 wt%-Cu/AC-600 catalyst (derived at 600 °C) exhibits best bifunctional catalysis of aqueous-phase hydrodeoxygenation (HDO) and organic-phase transfer-hydrogenation reaction (THR) to selectively transform vanillin to 2-methoxy-4-methylphenol (MMP). In HDO of vanillin, the as-prepared catalyst achieves a 99.9% vanillin conversion and 93.2% MMP selectivity under 120 °C, 2.0 MPa H2 within 5 h. Meanwhile, near-quantitative vanillin conversion and 99.1% MMP selectivity are also obtained under 180 °C within 5 h in THR of vanillin by using 2-propanol as hydrogen donor. The transforming pathways of vanillin are also proposed: vanillin is transformed into MMP via intermediate of 4-hydroxymethyl-2-methoxyphenol in HDO case and by direct hydrogenolysis of vanillin in THR course. More importantly, the activity and the selectivity do not change after 5 cycles, indicating the catalyst has excellent stability. The Cu-based catalyst is relatively cheap and preparation method is facile, green, and easy scale-up, thus achieving a low-cost transformation of biomass to bio-oils and chemicals.

13.
EBioMedicine ; 32: 43-49, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29885866

RESUMO

The prevalence of allergic rhinitis (AR) and obesity in children increased concurrently during recent decades. However, the molecular pathway involved in the interaction between obesity and AR is still unclear. We aimed to investigate the interaction between leptin and osteopontin (OPN) and their effect on T helper (TH) response in the development of AR in children. Thirty AR and 30 healthy children with or without obesity were enrolled. Serum leptin and OPN levels were measured and their relationship with TH1/2 cytokines was analyzed. TH cell differentiation and cytokine production in peripheral blood mononuclear cells (PBMCs) stimulated by leptin and/or OPN were analyzed by enzyme linked immunosorbent assay (ELISA). Obese AR mice models were established to verify the effect of obesity on leptin and OPN as well TH regulation. Immunoprecipitation was performed to confirm the interaction between OPN and leptin in CD4+ T cells. Our results showed elevated serum leptin and OPN in AR children correlated with TH2 cytokines expression. Leptin and OPN enhanced TH2 inflammation in house dust mite stimulated PBMCs from AR children synergistically. Obese AR mice showed as more severe inflammatory reaction, symptoms and expression of nasal leptin and OPN compared with other groups. Immunoprecipitation suggested that OPN and leptin may interact with each other and this process may be mediated by α4 integrin and PI3K/AKT pathway in CD4+ T cells. Our data provide evidence that leptin-mediated OPN upregulation promote TH2 inflammation in AR and this process is achieved through the α4 integrin and PI3K/AKT signaling pathways.


Assuntos
Leptina/genética , Obesidade/genética , Osteopontina/genética , Rinite Alérgica/genética , Animais , Linfócitos T CD4-Positivos/metabolismo , Criança , Feminino , Humanos , Integrina alfa4/genética , Integrina alfa4/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Camundongos , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Rinite Alérgica/complicações , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Transdução de Sinais/genética , Células Th1/metabolismo , Equilíbrio Th1-Th2/genética
14.
Biomed Pharmacother ; 103: 1052-1060, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29710663

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The deficiency of kidney Yin is the main pathogenesis of postmenopausal osteoporosis (PMOP) according to traditional Chinese medicine (TCM). Zuoguiwan (ZGW) is among the classical prescriptions in TCM and has been applied to various diseases that are due to deficiency of kidney Yin, including osteoporosis, fractures, menopausal syndromes. However, the underlying mechanism of ZGW in treating PMOP remains poorly understood. AIM OF THE STUDY: ZGW, a traditional Chinese prescription, has been used to nourish Yin and reinforce the kidney since ancient times. The investigation aimed to explore the mechanism of ZGW via the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway as mediated by the ß2-adrenergic receptor (ß2AR) in an osteoporosis rat model. MATERIALS AND METHODS: An osteoporosis model induced by ovariectomy was established in rats. A total of 40 female Sprague-Dawley rats were randomly assigned into bilateral ovariectomy group (OVX), sham operated group (Sham), 17ß-estradiol-treated positive group (E2, 25 µg/kg/d), ZGW low-dose group (ZGW-L, 2.3 g/kg/d lyophilized powder) and ZGW high-dose group (ZGW-H, 4.6 g/kg/d lyophilized powder). The serum markers of bone turnover were measured using enzyme-linked immunosorbent assay (ELISA). The morphological structure changes in bones were detected through H&E staining. Local bone mineral density (BMD) and trabecular bone microarchitecture of the right distal femur were measured and evaluated by using micro-CT. Furthermore, the mRNA and protein expressions levels of ß2AR, OPG and RANKL were measured by qPCR and Western blot analysis. RESULTS: Compared with the OVX group, ZGW groups showed significantly reduced levels of serum tartrate-resistant acid phosphatase 5b (TRACP-5b) and ß-cross-linked c-telopeptide of type I collagen (ß-CTX) (P < 0.01), increased levels of serum bone-specific alkaline phosphatase (BALP) (P < 0.01) and OPG (P < 0.05), prevention of OVX-induced bone loss, and improved microarchitecture of the trabecular bone of distal femur. Moreover, ZGW mediated the osteoporosis syndrome by reducing the empty bone lacunae, promoting the ordered arrangement of trabeculae structure, and increasing the trabeculae structure thickness. Furthermore, in ZGW groups, the protein expression of OPG in the tibia was notably up-regulated (P < 0.01), whereas the mRNA and protein expression of ß2AR in the hippocampus (P < 0.01), and the protein expressions levels of ß2AR (P < 0.01) and RANKL (P < 0.05) in the tibia were down-regulated compared with OVX group. CONCLUSIONS: ZGW through its protective effects, stimulates bone formation and suppresses bone resorption. The underlying mechanism of ZGW in improving perimenopausal syndrome and increasing bone mass might be attributed to the regulation of RANKL/OPG, as mediated by ß2AR. Therefore, ZGW may be used as an alternative treatment for PMOP.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/tratamento farmacológico , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Animais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Ratos Sprague-Dawley , Transdução de Sinais
15.
Allergy Asthma Immunol Res ; 10(3): 236-243, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29676070

