Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G−LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G−LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G−LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment.
With the improvement of the average life expectancy and increasing incidence of obesity, the burden of liver disease is increasing. Liver disease is a serious threat to human health. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, liver transplantation still faces unavoidable difficulties. Mesenchymal stem cells (MSCs) can be used as an alternative therapy for liver disease, especially liver cirrhosis, liver failure, and liver transplantation complications. However, MSCs may have potential tumorigenic effects. Exosomes derived from MSCs (MSC-Exos), as the important intercellular communication mode of MSCs, contain various proteins, nucleic acids, and DNA. MSC-Exos can be used as a delivery system to treat liver diseases through immune regulation, apoptosis inhibition, regeneration promotion, drug delivery, and other ways. Good histocompatibility and material exchangeability make MSC-Exos a new treatment for liver diseases. This review summarizes the latest research on MSC-Exos as delivery vehicles in different liver diseases, including liver injury, liver failure, liver fibrosis, hepatocellular carcinoma (HCC), and ischemia and reperfusion injury. In addition, we discuss the advantages, disadvantages, and clinical application prospects of MSC-Exos-based delivery vectors in the treatment of liver diseases.
移植病理学是器官移植领域的重要学科,在肝移植精准诊治中发挥重要作用[1].随着全视野数字图像(whole slide imaging, WSI)技术和数字病理学(digital pathology,DP)的兴起,通过人工智能(artificial intelligence,AI)对组织病理图像进行深度学习,可以有效挖掘组织图像中人类视觉无法发现的隐匿信息,并对其进行定量分析.AI辅助移植病理提高了病理学家对移植组织病理的分析效率和诊断准确性.在肝移植领域,基于AI的移植病理在肝移植供肝评估、受者原发病诊断、术中快速病理评估、术后病理诊断和肝移植结局预测等方面得到了广泛应用.基于AI的移植病理在辅助肝移植精准诊断和治疗中具有良好的潜力、广泛的前景和巨大的临床应用价值.
目的 调查在校大学生对新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的认知、态度和行为(简称知信行,KAP)情况,并分析其影响因素,为高校常态化疫情防控提供参考.方法 采用随机抽样法,自编调查问卷,通过微信+问卷星形式对山东省3所高校1268名在校大学生进行问卷调查,内容包括人口学信息和对COVID-19的知信行情况.结果 知信行现状方面,认知均分为(12.25±1.19)分,态度(行为技巧)得分为(38.10±4.57)分,行为(有效行为)得分为(55.66±5.35)分.性别、年级、专业不同的大学生对COVID-19的认知存在差异(P<0.05).户口类型、是否有医疗保险、目前健康状况不同的大学生对COVID-19的态度存在差异(P<0.05).户口类型、是否有医疗保险、年级、专业、目前健康状况不同的大学生对COVID-19的行为存在差异(P<0.05).相关性分析结果显示,大学生的认知和行为无相关性(r=0.022,P=0.431),态度和行为呈正相关(r=0.450,P<0.001).大学生采取有效行为的因素为态度(行为技巧)、年级、目前健康状况.结论 大学生对COVID-19总体认知水平较高,态度较积极,多数大学生能采取有效措施积极防控,建议学校根据不同专业、不同年级、不同健康状况的学生继续加强对COVID-19知识的宣教,做好常态化疫情防控措施.