ORAL DISEASES
·
2023
·
IF 3.8
Sitong Hu,Yihui Zhu,Shujia Yu,Yanchuan Guo,Yihu Wang,Menghao Lv,Wei Bai,Pan Ma
Objective The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. Methods Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. Results IL-10 induced expression of arginase 1, TGF-β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. Conclusions IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.
研究领域:
免疫学
·
骨科
·
再生医学
·
口腔科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 06
·1527-1546
·
IF 5.7
Cheng-Xi Li,Yu-Meng Wang,Wen-Jing Zhang,Shu Zhang,Jian-Ping Li,Tong Zhou,Jin-Ao Duan,Jian-Ming Guo
Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10 − ∕ − ). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF- α levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10 − ∕ − mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae , Sutterellaceae , Erysipelotrichaceae , Burkholderiaceae , Desulfovibrionaceae , and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.
研究领域:
免疫学
·
微生物学
·
药理学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Mengxing Cui,Qianmei He,Ziwei Wang,Yongjiang Yu,Huan Gao,Ziqi Liu,Honghao Peng,Han Wang,Xue Zhang,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Qing Wang
Micro/nano-plastics (MPs/NPs) are a newly discovered environmental pollutant that can be ingested by humans through food and drinking water. In this study we evaluated the impact of MPs/NPs on the intestinal barrier and its mechanism. Doses of MPs/NPs were used to treat Caco-2/HT29-MTX in-vitro model and in-vivo model. In in-vitro model, 20 nm polystyrene nanoplastics (PS-NPs) had higher cytotoxicity than larger particles (200 nm and 2000 nm), and led to the increase of the permeability along with the decreased expression of tight junction proteins. Intriguingly, 20 nm PS-NPs elevated the expression of MUC2 simultaneously. Further studies revealed that PS-NPs increased the expression of HO1 through ROS generation, and then activated p38 to elevate IL-10 secretion in Caco-2 cell. The IL-10 secreted by Caco-2 cell promoted the expression of MUC2 in HT29-MTX cell through STAT1/3. Elevated MUC2 expression alleviates the cytotoxicity of PS-NPs. Besides, increased intestinal permeability and up-regulation of MUC2 through Ho1/p38/IL-10 pathway was also observed in 20 nm PS-NPs treated mouse model. In conclusion, PS-NPs can induce the intestinal toxicity and result in the increased adaptive expression of MUC2 to resist this adverse effect. People with inadequate mucin expression need to pay more attention to the toxicity of PS-NPs. This study provided a valuable insight for clarifying the mechanism and potential risk of intestinal toxicity induced by nanoplastics.
研究领域:
环境科学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Wei Wang,Yingzhuo Ding,Chunxia Yu,Qingqing Chi,Xia Fu,Mengjiao Deng,Dongxia Duan,Jinbao Wei,Ronghua Ding,Yufei Xi,Qin Li,Le Ma
Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 μg and 36.80 μg, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-α, IL-1β, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.
研究领域:
药理学
·
神经科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Zhejie Chen,Wei Hao,Caifang Gao,Yangyang Zhou,Chen Zhang,Jinming Zhang,Ruibing Wang,Yitao Wang,Shengpeng Wang
With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.
研究领域:
药学
·
分子生物学
·
纳米技术
·
炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
·
2023
·Vol. 21
·期 1
·1-18
·
IF 8.4
Liao Zhaohong,Lan Haiqiang,Jian Xiaoting,Huang Jingwen,Wang Han,Hu Jijie,Liao Hua
Background To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection. Methods CTX myoinjury was manipulated in TGF-βr2 flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2 −/− ). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation. Results In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V − F4/80 + Tunel + macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67 + apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages. Conclusions Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.
