铁死亡在神经胶质瘤治疗中的作用

铁死亡是一种铁依赖性脂质过氧化物损伤诱导的调节性细胞死亡形式,其在分子生物学、形态学和遗传学等方面都不同于凋亡、自噬和坏死等细胞死亡形式。铁死亡在神经胶质瘤的治疗中发挥重要作用,诱导胶质瘤细胞铁死亡将成为治疗肿瘤的新策略。本文对铁死亡的相关基因xCT、Nox4、NCOA4、BECN1在神经胶质瘤治疗中的作用及中药在神经胶质瘤中对铁死亡的治疗作用进行阐述,以期为神经胶质瘤的临床治疗提供新方向和新思路。     

铁死亡抑制蛋白1在铁死亡相关疾病中的研究进展

铁死亡抑制蛋白1(ferroptosis-suppressor-protein 1,FSP1)是一种黄素蛋白,具有还原型烟酰胺腺嘌呤二核苷酸（NADH）：泛醌（CoQ）10氧化还原酶活性,能够将CoQ10还原为二氢泛醌（CoQH2）,后者可以清除细胞内的活性氧和脂质自由基,达到抑制铁死亡的作用。因此,高表达FSP1的肿瘤细胞表现为对多种通过诱导细胞铁死亡发挥作用的抗癌药物的耐药;反之组织中FSP1表达水平的降低会增加其对铁死亡和氧化应激的敏感性,导致部分铁死亡相关疾病的发生和进展。     

抑制铁死亡治疗实验性帕金森病研究进展

帕金森病（PD）是一种与大脑铁稳态失调有关的神经退行性疾病,其特征是多巴胺能神经元退行性变。铁死亡是一种由脂质过氧化过度驱动的铁依赖性调节性细胞死亡,参与帕金森病的发病机制。PD患者表现出的脂质过氧化水平升高、谷胱甘肽耗竭、DJ-1和辅酶Q10缺乏、谷胱甘肽过氧化酶4减少、线粒体病变、铁累积和α突触核蛋白聚集均与铁死亡相关。越来越多证据显示,抑制铁死亡具有神经保护作用,在体外和体内PD模型中具有干预帕金森病发展的作用。本文总结了铁死亡参与PD发病机制研究进展,重点总结了铁死亡抑制剂干预PD的应用,为靶向干预铁死亡治疗和预防PD提供参考依据。     

铁死亡在骨代谢中的调控机制

铁死亡是一种新型的细胞死亡方式,以细胞内铁过载和脂质过氧化物过度积累为特征,与多种骨科疾病的发生密切相关。骨质疏松是以骨密度降低为主要病理表现的慢性代谢性骨病,近年来随着研究的不断深入,发现铁死亡对骨代谢着重要的影响,而通过对铁死亡的调节以维持骨稳态,在骨质疏松的防治领域取得了一定的突破,展现出了良好的应用前景。该文阐述了铁死亡的发生机制和调节途径,梳理了铁死亡对骨代谢的调控机制,并总结了铁死亡在骨质疏松症发病及治疗中的研究进展,以期拓宽骨代谢的研究思路。     

细胞铁死亡在急性肾功能损伤中的研究进展

急性肾损伤是由各种病理、药物等因素引起的短时间内肾功能突然或持续下降。近年来,铁死亡作为一种新的调控性细胞死亡方式被逐渐认识,其由细胞谷胱甘肽抗氧化防御系统的失活,导致脂质过氧化产物和活性氧堆积诱发。铁死亡代谢网络和体内分子信号网络以及多种病理反应途径存在交互作用,并被认为与急性肾损伤的病理生理过程密切相关,抑制肾小管上皮细胞铁死亡可有效缓解急性肾损伤的发生发展,目前围绕靶向铁死亡的急性肾损伤治疗策略在肾脏疾病研究中已成为一大研究热点。该文主要就铁死亡的发生调控机制、与急性肾损伤的关系以及靶向铁死亡的治疗策略进行综述,以期为急性肾损伤的治疗提供新的视角。     

