Nannocystins are a family of 21-membered cyclodepsipeptides with excellent anticancer activity. Yet their macrocyclic architecture poses a significant challenge to structure modification. Herein this issue has been addressed by leveraging...
Network pharmacology, as a novel way using bioinformatics to explore drug targets and interactions in cancer, broadens our understanding of drug action, thereby facilitating drug discovery. Here, we utilized network pharmacology to explore the role and mechanism by which cinobufotalin functions in colon adenocarcinoma (COAD). We found that cinobufotalin represses the growth and proliferation of colon cancer cells, and integrated public databases for targets reported to be associated with COAD, together with those predicted to be targets of cinobufotalin. Targets overlapped between COAD-associated proteins and cinobufotalin target proteins were used to filter candidate targets of cinobufotalin in COAD. The following proteins were thought to occupy a key position in COAD-cinobufotalin target networks: SRC, PIK3R1, MAPK1, PIK3CA, HSP90AA1, CTNNB1, GRB2, RHO1, PTPN11, and EGFR. The networks regulated by cinobufotalin were involved mainly in extracellular signal stimulation and transduction, including MAPK signaling pathway, PI3K-AKT signaling pathway, and JAK-STAT signaling pathway. Besides, transcriptome sequencing results also indicated that cinobufotalin inhibits the response of colon cancer cells to extracellular stimulation and promotes cell apoptosis. Molecular docking results showed that cinobufotalin matches in the pocket of the top candidate cinobufotalin target proteins (SRC, PIK3R1, MAPK1 and PIK3CA). These findings demonstrate cinobufotalin can be developed as potential anti-cancer therapeutics.
Background: Up-regulated expression of copper chaperone for superoxide dismutase (CCS) is identified in a multitude of tumors and is closely related to more malignant tumoral biological behaviors. However, little is known about the role of CCS in hepatocellular carcinoma (HCC). This study aims to explore the expression pattern and the significance of CCS in human HCC.Methods: Fresh samples of HCC with paired adjacent tissues were obtained from 32 patients who underwent hepatectomy. The expression levels of CCS and representative malignant biomarkers in HCC were investigated by western blotting and immunohistochemistry staining, respectively. The correlation between the expression status of CCS and the activities of selected malignant biomarkers and important drive genes of HCC oncogenesis, patient’s clinicopathological features and prognosis, were analyzed. Additional bioinformatics investigation of dataset retrieved from database were performed to further explore the role of CCS in human HCC. Results: The majority of the HCC tumor (78.1%, 25/32) presented a lower expression of CCS, whereas in the minority of the tumor (22.9%, 7/32) the expression of CCS was determined as higher. Furthermore, it was found that the expression level of CCS was significantly correlated with malignant biomarkers. The expression of CCS was reversely correlated with ES grade and TNM stage to some extent. And there is a significant correlation between the CCS gene and a series of genes in the development and progression of HCC. Patients with higher CCS expression level were prone to have a better prognosis. Conclusion: HCC presented a unique lower expression pattern of CCS which reversely correlated with the more malignant tumoral features and poor prognosis.
The current coronavirus disease-19 (COVID-19) caused by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has seriously disrupted the daily life of human, mainly attributed to the fact that we know too little about SARS-CoV-2. Increasing studies show that viral infection alters host cells glucose metabolism, which is crucial for viral nucleic acid replication. Here, we integrated RNA-sequencing results and found that SARS-CoV-2 infection alters the aerobic glycolysis, pentose phosphate pathway (oxiPPP), and DNA replication in lung tissues and cells. However, the direction of metabolic flux and DNA replication were dominated by angiotensin-converting enzyme 2 (ACE2), a host cell-expressed viral receptor protein. More interesting, although hosts with high expression of ACE2 are more likely to be infected with SARS-CoV-2, the invading virus cannot perform nucleic acid replication well due to the restriction of glucose metabolism, and eventually resulting prolonged infection-cycle or infection failure. Our findings, after a typical epidemiological investigation and modeling analysis, preliminarily explain the reasons for the emergence of asymptomatic infections or lower copy virus at early stage in host with higher ACE2 levels, which will provide important help for the development of more accurate and effective detection methods for diagnosing COVID-19.
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