Recent advances in drug repurposing for dentin repair.

Bioengineered polycaprolactone nanofibers co-loaded with RGD and asiatic acid for dentin-pulp regeneration.

Berberine pretreatment enhances the homing and anti-inflammatory efficacy of dental pulp mesenchymal stem cells in TNBS-induced inflammatory bowel disease via activating the CXCR4/SDF-1 signaling pathway.

This study evaluated the biocompatibility of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSC) loaded in gelatin methacryloyl hydrogel microspheres (sEVs@GM-MS), and examined their effects on the proliferation and migration of human dental pulp stem cells (hDPSCs)/human umbilical vein endothelial cells (HUVECs), as well as their capacity to promote endothelial cell tube formation. Pulpotomy in a rat molar model was used to assess sEVs@GM-MS as a potential pulp-capping agent. sEVs@GM-MS were prepared and physicochemically characterized. In vitro assessments included live/dead staining, Cell Counting Kit-8 (CCK-8), migration assay and tube formation assay. In vivo, 7 and 14days after pulpotomized with sEVs@GM-MS, GM-MS, iroot BP or without any pulp capping material, rat molars were evaluated using hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining. GM-MS exhibited a porous surface via scanning electron microscopy. PKH67-labeled sEVs@GM-MS showed sustained release of sEVs. The cell proliferation, migration, tube formation in the sEVs@GM-MS group were significantly enhanced compared with those of the NC and GM-MS groups (p < 0.05). In rat pulpotomy model, sEVs@GM-MS group exhibited significant cell proliferation, angiogenesis, and reparative dentinogenesis with immunocytochemical localization of PCNA, CD31 and DMP-1 compared to NC and GM-MS groups (p < 0.05). Compared with the BP group, the sEVs@GM-MS group showed no significant difference in DMP-1 positive expression (p > 0.05). sEVs@GM-MS demonstrated excellent biocompatibility, sustained hUCMSC-sEV release, and enhanced pulp/dentin repair and regenaration, highlighting their potential as a pulp-capping agent.

Mechanical Signaling in the Microenvironment Regulates the Differentiation of Dental Pulp Stem Cells: A Novel Strategy For Pulp-Dentin Complex Regeneration.

To delineate the mechanisms underlying the role of lactate-related lactylation, a novel post-translational modification, in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Dynamic levels of key glycolytic enzymes and histone lactylation along odontogenic differentiation in hDPSCs were evaluated by Western Blot and quantitative PCR (qPCR). Odontogenic differentiation was assessed via Alkaline Phosphatase and Alizarin Red S staining after treatment with sodium lactate, both with and without p300 knockdown. CUT&Tag sequencing of histone H3K18 lactylation (H3K18la) was performed, and genes identified through this analysis were subjected to pathway enrichment. WNT5A-knockdown hDPSCs were generated to elucidate the impact of both WNT5A and WNT5A/Ca2+ signalling axis in odontogenesis. Finally, we validated the critical function of lactylation in dentine regeneration using a subcutaneous ectopic transplantation model in nude mice with and without sodium lactate via intraperitoneal injection. The similar dynamic trends were observed in glycolytic enzyme expression, intracellular lactate and lactylation levels in hDPSCs. Exogenous lactate dose-dependently increased H3K18 lactylation and significantly promoted hDPSC odontogenic differentiation. Mechanistically, the key lactyltransferase p300 was demonstrated to be a regulator that enhanced lactate-induced H3K18la modification and odontogenic differentiation in hDPSCs. CUT&Tag sequencing identified WNT5A as a target gene whose promoter exhibited increased H3K18la enrichment upon lactate treatment. Lactate upregulated WNT5A expression and activated the WNT5A/Ca2+ signalling pathway via p300-mediated H3K18la, consequently accelerating the odontogenic differentiation. Further invivo evidence revealed that lactate administration promoted pulp-like tissue regeneration, accompanied by increased hDPSC odontogenic marker expression and H3K18la levels in nude mice with subcutaneously transplanted dentine slices. The lactate-driven mechanism acts through the p300-mediated H3K18la-WNT5A/Ca2+ signalling axis to promote the odontogenic differentiation of hDPSCs. The crosstalk between metabolism, epigenetic modifications and signalling pathways of hDPSCs might offer novel strategies for dental pulp regeneration.

