RESUMO
CD4(+) helper T cells acquire effector phenotypes that promote specialized inflammatory responses. We show that the ETS-family transcription factor PU.1 was required for the development of an interleukin 9 (IL-9)-secreting subset of helper T cells. Decreasing PU.1 expression either by conditional deletion in mouse T cells or the use of small interfering RNA in human T cells impaired IL-9 production, whereas ectopic PU.1 expression promoted IL-9 production. Mice with PU.1-deficient T cells developed normal T helper type 2 (T(H)2) responses in vivo but showed attenuated allergic pulmonary inflammation that corresponded to lower expression of Il9 and chemokines in peripheral T cells and in lungs than that of wild-type mice. Together our data suggest a critical role for PU.1 in generating the IL-9-producing (T(H)9) phenotype and in the development of allergic inflammation.
Assuntos
Diferenciação Celular , Hipersensibilidade , Interleucina-9/metabolismo , Proteínas Proto-Oncogênicas/imunologia , Linfócitos T/imunologia , Transativadores/imunologia , Animais , Feminino , Humanos , Inflamação , Interleucina-9/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine important for the initiation and development of T helper (Th2) cell-mediated allergic inflammation. In this study, we identified a positive association between interleukin-9 (IL-9) and TSLP concentration in the serum of infants with atopic dermatitis. In primary cell cultures, the addition of TSLP led to an increase in IL-9 production from human and mouse Th9 cells, and induced an increase in signal transducer and activator of transcription 5 (STAT5) activation and binding to the Il9 promoter. In vivo, use of an adoptive transfer model demonstrated that TSLP promoted IL-9-dependent, Th9 cell-induced allergic inflammation by acting directly on T cells. Moreover, transgenic expression of TSLP in the lung stimulated IL-9 production in vivo, and anti-IL-9 treatment attenuated TSLP-induced airway inflammation. Together, our results demonstrate that TSLP promotes Th9 cell differentiation and function and define a requirement for IL-9 in TSLP-induced allergic inflammation.
Assuntos
Citocinas/imunologia , Dermatite Atópica/imunologia , Inflamação/imunologia , Interleucina-9/imunologia , Fator de Transcrição STAT5/imunologia , Células Th2/imunologia , Transferência Adotiva , Animais , Anticorpos Neutralizantes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/farmacologia , Dermatite Atópica/genética , Dermatite Atópica/patologia , Expressão Gênica/efeitos dos fármacos , Humanos , Lactente , Inflamação/genética , Inflamação/patologia , Interleucina-9/antagonistas & inibidores , Interleucina-9/genética , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Cultura Primária de Células , Regiões Promotoras Genéticas , Ligação Proteica , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/imunologia , Sistema Respiratório/patologia , Fator de Transcrição STAT5/agonistas , Fator de Transcrição STAT5/genética , Transdução de Sinais/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/patologia , Linfopoietina do Estroma do TimoRESUMO
BACKGROUND: IL-9 is important for the growth and survival of mast cells. IL-9 is produced by T cells, natural killer T cells, mast cells, eosinophils, and innate lymphoid cells, although the cells required for mast cell accumulation during allergic inflammation remain undefined. OBJECTIVE: We sought to elucidate the role of TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation. METHODS: Adoptive transfer of ovalbumin-specific TH2 and TH9 cells was used to assess the ability of each subset to mediate mast cell accumulation in tissues. Mast cell accumulation was assessed in wild-type mice and mice with PU.1-deficient T cells subjected to acute and chronic models of allergic inflammation. RESULTS: Adoptive transfer experiments demonstrated that recipients of TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 recipients. Mast cell accumulation was dependent on IL-9, but not IL-13, a cytokine required for many aspects of allergic inflammation. In models of acute and chronic allergic inflammation, decreased IL-9 levels in mice with PU.1-deficient T cells corresponded to diminished tissue mast cell numbers and expression of mast cell proteases. Mice with PU.1-deficient T cells have defects in IL-9 production from CD4(+) T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1(-/-) mice subjected to a chronic model of allergic inflammation displayed reduced mast cell infiltration comparable with accumulation in mice with PU.1-deficient T cells, emphasizing the importance of IL-9 produced by T cells in mast cell recruitment. CONCLUSION: TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.
