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BIOSCIENCE REPORTS · 2021 · IF 3.84

Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-κB-induced transcription of PKM2

Yao Qiuwen,Jing Guiying,Zhang Xiaowen,Li Meiling,Yao Qihuan,Wang Longhui

Background:  Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. Here, we investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells. Methods:  Immunohistochemistry was used to examine protein expression and cell purity. Quantitative RT-PCR was conducted to assess mRNA expression, and Western blot was performed to determine protein level. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Glycolysis and mitochondrial function were evaluated by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) of cells, respectively. Lastly, plasmid transfection and inhibitor treatment were used for overexpression and inhibition studies. Results: Cinnamic acid inhibited cell viability and cell invasion, as well as decreased ECAR and OCR, in primary endometrial stromal cells. Cinnamic acid suppressed the effects of PKM2 overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid. Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2. Conclusions:  Our study identified cinnamic acid as a novel compound from Cinnamomum cassia Presl that displays potent effects on primary endometrial stromal cell viability, invasion, and glycolysis, suggesting its potential use for endometriosis treatment.

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EXPERIMENTAL AND MOLECULAR PATHOLOGY · 2020 · IF 2.28

Icariside II attenuates eosinophils-induced airway inflammation and remodeling via inactivation of NF-κB and STAT3 in an asthma mouse model

Chunyan Tian,Fengli Gao,Xing Li,Zhuying Li

Asthma is a chronic inflammatory airway disease. Icariside II has been reported to exert anti-inflammatory effect in multiple human diseases . The present study aimed to investigate the effects and mechanisms of Icariside II on airway inflammation and remodeling in asthma. We established an asthma mouse model with ovalbumin (OVA) immunization. Histological analysis using H&E, PAS and Masson staining showed that administration of Icariside II attenuated OVA-induced airway inflammation and remodeling. Icariside II reduced the numbers of total white blood cells and eosinophils in bronchoalveolar lavage fluid (BALF). The levels of interleukin (IL)-4, IL-5, IL-13 and transforming growth factor (TGF)-β1 in peripheral blood and the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), eotaxin-1, CC-chemokine receptor-3 (CCR-3), Toll-like receptor (TLR)-2 and TLR-4 were significantly down-regulated in lung tissues of OVA-induced mouse model. These results suggested that Icariside II inhibited eosinophil activation and thus decreased eosinophils-induced airway inflammation and remodeling in asthma. Moreover, Icariside II suppressed TGF-β1-induced cell proliferation , migration, and CTGF expression in airway smooth muscle cells (ASMCs). In both OVA-induced mouse model of asthma and TGF-β1-induced ASMCs, Icariside II decreased IκBα degradation, nuclear translocation of NF-κB p65 and STAT3 phophorylation, indicating an inactivation of NF-κB and STAT3 in the presence of Icariside II. Therefore, we demonstrate that Icariside II attenuates eosinophils-induced airway inflammation and remodeling in asthmatic mice and inhibits TGF-β1-induced cell proliferation and migration in ASMCs via suppressing NF-κB and STAT3 signalings.

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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Nanogel-encapsulated Rosa roxburghii Tratt fruit polyphenols ameliorated ulcerative colitis by regulating gut microbiota and PI3K/Akt and NF-κB pathways

Mingxiu Long,Hui Wang,Fang Zhang,Yaoqi Ran,Yongfu Li,Jingwen Luo,Zhaojun Chen,Zhuxi Tian,Shuming Tan,Xiong Liu

