Drug Delivery and Translational Research
·
2026
·
IF 6.9
Rao Qing,Pan Binbin,Peng Zheng,Yu Qimin,Yu Yulong,Wang Huijun
Dysregulated immune responses and excessive inflammation are central drivers of early sepsis progression. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. However, the therapeutic potential and mechanistic basis of IL-10 mRNA delivery in correcting early immune dysfunction during sepsis remain poorly defined. In this study, we developed a mannose-modified mesoporous silica nanoparticle system (MMP/IL-10 mRNA) to stabilize IL-10 mRNA and enable sustained release for the immunoregulatory treatment of sepsis. The nanoparticles exhibited uniform size, structural stability, efficient mRNA protection, and sustained IL-10 expression. In LPS-stimulated macrophages, MMP/IL-10 mRNA enhanced cell viability, promoted M2 polarization, suppressed pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-17A), and restored the IL-10/IL-17A balance. In a cecal ligation and puncture–induced murine sepsis model, MMP/IL-10 mRNA improved 7-day survival, enhanced bacterial clearance, alleviated lung and liver injury, and ameliorated systemic inflammatory imbalance. Mechanistically, treatment reduced TLR4 expression, prevented IκBα degradation, inhibited NF-κB p65 phosphorylation, and upregulated endogenous IL-10 and DEL-1. Importantly, no detectable toxicity or organ damage was observed. These findings demonstrate that MMP/IL-10 mRNA enables efficient, sustained, and safe delivery of IL-10 mRNA, attenuates early hyper-inflammation, and improves immune dysregulation in sepsis, highlighting its potential as a promising immunoregulatory therapeutic strategy. Graphical abstract
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Wenwei Li,Yang Liu,Ming Wei,Zhichao Yang,Zhaoyu Li,Zezhong Guo,Liang Yan,Yang Lu,Hao Tang,Bofeng Li,Wei Huang
Osteoarthritis (OA) is a low-grade inflammatory disease that is highly associated with severe hyperplasia of the synovial membrane and the degeneration of cartilage. Interleukin-10 (IL-10), has been extensively studied, while its receptor, IL-10Rα, has not been widely mentioned in the context of OA. A significant difference is found in the expression of IL-10Rα in synovial macrophages from normal and OA patients, along with a marked increase in the glycolytic activity of synovial macrophages. In IL-10Rα Lysm OA mice, the specific deficiency of IL-10Rα exacerbated the progression of OA. Mechanistically, hypoxia-inducible factor-1α (HIF-1α) is identified as a key transcription factor, and its inhibition significantly weakened the glycolytic process. Additionally, differences in ferroptosis of chondrocytes are observed. After co-culturing the two types of cells in vitro, a significant connection is found between the glycolytic state of synovial macrophages and the ferroptosis of chondrocytes. To achieve targeted therapy, MI@UN, a biomimetic nanoparticle encapsulating NO-prednisolone in UIO-66-NH 2 , surface-modified with IL-10, and coated with macrophage membranes (MM), is developed. It significantly slows osteoarthritis progression in mice. This offers new insights into OA pathogenesis, highlighting IL-10Rα as a therapeutic target and supporting MI@UN's translational use for OA treatment.
研究领域:
免疫学
·
骨科
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纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2025
·
IF 2.5
Zhihua Wang,Denghui Li,Yanghao Wang,Ping Yuan,Wan Zhang,Yihe Zhang,Fei He,Jianyi Yang,Hangchuan Bi,Hao Duan
(1)Background: Inflammation plays a key role in spinal cord injury (SCI), where excessive inflammatory responses exacerbate neural damage and hinder regeneration. Modulating macrophage polarization, particularly through the sustained release of IL-10 to promote the anti-inflammatory M2 phenotype, represents a promising strategy to mitigate inflammation. In this study we developed a Hyaluronic Acid Methacryloyl (HAMA) hydrogel capable of sustained IL-10 release to regulate macrophage polarization and explore its therapeutic potential. (2)Methods: A photo-curable HAMA hydrogel was synthesized via methacrylation and designed for the sustained release of IL-10. The structural and functional properties were characterized using NMR and FT-IR. In vitro assays, including immunofluorescence, flow cytometry, and Western blotting, were performed to evaluate IL-10’s effect on macrophage polarization. The anti-inflammatory and reparative effects of the hydrogel were further validated in a rat SCI. (3)Results: The HAMA hydrogel with sustained IL-10 release demonstrated excellent biocompatibility. It significantly promoted macrophage polarization to the anti-inflammatory M2 phenotype by increasing the expression of CD206. In vivo studies demonstrated that the group treated by HAMA with IL-10 exhibited recovery of sensory and motor functions, along with improvement of the inflammatory microenvironment at the site of injury. (4)Conclusion: The HAMA hydrogel with sustained IL-10 release effectively alleviates inflammation, enhances motor function after SCI, and serves as a promising immunomodulatory platform. This novel approach presents considerable potential for improving neural regeneration.