Video Abstract
研究领域:
免疫学
·
肌肉生物学
·
细胞信号传导
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2021
·Vol. 27
·期 10
·1157-1172
·
IF 5.243
Le Ma,Shiyu Peng,Jinbao Wei,Mengjing Zhao,Khalil Ali Ahmad,Jinghong Chen,Yong-Xiang Wang
Aim This study aimed to investigate the regulation of pain hypersensitivity induced by the spinal synaptic transmission mechanisms underlying interleukin (IL)-10 and glucagon-like peptide 1 receptor (GLP-1R) agonist exenatide-induced pain anti-hypersensitivity in neuropathic rats through spinal nerve ligations. Methods Neuropathic pain model was established by spinal nerve ligation of L5/L6 and verified by electrophysiological recording and immunofluorescence staining. Microglial expression of β-endorphin through autocrine IL-10- and exenatide-induced inhibition of glutamatergic transmission were performed by behavioral tests coupled with whole-cell recording of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) through application of endogenous and exogenous IL-10 and β-endorphin. Results Intrathecal injections of IL-10, exenatide, and the μ-opioid receptor (MOR) agonists β-endorphin and DAMGO inhibited thermal hyperalgesia and mechanical allodynia in neuropathic rats. Whole-cell recordings of bath application of exenatide, IL-10, and β-endorphin showed similarly suppressed enhanced frequency and amplitude of the mEPSCs in the spinal dorsal horn neurons of laminae II, but did not reduce the frequency and amplitude of mIPSCs in neuropathic rats. The inhibitory effects of IL-10 and exenatide on pain hypersensitive behaviors and spinal synaptic plasticity were totally blocked by pretreatment of IL-10 antibody, β-endorphin antiserum, and MOR antagonist CTAP. In addition, the microglial metabolic inhibitor minocycline blocked the inhibitory effects of IL-10 and exenatide but not β-endorphin on spinal synaptic plasticity. Conclusion This suggests that spinal microglial expression of β-endorphin mediates IL-10- and exenatide-induced inhibition of glutamatergic transmission and pain hypersensitivity via presynaptic and postsynaptic MORs in spinal dorsal horn.
研究领域:
神经科学
·
药理学
·
疼痛研究
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2021
·
IF 7.561
Wu Binxin,Gao Furong,Lin Jianhua,Lu Lixia,Xu Huiming,Xu Guo-Tong
Allergic conjunctivitis (AC) is the most prevalent form of mucosal allergy, and the conditioned medium (CM) from mesenchymal stem cells has been reported to attenuate some allergic diseases. However, the therapeutic effects of CM from different tissue stem cells (TSC-CM) on allergic diseases have not been tested. Here, we studied the effects of topical administration of different human TSC-CM on experimental AC (EAC) mice. Only human amniotic epithelial cell-CM (AECM) significantly attenuated allergic eye symptoms and reduced the infiltration of immune cells and the levels of local inflammatory factors in the conjunctiva compared to EAC mice. In addition, AECM treatment decreased immunoglobulin E (IgE) release, histamine production, and the hyperpermeability of conjunctival vessels. Protein chip assays revealed that the levels of anti-inflammatory factors, interleukin-1 receptor antagonist (IL-1ra) and IL-10, were higher in AECM compared to other TSC-CM. Furthermore, the anti-allergic effects of AECM on EAC mice were abrogated when neutralized with IL-1ra or IL-10 antibody, and the similar phenomenon was for the activation and function of B cells and mast cells. Together, the present study demonstrated that AECM alleviates EAC symptoms by multiple anti-allergic mechanisms mainly via IL-1ra and IL-10. Such topical AECM therapy may represent a novel and feasible strategy for treating AC.
研究领域:
眼科学
·
免疫学
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-18
·
IF 10.1
Yao Yu,Liu Yu-ying,Li Jian-feng,Chen Yun-shuo,Shi Lei,Shen Yang,Yang Li-li,Yang Qing
Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients’ bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.