Rosa roxburghii Tratt fruit polyphenols (RP) possess antioxidant, anti-inflammatory, and immunomodulatory properties, showing potential for ulcerative colitis (UC) treatment. However, their efficacy is limited by bioavailability and targeting efficiency. To address this, RP were encapsulated into acylated chitosan-crosslinked carboxymethyl konjac glucomannan (ACs-CKGM) nanogel (RPNG). Experimental results demonstrated that RPNG significantly enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1, Occludin and Claudin-3) and mucus secretion (MUC2). It effectively mitigated oxidative stress by restoring antioxidant enzymes (SOD, GSH-Px and CAT) while reducing MPO, COX-2 and iNOS activation. Through integrated ELISA, western blot, and transcriptomic analyses, we emonstrated that RPNG specifically inhibited PI3K/Akt/mTOR and NF-κB signaling pathways, decreasing inflammatory cytokines (e.g., TNF-α, IL-6) while increasing anti-inflammatory mediators (e.g., IL-10). Gut microbiome analysis showed RPNG reversed DSS-induced dysbiosis by enriching beneficial bacteria (e.g., Muribaculum sp.) and suppressing pathogens (e.g., Escherichia coli ). These findings highlight RPNG as a novel targeted strategy for UC management, supported by multi-omics mechanistic insights.

CAS / MDL: 9011-18-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Immunity Inflammation and Disease · 2023 ·Vol. 11 ·期 4 ·e820 · IF 3.2

Luteolin suppresses inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibition of the NOX4-mediated NF-κB signaling pathway

Mingfei Li,Huifang Wang,Yun Lu,Jinwen Cai

Introduction Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation that predominantly affects the lung and peripheral airways. Previous investigation has underlined the efficacy of luteolin in the treatment of inflammation-related symptoms. Accordingly, our study concentrates on unveiling the effect of luteolin on COPD. Methods Mice or A549 cells were treated with cigarette smoke (CS) to establish COPD models in vivo and in vitro. Then, the serum and bronchoalveolar lavage fluid of mice were harvested. The lung tissues of mice were subjected to hematoxylin-eosin staining to observe the degree of damage. The inflammation and oxidative stress factors level were calculated via enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The expressions of nuclear factor-kappa B (NF-κB) pathway-related factors were detected by Western blot. Results In in vivo experiments, CS treatment reduced the weight of mice and promoted lung tissue damage, while luteolin attenuated the effect of CS on the mice. Moreover, luteolin inhibited the inflammation factors level, oxidative stress, and NADPH oxidase 4 (NOX4)-mediated NF-κB signaling pathway in CS-induced COPD mice. Similar results were obtained in in vitro experiments that luteolin alleviated CS-induced inflammation, oxidative stress, and NOX4-mediated NF-κB signaling pathway activation in CS-treated A549 cells. Besides, NOX4 overexpression offset the impacts of luteolin on the CS-induced A549 cells. Conclusion Luteolin alleviates inflammation and oxidative stress in COPD via NOX4-mediated NF-κB signaling pathway, which provides a theoretical basis for the treatment of COPD with luteolin.

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iScience · 2025 · IF 4.1

LAR1 activates NF-κB signaling pathway by binding to APOC1 mRNA and enhancing its expression: a novel mechanism underlying breast carcinogenesis

Jiayi Xiao,Qi Li,Zhu Li,Lingxin Kong,Yang Shang,Yongliang Xu,Mo Dong,Sijin Zhang,Zitao Li,Caijuan Li

Breast cancer (BC) remains a leading cause of cancer-related mortality in women worldwide. Through online data mining, we identified the significant upregulation of the RNA-binding protein La Ribonucleoprotein 1 (LAR1) in BC. Functionally, LAR1 knockdown impeded S-phase entry, migration, and invasion of BC cells in vitro . Consistently, it markedly suppressed tumor growth and liver metastasis in BALB/c nude mice. Mechanistically, LAR1 promoted AKT phosphorylation and IκBα degradation, leading to NF-κB activation, with the NF-κB inhibitor PDTC rescuing LAR1's effects. Integrated analysis of transcriptome and previous data of LAR1-mRNA interactome revealed Apolipoprotein C1 (APOC1) as a key target. LAR1 bound to the APOC1 3'-UTR to stabilize its mRNA, and APOC1 overexpression counteracted the effects of LAR1 knockdown. In conclusion, our study defines the LAR1-APOC1-NF-κB axis as a crucial driver of BC progression, offering a promising therapeutic strategy for BC treatment.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 13.2

