Nature Nanotechnology
·
2024
·
IF 38.1
Wei Tingting,Pan Tiezheng,Peng Xiuping,Zhang Mengjuan,Guo Ru,Guo Yuqing,Mei Xiaohan,Zhang Yuan,Qi Ji,Dong Fang,Han Meijuan,Kong Fandi,Zou Lina,Li Dan,Zhi Dengke,Wu Weihui,Kong Deling,Zhang Song,Zhang Chunqiu
Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus -infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1 −/− mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.
研究领域:
药学
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生物医学工程
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免疫学
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伤口愈合
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组织工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Guangyu Xu,Xi Lv,Yanbo Feng,Han Li,Cong Chen,Hao Lin,He Li,Chunmei Wang,Jianguang Chen,Jinghui Sun
The aim of this study was to analyze the active components of Schisandra chinensis on liver injury and its mechanism in mice by network pharmacology . The active components of S. chinensis were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and their corresponding targets were predicted. The targets of liver injury were searched through Therapeutic Targets Database (TTD), DisGeNET and drugbank databases, and the Venn diagram was constructed to obtain the action targets. The “drug-active component-target” network and protein-protein interaction network (PPI) were constructed by using STRING database and Cytoscape software, and the key targets were further screened by the enrichment analysis of relevant KEGG pathways. Finally, a CCl 4 -induced mouse liver injury model was established to verify the efficacy and related targets of S. chinensis and clarify its mechanism. Eight active components and 56 related targets of S. chinensis were screened out based on their oral bioavailability (OB) and drug likeness (DL). Five targets of S. chinensis related to liver injury were found by using the Venn diagram. The key targets, namely Ptgs2 and Nos2 genes, were further screened out by constructing a PPI network, and Schisandrol B (SCB) was considered the key component most closely related to the liver injury in S. chinensis . The results indicate that SCB may play a role in the treatment of the CCl 4 -induced liver injury by down-regulating the expression of iNOS and COX-2, and regulating the expression of NF-κB and IL-17 signaling pathway to inhibit the expression of proinflammatory factors.
研究领域:
药理学
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分子生物学
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网络药理学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PARASITOLOGY
·
2023
·
IF 2.1
Muhammad Ehsan,Rui-Si Hu,Meng Wang,Jun-Ling Hou,Muhammad Rashid,Muhammad Irfan Malik
Legumains belonging to C_13 peptidase family of proteins, and are ubiquitously disseminated among all vertebrate and invertebrate organisms, and have been implicated in innumerable biological and cellular functionality. Herein, we characterized and evaluated immunoregulatory characteristics of Legumain-1 from Fasciola gigantica (Fg-LGMN-1) during its interaction with host immune cells . The isopropyl-ß-d-thiogalactopyranoside (IPTG) stimulated RFg-LGMN-1 protein was positively detected by rat serum containing anti-RFg-LGMN-1 polyclonal antibodies . Furthermore, the uptake of RFg-LGMN-1 by goat monocytes was successfully confirmed using Immunofluorescence Assay (IFA). The immunohistochemical analysis revealed the native localization of LGMN-1 protein on the periphery and internal structures such as suckers, pharynx, and genital pore of the adult parasite, thereby validating its presence in excretory-secretory (ES) products of F. gigantica . The RFg-LGMN-1 co-incubated with concanavalin-A (Con-A) stimulated the increase of interleukin 2 (IL-2), IL-10, and IL-17 in monocytes derived from peripheral blood mononuclear cells (PBMCs) in the concentration-dependent manner. However, the IL-4 cytokine in response to the RFg-LGMN-1 protein declined. These results illuminated the role of LGMN-1 during the parasite-host interface. Our findings elaborated additional evidence that Legumain protein play a role in the manipulating host immune responses during parasite infections. However, further evaluation of RFg-LGMN-1 protein in context of its immunomodulatory roles should be conducted to enhance our understandings of the mechanisms employed by F. gigantica to evade host immune responses.
研究领域:
免疫学
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寄生虫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORAL PATHOLOGY & MEDICINE
·
2021
·Vol. 51
·期 1
·74-85
·
IF 4.253
Jing-Ya Yang,Fang Wang,Gang Zhou
Background Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. Methods Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. Results Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 + , CD69 + , CD103 + and PD-1 + MAIT cells was increased in OLP, while that of CD8 + and CD49d + MAIT cells was decreased. The percentage of CD103 + , PD-1 + and PD-L1 + γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. Conclusion The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.
