ABSTRACT
BACKGROUND@#The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies.@*METHODS@#The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model.@*RESULTS@#The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population.@*CONCLUSION@#This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Subject(s)
Adult , Humans , Asian People , China/epidemiology , Cross-Sectional Studies , Health Surveys , Hypertension/epidemiology , Nomograms , EthnicityABSTRACT
OBJECTIVE To explore the potential neurotoxicity of nano-alu mina (<50 n m)in vivo, we treated the ICR mouse with the nano-alu mina to investigate the mitochondrial da mage of nerve cells on morphology and function.METHODS Adult male mice were exposed to nano-alu mina (<50 n m)of 0,25,50 and 75 mg·kg -1 by nasal instillation for 1 month.Then we observed the mitochondrial ultra-structure of the nerve cells in CA3 region of hippoca mpus,and measured the mean dia meter in every group.The activities of Na +-K +-ATPase and Ca2 +-Mg2 +-ATPase were tested by the determination of the inorganic phosphorus,which was the deco mposition product of ATPase.Western blot analysis was used to detect the expression of COX-Ⅳ,Beclin1 ,LC3Ιand LC3Ⅱ.RESULTS Co mpared with 0 and 25 mg·kg -1 groups exposed to Al2 O3 nanopartilces (Al2 O3 NPs),the mitochondria of CA3 region in hip-poca mpus in 50 mg·kg -1 group beca me ede matous and swollen with sparse and broken cristae sur-rounding the nuclear,and the mean dia meter was higher(0.49 ±0.02 μm,P <0.05).But co mpared with 50 mg·kg -1 group,the mitochondria in 75 mg·kg -1 group beca me s maller with inner cristae of high density,and the mean dia meter was lower(0.36 ±0.02 μm,P<0.05).The enzy me activity of the mito-chondria in cerebral cortex decreased dose-dependently with exposure,the activities of Na +-K +-ATPase in 50 and 75 mg·kg -1 groups(6.37 ±0.22 kU·g -1 protein,5.48 ±1 .53 kU·g -1 protein)and Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups (3.21 ±0.99 kU·g -1 protein,3.28 ±0.15 kU·g -1 protein)were lower than the 0 mg·kg -1 group(P<0.05).Meanwhile,the Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups showed lower activities in co mparison with the 25 mg·kg -1 group.The 75 mg·kg -1 group expressed higher level of the COX-Ⅳ protein 1 .35 ±0.66(P<0.05)than other groups.Both expression of Beclin1 protein and rate of LC3Ⅱ/LC3Ⅰin 75 mg·kg -1 group were more than the 0 mg·kg -1 group. CONCLUSION The mitochondrial dysfunction may be the potential neurotoxicity of nano-alu mina,and the da maged mitochondria were cleared by autophagy.
ABSTRACT
OBJECTIVE To study the effect of nano-alumina(nano-Al2 O3 )on mitophagy in primary cortical neuronal cells from Wistar newborn rats. METHODS The purity of neuronal cells was detected by immunohistochemistry,and the lactate dehydrogenase(LDH)assay was performed to determine the viability of the cells treated with 13 nm nano-Al2 O3 0.5 mmol·L-1 for 12,24 and 48 h,respectively. The mitochondrial membrane potential(MMP)was detected by flow cytometry analysis . The ultrastructure of mitochondria and mitophagy vacuoles was observed by transmission electron microscopy(TEM). Auto-phagic vacuoles were observed by dansylpentanediamine(MDC)staining and the expression of autoph-agy related protein Beclin1 and LC3Ⅱ/ Ⅰ was determined by Western blotting. Mitophagy was observed by Lysotracker and Mitotracker staining respectively. RESULTS More than 95% cells were neuronal cells. The activity of LDH in the supernatant liquid exposed to nano-Al2 O3 for 12 and 24 h groups was sig-nificantly increased compared with the control group(P﹤0.05). After exposure to nano-Al2 O3 ,the mito-chondrial membrane potential was significantly decreased compared with the control group( P ﹤0.01). The results of TEM displayed mitochondrial swelling and the formation of vacuoles and mitophagy in nano-Al2 O3 groups. MDC positive fluorescence particles were observed and the expression of autophagy related protein Beclin1 and LC3Ⅱ/ Ⅰ was increased in nano-Al2 O3 groups compared with the control group( P ﹤ 0. 05 ). The result of Lysotracker and Mitotracker colocalization showed the fusion of mitochondria and lysosomals. CONCULSION Nano-Al2 O3 may induce autophagy and mitochondria damage in neuronal cells while the damaged mitochondria may be removed by mitophagy.
ABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Invasion and metastasis are the primary causes of death in patients with pulmonary carcinoma. The epidermal growth factor (EGF) stimulates A549 cells invasion greatly through activating ERK and PI3K-Akt signaling pathway. The aim of this study is to elucidate the inhibitory effect of Resveratrol on EGF-induced invasive ability of A549 cells in vitro and explore the molecular mechanism.</p><p><b>METHODS</b>The cytotoxicity of Resveratrol was evaluated by methyl thiazolyltetrazolium (MTT) assay. Then, the A549 cells were treated with EGF and non-cytotoxic concentration of Resveratrol. The cells' invasion were detected by Boyden chamber assay; MMP-2 activity was determined by gelatine zymography assay; the changes of the related proteins were detected by Western blot.</p><p><b>RESULTS</b>Resveratrol was not toxic to A549 cells at the concentration between 0 to 30 microM. The invasion ability of EGF-induced A549 cells was decreased after treatment with 20 microM resveratrol for 24 h, accompanied by the inhibition of MMP-2 secretion. And the levels of p-ERK1/2, PI3K (within 6 h) were suppressed too.</p><p><b>CONCLUSION</b>20 microM Resveratrol inhibits A549 cells' invasion possibly through the suppression of the activation of ERK and PI3K-Akt signaling pathways, subsequently exerting inhibitory effect on MMP-2.</p>