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Background and purpose: The role of neddylation modification in breast cancer has rarely been reported. Previous study found that neddylation modification blocking induced cellular senescence in breast cancer, however, the potential mechanism has not yet been fully elucidated. It is reported that lamin B1 deletion leads to cellular senescence. The purpose of this study was to investigate the correlation between neddylation modification and lamin B1 expression in breast cancer and its possible mechanism. Methods: Neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) and NEDD8-activating enzyme 1 (NAE1), two key proteins of neddylation modification process, in addition to lamin B1 were immunohistochemically stained in tissue microarray from 113 breast cancer patients. The correlation of NEDD8 and NAE1 with lamin B1 was analyzed using Spearman’s rank analysis. The expression of NEDD8 was knocked down to block neddylation modification by CRISPR/Cas9 technique. Western blot assay was used to detect the regulation of lamin B1 by neddylation modification and its mechanisms. Results: Lamin B1 expression was positively correlated with NEDD8 (r=0.817, P

The transient outward current ([I.sub.to]) is a major repolarizing current in the heart. Marked reduction of Ito density occurs in heart failure and is accompanied by significant action potential duration (APD) prolongation. To understand the species-dependent role of [I.sub.to] in regulating the ventricular action potential morphology and duration, we introduced simulated [I.sub.to] conductance in guinea pig and canine endocardial ventricular myocytes using the dynamic clamp technique and perforated patch-clamp recordings. The effects of simulated [I.sub.to] in both types of cells were complex and biphasic, separated by a clear density threshold of ~40 pA/pF. Below this threshold, simulated [I.sub.to] resulted in a distinct phase 1 notch and had little effect on or moderately prolonged the APD. [I.sub.to] above the threshold resulted in all-or-none repolarization and precipitously reduced the APD. Qualitatively, these results agreed with our previous studies in canine ventricular cells using whole cell recordings. We conclude that 1) contrary to previous gene transfer studies involving the Kv4.3 current, the response of guinea pig ventricular myocytes to a fully inactivating [I.sub.to] is similar to that of canine ventricular cells and 2) in animals such as dogs that have a broad cardiac action potential, [I.sub.to] does not play a major role in setting the APD. dynamic clamp; transient outward current; ventricular myocytes doi:10.1152/ajpheart.00084.2006

Background: Jianpi formulas have been widely used to treat atopic dermatitis (AD) by traditional Chinese medicine (TCM) practitioners, but the efficacy and safety need further evaluation. A meta‐analysis of randomized controlled trials was performed to assess the efficacy and tolerability of Jianpi formulas for AD. Methods: We searched the following databases up to October 2020: PubMed, Embase, China National Knowledge Infrastructure database (CNKI), and Wanfang database. All randomized controlled trials (RCTs) evaluated Jianpi formulas add‐on effect for AD were included for meta‐analysis. The primary outcome was minor remission. Secondary outcomes include complete remission, marked remission, and decrease of SCORAD. Results: Totally eleven studies were included. Nine studies were included in qualitative analysis and seven were included in quantitative analysis. The common herbs were poria, glycyrrhiza uralensis, rhizoma atractylodis, atractylodes macrocephala, and semencoicis. The Jianpi formulas add‐on therapy showed consistent higher effectiveness rate in complete remission (RR1.528, 95%CI 1.176–1.984. p<0.01; Q=2.31, I2=0%), marked remission (RR 1.388, 95% CI 1.234–1.562. p<0.01; Q=3.682, I2=0%), and minor remission (RR 1.170, 95% CI 1.105–1.239, p<0.01; Q=14.355, I2=44.27%). The decrease of the scoring atopic dermatitis (SCORAD) in Jianpi formulas was significantly higher than in control group (SMD=0.671, 95% CI 0.018 to 0.937). Jianpi formulas were generally well tolerated, with no significantly increased risk of adverse events (AE). Conclusions: The combinations of Jianpi formulas showed moderate positive add‐one effects in AD patients. Further well‐designed clinical trials are needed to evaluate long‐term effect of this therapy. [ABSTRACT FROM AUTHOR]