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1.
Biomed Pharmacother ; 137: 111271, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561643

RESUMO

Cigarette smoking-related lung injury is one of the most common and fatal etiologies of many respiratory diseases, for which no effective interventions are available. Astragaloside Ⅳ (ASⅣ) is an active component extracted from Astragalus membranaceus. It is prescribed as a treatment for upper respiratory tract infections. Here, we report the potential anti-inflammatory effects and mechanisms of ASⅣ on cigarette smoking extract- (CSE)-exposed RAW264.7 cells. Murine macrophages were exposed to CSE, followed by administration of ASⅣ at 25-100 µg/mL for 24 h. ASⅣ significantly rescued CSE-induced cell death by inhibition of release pro-inflammatory cytokines. We measured autophagy as an intracellular scavenger by analyzing autophagic flux using tandem mRFP-GFP-LC3 fluorescence microscopy. Following administration with ASⅣ in CSE-exposed RAW264.7 cells, there was a notable increase in autophagosomes and a range of autophagic vacuoles were generated, as seen with transmission electron microscopy. Loss of autophagy following transfection siRNA aggravated inflammatory injury and release of inflammatory cytokines. Mechanistically, ASⅣ-triggered autophagy is mediated by the TLR4/NF-κB signaling pathway to reduce inflammation. Taken together, our findings suggest that ASⅣ acts stimulates autophagy, and that ASⅣ induces autophagy by inhibiting the TLR4/NF-κB signaling pathway, contributing to alleviation of inflammation.

2.
PLoS Pathog ; 16(8): e1008766, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32857822

RESUMO

Pathogens commonly disrupt the intestinal epithelial barrier; however, how the epithelial immune system senses the loss of intestinal barrier as a danger signal to activate self-defense is unclear. Through an unbiased approach in the model nematode Caenorhabditis elegans, we found that the EGL-44/TEAD transcription factor and its transcriptional activator YAP-1/YAP (Yes-associated protein) were activated when the intestinal barrier was disrupted by infections with the pathogenic bacterium Pseudomonas aeruginosa PA14. Gene Ontology enrichment analysis of the genes containing the TEAD-binding sites revealed that "innate immune response" and "defense response to Gram-negative bacterium" were two top significantly overrepresented terms. Genetic inactivation of yap-1 and egl-44 significantly reduced the survival rate and promoted bacterial accumulation in worms after bacterial infections. Furthermore, we found that disturbance of the E-cadherin-based adherens junction triggered the nuclear translocation and activation of YAP-1/YAP in the gut of worms. Although YAP is a major downstream effector of the Hippo signaling, our study revealed that the activation of YAP-1/YAP was independent of the Hippo pathway during disruption of intestinal barrier. After screening 10 serine/threonine phosphatases, we identified that PP2A phosphatase was involved in the activation of YAP-1/YAP after intestinal barrier loss induced by bacterial infections. Additionally, our study demonstrated that the function of YAP was evolutionarily conserved in mice. Our study highlights how the intestinal epithelium recognizes the loss of the epithelial barrier as a danger signal to deploy defenses against pathogens, uncovering an immune surveillance program in the intestinal epithelium.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Permeabilidade da Membrana Celular , Células Epiteliais/imunologia , Microbioma Gastrointestinal/imunologia , Salmonelose Animal/imunologia , Salmonella typhimurium/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Camundongos , Salmonelose Animal/metabolismo , Salmonelose Animal/microbiologia , Salmonelose Animal/patologia , Transdução de Sinais
3.
Mol Immunol ; 124: 109-116, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32554101

RESUMO

Disordered collagen production by fibroblasts in response to tissue injury contributes to pulmonary fibrosis (PF). Therefore, elimination of collagen deposition has becoming a potential target in PF treatment which despite standard anti-fibrosis regiment still remains challenge. Curcumin and curcumol are regarded as the main active components extraction from the rhizomes of Curcuma zedoaria, which is widely used for inhibition the proliferation of multiple cells. However, the molecular basis for the function of curcumin and curcumol in limiting fibrogenesis still unknown. In this study, we have investigated the effects of curcumin and curcumol in the fibroblast overproliferation model human lung fibroblast (HLF) inducing by TGF-ß1. The growth-inhibitory effects of the components wasn't observed from 8 to 64 µg/ml. Administration of curcumin or curcumol significantly diminished the level of hydroxyproline hydroxyproline and α-smooth muscle actin (α-SMA), also the collagen Ⅰ (Col-Ⅰ) and collagen Ⅲ (Col-Ⅲ) deposition were reduced in the HLF. Furthermore, related to the collagen synthesis proteins including N-terminal pro-peptide for Type Ⅰ collagen (PⅠNP), N-terminal pro-peptide for Type Ⅲ collagen (PⅢNP) and prolyl-hydroxylase (PHD) were degraded gracefully at dose-dependent manner. Autophagy as the scavenger was crippled in TGF-ß1-fibroblast overproliferation HLF, conversely the increased autophagosomes have been spotted in cytoplasm under transmission electron microscope which is consistent with up-regulation of Beclin1 and ATG7 after treatment with curcumin or curcumol in this study. Additionally, blocking autophagy by inhibitor chloroquine (CQ) caused collagen deposition, providing further evidence regard to autophagy activation capacity of curcumin and curcumol. Our findings provide a detailed understanding that the function of curcumin and curcumol on decreasing collagen deposition mediating by autophagy mechanism, which may also inspire the further research on PF at different perspectives.


