Search Results (1,039)

Background: Hypertrophic cardiomyopathy (HCM) is increasingly recognized as a disorder shaped not only by sarcomeric mutations but also by complex immunogenetic and metabolic interactions. Emerging transcriptomic and single-cell analyses implicate immune dysregulation, RNA methylation, and necroptosis as critical modulators of myocardial remodeling. Objectives: This scoping review synthesizes bioinformatic, transcriptomic, and experimental data to delineate the immunogenetic architecture of HCM and identify candidate molecular targets for immune–metabolic modulation. Methods: Following Joanna Briggs Institute and PRISMA-ScR guidelines, we systematically searched PubMed, Embase, Web of Science, and GEO through September 2025 for studies evaluating immune infiltration, RNA regulation, and necroptosis in human HCM. Data were narratively synthesized across histologic, clinical, and multi-omics domains. Results: Among 8191 screened records, 25 studies met the inclusion criteria. Key immune–epigenetic regulators included the lncRNA–mRNA pair MIR210HG–BPIFC, m6A readers IGFBP3 and YTHDC1, and necroptosis gene JAK2. The HCM myocardium exhibited the depletion of reparative M2 macrophages and Tregs; enrichment of cytotoxic CD8⁺ T cells; and activation of the TNFα–NFκB, IL-6–JAK–STAT3, and PI3K–Akt pathways. Machine learning biomarkers (RASD1, FCN3, and PIK3R1) exhibited diagnostic accuracy (AUC > 0.85). Drug target predictions identified ruxolitinib and celecoxib as potential immunometabolic modulators (agents predicted to modulate both immune and metabolic pathways based on gene expression signatures). Conclusions: These findings support a hypothesis that HCM may involve immunogenetic mechanisms, rather than being exclusively sarcomeric in nature, although this remains to be validated. The integration of molecular and imaging biomarkers may enable precision immunotherapy, redefining HCM from a structural cardiomyopathy to a biologically stratified condition. Full article

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies. Full article

Neuroinflammation, a key contributor to neurodegenerative diseases, results from excessive microglial activation. Microglia that respond to pathogenic molecules switch to the M1 type and secrete various immune cytokines, which can cause neuronal damage. Therefore, our study focused on molecules that can enhance the neuroprotective role of microglia and reduce neuronal damage. The adipocyte enhancer-binding protein 1 (AEBP1) gene is known for its role in regulating immune responses in macrophages. However, its role in neuroinflammation has not been fully explored. Therefore, we investigated the role of AEBP1 in microglial cells activated by lipopolysaccharide (LPS). First, we confirmed that AEBP1 is expressed in LPS-activated microglia and demonstrated that downregulation of AEBP1 using shRNA in activated microglia reduced the immune response via the nuclear factor-kappa-B (NFκB) pathway. These results promote a shift toward neuroprotective M2 microglia, thereby reducing neuronal damage. Next, we confirmed that the expression of AEBP1 was elevated in the brains of Alzheimer’s disease (AD) mice. Additionally, animal experiments to assess the therapeutic effects of AEBP1 showed that microglia gathered around amyloid beta (Aβ) and reduced its size. Taken together, our results provide the first evidence that AEBP1 can reduce inflammatory activity in microglia, suggesting its potential as a target molecule for immunotherapy. Full article

