Sex Differences in the Association Between Body Composition, Sarcopenic Obesity, and Periodontitis: Mediating Role of Oxidative Stress Markers.

Diabetic oral ulcers are highly prevalent, affecting over 80% of diabetic individuals, and pose a significant clinical challenge due to their recurrence, severe pain, and impact on eating and speaking [, ]. The pathogenesis of these ulcers is intricately linked to the hyperglycemic microenvironment, which disrupts local tissue homeostasis and drives chronic inflammation [–]. Prolonged high glucose levels promote the accumulation of advanced glycation end products and induce oxidative stress, leading to excessive production of reactive oxygen species (ROS) from mitochondria [, ]. This mitochondrial ROS (mROS) overload not only fuels inflammatory signaling but also impairs mitophagy — the essential quality control mechanism that clears damaged mitochondria [–]. The resultant accumulation of dysfunctional mitochondria exacerbates oxidative damage and inflammatory responses, ultimately compromising the integrity of the oral mucosal barrier and creating a vicious cycle that impedes healing []. Mitochondrial integrity is critically dependent on selenoproteins, a family of enzymes central to antioxidant defense and redox homeostasis []. Selenium, an essential trace element, is a key component of selenoproteins such as glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs), which directly mitigate mROS and maintain mitochondrial electron transport chain function [, ]. Selenium-binding protein 1 (SELENBP1) binds exogenous selenium and participates in its intracellular transport and distribution, providing raw material for selenoprotein synthesis []. Selenium deficiency or dysregulation of SELENBP1 compromises selenoprotein synthesis, abrogating their protective effects and leading to unchecked oxidative stress, impaired mitophagy, and exacerbated inflammation [, ]. This mechanistic link establishes selenium homeostasis as a critical determinant in the pathogenesis of diabetic oral ulcers through the regulation of mitochondrial function and inflammatory responses. Consequently, restoring selenoprotein function via targeted selenium delivery may represent a promising therapeutic strategy. Conventional selenium supplements suffer from poor stability and high toxicity []. Moreover, orally administered selenium is prone to metabolic degradation in the gastrointestinal tract, resulting in low bioavailability and limited therapeutic efficacy at ulcer sites []. To address these two major challenges, we designed a novel therapeutic system. Given that proteins have been shown to improve nanoparticle stability and reduce biotoxicity through their polar functional groups, a green synthesis method was developed using sericin, a natural silk-derived protein, as a biological template to form stable selenium nanoparticles (Ser-SeNPs) [, ]. Meanwhile, as microneedle (MN) patches have been reported as an effective drug delivery platform enabling direct and efficient release of therapeutic agents to target sites, Ser-SeNPs were integrated into a microneedle patch (Ser-SeNPs@MN) to achieve localized and sustained delivery []. Specifically, the microneedle tips were fabricated using rapidly dissolving hyaluronic acid (HA) to facilitate prompt release of SeNPs upon mucosal penetration. Considering the dynamic oral environment characterized by speech, mastication, and salivary flow, the backing layer was composed of polyvinyl alcohol (PVA) to provide wet-adhesive properties, ensuring prolonged retention of the patch and sustained release of SeNPs from the tips [–] (Fig. A). Collectively, this Ser-SeNPs@MN system was designed to offer a targeted, stable, and highly bioavailable platform that overcomes the inherent limitations of systemic selenium supplementation.