Integrative approach using network pharmacology, bioinformatics, and experimental methods to explore the mechanism of cantharidin in treating colorectal cancer.

Cantharidin, a terpenoid produced by blister beetles, has been used in traditional Chinese medicine to treat various ailments and cancers. However, its biological activity, impact, and anticancer mechanisms remain unclear. The Cantharidin chemical gene connections were identified using various databases. The GSE21815 dataset was used to collect the gene expression information. Differential gene analysis and gene ontology analyses were performed. Gene set enrichment analysis was used to assess the activation of disease pathways. Weighted gene co-expression network analysis and differential analysis were used to identify illness-associated genes, examine differential genes, and discover therapeutic targets via protein-protein interactions. MCODE analysis of major subgroup networks was used to identify critical genes influenced by Cantharidin, examine variations in the expression of key clustered genes in colorectal cancer vs. control samples, and describe the subject operators. Single-cell GSE188711 dataset was preprocessed to investigate Cantharidin's therapeutic targets and signaling pathways in colorectal cancer. Single-cell RNA sequencing was utilized to identify 22 cell clusters and marker genes for two different cell types in each cluster. The effects of different Cantharidin concentrations on colorectal cancer cells were studied in vitro. One hundred and ninety-seven Cantharidin-associated target genes and 480 critical genes implicated in the development of the illness were identified. Cantharidin significantly inhibited the proliferation and migration of HCT116 cells and promoted apoptosis at certain concentrations. Patients on current therapy develop inherent and acquired resistance. Our study suggests that Cantharidin may play an anti-CRC role by modulating immune function.

Dexmedetomidine suppresses the isoflurane-induced neurological damage by upregulating Heme Oxygenase-1 via activation of the mitogen-activated protein kinase kinase 1/extracellular regulated protein kinases 1/nuclear factor erythroid 2-related factor 2 axis in aged rats.

Dexmedetomidine (DEX) displays a neuroprotective role in aged rats with isoflurane (ISO)-induced cognitive impairment through antioxidant, and anti-inflammatory, and anti-apoptotic effects. Therefore, the present study was performed to define the molecular mechanism of DEX on ISO-induced neurological impairment in aged rats in relation to the MEK1/ERK1/Nrf2/HO-1 axis. The study enrolled elderly patients undergoing ISO anesthesia. Patient cognitive function following treatment with DEX was evaluated using mini-mental state examination (MMSE). The results revealed that DEX supplementation of anesthesia contributed to higher MMSE scores in patients one week post treatment. Rat model of neurological impairment was also induced in 18-month-age Wistar rats by ISO, followed by DEX treatment. Based on the results of Morris water maze experiment, ELISA, and TUNEL and hematoxylin-eosin staining, in vivo experiments confirmed that DEX could reduce the oxidative stress and neurological damage induced by ISO in rats. DEX activated the nuclear factor erythroid 2-related factor (Nrf2)/Heme Oxygenase 1 (HO-1) pathway. DEX upregulated the expression of Nrf2 and HO-1 by activating the MEK1/ERK1 pathway, whereby attenuating the ISO-caused oxidative stress and neurological damage in rats. Collectively, DEX suppresses the ISO-induced neurological impairment in the aged rats by promoting HO-1 through activation of the MEK1/ERK1/Nrf2 axis.