Inflammatory bowel disease (IBD) involves chronic inflammation and disruption of the intestinal barrier, often accompanied by alterations in gut microbiota composition. This study examined the protective potential of a prebiotic mixture extract (PME) prepared from Vigna radiata (mung bean), Vigna angularis (red bean), and Foeniculum vulgare (fennel) using the HT-29 cell and colitis animal model. PME exhibited concentration-dependent antioxidant activity, with greater radical-scavenging capacity in the ABTS assay than in the DPPH assay. In LPS-stimulated HT-29 epithelial cells, PME reduced the mRNA expression of inflammation-associated genes (TNF-α, IL-1β, NF-κB) and upregulated tight junction markers (CLDN1 and OCLN), demonstrating its anti-inflammatory and supportive effects on the intestinal barrier. Vitexin, a C-glycosylated flavonoid, was detected in PME and is expected to mediate these protective effects. In a DSS-induced colitis mouse model, PME administration alleviated disease severity by increasing colon length, reducing serum levels of inflammatory cytokines and COX-2/PGE2, and restoring intestinal permeability. Furthermore, PME modulated the gut microbiota by enhancing beneficial bacteria such as Bifidobacterium and Faecalibaculum while suppressing inflammation-associated taxa, including Escherichia, Bacteroides, and Mucispirillum. These improvements collectively suggest that PME reinforces epithelial barrier integrity and promotes intestinal homeostasis through both anti-inflammatory and microbiota-regulating actions. Full article

Fine particulate matter (PM2.5) is a major air pollutant linked to lung cancer progression. In Southeast Asia, seasonal smoke-haze produces biomass-derived PM2.5, yet its acute effects on genetically diverse lung tumours remain unclear. We investigate how Chiang Mai haze-derived PM2.5 impacts oxidative stress and gene expression in three non-small-cell lung cancer (NSCLC) cell lines: A549 (KRAS-mutant), NCI-H1975 (EGFR-mutant), and NCI-H460 (KRAS/PIK3CA-mutant). Cells were exposed to PM2.5 (0–200 µg/mL) and assessed for viability (MTT), reactive oxygen species (ROS; H₂O₂, •OH) and malondialdehyde (MDA) levels, mitochondrial-associated fluorescence, and whole-transcriptome responses. Acute exposure caused dose- and time-dependent viability loss, with A549 and NCI-H1975 more sensitive than NCI-H460. ROS profiling normalized to viable cells revealed genotype-specific oxidative patterns: cumulative increases in A549, sharp reversible spikes in NCI-H1975, and modest changes in NCI-H460. MitoTracker intensity trended downward without significance, with subtle fluorescence changes and particulate uptake. RNA-seq identified robust induction of xenobiotic metabolism (CYP1A1, CYP1B1), oxidative/metabolic stress mediators (GDF15, TIPARP), and tumour-associated genes (FOSB, VGF), alongside repression of tumour suppressors (FAT1, LINC00472). Pathway enrichment analyses highlighted oxidative stress, IL-17, NF-κB, and immune checkpoint signaling. Together, biomass haze-derived PM2.5 from Northern Thailand drives genotype-dependent oxidative stress and transcriptional remodeling in NSCLC cells. Full article

Osteoporosis is a systemic skeletal disease that severely impairs the health of the elderly population. The interaction between the receptor activator of the NF-κB ligand (RANKL) and its receptor RANK is critical for osteoclast differentiation and function. Therefore, targeting the RANKL/RANK interaction represents a promising strategy for osteoporosis. In this study, we employed a newly established yeast two-hybrid system based on RANKL/RANK interaction and identified IMB-R38, a novel benzamide compound that dose-dependently blocked RANKL/RANK interaction by inhibiting the growth of AH109 cells harboring pAD-RANKL/pBD-RANK plasmids in quadruple-dropout medium. IMB-R38 significantly suppressed osteoclast differentiation, disrupted F-actin ring formation, and downregulated the expression of osteoclast-specific genes, including NFATc1 and MMP9 in RANKL-induced RAW264.7 macrophages. IMB-R38 also promoted osteoblast differentiation by upregulating the expression of osteogenic genes. Importantly, in a dexamethasone (DXM)-induced osteoporotic zebrafish model, IMB-R38 significantly increased bone mineralization, with anti-osteoporosis efficacy superior to that of alendronate sodium (Alen). RT-qPCR assays showed that IMB-R38 significantly upregulated the mRNA expression of osteogenesis genes (Bmp2, Runx2a, Runx2b, Sp7, Alp, and Oc) while markedly downregulating that of the osteoclastogenesis genes (Mmp9, Mmp13, and Mmp2) compared with the DXM group. Mechanistically, an SPR assay confirmed that IMB-R38 directly binds with RANK but not RANKL to disrupt RANKL/RANK interaction. Furthermore, Asp168 of RANK was identified as a key amino acid that mediates both RANKL interaction and IMB-R38 binding. The inhibition of RANKL/RANK by IMB-R38 suppressed JNK phosphorylation and, consequently, osteoclast differentiation and function. Collectively, our findings identify IMB-R38 as a novel RANKL/RANK inhibitor with therapeutic potential for osteoporosis through its regulation of bone metabolism. Full article

