Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.

中文翻译：

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缺氧在人类疾病中的病理生理影响

大多数真核生物基本上都需要氧气作为清除有害电子和氢离子的清除剂，或作为确保酶促反应正确执行的关键底物。所有有核细胞都可以感觉到氧气浓度，并对氧气供应减少（缺氧）做出反应。当氧气输送被破坏或减少时，生物体将发展出多种适应性机制，以促进细胞在低氧条件下存活。通常，当氧水平恢复时，这种低氧反应将停止。但是，如果持续存在低氧应激（慢性缺氧）或发生循环性缺氧-缺氧现象（间歇性缺氧），情况就会变得复杂。一系列连锁反应样基因的表达级联，称为缺氧介导的基因调控网络，在这种长期或间歇性的缺氧条件下会引发细胞凋亡，随后导致细胞功能和/或行为改变。结果，发生不可逆的过程，可能导致生理失调甚至病理后果。越来越多的证据表明，缺氧在包括癌症，心肌缺血，代谢性疾病和慢性心脏和肾脏疾病在内的主要死亡原因的发病机理中以及在诸如先兆子痫和子宫内膜异位的生殖疾病中起关键作用。这篇综述文章将总结目前对这些常见和重要疾病中低氧分子机制的理解。发生不可逆过程，可能导致生理失调甚至病理后果。越来越多的证据表明，缺氧在包括癌症，心肌缺血，代谢性疾病和慢性心脏和肾脏疾病在内的主要死亡原因的发病机理中以及在诸如先兆子痫和子宫内膜异位的生殖疾病中起关键作用。这篇综述文章将总结目前对这些常见和重要疾病中低氧分子机制的理解。发生不可逆过程，可能导致生理失调甚至病理后果。越来越多的证据表明，缺氧在包括癌症，心肌缺血，代谢性疾病和慢性心脏和肾脏疾病在内的主要死亡原因的发病机理中以及在诸如先兆子痫和子宫内膜异位的生殖疾病中起关键作用。这篇综述文章将总结目前对这些常见和重要疾病中低氧分子机制的理解。以及子痫前期和子宫内膜异位等生殖疾病。这篇综述文章将总结目前对这些常见和重要疾病中低氧分子机制的理解。以及子痫前期和子宫内膜异位等生殖疾病。这篇综述文章将总结目前对这些常见和重要疾病中低氧分子机制的理解。