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1.
Chem Commun (Camb) ; 57(96): 13020-13023, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34807198

RESUMO

The transmetalation as the rate-limiting step was effectively accelerated by newly designed N-heterocyclic carbenes with triazine wingtips (T-NHC). By using a ppm-level precatalyst T-NHC-Pd (8), the highly efficient coupling of aryl iodide, alkyne and carbon monoxide furnished a variety of ynone compounds. T-NHC-Pd (5), which deprotonated 4-methyl-phenylacetylene under mild conditions, converted into alkynyl-coordinated catalytic active species PdCl(T-NHC)(Py)(alkynyl). In the putative Pd/Pd catalytic cycle, both triazine-wingtips and NHCs are key players for establishing the carbonylative cross-couplings with high TON and TOF.

2.
Dev Sci ; : e13190, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34750930

RESUMO

Cheating is a common human behavior but few studies have examined its emergence during early childhood. In three preregistered studies, a challenging math test was administered to 5- to 6-year-old children (total N = 500; 255 girls). An answer key was present as children completed the test, but they were instructed to not peek at it. In Study 1, many children cheated, but manipulations that reduced the answer key's accessibility in terms of proximity and visibility led to less cheating. Two follow-up studies showed that the answer key's visibility played a more significant role than its proximity. These findings suggest that subtle and seemingly insignificant alterations of the physical environment can effectively nudge young children away from acting dishonestly.

3.
ACS Appl Mater Interfaces ; 13(36): 43449-43457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472846

RESUMO

Composites based on a shape-memory polymer doped with conductive particles are considered as soft actuators for artificial muscles and robots. Low-voltage actuating is expected to reduce equipment requirement and safety hazards, which requires a highly conductive particle content but weakens the reversible deformation. The spatial distribution of the conductive particle is key to decreasing the actuating voltage and maintaining the reversible deformation. Herein, an approach of fabricating a low-voltage actuator that can perform various biomimetic locomotions by spraying and hot pressing is reported. Carbon nanotubes (CNTs) are enriched inside the surface layer of poly(ethylene-co-vinyl acetate) (EVA) to form a high-density conductive network without degradation of the reversible deformation. The bilayer CNT/EVA actuator exhibits a reversible transformation of more than 10% even with 100 cycles, which requires an applied voltage of just 15 V. Taking advantage of the reprogrammability of the CNT/EVA actuator and reversible shift between the different shapes, different biomimetic locomotions (sample actuator, gripper, and walking robot) are demonstrated without any additional mechanical components. A scheme combining the electrical properties and the shape-memory effect provides a versatile strategy to fabricate low-voltage-actuated polymeric actuators, providing inspiration in the development of electrical soft actuators and biomimetic devices.

4.
Can Respir J ; 2021: 9999122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394777

RESUMO

Asthma is a heterogeneous disease, and abnormal activation of T cells is the driving link of asthma's pathophysiological changes. Dual-positive Th2-Th17 cells, as newly discovered T-helper cells, have the functions of Th2 and Th17 cells and can coproduce Th2 and Th17 cytokines. Previous studies have shown that dual-positive Th2-Th17 cells increase the chances of asthma and correlate with asthma severity. However, the exact role of dual-positive Th2-Th17 cells in asthma is not known. Since there is no mature differentiation method for dual-positive Th2-Th17 cells, the present study aimed to clarify the strict differentiation conditions and reveal how dual-positive Th2-Th17 cells regulate asthma phenotypes. In this study, we confirmed that IL-1ß, IL-6, anti-IFN-γ, and IL-21 promoted biphenotypic cell differentiation. Moreover, more proportion of dual-positive Th2-Th17 cells can be obtained by conditioned differentiation of mouse CD4+ T cells after classical allergic asthma modeling. Before asthma modeling, adoptive dual-positive Th2-Th17 cells promoted T cells to differentiate into the same biphenotype cells and exacerbated the severity of asthma. Together, our results clarify the differentiation conditions of dual-positive Th2-Th17 cells and further confirm that it stimulates asthma T cells to differentiate into the same biphenotype cells, leading to exacerbation of asthma.