Physical exercise is a potent non-pharmacological strategy for the prevention and management of chronic non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular diseases, obesity, and certain cancers. Growing evidence demonstrates that the benefits of exercise extend beyond its physiological effects and are largely mediated by coordinated molecular and cellular adaptations. This review synthesizes current knowledge on the key mechanisms through which exercise modulates metabolic health, emphasizing intracellular signaling pathways, epigenetic regulation, and myokine-driven inter-organ communication. Exercise induces acute and chronic activation of pathways such as AMPK, PGC-1α, mTOR, MAPKs, and NF-κB, leading to enhanced mitochondrial biogenesis, improved oxidative capacity, refined energy sensing, and reduced inflammation. Additionally, repeated muscle contraction stimulates the release of myokines—including IL-6, irisin, BDNF, FGF21, apelin, and others—that act through endocrine and paracrine routes to regulate glucose and lipid metabolism, insulin secretion, adipose tissue remodeling, neuroplasticity, and systemic inflammatory tone. Epigenetic modifications and exercise-responsive microRNAs further contribute to long-term metabolic reprogramming. Collectively, these molecular adaptations establish exercise as a systemic biological stimulus capable of restoring metabolic homeostasis and counteracting the pathophysiological processes underlying NCDs. Understanding these mechanisms provides a foundation for developing targeted, personalized exercise-based interventions in preventive and therapeutic medicine. Full article

Objectives: As a novel member of the interleukin(IL)-1 family, IL-38 has shown therapeutic effects in various chronic inflammatory diseases. However, its role and underlying mechanisms in cardiovascular diseases, particularly atherosclerosis, remain unclear. This study aimed to explore the effects of IL-38 on atherosclerosis progression and its mechanisms in regulating macrophage function during the atherosclerotic process. Methods: To evaluate the therapeutic potential of IL-38 in atherosclerosis, we performed histopathological examinations and biochemical analyses in vivo. In vitro, we used primary bone marrow-derived macrophages (BMDMs) stimulated with oxidized low-density lipoprotein (ox-LDL) to assess the anti-inflammatory effects of IL-38 and quantified its impact on ox-LDL-induced macrophage polarization. To further elucidate the specific mechanisms by which IL-38 regulates macrophage function, we conducted mRNA sequencing and validated downstream regulatory signaling pathways. Results: IL-38 exhibited therapeutic potential in atherosclerosis by reducing atherosclerotic plaque formation, modulating plaque composition, suppressing the production of proinflammatory cytokines within plaques, and potentially regulating macrophage cholesterol metabolism. Moreover, IL-38 exerted significant anti-inflammatory effects on macrophages both in vivo and in vitro. Notably, it inhibited the polarization of macrophages toward the proinflammatory M1-like phenotype in both settings. Additionally, IL-38 impeded the phosphorylation and nuclear translocation of p65 in BMDMs and reduced ox-LDL-induced macrophage apoptosis. Conclusion: IL-38 holds therapeutic potential for atherosclerosis, as it alleviates disease progression, inhibits macrophage polarization toward the M1-like phenotype, suppresses nuclear factor-κB (NF-κB) signaling activation, and reduces macrophage apoptosis. This study provides new insights into the anti-inflammatory mechanisms by which IL-38 mitigates atherosclerosis. Full article

Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis due to aggressive invasion and therapy resistance. Cancer-associated fibroblasts (CAFs) are key stromal components that promote tumor progression; however, their specific roles in ESCC remain unclear. Using a direct co-culture model of ESCC cell lines (TE-9, -10, and -15) and mesenchymal stem cells (MSCs) to generate CAF-like cells, we identified biglycan (BGN) as a significantly upregulated gene in CAF-like cells via cDNA microarray analysis. Public single-cell RNA sequencing data also demonstrated elevated BGN expression in CAF clusters. We confirmed that CAF-like cells exhibited elevated BGN expression and secretion at both the mRNA and protein levels. Recombinant human BGN enhanced ESCC cell proliferation and migration by activating Erk and NF-κB signaling pathways, effects abrogated by TLR4 blockade. Furthermore, BGN promoted CAF marker expression in MSCs, M2-like macrophage polarization, and enhanced proliferation and migration abilities in both cell types. Immunohistochemical analysis of 66 ESCC tissues revealed that high stromal BGN expression correlated with greater tumor invasion, lymphatic invasion, and shorter disease-free survival. These findings indicate that CAF-derived BGN promotes ESCC progression via TLR4-mediated signaling and modulates stromal cell behavior, highlighting its potential as a prognostic biomarker and therapeutic target. Full article

The marine angiosperm Posidonia oceanica (Linnaeus) Delile, 1813 is a rich source of phytotherapeutic compounds whose potential applications for human health remain largely uninvestigated. Here, we determined the differential impact of aqueous extracts from P. oceanica’s green leaves (GLE) and rhizomes (RE) on the inflammation-related mRNA expressions and protein levels, nitric oxide (NO) release, and endocytic activity in LPS-stimulated RAW 264.7 macrophages. We also examined the influence of the extracts in modulating the activation of components of intracellular signaling pathways. Co-treatments of LPS-stimulated RAW 264.7 cells in the presence of either GLE or RE resulted in a reduction in NO production, associated with a down-regulation of Nos2 expression, reduced levels of COX-2 and TNFα proteins, and a decrease in Nfkb1 expression and NF-κB activation. No effect was exerted on the release of IL-6. Moreover, co-exposures to LPS and the extracts led to an elevation in pJNK and pAKT levels alongside a reduction in pERK. In contrast to GLE, RE specifically lowered IL-1β production, induced a more robust increase in IL-10, positively influenced the endocytic function of RAW 264.7 cells, and drastically up-regulated the phosphorylation of p38. The data obtained indicate that GLE and RE exhibit considerable promise as prospective anti-inflammatory and immunomodulatory agents. Full article

Intestinal health is critical for nutrient absorption and disease resistance in cultured fish. Yet, the effects of dietary Eucalyptus-derived biochar on the gut of largemouth bass (Micropterus salmoides) remain largely unexplored. This study evaluated whether supplementing diets with Eucalyptus biochar c profiles. In a 56-day feeding trial, M. salmoides were offered a standard diet containing either 0% (control) or graded levels of biochar. Juvenile fish (initial body weight 13.34 g) were randomly distributed into six groups with three replicates each (30 fish per replicate). Six extruded diets were formulated with 0, 2.5, 5.0, 10.0, 20.0, or 40.0 g kg⁻¹ of biochar, designated G0 through G5. Biochar had no significant effects on villus length, muscle layer thickness, villus width, or the activities of trypsin, amylase, and lipase, though goblet cell number was significantly higher in G5. mRNA expression of Claudin-3 and IL-10 was significantly upregulated in G1–G4, while IL-1β was significantly downregulated in G4 and G5, and TNF-α expression was reduced in G2 and G3. 16S rDNA sequencing showed increasing trends in the relative abundance of Firmicutes (43% to 49.17%) and Lactococcus (0% to 1.10%) in G3, accompanied by decreases in Proteobacteria and Klebsiella. Metabolomic analysis indicated significant upregulation of taurochenodeoxycholic acid-7-sulfate, apigenin, genistein, baicalein, taurocholic acid-3-sulfate, taurochenodeoxycholic acid-3-sulfate, and arginylmethionine in G3, whereas etoxazole and soyasaponin were significantly reduced. Dietary inclusion of 10 g kg⁻¹ Eucalyptus biochar improved intestinal health in largemouth bass by shaping the gut microbiota, promoting isoflavone biosynthesis and bile acid and amino acid metabolism, inhibiting the NF-κB pathway, and reinforcing the intestinal barrier. Full article

