Discovery of a novel small-molecule activator of SIRT3 that inhibits cell proliferation and migration by apoptosis and autophagy-dependent cell death pathways in colorectal cancer.

Colorectal cancer (CRC) is well known as a prevalent malignancy affecting the digestive tract, yet its precise etiological determinants remain to be elusive. Accordingly, identifying specific molecular targets for colorectal cancer and predicting potential malignant tumor behavior are potential strategies for therapeutic interventions. Of note, apoptosis (type I programmed cell death) has been widely reported to play a pivotal role in tumorigenesis by exerting a suppressive effect on cancer development. Moreover, autophagy-dependent cell death (type II programmed cell death) has been implicated in different types of human cancers. Thus, investigating the molecular mechanisms underlying apoptosis and autophagy-dependent cell death is paramount in treatment modalities of colorectal cancer. In this study, we uncovered that a new small-molecule activator of SIRT3, named MY-13, triggered both autophagy-dependent cell death and apoptosis by modulating the SIRT3/Hsp90/AKT signaling pathway. Consequently, this compound inhibited tumor cell proliferation and migration in RKO and HCT-116 cell lines. Moreover, we further demonstrated that the small-molecule activator significantly suppressed tumor growth in vivo. In conclusion, these findings demonstrate that the novel small-molecule activator of SIRT3 may hold a therapeutic potential as a drug candidate in colorectal cancer.

Exploring non-curative endoscopic submucosal dissection: Current treatment optimization and future indication expansion.

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.

The value of endoscopically-placed metal clips for transcatheter arterial embolization in the treatment of recurrent acute non-variceal upper gastrointestinal bleeding.

OBJECTIVE: Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is a common clinical emergency. Transcatheter arterial embolization (TAE) is usually used to locate the bleeding site and provide interventional embolization. During TAE, there is a low positive rate of angiography, and localization of the culprit vessel is difficult. The purpose of this study was to demonstrate the role of preplaced metal clips in TAE for ANVUGIB patients. MATERIALS AND METHODS: Patients with ANVUGIB in whom bleeding sites were identified endoscopically and treated with TAE from January 1st, 2005 to July 1st, 2021 were retrospectively included. According to the presence or absence of preplaced metal clips, they were divided into two groups. The main outcome measurements included the clinical success rate and rebleeding rate. Secondary outcome measurements included the mortality rate and the need for surgery. Predictors of the clinical success rate were assessed with univariate analysis and multivariate analysis. RESULTS: A total of 102 patients were included in this study, and all of them had undergone arterial embolization. There were 73 cases in the group with metal clips and 29 cases in the group without metal clips with consistent baseline information. The group with metal clips had a higher clinical success rate (82.2% vs. 45.0%, P < 0.001), lower rebleeding rate (8.2% vs 27.6%, P = 0.039) and additional surgery rate (11.0% vs 20.7%, P < 0.001) than the group without metal clips. In univariate analysis, ROCKALL score and preplaced metal clip marking were shown to affect clinical success rate. In multivariate analysis, metal clip marking was found to facilitate clinical success (OR = 3.750, 95CI = 1.456-9.659, P = 0.004). CONCLUSION: In ANVUGIB patients, preplaced metal clips could improve the clinical success rate of TAE and reduce the mortality rate and the risk of rebleeding.