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Cancer is a complex disease with several distinct characteristics, referred to as "cancer markers" one of which is metabolic reprogramming, which is a common feature that drives cancer progression. Over the last ten years, researchers have focused on the reprogramming of glucose metabolism in cancer. In cancer, the oxidative phosphorylation metabolic pathway is converted into the glycolytic pathway in order to meet the growth requirements of cancer cells, thereby creating a microenvironment that promotes cancer progression. The precise mechanism of glucose metabolism in cancer cells is still unknown, but it is thought to involve the aberrant levels of metabolic enzymes, the influence of the tumor microenvironment (TME), and the activation of tumor-promoting signaling pathways. It is suggested that glucose metabolism is strongly linked to cancer progression because it provides energy to cancer cells and interferes with antitumor drug pharmacodynamics. Therefore, it is critical to unravel the mechanism of glucose metabolism in tumors in order to gain a better understanding of tumorigenesis and to lay the groundwork for future research into the identification of novel diagnostic markers and therapeutic targets for cancer treatment. Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, multiple components, and less toxic side effects and has unique advantages in tumor treatment. In recent years, researchers have found that a variety of Chinese medicine monomers and compound recipes play an antitumor role by interfering with the reprogramming of tumor metabolism. The underlying mechanisms of metabolism reprogramming of tumor cells and the role of TCM in regulating glucose metabolism are reviewed in this study, so as to provide a new idea for antitumor research in Chinese medicine.

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Background: Houttuynia cordata Thunb. is a traditional Chinese herb widely used mainly because of the pharmacological effects related to heat clearance and detoxification. Emerging clinical evidence indicates that the efficacy of Houttuynia cordata Thunb. on RILI is upstanding. Nevertheless, its underlying therapeutic mechanism remains unclear and warrants further elucidation. Methods: The major active components and corresponding targets of Houttuynia cordata Thunb. were retrieved from the traditional Chinese medicine system pharmacology database (TCMSP) and literature review. The related targets of RILI were retrieved from the GeneCards database. Common targets among the active compounds and diseases were identified through Venn diagram analysis. Cytoscape was employed to construct and visualize the network relationship among the drug, active compounds, targets, and disease. The protein interaction network (PPI) was constructed by STRING. The reliability (the binding affinity) of the core targets and active compounds was verified by molecular docking. Results: A search of the TCMSP database and related literature revealed 12 active compounds of Houttuynia cordata Thunb. against RILI. The core active compounds included quercetin, kaempferol, hyperoside, and rutin. Hub nodes including TP53, VEGFA, JUN, TNF, and IL-6 were identified in the PPI network. The GO categories were classified into three functional categories: 112 biological processes, 9 molecular functions, and 32 cellular components of the active compounds of Houttuynia cordata Thunb. The KEGG pathway enrichment analysis demonstrated the enrichment of target genes in several key cancer-related signaling pathways, including the cancer pathways, TNF signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. Molecular docking analysis validated the effective binding capacity of the main active compounds with the core targets. Conclusion: The main active components of Houttuynia cordata Thunb. have a potential pharmacological effect against RILI via the cancer pathways, TNF signaling pathway, and PI3K-Akt signaling pathway.

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Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia-reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA-23b (miR-23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR-23b, MDM4, and the p53 signaling pathway-related genes was characterized in cartilaginous tissues. Then, miR-23b mimics or inhibitors were applied for the elevation or the depletion of the miR-23b expression and siRNA-MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR-23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR-23b through. Downregulated miR-23b increased the expression of MDM4, AKT, and Bcl-2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR-23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR-23b was observed after MDM4 knocked down. Our results indicate that silencing miR-23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.

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OBJECTIVE: To investigate the tumor-suppressing effect of microRNA-218 (miR-218) in osteosarcoma (OS) and explore its molecular mechanism. METHODS: We examined the expression levels of miR-218 in 68 pairs of OS and adjacent tissue samples using qRT-PCR. Cultured human OS cell line Saos-2 was transfected with miR-218 mimics or anti-miR-218 mimics, and the cell apoptosis was assessed using CCK-8 assay, annexin V-FITC staining and Western blotting. We also analyzed the potential functional targets of miR-218 in Saos-2 cells using luciferase assay, qRT-PCR and Western blotting. RESULTS: The expression level of miR-218 was lowered by at least 8 folds in OS tissues as compared with the adjacent tissues. In cultured Saos-2 cells, transfection with miR-218 mimics for 24, 36, and 48 h resulted in a significant reduction in the cell viability, while transfection with anti-miR-218 mimics significantly increased the cell viability. The cells transfected with miR-218 mimics showed an obviously enhanced expression of cleaved poly(ADP-ribose) polymerase (C-PARP) as compared with the cells transfected with anti-miR-218 mimics and the control cells. Flow cytometry demonstrated obviously increased apoptosis of the cells following miR-218 mimics transfection. We identified the oncogene B lymphoma mouse Moloney leukemia virus insertion region 1 (BMI-1) as a specific target of miR-218 in Saos-2 cells. BMI-1 expressions at both the mRNA and protein levels were significantly reduced in Saos-2 cells overexpressing miR-218 but increased in the cells with miR-218 knockdown as compared to the control cells. Luciferase reporter assay indicated that miR-218 directly inhibited the expression of BMI-1 via binding to its 3'-UTR in OS cells. CONCLUSION: miR-218 can promote OS cell apoptosis and plays the role as a tumor suppressor by down-regulating BMI-1.

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The mitochondrial flavoprotein apoptosis-inducing factor (AIF) has proved to be either the main mediator of apoptosis or an anti-apoptotic factor via its putative oxidoreductase and peroxide scavenging activities. We report here that 100 muM hydrogen peroxide (H2O2) induced the proliferation of C2C12 myoblasts and over-expression of AIF simultaneously in vitro. Immunofluorescence showed that the over-expression of AIF was located in the cytoplasm. The immunopositive AIF was detected in nuclei 27 days after denervation of skeletal muscle, but in the cytoplasm it was detected 27 days after fiber-damaged skeletal muscle. AIF may be a factor involved in skeletal muscle regeneration.

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