A Review of Vagus Nerve Stimulation for Disease: Comprehensive Theory and Evidence for Mechanisms of Action

Comprehensive physiology · 2026-03-04 · 1 citations

Vagus nerve stimulation (VNS) is an established neuromodulatory therapy approved for epilepsy, depression, obesity, stroke rehabilitation, rheumatoid arthritis, migraine, and cluster headaches. Its therapeutic potential has expanded dramatically, with growing evidence supporting its efficacy across a wide spectrum of neurological, psychiatric, cardiovascular, immunological, metabolic, and gastrointestinal disorders. Despite this progress, the field has lacked a comprehensive synthesis that unifies mechanistic insights with translational applications across organ systems. This review addresses that gap by systematically integrating current knowledge in the multifactorial mechanisms through which VNS modulates central and peripheral functions, including neuromodulator release, synaptic plasticity, autonomic regulation, neuroimmune control, and endocrine integration. In addition, this review identifies key limitations of VNS, including biological heterogeneity, technical constraints, and methodological variability, and proposes future innovations such as selective fiber targeting, closed-loop systems, and artificial intelligence-guided personalization. By providing a rigorous, system-level overview of VNS mechanisms and their translational relevance, this article serves as a foundational resource for advancing the science and clinical deployment and helping illustrate future directions for precision neuromodulation and bioelectronic medicine.

Su1707 IDIOPATHIC GASTROPARESIS IS ASSOCIATED WITH LOSS OF PDGFRA TELOCYTES AND EXPANSION OF PDGFRB CELLS

Gastrointestinal Endoscopy · 2026-05-01

Su1707 IDIOPATHIC GASTROPARESIS IS ASSOCIATED WITH LOSS OF PDGFRA TELOCYTES AND EXPANSION OF PDGFRB CELLS

Gastroenterology · 2026-05-01

Pyloric Dysfunction: A Review of the Mechanisms, Diagnosis, and Treatment

Gut and Liver · 2025-03-10 · 5 citations

Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy

The Journal of Experimental Medicine · 2025-03-27 · 10 citations

Monocytes infiltrating tumors acquire various states that distinctly impact cancer treatment. Here, we show that resistance of tumors to radiotherapy (RT) is controlled by the accumulation of monocyte-derived dendritic cells (moDCs). These moDCs are characterized by the expression of CD301b and have a superior capacity to generate regulatory T cells (Tregs). Accordingly, moDC depletion limits Treg generation and improves the therapeutic outcome of RT. Mechanistically, we demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) derived from radioresistant tumor cells following RT is necessary for the accumulation of moDCs. Our results unravel the immunosuppressive function of moDCs and identify GM-CSF as an immunotherapeutic target during RT.

Benchmarking cell type and gene set annotation by large language models with AnnDictionary

Nature Communications · 2025-10-28 · 4 citations

We develop an open-source package called AnnDictionary to facilitate the parallel, independent analysis of multiple anndata. AnnDictionary is built on top of LangChain and AnnData and supports all common large language model (LLM) providers. AnnDictionary only requires 1 line of code to configure or switch the LLM backend and it contains numerous multithreading optimizations to support the analysis of many anndata and large anndata. We use AnnDictionary to perform the first benchmarking study of all major LLMs at de novo cell-type annotation. LLMs vary greatly in absolute agreement with manual annotation based on model size. Inter-LLM agreement also varies with model size. We find that LLM annotation of most major cell types to be more than 80-90% accurate, and will maintain a leaderboard of LLM cell type annotation. Furthermore, we benchmark these LLMs at functional annotation of gene sets, and find that Claude 3.5 Sonnet recovers close matches of functional gene set annotations in over 80% of test sets. Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

The Role of Microglia in the Effects of Steroid Hormones on Brain Inflammation

Digital Commons - RU (Rockefeller University) · 2025-09-08

The conditions defining whether microglial activation is detrimental or beneficial to neuronal survival are still poorly understood. Better understanding of the factors regulating microglia activation may lead to improved therapies for neurodegenerative diseases. Clinical and animal studies point to the neuroprotective and anti-inflammatory effects of steroid hormones. However, our comprehension of the cellular targets and mechanisms of action of these hormones in the CNS is still unresolved. In view of these limitations, the main question addressed in this dissertation was the role that microglia play in the anti-inflammatory effects of steroid hormones in the brain, with particular emphasis on the neuroprotective hormone 17β-estradiol (E2), and the anti-inflammatory steroid, corticosterone. To address this problem, microglia culture models were established using a microglia cell line and primary cultures from transgenic mice that facilitate the identification of microglia by EGFP expression. Collaborative studies were also done in mice in vivo. The expression of steroid hormone receptors was studied as well as their function. This dissertation shows that microglia cells are not direct targets of estrogen actions, but respond profoundly to glucocorticoids, which exert anti-inflammatory effects on the production of cytokines like TNFα, IL-6 and NO. Steroid hormones can be produced within the brain. In this dissertation, microglia cells are shown to participate in the metabolism of steroids through expression of steroidconverting enzymes. Expression of 11βHSD1 in microglia mediated an autocrine re-activation of glucocorticoids, whereas, expression of enzymes like 17βHSD1 and 5αR catalyzed the conversion of active androgens and estrogens from steroid hormone precursors AD and DHEA. These microglia-derived hormones had estrogenic effects on neuronal cells, as described in the last section of this dissertation where the characterization and responsiveness of a neural progenitor cell line are presented. In summary, microglia cells are highly susceptible to the action of glucocorticoids, but not estrogens. This specificity is dictated by the abundant expression of glucocorticoid receptors, and a minimal expression of estrogen receptors. A novel role of microglia is also presented. Microglia express steroid-metabolizing enzymes, which mediate the autocrine reactivation of glucocorticoids, or the production of active androgens and estrogens from steroid hormone precursors.

Publisher Correction: TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells

Nature Immunology · 2025-09-05

TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells

Nature Immunology · 2025-08-12 · 11 citations

Plasmacytoid dendritic cells (pDCs) are major producers of type I interferon (IFN-I), an important antiviral cytokine, and activity of these cells must be tightly controlled to prevent harmful inflammation and autoimmunity. Evidence exists that one regulatory mechanism is a fate-switching process from an IFN-I-secreting pDC to a professional antigen-presenting conventional dendritic cell (cDC) that lacks IFN-I-secreting capacity. However, this differentiation process is controversial owing to limitations in tracking the fate of individual cells over time. Here we use single-cell omics and functional experiments to show that activated human pDCs can lose their identity as IFN-I-secreting cells and acquire the transcriptional, epigenetic and functional features of cDCs. This pDC fate-switching process is promoted by tumor necrosis factor but blocked by IFN-I. Importantly, it occurs in vivo during human skin inflammatory diseases and injury, and physiologically in elderly people. This work identifies the pDC-to-cDC reprogramming trajectory and unveils a mechanistic framework for harnessing it therapeutically.

Clinical applications of vagal nerve stimulation for gastrointestinal motility disorders and chronic abdominal pain

Elsevier eBooks · 2024-11-22