High-resolution fluorescence microscopy dataset for neuron segmentation and morphological analysis

The clinical management of dental caries encompasses a spectrum of therapeutic approaches, ranging from conservative restorative procedures to complex endodontic interventions. In cases involving pulp exposure or reversible pulpal injury, vital pulp therapy procedures are considered essential strategies for preserving pulp vitality and maintaining tooth function. This explains the focus of some recent works on developing tissue engineering (TE) approaches, particularly those involving dental stem or progenitor cells, to produce functional dental tissues. Hydrogel-based scaffolds, highly biocompatible three-dimensional (3D) bio/polymeric networks, are particularly attractive because of their ability to mimic the native extracellular matrix and thus serve as suitable scaffolds for tissue engineering, especially for dental pulp regeneration. Their versatility makes them a good candidate for a range of tissue engineering models, and hydrogel-based scaffolds are proving particularly valuable in regenerative medicine. This work reviews both natural and synthetic polymers, focusing on their structures and emerging uses in the regeneration of the dentin-pulp complex.

Adult stem cells (SCs) maintain tissue homeostasis through a balance of self-renewal and differentiation regulated by biochemical and mechanical cues. While biochemical pathways are well studied, the in vivo mechanisms by which external forces influence SCs and their progeny remain poorly understood. The continuously growing mouse incisor offers a tractable model for investigating these mechanisms because dental epithelial stem cells (DESCs) reside in a spatially restricted apical niche, and their progeny undergo stereotyped proliferation and differentiation along the apical-incisal axis. We investigated how intrusive mechanical loading affects dental epithelial cell kinetics and enamel regeneration during injury repair. A modified orthodontic tooth movement device was adapted to apply controlled intrusive forces (0.05-0.5N) to the mouse mandibular incisor. To stimulate regeneration, the incisal tip was trimmed, and mice were subjected to force application for three days, followed by recovery after device removal. Dental epithelial responses were evaluated using histology, dual EdU/BrdU labeling, in situ hybridization, and micro-computed tomography. Expression of proliferation (Ccnb1) and differentiation (Igfbpl1) markers, as well as nuclear localization of the mechano-responsive transcription co-factor YAP, were analyzed. Forces ≥ 0.2N caused adverse health effects, whereas 0.05N induced consistent epithelial changes without systemic consequences. At 0.05N loading, incisors showed delayed regeneration and hypomineralized enamel. The apical epithelium exhibited folds, tears, reduced proliferation, and premature amelogenin expression. These effects reversed after load removal, coinciding with restored proliferation and enamel deposition. Gene expression analysis revealed apical-incisal shifts in Ccnb1 and Igfbpl1 domains, consistent with altered cell kinetics. Mechanistically, loading decreased nuclear YAP localization in the central body of the labial cervical loop, suggesting a role for this mechanosensitive pathway in mediating the cellular response to mechanical force. This study presents an in vivo model for examining mechanical influences on dental epithelial progenitor cells. Intrusive loading suppresses proliferation, promotes precocious differentiation, and alters epithelial architecture. These findings support a role for mechanical cues in modulating tissue regeneration and provide a framework for future mechanistic studies in tooth biology.

This study characterized the expression profile of miR-153-3p in deciduous pulpitis in children, validated its role in regulating inflammation, oxidative stress, and apoptosis via PTEN targeting, and evaluated its biomarker and therapeutic potential. In a prospective design, pulp tissue was collected from 180 children with deciduous-tooth pulpitis (mild, moderate, or severe) and 180 caries-free controls. qRT-PCR was used to quantify miR-153-3p and PTEN expression, VAS pain scores were recorded, and ROC analysis was performed. An LPS-induced inflammatory model (5µg/mL, 24h) was established in human dental pulp stem cells, which were transfected with miR-153-3p mimic or PTEN overexpression plasmid. Cell viability, apoptosis, inflammatory cytokines, and oxidative stress markers were subsequently assessed, and correlations among miR-153-3p, VAS, and PTEN were evaluated. miR-153-3p was significantly downregulated in inflamed pulp and inversely correlated with disease severity and VAS score (r = - 0.323, P < 0.001), with an ROC AUC of 0.814. LPS suppressed miR-153-3p and elevated PTEN in a concentration- and time-dependent manner. miR-153-3p upregulation restored viability, reduced apoptosis, decreased cytokine release, increased SOD activity, and lowered MDA content. Dual-luciferase assays confirmed PTEN as a direct target, and PTEN overexpression reversed the protective effects of miR-153-3p. These findings indicate that miR-153-3p downregulation is associated with inflammation severity, and that miR-153-3p attenuates LPS-induced cellular responses by inhibiting PTEN. Its utility in assessing tissue inflammation and potential as a therapeutic target warrant further in vitro and in vivo validation.

