Objective To investigate whether degradation of bromodomain-containing protein 4(BRD4)protein with dBET1 can inhibit neuroinflammation and oxidative stress caused byα-synuclein(α-syn)oligomers.Methods After BV2 cells or SH-SY5Y cells were treated with dBET1 and α-syn oligomers,the cells were divided into Control group,α-syn group,α-syn+500 and 1000 nmol/L dBET1 groups,and dBET1 group(1000 nmol/L).Real-time quantitative fluo-rescent PCR(qPCR)was used to detect the expression of inflammatory factors and anti-inflam-matory factors,and Western blotting was employed to measure the expression of BRD4,nuclear factor 2 associated factor 2(Nrf2),phosphorylated nuclear transcription factor-κB(p-NF-κB)and phosphorylated α-synuclein(p-α-synuclein).Results The α-syn+1000 nmol/L dBET1 group had lower mRNA levels of inflammatory factors and reduced protein levels of BRD4,p-NF-κB and p-α-synuclein,but higher mRNA levels of anti-inflammatory factors and decreased Nrf2 protein level(2.02±0.14 vs 0.96±0.24,P＜0.05)when compared with the α-syn group.Conclusion dBET1 can inhibit neuroinflammation and oxidative stress caused by α-synuclein through p-NF-KB and Nrf2 to a certain extent,which further provides a theoretical basis for its application in the treatment of Parkinson's disease.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.