5.
Int Immunopharmacol ; 97: 107702, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33930706

RESUMO

BACKGROUND: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. METHODS: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. RESULTS: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. CONCLUSION: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.


Assuntos
Amidas/administração & dosagem , Antivirais/administração & dosagem , COVID-19/tratamento farmacológico , Pirazinas/administração & dosagem , Reinfecção/tratamento farmacológico , Administração Oral , Adulto , Idoso , Amidas/efeitos adversos , Antivirais/efeitos adversos , COVID-19/sangue , Feminino , Humanos , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Pirazinas/efeitos adversos , RNA Viral/análise , RNA Viral/efeitos dos fármacos , Reinfecção/sangue , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento
6.
ACS Appl Mater Interfaces ; 12(47): 53230-53238, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33179903

RESUMO

Conductive textiles (CTs) are promising electromagnetic interference (EMI) shielding materials. Nevertheless, limited stretchability and poor reliability restrict their potential applications in stretchable electronic devices because of the rigid conductive networks. Herein, a highly stretchable and reliable CT is developed for effective EMI shielding by designing a deformable liquid-metal (LM) coating and polydimethylsiloxane (PDMS) protective layer. The resultant PDMS-LM/Textile exhibits an outstanding EMI shielding efficiency (EMI SE) of 72.6 dB at a thickness of only 0.35 mm while maintaining EMI SEs of 66.0 and 52.4 dB under strains of 30 and 50%, respectively. The corresponding EMI SEs hold 91.7 and 80.3% retention after 5000 stretching-releasing cycles, respectively. The superior and durable EMI SE should be ascribed to the perfect connectivity and good deformability of conductive LM networks. Moreover, the LM coating has a robust fastness to the textile substrate, without any obvious decrease in EMI SE after 10 min of ultrasonic treatment and 100 peeling cycles because of the protective effect of the PDMS layer. This work provides a novel route to developing highly stretchable CTs for advanced EMI shielding applications, especially in the field of highly stretchable electronic devices.

7.
BMJ ; 369: m1849, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409561

RESUMO

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , COVID-19 , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Resultado do Tratamento
8.
ACS Appl Mater Interfaces ; 12(7): 8704-8712, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31971778

RESUMO

Excellent electromagnetic interference (EMI) shielding ability, light weight, and good heat resistance are highly required for practical applications of EMI shielding materials, such as in areas of aerospace, aircraft, and automobiles. Herein, a lightweight and robust carbon nanotube (CNT)/polyimide (PI) foam was developed for efficient and heat-resistant EMI shielding. Thanks to poly(vinyl pyrrolidone) (PVP) as a surfactant that not only promotes the uniform dispersion of CNTs to form perfect CNT conductive networks but also can be removed in situ during the polymerization process, the density of resultant CNT/PI foam is only 32.1 mg·cm-3, and the EMI shielding effectiveness (EMI SE) is up to 41.1 dB, which represents one of the highest EMI SE values compared to previously reported polymer-based foams. The CNT/PI foam also achieves the absorption coefficient (A) of up to 82.3%, which is very impressive in CNT/polymer foams at comparable EMI SE levels. The PI matrix endows the foam with excellent heat resistance. The as-prepared CNT/PI foam presents a higher EMI SE than 35 dB even after being subjected to the flame of an alcohol burner. Moreover, the compressive strength and compressive modulus are up to 240.9 and 323.9 kPa. These results indicate its certain application potential in the harsh requirement of aeronautics and aerospace industries as a highly efficient and lightweight EMI shielding material.

9.
Dev Sci ; 23(5): e12930, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31811686

RESUMO

Research on moral socialization has largely focused on the role of direct communication and has almost completely ignored a potentially rich source of social influence: evaluative comments that children overhear. We examined for the first time whether overheard comments can shape children's moral behavior. Three- and 5-year-old children (N = 200) participated in a guessing game in which they were instructed not to cheat by peeking. We randomly assigned children to a condition in which they overheard an experimenter tell another adult that a classmate who was no longer present is smart, or to a control condition in which the overheard conversation consisted of non-social information. We found that 5-year-olds, but not 3-year-olds, cheated significantly more often if they overheard the classmate praised for being smart. These findings show that the effects of ability praise can spread far beyond the intended recipient to influence the behavior of children who are mere observers, and they suggest that overheard evaluative comments can be an important force in shaping moral development.