Stem cell transplantation holds great promise for facial nerve repair, yet its efficacy is largely constrained by the excessive accumulation of reactive oxygen species (ROS) and the highly inflammatory microenvironment. Thus, developing bioactive scaffolds with robust antioxidant capacity for stem cell transplantation remains a challenge. In this study, an injectable and self-healing composite hydrogel composed of chitosan, graphene oxide, and cerium oxide nanoparticles (CeNPs) was developed to provide structural support for the neural conduit, create a favorable microenvironment for human dental pulp stem cells (hDPSCs), and effectively promote facial nerve regeneration. The hydrogel exhibited intrinsic shear-thinning, self-recovery, and self-healing properties, ensuring its adaptability to irregular nerve defects and suitability for minimally invasive delivery, while its ROS-scavenging activity effectively reshaped the injury microenvironment to mitigate oxidative stress and inflammatory responses in the transplanted cells. In vitro, the composite hydrogel promoted the specific migration of hDPSCs, while alleviating cellular oxidative damage by modulating the PI3K/AKT signaling pathway to facilitate M2 polarization of macrophages. In a facial nerve defect model, treatment with the hydrogel in combination with hDPSCs significantly improved neurological function and tissue regeneration, achieving morphological and functional outcomes comparable to those of autologous nerve grafts. Collectively, this CeNPs-integrated hydrogel provides adaptive structural support, modulates the injury microenvironment, and promotes stem cell migration, representing a promising bioactive platform with clinical translational potential for facial nerve repair.

Dental pulp inflammation triggers immune responses involving macrophages and dental pulp stem cells (DPSCs), which interact to regulate angiogenesis essential for tissue repair. M1 pro-inflammatory macrophages predominate early in pulpitis, and clarifying their angiogenic role is vital in identifying inflammatory regenerative mechanisms. THP-1 cells and peripheral blood monocyte (PBM)-derived macrophages were polarized to M1 or M2 phenotypes, characterized by qRT-PCR, ELISA, and angiogenesis arrays. A vasculature-on-a-chip comprising DPSCs, human umbilical vein endothelial cells (HUVECs) and THP-1-derived macrophages was imaged, and the vascular segments/sprouts were quantified using ImageJ. Density effects used 5 × 104 versus 7.5 × 104 M1 macrophages/device, with propidium iodide staining for cytotoxicity. IL-8 effects on DPSC VEGF secretion were assessed by ELISA (with/without Reparaxin 1 μM), Matrigel tube formation assays, and exogenous IL-8 (0.5 ng/mL). Transwell co-cultures underwent RNA sequencing and bioinformatics analysis, which identified candidate hub genes and signalling pathways; the results were validated by Western blotting (p-ERK, HIF-1α; ERK inhibitor SCH772984, 25 nM). Statistical testing was performed using ANOVA with Tukey's post hoc test (p < 0.05). M1 macrophages at low density (5 × 104 cells/device) significantly enhanced vascularization in the vasculature-on-a-chip, increasing vascular segments (p < 0.0001) and free sprouts (p < 0.05-0.01) compared to M0 or no-macrophage controls, with effects comparable to M2. High-density M1 seeding (7.5 × 104 cells/device) reduced sprouts (p < 0.0001 day 4, p < 0.01 day 5) due to increased cytotoxicity (p < 0.0001). Both THP-1- and PBM-derived M1-conditioned media (CM) showed significantly elevated IL-8 levels. M1 CM (THP-1/PBM) induced DPSC VEGF secretion, blocked by Reparaxin (p < 0.01-0.0001), confirming IL-8 mediation via CXCR1/2. Exogenous IL-8 (0.5 ng/mL) upregulated DPSC VEGF protein/mRNA (p < 0.05) and Matrigel tube formation (segments/junctions p < 0.05). M1-DPSC CM enhanced vascular meshes/segments on Matrigel (p < 0.05), reduced by Reparaxin. RNA-seq of M1 co-cultured DPSCs identified 17 angiogenic genes (logFC > 1.2), with HIF-1α as a hub gene and an enriched MAPK/ERK pathway. Western blot analysis confirmed MAPK/ERK-HIF-1α as a contributory pathway in IL-8-induced upregulation of VEGF in DPSCs. M1 macrophages promote angiogenesis via IL-8-induced DPSC VEGF secretion through CXCR1/2-MAPK/ERK-HIF-1α signalling density-dependently, suggesting that therapeutic modulation rather than total suppression of M1 activity could improve outcomes in vital pulp therapy.