Assuntos
Autofagia/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Curcumina/farmacologia , Fibroblastos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Cultivadas , Curcuma , Humanos , Extratos Vegetais/farmacologia , Fibrose Pulmonar/patologia
4.
Biosci Rep ; 40(4)2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32323724

RESUMO

The association between lung and intestine has already been reported, but the differences in community structures or functions between lung and intestine bacteria yet need to explore. To explore the differences in community structures or functions, the lung tissues and fecal contents in rats were collected and analyzed through 16S rRNA sequencing. It was found that intestine bacteria was more abundant and diverse than lung bacteria. In intestine bacteria, Firmicutes and Bacteroides were identified as major phyla while Lactobacillus was among the most abundant genus. However, in lung the major identified phylum was Proteobacteria and genus Pseudomonas was most prominent genus. On the other hand, in contrast the lung bacteria was more concentrated in cytoskeleton and function in energy production and conversion. While, intestine bacteria were enriched in RNA processing, modification chromatin structure, dynamics and amino acid metabolism. The study provides the basis for understanding the relationships between lung and intestine bacteria.

5.
Biomed Pharmacother ; 118: 109293, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401393

RESUMO

Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.


Assuntos
Autofagia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Autofagia/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Humanos , Inflamação/complicações , Inflamação/patologia , Pulmão/patologia , Masculino , Fosforilação/efeitos dos fármacos , Fibrose Pulmonar/complicações , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-31007701

RESUMO

E-Zhu (Curcuma zedoaria) is known as a classical traditional Chinese medicine and widely used in the treatment of cancers, cardiovascular disease, inflammation, and other diseases. Its main components include curcumol and curcumin, which have anti-inflammatory and antifibrosis effects. Here we established an in vitro inflammatory injury model by stimulating RAW246.7 cells with cigarette smoke extract (CSE) and detected the intervention effects of curcumin and curcumol on CSE-treated Raw246.7 macrophage cells to explore whether the two compounds inhibited the expression of inflammatory cytokines by inhibiting the NF-κB signaling pathway. We detected the antifibrosis effects of curcumin and curcumol via TGF-ß 1/Smads signaling pathways. The model of macrophage damage group was established by CSE stimulation. Curcumol and curcumin were administered to Raw246.7 macrophage cells. The efficacy of curcumol and curcumin was evaluated by comparing the activation of proinflammatory factors, profibrotic factors, and NF-κB and TGF-ß 1/Smads signaling pathway. In addition, CSE-treated group was employed to detect whether the efficacy of curcumol and curcumin was dependent on the NF-κB signaling via the pretreatment with the inhibitor of NF-κB. Our findings demonstrated that curcumol and curcumin could reduce the release of intracellular ROS from macrophages, inhibit the NF-κB signaling pathway, and downregulate the release of proinflammatory factor. Curcumol and curcumin inhibited the TGF-ß 1/Smads signaling pathway and downregulated the release of fibrotic factors. Curcumin showed no anti-inflammatory effect in CSE-treated cells after the inhibition of NF-κB. Curcumol and curcumin showed an anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30532794

RESUMO

Flora and mucosal immunity are considered to be the barrier, which is associated with multiple respiratory diseases, including recurrent respiratory tract infection (RRTI). Fei-Xi-Tiao-Zhi-Fang (FTF) is a traditional Chinese herbal formula used in the treatment of RRTI. However, the mechanism is little known. This study aims to identify the function of FTF in flora and mucosal immune secretory immunoglobulin A (sIgA) in the model of RRTI rats. The samples of intestine and lung were collected to detect sIgA, short chain fatty acids (SCFAS), and flora with enzyme-linked immunosorbent assay (ELISA), gas chromatography, and 16S rDNA sequencing. The body weight and viscera index were increased dynamically in RRTI rats after the administration of FTF. Furthermore, the types and proportions of aboriginal flora were significantly changed in the model group, whereas the altered flora was rescued in the FTF administration group. Desulfovibrio increased in the intestinal microflora and Ralstonia and Blautia decreased in the pulmonary microflora at the genus level, similar to that in the normal group. In addition, the expressions of sIgA in pulmonary and intestinal tissues were significantly upregulated and the level of SCFAS was increased in FTF group compared to the RRTI model group. Our study suggests that FTF can alleviate the symptoms of RRTI by increasing sIgA and SCFAS, recovering flora, and improving the immunity.

