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Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.

ABSTRACT: TOLLIP (Toll-interacting protein) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic-reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole trafficking. The distinct functions of this protein have been linked to innate immune responses and lung epithelial-cell apoptosis. TOLLIP genetic variants have been associated with a variety of chronic lung diseases, including idiopathic pulmonary fibrosis, asthma, and primary graft dysfunction after lung transplantation, and with infections, such as tuberculosis, Legionella pneumonia, and respiratory viruses. TOLLIP exists in a delicate homeostatic balance, with both positive and negative effects on the trajectory of pulmonary diseases. This translational review summarizes the genetic and molecular associations that link TOLLIP to the development and progression of noninfectious and infectious pulmonary diseases. We highlight current limitations of in vitro and in vivo models in assessing the role of TOLLIP in these conditions, and we describe future approaches that will enable a more nuanced exploration of the role of TOLLIP in pulmonary conditions. There has been a surge in recent research evaluating the role of this protein in human diseases, but critical mechanistic pathways require further exploration. By understanding its biologic functions in disease-specific contexts, we will be able to determine whether TOLLIP can be therapeutically modulated to treat pulmonary diseases.

SUBMITTER: Li X

PROVIDER: S-EPMC8086045 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMinimally invasive surgery had been tailored to individual cases of gastric subepithelial tumors (SETs) after comparing the clinical outcomes of endoscopic resection (ER), laparoscopic resection (LR), and hybrid methods.AimTo study the use of Goldilocks principle to determine the best form of minimally invasive surgery for gastric SETs.MethodsIn this retrospective study, 194 patients of gastric SETs with high probability of surgical intervention were included. All patients underwent tumor resection in the operating theater between January 2013 and December 2021. The patients were divided into two groups, ER or LR, according to the tumor characteristics and the initial intent of intervention. Few patients in the ER group required further backup laparoscopic surgery after an incomplete ER. The patients who had converted open surgery were excluded. A logistic regression model was used to assess the associations between patient characteristics and the likelihood of a treatment strategy. The area under the curve was used to assess the discriminative ability of tumor size and Youden's index to determine the optimal cut-off tumor size.ResultsOne-hundred ninety-four patients (100 in the ER group and 94 in the LR group) underwent tumor resection in the operating theater. In the ER group, 27 patients required backup laparoscopic surgery after an incomplete ER. The patients in the ER group had small tumor sizes and shorter procedure durations while the patients in the LR group had large tumor sizes, exophytic growth, malignancy, and tumors that were more often located in the middle or lower third of the stomach. Both groups had similar durations of hospital stays and a similar rate of major postoperative complications. The patients in the ER group who underwent backup surgery required longer procedures (56.4 min) and prolonged stays (2 d) compared to the patients in the LR group without the increased rate of major postoperative complications. The optimal cut-off point for the tumor size for laparoscopic surgery was 2.15 cm.ConclusionMultidisciplinary teamwork leads to the adoption of different strategies to yield efficient clinical outcomes according to the tumor characteristics.

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Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.

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