Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma

Background Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. Methods Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. Results The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. Conclusion By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

Mechanism of Anticancer Activity of Compounds Isolated from Two Species of Ziziphus (Z. jujube and Z. mauritiana)

Medicinal plants have been used to treat diseases for centuries. One group of such plants is Ziziphus species belonging to Rhamnaceae family. The extracts from plants of this genus has been found beneficial for the treatment of cancer caused by high production of reactive oxygen species resulting from different oxidative stress mediated conditions. The mechanism of anticancer activity of two different species of this plant (Z.jujube and Z.mauritiana) have been discussed in this review. The constituents of this plant include the flavonoids, triterpenes, potassium, calcium, phosphorus, iron, zinc, copper and polysaccharides such as reducing and non-reducing sugars. The underlying mechanisms of both species include the (Tumor protein P53) P53, (signal transducer and activator of transcription) STAT, (Matrix metalloproteinases) MMPs, (clustered regularly interspaced short palindromic repeats) CRISPR and flavonoids and triterpenic acid mechanisms. The effects of the extract on different cells lines in both in vitro and in vivo models have been studied by observing the induction of apoptosis and reduction in angiogenesis leading to reduction in progression and proliferation of cancer cell lines. The biological properties of Ziziphus include the anti-inflammatory, antioxidant, anticancer and hepato-protective characteristics.

Bioinformatics Analysis Identifies Precision Treatment with Paclitaxel for Hepatocellular Carcinoma Patients Harboring Mutant TP53 or Wild-Type CTNNB1 Gene

Hepatocellular carcinoma (HCC) is an aggressive and chemoresistant cancer type. The development of novel therapeutic strategies is still urgently needed. Personalized or precision medicine is a new trend in cancer therapy, which treats cancer patients with specific genetic alterations. In this study, a gene signature was identified from the transcriptome of HCC patients, which was correlated with the patients’ poorer prognoses. This gene signature is functionally related to mitotic cell cycle regulation, and its higher or lower expression is linked to the mutation in tumor protein p53 (TP53) or catenin beta 1 (CTNNB1), respectively. Gene–drug association analysis indicated that the taxanes, such as the clinically approved anticancer drug paclitaxel, are potential drugs targeting this mitotic gene signature. Accordingly, HCC cell lines harboring mutant TP53 or wild-type CTNNB1 genes are more sensitive to paclitaxel treatment. Therefore, our results imply that HCC patients with mutant TP53 or wild-type CTNNB1 genes may benefit from the paclitaxel therapy.

Research on Mechanism of miRNA-22 Related with Hepatocellular Carcinoma Metastasis for Regulating Process of Tumor Protein P53

The action of miRNA-22 related with HCC metastasis was analyzed in our study and the mechanism of miRNA-22 related with HCC metastasis was discussed. The HCC hep2 cell was transfected with miRNA-22 mimics and miRNA-22 NC instantaneously followed by analysis of cell migration by Transwell assay, cell viability by MTT and clone formation and cell apoptosis by flow cytometry. The action of miRNA-22 mimics and miRNA-22 on the expression of P53 mRNA in HCC Hep2 cell was detected by RT-PCR. The cell activity in miRNA-22 mimics group was significantly elevated compared with miRNA-22 NC group (P < 0.01). Meanwhile, the apoptotic rate, migrated and invaded capacity of HCC cell was significantly elevated (P < 0.01). The expression level of P53 mRNA was reduced (P < 0.01). In conclusion, overexpression of miRNA-22 could restrain the apoptosis of HCC hep2 cell and down-regulated the expression of P53 so as to prompt cell invasion capacity.

A Ferroptosis-Related Prognostic Signature Based on Antitumor Immunity and Tumor Protein p53 Mutation Exploration for Guiding Treatment in Patients With Head and Neck Squamous Cell Carcinoma

