[Effective constituents of essential oil from Gleditsiae Fructus Abnormalis and anti-cerebral ischemia/reperfusion injury mechanism: based on GC-MS, network pharmacology, and experimental verification].

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1ß, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.

LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma.

Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that CRNDE was significantly overexpressed in HCC tissues and cell lines, and was statistically correlated with poor clinical outcome. CRNDE knockdown markedly decreased HCC cell proliferation, migration, and chemoresistance. In addition, in vivo experiments confirmed the suppressive effect of CRNDE knockdown on HCC progression. Mechanically, CRNDE directly bound to EZH2 (enhancer of zeste homolog), SUZ12 (suppressor of zeste 12), SUV39H1, and mediated their inhibition of tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2). CELF2 exerted tumor suppressive effect in HCC and was involved in CRNDE-mediated oncogenic effect. In addition, the oncogenic effects of CRNDE on HCC proliferation, migration and tumorigenesis, as well as its inhibition of Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated the importance of CRNDE in HCC progression and elucidated the underlying molecular mechanisms. These findings provided new insights into HCC pathogenesis and chemoresistance mediated by CRNDE.