ABSTRACTObjectivesTo investigate the effects of dental pulp stem cell‐derived conditioned medium (DPSC‐CM) on the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Primary goals were to (i) identify the optimal DPSC‐CM' concentration and (ii) evaluate its effect both independently (under Growth Medium, [GM]) and synergistically (under Osteogenic Medium [OM]).Materials and MethodsDPSC‐CM was collected, and an initial screen was conducted to determine their maximum non‐toxic concentration (MNTS). For functional assays, three non‐cytotoxic concentrations (V/V) (10% [CM‐10], 30% [CM‐30], 50% [CM‐50]) were selected. While cytokine release profile, cell proliferation, and migration were assessed under GM conditions, differentiation was evaluated over 14d under both GM and OM conditions (p < 0.05).ResultsThe MNTS was established as CM‐50. DPSC‐CM promoted all cellular activities in a non‐linear, concentration‐specific manner. CM‐10 demonstrated the most beneficial effects; it yielded the highest levels of TGF‐β1 and VEGF secretion (p < 0.05), and significantly increased proliferation, alkaline phosphatase activity, and expression of osteogenic/angiogenic markers than CM‐50 and CM‐30 over time. However, peak cell migration was observed on Day 2 for both CM‐30 and CM‐10. While DPSC‐CM alone enhanced osteogenesis, the highest induction was achieved under OM conditions.ConclusionsDPSC‐CM is a potent osteoinductive agent, enhancing proliferation, migration, and differentiation in a non‐linear concentration‐specific manner. The lowest concentration proved optimal for their proliferative and osteogenic properties, suggesting a Hormesis‐like effect where higher doses may become sub‐optimal due to inhibitory factors.

The pathogenesis of pulpitis remains unclear. This study sought to investigate the molecular mechanism by which the long noncoding RNA FOXD2-AS1 participates in pulpitis through regulating the miR-338-3p/THBS1 axis. 110 irreversible pulpitis patients and 80 healthy orthodontic patients were enrolled as the pulpitis and control groups, respectively. Human dental pulp stem cells (hDPSCs) were cultured and stimulated with lipopolysaccharide (LPS) to establish a pulp inflammation model. Expression of FOXD2-AS1, miR-338-3p, and THBS1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, while levels of inflammatory cytokines and osteogenesis-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). THBS1 protein expression was validated by Western blot. The target regulation was verified by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. In pulpitis tissues, FOXD2-AS1 and THBS1 expression were significantly upregulated, while miR-338-3p expression was significantly downregulated. Furthermore, FOXD2-AS1 demonstrated high diagnostic value for pulpitis. Functional experiments demonstrated that FOXD2-AS1 negatively regulated osteoblast differentiation and promoted LPS-induced inflammatory responses. Specifically, it inhibited alkaline phosphatase (ALP) activity and odontogenic differentiation-related protein expression, reduced cell viability, and promoted inflammatory cytokine release. Moreover, FOXD2-AS1 targeted and adsorbed miR-338-3p, while miR-338-3p directly targeted and inhibited THBS1 expression, forming the FOXD2-AS1/miR-338-3p/THBS1 regulatory axis. Rescue experiments demonstrated that knocking down FOXD2-AS1 exerted anti-inflammatory and pro-osteogenic effects by upregulating miR-338-3p and inhibiting THBS1. Conversely, inhibiting miR-338-3p reversed these protective effects, manifesting as exacerbated inflammation and diminished odontogenic differentiation capacity. On this basis, further knocking down THBS1 reinstates the anti-inflammatory and pro-osteogenic phenotype. In conclusion, FOXD2-AS1 mediates pulpitis inflammation and odontogenic differentiation imbalance by competitively binding to miR-338-3p to upregulate THBS1 expression.