研究领域:
生物材料学
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神经科学
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免疫学
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DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2026
·
IF 8.2
Jiawei Yang,Qiong Zhang,Haichen Zhang,Tao Zhou,Lening Chen,Qianqian Xiao,Qinghe Meng,Jianjun Jiang,Weidong Hao,Xuetao Wei
Bis(2-ethylhexyl) tetrabromophthalate (TBPH), an emerging brominated flame retardant, has raised environmental concern due to its endocrine-disrupting potential. While epidemiological evidence and our previous animal studies have linked TBPH to thyroid disruption, the molecular mechanisms remain unclear. This study aimed to identify potential molecular targets and downstream pathways involved in TBPH-induced effects on thyroid. We found that TBPH (100 nM) significantly upregulated the expression of key thyroid hormone synthesis markers PAX-8, TPO, and TG in human thyroid follicular cells (Nthy-ori 3-1). In silico docking identified S1PR3 as a potential interactor with moderate predicted affinity, and cellular thermal shift assay (CETSA) provided initial evidence of target engagement. S1 pr 3 knockdown partially attenuated TBPH-induced marker upregulation. Mechanistically, TBPH increased interleukin-10 (IL-10) in an S1PR3-dependent manner, coupled with activation of a non-canonical JAK-STAT pathway (JAK3, TYK2, STAT2, and STAT5). Further, overexpression of Il-10 enhanced downstream effector expression, whereas overexpression of Jak3 similarly promoted PAX-8 and TPO levels; conversely, Tyk2 knockdown reduced these markers, supporting a functional role for this alternative signaling cascade. Importantly, key elements of this pathway were recapitulated in thyroid tissues of TBPH-treated rats, providing in vivo corroboration for the cellular observations. Collectively, our results suggest a S1PR3/IL-10/non-canonical JAK-STAT axis as a candidate mechanism for TBPH-induced thyroid marker upregulation, providing a hypothesis-generating framework for future toxicological investigations of TBPH and related emerging brominated flame retardants.
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
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IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Jie Zhao,Tao Xue,Zhiyuan Liu
Managing neuropathic pain is challenging due to the complex pathogenetic mechanisms and limited available drugs and therapeutic options. Innovative nanofiber systems offer a novel method to effectively administer therapeutic cytokines, drugs, or small molecule compounds to achieve better relief of neuropathic pain. Here, we report a novel nanofiber with controlled release of IL-10 for implantation into ligated nerve roots and hemisection-injured spinal cords to exert anti-inflammatory effects and attenuate neuropathic pain. An electrospun poly(l-lactide) (PLLA) nanofiber was modified by a polydopamine (PDA) coating, and this nanofiber demonstrated sustained release of IL-10 in vitro. We showed that L5 spinal nerve ligation and T13 spinal cord hemisection induced peripheral and below-level central neuropathic pain in rats, along with the development of neuroinflammation. Spinal IL-10 was also markedly changed after spinal nerve ligation (SNL) or spinal cord injury (SCI), especially in the spinal dorsal horn. Rats were treated postsurgically with IL-10 that was loaded on PDA@PLLA nanofibers as an implantable cytokine delivery system. IL-10 levels were significantly upregulated after the implantation of PDA@PLLA nanofibers in SNL and SCI rats. We further demonstrated that the implantation could inhibit glial activation and neuronal excitability in vivo, along with suppressing the expression levels of pro-inflammatory cytokines. Most importantly, IL-10-loaded PDA@PLLA nanofiber treatment attenuated the development and maintenance of peripheral and central neuropathic pain. Together, the combination of IL-10 and PDA@PLLA nanofibers provides a novel implantable delivery system for treating neuroinflammatory conditions and may emerge as a promising agent to prevent chronic neuropathic pain.
研究领域:
纳米医学
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神经科学
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疼痛管理
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生物材料
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药物递送
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
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IF 3.973
Menghang Zu,Heliang Song,Jiabin Zhang,Qiubing Chen,Shiqin Deng,Brandon S.B. Canup,Yi Yuan,Bo Xiao
Edible plant-derived nanoparticles (NPs) have attracted increasing attention in the treatment of ulcerative colitis (UC). Lycium barbarum (LB), a popular functional fruit, possesses various biological functions. Here, fat-soluble contents were extracted from LB and further processed into LB lipid-derived NPs (LBLNs). The resultant NPs had an average hydrodynamic diameter around 189.2 nm, narrow size distribution (polydispersity index = 0.2), and negative surface charge (-34.9 mV). Moreover, they could be efficiently taken up by UC therapy-related target cells (macrophages), and over 69.0 % of macrophages internalized LBLNs after 4 h co-incubation. We further found from the in vitro results that LBLNs had strong capacities to inhibit the secretion of the main pro-inflammatory cytokines (TNF-α and IL-12) and up-regulate the expression of the typical anti-inflammatory factor (IL-10). Finally, mice experiments confirmed that LBLNs after oral administration could specifically accumulate into inflamed colon tissues, and further attenuate UC-relevant symptoms ( e.g. , bodyweight loss, colon shortening, increase of spleen weight, and histopathological appearance, as well as ulceration). Collectively, this study demonstrates the excellent therapeutic outcomes of LBLNs against UC and provides a promising edible nanotherapeutic for UC treatment.
