Selective blockade of interleukin 6 trans-signaling depresses atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) has been accepted as an inflammatory atrial myopathy. Interleukin 6 (IL-6)-dependent inflammatory signaling pathways take context-dependent effects on cardiovascular diseases. IL-6 trans-signaling is predominantly pro-inflammatory. However, its effect on AF is unclear. OBJECTIVE: The purpose of this study was to investigate the role of IL-6 trans-signaling in AF. METHODS: Circulating levels of IL-6, soluble IL-6 receptor, and soluble glycoprotein 130 (sgp130) in patients with AF and controls were measured to estimate the activation of IL-6 trans-signaling. A mouse model of AF was established by transverse aortic constriction surgery. Sgp130Fc administration was used for the selective blockade of IL-6 trans-signaling. Studies were conducted to evaluate the effects and underlying mechanisms of sgp130Fc on AF inducibility and atrial conduction abnormalities and structural remodeling. RESULTS: In patients, the elevation of IL-6 trans-signaling level was positively associated with AF occurrence. IL-6 trans-signaling activation was recapitulated in the mouse model of AF. In transverse aortic constriction-challenged mice, the selective blockade of IL-6 trans-signaling with sgp130Fc attenuated AF inducibility, which was attributable to the amelioration of slow conduction and conduction heterogeneity induced by atrial dilation, fibrosis, and reduction in connexin 40 and redistribution of connexin 43. Sgp130Fc administration also reduced immune cell infiltration and oxidative stress in the mouse atrium and abrogated IL-6 trans-signaling activation-mediated connexin dysregulation and reactive oxygen species production in atrial myocytes. CONCLUSION: IL-6 trans-signaling activation contributes to AF development, and its selective blockade may promise a novel therapeutic strategy.

Comparative Analysis of Phytochemical Profiles and Antioxidant Activities between Sweet and Sour Wampee (Clausena lansium) Fruits.

As a local medicine and food, wampee fruit, with abundant bioactive compounds, is loved by local residents in Southern China. Titratable acid (TA), total sugar (TS), and total phenolic and flavonoid contents were detected, and phytochemical profiles and cellular antioxidant activities were analyzed by the HPLC and CAA (cellular antioxidant activity) assay in five sweet wampee varieties and five sour wampee varieties. Results showed that the average TS/TA ratio of sweet wampee varieties was 29 times higher than sour wampee varieties, while TA content was 19 times lower than sour wampee varieties. There were much lower levels of total phenolics, flavonoids, and antioxidant activities in sweet wampee varieties than those in sour wampee varieties. Eight phytochemicals were detected in sour wampee varieties, including syringin, rutin, benzoic acid, 2-methoxycinnamic acid, kaempferol, hesperetin, nobiletin, and tangeretin, while just four of them were detected in sweet wampee varieties. Syringin was the only one that was detected in all the sour wampee varieties and was not detected in all sweet wampee varieties. Correlation analysis showed significant positive correlations between TA with phenolics, flavonoids, and total and cellular (PBS wash) antioxidant activities, while there were significant negative correlations between TS/TA with phenolic and cellular (no PBS wash) antioxidant activities. This suggested that the content of titratable acid in wampee fruit might have some relationship with the contents of phenolics and flavonoids. Sour wampee varieties should be paid much attention by breeders for their high phytochemical contents and antioxidant activities for cultivating germplasms with high health care efficacy.

Comparison of phytochemical profiles and health benefits in fiber and oil flaxseeds (Linum usitatissimum L.).

Flaxseed (Linum usitatissimum L.) is a rich source of nutritive and bioactive compounds. The research evaluated the disparity in phytochemical profiles along with total and cellular antioxidant activities between oil and fiber flaxseeds. There were significant differences in total phenolics, total flavonoids and antioxidant activities among the six cultivars of fiber and oil flaxseed, respectively. Four phytochemical compounds including caffeic acid, p-coumaric acid and ferulic acid, and secoisolariciresinol diglucoside (SDG) were identified and quantified in the cultivars of oil and fiber flaxseed by HPLC analysis. Notably, the average of total phenolic and flavonoid contents, along with total antioxidant activities between fiber and oil flaxseeds were not different significantly; even the cellular antioxidant activity of fiber flaxseed was superior to oil flaxseed. These results suggest that fiber flaxseeds would be valuable candidates as functional products and dietary supplements production owing to the higher bioactive values as well as oil flaxseeds.