铁死亡的调控机制及其在肝疾病中的作用研究进展

铁死亡是近年来新发现的一种细胞死亡方式,是由于细胞内铁离子水平异常升高,导致氧化还原失衡,细胞膜发生脂质过氧化,最终细胞膜破裂导致细胞死亡。目前认为铁死亡的中心环节是铁代谢和活性氧代谢。铁死亡涉及多种生理和病理过程,包括癌细胞死亡、神经毒性、缺血再灌注损伤和T细胞免疫等。越来越多的研究表明,在多种肝病的发生发展过程中,均出现不同程度的铁过载以及脂质活性氧堆积等铁死亡特征,而铁死亡可以通过调节细胞内铁离子水平及脂质过氧化程度,影响肝疾病的进程。因此,调控铁死亡可能是一种新的治疗肝疾病的策略。本文综述了铁死亡及其在肝疾病中的研究进展,为探索肝疾病的治疗方法提供理论基础。     

铁死亡与胃癌治疗的研究进展

铁死亡是由铁依赖的细胞膜脂质过氧化物超载驱动的调节性细胞死亡形式,因具有独特的形态学和生化学特征而区别于细胞凋亡、自噬和坏死。胃癌发病率高,对化疗药物耐药率高,预后差,急需寻求更好的治疗方法。近年来铁死亡与恶性肿瘤、神经系统疾病、急性肾损伤、肠缺血/再灌注损伤等多种疾病的研究取得了较大进展,已经引起了全世界的关注,并可能成为未来一个新的治疗靶点。本文综述铁死亡分子机制及其作用于胃癌的研究进展。了解铁死亡在消化道肿瘤发病机制中的作用,有助于提出癌症治疗的新靶点。     

肝移植围术期诱发肠损伤铁死亡的研究新进展

铁死亡（ferroptosis）是近年来新发现的,以铁依赖性的脂质活性氧（lipid reactive oxygen species,L-ROS）过度积累为特征的一种新的细胞程序性死亡方式,其与铁代谢、脂质代谢和氨基酸代谢等多种代谢调控途径相关。本文概述铁死亡相关概念、形态及生化特征、调控机制,以及铁死亡在肝移植围术期...     

肿瘤内源性代谢异常在前列腺癌发生发展中的研究进展

近年来,前列腺癌的发病率在我国逐年上升,严重影响男性的健康状况,而以雄激素阻断为主线的前列腺癌治疗方案总是面临着去势抵抗的困境.随着代谢组学概念在肿瘤领域的深入拓展,前列腺癌细胞内的代谢重编程受到越来越多研究者的关注.了解前列腺癌细胞内的代谢变化及其相关的分子机制,可为探究前列腺癌的病因和寻找有效的诊断标志物及治疗策略...     

靶向铁死亡的癌症疗法

铁死亡是一种铁依赖性的,由脂质活性氧累积所引发的调节性细胞死亡方式。铁死亡的启动和执行取决于铁稳态、脂质代谢和抗氧化系统的交集。基于对铁死亡与癌症相关信号通路之间交互作用的深入了解,已设计和开发了一系列诱导癌细胞铁死亡的试剂,包括实验性化合物、临床药物和纳米材料。本文综述了铁死亡的调节机制和靶向铁死亡的癌症疗法。     

Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.     

Role of metabolism and viruses in aflatoxin-induced liver cancer

The use of biomarkers in molecular epidemiology studies for identifying stages in the progression of development of the health effects of environmental agents has the potential for providing important information for critical regulatory, clinical and public health problems. Investigations of aflatoxins probably represent one of the most extensive data sets in the field and this work may serve as a template for future studies of other environmental agents. The aflatoxins are naturally occurring mycotoxins found on foods such as corn, peanuts, various other nuts and cottonseed and they have been demonstrated to be carcinogenic in many experimental models. As a result of nearly 30 years of study, experimental data and epidemiological studies in human populations, aflatoxin B(1) was classified as carcinogenic to humans by the International Agency for Research on Cancer. The long-term goal of the research described herein is the application of biomarkers to the development of preventative interventions for use in human populations at high-risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiological studies and are now being used as intermediate biomarkers in prevention studies. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have subsequently been utilized in experimental models to provide data on the modulation of these markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases.     