研究领域:
药理学
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纳米技术
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炎症性肠病
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Xiaodong Liu,Tianyi Jiang,Huiyun Jin,Chenxi Yan,Yuqi Tong,Jiaquan Ding,Yaqi Li,Lian Huang,Zhaohui Zhang
Beryllium sulfate (BeSO 4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO 4 -induced inflammatory response in 16HBE cells, we established the BeSO 4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ 0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO 4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO 4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-β. This study revealed a novel mechanism of BeSO 4 -induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.
研究领域:
毒理学
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-11
·
IF 4.8
Huang Ni,Yang Yi-Na,Huang Jia,Shao Hui-Yan,Li Yan-Lang,Qin Shi-Hui,Li Han-Fen,Shen Xiao-Jiang,Yang Liu,Hu Jiang-Miao
Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D. rubrovalvata . Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 10 3 and 1.25 × 10 4 Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)- α -D-Gal p -(1 → 6)- α -D-Gal p -(2,1 → 6)- α -D-Man p -(2,1 → 6)- α -D-Gal p -(1, and branch chains were β -D-Xyl p -(1 → 3)- α -L-Fuc p -(1 → 4)- α -D-Man p -(1 → and α -D-Gal p -(1 → 3)- α -D-Gal p -(1 → . The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity. Graphical Abstract
研究领域:
真菌学
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免疫学
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生物化学
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2021
·
IF 6.576
Yuan Li,Chu Qian,Wu Xiaoyun,Yang Bei,Zhang Wei,Jin Wengang,Gao Ruichang
Research has shown that cartilage containing chondroitin sulfate and protein presents versatile bioactivities. Chondroitin sulfate in cartilage is beneficial to activate the immune system while the protein/peptide has not been fully understood. The current study investigated the antioxidant and anti-inflammatory properties of ethanol-soluble hydrolysates of sturgeon cartilage (ESCH) prepared through hot-pressure, enzymatic hydrolysis and ethanol extraction. UV spectrum, IR and agarose gel electrophoresis results suggested the successful exclusion of chondroitin sulfate from peptides. Nitric oxide (NO) floods in cells activated by inflammation. It was inhibited when administrated with ESCH. To further explain the observed anti-inflammatory activity, ESCH was separated with Sephadex G-15 into 3 components, among which F3 showed a higher NO inhibition rate and significantly reduced the production of the proinflammatory cytokine IL-6. In addition, the yield of IL-10 increased. Western blotting suggested that F3 downregulated the NO content and IL-6 level by suppressing Mitogen-activated protein kinases (MAPK) channels. Moreover, both ESCH and F3 showed DPPH and ABTS free radical scavenging abilities which was possibly related to the anti-inflammatory property. These results indicated that ESCH behaved anti-inflammatory and antioxidant activities. Cartilage may be a good source to produce anti-inflammatory peptides.
研究领域:
生物化学
·
免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Xiaoli Huang,Senyue Liu,Fengyuan Zuo,Lin Luo,Defang Chen,Yangping Ou,Yi Geng,Yufan Zhang,Gang Lin,Shiyong Yang,Wei Luo,Lizi Yin,Zhi He
Methods of supporting mucosal immune barrier integrity and prevention of some pathogenic infections in aquatic species , are key areas of active study, often focusing on feed additives . The objectives of this study were to explore the effects of feeding cMOS (concentrated mannan oligosaccharide) on the gill and skin mucosal barriers of goldfish ( Carassius auratus Linnaeus ) and evaluate health status during Ichthyophthirius multifiliis infection. After feeding the cMOS-containing diet for 60 days, Hematoxylin and eosin (H&E) staining showed greater length of gill lamella and thicker dermal dense layer, while Alcian Blue and Periodic acid–Schiff (AB-PAS) staining showed higher numbers of mucin cells in cMOS fed fish. Chemical analysis showed that fish fed cMOS had greater enzyme activity of lysozyme (LZM) and alkaline phosphatase (AKP) in gill and skin tissues, while qRT-PCR revealed higher expression of Muc-2 and IL-1β , as well as lower expression of IL-10 . After Ichthyophthirius multifiliis challenge, goldfish fed the cMOS diet had lower mortality and infection rates, as well as fewer visible white spots on the body surfaces. Histologically, the gill and skin of these fish presented less tissue damage and fewer parasites, and had a greater number of mucus cells. In addition, the expression of Muc-2 and IL-10 were notably higher while the expression of IL-1β was significantly lower in cMOS fed goldfish than control fed fish. In this study, cMOS fed goldfish had stronger immune barrier function of skin and gill mucous, and better survival following Ichthyophthirius multifiliis infection.
研究领域:
水生生物学
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免疫学
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渔业科学
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兽医学
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DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-14
·
IF 3.8
Kong Chenfan,Sun Jianrong,Hu Xinzi,Li Guangzhi,Wu Song
Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.
研究领域:
癌症治疗
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纳米技术
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药学
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免疫学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）