Assuntos
Hipersensibilidade a Ovo/imunologia , Interleucina-9/imunologia , Mastócitos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th2/imunologia , Transferência Adotiva , Animais , Linhagem da Célula/imunologia , Movimento Celular , Hipersensibilidade a Ovo/genética , Hipersensibilidade a Ovo/patologia , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Genótipo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-9/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Fenótipo , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Auxiliares-Indutores/transplante , Células Th2/patologia , Células Th2/transplante , Transativadores/deficiência , Transativadores/genética , Transativadores/imunologiaRESUMO
Foxp3(+) regulatory T (Treg) cells are essential to maintain immune homeostasis, yet controversy exists about the stability of this cell population. Bcl6-deficient (Bcl6(-/-) ) mice develop severe and spontaneous T helper type 2 (Th2) inflammation and Bcl6-deficient Treg cells are ineffective at controlling Th2 responses. We used a lineage tracing approach to analyse the fate of Treg cells in these mice. In the periphery of Bcl6(-/-) mice, increased numbers of Foxp3-negative 'exTreg' cells were found, particularly in the CD25(+) population. ExTreg cells from Bcl6(-/-) mice expressed increased interleukin-17 (IL-17) and extremely elevated levels of Th2 cytokines compared with wild-type exTreg cells. Although Treg cells normally express only low levels of cytokines, Treg cells from Bcl6(-/-) mice secreted higher levels of IL-4, IL-5, IL-13 and IL-17 than wild-type conventional T cells. Next, Treg-specific conditional Bcl6-deficient (Bcl6(Foxp3-/-) ) mice were analysed. Bcl6(Foxp3-/-) mice do not develop inflammatory disease, indicating a requirement for non-Treg cells for inflammation in Bcl6(-/-) mice, and have normal numbers of exTreg cells. We induced Th2-type allergic airway inflammation in Bcl6(Foxp3-/-) mice, and found that while exTreg cytokine expression was normal, Bcl6-deficient Treg cells expressed higher levels of the Th2-specific regulator Gata3 than Bcl6(+) Treg cells. Bcl6(Foxp3-/-) mice had increased numbers of Th2 cells after induction of airway inflammation and increased T cells in the bronchoalveolar lavage fluid. These data show both Treg-intrinsic and Treg-extrinsic roles for Bcl6 in controlling Treg cell stability and Th2 inflammation, and support the idea that Bcl6 expression in Treg cells is critical for controlling Th2 responses.
Assuntos
Asma/imunologia , Proteínas de Ligação a DNA/imunologia , Regulação da Expressão Gênica/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Animais , Asma/genética , Asma/patologia , Citocinas/genética , Citocinas/imunologia , Proteínas de Ligação a DNA/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Regulação da Expressão Gênica/genética , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-6 , Linfócitos T Reguladores/patologia , Células Th2/patologiaRESUMO
Childhood asthma is often characterised by elevated exhaled nitric oxide (eNO), decreased lung function, increased airway reactivity and atopy; however, our understanding of when these phenotypic airway characteristics develop remains unclear. This study evaluated whether eNO, lung function, airway reactivity and immune characteristics during infancy are risk factors of asthma at age 5 years. Infants with eczema, enrolled prior to wheezy illness (n=116), had eNO, spirometry, airway reactivity and allergen sensitisation assessed at entry to the study and repeated at age 5 years (n=90). Increasing eNO at entry was associated with an increased risk of asthma (p=0.037) and increasing airway reactivity (p=0.015) at age 5 years. Children with asthma at 5 years of age had a greater increase in eNO between infancy and age 5 years compared with those without asthma (p=0.002). Egg sensitisation at entry was also associated with an increased risk of asthma (p=0.020), increasing eNO (p = 0.002) and lower forced expiratory flows (p=0.029) as a 5 year-old. Our findings suggest that, among infants at high risk for developing asthma, eNO early in life may provide important insights into the subsequent risk of asthma and its airway characteristics.