8.
Iran J Basic Med Sci ; 19(9): 993-1002, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27803787

RESUMO

OBJECTIVES: Yu-Ping-Feng-San (YPFS) is a classical traditional Chinese medicine that is widely used for treatment of the diseases in respiratory systems, including chronic obstructive pulmonary disease (COPD) recognized as chronic inflammatory disease. However, the molecular mechanism remains unclear. Here we detected the factors involved in transforming growth factor beta 1 (TGF-ß1)/Smad2 signaling pathway and inflammatory cytokines, to clarify whether YPFS could attenuate inflammatory response dependent on TGF-ß1/Smad2 signaling in COPD rats or cigarette smoke extract (CSE)-treated human bronchial epithelial (Beas-2B) cells. MATERIALS AND METHODS: The COPD rat model was established by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharide, YPFS was administered to the animals. The efficacy of YPFS was evaluated by comparing the severity of pulmonary pathological damage, pro-inflammation cytokines, collagen related genes and the activation of TGF-ß1/Smad2 signaling pathway. Furthermore, CSE-treated cells were employed to confirm whether the effect of YPFS was dependent on the TGF-ß1/Smad2 signaling via knockdown Smad2 (Si-RNA), or pretreatment with the inhibitor of TGF-ß1. RESULTS: Administration of YPFS effectively alleviated injury of lung, suppressed releasing of pro-inflammatory cytokines and collagen deposition in COPD animals (P<0.05), whereas exogenous TGF-ß1 promoted releasing of IL-1ß, IL-6, TNFα (P<0.05). Administration YPFS reduced inflammatory response significantly, also down-regulated TGF-ß1/Smad2 signaling in vivo and in vitro. Unexpectedly, knockdown Smad2 or inhibition of TGF-ß1 abolished anti-inflammatory effect of YPFS in CSE-treated cells. CONCLUSION: YPFS accomplished anti-inflammatory effects mainly by suppressing phosphorylation of Smad2, TGF-ß1/Smad2 signaling pathway was required for YPFS-mediated anti-inflammation in COPD rats or CSE-treated Beas-2B cells.

9.
Sci Adv ; 2(5): e1501372, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27386520

RESUMO

Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine ß-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms.


Assuntos
Sinais (Psicologia) , Alimentos , Metabolismo dos Lipídeos , Fenômenos Fisiológicos da Nutrição , Octopamina/metabolismo , Inanição , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica , Lipase/genética , Lipase/metabolismo , Redes e Vias Metabólicas , Ligação Proteica
10.
Autophagy ; 12(6): 1015-28, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27159636

RESUMO

Pseudomonas aeruginosa can establish life-long chronic infection in patients with cystic fibrosis by generating genetic loss-of-function mutations, which enhance fitness of the bacterium in the airways. However, the precise role of the pathoadaptive mutations in persistence in chronic airways infection remains largely unknown. Here we demonstrate that pyocyanin, a well-described P. aeruginosa virulence factor that plays an important role in the initial infection, promotes autophagy in bronchial epithelial cells. Disruption of phzM, which is required for pyocyanin biosynthesis, leads to a significant reduction in autophagy in Beas-2B cells and lung tissues. Pyocyanin-induced autophagy is mediated by the EIF2AK4/GCN2-EIF2S1/eIF2α-ATF4 pathway. Interestingly, rats infected with the phzMΔ mutant strain have high mortality rate and numbers of colony-forming units, compared to those infected with wild-type (WT) P. aeruginosa PA14 strain, during chronic P. aeruginosa infection. In addition, the phzMΔ mutant strain induces more extensive alveolar wall thickening than the WT strain in the pulmonary airways of rats. As autophagy plays an essential role in suppressing bacterial burden, our findings provide a detailed understanding of why reduction of pyocyanin production in P. aeruginosa in chronic airways infections has been associated with better host adaptation and worse outcomes in cystic fibrosis.


