Electroacupuncture-mediated lncRNA TUG1 regulates the miR-127-3p/NF-κB p65 axis to inhibit IBS-D low-grade intestinal inflammation.

Idiopathic pulmonary fibrosis (IPF) is one of the most progressive interstitial lung diseases, and current therapeutics are known to slow disease progression, but not cure the disease []. Even though extensive research has been conducted for the last 50 years, including nearly 62,023 studies, there has been no significant progress in therapeutic intervention for IPF []. This study aims to inspire the field to embrace systems biology approaches to advance IPF research. Specifically, this study hypothesizes that the development of a molecular systems architecture of the fibrotic lung microenvironment is necessary for such advancement. The fibrotic lung microenvironment in IPF is illustrated in . This microenvironment is the locus wherein fibrosis of the lung manifests, and comprises proximal airways including ciliated, secretory, and mucus-producing goblet epithelial cells, and distal airways including alveoli. Although presents the fibrotic lung microenvironment as a schematic systems-level framework, it does not quantitatively resolve the spatial organization of cells within lung tissue. Structural cell types in the fibrotic lung microenvironment include Type I alveolar epithelial cells (AECI), Type II alveolar epithelial cells (AECII), pulmonary smooth muscle cells, mesenchymal stem cells, fibroblasts, pericytes, and endothelial cells. The distal airways in the IPF lung are shown schematically. A molecular systems architecture of this microenvironment may: (1) enable the visualization of complex bimolecular systems interactions across the fibrotic lung microenvironment involving sixteen cell types; (2) reveal the biological processes and the underlying molecular pathways leading to disease pathogenesis; (3) identify potential targets for treatment; and (4) provide a framework to develop predictive and quantitative models for drug development. Systems biology explores the interactions in living systems at multiple levels, including molecular, cellular, tissue, organ, and environmental levels, to elucidate physiological processes []. A systems biology approach aids analyses of disease conditions by quantitatively examining disrupted cellular signaling cascades that cause gain or loss of function, thereby developing targeted therapies []. Reductionist strategies still dominate current drug development, but this paradigm carries notable limitations, including a limited capacity to design curative combination therapies, an inability to fully capture the complexity of molecular interactions, and a shortage of computational tools capable of predicting systems-level adverse effects [,]. Systems biology deciphers complex biochemical networks across cellular systems, driving disease pathways and clinical phenotypes, enabling the discovery of targeted therapies. It offers a new drug development paradigm, enhancing efficacy via combinations with approved drugs [,].