Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide. Despite intense efforts to elucidate its pathogenesis, the molecular mechanisms and genetic characteristics of this cancer remain unknown. In this study, three expression profile data sets (GSE15641, GSE16441 and GSE66270) were integrated to identify candidate genes that could elucidate functional pathways in ccRCC. Expression data from 63 ccRCC tumors and 54 normal samples were pooled and analyzed. The GSE profiles shared 379 differentially expressed genes (DEGs), including 249 upregulated genes, and 130 downregulated genes. A protein-protein interaction network (PPI) was constructed and analyzed using STRING and Cytoscape. Functional and signaling pathways of the shared DEGs with significant p values were identified. Kaplan-Meier plots of integrated expression scores were used to analyze survival outcomes. These suggested that FN1, ICAM1, CXCR4, TYROBP, EGF, CAV1, CCND1 and PECAM1/CD31 were independent prognostic factors in ccRCC. Finally, to investigate early events in renal cancer, we screened for the hub genes CCND1 and PECAM1/CD31. In summary, integrated bioinformatics analysis identified candidate DEGs and pathways in ccRCC that could improve our understanding of the causes and underlying molecular events of ccRCC. These candidate genes and pathways could be therapeutic targets for ccRCC. www.aging-us.com 12060 AGING Table 1. GO and KEGG pathway enrichment analysis of DEGs in ccRCC samples.

Clear cell renal cell carcinoma (ccRCC) is the most common malignant type of kidney cancer. This study aims to explore the underlying mechanism and potential targets of the traditional Chinese medicine Bu-Shen-Jian-Pi-Fang (BSJPF) in the treatment of ccRCC based on network pharmacology. After obtaining the complete composition information for BSJPF from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we analyzed its chemical composition and molecular targets and then established a pharmacological interaction network. Twenty-four significantly differentially expressed genes and 9 pathways mainly related to tumor proliferation were identified and screened. Functional enrichment analysis indicated that the potential targets might be significantly involved in glycolysis and the HIF-1 signaling pathway. To further confirm the effect of BSJPF on ccRCC cell proliferation, a BALB/c xenograft mouse model was constructed. Potential targets involved in regulating glycolysis and the tumor immune microenvironment were evaluated using RT-qPCR. VEGF-A expression levels were markedly decreased, and heparin binding-EGF expression was increased in the BSJPF group. BSJPF also inhibited tumor proliferation by enhancing GLUT1- and LDHA-related glycolysis and the expression of the immune checkpoint molecules PD-L1 and CTLA-4, thereby altering the immune-rejection status of the tumor microenvironment. In summary, this study demonstrated that the mechanism of BSJPF involves multiple targets and signaling pathways related to tumorigenesis and glycolysis metabolism in ccRCC. Our research provides a novel theoretical basis for the treatment of tumors with traditional Chinese medicine and new strategies for immunotherapy in ccRCC patients.

It was to investigate the role of Gegen Qinlian decoction (GQD) in the regulation of ABTB1 gene based on PI3K/AKT/FOXO1 signaling pathway in colorectal cancer (CRC) metastasis. In this study, 10 cases of the CRC mouse model were established by inoculating CT26 cells into the spleen of mice, which were divided into the experimental group and the control group, 5 cases in each group; the control group was intragastrically administered with normal saline 0.3 mL/d, and the experimental group was intragastrically administered with GQD 0.2 mL/d at a ratio of 0.2 g medicinal materials/10 g for 10 days and sacrificed, and pathological sections were made. The expression density of signaling pathway PI3K/AKT/FOXO1 as well as gene ABTB1 was detected in the sections of the two groups, and the mechanism of action of this gene in the two groups of mice was studied. It was found that the densities of p-PI3K, p-AKT, and p-FOXO1 in the experimental group of mice were 26.55 g/cm3, 70.2 g/cm3, and 24.36 g/cm3, respectively, which were significantly increased compared with the control group, P < 0.05 ; the density of ABTB1 was 35.4 g/cm3, which was significantly increased compared with the control group, P < 0.05 ; the proliferation and migration ability of CRC cells in the experimental group were significantly decreased, P < 0.05 . GQD can promote the expression of ABTB1 by activating the PI3K/AKT/FOXO1 signaling pathway, in order to inhibit the proliferation and growth ability of CRC cells.

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The high accumulation and poor penetration of nanocarriers in tumor is a contradiction of nanomedicine, which reduces the efficacy of chemotherapy. Due to the positive effect of hyperthermia on in vivo drug diffusion, we designed a magnetothermally sensitive micelle (MTM) by integrating magnetic targeting (MT), magnetic hyperthermia (MH), and magnetothermally responsive drug release to facilitate simultaneous drug accumulation and penetration in tumor. Accordingly, we synthesized a cyanine7-modified thermosensitive polymer with phase transition at 42.3°C, and utilized it to prepare drug-loaded MTMs by encapsulating superparamagnetic MnFe2O4 nanoparticles and doxorubicin (DOX). The obtained DOX–MTM had not only high contents of DOX (9.1%) and MnFe2O4 (38.7%), but also some advantages such as superparamagnetism, high saturation magnetization, excellent magnetocaloric effect, and magnetothermal-dependent drug release. Therefore, DOX–MTM improved in vitro DOX cytotoxicity by enhancing DOX endocytosis under the assistance of MH. Furthermore, MT and MH enhanced in vivo DOX–MTM accumulation and DOX penetration in tumor, respectively, substantially inhibiting tumor growth (84%) with excellent biosafety. These results indicate the development of an optimized drug delivery system with MH and MH-dependent drug release, introducing a feasible strategy to enhance the application of nanomedicines in tumor chemotherapy.

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