Dual-modal antioxidant nanozyme hydrogel for protection against noise-induced hearing loss via attenuation of oxidative stress and NF-κB/MAPK signaling

Liang Xia,Ru Tang,Yi Chen,Ning Ma,Lili Xiao,Xiaoyan Chen,Xiaoyin Mao,Keyi Li,Yanmei Feng,Jingjing Liu,Amin Zhang

Noise-induced hearing loss (NIHL) is a prevalent condition caused by irreversible cochlear hair cell damage resulting from an oxidative stress imbalance. To combat this, we engineered a yolk-shell shaped hollow Prussian blue nanozyme, loaded with N -acetylcysteine (NAC) and surface-modified with reactive oxygen species (ROS)-responsive liposomes, which was then incorporated into a tissue-adhesive hydrogel (HN@TK-Lipo gel ). This system establishes a dual-modal antioxidant mechanism, where the nanozyme acts as a continuous ROS scavenger and NAC replenish intrinsic antioxidant capacity. The hydrogel exhibits superior adhesiveness, effectively overcoming rapid drainage challenges in the middle ear. In vitro, HN@TK-Lipo gel demonstrated potent antioxidative capabilities, successfully scavenging intracellular ROS and preserving mitochondrial function. Crucially, in an NIHL animal model, the hydrogel treatment significantly alleviated auditory threshold shifts and minimized hair cell apoptosis and ribbon synapse loss. Transcriptomic analysis (RNA-seq) uncovered that the hydrogel exerts its protective effects by specifically downregulating inflammation-related pathways. Further mechanistic validation confirmed that HN@TK-Lipogel elicits an enhanced therapeutic effect by robustly upregulating antioxidant defenses (NRF2/SOD2) and suppressing lipid peroxidation (4-HNE) via the regulation of the identified NF-κB and MAPK signaling cascades. This biomaterial combines targeted delivery with enhanced catalytic and biological functions, improving the safety and effectiveness of inner ear therapy. Therefore, this nanozyme hydrogel system offers a promising therapeutic strategy for auditory medicine.

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DESALINATION · 2026 · IF 9.8

In situ growing ZIF-L particles by cross-substrate counter diffusion: Breaking the trade-off between NF permeation and Li+/Mg2+ selectivity

Mengyao Chen,Yangxiang Huang,Yeqiang Lu,Congjie Gao,Lixin Xue

Polyamide/polyethylene (PA/PE) nanofiltration (NF) membranes based on polyethyleneimine (PEI) had demonstrated excellent Li + /Mg 2+ selectivity, but showing trade-off between their permeance and Li + /Mg 2+ selectivity. In this work, a novel cross-substrate counter diffusion (CSCD) method was introduced to grow and secure ZIF-L particles in the PA layers. Specifically, rather than directly contacting the PA layers containing Zn(II) cation (PA/Zn) with an aqueous solution of 2-methylimidazole (2-MIM) ligand from the top sides, 2-MIM ligand molecules were diffused across the PE substrate from the bottom sides to react with Zn(II) secured on the top sides of PA layers. Compared with the top-down method, the bottom-up approach had yield PA/ZIF-B NF membranes with higher surface roughness, larger average pore size and narrower pore size distribution. Notably, the pure water permeance of PA/ZIF-B membrane was increased by 2.6-folds to 15.1 L·m −2 ·h −1 ·bar −1 at a high Li + /Mg 2+ separation factor (S Li/Mg ) of 16.5, breaking the trade-off performance upper bound between water permeance and Li + /Mg 2+ separating selectivity and outperforming most of the reported TFN NF membranes.

