It has been suggested that multi-omic, single-cell studies may be deployed to disclose the underlying switches or bifurcations behind the development of a disease. In the paragraph “Limitations to the hypothesis”, it has been considered that the multistability of molecular feedback loops concerns behaviors at the level of individual cells that not necessarily spread uniformly to whole tissues or organs. Conversely, the article hypothesis assumes the occurrence of, and is focused on, multistable transitions as point-like events at the root of these processes. In the paragraph “A loopomic hypothesis in pathophysiology”, it has been clarified that the development of diseases observed in clinical setting, appearing as gradual progressions rather than abrupt changes, is the result of cascade events realizing complex patterns that hinder disease management. A total of five new references have been introduced. Two new paragraphs have been introduced: “Limitations to the hypothesis” and “Hypothesis validation”. Major differences with respect to the previous version. Consequently, the hypothesis holds that the starting mechanism of any disease that affects a healthy human can be conceptually reduced to a bistable or multistationary loop system, thus providing a unifying model leading to the discovery of critical therapeutic targets. The present hypothesis makes a generalization, by assuming that any functional element of a biological system is involved in a positive or a negative feedback loop. Negative feedback loops have been known for a long time to maintain homeostasis, while more recently, different life processes involved in transitions or changes have been modeled by positive loops giving rise to bistable switches, also including various diseases. The stability of metabolism, despite the enormous complex of chemical reactions, suggests that reciprocal control is a prerequisite of life. A hypothesis is proposed here assuming that these difficulties are due to an unsuitable approach to the mechanisms of life, which is subjugated by an apparent complexity and fails to grasp the uniformity that lays behind. Despite intensive investigations numerous diseases remain etiologically puzzling and recalcitrant to treatments.
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