Assuntos
Asma/metabolismo , Testes Respiratórios/métodos , Óxido Nítrico/análise , Alérgenos/química , Pré-Escolar , Citocinas/metabolismo , Eczema/metabolismo , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Masculino , Fenótipo , Respiração , Sons Respiratórios , Fatores de Risco , EspirometriaRESUMO
Secondary metabolites with bioactivity are allelochemicals. This study adopted direct contact (R0) and indirect contact (separated by 0.45 µm membrane, R1-A for algae, R1-S for sludge) to reveal the role of metabolites especially allelochemicals on interaction of bacteria and algae. Direct contact exhibited better nutrients removal than indirect contact, due to less antibacterial allelochemicals and oxidative stress. Bacterial signaling molecules were not detected. The major algae-derived allelochemicals were 13-Docosenamide, 9-Octadecenamide, n-Hexadecanoic acid, erucic acid, octadecanoic acid, ß-sitosterol, and E,E,Z-1,3,12-Nonadecatriene-5,14-diol. Furthermore, presence of 13-Docosenamide and 9-Octadecenamide was associated with succession of Flavobacterium and suppression of nitrifying bacteria (Nitrosomonas, Ellin6067, and Nitrospira). Direct contact stimulated denitrifying bacteria Saccharimonadales and algae Scenedesmus, whereas indirect contact is friendly to Dechloromonas, Competibacter, nitrifying bacteria, algae Desmodesmus and Dictyosphaerium. This study highlights the essentiality of cell contact of bacteria-algae in establishing synergy, as cell contact mitigates antagonistic effect induced by metabolites.
Assuntos
Feromônios , Scenedesmus , Feromônios/farmacologia , Bactérias , Plantas , Esgotos/microbiologiaRESUMO
Unsaturated polyester resin (UPR) with excellent flame retardant is mainly obtained by adding large amounts of flame retardants, usually at the expense of mechanical properties. In this work, a reactive flame retardant containing phosphorus and nitrogen (DOPO-N) was successfully synthesized and incorporated in UPR as a crosslinker. The mechanical and flame-retardant properties of UPR composites were enhanced. UPR/30DOPO-N passed a UL-94 V-1 rating with a limiting oxygen index (LOI) of 30.8%. The tensile strength of UPR/30DOPO-N increased by 24.4%. On this basis, a small amount of modified HNTs (VHNTs) was added to further improve the flame-retardant properties of the composite. With the introduction of 3 wt% VHNTs, the composite passed the UL-94 V-0 rating. The peak of heat release rate (PHRR) and total heat release (THR) of it decreased by 60.7% and 48.3%, respectively. Moreover, the detailed flame-retarding mechanism of DOPO-N and VHNTs was investigated by thermogravimetric infrared spectroscopy (TG-IR), Raman spectra, and X-ray photoelectron spectroscopy (XPS). It was found that DOPO-N played a role in quenching the flame in the gas phase and cooperated with VHNTs to enhance the barrier effect in the condensed phase.
RESUMO
In this paper, a novel TiO(2) nanoparticle thin film coated optical fiber Fabry-Perot (F-P) sensor had been developed for refractive index (RI) sensing by monitoring the shifts of the fringe contrast in the reflectance spectra. Using in situ liquid phase deposition approach, the TiO(2) nanoparticle thin film could be formed on the fiber surface in a controlled fashion. The optical properties of as-prepared F-P sensors were investigated both theoretically and experimentally. The results indicated that the RI sensitivity of F-P sensors could be effectively improved after the deposition of nanoparticle thin-films. It was about 69.38 dB/RIU, which was 2.6 times higher than that of uncoated one. The linear RI measurement range was also extended from 1.333~1.457 to 1.333~1.8423. More importantly, its optical properties exhibited the unique temperature-independent performance. Therefore, owing to these special optical properties, the TiO(2) nanoparticle thin film coated F-P sensors have great potentials in medical diagnostics, food quality testing, environmental monitoring, biohazard detection and homeland security, even at elevated temperature.
Assuntos
Interferometria/instrumentação , Membranas Artificiais , Nanopartículas/química , Fibras Ópticas , Refratometria/instrumentação , Titânio/química , Transdutores , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
Thymic stromal lymphopoietin (TSLP) is an essential cytokine for the initiation and development of allergic inflammation. In this study, we have investigated the role of TSLP in the breakdown of immune tolerance and generation of inducible regulatory T cells (iTregs). Our results demonstrated that TSLP diverted airway tolerance against OVA to Th2 sensitization and inhibited the generation of OVA-specific iTregs. TSLP exerted a direct inhibitory effect on both human and mouse iTreg development in vitro. Low doses of TSLP were capable of inhibiting iTreg induction without significantly promoting Th2 development, indicating that these two functions of TSLP are separable. Moreover, the TSLP-mediated inhibition of iTreg generation was only partially dependent on IL-4 and Stat6, and was effective when TSLP was present for the first 24 h of T cell activation. These results define a novel role for TSLP in regulating the balance of airway tolerance and allergic inflammation.
