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维生素 D 状态与肾细胞癌患者的血清 C 反应蛋白和黏附分子相关。

The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma.

机构信息

Department of Oncology, First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China.

Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, China.

出版信息

Sci Rep. 2019 Nov 13;9(1):16719. doi: 10.1038/s41598-019-53395-9.

Abstract

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.

摘要

维生素 D 状态低下与肾细胞癌(RCC)的风险增加有关。本研究调查了维生素 D 状态与 RCC 患者血清 C 反应蛋白(CRP)和黏附分子之间的关系。招募了 50 名新诊断的 RCC 患者和 100 名年龄和性别匹配的对照者。正如预期的那样,RCC 患者的血清 25(OH)D 水平低于对照组。相比之下,RCC 患者的血清 CRP 水平(一种炎症分子)和 ICAM、LAMA4 和 EpCAM(三种黏附分子)水平高于对照组。所有 RCC 患者均分为两组:H-VitD(>20ng/ml)或 L-VitD(<20ng/ml)。有趣的是,L-VitD 组的 RCC 患者的血清 CRP 和所有黏附分子水平均高于 H-VitD 组。癌细胞中的核维生素 D 受体(VDR)下调,核因子 κB(NF-κB)被激活。体外实验发现 VitD3 抑制了 RCC 细胞中的 NF-κB 激活和黏附分子。此外,VitD3 通过在 RCC 细胞中增强 VDR 和 NF-κB p65 亚基之间的物理相互作用来抑制 NF-κB。这些结果为维生素 D 状态低下、局部炎症和 RCC 患者黏附分子表达增加之间的关联提供了机制解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e0/6853912/3702587c3008/41598_2019_53395_Fig1_HTML.jpg

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