Harnessing the powerful antioxidant and anti-inflammatory properties of Scutellaria baicalensis and Lonicera japonica (SL), SL extract emerges as a natural and effective dietary strategy to enhance sow reproductive performance and overall health. In this study, 100 multiparous Duroc × Landrace × Yorkshire sows were assigned to either a control diet or a diet supplemented with 0.05% SL extract (n = 100), beginning on day 85 of gestation and continuing until day 21 of lactation, with 50 sows in each group. Duroc boars were the source of semen for artificial insemination. While SL supplementation did not affect litter size, birth weight, or milk composition, it significantly reduced piglet mortality during lactation, from 13.11% to 9.72% (p < 0.05). Compared with the control group, feed intake of sows in the SL group increased from 4.56 kg to 4.70 kg (p < 0.01) during lactation. Furthermore, SL extract enhanced the antioxidant capacity of the sows, reduced malondialdehyde and levels of IL-1β, IL-6, and TNF-α, and increased the plasma soluble cluster of differentiation 14 (sCD14) concentrations (p < 0.05). In vitro, pretreatment of mammary epithelial cells with SL extract (2 μg/mL for 24 h) before lipopolysaccharide stimulation significantly upregulated antioxidant markers, suppressed pro-inflammatory cytokine mRNA expression, and inhibited activation of the NF-κB and MAPK pathways (p < 0.05). These findings highlight the potential of SL extract as a natural feed additive to mitigate oxidative stress and inflammation, ultimately supporting improved reproductive performance and health in sows. Full article

The diseases caused by genotype VII Newcastle disease virus (NDV), H9N2 avian influenza virus (AIV), and fowl adenovirus serotype 4 (FAdV-4) continue to threaten the global poultry industry. However, no broad-spectrum vaccines provide simultaneous protection against these three pathogens. This study employed bioinformatics and immunoinformatics approaches to design a multi-epitope vaccine, named NFAF, which consists of B-cell, cytotoxic T lymphocyte (CTL) epitopes, and helper T lymphocyte (HTL) epitopes derived from hemagglutinin-neuraminidase (HN) and fusion (F) proteins of genotype VII NDV, hemagglutinin (HA) protein of H9N2, and Fiber2 protein of FAdV-4. The vaccine candidate was predicted to have non-allergenic properties, non-toxicity, high antigenicity, and favorable solubility. Each of its constituent antigenic epitopes has a high degree of conservation. Molecular docking demonstrated stable binding between NFAF and chicken Toll-like receptor (TLRs) and major histocompatibility complex (MHC) molecules. NFAF was expressed in soluble form in Escherichia coli and purified. Polyclonal antibodies against all three target viruses showed specific binding to NFAF. In vitro experiments revealed that NFAF effectively stimulated chicken peripheral blood mononuclear cells (PBMCs) and induced Th1, Th2, and pro-inflammatory cytokine production, confirming its immunogenicity, and increased the mRNA expression of the key signaling molecules MyD88 and NF-κB. These results suggested that NFAF could therefore be an efficacious multi-epitope vaccine against genotype VII NDV, H9N2, and FAdV-4 infections. Full article