Assuntos
Asma/imunologia , Citocinas/fisiologia , Epitopos de Linfócito T/imunologia , Inibidores do Crescimento/fisiologia , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Timo/imunologia , Timo/metabolismo , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Asma/tratamento farmacológico , Asma/patologia , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Citocinas/administração & dosagem , Citocinas/sangue , Epitopos de Linfócito T/biossíntese , Técnicas de Introdução de Genes , Inibidores do Crescimento/administração & dosagem , Inibidores do Crescimento/sangue , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Células Estromais/imunologia , Células Estromais/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th2/imunologia , Células Th2/patologia , Timo/citologia , Linfopoietina do Estroma do TimoRESUMO
Periostin is a 90-kDa member of the fasciclin-containing family and functions as part of the extracellular matrix. Periostin is expressed in a variety of tissues and expression is increased in airway epithelial cells from asthmatic patients. Recent studies have implicated a role for periostin in allergic eosinophilic esophagitis. To further define a role for periostin in Th2-mediated inflammatory diseases such as asthma, we studied the development of allergic pulmonary inflammation in periostin-deficient mice. Sensitization and challenge of periostin-deficient mice with OVA resulted in increased peripheral Th2 responses compared with control mice. In the lungs, periostin deficiency resulted in increased airway resistance and significantly enhanced mucus production by goblet cells concomitant with increased expression of Gob5 and Muc5ac compared with wild type littermates. Periostin also inhibited the expression of Gob5, a putative calcium-activated chloride channel involved in the regulation of mucus production, in primary murine airway epithelial cells. Our studies suggest that periostin may be part of a negative-feedback loop regulating allergic inflammation that could be therapeutic in the treatment of atopic disease.
Assuntos
Moléculas de Adesão Celular/imunologia , Células Caliciformes/imunologia , Hipersensibilidade/imunologia , Pneumonia/imunologia , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Western Blotting , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Humanos , Hipersensibilidade/genética , Hipersensibilidade/metabolismo , Imuno-Histoquímica , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Metaplasia , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muco/imunologia , Muco/metabolismo , Pneumonia/genética , Pneumonia/metabolismo , Baço/citologia , Baço/imunologia , Baço/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
BACKGROUND: Treatment with angiotensin receptor blockers (ARBs) is successful in mitigating IgA nephropathy (IgAN), independent of blood pressure changes, but the therapeutic role of ARB in advanced IgAN with impaired renal function is to be ascertained. The present study was performed to investigate the effect of losartan on advanced IgAN induced by staphylococcal enterotoxin B (SEB) combined with 5/6 nephrectomy in rats. METHODS: Fifty-four male SD rats were randomly divided into three group: Rats in the model group were treated with SEB plus 5/6 nephrectomy, and those in the losartan group were gavaged with losartan (33.3 mg kg(-1 )d(-1)) besides the treatment with SEB plus 5/6 nephrectomy. The urine and blood biochemical changes of rats were tested. IgA, IgG, IgM and C3 depositions were studied dynamically with immunofluorescence. The renal tissue structures were observed under light microscopy. The expressions of TGF-ß1, FN, alpha-SMA and FGF-1 in rat renal tissues were determined with immunohistochemical methods and real-time PCR. RESULTS: At 12 weeks, rats with SEB treatment plus 5/6 nephrectomy showed gradually increased urinary red blood cell (URBC) with a gradual elevation of the 24 h urinary protein, serum BUN and Scr, but losartan treatment lowered the levels of 24 h urinary protein, serum BUN and Scr. A large number of IgA depositions in the mesangial area, glomerulosclerosis and tubulointerstitial fibrosis were found in the model group, and the losartan group showed relieved injury. The expressions of TGF-ß1, FN, alpha-SMA and FGF-1 were significantly elevated in the model. Losartan lessened their expressions. CONCLUSION: Losartan treatment can delay the progression of advanced IgA nephropathy with impaired renal function.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Testes de Função Renal , Losartan/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/urina , Avaliação Pré-Clínica de Medicamentos , Enterotoxinas , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/urina , Testes de Função Renal/métodos , Losartan/farmacologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
In this work, a novel P/N flame-retardant monomer (PDHAA) was synthesized through reacting phenyl dichlorophosphate (PDCP) with N-hydroxyethyl acrylamide (HEAA). The structure of PDHAA was confirmed using Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (NMR) spectroscopy. PDHAA monomer and 2-hydroxyethyl methacrylate phosphate (PM-2) monomer were mixed at different mass ratios, to prepare UV-curable coatings, and then applied to the surface of fiber needled felts (FNFs), to improve their flame retardancy. PM-2 was introduced to reduce the curing time of the flame-retardant coatings and improve the adhesion between the coating and the fiber needled felts (FNFs). The research results indicated that the surface flame-retardant FNFs had a high limiting oxygen index (LOI) and rapidly self-extinguished in a horizontal combustion test and passed a UL-94 V-0 test. At the same time, the CO and CO2 emissions were greatly reduced, and the carbon residue rate was increased. In addition, the introduction of the coating improved the mechanical properties of the FNFs. Therefore, this simple and efficient UV-curable surface flame-retardant strategy has broad application prospects in the field of fire protection.