Assuntos
Comportamento Infantil , Desenvolvimento Moral , Reforço Verbal , Adulto , Pré-Escolar , Decepção , Feminino , Humanos , Masculino , Socialização , Estudantes/psicologia
10.
Oxid Med Cell Longev ; 2020: 7101407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33456673

RESUMO

Objective: Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. Methods: Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKß, TGF-ß, and IL-1ß through Western blot or RT-qPCR. Results: It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKß/IKKß, TGF-ß, and IL-1ß, with similar effects from butyric acid. Conclusion: The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.


Assuntos
Asma/tratamento farmacológico , Asma/microbiologia , Dipeptídeos/uso terapêutico , Microbioma Gastrointestinal , Metaboloma , Aminoácidos/análise , Animais , Antibacterianos/farmacologia , Asma/complicações , Biodiversidade , Ácido Butírico/farmacologia , Citocinas/metabolismo , Dipeptídeos/farmacologia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hipersensibilidade/complicações , Hipersensibilidade/microbiologia , Inflamação/patologia , Masculino , Metaboloma/efeitos dos fármacos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
11.
J Exp Child Psychol ; 188: 104679, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31499456

RESUMO

Although there has been extensive research on how children distribute resources with respect to quantity, little is known about how these decisions are affected by resource quality. The current research addressed this question by conducting two preregistered studies in which 3-, 5-, and 7-year-old children (total N = 360) made anonymous distributions of high-quality and low-quality items. Quantitative fairness entailed distributing an equal number of items irrespective of quality, and qualitative fairness entailed distributing equal numbers of high-quality and low-quality items. In Study 1, a majority of 7-year-olds distributed resources equally between themselves and another child in terms of both quality and quantity, whereas a majority of 3- and 5-year-olds did so only in terms of quantity while giving themselves a qualitative advantage. In Study 2, a majority of children in all three age groups distributed resources equally between two other children in terms of both quality and quantity. Together with prior findings, these results suggest that children selectively ignore the dimension of quality when it serves their own interests. The results also show, for the first time, that by 7 years of age children consider quality even at the expense of their own interests and that children as young as 3 years have the capacity to take into account resource quality when making distributions.


Assuntos
Tomada de Decisões , Alocação de Recursos , Criança , Pré-Escolar , Família , Feminino , Humanos , Masculino
12.
ACS Appl Mater Interfaces ; 11(40): 37094-37102, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31512856

RESUMO

Flexible strain sensors based on elastomeric conductive polymer composites (ECPCs) play an important role in wearable sensing electronics. However, the achievement of good conjunction between broad detection range and high sensitivity is still challenging. Herein, a highly stretchable and sensitive strain sensor was developed with the formation of porous segregated conductive network in the carbon nanotube/thermoplastic polyurethane composite via a facile and nontoxic compression-molding plus salt-leaching method. The strain sensor with porous segregated conductive network exhibited perfect combination of ultrawide sensing range (800% strain), large sensitivity (gauge factor of 356.4), short response time (180 ms) and recovery time (180 ms), as well as superior stability and durability. The integrated porous structure intensifies the deformation of segregated conductive network when tension strain is applied, which benefits enhancement of the sensitivity. Our sensor could monitor not only subtle oscillation and physiological signals but also energetic human motions efficiently, revealing promising potential applications in wearable motion monitoring systems. This work provides a unique and effective strategy for realizing ECPCs based strain sensors with excellent comprehensive sensing performances.

