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OBJECTIVE: This study aimed to identify the mechanism of Yiqi Huayu Decoction (YQHY) induced ferroptosis in gastric cancer (GC) by using network pharmacology and experimental validation. METHODS: The targets of YQHY, ferroptosis-related targets, and targets related to GC were derived from databases. Following the protein-protein interaction (PPI) network, the hub targets for YQHY induced ferroptosis in GC were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the hub targets from a macro perspective. We verified the hub targets by molecular docking, GEPIA, HPA, and the cBioPortal database. Finally, we performed cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, lipid peroxidation, and GSH assays to explore the mechanism of YQHY induced ferroptosis in GC. RESULTS: We identified the main active compounds and hub targets: Quercetin, DIBP, DBP, Mipax, Phaseol and TP53, ATM, SMAD4, PTGS2, and ACSL4. KEGG enrichment analyses indicated that the JAK2-STAT3 signaling pathway may be a significant pathway. Molecular docking results showed that the main active compounds had a good binding activity with the hub targets. The experimental results proved that YQHY could induce ferroptosis in AGS by increasing the MDA content and reducing the GSH content. qRT-PCR and Western blot results showed that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4. CONCLUSIONS: This study indicated that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4, and induction of ferroptosis may be one of the possible mechanisms of YQHY's anti-recurrence and metastasis of GC.
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OBJECTIVE: To evaluate the correlation between the advanced lung cancer inflammation index (ALI) and the L3 skeletal muscle index (L3SMI) and their prognostic value in elderly patients with esophageal cancer (EC). MATERIALS AND METHODS: The clinical data of 158 elderly patients with EC were collected retrospectively. The L3SMI measures the area of skeletal muscle at the level of the third lumbar (L3) vertebra using computed tomography (CT). A high L3SMI and low L3SMI group were created using sex-based quartiles. The ALI, prognostic nutrition index (PNI), and geriatric nutrition risk index (GNRI) were calculated according to standard laboratory protocols. RESULTS: The CT diagnostic criteria for senile sarcopenia in South China are height ≤32.96 cm2/m2 for females and height ≤35.4 cm2/m2 for males. The logistic regression analysis showed that a low L3SMI was significantly associated with a low ALI. Survival analysis revealed EC patients with a low L3SMI and a low ALI had poorer overall survival (OS) than patients with a high L3SMI and a high ALI. Univariate and multivariate Cox analyses showed that the L3SMI and ALI were independent predictors of EC prognosis in elderly individuals. CONCLUSION: There was a significant correlation between the PNI, GNRI, ALI, and L3SMI. Overall, our findings show the L3SMI and ALI are clinical indicators that can potentially be used to independently predict the prognosis of elderly EC patients and display good predictive value.