Background: Among cancer-related deaths, hepatocellular carcinoma (HCC) ranks fourth, and traditional Chinese medicine (TCM) treatment is an important complementary alternative therapy for HCC. Curcumin is a natural ingredient extracted from Curcuma longa with anti-HCC activity, while the therapeutic mechanisms of curcumin remain unclear, especially on ferroptosis and cuproptosis. Methods: Differentially expressed genes (DEGs) of curcumin treatment in PLC, KMCH, and Huh7 cells were identified, respectively. The common genes among them were then obtained to perform functional enrichment analysis and prognostic analysis. Moreover, weighted gene co-expression network analysis (WGCNA) was carried out for the construction of the co-expression network. The ferroptosis potential index (FPI) and the cuproptosis potential index (CPI) were subsequently used to quantitatively analyze the levels of ferroptosis and cuproptosis. Finally, single-cell transcriptome analysis of liver cancer was conducted. Results: We first identified 702, 515, and 721 DEGs from curcumin-treated PLC, KMCH, and Huh7 cells, respectively. Among them, HMOX1, CYP1A1, HMGCS2, LCN2, and MTTP may play an essential role in metal ion homeostasis. By WGCNA, grey60 co-expression module was associated with curcumin treatment and involved in the regulation of ion homeostasis. Furthermore, FPI and CPI assessment showed that curcumin had cell-specific effects on ferroptosis and cuproptosis in different HCC cells. In addition, there are also significant differences in ferroptosis and cuproptosis levels among 16 HCC cell subtypes according to single-cell transcriptome data analysis. Conclusions: We developed CPI and combined it with FPI to quantitatively analyze curcumin-treated HCC cells. It was found that ferroptosis and cuproptosis, two known metal ion-mediated forms of programmed cell death, may have a vital effect in treating HCC with curcumin, and there are significant differences in various liver cancer cell types and curcumin treatment which should be considered in the clinical application of curcumin.

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Traditional Chinese medicine (TCM) has special advantages in relieving HCC, while Astragalus membranaceus is commonly used in TCM treatment. However, its underlying mechanisms for treatment of HCC are unclear. Methods: Differentially expressed genes (DEGs) of Astragalus membranaceus treatment in HepG2 cells were identified, and Astragalus membranaceus-gene network was constructed. The hub genes were then obtained via protein-protein interaction (PPI) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) were subsequently performed. Furthermore, prognosis genes related to HCC from The Cancer Genome Atlas Program (TCGA) was identified to explore the correlation between Astragalus membranaceus treatment and prognosis of HCC. Finally, Astragalus membranaceus-component-target network was established through SymMap. Results: Twenty five DEGs (15 up-regulated and 10 down-regulated) of Astragalus membranaceus treatment in HepG2 cells were identified. Among the 25 genes, MT1F, MT1G, MT1X and HMOX1 may play essential roles. Astragalus membranaceus mainly affects the Mineral absorption pathway in HCC. A total of 256 genes (p < 0.01) related to prognosis of HCC were identified, and MT1G is a common gene between prognosis genes and DEGs. Furthermore, Astragalus membranaceus may directly down-regulate MT1G through daidzein to promote ferroptosis of HCC cells and improve prognosis for HCC. Conclusion: Our study provided new understandings of the pharmacological mechanisms by which Astragalus membranaceus improves the prognosis of HCC, and showed that the combination of transcriptomics and network pharmacology is helpful to explore mechanisms of TCM and traditional medicines from other nations.

Hepatocellular carcinoma (HCC) is the fourth main reason of cancer-related death. Codonopsis pilosula is a commonly used traditional Chinese medicine (TCM) for patients with HCC. However, its potential mechanism for treatment of HCC remains unclear. Here, we used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula. In our study, twelve differentially expressed genes (DEGs) (5 upregulated and 7 downregulated) of Codonopsis pilosula treating HepG2 cells (a kind of HCC cell) were identified. Among the 12 DEGs, HMOX1 may play an essential role. Codonopsis pilosula mainly affects the mineral absorption pathway in HCC. We acquired 2957, 1877, and 255 targets from TCMID, SymMap, and TCMSP, respectively. Codonopsis pilosula could upregulate HMOX1 via luteolin, capsaicin, and sulforaphane. Our study provided new understanding of the potential pharmacological mechanisms of Codonopsis pilosula in treating HCC and pointed out a direction for further experimental research.

MLN4924 (pevonedistat), a selective inhibitor of the NEDD8-activating enzyme, has inhibitory effects on various tumors by blockade of the neddylation pathway. Conversely, recent studies show that low-dose MLN4924 exerts pro-survival effects in both cancer cells and neurons, however, its actions on SH-SY5Y cells remain unclear. In this study, the effects of low-dose MLN4924 in SH-SY5Y cells were assessed by CCK-8 and Transwell assay, respectively. SH-SY5Y cells were transfected with enhanced green fluorescent protein plasmid to further observe neurite changes. The expression of SOCS3, p-JAK2 and p-STAT3 were analyzed by Western blot, and the potential interaction between MLN4924 and SOCS3 was explored via in silico molecular docking. Our results showed that 0.1 μM MLN4924 significantly enhanced SH-SY5Y cell viability and migration while concurrently reducing neurite outgrowth. The expression level of SOCS3 was significantly increased in the MLN4924 treatment group compared with the control group, but the phosphorylation levels of JAK2 and STAT3 showed no changes. Molecular docking further predicted that Glu63 of SOCS3 serves as a key residue for MLN4924 binding. Together, low-dose MLN4924 enhances SH-SY5Y cell viability and migration by targeting SOCS3 signaling, independent of JAK2/STAT3 signaling.

At present, mixed-criticality systems have become the development trend of embedded systems, such as in power edge computing, avionics safety control and car safety driving scenarios. In the existing advanced flexible mixed-criticality (FMC) model, the method of calculating compensation requirements may have a large number of low-criticality invalid compensation, which will greatly reduce the overall performance of low-criticality tasks. In response to this problem, our paper improves the method of reducing the service level of low-criticality tasks, from reducing the execution time of low-criticality tasks to now extending the period of low-criticality tasks, and proposes the corresponding FMCI-EDF-VD scheduling algorithm. Experimental results show that flexible mixed criticality improved (FMCI) model can manage the decline in service levels of low-criticality tasks more wisely and reduce invalid compensation for low-criticality tasks. Compared with existing FMC, our method can always perform better in ensuring the completion of high-criticality tasks while scheduling more low-criticality tasks under different circumstances.