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2026 · IF 6.6

Autophagy-related responses in Pacific oyster Crassostrea gigas exposed to phenanthrene: Association with a putative E3 ubiquitin ligase-NF-κB regulatory axis

Ziyi Guo,Zengguang Zhu,Hongyue Ma,Houqiang Du,Rong Tan,Weiwei Wang,Shaoguo Ru,Pengfei Cui

Phenanthrene (PHE) is a common marine pollutant, but whether it induces autophagy-related responses in bivalves and how such responses contribute to cellular adaptation under pollutant stress remain incompletely understood. Here, using multimodal imaging, ultrastructural analysis, proteomics, and gene-expression assays, we found evidence consistent with the engagement of an E3 ubiquitin ligase-NF-κB-autophagy regulatory axis in hemocytes of the Pacific oyster Crassostrea gigas following phenanthrene exposure. Confocal laser scanning microscopy, Cyto-ID flow-cytometry screening, and transmission electron microscopy revealed increased autophagy-related signals and the presence of autophagic vesicle-like structures in PHE-exposed hemocytes. The proteomics results showed that protein levels of HUWE1, TRIM36, and ATG7 were significantly upregulated. The expression of axis-related genes was significantly upregulated after PHE exposure, while CAPE-mediated inhibition of NF-κB attenuated the PHE-associated induction of LC3 and p62/SQSTM1 transcripts, supporting the involvement of NF-κB signaling in the autophagy-related transcriptional response. Similar upregulation of axis-related transcripts in RAW264.7 macrophages supported a comparable direction of transcriptional response, but did not establish conserved pathway activation or causality. Together with changes in hemocyte number, apoptosis rate, phagocytic capacity, and ROS levels, these findings are consistent with a cellular adaptation response under PHE stress. This study provides integrated evidence for autophagy-associated stress responses in Pacific oysters exposed to phenanthrene and offers a mechanistic framework for future validation of pollutant tolerance in marine bivalves.

CAS / MDL: 85-01-8
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SOUTH AFRICAN JOURNAL OF BOTANY · 2026 · IF 3.1

Core constituents and pharmacodynamically equivalent ratios of Polygonum capitatum against urinary tract infection: involvement of Nrf2/HO-1 and NF-κB pathways

Xian Dong Lv,Meiherinisa Maitituersun,Fei Li

This study established HPLC fingerprints of PCAE 70% and RLQ, supported by the 2020 edition of the Chinese Pharmacopeia and relevant literature, and performed network pharmacology prediction for the common constituents. • Multi-index regression analysis of uniform design data was conducted by partial least squares, by which seven active components were optimized and determined as six important active components, and their rationality was experimentally validated. • The entropy weight method was employed to unify heterogeneous data from in vitro and in vivo experiments, and the integrated important active component combination was subjected to in vivo activity validation through a mouse urinary tract infection model. • This study suggests that the active components centered on gallic acid, myricitrin, and quercitrin may constitute the major pharmacodynamic material basis of Polygonum capitatum against UTI, and preliminarily explored the underlying mechanism. Ethnopharmacological relevance As a cornerstone herb in the traditional medicine of the Miao ethnic group in Guizhou Province, Polygonum capitatum has long been used to treat diseases of the urinary system. Documented in Miao medical theory as cold in nature and bitter-pungent in taste, and as acting on the kidney and bladder meridians, it is traditionally used to clear heat, promote diuresis, relieve stranguria, and detoxify, thereby relieving pain. The aqueous extract of this herb is the sole component of Relinqing Granules (RLQ), a clinically widespread formulation. Despite its broad clinical application, the underlying material basis of its pharmacological activity remains to be fully elucidated. Materials and methods The target compounds were identified through literature investigation, and their presence in both the Polygonum capitatum 70% aqueous ethanol extract (PCAE 70%) and RLQ was subsequently verified. The common constituents shared by the two were identified by comparing the fingerprint chromatograms with reference standards, and network pharmacology was employed to predict the potential targets of these components. The constituents were then combined through uniform design to evaluate their antibacterial, anti-inflammatory, and antioxidant activities, optimized via partial least squares regression and the entropy weight method, and ultimately validated in a mouse model of UTI. Results A total of seven common constituents were identified: gallic acid, protocatechuic acid, catechin, myricitrin, quercitrin, quercetin, and kaempferol. Network pharmacology predicted that these constituents might exert anti-UTI effects through modulation of the PI3K-Akt signaling pathway. The optimal ratio combination demonstrated significant antibacterial activity against Escherichia coli and Staphylococcus aureus , while another optimal ratio enhanced catalase activity and modulated the expression of AKT-1/Nrf 2 / HO-1/NF-κB 3 in zebrafish. Following data integration using the entropy weight method, mouse validation results revealed decreased TNF-α/IL-1β levels and increased IL-10 levels, with superior efficacy compared to PCAE 70% and RLQ, without dose-dependent differences. The results implied that gallic acid, myricitrin, and quercitrin represent the potential principal active components of P. capitatum. Conclusion The optimized combination dominated by gallic acid, myricitrin, and quercitrin, identified from P. capitatum , exhibited antibacterial, anti-inflammatory, and antioxidant performance superior or equivalent to existing preparations, holding significant theoretical and practical value. Download: Download high-res image (228KB) Download: Download full-size image Graph A illustrates the experimental procedure for determining the in vitro antibacterial activity of target drugs by the MTT method; Graph B illustrates the experimental procedure for the acute toxicity assay in zebrafish; Graph C illustrates the mechanism diagram of drug administration in the zebrafish oxidative stress model; Graph D illustrates the simplified experimental procedure and mechanism diagram before drug administration in the mouse UTI model.