研究领域:
免疫学
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炎症
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口腔疾病
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细胞生物学
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DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 10
·1-12
·
IF 2.6
Bi Jinli,Huang Xin,Meng Liqin,Li Jinghan,He Yu,Jin Jing,Li Taijie
Hypervirulent Klebsiella pneumoniae (hvKP) possesses multiple virulence factors and causes severe infections with elevated mortality rates. It induces a strong inflammatory response in the host, with macrophages playing a key role in defense and inflammation. However, the signaling pathways of macrophages involved in response to hvKP infection remain unclear. In this study, we developed a stable hvKP infection model in differentiated THP-1 macrophages, confirmed by CFU assay and LDH cytotoxicity assay, and subsequently performed transcriptomic profiling analysis of hvKP-infected cells to characterize infection-induced gene expression changes. Pathway and differential gene correlation network analyses identified 14 potential regulatory genes primarily involved in inflammation. These changes in gene expression were further validated by Reverse transcription quantitative PCR (RT-qPCR). KEGG and GO analyses revealed several key signaling pathways involved in inflammation and immune response, particularly the TNF, IL-17, NF-κB, and JAK-STAT pathways. Further analysis indicated that the NF-κB signaling pathway plays a central role in the inflammatory response to hvKP infection, whereas the TNF and IL-17 pathways act synergistically to upregulate pro-inflammatory cytokines and chemokines. Western blot analysis confirmed the expression of TRAF6 and NF-κB p65 protein during hvKP infection. This study provides valuable insights into the molecular mechanisms of macrophage responses to hvKP, offering potential targets for therapeutic intervention.
研究领域:
微生物学
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免疫学
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分子生物学
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传染病学
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基因组学
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细胞生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
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IF 5.811
Zhu Zhaoming,Chen Tingting,Wang Zhuxian,Xue Yaqi,Wu Wenfeng,Wang Yuan,Du Qunqun,Wu Yufan,Zeng Quanfu,Jiang Cuiping,Shen Chunyan,Liu Li,Zhu Hongxia,Liu Qiang
The label-free methods of proteomic combined with metabolomics were applied to explore the mechanisms of Cryptotanshinone (CPT) intervention in rats with acne. The model group consisted of rats given oleic acid (MC), then treated with CPT, while control groups did not receive treatment. The skin samples were significantly different between control, model and CPT-treated groups in hierarchical clustering dendrogram. Obvious separations of the skin metabolic profiles from the three groups were found through PCA scoring. In total, 231 and 189 differentially expressed proteins (DEPs) were identified in MC and CPT groups, respectively. By the KEGG analysis, five protein and metabolite pathways were found to be significantly altered. These played important roles in response to oleic acid-induced acne and drug treatment. CPT could negatively regulate glycolysis/gluconeogenesis and histidine metabolisms to decrease keratinocyte differentiation and improve excessive keratinization and cellular barrier function. CPT could down-regulate the IL-17 signaling pathway and regulate the acne-driven immune response of sebum cells. The biosynthesis of unsaturated fatty acids metabolism, glycerophospholipid metabolism and linoleic acid pathways could significantly alter sebum production and control sebaceous gland secretion after CPT treatment. The gap junction was up-regulated after CPT treatment and the skin barrier turned back to normal. Krt 14, Krt 16 and Krt 17 were significantly down-regulated, decreasing keratinization, while inflammatory cell infiltration was improved by down-regulation of Msn, up-regulation of linoleic acid and estrogen pathways after CPT treatment. These results propose action mechanisms for the use of CPT in acne, as a safe and potential new drug.
