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ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.
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OBJECTIVE: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). METHODS: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. RESULTS: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. CONCLUSION: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.
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Lesão Pulmonar Aguda , Pós-Condicionamento Isquêmico , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Masculino , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Camundongos Endogâmicos C57BL , Pulmão/patologia , Interleucina-6 , Fator de Necrose Tumoral alfa/metabolismo , Apoptose , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/metabolismo , Estresse do Retículo Endoplasmático , Traumatismo por Reperfusão/patologiaRESUMO
ABSTRACT Introduction: The objective of this study is to investigate the protective mechanism of dexmedetomidine (Dex) in myocardial ischemia/reperfusion (MIR)-induced acute lung injury (ALI) of diabetic rats by inhibiting hypoxia-inducible factor-1α (HIF-1α). Methods: Initially, healthy male Sprague Dawley rats were treated with streptozocin to induce diabetes. Then, three weeks after the induction, Dex or lentiviral vector (LV)-HIF-1α was injected into the rats 30 minutes prior to the MIR modeling. After four weeks, lung tissues were harvested for pathological changes observation and the wet/dry weight (W/D) ratio determination. Afterwards, oxidative stress indicators and pro-inflammatory factors were measured. In addition, HIF-1α expression was assessed by immunohistochemistry and western blot analysis. Results: Dex could suppress inflammatory cell infiltration, improve lung tissue structure, reduce pathological score and the W/D ratio, and block oxidative stress and inflammatory response in MIR-induced ALI of diabetic rats. Besides, Dex could also inhibit HIF-1α expression. Moreover, Dex + LV-HIF-1α reversed the protective role of Dex on diabetic MIR-induced ALI. Conclusion: Our study has made it clear that Dex inhibited the upregulation of HIF-1α in diabetic MIR-induced ALI, and thus protect lung functions by quenching the accumulation of oxygen radical and reducing lung inflammatory response.
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INTRODUCTION: The objective of this study is to investigate the protective mechanism of dexmedetomidine (Dex) in myocardial ischemia/reperfusion (MIR)-induced acute lung injury (ALI) of diabetic rats by inhibiting hypoxia-inducible factor-1α (HIF-1α). METHODS: Initially, healthy male Sprague Dawley rats were treated with streptozocin to induce diabetes. Then, three weeks after the induction, Dex or lentiviral vector (LV)-HIF-1α was injected into the rats 30 minutes prior to the MIR modeling. After four weeks, lung tissues were harvested for pathological changes observation and the wet/dry weight (W/D) ratio determination. Afterwards, oxidative stress indicators and pro-inflammatory factors were measured. In addition, HIF-1α expression was assessed by immunohistochemistry and western blot analysis. RESULTS: Dex could suppress inflammatory cell infiltration, improve lung tissue structure, reduce pathological score and the W/D ratio, and block oxidative stress and inflammatory response in MIR-induced ALI of diabetic rats. Besides, Dex could also inhibit HIF-1α expression. Moreover, Dex + LV-HIF-1α reversed the protective role of Dex on diabetic MIR-induced ALI. CONCLUSION: Our study has made it clear that Dex inhibited the upregulation of HIF-1α in diabetic MIR-induced ALI, and thus protect lung functions by quenching the accumulation of oxygen radical and reducing lung inflammatory response.
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Lesão Pulmonar Aguda , Dexmedetomidina , Diabetes Mellitus Experimental , Traumatismo por Reperfusão Miocárdica , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
The molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.