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EUROPEAN JOURNAL OF PHARMACOLOGY · 2026 · IF 5.7

Deoxyelephantopin, a natural sesquiterpene lactone, suppresses IL-2 production of ConA-activated T lymphocytes through inhibiting NF-κB and calcineurin/NFAT signaling

Min Cai,Ruijuan Qi,Muqing Wang,Congyu Wu,Qian Chen,Yilin Guo,Yu Liu,Xin Huang,Yuan Gao,Yun Qi

DET decreases the transcription and translation of IL-2 in ConA-activated T cells. • DET inhibits ConA-activated NF-κB pathway, but fails to suppress MAPK signaling. • DET dampens ConA-induced nuclear translocation of NFAT. • DET directly suppresses calcineurin (CaN) activity not by reducing cytoplasmic Ca 2+ . • DET lowers serum IL-2 level of anti-CD3 antibody-treated mice. Deoxyelephantopin (DET) is a sesquiterpene lactone isolated from Elephantopus scaber , a traditional medicinal plant valued for its heat-clearing and detoxifying properties. As one of the major bioactive components, DET exhibits a variety of pharmacological activities, such as antitumor, antimicrobial, and anti-inflammatory effects. Nevertheless, its effect on T cell activation remains underexplored. Our study indicated that DET suppressed the proliferation and interleukin-2 (IL-2) production in T cells activated by various stimuli for T cell receptor (TCR)/CD3 signaling (i.e., concanavalin A (ConA), anti-CD3 antibody, and allogeneic major histocompatibility complex (MHC)). Mechanistically, DET lowered IL-2 mRNA level without affecting its stability in ConA-activated Jurkat T cells. Among three nuclear transcriptional pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT)) triggered by ConA, DET did not suppress MAPK signaling, but significantly inhibited NF-κB activation by hindering inhibitor of kappa-B alpha (IκBα) phosphorylation and degradation, thereby preventing p65 nuclear translocation. Concurrently, DET could dampen the activation of NFAT signaling through inhibiting the activity of calcineurin (CaN) to impede NFAT nuclear translocation independent of decreasing cytoplasmic Ca 2+ (Ca 2+ [c] ). Unlike classical CaN inhibitors (CNIs), DET inhibits CaN activity without involving immunophilins. In vivo , DET could also reduce serum IL-2 level in acute T-cell activation mouse model induced by intravenous injection of anti-CD3 antibody. In conclusion, our findings reveal DET's dual mechanisms (NF-κB and NFAT inhibition) responsible for repressing IL-2 expression in the activated T cells, which may provide a promising candidate for the development of a novel IL-2 suppressive agent. Download: Download high-res image (270KB) Download: Download full-size image