Assuntos
Adaptação Fisiológica , Autofagia/efeitos dos fármacos , Toxinas Bacterianas/farmacologia , Mutação/genética , Pseudomonas/metabolismo , Piocianina/farmacologia , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Toxinas Bacterianas/química , Brônquios/patologia , Doença Crônica , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Inflamação/complicações , Inflamação/patologia , Pneumonia/complicações , Pneumonia/microbiologia , Pneumonia/patologia , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Piocianina/química , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
11.
Chem Biodivers ; 7(7): 1790-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20658667

RESUMO

A fungal strain named MFF-1 was isolated from the flower of Pyrethrum cinerariifolium. Based on the sequence at the internal transcribed spacer (ITS) region, this strain was identified as a Trichoderma sp. Two new compounds, including a mitorubrin derivative and its potential biogenetic precursor, together with a known compound, were isolated from the cultures of the endophytic fungus. Their structures were established by spectroscopic methods and determined to be (3S*,6R*,7R*)-3,4,5,6,7,8-hexahydro-7-hydroxy-7-methyl-8-oxo-3-[(E)-prop-1-enyl]-1H-isochromen-6-yl 2,4-dihydroxy-6-methylbenzoate (1), named deacetylisowortmin, (E)-2-(hydroxymethyl)-3-(2-hydroxypent-3-enyl)phenol (2), and wortmannin (3). All compounds were assayed for antimicrobial activity. Compound 3 showed activity against Candida albicans and Bacillus cereus.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Chrysanthemum cinerariifolium/parasitologia , Trichoderma/química , Anti-Infecciosos/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Benzoatos/química , Benzoatos/isolamento & purificação , Benzoatos/farmacologia , Candida albicans/efeitos dos fármacos , Flores/parasitologia , Testes de Sensibilidade Microbiana , Trichoderma/isolamento & purificação
12.
Huan Jing Ke Xue ; 27(8): 1544-8, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17111608

RESUMO

Supported by the integrated model of nutrients for the Miyun Reservoir in part I, effects of different control measures were studied on the water quality of the reservoir. Four scenarios were assumed and analyzed. Results of the base case scenario showed that TN concentration of the Miyun Reservoir had highly exceeded the environmental quality standard for surface water, and TP was relatively better. Furthermore, there were many regions that chlorophyll-a concentration exceeded 10 microg/L in the reservoir, and centralized in the reservoir area of Chaohe River. Scenario 1, 2 and 3 investigated effects of different pollution control measures on the water quality of the reservoir. Results showed that the control of nutrient input loads could improve the water quality greatly, especially control of TP loadings would limit algae growth effectively, and regions that chlorophyll-a concentration exceeded 10 microg/L even disappeared. The results indicated that some control measures, such as changing farming style, part treatment on stockbreeding pollution and reducing point source pollutant loadings were very effective and essential to decrease the eutrophic level of the reservoir.


Assuntos
Modelos Teóricos , Nitrogênio/análise , Fósforo/análise , Poluentes da Água/análise , Abastecimento de Água/análise , China , Clorofila/análise , Clorofila A , Eutrofização , Sistemas de Informação Geográfica , Poluição da Água/prevenção & controle
13.
Huan Jing Ke Xue ; 27(7): 1286-91, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16881296

RESUMO

In recent years, the Miyun Reservoir faces severe problems of water quality and quantity due to continuous drought. In order to simulate and predict the eutrophic status of the Miyun Reservoir and its watershed, an integrated model was developed based on GIS and RS technology, which was composed of non-point source (NPS) simulation model, aquatic ecological-hydrodynamic model, and river water quality model. Ecological-hydrodynamic model was developed through coupling water quality analysis simulation program (WASP) with environmental fluid dynamics Code (EFDC). SWAT was selected as NPS simulation model, which could also perform water quality simulation in the river. Then the integrated model was calibrated using Markov Chain Monte Carlo method and verified using observed data. Results indicated that observed water quality data laid around the mode curves of simulation distribution, and which also dropped into the confidence interval on 80 percent credibility of water quality simulation distribution. In conclusion, the results show that the integrated model can meet the need of application.


Assuntos
Monitoramento Ambiental/métodos , Eutrofização , Poluentes da Água/análise , Abastecimento de Água/análise , China , Sistemas de Informação Geográfica , Método de Monte Carlo
14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 26(5): 347-51, 2002 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-16104265

RESUMO

In this paper we briefly introduce some microdevices which have been developed recently for biomedical applications by micro-fabrication technology. These applications mainly include areas of diagnostics, drug delivery, tissue engineering and minimally-invasive surgery.


Assuntos
Técnicas de Laboratório Clínico/instrumentação , Miniaturização , Engenharia Biomédica/instrumentação , Engenharia Biomédica/métodos , Técnicas de Laboratório Clínico/métodos , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Desenho de Equipamento , Humanos , Microcirurgia/instrumentação , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
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