Daidzein affects proliferation and apoptosis in non-small cell lung cancer cells:role of p53 signaling pathway / 中国药理学通报

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Evolution of associating liver partition and portal vein ligation for staged hepatectomy from 2012 to 2021: A bibliometric analysis. Review.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has become increasingly popular during the past few decades, and its indications have extended from patients with normal liver to post-chemotherapy patients and even patients with cirrhosis. However, few studies have assessed the publications in relation to ALPPS. METHODS: Web of Science was searched to identify studies related to ALPPS published from 2012 to 2021. The analysis was performed using the bibliometric package (Version 3.1.0) in R software. RESULTS: In total, 486 publications were found. These articles were published in 159 journals and authored by 2157 researchers from 694 organizations. The most prolific journal was Annals of Surgery (24 articles and 1170 citations). The most frequently cited article was published in Annals of Surgery (average citations, 72.7; total citations, 727). China was the most productive country for ALPPS publications but had comparatively less interaction with other countries. Both thematic evolution and co-occurrence network analysis showed low numbers of topics such as failure, resection, and safety among the publications but large numbers of highly cited papers on outcomes, prediction, mechanisms, multicenter analysis, and novel procedures such as liver venous deprivation. A total of 196 studies focused the clinical application of ALPPS, and most studies were IDEAL Stages I and II. The specific mechanism of ALPPS liver regeneration remains unclear. CONCLUSIONS: This is the first bibliometric analysis offering an overview of the development of ALPPS research publications. Our findings identified prominent studies, countries, institutions, journals, and authors to indicate the future direction of ALPPS research. The role of ALPPS in liver regeneration and the long-term results of ALPPS need further study. Future research directions include comparison of ALPPS with portal vein embolization, liver venous deprivation, and other two-stage hepatectomies as well as patients' quality of life after ALPPS.

Dihydromyricetin ameliorates chronic liver injury by reducing pyroptosis.

BACKGROUND: Chronic liver injury (CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin (DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosis-related molecules. Therefore, we studied the influence of DHM on CLI and pyroptosis. AIM: To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of DHM. METHODS: Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride (CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-ß-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related molecules. RESULTS: Serum total cholesterol, low density lipoprotein, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and gasdermin D (GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these proteins in the DHM group was lower than that in the vehicle group. Quantitative reverse transcription PCR results showed that the expression of the pyroptosis-related genes caspase-1, NLRP3, GSDMD and interleukin-1ß (IL-1ß) in the CCl4 group was higher than that in the control group, while there was no significant change in NLRP3 and caspase-1 expression in the DHM group compared with that in the vehicle group, and the expression of GSDMD and IL-1ß was decreased. CONCLUSION: DHM improves CCl4-induced CLI and regulates the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic agent for CLI.