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Food Science & Nutrition · 2026 ·Vol. 14 ·期 4 ·e71768 · IF 5

The Herbal Pair Daphniphyllum calycinum– Polygonum hydropiper Alleviates Gastric Mucosal Injury via Regulating Autophagy and Targeting the TLR4/NF‐κB/NLRP3 Pathway

Yunyun Zhi,Keli Zhou,Xueqing Huang,Yonghui Li,Ye Zhu,Yiqiang Xie,Shouzhong Ren

Gastric mucosal injury refers to the pathological changes characterized by congestion, edema, bleeding and erosion of the gastric mucosa caused by various factors. This condition is a significant feature of gastritis in which the inflammatory response plays a critical role in its pathogenesis. The herbal pair Daphniphyllum calycinum – Polygonum hydropiper (DCPH), known for its anti‐inflammatory and antioxidant properties, has been shown to alleviate gastric mucosal injury. This study aimed to elucidate the mechanism by which DCPH alleviates gastric mucosal injury by integrating network pharmacology with both in vivo and in vitro experimental validation. The results indicated that DCPH treatment significantly increased the antioxidant capacity of the cells and decreased the expression of inflammation‐related factors. DCPH suppressed macrophage M1 polarization while inducing apoptosis in damaged cells. Furthermore, DCPH diminished structural gastric mucosal damage and gastric inflammation. DCPH promotes autophagy by upregulating the expression of LC3II/I and Beclin1, and downregulating P62 accumulation, thereby inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway and M1 polarization, and reducing the release of inflammatory factors. However, these effects can be reversed by the autophagy inhibitor chloroquine (CQ). In conclusion, DCPH alleviates gastric mucosal injury via regulating autophagy and targeting TLR4/NF‐κB/NLRP3, thereby offering insights for the treatment of gastrointestinal diseases. The schematic diagram illustrated the proposed mechanism of DCPH in mouse macrophages. DCPH promotes autophagy to suppress the TLR4/NF‐κB/NLRP3 pathway and M1 polarization, thereby attenuating cellular oxidative stress and inflammation.

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INTERNATIONAL IMMUNOPHARMACOLOGY · 2026 · IF 5.6

DEC-205-mediated liposomal delivery of OVA and Eucommia polysaccharides: dendritic cell targeting, adjuvant activity, and TLR-NF-κB-mediated immune enhancement

Shuhui Yang,Yan Yang,Qian Yang,Ziwei Liu,Hangyu Li,Yanwen Yang,Yao Wang,Shanshan Li,Juan Liu,Haibo Feng

DEC-205 monoclonal antibodies were assembled on the surface of liposomes carrying OVA antigen and Eucommia ulmoides polysaccharides to generate a delivery system with targeted dendritic cells. The liposomal encapsulation process of Eucommia ulmoides polysaccharide was optimized, and DEC-205-EUPS-OVA-LP was synthesized under optimal conditions to improve the utility of Eucommia ulmoides polysaccharide. Meanwhile, the physicochemical properties and adjuvant activity of the delivery system were evaluated in vitro .The optimized liposomes exhibited uniform particle size (<220 nm), suitable zeta potential (−11 to −15 mV), good dispersity (PDI < 0.3), and favorable encapsulation efficiency. 39.1 μg/mL DEC-205-EUPS-OVA-LP can promote the proliferation of dendritic cells and promote their antigen uptake. Furthermore, DEC-205-EUPS-OVA-LP significantly enhanced the secretion of IL-2, IL-6, IFN-γ, and TNF-α and elevated the expression of the co-stimulatory molecules CD80, CD86, and MHC-II on dendritic cells. High-throughput sequencing and Western blot results showed that DEC-205-EUPS-OVA-LP upregulated immune-related genes in dendritic cells and enhanced immunity via the TLR-NF-κB pathway. In summary, DEC-205-EUPS-OVA-LP targets dendritic cells to facilitate antigen uptake, processing, and presentation, promotes dendritic cell maturation, and enhances the immune response.

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