RESUMO
Dual-component epoxy resins are widely used for bonding different materials in automotive interior processing. However, due to the complexity and variability of automotive interior parts, uneven temperature distribution on curved surfaces during the thermoforming process can lead to uneven thermal stress distribution, damaging the interior components. This study focuses on addressing the damage issues caused by uneven thermal stress distribution during the thermoforming of automotive interior components. By monitoring the temperature and strain on the adhesive surface of the interior components during processing, using sensors and combining the readings with a finite element simulation, damage to the adhesive during processing was simulated. Based on this, a segmented thermoforming method for the model surface was employed, but it was found that this method did not significantly reduce the level of damage to the adhesive during application. Building upon the segmented simulation, significant results were achieved by applying temperature modulation at a certain frequency to adjust the damage of the interior components during processing. The techniques used in this study successfully reduced the unevenness of the adhesive surface temperature, improved the performance of the adhesive during application through segmented optimization and the application of ultrasound-assisted techniques, and markedly reduced the manufacturing process's energy consumption.
RESUMO
Patients with atopic dermatitis (AD) are predisposed to infection with Staphylococcus aureus, which worsens their skin disease; it has been postulated that the lack of antimicrobial peptides due to aberrant allergic inflammation in skin with AD could mediate this enhanced bacterial susceptibility. We sought to characterize the amounts of S. aureus and biological products found in infected AD lesions and whether treatment with topical corticosteroids and oral cephalexin as the only antimicrobial improved outcomes. Fifty-nine children with clinically and S. aureus-positive impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index, and wash fluid was obtained from the lesion for quantitative bacterial culture and antibiotic sensitivities and measurement of bacterial products and cytokines. Subjects were re-evaluated 2 weeks after treatment. Improvement in the clinical and inflammatory characteristics of impetiginized lesions were noted, even in the 15% of lesions infected with Methicillin-resistant S. aureus (MRSA). In a subgroup of subjects whose lesions did not contain S. aureus 2 weeks after initiating treatment, beta-defensin levels were higher at both visits than in normal skin. Treatment of uncomplicated impetiginized pediatric AD with topical corticosteroids and cephalexin results in significant clinical improvement, even in subjects infected with MRSA. We propose that the inhibition of abnormal inflammation by the treatment regimen, resulting in the high levels of defensins, is involved in the improvement of AD and that systemic antibiotics do not appear to be necessary in secondary impetiginized AD.
