RESUMEN
Introduction: Acute respiratory distress syndrome (ARDS) is a common complication of sepsis, which significantly increases the mortality rate. This work explored the diagnostic value of serum NOD-like receptor family pyrin domain containing 3 (NLRP3) concentration in patients with sepsis for ARDS, and the predictive value of serum NLRP3 concentration at the time of diagnosis for death 28 days after treatment. Methods: A total of 150 sepsis patients were included in this study, including age-matched two groups of patients, 75 patients with ARDS and 75 patients without ARDS. In addition, 60 age-matched healthy patients with physical examination were recruited in this study. Serum NLRP3 concentration was determined by enzyme-linked immunosorbent assay (ELISA). The diagnostic values of serum NLRP3 concentration for ARDS in sepsis patients were evaluated by receiver operating characteristics (ROC) analysis. Correlation of serum NLRP3 with APACHE II score and SOFA were performed by Spearman correlation analysis. Results: Pulmonary infection, APACHE II score and serum NLRP3 concentration were risk factors for patients with sepsis complicated with ARDS. ROC curve results showed that the specificity of serum NLRP3 concentration was 74.67%, the sensitivity was 76.00%, and the area under the curve (AUC) was 0.82 (p<0.001). APACHE II score and SOFA were significantly positively correlated with serum NLRP3 concentration. Baseline serum NLRP3 levels had significant predictive value for 28-day mortality in sepsis patients complicated with ARDS. Conclusion: Serum NLRP3 concentration has clinical value in the diagnosis of sepsis complicated with ARDS.
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Síndrome de Dificultad Respiratoria , Sepsis , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR , Pronóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/etiología , Sepsis/complicaciones , Sepsis/diagnóstico , Área Bajo la CurvaRESUMEN
BACKGROUND: IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. METHODS: Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. RESULTS: IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. CONCLUSION: IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.
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Células Epiteliales/metabolismo , Pulmón/metabolismo , Antígenos de Histocompatibilidad Menor/metabolismo , Fibrosis Pulmonar/metabolismo , Receptores de Citocinas/metabolismo , Factor de Transcripción STAT3/metabolismo , Adulto , Animales , Sitios de Unión , Bleomicina , Estudios de Casos y Controles , Células Cultivadas , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-6/farmacología , Interleucinas/genética , Interleucinas/metabolismo , Interleucinas/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor/genética , Fosforilación , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Receptores de Citocinas/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT4/metabolismo , Adulto JovenRESUMEN
Beta-cypermethrin (beta-CYP), which is widely used for the control of indoor and field pests, is a highly lipophilic insecticide with environmental estrogenic effects. Selenium-enriched Spirulina (Se-SP) is a novel natural antioxidant agent with a high nutritional value. This study was aimed at the investigation of the protective effects of Se-SP on the reproductive system of male zebrafish (Danio rerio) exposed to beta-CYP. We determined the protective effect of Se-SP on male zebrafish exposed to 7 nmol L-1 beta-CYP by measuring the activity of sperm and antioxidants, examining tissue sections, measuring hormone secretion levels, and analyzing the expression of related proteins and genes during spermatogenesis. We found that beta-CYP enhanced VTG synthesis and estrogen (E2) secretion, increased the number of spermatogonia and spermatocytes, and decreased the number of spermatids and Sertoli cells. However, treatment with 50 mg L-1 Se-SP (Se: 25 µmol g-1 Se-SP) almost completely ameliorated the deleterious effects of beta-CYP. The protective mechanism of Se-SP in the testes of beta-CYP-treated fish involved an enhancement of antioxidant enzyme activity and an increase in androgen secretion by the downregulation of the expression of cyp19a, nanos2, piwil1, dazl and sycp3, and the upregulation of the expression of odf3b, igf3, insl3 and dmrt1, which affected testosterone production and spermatogenesis. Our study strongly indicates that treatment with Se-SP can effectively prevent the oxidative damage to the reproductive system during spermatocyte differentiation induced by beta-CYP exposure.
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Piretrinas/toxicidad , Selenio/farmacología , Espermatogénesis/efectos de los fármacos , Spirulina/química , Animales , Aromatasa/genética , Aromatasa/metabolismo , Biomarcadores/sangre , Diferenciación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Masculino , Estrés Oxidativo/efectos de los fármacos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Reproducción , Somatomedinas/genética , Somatomedinas/metabolismo , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo , Testosterona/metabolismo , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
The aim of this study was to investigate the protective effect and mechanism of selenium-enriched Spirulina platensis (S. platensis) on chronic alcohol-induced liver injury. Selenium incubation raises the nutrition quality of S. platensis by absorption enhancement of functional elements. Our results demonstrated that the effective dose of selenium-enriched S. platensis on HL7702 cells treated with alcohol was 200 µg ml-1, containing 20% selenium. Selenium-enriched S. platensis could raise the cell survival rate by decreasing the expression of p53, Caspase3, LC3, and Caspase1 and by increasing the expression of p70s6k. In vivo experiments, where mice were pretreated with selenium-enriched S. platensis, exhibited obvious inhibition of the liver function index and this pretreatment enhanced the activity of GSH-Px and SOD in alcohol induced mice. In summary, our results indicate that the protective mechanism of selenium-enriched S. platensis on chronic alcoholic liver injury is associated with the activity enhancement of antioxidant enzymes and immunity, the inhibition of DNA damage and apoptosis, accompanied with autophagy and pyroptosis.
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Alcoholes/efectos adversos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/prevención & control , Selenio/administración & dosificación , Spirulina/química , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Daño del ADN , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Humanos , Hígado/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Signal transducer and activator of transcription factor 3 (STAT3) plays an important role in the proliferation and angiogenesis in human glioma. Previous research indicated that saw palmetto extract markedly inhibited the proliferation of human glioma cells through STAT3 signal pathway. But its effect on tumor metastasis and antiangiogenesis is not clear. This study is to further clear the impact of saw palmetto extract on glioma cell metastasis, antiangiogenesis, and its mechanism. TUNEL assay indicated that the apoptotic cells in the saw palmetto treated group are higher than that in the control group (p < 0.05). The apoptosis related protein is detected and the results revealed that saw palmetto extract inhibits the proliferation of human glioma. Meanwhile pSTAT3 is lower in the experimental group and CD34 is also inhibited in the saw palmetto treated group. This means that saw palmetto extract could inhibit the angiogenesis in glioma. We found that saw palmetto extract was an important phytotherapeutic drug against the human glioma through STAT3 signal pathway. Saw palmetto extract may be useful as an adjunctive therapeutic agent for treatment of individuals with glioma and other types of cancer in which STAT3 signaling is activated.