Methyl Cinnamate (MC) Alleviates Free Fatty Acids (FFAs) Induced Lipid Accumulation Through the AMPK Pathway in HepG2 Cells.

Background: AMP-activated protein kinase (AMPK) plays a critical role in energy metabolism. Its activation leads to the phosphorylation of downstream proteins such as acetyl-CoA carboxylase (ACC) and sterol regulatory element-binding protein-1 (SREBP1), subsequently inhibiting de novo fatty acid synthesis, thereby reducing intracellular triglyceride accumulation. MC is a compound found in extracts from Zanthoxylum armatum DC plants. Research has shown that MC can inhibit the differentiation of 3T3-L1 adipocytes through the CAMKK2-AMPK pathway. However, the biological effect of MC in HepG2 cells remains unknown. Methods: In this study, we utilized HepG2 cells to establish a model of MAFLD through FFAs stimulation. We investigated the biological effects of MC on HepG2 cells and studied its impact on lipid metabolism. Small interfering RNA was employed to explore the mechanism by which MC activates AMPK. Finally, molecular docking was conducted, establishing a model of the interaction between AMPK and MC. Results: We observed that MC can alleviate triglyceride accumulation in HepG2 cells. We observed the elevated p-AMPK/AMPK, P-ACC/ ACC, and elevated CPT1a after treatment of MC in HepG2 cells. The interference of CAMKK2 mRNA did not impact the ability of MC to phosphorylate AMPK. Compound C attenuates the ability of MC to increase p-AMPK. Molecular docking results led us to hypothesize that MC directly interacts with AMPK, resulting in AMPK phosphorylation and improved lipid accumulation in HepG2 cells.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study.

Background: The prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). Method: The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson's chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. Result: A total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. Conclusion: The combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.

The epidemiological trends of biliary tract cancers in the United States of America.

BACKGROUND: Biliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). METHODS AND RESULTS: The present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018. CONCLUSIONS: The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.

Effect of lymph node resection on prognosis of resectable intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

Background: The purpose of this meta-analysis was to evaluate the efficacy of lymph node dissection in patients with intrahepatic cholangiocarcinoma (ICC). Methods: The literature from January 2009 to December 2021 was searched to determine the comparative study of lymph node dissection and non-lymph node dissection in patients with ICC. Results: Seventeen studies were included in the analysis. There were no significant differences in 1-, 3-, and 5-year overall survival (OR = 0.80, p = 0.10; OR = 0.93, p = 0.71; OR = 0.80, p = 0.21) and 1-, 3-, and 5-year disease-free survival (OR = 0.89, p = 0.73; OR = 0.92, p = 0.81; OR = 0.85, p = 0.62). Conclusions: Lymph node dissection does not seem to have a positive effect on the overall survival and disease-free survival.