Single-Cell Transcriptional Profiling Reveals Low-Level Tragus Stimulation Improves Sepsis-Induced Myocardial Dysfunction by Promoting M2 Macrophage Polarization

Abstract

Background. Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. Methods. A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Results. Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1β expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Conclusion. Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.

Hormesis Responses of Growth and Photosynthetic Characteristics in Lonicera japonica Thunb. to Cadmium Stress: Whether Electric Field Can Improve or Not?

“…It is known that numerous studies focus on the toxicity of high-dose environmental contaminants [ 31 , 32 , 33 , 34 ]; however, some low-dose environmental contaminants may have beneficial effects on organisms [ 35 , 36 , 37 ]. The beneficial effects of low-dose environmental contaminants is widely recognized in the field of toxicology and medicine, where it is defined as “hormesis”, characterized by a biphasic adaptive response [ 38 , 39 , 40 ].…”

Maresin-2 Fine-tunes ULK1 O-GlcNAcylation to Improve Post Myocardial Infarction Remodeling

“…Auricular tragus vagus nerve stimulation (tVNS) which evidently improved cardiac vagus activity was performed as ever reported 29,30 . Briefly, a chronic intermittent low-grade tVNS was delivered (20 Hz frequency, 1 ms pulse width, 1 mA aptitude, 1s interval bilateral) per day over the auricular cymba conchae region at each ear via a (Yuyan Ltd, Shanghai) for 30 min over 4-week period, following which myocardial infarction was induced.…”

“…To assess the extent of myocardial injury, hematoxylin-eosin staining and sirius red staining were performed to assess the myocardial injury as previously described 29 .…”

Retracted: Single-Cell Transcriptional Profiling Reveals Low-Level Tragus Stimulation Improves Sepsis-Induced Myocardial Dysfunction by Promoting M2 Macrophage Polarization

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”