13.
Biosci Rep ; 39(2)2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30541898

RESUMO

To determine whether or not house dust mite (HDM) and HDM+lipopolysaccharide (LPS) exposure causes a difference in T-cell subsets from young and old mice. The bronchial epithelial cells (BECs) from young and old mice were divided into three groups (PBS (control), HDM, and HDM+LPS). CD4+ naive T cells from the spleen and lymph nodes were collected after 24 h of co-culture with BECs. The number of Th2 and Th17 cells was elevated in the HDM and HDM+LPS groups compared with the control group; these responses were exacerbated when exposed to HDM+LPS. The number of HDM- and HDM+LPS-specific Th2/Th17 cells in young mice was higher than old mice; however, the Th2:Th17 cell ratio was greater in young mice, whereas the Th17:Th2 cell ratio was greater in old mice. The expression of GATA-3 and RORc was increased in the HDM+LPS and HDM groups compared with the PBS group and exhibited most in HDM+LPS group. The expression of HDM+LPS-specific GATA-3 in young mice was higher, while the expression of HDM+LPS-specific RORc in old mice was higher. Murine BECs directly regulated CD4+ naive T-cell differentiation under allergen exposure.


Assuntos
Asma/patologia , Brônquios/citologia , Células Th17/citologia , Células Th2/citologia , Fatores Etários , Animais , Asma/imunologia , Linfócitos T CD4-Positivos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fator de Transcrição GATA3/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Pyroglyphidae , Células Th17/imunologia , Células Th2/imunologia
14.
J Exp Child Psychol ; 177: 187-196, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30216777

RESUMO

The current research examined whether young children engage in unethical behavior to a greater extent when they have a prosocial justification for doing so. Participants (3- and 5-year-olds, N = 240) played a guessing game in which they were tempted to cheat to win a prize after promising not to do so. In Study 1, children were randomly assigned to either an experimental prosocial condition in which they were told that the prize would be given to a child who was unable to play the game or a control condition in which they were told that they would get to keep the prize for themselves. The 5-year-olds, but not the 3-year-olds, were more likely to cheat in the prosocial condition than in the control condition. Studies 2a and 2b revealed that older children's tendency to engage in prosocial cheating was driven by their concern with signaling to others that they are prosocial. These findings suggest that the tendency to act unethically to benefit others emerges early in development and that this tendency may reflect children's interest in prosocial signaling.


Assuntos
Comportamento Infantil/psicologia , Decepção , Ética , Comportamento Social , Pré-Escolar , Feminino , Humanos , Masculino , Psicologia da Criança
15.
ACS Appl Mater Interfaces ; 11(1): 1680-1688, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30520621

RESUMO

Superhydrophobic electromagnetic interference (EMI) shielding textile (EMIST) is of great significance to the safety and long-term service of all-weather outdoor equipment. However, it is still challenging to achieve long-term durability and stability under external mechanical deformations or other harsh service conditions. Herein, by designing and implementing silver nanowire (AgNW) networks and a superhydrophobic coating onto a commercial textile, we demonstrate a highly robust superhydrophobic EMIST. The resultant EMIST shows a synergy of high water contact angle (160.8°), low sliding angle (2.9°), and superior EMI shielding effectiveness (51.5 dB). Remarkably, the EMIST still maintains its superhydrophobic feature and high EMI shielding level (42.6 dB) even after 5000 stretching-releasing cycles. Moreover, the EMIST exhibits strong resistance to ultrasonic treatment up to 60 min, peeling test up to 100 cycles, strong acidic/alkaline solutions, and different organic solvents, indicating its outstanding mechanical robustness and chemical durability. These attractive features of the EMIST are mainly a result of the joint action of AgNWs, carbon nanotubes, polytetrafluoroethylene nanoparticles, and fluoroacrylic polymer. This work offers a promising approach for the design of future durable, superhydrophobic EMISTs, which are capable of remaining fully functional against long-time exposure to extreme conditions, for example, wet and corrosive environments.

