EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis.

Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.

Effects of 12 weeks of Tai Chi Chuan intervention on the postural stability and self-reported instability in subjects with functional ankle instability: Study protocol for a randomized controlled trial.

Background: Tai Chi Chuan (TCC) is a physical activity modality that originated in China and is now widely popular around the world. Although there are a series of articles reporting that TCC can improve balance and other functional symptoms in a variety of populations, including the elderly, patients with stroke, and patients with Parkinson's disease, its efficiency has not been scientifically and methodically evaluated in subjects with functional ankle instability (FAI). Moreover, there is no literature directly comparing TCC and conventional balance training (CBT) interventions for FAI. The objective of this study is to investigate the comparative effects of TCC intervention and CBT protocols in improving postural balance and subjective instability feelings in patients with FAI. Methods: This study will be a single-center, parallel group, randomized controlled trial. Sixty-eight patients with FAI will be included and randomly assigned in a 1:1 ratio to either an intervention group (n =34) or a control group (n = 34). The participants in the intervention group will complete 12 weeks of TCC intervention (40 min/time, 3 times/week for 12 weeks) on the basis of health education treatment. The control group will receive health education and 36 CBT sessions during a 12-week period. Outcome measures include postural stability and self-reported feelings of instability at baseline, after the end of the intervention, and 3-month follow-up. The postural stability assessment of patients with FAI will be detected by performing static and dynamic postural tests, which will be carried out through a specific balance platform (TecnoBody ProKin). Self-reported feelings of instability will be assessed by Cumberland Ankle Instability Tool (CAIT), American Orthopedics Foot and Ankle Society's Ankle-Hindfoot Evaluation Scale (AOFAS-AHES), and the MOS item Short Form Health Survey (SF-36). Discussion: This trial will demonstrate whether a 12-week TCC intervention positively affects postural stability and self-reported outcomes in patients with FAI. At the same time, the superiority of its clinical efficacy will also be compared with that of CBT. This study may also help to redefine the value of traditional Chinese exercises in the treatment of chronic ankle instability. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR2100041790. Registration date: 22 March 2021. http://www.chictr.org.cn/edit.aspx?pid=119501&htm=4.