Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown. Gene ontology (GO) and pathway enrichment analyses were performed to investigate the functions and pathways of DEGs. Pathway-net and signal-net analyses were conducted to identify the key genes and pathways related to PHF20. Expression of 540 genes, including FEN1 and CCL3, were significantly altered upon PHF20 gene silencing. GO analysis results showed that DEGs were significantly enriched in small molecule metabolic and apoptotic processes. Pathway analysis indicated that DEGs were mainly involved in cancer and metabolic pathways. The MAPK, apoptosis and p53 signaling pathways were identified as the hub pathways in the pathway network, while PLCB1, NRAS and PIK3 s were hub genes in the signaling network. Our findings indicated that PHF20 is a pivotal upstream regulator. It affects the occurrence and development of glioma by regulating a series of tumor-related genes, such as FEN1, CCL3, PLCB1, NRAS and PIK3s, and activation of apoptosis signaling pathways. Therefore, PHF20 might be a novel biomarker for early diagnosis, and a potential target for glioblastoma therapies.
Background: Jaranol has shown a wide range of pharmacological activities; however, no study has yet examined in vivo toxicity. The study aimed to investigate the oral acute and sub-acute toxicity of jaranol in mice.Methods: The acute toxicity was determined by a single oral dose of jaranol (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The jaranol (50, 100 and 200 mg/kg BW·d−1) was given by gavage for 28 days daily in the sub-acute study. The mouse body weight (BW), organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied in acute and sub-acute toxicity.Results: During the acute toxicity test, a single oral dose (2000 mg/kg) jaranol did not cause significant alteration in majority of the hematological indices. However, jaranol decreased the level of serum alanine aminotransferase and aspartate aminotransferase. Those results showed that the oral lethal dose 50 (LD50) of jaranol was higher than 2000 mg/kg BW, regardless of sex. In repeated daily oral doses (50, 100 and 200 mg/kg BW·d−1), no mortality was recorded in the various experimental groups. The jaranol reduced body weight gain (200 mg/kg BW·d−1), the relative spleen weight (all doses) and serum alanine aminotransferase activity (200 mg/kg BW·d−1). On the other hand, jaranol significantly elevated red blood cell count (100 and 200 mg/kg BW·d−1) and serum creatinine levels (200 mg/kg BW·d−1). Histological study revealed that spleen bleeding was identified in 200 mg/kg jaranol-treated mice.Conclusion: Jaranol was relatively safe in Kunming Mice when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on jaranol to ensure that its use is free of potential toxicity to humans.
Prostate cancer (Pca) is the second common cancer in men worldwide. Although prostate-specific antigen (PSA) screen can serve as a diagnostic marker in most of the patients with Pca, its diagnostic specificity is insufficient, and the false positive rate can result in unnecessary biopsy increasing pain and treatment costs in patients. Exosomes are source for mRNA, microRNA, non-encoded RNA, protein, and lipids. In recent years, exosome are used for assessment of tumors and serve as tumor markers for early diagnosis and disease prognosis. This article highlights the application of exosomes in connection with diagnosis, treatment and prognosis of Pca.