16.
Exp Cell Res ; 371(1): 196-204, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098334

RESUMO

T helper 17 (Th17) cells has proven to be crucial in the pathogenesis of severe asthma. Although it is known that Suppressor of cytokine signaling 3 (SOCS3) is involved in differentiation of Th17 cells but, how it affects severe asthma is uncertain. Since previous studies indicated that Methtyl-CpG binding domain protein 2 (MBD2) null mice was deficient in Th17 cell differentiation, the aim of the present study was to understand how MBD2 interacts with SOCS3 to regulate Th17 cell differentiation in severe asthma. Here, we show that SOCS3 expression was significantly decreased in Th17-mediated severe asthmatic mice, accompanied by elevated STAT3 phosphorylation and RORγt expression. Knock-down of SOCS3 promoted the differentiation of naïve T cells into Th17 cells through STAT3/RORγt pathway. Meanwhile, MBD2 was overexpressed in Th17-mediated severe asthmatic mice. Intervention of MBD2 expression lead to a negative change of SOCS3 expression, whereas the differentiation of Th17 cells showed positive change. In addition, MBD2 knockout (MBD2-KO) mice displayed increased SOCS3 expression and decreased Th17 differentiation after severe asthma modeling. Taken together, our results suggest that MBD2 might facilitate Th17 cell differentiation via down-regulating SOCS3 expression in severe asthma. These findings uncover new roles for SOCS3 and MBD2, and provide a potential target for treatment of severe asthma.


Assuntos
Asma/genética , Proteínas de Ligação a DNA/genética , Pulmão/imunologia , Proteína 3 Supressora da Sinalização de Citocinas/genética , Células Th17/imunologia , Alérgenos/administração & dosagem , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/patologia , Diferenciação Celular , Proteínas de Ligação a DNA/imunologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/administração & dosagem , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Ovalbumina/administração & dosagem , Fosforilação , Pyroglyphidae/química , Pyroglyphidae/imunologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/imunologia , Células Th17/patologia
17.
Exp Ther Med ; 14(3): 2126-2134, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962133

RESUMO

Neutrophilic asthma (NA) is associated with a severe disease course and poor response to corticosteroids. The present study aimed to compare the effects of various concentrations of house dust mite (HDM) allergens, ovalbumin (OVA), the major egg allergen, and lipopolysaccharide (LPS) in combination on the onset of severe NA. Female C57BL/6 mice were grouped according to a random number table and intranasally sensitized with HDM/LPS/OVA extracts on days 0, 1 and 2 of the study. In group 1, mice received 50 µg HDM + 50 µg OVA + 15 µg LPS, mice in group 2 received 50 µg HDM + 100 µg OVA + 15 µg LPS, mice in group 3 received 100 µg HDM + 50 µg OVA + 15 µg LPS and those in group 4 received 100 µg HDM + 100 µg OVA + 15 µg LPS, while mice in the control group received saline only. The mice were then challenged by OVA solution with atomized excitation on days 14, 15, 18, 19 and 20 for 30 min each. Ethology, airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and specific cytokines interleukin 17A (IL-17A) and IL-4 in serum were assessed. Histological examination of inflammation by hematoxylin and eosin staining and immunohistochemical assessment of neutrophils (NEU), eosinophils (EOS), IL-17A and IL-4 were also performed. Compared with the control group, the HDM/OVA/LPS-sensitized groups 1-4 had markedly increased BALF cells, serum interleukin IL-17A and IL-4, inflammatory cell infiltration, EOS as well as IL-17A and IL-4 by immunohistochemical staining (all P<0.05). Among the four HDM/OVA/LPS-sensitized groups, mice of group 4 had higher AHR, a significantly higher total cell number, NEU and EOS in BALF as well as significantly higher NEU and NEU/EOS ratios according to immunohistochemical staining when compared to groups 1-3 (P<0.05 for all). In conclusion, sensitization with 100 µg HDM + 100 µg OVA + 15 µg LPS successfully established a severe asthma model with a predominantly neutrophilic inflammatory phenotype.

18.
Mediators Inflamm ; 2017: 6249685, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28808358

RESUMO

Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4+ T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4+ T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. Under overexpression or silencing of the MBD2 and IRF4 gene, the differentiation of Th17 cells and IL-17 secretion showed positive changes. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was no significant difference in the expression of MBD2 under overexpression or silencing of the IRF4 gene. These data provide novel insights into epigenetic regulation of severe asthma.