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Proteína de Ligação a CREB/metabolismo , Sistemas de Liberação de Medicamentos , Síndrome Metabólica/metabolismo , Camundongos Obesos/metabolismo , Própole/metabolismo , Fatores de Transcrição/metabolismo , Animais , Glicemia , Brasil , Proteína de Ligação a CREB/genética , Desenvolvimento de Medicamentos , Descoberta de Drogas , Gluconeogênese , Resistência à Insulina , Fígado/metabolismo , Síndrome Metabólica/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Obesos/genética , Obesidade/metabolismo , Própole/genética , Fatores de Transcrição/genéticaRESUMO
PURPOSE: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. METHODS: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. RESULTS: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. CONCLUSION: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
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Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Imunomodulação/efeitos dos fármacos , Pneumonia Estafilocócica/prevenção & controle , Polygonum/química , Substâncias Protetoras/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/química , Quimiocina CCL2/análise , Contagem de Colônia Microbiana , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-6/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Pneumonia Estafilocócica/tratamento farmacológico , Pneumonia Estafilocócica/patologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análiseRESUMO
Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
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Animais , Pneumonia Estafilocócica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Polygonum/química , Imunomodulação/efeitos dos fármacos , Antibacterianos/farmacologia , Pneumonia Estafilocócica/patologia , Pneumonia Estafilocócica/tratamento farmacológico , Fatores de Tempo , Ensaio de Imunoadsorção Enzimática , Líquido da Lavagem Broncoalveolar/química , Imuno-Histoquímica , Contagem de Colônia Microbiana , Reprodutibilidade dos Testes , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Resultado do Tratamento , Quimiocina CCL2/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BLRESUMO
Purpose:To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine.Methods:With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay.Results:rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection.Conclusion:rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.(AU)
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Animais , Camundongos , Polygonum , Plantas Medicinais , Staphylococcus aureus , Fatores Imunológicos/análise , Camundongos Endogâmicos C57BL , Controle de InfecçõesRESUMO
Microorganisms play an important role in the biodegradation of petroleum contaminants, which have attracted great concern due to their persistent toxicity and difficult biodegradation. In this paper, a novel hydrocarbon-degrading bacterium HZ01 was isolated from the crude oil-contaminated seawater at the Daya Bay, South China Sea, and identified as Achromobacter sp. Under the conditions of pH 7.0, NaCl 3% (w/v), temperature 28 °C and rotary speed 150 rpm, its degradability of the total n-alkanes reached up to 96.6% after 10 days of incubation for the evaporated diesel oil. Furthermore, Achromobacter sp. HZ01 could effectively utilize polycyclic aromatic hydrocarbons (PAHs) as its sole carbon source, and could remove anthracene, phenanthrene and pyrence about 29.8%, 50.6% and 38.4% respectively after 30 days of incubation. Therefore, Achromobacter sp. HZ01 may employed as an excellent degrader to develop one cost-effective and eco-friendly method for the bioremediation of marine environments polluted by crude oil.
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Achromobacter/isolamento & purificação , Poluição por Petróleo/prevenção & controle , Petróleo/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Água do Mar/microbiologia , Achromobacter/metabolismo , Alcanos/metabolismo , Baías/microbiologia , Biodegradação Ambiental , China , Petróleo/análise , Petróleo/microbiologia , Fenantrenos/metabolismoRESUMO
The aim of this study was to test whether a low dose of interferon-α-2b (IFN-α2b) enhances the clinical outcome of docetaxel (DXT) in patients with castration-resistant prostate cancer (CRPC). A prospective controlled trial of 40 CRPC patients receiving 5 mg of prednisone twice daily was conducted, where patients were randomly assigned to be administered 75 mg/m2 DXT plus 3 mIU/m2 IFN-α2b (group A, n=20) or 75 mg/m2 DXT alone (group B, n=20). The prostate-specific antigen (PSA) response, tumor response, progression-free survival (PFS) and overall survival (OS) were evaluated. There was no statistically significant difference in PSA response rate between groups A and B (65 vs. 47.4%, P=0.341). The tumor response rate in group A was significantly greater compared with that in group B (55 vs. 21.1%, P=0.048). The median PFS was longer in group A compared with that in group B (10 vs. 8 months, P=0.043). There was no statistically significant difference in median OS between the two groups (19 vs. 17 months, P=0.348), but one patient displayed a complete tumor response in group A. In groups A and B, transient grade 3 to 4 neutropenia was observed in nine and six patients, grade 3 to 4 anemia was observed in three and five patients, and grade 3 to 4 general fatigue was observed in four and one patient(s), respectively. The proportion of patients with grade 3 to 4 toxicity was not statistically different between the two groups. A low dosage of IFN-α2b may improve the antitumor activity of DXT with an acceptable toxicity profile in patients with CRPC.