Sesamin ameliorates lipotoxicity and lipid accumulation through the activation of the estrogen receptor alpha signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) has been linked to fat accumulation in the liver and lipid metabolism imbalance. Sesamin, a lignan commonly found in sesame seed oil, possesses antioxidant, anti-inflammatory, and anticancer properties. However, the precise mechanisms by which sesamin prevents hepatic steatosis are not well understood. This study aimed to explore the molecular mechanisms by which sesamin may improve lipid metabolism dysregulation. A in vitro hepatic steatosis model was established by exposing HepG2 cells to palmitate sodium. The results showed that sesamin effectively mitigated lipotoxicity and reduced reactive oxygen species production. Additionally, sesamin suppressed lipid accumulation by regulating key factors involved in lipogenesis and lipolysis, such as fatty acid synthase (FASN), sterol regulatory element-binding protein 1c (SREBP-1c), forkhead box protein O-1, and adipose triglyceride lipase. Molecular docking results indicated that sesamin could bind to estrogen receptor α (ERα) and reduce FASN and SREBP-1c expression via the Ca2+/calmodulin-dependent protein kinase kinase ß (CaMKKß)/AMP-activated protein kinase (AMPK) signaling pathway. Sesamin attenuated palmitate-induced lipotoxicity and regulated hepatic lipid metabolism in HepG2 cells by activating the ERα/CaMKKß/AMPK signaling pathway. These findings suggest that sesamin can improve lipid metabolism disorders and is a promising candidate for treating hepatic steatosis.

A randomized controlled trial of minor hand surgeries comparing wide awake local anesthesia no tourniquet and local anesthesia with tourniquet.

INTRODUCTION: Epinephrine and sodium bicarbonate (NaHCO3) used in wide-awake local anesthesia no tourniquet (WALANT) affect many areas such as hemostasis, injection pain, anesthetic effect and others. However, few clinical trials have focused on injection pain and the duration of anesthetic effect, and no prospective studies have reported the benefits of WALANT post operation. This study compared WALANT with conventional local anesthesia with tourniquet in minor hand surgeries, and aimed to answer following questions: (1) Does WALANT have enough benefits for injection pain and duration of anesthetic effect?; (2) How does WALANT affect postoperative management (such as postoperative pain and use of analgesics)?; (3) How satisfied are the patients with the surgery? HYPOTHESIS: We hypothesized that WALANT had advantages in injection pain, duration of anesthetic effect, and postoperative management compared to conventional local anesthesia. MATERIALS AND METHODS: The present study is designed as a randomized prospective one center study. This study included 185 patients who received surgical treatment for the diagnosis of carpal tunnel syndrome, trigger finger, or de Quervain's disease between 2017 and 2019. We randomly allocated the patients to either the WALANT group or the conventional group. We inquired and recorded patients' injection pain, duration of anesthetic effect, postoperative pain, the use of analgesics, and satisfaction with the surgery. RESULTS: The injection pain was significantly lower in the WALANT group in all procedures (p<0.001). The duration of anesthetic effect was significantly longer in the WALANT group in all procedures (p<0.001). As for the postoperative management of all procedures, the pain score was significantly lower in the WALANT group until the first day after surgery, with the biggest difference at 6hours after surgery. The use of analgesics was significantly lower in the WALANT group until the second day after surgery. Satisfaction with surgery was significantly higher in the WALANT group in all procedures: A1 pulley release (p=0.026), 1st extensor retinaculum (p=0.045), and carpal tunnel release (p=0.003). DISCUSSION: Our study showed better results in WALANT than in the conventional method, with no tourniquet pain, lower injection pains, longer anesthetic duration, and less postoperative pain. It provided patients with great satisfaction. In addition, WALANT has the potential benefits of no time limit due to tourniquet pain and long anesthetic effect. Therefore, WALANT is comfortable and cost effective, and could be a good alternative to conventional local lidocaine anesthesia. LEVEL OF EVIDENCE: II.