Targeting sphingolipid metabolism in head and neck cancer: rational therapeutic potentials

Importance of the field: Ceramide accumulation has been shown to be a conserved mechanism of apoptosis initiation in normal physiological processes as well as in response to cancer treatments. Therefore, it is unsurprising that many cancers develop aberrations of sphingolipid metabolism that prevent the accumulation of ceramide, whether by reduction of ceramide generation or by enhanced ceramide catabolism, particularly dangerous when catabolism leads to generation of pro-tumor sphingosine-1-phosphate and ceramide-1-phosphate. Numerous studies have now implicated dysregulation of sphingolipid metabolism in head and neck cancers.

Areas covered in this review: This review highlights the importance of sphingolipid metabolism and brings sphingolipid metabolism to the forefront in the investigation of novel therapies for head and neck cancer. It reviews sphingolipid-centric therapies under investigation in preclinical and clinical trials of cancers of the head and neck.

What the reader will gain: The roles of sphingolipids and sphingolipid metabolism in cancer are reviewed and the reader will be brought up to date with discoveries in the field of sphingolipid metabolism in head and neck cancer.

Take home message: As treatments for head and neck cancers are currently limited, the potential of targeting sphingolipid metabolism should be taken into consideration as we seek novel ways to combat this group of tumors.     

肝脏脂代谢与非酒精性脂肪肝研究进展

非酒精性脂肪肝（NAFLD）是指除酒精和其他明确的损伤肝脏的因素所致的,以弥漫性肝细胞肥大、泡性肝脂肪变性为主要特征的临床病理综合征。近年来,非酒精性脂肪肝患者数量在逐年升高,已严重威胁人类健康。本文主要从肝脏脂代谢的过程讨论了肝脏脂代谢和非酒精性脂肪肝的关系的研究进展。     

青蒿琥酯通过介导铁死亡逆转结肠癌细胞5-氟尿嘧啶耐药的作用研究

目的 探讨青蒿琥酯(ART)通过介导铁死亡逆转结肠癌细胞对5-氟尿嘧啶(5-FU)耐药的作用。方法 以人结肠癌HT-29/5-FU耐药细胞株为研究对象,采用MTS法检测5-FU、ART以及5-FU+ART对HT-29/5-FU细胞的抑制作用,并计算其逆转耐药倍数;克隆形成实验检测HT-29/5-FU细胞克隆形成能力;流式细胞术检测细胞内活性氧(ROS)水平;试剂盒检测细胞内丙二醛(MDA)水平;Western blotting检测细胞内Nrf2和GPX4蛋白表达水平。结果 40μmol·L^-1ART可逆转HT-29/5-FU细胞对5-FU的耐药,逆转倍数为2.9倍;5-FU联合ART可抑制HT-29/5-FU细胞的克隆形成能力,升高细胞内ROS和MDA水平,并降低Nrf2及GPX4蛋白表达水平,且这些效应能够被铁死亡抑制剂Ferrostatin-1所逆转。结论 ART能够通过抑制Nrf2、GPX4表达诱导铁死亡,从而逆转HT-29/5-FU细胞对5-FU的耐药。     

小鼠肝癌模型研究进展

我国是全球肝癌发病率最高和病死数最多的国家,肝癌患者约占全球的55%,因此肝癌的研究一直是我国临床和基础研究的热点.肝癌动物模型,尤其是小鼠肝癌模型,是研究肝癌生物学特性、发病机理、药物筛选和肝癌治疗的重要工具.本文简要回顾近年来常用的小鼠肝癌模型,为肝癌发生相关的基因功能研究提供思路和方向.     

蜂毒素治疗肝癌的机制及相关制剂研究进展

蜂毒素作为蜂毒的主要组成成分和活性单位,是由26个氨基酸残基组成的碱性多肽,具有抗菌、抗关节炎、镇痛、抗辐射等广泛的生物学功能;近年来蜂毒素的抗肿瘤作用受到越来越多的关注和研究。本篇对蜂毒素抑制肝癌发展进程中诱导肝癌细胞凋亡、抑制肿瘤细胞转移和抗血管生成,调节免疫等机制研究,以及针对蜂毒素肽存在过敏反应、溶血等副作用进行减毒增效的改造研究作一综述,旨在探讨蜂毒素治疗肝癌的机制及可能应用于临床的制剂类型。