RESUMEN
BACKGROUD: Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development. METHOD: Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT-PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays. RESULTS: Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived. CONCLUSIONS: We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.
Asunto(s)
Células Epiteliales Alveolares , Animales Recién Nacidos , Apoptosis , Ferroptosis , Hiperoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Animales , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Epiteliales Alveolares/metabolismo , Ferroptosis/fisiología , Hiperoxia/metabolismo , Ratas Sprague-Dawley , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación hacia Abajo , Humanos , Proliferación CelularRESUMEN
Background: Uncertainty exists about the link between omega-3 fatty acid, omega-6 fatty acid, and total polyunsaturated fatty acid (PUFA) intake and mortality in atherosclerotic cardiovascular disease (ASCVD) patients, and no meta-analyses summarize the relationship between these various types of PUFAs and ASCVD. Methods: Web of Science, PubMed, EBSCO and Cochrane Library up to November 30, 2022 were searched for prospective randomized controlled studies investigating the relationships among omega-3, omega-6, and PUFA intake and mortality and cardiovascular events in ASCVD patients. This study has been registered at PROSPERO (No. CRD42023407566). Results: This meta-analysis included 21 publications from 17 studies involving 40 861 participants published between 1965 and 2022. In ASCVD patients, omega-3 may lower all-cause mortality (RR: 0.90, 95% CI [0.83, 0.98], I2 = 8%), CVD mortality (RR: 0.82, 95% CI [0.73, 0.91], I2 = 34%) and CVD events (RR: 0.90, 95% CI [0.86, 0.93], I2 = 79%). Subgroup analyses showed that EPA or EPA ethyl ester supplementation reduced CVD events, while the mixture of EPA and DHA had no significant impact. Long-chain omega-3 consumption of 1.0-4.0 g per d reduced death risk by 3.5% for each 1 g per d increase. Omega-6 and PUFA had no significant effect on mortality or CVD events, with low-quality evidence and significant heterogeneity. Conclusions: omega-3 intake is associated with a reduced risk of all-cause mortality, CVD mortality, and CVD events in ASCVD patients, while omega-6 or total PUFA intake showed no significant association. Increasing the omega-3 intake by 1 g per d resulted in a 3.5% decrease in the risk of death. These findings support the recommendation of supplements with omega-3 fatty acids for the secondary prevention of ASCVD.
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Aterosclerosis , Enfermedades Cardiovasculares , Ácidos Grasos Omega-3 , Humanos , Estudios Prospectivos , Ácidos Grasos Omega-3/efectos adversos , Ácidos Grasos Insaturados , Suplementos Dietéticos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Aterosclerosis/inducido químicamenteRESUMEN
OBJECTIVE: To study the association between single nucleotide polymorphisms(SNP) in toll-like receptors (TLR) 2 and 5 genes and the susceptibility to neonatal sepsis. METHODS: One hundred and fourteen newborn infants who were diagnosed with clinical sepsis (case group) between May 2011 and January 2014 and 172 newborn infants without infection(control group) were enrolled in this study. The polymorphisms of TLR2 (rs5743708 and rs3804099) and TLR5 (rs5744105) were analyzed using a SNaPshot multiplex reaction to compare the genotypic and allelic frequencies between two groups. The relationship between TLR genotypes and susceptibility to sepsis was analyzed by logistic regression models. RESULTS: Significant differences in genotypic frequencies of TLR2 rs3804099 (C/T) and TLR5 rs5744105 (C/G) were found between the two groups (P<0.05), but there was no significant difference in allelic frequencies of all the SNPs above between the two groups (P>0.05). The genotype on TLR2 rs5743708 was GG and no mutation was found in both groups. In regression models, birth weight (OR=3.065; P<0.05) and gestational age (OR=3.301; P<0.05) were closely associated with neonatal sepsis. Sex (OR=1.107, P>0.05), polymorphisms in rs3804099 (OR=0.876; P>0.05) and polymorphisms in rs5744105 (OR=0.820; P>0.05) genes were not risk factors for neonatal sepsis. CONCLUSIONS: TLR2 and 5 polymorphisms (rs5743708, rs3804099 and rs5744105) may not serve as the susceptible gene for sepsis in newborn infants.
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Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Sepsis/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 5/genética , Femenino , Humanos , Recién Nacido , Modelos Logísticos , MasculinoRESUMEN
AIM: To investigate protective effect and possible mechanisms of erythropoitin (EPO) on cortical neuron against damage induced by glutamate(Glu). METHODS: Cortical neurons were removed from 1-day-old newborn rat and then cultured in vitro. The model of damage induced by Glu was established. The experiment was designed as: control group, Glu treatment group,the group of pretreatment with EPO, pyrrolidine dithiocarbamates(PDTC) treatment group. The changes of morphology were observed under inverted microscopy; the cell viability was detected by MTT assay; and the apoptosis rate of neuron was measured by flow cytometry. RESULTS: After exposure to Glu, neurons were obviously damaged. Neurons morph of EPO pretreatment group was similar to that of blank group. However, in PDTC treatment group, cells were obviously damaged, and morph of cells was similar to that of Glu treatment group. Compared with control group, survival of neurons of Glu treatment group significantly decreased, while the neurons apoptotis of Glu treatment group was significantly increased (P<0h01). Compared with Glu treatment group, the neurons, survival of EPO pretreatment group significantly increased, the neurons apoptotis can significantly decrease (P<0h01)ls. Compared with EPO pretreatment group, the cells survival of PDTC treatment group was significantly decreased, while the neurons, apoptotis of Glu treatment group was significantly increased (P<0h01), and similar to that of Glu treatment group. CONCLUSION: EPO could protect cortical neuron from Glu toxicity,which might related to signal transduction of NF-kappaB.
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Ácido Glutámico/toxicidad , FN-kappa B/metabolismo , Neuronas/efectos de los fármacos , Quinolinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas WistarAsunto(s)
Proteínas de Ciclo Celular/análisis , Minas de Carbón , Neumoconiosis/metabolismo , Proteínas Supresoras de Tumor/análisis , Adulto , Anciano , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Humanos , Inmunohistoquímica , Pulmón/química , Pulmón/patología , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/metabolismoRESUMEN
OBJECTIVE: To study the difference in the expressions of C-erbB-2 gene between the coal miners with pneumoconiosis complicated by pulmonary cancer and the controls with single pulmonary cancer, and its relation to clinical pathology. METHOD: Measuring the expressions of C-erbB-2 in 32 cases of pneumoconiosis complicated by pulmonary cancer and those in 30 cases of pulmonary cancer by means of immunohistochemistry. RESULTS: The positive expression rate in 32 cases of pneumoconiosis complicated by pulmonary cancer was 53.13% whereas that in 30 cases of single pulmonary cancer was 26.67% (P < 0.05); the positive expressions of C-erbB-2 in patients with lymph node metastasis (70.59% in pneumoconiosis group, 50.00% in controls) were significantly different from those without lymph node metastasis (33.33% in pneumoconiosis group, 11.11% in controls) (P < 0.05). The prognosis on patients with positive expressions of C-erbB-2 was poor, and was not related to pathologic category. CONCLUSION: C-erbB-2 gene may be an important regulating gene in the coal miners with pneumoconiosis complicated by pulmonary cancer, and as a reference index to determine lymph node metastasis and prognosis.