Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I.

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.

High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR-663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor-ß1.

BACKGROUND: Whether microRNAs participate in endothelial dysfunction HUA remains unknown. A previous study indicated that miR-663 was the most significantly differentially expressed endothelial microRNA under HUA conditions. Some studies have demonstrated that the miR-663 target gene and TGF-ß1, promoted endothelial cell migration by inhibiting PTEN deleted on chromosome 10. Therefore, we hypothesized that HUA inhibits endothelial migration via miR-663, which regulates PTEN by targeting TGF-ß1. METHODS: PCR analysis was performed to determine miR-663 expression levels. A luciferase assay was performed to validate whether miR-663 targets TGF-ß1 directly. Western blot analysis was performed to determine TGF-ß1 and PTEN expression levels. An miR-663 inhibitor and TGF-ß1- and PTEN-specific siRNAs were transfected into EA.hy926 cells to inhibit miR-663, TGF-ß1, and PTEN expression, respectively. A wound healing assay was performed to determine the migratory ability of EA.hy926 cells. RESULTS: miR-663 had higher expression levels in HUA-stimulated endothelial cells and in the sera of hyperuricemic patients and animals. TGF-ß1 was targeted directly by miR-663. Endothelial miR-663 was up-regulated under HUA conditions, and HUA inhibited endothelial cell migration via miR-663, which targeted TGF-ß1. Thus, TGF-ß1 regulated cell migration in a PTEN-dependent manner. CONCLUSION: HUA inhibits endothelial cell migration via miR-663, which regulates PTEN by targeting TGF-ß1.