This study aimed at investigating the inhibitory effects and the anti-tumor mechanisms of co-administration of fusion pro-teins gonadotropin-releasing hormone(GnRH)and hVEGF-GnRH3(VG)on B16F10 melanoma in C57BL/6J mice model.The metastasis of melanoma can be promoted by overexpression of the targeting antigens GnRH and VG.VG vaccine has been shown to elicit an immune inflammatory response against prostate cancer.Hence the authors hypothesized VG also has potential to prevent melanoma angiogenesis,progression and recurrence.Recombinant protein hVEGF-GnRH3 was extracted by E.coli expression system and purified by DEAE anion exchange chromatography to prepare protein vaccine.B16F10 melanoma cells were transplanted into male C57BL/6J mice(1 x 106 cells per mouse)to construct a melanoma model.The tumor-bearing mice were immunized with VG protein vaccine for three cycles.Thereafter,the tumor suppressing effect of the vaccine was evaluated from the aspects of tumor growth,angiogenesis and tumor histology,periphery and splenocytes humoral,cellular,and intracellular immunomodulation also included.The results showed that the volumes and angiogenesis of melanoma were significantly inhibited in VG group(P<0.01).Compared to the PBS group,VG increased the levels of anti-GnRH,anti-VEGF IgG and circulating interferon-gamma(IFN-γ)in mice serum,while the level of IL-6 was significantly decreased.In the spleen-related experiments,the MTT assay showed that VG vaccine promoted splenocytes prolife-ration and cytotoxicity.At the same time,further analysis of intracellular cytokines revealed a significant increase in CD3+CD4+INF-γ+cells.The results above indicate that VEGF-GnRH3 is a promising vaccine for the treat-ment of melanoma.
糖尿病是当今世界上最常见且普遍的慢性代谢性疾病之一,对于肾脏、心脑血管、神经、眼睛等均有极大的危害性.目前糖尿病主要包括以下四种:1型糖尿病、2型糖尿病、妊娠期糖尿病和特殊类型糖尿病.2017年我国糖尿病患病率持续上升至17.2%,其中2型糖尿病(Type 2 diabetes mellitus,T2DM)比例高达90%以上,因此糖尿病也已成为实施健康中国战略,提升健康水平亟待攻克的难题.肥胖是一种由环境、遗传、饮食、年龄等多种因素相互作用而引起的一种机体代谢紊乱综合征,也是糖尿病发生的重要诱因.T2MD患者和许多肥胖患者都表现出胰岛素刺激的葡萄糖吸收和利用的效率下降,胰岛β细胞出现代偿性增殖并增加总胰岛素的分泌水平从而达到稳定血糖的作用,这一现象被称为胰岛素抵抗(Insulin resistance,IR).胰岛素是通过其信号通路从而在机体中发挥调控作用,如果整个通路中的某一部分受到损害发生损伤,通路因此无法将上游信息正常传递至下游,胰岛素的调控作用将受到削弱甚至可能消失.当IR发生时,若通路受损,胰岛素无法调控全身葡萄糖稳态.随着IR的发展,当胰腺不能提供过量的胰岛素时,就会导致全身葡萄糖稳态的严重失衡,这将会诱发T2MD以及许多代谢性疾病.近年来已有大量以IR病理机制为主题的研究被报道,文章聚焦于以肥胖及胰岛素信号通路受损为主的IR诱导机制,整理并阐述了相关研究进展,以期为未来的进一步研究提供思路与依据.
实验探究了重组Monellin菌株的最佳培养条件,并对其进行了甜味阈值确认和血糖值影响实验.实验所用菌种为实验室构建保存的BL21(DE3)-pET28a Monellin菌种,利用不同浓度的乳糖和IPTG诱导该菌种生成目的蛋白,探究其最佳诱导条件,利用镍柱亲和层析纯化目的蛋白后进行相对甜度和甜味阈值实验,随后设置甜度梯度,对小鼠进行灌胃比较蔗糖和Monellin的升血糖作用及不同浓度Monellin对血糖的影响.实验结果表明,0.9 mmol/L IPTG诱导5 h的Monellin表达量最多,其甜味阈值为100μg/mL,相对甜度为蔗糖的800倍.灌胃结果表明,Monellin升血糖作用不显著,并且在一定范围内对血糖的影响不随其浓度的改变而发生变化.该实验为Monellin在糖尿病等代糖食品市场上的应用提供了科学的理论依据.
前列腺六段跨膜上皮抗原(Six-segment transmembrane epithelial antigen of prostate,STEAP)家族属于跨膜蛋白,其在细胞与细胞之间的通讯方面起着重要作用.STEAP具有离子通道功能,在体内可发挥金属氧化还原酶活性,广泛参与调控细胞增殖、凋亡、迁移和侵袭等生命活动.在多数肿瘤细胞中STEAP均呈现过表达的趋势,与正常的组织细胞表达量形成显著差异,这种表达特异性,预示其可作为治疗癌症的潜在靶标.文章主要针对STEAP家族中的成员STEAP1,对其蛋白结构功能、正常细胞与肿瘤细胞之间的表达差异以及靶向策略作一简要综述,用以评估其作为肿瘤治疗靶点的可行性.