Assuntos
Antibacterianos/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Administração Cutânea , Administração Oral , Corticosteroides/administração & dosagem , Criança , Pré-Escolar , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Fármacos Dermatológicos/administração & dosagem , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Índice de Gravidade de Doença , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: To investigate the renal microvascular injury in chronic aristolochic acid nephropathy (AAN) and the protective effects of Cozaar. METHODS: Male Sprague-Dawley rats were randomized into three groups. Rats in the model group received Caulis Aristolochiae manshuriensis (CAM) decoction by gavage (10 mL/kg/day); those in the Cozaar group were gavaged with CAM and Cozaar (33.3 mg/kg/day); and those in the control group only received an equal daily volume of saline solution by gavage. Kidney tissues were observed under a light and electron microscope. CD34, caspase-3, and bone morphogenetic protein-7 (BMP-7) were determined by immunohistochemistry, and expressions of angiopoietin (Ang) 1 and 2, Tie-2, BMP-7, and vascular endothelial growth factor (VEGF) mRNA were monitored via real-time polymerase chain reaction (PCR). RESULTS: (1) The kidney tissue injury in the chronic AAN model group was apparent, compared to the normal structure in the normal control group, and the Cozaar group showed relieved injury. (2) The expression of caspase-3 in the model group was elevated, while expressions of BMP-7 and CD34 were decreased (p < 0.05). Cozaar lessened caspase-3 expression (p < 0.05) and promoted BMP-7 and CD34 expressions (p < 0.05). (3) Real-time PCR demonstrated a downregulation of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05) and an upregulation of Ang-2 mRNA (p < 0.01) in the renocortex, while Cozaar upregulated the expression of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05). CONCLUSION: Renal microvascular injury was observed in chronic AAN, which was hypothetically correlated with a lack in the expressions of Ang-1, BMP-7, Tie-2, and VEGF and an excess in caspase-3 and Ang-2. Cozaar can significantly ameliorate the renal microvascular injury and protect renal function.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Rim/irrigação sanguínea , Losartan/uso terapêutico , Microvasos/efeitos dos fármacos , Doenças Vasculares/complicações , Doenças Vasculares/prevenção & controle , Animais , Doença Crônica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Conductive carbon black (CCB) is an important filler in stretchable conductive silicone rubber (CSR) composites. However, due to the active oxygen-containing groups on CCB, introducing it into silicone rubber (SR) may cause SR to not completely cure. Surface modification of CCB may ease the problem but at the cost of reducing the electrical conductivity of pristine CCB. In this work, the curing and crosslinking performance of CCB/SR is detected in detail, the hydroxyl groups (-OH) carried by CCB can react with the silicon-hydrogen group (Si-H) with the existence of Pt catalyst, causing insufficiency of the hydrosilylation reaction thus hindering the solidifying process of silicon rubber. To take advantage of this reaction, more hydrogen silicone oil (PHMS) possessing silicon-hydrogen bonds is introduced into the system to improve the curing degree as well as fix the CCB in the crosslinked network. Due to the lock-in effect of CCB, the resistance of CSR samples is stable after several hundred bending cycles, and the composite's tensile strength is three times that of the pure SR samples. Besides, the size of the composites can expand to dozens of centimeters or even a few meters with uniform electric conductivity. This composite has resistance as low as 10.20 Ω and is suitable to make electroplating mold, and a rapid plating rate of 2.4 mm/24 h can be achieved. Meanwhile, the overall properties make this CSR composite have potential applications in mold manufacture, flexible electronics, and other related fields.
RESUMO
BACKGROUND: Diabetic nephropathy (DN) is a kidney damage caused by diabetes and the main cause of end-stage renal disease. However, the current treatment of DN has many limitations. Quercetin is a bioflavonoid compound with therapeutic benefits in metabolic diseases. This study aims to determine the therapeutic potentials and underlying mechanism of quercetin on DN. METHODS: We collected blood samples from DN patients and healthy controls and treated human mesangial cells (HMCs) with high glucose (HG) to establish an in vitro model of DN. Then we assessed the expression difference of miR-485-5p as well as YAP1 in serum of DN patients and healthy controls and between HG-induced HMCs and control cells. qRT-PCR and western blot were performed to assess miR-485-5p and YAP1 expression levels; CCK-8 and ELISAs were used to examine cell proliferation, inflammation, and oxidative stress. Dual luciferase reporter assay was implemented to detect the binding of miR-485-5p and YAP1 mRNA sequence. RESULTS: Quercetin suppressed proliferation, inflammation, and oxidative stress of HMCs induced by HG. As for mechanism, miR-485-5p directly bound to YAP1 and inhibited YAP1 expression. The downregulation of miR-485-5p and upregulation of YAP1 were also observed in the serum of DN patients. Quercetin modulated miR-485-5p/YAP1 axis to regulate HG-induced inflammation and oxidative stress. CONCLUSION: Quercetin inhibits the proliferation, inflammation, and oxidative stress of HMCs induced by HG through miR-485-5p/YAP1 axis, which might provide a novel treatment strategy for DN.
