Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada.
Biomolecules. 2024 Oct 9;14(10):1271. doi: 10.3390/biom14101271.
Each life is challenged to adapt to an ever-changing environment with integrity-simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer.
每一种生命都面临着一个挑战,那就是要在不断变化的环境中保持完整性,也就是保持其身份,以适应环境。简单来说,就是要维持体内的动态平衡。我们假设这种自适应稳态的任务说明在适应性反应中尤为突出,如炎症。如果炎症反应没有得到解决,就会导致慢性疾病的发生。我们提出了分子指纹的概念:这是一种身份丧失的生物特征,作为衡量炎症反应后不完全恢复到体内平衡的指标。随着时间的推移,个人的分子指纹可以衡量慢性炎症性疾病的动态和精确轨迹,以及进一步向癌症发展的过程中自我的丧失。为什么这很重要呢?因为已确立的复杂炎症性疾病的表型和分子特征与复杂问题的根源相去甚远,更不用说最初的根源了。了解疾病关键萌芽种子背后的科学,可以帮助我们识别疾病易感性、恢复力和早期饮食或药物干预的分子因素。我们在大鼠结肠炎模型中验证了这一假设,该模型在理解结肠健康、疾病以及结肠炎向癌症的转变的分子机制方面已经得到了很好的建立。