Assuntos
Asma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores Reguladores de Interferon/metabolismo , Pulmão/metabolismo , Células Th17/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Feminino , Imuno-Histoquímica , Fatores Reguladores de Interferon/genética , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
19.
J Endourol ; 29(8): 855-63, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25746718

RESUMO

PURPOSE: To compare the clinical efficacy and safety of selective vs hilar clamping during minimally invasive partial nephrectomy (PN). METHODS: Studies comparing the effect and safety of selective versus hilar clamping during PN were identified by a systematic search using MEDLINE and EMBASE from January 2000 to November 2014. Quality of the selected studies was assessed according to the Newcastle-Ottawa Scale (NOS). RESULTS: A total of seven retrospective studies were included. No significant differences were observed between the two groups in age, body mass index, tumor size, pre-estimated glomerular filtration rate (eGFR), operative time, and length of stay. The selective clamping group had greater estimated blood loss (P<0.01) but similar blood transfusion rate (P=0.78) compared with the hilar clamping group. There were no significant differences between the two groups in terms of urinary leaks, overall complication rate, and positive margin rate. Patients who underwent selective clamping had a lower change in eGFR (mean difference [MD]: 13.95; 95% CI 8.85 to 19.05; P<0.01) and a lower percent change in eGFR (MD: 18.51; 95% CI 14.18 to 22.84; P<0.01) at 1 week. Combined results from two studies showed a trend toward a lower percent change in eGFR at 3 months (MD: 5.47; 95% CI -0.28 to 11.22; P=0.06). At 6 months, two studies showed no significant differences in percent change of renal function between the two groups (MD: 16.85; 95% CI -10.47 to 44.16; P=0.23). CONCLUSIONS: Although selective clamping resulted in greater estimated blood loss, it provided comparable perioperative safety and superior short-term renal function preservation. The advantage of selective clamping in preservation of intermediate-term renal function remains to be evaluated in the future, however. There is a need for properly designed studies to confirm our founding.


Assuntos
Neoplasias Renais/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrectomia/métodos , Perda Sanguínea Cirúrgica , Constrição , Taxa de Filtração Glomerular , Humanos , Duração da Cirurgia , Estudos Retrospectivos
20.
PLoS One ; 9(12): e114564, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25478952

RESUMO

BACKGROUND: Stromal cell-derived factor-1(SDF-1) is a chemotactic and angiogenic factor that mediates the repair of various tissues. As macrophages are important contributors to ischemic kidney injury, we examine the role of SDF-1 in a rodent model of ischemia-reperfusion (I/R) injury. METHODS: Male wild-type (WT) (C57BL/6) mice were subjected to bilateral I/R injury or sham operation in the presence or absence of macrophage depletion (liposomal clodronate [0.2 ml/20-25 g body weight i.p.]). Macrophage accumulation was assessed by immunohistochemistry. Tissue levels of SDF-1 (ELISA) and SDF-1 mRNA expression (real-time PCR) were measured. The cellular location of SDF-1 was assessed using immunohistochemical staining. RESULTS: Immunofluorescence staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. SDF-1 production was elevated in response to I/R injury and was significantly increased upon macrophage depletion. SDF-1 positive cells initially appeared initially in the cortex, and subsequently diffused to the outer medulla after I/R injury. CONCLUSIONS: Our study demonstrates that SDF-1 is significantly upregulated during renal I/R. We hypothesize that SDF-1 upregulation may be an important macrophage effector mechanism during I/R injury.


Assuntos
Movimento Celular/imunologia , Quimiocina CXCL12/imunologia , Rim/imunologia , Macrófagos/imunologia , Traumatismo por Reperfusão/imunologia , Regulação para Cima/imunologia , Animais , Modelos Animais de Doenças , Rim/patologia , Macrófagos/patologia , Masculino , Camundongos , Traumatismo por Reperfusão/patologia
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