Assuntos
Nefropatias Diabéticas , MicroRNAs , Proliferação de Células , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Glucose/metabolismo , Glucose/farmacologia , Humanos , Inflamação/tratamento farmacológico , Células Mesangiais/metabolismo , MicroRNAs/metabolismo , Estresse Oxidativo , Quercetina/farmacologia , Proteínas de Sinalização YAPRESUMO
We have reported first example of 3D hierarchy structure from self-assembly of water-soluble QDs followed by chemical reaction control. After addition of ethylenediaminetetraacetic acid, dipotassium salt dehydrate (EDTA) into L-cysteine-stabilized CdTe QD solution, the color of solution was observed to become lighter and shallower, and finally white precipitates appeared. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results confirm that the morphology transformation from zero dimensional (0D) QDs via two-dimensional (2D) nanoflakes to 3D microflowers occurs among those QD assemblies. Meanwhile, EDX results demonstrate that the as-formed QD-assemblies are not CdTe but CdS. The turnover of chemistry nature from CdTe to CdS after addition of EDTA is mainly due to the oxidation of Te followed by a series of chemical reactions. The photoluminescence (PL) spectroscopy and confocal laser scanning microscopy (CLSM) results reveal that such 3D hierarchy structure of CdS QDs have good optical property.
RESUMO
BACKGROUND: Childhood asthma is most often characterized by recurrent wheezing, airway hyperreactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory tract illnesses and atopic sensitization early in life might produce an interaction between innate and acquired immune responses, leading to airway inflammation and heightened airway reactivity. OBJECTIVE: We hypothesized that premorbid airway reactivity and immunologic characteristics of infants without prior episodes of wheezing would be associated with subsequent wheezing during a 1-year follow-up. METHODS: One hundred sixteen infants with chronic dermatitis were enrolled before episodes of wheezing. Airway reactivity, allergen-specific IgE levels, cytokine production by stimulated PBMCs, and percentages of dendritic cells were measured on entry, and airway reactivity was reassessed at the 1-year follow-up. Linear regression models were used to evaluate a predictor's effect on continuous outcomes. RESULTS: Milk sensitization, egg sensitization, or both were associated with heightened airway reactivity before wheezing and after the onset of wheezing; however, these factors were not associated with an increased risk of wheezing. There was an interaction between initial airway reactivity and wheezing as a determinant of airway reactivity at follow-up. In addition, cytokine production by stimulated PBMCs was a risk factor for wheezing, whereas increased percentages of conventional dendritic cells were protective against wheezing. CONCLUSION: Our data in a selected cohort of infants support a model with multiple risk factors for subsequent wheezing that are independent of initial airway reactivity; however, the causative factors that produce wheezing very early in life might contribute to heightened airway reactivity.
Assuntos
Asma/imunologia , Sons Respiratórios/imunologia , Idade de Início , Asma/epidemiologia , Asma/fisiopatologia , Citocinas/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Seguimentos , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/sangue , Lactente , Leucócitos Mononucleares/imunologia , Masculino , Testes de Função Respiratória , Fatores de RiscoRESUMO
BACKGROUND: Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown. OBJECTIVE: We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions. METHODS: Eighty-nine children with clinically impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically by using the Eczema Area and Severity Index (EASI), wash fluid obtained from the lesion for quantitative bacterial culture, and measurement of LTA and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities. The patients were treated with a regimen that included topical corticosteroids and systemic antibiotics, and the lesion was reanalyzed after 2 weeks. RESULTS: S aureus was identified in 79 of 89 children enrolled in the study. The bacterial colony-forming unit (CFU) counts correlated with the EASI lesional score (P = .04). LTA levels as high as 9.8 mug/mL were measured in the wash fluid samples, and the amounts correlated with the lesional EASI scores (P = .01) and S aureus CFU (P < .001). Approximately 30% of clinically impetiginized AD lesions contained greater than 1 mug/mL LTA, amounts that exert effects on various cell types in vitro. Moreover, injection of skin tissue ex vivo with amounts of LTA found in AD lesions resulted in epidermal cytokine gene expression. CONCLUSION: Pharmacologic levels of LTA are found in many infected atopic dermatitis lesions.