Background: Due to the lack of accurate guidance of biomarkers, the treatment of head and neck squamous cell carcinoma (HNSCC) has not been ideal. Ferroptosis plays an important role in tumor suppression and treatment of patients. However, tumor protein p53 (TP53) mutation may promote tumor progression through ferroptosis. Therefore, it is particularly important to mine prognostic-related differentially expressed ferroptosis-related genes (PR-DE-FRGs) in HNSCC to construct a prognostic model for accurately guiding clinical treatment.Methods: First, the HNSCC data obtained from The Cancer Genome Atlas (TCGA) was used to identify PR-DE-FRGs for screening candidate genes to construct a prognostic model. We not only used a variety of methods to verify the accuracy of the model for predicting prognosis but also explored the role of ferroptosis in the development of HNSCC from the perspective of the immune microenvironment and mutation. Finally, we explored the correlation between the prognostic model and clinical treatment and drew a high-precision nomogram to predict the prognosis.Results: Seventeen of the 29 PR-DE-FRGs were selected to construct a prognostic model with good predictive performance. Patients in the low-risk group were found to have a greater number of CD8 + T cells, follicular helper T cells, regulatory T cells, mast cells, T-cell costimulations, and type II interferon responses. A higher tumor mutation burden (TMB) was observed in the low-risk group and was associated with a better prognosis. A higher risk score was found in the TP53 mutation group and was associated with a worse prognosis. The risk score is closely related to the expression of immune checkpoint inhibitors (ICIs)-related genes such as PD-L1 and the IC50 of six chemotherapeutic drugs. The nomogram we constructed performs well in predicting prognosis.Conclusion: Ferroptosis may participate in the progression of HNSCC through the immune microenvironment and TP53 mutation. The model we built can be used as an effective predictor of immunotherapy and chemotherapy effects and prognosis of HNSCC patients.

Inhibitory Effect of the Zinc Metallochaperone NSC319726 on Ovarian Cancer Cells via the Regulation of P53

Ovarian cancer is the leading cause of death from malignancies of the female reproductive system. In recent years, there has been little development regarding the treatment of ovarian cancer. Wild-type tumor protein p53 (P53) can inhibit the development of tumor, however, mutations in P53 have been shown in most cases of ovarian cancer. The mutated gene encoded P53 transforms from a tumor suppressor gene to an oncogene, losing its original anti-tumor function. Studies have shown that the zinc metallochaperone NSC319726 can promote the correct folding of P53 in cancer cells and restore its physiological function, however, the function of NSC319726 in ovarian cancer has not been elaborated. So we investigated the role of NSC319726 on biological functions of ovarian cancer and preliminarily determined the specific molecular mechanism. The results showed that NSC319726 could inhibit proliferation, migration and invasion of ovarian cancer cells and promote their apoptosis. Mechanically, NSC319726 regains the tumor-suppressed function of P53, further activates the downstream cyclin-dependent kinase CDK inhibited protein P21, thereby blocking the cell cycle and inhibiting cells proliferation. Therefore, NSC319726 has the potential to act as a novel drug for treating ovarian cancer.

High-resolution protein fragment interactions using AVA-Seq on a human reference set

Protein-protein interactions (PPIs) are important in understanding numerous aspects of protein function. Here, the recently developed all-vs-all sequencing (AVA-Seq) approach to determine protein-protein interactions was tested on a gold-standard human protein interaction set (hsPRS-v2). Initially, these data were interpreted strictly from a binary PPI perspective to compare AVA-Seq to other binary PPI methods tested on the same hsPRS-v2. AVA-Seq recovered 20 of 47 (43%) binary PPIs from this reference set comparing favorably with other methods. The same experimental data allowed for the determination of >500 known and novel PPIs including interactions between wildtype fragments of tumor protein p53 and minichromosomal maintenance complex proteins 2, and 5 (MCM2 and MCM5) that could be of interest in human disease. Additional results gave a better understanding of why interactions might be missed using AVA-Seq and aide future PPI experimental design for maximum recovery of information.

Study on HOXBs of Clear Cell Renal Cell Carcinoma and Detection of New Molecular Target

Our study examined the transcriptional and survival data of HOXBs in patients with clear cell renal cell carcinoma (ccRCC) from the ONCOMINE database, Human Protein Atlas, and STRING website. We discovered that the expression levels of HOXB3/5/6/8/9 were significantly lower in ccRCC than in normal nephritic tissues. In ccRCC, patients with a high expression of HOXB2/5/6/7/8/9 mRNA have a higher overall survival (OS) than patients with low expression. Further analysis by the GSCALite website revealed that the methylation of HOXB3/5/6/8 in ccRCC was significantly negatively correlated to gene expression, while HOXB5/9 was positively correlated to the CCT036477 drug target. As DNA abnormal methylation is one of the mechanisms of tumorigenesis, we hypothesized that HOXB5/6/8/9 are potential therapeutic targets for patients with ccRCC. We analyzed the function of enrichment data of HOXBs in patients with ccRCC from the Kyoto Encyclopedia of Genes and Genomes pathway enrichment and the PANTHER pathway. The results of the analysis show that the function of HOXBs might be associated with the Wnt pathway and that HOXB5/6/8/9 was coexpressed with multiple Wnt pathway classical genes and proteins, such as MYC, CTNNB, Cyclin D1 (CCND1), and tumor protein P53 (TP53), which further confirms that HOXBs inhibit the growth of renal carcinoma cells through the Wnt signaling pathway. In conclusion, our analysis of the family of HOXBs and their molecular mechanism may provide a theoretical basis for further research.