Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein–protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1β) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production—all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

The non-saponin (NS) fraction is an important active component of Panax ginseng, with multifunctional pharmacological activities including neuroprotective, immune regulatory, anti-inflammatory, and antioxidant effects. However, the effects of NSs on multiple sclerosis (MS), a chronic and autoimmune demyelinating disorder, have not yet been demonstrated. and Methods: The goal of the present study was to demonstrate the pharmacological actions of NSs on movement dysfunctions and the related mechanisms of action using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. NSs (p.o.) alleviated movement dysfunctions in EAE mice related to reduced demyelination in the lumbar spinal cord (LSC). NSs attenuated the recruitment of microglia (CD11b⁺/CD45^low) and macrophages (CD11b⁺/CD45^high) in LSCs from EAE model mice, consistent with the decreased mRNA expression levels of the main proinflammatory mediators (IL-1β, COX-2, MCP-1, MIP-1α, and RANTES). NSs blocked the migration of Th17 cells (CD4⁺/IL17A⁺) and mRNA expression levels of IL-17A (product of Th17 cells) in LSCs from EAE mice. NSs suppressed alterations in blood-brain barrier (BBB) components, such as astrocytes and cell adhesion molecules, associated with inhibiting NF-κB and p38 MAPK pathways in LSCs of EAE mice and lipopolysaccharide-induced bEND.3 cells. NSs could attenuate movement dysfunctions and related pathological/inflammatory changes by reducing BBB permeability through NF-κB and p38 MAPK pathway inhibition in LSCs of EAE model mice. These are the first results suggesting that NSs can be potential therapeutic agents for MS by reducing BBB permeability.

The relationship between sleep and epilepsy involves complex interactions between thalamocortical circuits, circadian mechanisms, and sleep architecture that fundamentally influence seizure susceptibility and cognitive outcomes. Epileptic activity disrupts essential sleep oscillations, particularly sleep spindles generated by thalamic circuits. Thalamic epileptic spikes actively compete with physiological sleep spindles, impairing memory consolidation and contributing to cognitive dysfunction in epileptic encephalopathy. This disruption explains why patients with epilepsy often experience learning difficulties despite adequate seizure control. Sleep stages show differential seizure susceptibility. REM sleep provides robust protection through enhanced GABAergic inhibition and motor neuron suppression, while non-REM sleep, particularly slow-wave sleep, increases seizure risk. These observations reveal fundamental mechanisms of seizure control within normal brain physiology. Circadian clock genes (BMAL1, CLOCK, PER, CRY) play crucial roles in seizure modulation. Dysregulation of these molecular timekeepers creates permissive conditions for seizure generation while being simultaneously disrupted by epileptic activity, establishing a bidirectional relationship. These mechanistic insights are driving chronobiological therapeutic approaches, including precisely timed antiseizure medications, sleep optimization strategies, and orexin/hypocretin system interventions. This understanding enables a paradigm shift from simple seizure suppression toward targeted restoration of physiological brain rhythms, promising transformative epilepsy management through sleep-informed precision medicine.