This study investigated the protective role and molecular mechanism of WNT4 in preserving the viability and neurogenic potential of dental pulp stem cells (DPSCs) within an inflammatory microenvironment following facial nerve injury (FNI). Human DPSCs (hDPSCs; authenticated by surface marker profiling and multi-lineage differentiation) and a rat model of facial nerve transection (n = 15 per group) were utilized. In vitro, hDPSCs were treated with TNF-α(10ng/mL) to model inflammation. In vivo, WNT4-overexpressing or control DPSCs (1 × 106 cells) were injected into the tail vein immediately after nerve transection. PANoptosis and neurogenic differentiation were assessed by Western blot, flow cytometry, and immunofluorescence staining. Transcriptional regulation was analyzed by dual-luciferase reporter assay and ChIP-qPCR. Protein interaction was examined by LC-MS/MS and docking. In vivo recovery was monitored by functional assessments and histology. WNT4 overexpression significantly attenuated TNF-α-induced PANoptosis in hDPSCs and restored their neurogenic potential. Mechanistically, KLF7 transcriptionally activated WNT4. WNT4 interacted with NOTCH1, activating Wnt/β-catenin signaling and upregulating c-Jun, CYCD1, and VEGFA. In vivo, engineered hDPSCs reduced local inflammation and accelerated functional recovery and histological repair. WNT4 protects DPSCs against inflammatory PANoptosis and enhances neuroreparative potential, providing a basis for optimizing stem cell therapy in FNI.

Secondary caries remains a leading cause of failure in resin composite restorations. To address the compromised mechanical properties and potential biosafety concerns associated with conventional quaternary ammonium salt (QAS) monomers, we developed quaternary ammonium-grafted mesoporous silica nanoparticles (QA-MSN) as antibacterial fillers for dental resin composites. The resulting QA-MSN-modified resin composites (QM-Resins) demonstrated potent and concentration-dependent antibacterial and antibiofilm activity against Streptococcus mutans. Specifically, the composite containing 10 wt% QA-MSN (10QM-Resin) achieved a 99.7% antibacterial rate and markedly suppressed biofilm formation after 48 h. Moreover, after 7 days of culture, the relative proliferation rates of human gingival fibroblasts and human dental pulp stem cells were 99.8% and 99.5%, respectively, indicating excellent cytocompatibility. Owing to the mechanical interlocking afforded by the mesoporous structure, QA-MSN incorporation increased the elastic modulus of the composites without adversely affecting flexural strength, degree of conversion, water sorption, or solubility. In a rat secondary caries, 10QM-Resin significantly reduced both Keyes' scores and lesion depth, demonstrating effective inhibition of caries progression. Collectively, these findings indicate that QA-MSNs represent promising antibacterial fillers for developing dental resin composites with enhanced resistance to secondary caries.

The regulatory role of vitamin D on dental pulp stem cells in inflammatory conditions: An in vitro study.