RESUMO

PURPOSE: Recent evidence suggests that B cells can both promote and inhibit the development and progression of allergic disease. However, the characteristics of B cell subsets in patients with allergic rhinitis (AR) have not been well documented. This study aimed to analyze the characteristics of B cell subsets in the peripheral blood of AR patients. METHODS: Forty-seven AR patients and 54 healthy controls were enrolled in this study, and the B cell subsets in peripheral blood of all subjects were analyzed by flow cytometry. Moreover, the serum total immunoglobulin E (IgE) and IgE concentrations secreted into the cultured peripheral blood mononuclear cells (PBMCs) were measured by using enzyme-linked immunosorbent assay. RESULTS: We found the peripheral blood of AR patients contained higher percentages of memory B cells, plasma cells, and CD19⁺CD24(hi)CD27⁺ regulatory B cells (Bregs) than those of age-matched healthy controls (P<0.05), while the percentages of naïve B cells and CD19⁺CD24(hi)CD38(hi) Bregs were significantly lower in AR patients than in healthy individuals (P<0.05). In addition, the serum total IgE and IgE concentrations secreted into the cultured PBMCs were elevated in AR patients than in the healthy controls (P<0.05). CONCLUSIONS: Our findings indicate that AR patients were characterized by increase in terminally differentiated memory B cells or plasma cells and decreases in CD19⁺CD24(hi)CD38(hi) Breg cells in the peripheral blood.

16.
Sci Signal ; 11(521)2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535261

RESUMO

Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion. Inhibition of p38 activity through either pharmacological inhibition or genetic deletion also reduced the severity of established psoriasiform skin inflammation. Together, our findings indicate a critical role for p38α signaling in LCs in promoting inflammatory responses in the skin and suggest that targeting p38α signaling in LCs may offer an effective therapeutic approach to treat psoriasis.


Assuntos
Células de Langerhans/imunologia , Proteína Quinase 14 Ativada por Mitógeno/imunologia , Psoríase/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Células Th17/imunologia , Animais , Células Cultivadas , Células Dendríticas/imunologia , Modelos Animais de Doenças , Imidazóis/farmacologia , Imiquimode , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Células de Langerhans/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Psoríase/induzido quimicamente , Psoríase/metabolismo , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Pele/patologia , Linfócitos T/metabolismo , Células Th17/metabolismo
17.
Appl Radiat Isot ; 135: 232-238, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29438894

RESUMO

Tomographic Gamma Scanning (TGS) is a method used for the nondestructive assay of radioactive wastes. In TGS, the actual irregular edge voxels are regarded as regular cubic voxels in the traditional treatment method. In this study, in order to improve the performance of TGS, a novel edge treatment method is proposed that considers the actual shapes of these voxels. The two different edge voxel treatment methods were compared by computing the pixel-level relative errors and normalized mean square errors (NMSEs) between the reconstructed transmission images and the ideal images. Both methods were coupled with two different interative algorithms comprising Algebraic Reconstruction Technique (ART) with a non-negativity constraint and Maximum Likelihood Expectation Maximization (MLEM). The results demonstrated that the traditional method for edge voxel treatment can introduce significant error and that the real irregular edge voxel treatment method can improve the performance of TGS by obtaining better transmission reconstruction images. With the real irregular edge voxel treatment method, MLEM algorithm and ART algorithm can be comparable when assaying homogenous matrices, but MLEM algorithm is superior to ART algorithm when assaying heterogeneous matrices.

