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AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.bbi.2020.02.009
Junyang Li 1 , Meicen Liu 1 , Jin Gao 1 , Yu Jiang 1 , Limin Wu 2 , Yuen-Ki Cheong 3 , Guogang Ren 3 , Zhuo Yang 1
Affiliation  

Abstract Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.

中文翻译:

AVNP2 通过抑制大鼠肿瘤相关炎症来防止 C6 神经胶质瘤引起的认知障碍

摘要 胶质母细胞瘤是一种起源于中枢神经系统的恶性肿瘤。在上个世纪,一些研究人员和临床医生注意到,恶性胶质瘤患者的社会心理和神经认知功能可能会受损。许多临床研究表明,部分诊断为胶质母细胞瘤的患者,无论是成人还是儿童,在临床过程中都会出现认知缺陷,尤其是长期存活者。许多纳米颗粒 (NPs) 可以通过调节肿瘤相关炎症来抑制肿瘤的生物学功能,从而引发血管生成和肿瘤生长。作为最好的抗病毒纳米粒子 (AVNP) 之一,AVNP2 是第二代 AVNP2,已与石墨-石墨烯共轭以提高理化性能并降低毒性。AVNP2 可以灭活病毒,例如 H1N1 和 H5N1 流感病毒,甚至 SARS 冠状病毒,同时它抑制细菌,例如 MRSA 和大肠杆菌。作为抗菌剂,纳米颗粒被认为是治疗化合物给药的载体之一。然而,人们对它们对癌症神经毒性作用的潜在功能和毒性知之甚少。在此,我们探讨了 AVNP2 在抑制胶质瘤大鼠 C6 方面的功能。新的物体识别测试和开放场测试表明,AVNP2 显着改善了受 C6 胶质瘤影响的神经行为。AVNP2 还缓解了 C6 诱导的长时程增强 (LTP) 的下降和 CA1 区域树突棘密度的降低。Western印迹分析和免疫荧光染色显示突触相关蛋白(PSD-95和SYP)的表达增加,这些发现与上述结果一致。结果表明,在用AVNP2治疗后,荷C6胶质瘤大鼠的肿瘤体积更小。Western blotting 和 ELISA 检测炎症因子(IL-1β、IL-6 和 TNF-α)表达降低,Western blotting 检测血管生成蛋白(VEGF)和其他相关蛋白(BDNF、NF-ĸB、iNOS 和 COX- 2)通过在肿瘤周围组织中的蛋白质印迹分析表明,AVNP2 可以控制肿瘤相关炎症,从而有效地改善局部炎症状况,并在一定程度上抑制荷 C6 大鼠的血管生成。综上所述,
更新日期:2020-07-01
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