Dendrobine Suppresses Tumor Growth by Regulating the PD-1/PD-L1 Checkpoint Pathway in Lung Cancer.

BACKGROUND: Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study. METHODS: Bioinformatics was performed to screen the potential targets of dendrobine. The in-tersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was es-tablished to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the ex-pression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-ß, and the changes of indicators of liver and renal function were measured. RESULTS: Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed pro-tein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, den-drobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-ß in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors. CONCLUSION: Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Ferroptosis-related gene signature predicts prognosis in kidney renal papillary cell carcinoma.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, the role of ferroptosis-related genes (FRGs) in kidney renal papillary cell carcinoma (KIRP) is unclear. In this study, we examined the mRNA expression profiles and clinical data of patients with KIRP from the TCGA cohort. Consequently, 41 differentially-expressed FRGs were screened using the limma package, and 17 prognostic-related FRGs were identified by survival analysis and univariate Cox regression analyses. Thereafter, a ferroptosis-related gene prognostic index (FRGPI) was constructed based on five FRGs (AKR1C3, SAT1, FANCD2, HSBP1 and SQLE), using lasso Cox and multivariate Cox regression analyses. KIRP patients with high FRGPI scores displayed worse outcomes. Furthermore, the FRGPI was shown to be a reliable independent prognostic factor in both the training and testing cohorts. Comprehensive analysis also showed that the FRGPI can distinguish gene mutation, functional enrichment of immune cells and molecular function-related pathways. Interestingly, low FRGPI score could be more benefit from immune checkpoint inhibitors (ICIs) therapy. Then, the two hub prognostic genes (AKR1C3 and FANCD2) as a risk gene for KIRP were identified based on the FRGPI module, and the expression profiles of these two genes were validated using human KIRP cells, besides, we furthermore discovered that Fancd2 is significantly up-regulated in most cancers and is associated with prognosis. In conclusion, these findings showed that FRGPI can accurately predict the prognosis of patients with KIRP, suggesting that this risk model is a promising prognostic biomarker for these patients. Moreover, targeting ferroptosis (FANCD2) could be a potential therapeutic alternative for various cancers.