Dl-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke. However, the precise underlying mechanism requires further investigation. In this study, we investigated the molecular mechanism of Dl-3-n-butylphthalide action by various means. We used hydrogen peroxide to induce injury to PC12 cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of Dl-3-n-butylphthalide. We found that Dl-3-n-butylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis. Furthermore, Dl-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3. Dl-3-n-butylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α, the key transcription factor that regulates Bax and Bnip3 genes. These findings suggest that Dl-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.

Hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Unfortunately, there are few reports on effective biomarkers for HCC, identification of novel cancer targets is urgently needed. Lysosomes are central organelles for degradation and recycling processes in cells, and how lysosome-related genes are involved in the progression of hepatocellular carcinoma remains unclear. The aim of the present study was to identify key lysosome-related genes affecting HCC. In the present study, lysosome-related genes involved in HCC progression were screened based on the TCGA (The Cancer Genome Atlas) dataset. Differentially expressed genes (DEGs) were screened, and core lysosomal genes were obtained in combination with prognostic analysis and protein interaction networks. Two genes were associated with survival, and their prognostic value was validated by prognostic profiling. After mRNA expression validation and IHC, the palmitoyl protein thioesterase 1 (PPT1) gene was identified as an important lysosomal-related gene. We demonstrated that PPT1 promotes the proliferation of HCC cells in vitro. In addition, quantitative proteomics and bioinformatics analysis confirmed that PPT1 acts by affecting the metabolism, localization, and function of various macromolecular proteins. The present study reveals that PPT1 could be a promising therapeutic target for the treatment of HCC. These findings provided new insights into HCC and identified candidate gene prognosis signatures for HCC.

Acute myelogenous leukemia (AML) is a common malignancy and is supposed to have the ability to escape host immune surveillance. The present study aimed to identify key genes in AML that may affect tumor immunity and to provide prognosis biomarkers of AML. The Cancer Genome Atlas (TCGA) dataset was screened for transcription factors (TFs) involved in immunity and influencing survival, combining Gene Expression Omnibus (GEO) data to validate the impact on patient survival. A prognostic signature was established using four transcription factors, and these genes play an important role in the immune system, with higher regulatory T cell (Treg) scores in high-risk patients compared with the low-risk group. Analysis of individual genes showed that STAT4 and Treg are closely related, which may be due to STAT4 transcribing related genes that affect immunity. STAT4 expression was positively correlated with the proportion of abnormal cells and promoted AML recurrence as verified by AML clinical patient samples. In addition, silencing of STAT4 significantly slowed down the proliferation capacity of HL60 cells. In conclusion, these findings suggest that STAT4 may be a potential biomarker for AML prognosis. As a key gene affecting the prognosis of AML patients, STAT4 has the potential to be a candidate diagnostic and prognostic biomarker for AML.