1.Mechanism of isochlorogenic acid A against hepatocellular carcinoma based on PI3K/Akt/mTOR signaling pathway combined with multi-omics
Weiwei SU ; Weibing JIA ; Houjian REN ; Xianhui SU ; Huijie GAO ; Zhongchao HUO ; Xin HOU ; Zhen WANG
China Pharmacy 2026;37(10):1258-1263
OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 (control group), 0.25 and 0.5 mg/mL isochlorogenic acid A were examined; mRNA expression of DEP domain-containing mTOR-interacting protein (DEPTOR), the protein expressions of mTOR, PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN), as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry, and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; transcriptomics monitoring was conducted by RNA sequencing, and differentially expressed genes were screened and subjected to gene ontology (GO) and KEGG pathway enrichment analyses. RESULTS Compared with the control group, intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells, significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN, and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein (except for 0.25 mg/mL isochlorogenic acid A) ( P <0.05). A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway, synergizing with metabolic reprogramming such as mTOR signaling pathway, ferroptosis, pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition, it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism, as well as the induction of ferroptosis,etc.
2.Correlation between lesion sites and post-stroke depression in patients with ischemic stroke
Jia HU ; Zhiming ZHOU ; Qian YANG ; Jian HAN ; Wei ZHOU ; Yan YAN ; Xianhui DING
International Journal of Cerebrovascular Diseases 2018;26(11):813-818
Objeetive To investigate the relationship between the lesion sites and post-stroke depression (PSD) in patients with acute ischemic stroke.Methods From January 2015 to June 2016,patients with first-ever acute ischemic stroke admitted to the Department of Neurology,Wuhu Yijishan Hospital were enrolled prospectively.The demographic and baseline clinical data were recorded.The stroke lesions were localized by imaging and clinical symptoms within 24 h after admission.The patients were divided into PSD group (≥8) and non-PSD group (<8) according to the Hamilton Depression Rating Scale score at l-month follow-up.Multivariate logistic regression analysis was used to investigate the independent correlation between PSD and lesion sites.Results A total of 376 patients with acute ischemie stroke were enrolled,including 177 females (47.07%) and 199 males (52.93%).Univariate analysis showed that there were significant differences in sex,years of education,hypertension,etiological classification of stroke (small vessel occlusion,cardiogenic embolism),baseline National Institutes of Health Stroke Scale (NIHSS) score,baseline Mini-Mental State Examination (MMSE) and left frontal lobe,left temporal lobe,and left basal ganglia lesions between the PSD group and the non-PSD group (all P <0.05).Multivariate logistic regression analysis showed that after adjusting for age,sex,years of education,hypertension,etiological classification of stroke,NIHSS score,and MMSE score,there was an independent correlation between the lesions in the left frontal lobe (odds ratio [OR] 1.838,95% confidence interval [CI] 1.028-3.947;P =0.034),the left basal ganglia (OR 1.672,95% CI 1.103-2.883;P=0.023),hypertension (OR 1.764,95% CI 1.179-3.365;P =0.016) and PSD.Conclusions One month after the onset of ischemic stroke,there was a significant correlation between PSD and the lesion sites.Left frontal lobe lesion and left basal ganglia lesion were the independent predictors.

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