Anemia of chronic disease(ACD)is the most frequent clinical issue in patients with chronic disease.ACD is usually secondary to chronic kidney disease(CKD),cancer,and chronic infection,which is associated with poor hea...Anemia of chronic disease(ACD)is the most frequent clinical issue in patients with chronic disease.ACD is usually secondary to chronic kidney disease(CKD),cancer,and chronic infection,which is associated with poor health outcomes,increased morbidity and mortality,and substantial economic costs.Current treatment options for ACD are very limited.The discovery of the hypoxia-inducible factor-prolyl hydroxylase(HIF-PHD)pathway made it possible to develop novel therapeutic agents(such as hypoxia-inducible factor-prolyl hydroxylase inhibitor,HIF-PHI)to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin(EPO)production and iron absorption and utilization.Thus,HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism.Here,we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD.Specifically,we highlighted the key features of HIF-PHIs on ACD,such as stimulation of endogenous EPO,handling iron metabolism,inflammation-independent,and prolonging lifespan of red blood cells.In conclusion,the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.展开更多
肺癌是我国发病率和死亡率增长最快,对人群健康和生命威胁最大的恶性肿瘤,其发生发展机制尚未完全清楚。肿瘤的低氧微环境发现于1955年,而肺癌组织低氧直至2006年才被成功检测到。随着研究的深入,低氧对肺癌的影响不仅限于对放疗的抵抗...肺癌是我国发病率和死亡率增长最快,对人群健康和生命威胁最大的恶性肿瘤,其发生发展机制尚未完全清楚。肿瘤的低氧微环境发现于1955年,而肺癌组织低氧直至2006年才被成功检测到。随着研究的深入,低氧对肺癌的影响不仅限于对放疗的抵抗作用,而且还会通过一个重要的促癌分子低氧诱导因子(hypoxia inducible factor,HIF)以及其调节蛋白脯氨酸羟化酶(prolyl hydroxylase domain,PHD)和希佩尔林道病基因产物(product of von Hippel-Lindau gene,pVHL)对肺癌的发生发展、侵袭转移、化疗耐药以及预后等产生重要的调节作用。因此,低氧、HIF、PHD和pVHL必将成为十分有潜力的肺癌治疗靶点。展开更多
基金This work was supported by the grants from the National Natural Science Foundation of China(Nos.82230022and 82030024)the Natural Science Foundation of Jiangsu Province(No.BK20240212).
文摘Anemia of chronic disease(ACD)is the most frequent clinical issue in patients with chronic disease.ACD is usually secondary to chronic kidney disease(CKD),cancer,and chronic infection,which is associated with poor health outcomes,increased morbidity and mortality,and substantial economic costs.Current treatment options for ACD are very limited.The discovery of the hypoxia-inducible factor-prolyl hydroxylase(HIF-PHD)pathway made it possible to develop novel therapeutic agents(such as hypoxia-inducible factor-prolyl hydroxylase inhibitor,HIF-PHI)to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin(EPO)production and iron absorption and utilization.Thus,HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism.Here,we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD.Specifically,we highlighted the key features of HIF-PHIs on ACD,such as stimulation of endogenous EPO,handling iron metabolism,inflammation-independent,and prolonging lifespan of red blood cells.In conclusion,the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.
文摘肺癌是我国发病率和死亡率增长最快,对人群健康和生命威胁最大的恶性肿瘤,其发生发展机制尚未完全清楚。肿瘤的低氧微环境发现于1955年,而肺癌组织低氧直至2006年才被成功检测到。随着研究的深入,低氧对肺癌的影响不仅限于对放疗的抵抗作用,而且还会通过一个重要的促癌分子低氧诱导因子(hypoxia inducible factor,HIF)以及其调节蛋白脯氨酸羟化酶(prolyl hydroxylase domain,PHD)和希佩尔林道病基因产物(product of von Hippel-Lindau gene,pVHL)对肺癌的发生发展、侵袭转移、化疗耐药以及预后等产生重要的调节作用。因此,低氧、HIF、PHD和pVHL必将成为十分有潜力的肺癌治疗靶点。
