Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B₁ (AFB₁), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB₁-induced hepatocyte injury and the mechanisms underlying those effects were investigated. Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB₁-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB₁ was used to evaluate the effects of baicalin. In vitro, baicalin significantly attenuated AFB₁-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB₁-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB₁-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. Baicalin can alleviate AFB₁-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB₁.

Objective: To assess the diagnostic value and clinical significance of nucleoporin 107 (NUP107) in hepatocellular carcinoma (HCC), and explore the possible mechanisms.Methods: The transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and GEO databases. Tissue specimens were collected from HCC patients in the Guangxi area. According to the expression levels and prognostic characteristics of NUP107, ROC curves and nomogram models were constructed using the R package.Results: NUP107 was highly expressed in 26 human cancers including HCC, and was associated with advanced HCC staging and worse prognosis. NUP107 showed satisfactory ability to predict the prognosis of HCC patients (AUC >0.8). Results of gene set enrichment analysis (GSEA) further showed that NUP107 was mainly associated with cell cycle‐related pathways such as the cell cycle, DNA replication, G2M checkpoint, E2F target, and mitotic spindle. In addition, NUP107 was also associated with immune infiltration in HCC and showed significant positive correlation with immune checkpoints (PD‐L1 and TIM‐3).

Backgroud: In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods: The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results: Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions: Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.

The purpose of this investigation was to explore the prognostic value of phospholipase C delta (PLCD) genes in early stage pancreatic ductal adenocarcinoma (PDAC) and its potential molecular mechanisms. The prognostic value of PLCD genes in early stage PDAC was assessed using the Kaplan‐Meier method and multivariate Cox proportional hazards regression model. Genome‐wide correlation analysis was performed on PLCD3 to identify the highly correlated genes in the transcriptome. Then, PLCD3 and these correlated genes together underwent a bioinformatics analysis to elucidate the potential molecular biological functions of PLCD3 in PDAC. PLCD1 and PLCD3 are significantly overexpressed in PDAC. In PDAC patients, PLCD3 is overexpressed in certain groups of people with a history of alcoholism (P = .032). High expression of PLCD3 was found to be associated with lower overall survival (OS) of patients with early stage PDAC (P = .020; adjusted P = .016). A combination of PLCD3 and clinical variables was able to better predict the outcome of patients with early stage PDAC. These clinical variables are histological grade (P = .001; adjusted P = .001), targeted molecular therapy (P < .001; adjusted P < .001), radiation therapy (P = .002; adjusted P = .039), and residual resection (P = .001; adjusted P = .002). The bioinformatics analysis revealed that PLCD3 is associated with angiogenesis, intracellular signal transduction, and regulation of cell proliferation. In conclusion, PLCD3 may be a potential prognostic biomarker for early stage PDAC.

Hepatitis B virus (HBV) infection and Aflatoxin B1 (AFB1) exposure are major contributors to the high incidence of hepatocellular carcinoma (HCC) in Southern Africa and Southeast Asia. Investigating the synergistic mechanisms between these factors will help to elucidate the pathogenesis, identify potential therapeutic targets, and reduce disease incidence. Oxidative stress in the cell line was assessed using ROS, MDA, and 8-OHdG assays. DNA damage was evaluated through the Comet assay and γ-H2AX detection. Sanger sequencing was employed to detect TP53 R249S mutations. RIP and Me-RIP assays were performed to investigate the interaction between YTH N6-methyladenosine RNA Binding Protein 2 (YTHDF2) and Poly(ADP-ribose) polymerase 1 (PARP1). The exogenous Cytochrome P450 3A4(CYP3A4)-Sodium/Taurocholate Cotransporting Polypeptide(NTCP) expression cell model was validated for its ability to metabolize AFB1 and support HBV infection. HBV infection increased YTHDF2 expression while suppressing PARP1 both in vitro and in vivo. Additionally, HBV infection exacerbated AFB1-induced DNA damage in both experimental settings. Interference with or pharmacological inhibition of PARP1 significantly worsened HBV- and AFB1-induced DNA damage, while PARP1 overexpression partially alleviated the damage. These findings provide compelling evidence that HBV aggravates AFB1-induced DNA damage by inhibiting PARP1. Further investigation revealed that YTHDF2 interference reversed HBV's regulatory effect on PARP1, while exogenous YTHDF2 addition mimicked HBV's effect by promoting PARP1 degradation. RIP (RNA immunoprecipitation) experiments confirmed that YTHDF2 directly binds to PARP1 mRNA, and MeRIP experiments showed that YTHDF2 increases m6A methylation of PARP1 mRNA. CYP3A4-NTCP overexpression enables liver cell lines to metabolize AFB1 and support HBV infection. HBV enhances AFB1-induced DNA damage by promoting PARP1 degradation, thereby synergistically contributing to HCC development.