Peiminine is a compound isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), which has demonstrated antitumor activities. But its precise molecular mechanism underlying antitumor activity remain elusive. In this study, peiminine-induced apoptosis towards human hepatocellular carcinoma and its molecular mechanism were investigated. MTT assay was employed to assess anticancer effects of peiminine upon Hela, HepG2, SW480 and MCF-7 cell lines. Nuclear staining and flow cytometry were carried out to detect apoptosis induced by peiminine. Mitochondrial membrane potential evaluation and Western blot analysis were performed to investigate the mechanism of peiminine-induced apoptosis. The results showed peiminine reduced the viability of HepG2 cells in a time- and dose-dependent manner and had an IC₅₀ of 4.58 μg/mL at 24h. Peiminine significantly increased the percentage of apoptotic cells and the mitochondrial membrane potential dose-dependently in HepG2 cells. The results of Western blotting indicated the expressions of Bcl-2, procaspase-3, procaspase-8, procaspase-9, and PARP decreased in HepG2 cells treated with peiminine, while the expressions of Bax, caspase-3, caspase-8, caspase-9, and cleaved PARP₁ increased. The result suggests that peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways.

IARS2 encodes mitochondrial isoleucine-tRNA synthetase, which mutation may cause multiple diseases. However, the biological function of IARS2 on acute myeloid leukemia (AML) has not yet been identified. In the present study, qRT-PCR was used to determine the expression of IARS2 in K562, THP1, and HL-60 leukemia cells. Additionally the mRNA levels of IARS2 in CD34 cells and AML cells obtained from patients were detected by qRT-PCR. IARS2-shRNA lentiviral vector was established and used to infect acute myeloid leukemia HL-60 cells. qRT-PCR and Western blot analysis were employed to assess the knockdown effect of IARS2. The proliferation rate and cell cycle phase of HL-60 cells after IARS2 knockdown were evaluated by CCK-8 assay and flow cytometry. The PathScan Antibody Array was used to determine the expression of cell cycle-related proteins in HL-60 cells after IARS2 knockdown. The expression of proliferation-related proteins in HL-60 cells after IARS2 knockdown was determined by Western blot analysis. Results showed that IARS2 expression was stable and much higher in HL-60, THP-1, and K562 leukemia cells and AML cells obtained from patients than that of human CD34 cells. Compared with cells of the shCtrl group, IARS2 was markedly knocked down in cells that were transfected with lentivirus encoding shRNA of IARS2 in HL-60 cells (p < 0.05). IARS2 knockdown significantly inhibited the proliferation and induced cycle arrest at the G₁ phase in HL-60 cells. Additionally IARS2 knockdown significantly increased the expression of p53 and p21, and decreased the expression of PCNA and eIF4E in HL-60 cells. In conclusion, IARS2 knockdown can inhibit acute myeloid leukemia HL-60 cell proliferation and cause cell cycle arrest at the G₁ phase by regulating the p53/p21/PCNA/eIF4E pathways.

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

Purpose: To explore the therapeutic targets and regulatory mechanisms of the antitumor drug quercetin in the treatment of cervical cancer. Methods: Cervical cancer (HeLa) cells were treated with quercetin and subjected to RNA sequencing using the BGISEQ-500 platform. By combined analysis of GEO database and RNA-seq results, the differentially expressed genes (DEGs) (namely, the genes in the GEO database that were upregulated/downregulated in cervical cancer compared with normal cervix and downregulated/upregulated after quercetin treatment) were identified. Functional enrichment and protein–protein interaction analyses were carried out for the DEGs. The candidate genes were identified using the Gentiscape2.2 and MCODE plug-ins for Cytoscape software, and the upstream miRNAs, lncRNAs, and circRNAs of the candidate genes were predicted using the online tools MirDIP, TarBase, and ENCORI. Finally, the regulatory network was constructed using Cytoscape software. Results: Quercetin significantly inhibited the proliferation of cervical cancer cells. The combined analyses of the GEO database and RNA-seq results obtained 74 DEGs, and the functional enrichment analysis of the DEGs identified 861 biological processes, 32 cellular components, 50 molecular functions, and 56 KEGG pathways. Five therapeutic candidate genes, including EGFR, JUN, AR, CD44, and MUC1, were selected, and 10 miRNAs, 1 lncRNA, and 71 circRNAs upstream of these genes were identified. Finally, a lncRNA/circRNA-miRNA-mRNA-pathway regulatory network was constructed. Conclusion: In this study, data mining was used to identify candidate genes and their regulatory network for the treatment of cervical cancer to provide a theoretical basis for targeted therapy of cervical cancer.

Background: We designed this study to assess the effects and safety of Buyang-Huanwu Decoction (BYHWD) for the treatment of patients with acute ischemic stroke (AIS). Methods: Electronic databases of Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO, Scopus, Allied and Complementary Medicine Database, VIP Database, and China National Knowledge Infrastructure will be comprehensively and systematically searched from initial time of each electronic database to the present without limitations of language and publication status. Randomized controlled trials on BYHWD alone against any other interventions for the treatment of AIS will be included. All process of study selection, data collection, and methodological quality assessment will be independently undertaken by 2 investigators. Cochrane risk of bias tool and RevMan 5.3 software will be utilized for the performance of methodological quality assessment and statistical analysis, respectively. Results: This study will summarize most recent high quality evidence on investigating the effects and safety of BYHWD alone against any other interventions for the treatment of patients with AIS. Conclusions: The findings of this study will provide helpful evidence for the clinical practice for patients with AIS using BYHWD, as well as the relevant future researches. Study registration number: INPLASY202040169.