Background/Objectives: Changes in glucose metabolism impact central nervous system (CNS) homeostasis and, consequently, can lead to cognitive impairment and an increased risk for neurodegenerative and neuropsychiatric disorders. Astrocytes are glial cells that act as key regulators of brain glucose metabolism, thus representing important cellular targets for studies of different pathophysiological conditions, including hyperglycemia. Resveratrol, a natural polyphenol, has emerged as a potential protective strategy against diabetes and its complications; however, its glioprotective effects remain unclear. Based on these observations, we evaluated whether resveratrol could modify the inflammatory response in astroglial cells exposed to experimental hyperglycemic conditions. Methods: After reaching confluence, C6 astroglial cells were pre-incubated with 10 µM resveratrol in serum-free DMEM with 6 mM glucose for 24 h. The medium was then replaced with serum-free DMEM containing 12 mM glucose and 10 µM resveratrol for another 24 h. Controls were maintained in 6 mM glucose. Analyses included cell viability, metabolic activity, glucose and glutamate uptake, cytokine quantification by ELISA, and gene expression by RT-qPCR. Results: We show that high glucose levels modulate glucose and glutamate metabolism, and increase neuroinflammation, through the modulation of inflammatory mediators. In addition, high glucose upregulated the gene expressions of inducible nitric oxide synthase (iNOS), nuclear factor κB (NFκB), cyclooxygenase 2 (COX2), and Toll-like receptor 4 (TLR4) while decreasing mRNA levels of NLR family pyrin domain containing 3 (NLRP3) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). However, resveratrol was able to prevent most of these effects, particularly the high glucose-triggered inflammatory response. Resveratrol also modulated heme oxygenase 1 (HO-1) and nuclear factor erythroid-derived 2-like 2 (Nrf2), important targets associated with cellular protection. Conclusions: Our findings reinforce resveratrol as a potential glioprotective strategy against diabetes-related brain toxicity. Full article

Inflammation is a hallmark of atherosclerosis (AS), a complex chronic vascular disease. This study investigates the anti-atherosclerotic effects of the frog skin antimicrobial peptide(AMP) C-1b(3-13) in vitro and in vivo, focusing on the anti-inflammatory mechanism mediated by the miR-590-5p/KLF12/p300 axis in ox-LDL-induced PMA-THP-1 foam cells. MicroRNA(miRNA) sequencing was used to investigate the effects of AMP C-1b(3-13) on miRNA expression in ox-LDL-induced foam cells. Pro-inflammatory cytokine secretion regulated by miR-590-5p was detected by ELISA. Potential targets of miR-590-5p were bioinformatically predicted and validated through dual-luciferase reporter and RNA Immunoprecipitation(RIP)-qPCR assays. Western blot was used to assess the effects of C-1b(3-13) on Krüppel-like factor 12(KLF12), nuclear p300, and nuclear factor kappa B(NF-κB) pathway proteins; ApoE^−/− mice were utilized to establish the AS mouse model. Oil Red O (ORO) and hematoxylin and eosin (H&E) staining detected plaque formation and morphological changes in the aortic root. Immunohistochemistry analyzed CD68⁺(M1) and CD206⁺(M2) macrophage distribution within arterial plaques. miR-590-5p significantly suppressed pro-inflammatory cytokine secretion in ox-LDL-induced foam cells. Mechanistically, miR-590-5p directly targeted the 3′-untranslated region of KLF12 mRNA, inhibiting KLF12 expression, reducing nuclear p300 accumulation, and subsequently attenuating NF-κB signaling pathway activation. Furthermore, AMP C-1b(3-13) treatment effectively attenuated inflammatory responses by upregulating miR-590-5p, which downregulated KLF12 expression, diminished nuclear p300 levels, and inhibited NF-κB signaling. In ApoE^−/− AS mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, and suppressed inflammatory responses through the same signaling axis. These findings reveal a novel miR-590-5p-mediated regulatory mechanism in AS and identify AMP C-1b(3-13) as a promising therapeutic agent targeting miR-590-5p/KLF12/p300/NF-κB pathway. Full article