研究领域:
肿瘤学
·
免疫学
·
血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Weiling Tan,Yufang Fu,Wanyu Hu,Yating Lin,Jingni Cai,Xuelin Huang,Yinyi OuYang,Sheng Lin,Ling Ye
Loganic acid (LA), a major iridoid glycoside from Gentiana macrophylla Pall., possesses anti-inflammatory and immunomodulatory properties, but its therapeutic potential in rheumatoid arthritis (RA) and its interaction with the gut microbiota remain poorly defined. Here, we show that LA markedly and dose-dependently attenuates disease severity in collagen-induced arthritis mice, as evidenced by reduced clinical arthritis scores, systemic inflammatory cytokines, and synovial tissue damage. LA reshaped the gut microbiota, and fecal microbiota transplantation from LA-treated donors partially reproduced its protective effects, indicating a causal contribution of the altered microbial community. In particular, LA selectively enriched OTUs annotated as Lactobacillus murinus ( L. murinus ) and increased levels of the microbial tryptophan metabolite indole-3-acetic acid (IAA). Both LA and IAA activated aryl hydrocarbon receptor (AhR) signaling, suppressed tumor necrosis factor-α-induced inflammatory responses in human synoviocytes, and, in vivo, enhanced IAA–AhR–interleukin-10 (IL-10) signaling in arthritic joints. Pharmacological inhibition of AhR with CH223191 substantially reversed LA's therapeutic effects, demonstrating that AhR signaling plays a critical role in its anti-arthritic activity. Collectively, these findings demonstrate that LA protects against RA through a dual mechanism: direct activation of AhR in joint tissues and indirect reinforcement of AhR signaling through an L. murinus -associated microbial IAA axis. This study highlights a gut microbiota–metabolite–AhR pathway as a key mediator of LA's anti-arthritic effects and supports LA as a promising microbiota-informed therapeutic candidate for RA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Shuifang Mao,Bin Wang,Lin Yue,Wenshui Xia
In order to improve the anti-inflammatory activity of chitosan oligosaccharide (COS), chitosan oligosaccharide graft citronellol derivatives (COS-g-Cit1-3) were successfully synthesized via grafting citronellol (Cit) onto COS backbone. The degrees of substitution (DS) of COS-g-Cit1-3 were 0.165, 0.199 and 0.182, respectively. The structure of COS-g-Cit1-3 was confirmed by UV–vis, FT-IR, 1 H NMR and elemental analysis. The in vivo anti-inflammatory activity evaluation results displayed that COS-g-Cit1-3 drastically reduced the paw swelling, and the oedema inhibitions were 22.58 %, 29.03 % and 25.81 %, respectively. The results indicated that the anti-inflammatory effects of COS-g-Cit1-3 were significantly higher than COS and COS-g-Cit2 exhibited the highest anti-inflammatory ability. The results also presented that COS-g-Cit1-3 reduced the expression levels of TNF-α by promoting the secretion of IL-4 and IL-10. Moreover, western blot analysis data proved that COS-g-Cit1-3 inactivated the NF-κB signaling pathway via inhibiting the phosphorylation of p65, IKBα and IKKβ.
研究领域:
药学
·
生物技术
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aggregate
·
2025
·
IF 13.7
Shundong Cai,Mengdie Li,Jinfa Ye,Mingyou Zhang,Jingbin Zhuang,Yuhang Cheng,Hongjin Li,Lang Ke,Xingyuan Wei,Yun Han,Huanhuan Liu,Gang Liu,Chengchao Chu
Corneal neovascularization (CNV) is a debilitating ocular surface disease that severely compromises visual function and carries a significant risk of vision loss. Despite its clinical impact, the development of effective and safe pharmacological treatments for CNV remains an unmet medical need. The pathogenesis of CNV is largely driven by inflammation and excessive oxidative stress. In this study, we introduce a novel nanotherapeutic strategy utilizing vanadium carbide quantum dots (V 2 C QDs) with intrinsic nanozyme properties, co-encapsulated with a plasmid encoding interleukin-10 (IL-10) within a biomimetic metal-organic framework (MOF) for the treatment of CNV. To enhance targeting and biocompatibility, the nanoparticles (NPs) are further coated with mesenchymal stem cell (MSC)-derived cell membrane vesicles (CMVs), yielding the final nanomedicine designated as MOF-V 2 C-Plasmid@CMVs (MVPC). In vitro studies demonstrate that MVPC NPs effectively scavenge reactive oxygen species (ROS) induced by tert -butyl hydroperoxide (tBOOH), mitigating oxidative stress. Moreover, the successful delivery and expression of the IL-10 plasmid in RAW264.7 cells result in elevated IL-10 secretion, showcasing robust anti-inflammatory activity. The CMV coating facilitates targeted delivery, enabling the efficient accumulation of MVPC NPs in the CNV region following topical administration via eye drops. In vivo experiments in CNV model rats reveal that MVPC nanotherapeutics significantly suppress neovascularization without inducing adverse effects. Collectively, this study provides proof of concept for a multifunctional nanotherapeutic platform targeting CNV, offering a promising and clinically translatable approach for the treatment of this challenging ocular disease.
研究领域:
眼科
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）