18.
Toxicol Sci ; 162(2): 688-701, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301062

RESUMO

Lead (Pb) prevails among the environmental hazards against human health. Although increasing evidence highlights the epigenetic roles underlying the Pb-induced neurotoxicity, the exact mechanisms concerning histone acetylation and its causative agents are still at its infancy. In the present study, the roles of histone deacetylases 1 and 2 (HDAC1/2), as well as acetylation of Lys9 on histone H3 (Ac-H3K9), in Pb-induced neurotoxicity were investigated. Pb was administered to PC12 cells at 10 µM for 24 h. And Sprague Dawley rats were chronically exposed to Pb through drinking water containing 250 ppm Pb for 2 months. Owing to Pb exposure, it indicated that HDAC2 was up-regulated accompanied by Ac-H3K9 down-regulation. Meanwhile, chromatin immunoprecipitation assay revealed that the changes in HDAC2 were attributed to histone H3 Lys27 trimethylation occupancy on its promoter. Blockade of HDAC2 with either Trichostatin A or HDAC2-knocking down construct (shHDAC2) resulted in amelioration of neurite outgrowth deficits via increasing Ac-H3K9 levels. It implied that HDAC2 plays essential regulatory roles in Pb-induced neurotoxicity. And, coimmunoprecipitation trials revealed that HDAC2 colocalized with HDAC1, forming a so-called HDAC1/2 complex. Subsequently, it was shown that HDAC1/2 repression could markedly prevent neurite outgrowth impairment and rescue the spatial memory deficits caused by Pb exposure, unequivocally implicating this complex in the studied toxicological process. Furthermore, Notch2 maybe the functional target of the HDAC1/2 and Ac-H3K9 alterations. Our study provided insight into the precise roles of HDAC1/2 in Pb-induced neurotoxicity, and thereby provided a promising molecular target for medical intervention of neurological disorders with environmental etiology.


Assuntos
Poluentes Ambientais/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Intoxicação do Sistema Nervoso por Chumbo/enzimologia , Chumbo/toxicidade , Animais , Técnicas de Cultura de Células , Técnicas de Silenciamento de Genes , Intoxicação do Sistema Nervoso por Chumbo/genética , Intoxicação do Sistema Nervoso por Chumbo/patologia , Crescimento Neuronal/efeitos dos fármacos , Crescimento Neuronal/genética , Células PC12 , Ratos , Ratos Sprague-Dawley , Regulação para Cima
19.
Front Immunol ; 9: 3045, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619373

RESUMO

Fas-Fas ligand (FasL) signaling plays an important role in the development of allergic inflammation, but the cellular and molecular mechanisms are still not well known. By using the bone marrow-derived dendritic cell (BMDC) transfer-induced pulmonary inflammation model, we found that house dust mite (HDM)-stimulated FAS-deficient BMDCs induced higher Th2-mediated allergic inflammation, associated with increased mucus production and eosinophilic inflammation. Moreover, FAS-deficient BMDCs promoted Th2 cell differentiation upon HDM stimulation in vitro. Compared to wild-type BMDCs, the Fas-deficient BMDCs had increased ERK activity and decreased IL-12 production upon HDM stimulation. Inhibition of ERK activity could largely increase IL-12 production, consequently restored the increased Th2 cytokine expression of OT-II CD4+ T cells activated by Fas-deficient BMDCs. Thus, our results uncover an important role of DC-specific Fas signaling in Th2 differentiation and allergic inflammation, and modulation of Fas signaling in DCs may offer a useful strategy for the treatment of allergic inflammatory diseases.


Assuntos
Células Dendríticas/imunologia , Hipersensibilidade/imunologia , Eosinofilia Pulmonar/imunologia , Células Th2/imunologia , Receptor fas/metabolismo , Transferência Adotiva , Animais , Líquido da Lavagem Broncoalveolar/citologia , Comunicação Celular/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Ligante Fas/imunologia , Proteína Ligante Fas/metabolismo , Humanos , Pulmão/citologia , Pulmão/imunologia , Ativação Linfocitária , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Pyroglyphidae/imunologia , Receptor fas/genética , Receptor fas/imunologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-29107729

RESUMO

Chromium picolinate is one of the important Cr3+ resources and is widely used in animal production. A convenient, reliable and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of chromium picolinate in animal feeds. Feed samples were extracted with acetonitrile and subsequently cleaned up by solid phase extraction cartridges Supelclean™ LC-18. Chromium picolinate was efficiently separated with a Waters ACQUITY UPLC® BEH C18 column, ionized with electrospray ion source in positive mode (ESI+), and quantitatively determined by tandem mass spectrometry in multiple reaction monitoring mode. Standard calibration curve of chromium picolinate in the concentration range from 0.5 to 1000ng/mL was obtained with good linearity correlation coefficient (R2=0.9982). Average recoveries ranged from 95.37%∼105.54%, as detected by spiking 0.02∼640mg/kg of chromium picolinate in complete feed, concentrated feed and premix. Intra-day and inter-day coefficient of variation were 0.59%∼6.67% and 2.36%∼6.97%, respectively. The limits of quantitation were 0.02mg/kg, 0.025mg/kg, and 2mg/kg for complete feed, concentrated feed, and premix, respectively. Actual sample analysis indicated that the developed method can be an effective tool to monitoring CrPic content in animal feed.


Assuntos
Ração Animal/análise , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Picolínicos/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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