During angiogenesis, pericytes (PCs) drive vascular stabilization and maturation, a process largely regulated by the transcription factor serum response factor (SRF). Dental pulp stem cells (DPSCs) possess the potential to acquire PC-like properties and regulate angiogenesis. While EphB4/EphrinB2 signaling is reported to be involved in DPSC-mediated angiogenesis, its role in modulating PC-like function remains unexplored. Therefore, this study aims to investigate how EphB4/EphrinB2 signaling regulates the PC-like properties of DPSCs. DPSCs were transfected with lentivirus to knock down or overexpress EphB4. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and Ki-67 staining, and cell motility was evaluated using the Boyden chamber assay. To examine the PC-like function of DPSCs, the expression of contractile markers, including alpha-smooth muscle actin (α-SMA), calponin1, and smooth muscle 22-alpha (SM22-α), was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining, along with collagen contraction assay. Transcriptome profiling was performed to explore the potential downstream factor. The association between EphB4/EphrinB2 signaling and SRF was determined by Western blot and further verified using small interfering RNA (siRNA), followed by collagen contraction assay. Functional PC behavior of DPSCs was evaluated in a three-dimensional (3D) spheroid sprouting model with human umbilical vein endothelial cells (HUVECs). EphB4 knockdown in DPSCs suppressed the expression of contractile markers and impaired contractility, whereas its overexpression enhanced both. RNA sequencing results revealed an enrichment of differentially expressed genes (DEGs) involved in smooth muscle contraction and Ephrin pathway after EPHB4 silencing. Gene set enrichment analysis (GSEA) showed significant enrichment of smooth muscle contraction, angiogenesis, and neovascularisation-related genes among downregulated genes in EphB4-deficient DPSCs. Moreover, transcription factor binding site (TFBS) of SRF was significantly downregulated. SRF expression closely correlated with EphB4 levels, and SRF silencing abolished EphB4-induced functional enhancement of DPSCs, suggesting SRF as a downstream effector of EphB4/EphrinB2 signaling. 3D spheroid sprouting assay confirmed that EphB4-deficient and SRF-silenced DPSCs failed to restrain HUVEC sprouting due to the impaired PC-like function of DPSCs. This study elucidates a novel EphB4/EphrinB2/SRF signaling axis that is pivotal in regulating DPSCs into functional PC-like cells during angiogenesis.

Endochondral ossification is essential for the development of appendicular bones, physiological bone remodelling and fracture healing. Recent studies have identified mesenchymal stromal cell-derived FABP5+ septoclasts (SCs) as key mediators for the growth and repair of long bones, particularly in cartilage matrix degradation and growth plate remodelling via the secretion of matrix metalloproteinases. Our previous study has shown that soluble epoxide hydrolase (sEH) inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), promotes long bone growth and bone repair by enhancing H-type vessel-coupled osteogenesis. However, whether TPPU treatment regulates SC activity, thereby promoting long-bone growth and fracture healing, remains unclear. Here, our invitro and invivo results showed that TPPU treatment promoted long-bone growth in newborn mice and regulated the hypertrophic layer in the growth plate, with a reduced ratio of hypertrophic cartilage (HC) to proliferative cartilage (PC) width. Furthermore, TPPU treatment enhanced SC activity, as evidenced by elevated expression of MMP9 and FABP5 in the metaphysis near the growth plate. Simultaneously, TPPU induced FABP5+ SC-like cells to degrade chondrocytes in co-cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs). Mechanistically, TPPU enhanced the crosstalk of co-cultured HUVECs and hDPSCs to activate the NOTCH signalling pathway in hDPSCs by upregulating HIF-1α expression in HUVECs. Furthermore, TPPU enhanced fracture healing by inducing more FABP5+ SCs and MMP9 secretion at the fracture site. Collectively, these findings highlight sEH as a promising therapeutic target that regulates endochondral ossification through inducing SC activity, offering new opportunities for bone development and repair.

Atherosclerosis (AS), a leading cause of cardiovascular disease (CVD), is closely associated with excessive oxidative stress. Dietary nitrate has emerged as a promising intervention for cardiovascular protection through the nitrate–nitrite–nitric oxide (NO) pathway. Meanwhile, dental pulp stem cell (DPSC) possess potent antioxidant properties. However, the potential synergistic effect of sodium nitrate (NaNO3) and DPSC on AS remains unclear. In this study, ApoE−/− mice were fed a high‐fat diet (HFD) and treated with NaNO3 and/or DPSC. The combined treatment markedly attenuated atherosclerotic plaque formation, reduced oxidative stress, increased endothelial NO synthase (eNOS) expression, and decreased circulating monocyte levels. Furthermore, in vitro assays revealed that NaNO3 and DPSC synergistically alleviated oxidative stress and promoted macrophage polarization toward the M2 phenotype, thereby suppressing oxidized lipid uptake. Mechanistic studies revealed that these benefits were mediated by activation of the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and the subsequent upregulation of heme oxygenase‐1 (HO‐1). Collectively, our findings unveil a novel therapeutic strategy that combines NaNO3 with DPSC to alleviate oxidative stress and inflammation, presenting a promising approach for the treatment of AS.