研究领域:
药理学
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分子生物学
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皮肤科
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系统生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Xu Wenhao,Ye Shiqi,Liu Wangrui,Guo Huaqi,Zhang Linhui,Wei Shiyin,Anwaier Aihetaimujiang,Chang Kun,Malafaia Guilherme,Zhang Hailiang,Ye Dingwei,Wei Gang
In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8 + effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4 + macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4 + macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4 + macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals. Graphical Abstract
研究领域:
环境健康
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分子生物学
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免疫学
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肾病学
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癌症研究
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zili Guo,Tao Chen,Xuehuan Wen,Qiangchang Fu,Jiabin Lai,Jiajin Li,Jiayu Chen,Jie Weng,Wang Wen,Qihua Cao,Junxiong Zhu,Zhaoming Ye,Xiaohua Yu,Lifeng Jiang
Osteoarthritis (OA) pathogenesis is profoundly influenced by dysregulated immune dynamics, where persistent interleukin-17 (IL-17)/T helper 17 (Th17) cell mediated inflammation coordinates with failed regenerative processes to perpetuate joint destruction. Here, we unveil the role of myeloid-derived suppressor cells (MDSCs) as dual-phase regulators that paradoxically orchestrate both inflammatory escalation and tissue repair in OA progression. Intra-articular administration of MDSCs in OA mice amplified IL-17 dependent inflammatory cascades and chemokine-driven leukocyte recruitment, revealing a context-dependent pro-inflammatory phenotype. Unexpectedly, MDSC depletion failed to attenuate joint damage, implying their indispensable yet multifaceted role in OA pathogenesis. Mechanistically, MDSCs exhibited functional plasticity by upregulating arginase-1 to polarize M2 macrophages, fostering a regenerative niche alongside their inflammatory activity. To resolve this duality, we developed a bio-responsive hydrogel-microsphere system integrating transforming growth factor β1 (TGF-β1) and interleukin-1 β1 antibody (anti–IL-1β) loaded mesoporous silica nanoparticles (MSNs). This spatiotemporally controlled platform selectively suppressed MDSC-mediated Th17 cell expansion while harnessing their intrinsic capacity to drive M2 macrophage polarization and chondrogenesis. The resultant shift from a pro-inflammatory to pro-regenerative microenvironment significantly attenuated cartilage erosion and restored joint integrity in OA models. Our findings redefine MDSCs as bifunctional immune orchestrators in OA and establish precision biomaterial guided immune decoding as a paradigm-shifting therapeutic strategy. By engineering MDSC plasticity through antagonistic cytokine delivery, this work provides a blueprint for microenvironment remodeling in degenerative joint diseases.
研究领域:
免疫学
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再生医学
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生物材料
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纳米医学
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风湿病学
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组织工程
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产品关联
DOI
PubMed
高影响因子
iScience
·
2021
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IF 5.458
Yuying Zhang,Anqi Guo,Cheng Lyu,Ran Bi,Zhaozhao Wu,Wenjing Li,Peng Zhao,Yudi Niu,Jie Na,Jianzhong Jeff Xi,Yanan Du
Summary It is still a challenge for synthesizing ‘cellular niche-mimics’ in vitro with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis in vivo , here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.
研究领域:
干细胞生物学
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组织工程
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细胞微环境
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蛋白质组学
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类器官培养
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DOI
PubMed
高影响因子
Food & Function
·
2024
·Vol. 15
·期 6
·3008-3022
·
IF 5.1
Danyin Yang,Qi Liu,Qiongyao Xu,Lin Zheng,Silu Zhang,Shan Lu,Guoxun Xiao,Mouming Zhao
This work aimed to investigate the protective effects of collagen hydrolysates containing different contents of Gly-Pro-Xaa tripeptides on UV-induced photoaging mice and to identify potent anti-photoaging peptides. Results showed that oral ingestion of collagen hydrolysates with a higher content of Gly-Pro-Xaa tripeptides (∼11.4%, HCH) dramatically enhanced the absorption of Pro-Hyp, Hyp-Gly, and Gly-Pro-Hyp into the body, which were 1.77-, 2.18-, and 65.07-fold higher in area under the concentration–time curve (AUC) values than that of collagen hydrolysates with a lower content of Gly-Pro-Xaa tripeptides (∼3.8%, LCH), respectively. Furthermore, the protective effects of HCH on the photo-aged skin of mice were significantly stronger than those of LCH in terms of increases in the contents of hyaluronic acid and collagen, improvement in skin elasticity and epidermal thickness, alleviation in inflammation, and decreases in the contents of matrix metalloproteinase-1 (MMP-1) and MMP-3. More importantly, Gly-Pro-Hyp displayed potent anti-photoaging activities comparable to HCH based on an equivalent amount of Hyp. Network pharmacology analysis for potential mechanisms further indicated that Gly-Pro-Hyp might interact with JUN and FOS and regulate IL-17 and TNF signaling pathways. Collectively, our results suggested that HCH had great potential to be applied in functional foods for skin health and Gly-Pro-Hyp was found to be a potent collagen-derived anti-photoaging peptide, which might contribute to the excellent anti-photoaging effects of HCH.
研究领域:
药理学
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皮肤病学
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美容护肤品
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营养保健品
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2021
·
IF 9.147
Dongmei Wu,Shiguo Chen,Xingqian Ye,Shokouh Ahmadi,Weiwei Hu,Chengxiao Yu,Kai Zhu,Huan Cheng,Robert J. Linhardt,Qiaojun He
Administration of pectic polysaccharides is a therapeutic strategy in the management of gut inflammation. However, the knowledge about the effects of different dietary sources and structure are missing. This study explored the protective effects of six different pectic polysaccharides from Goji berry (G), dragon fruit (D), lemon (L), pomelo (P), potato (T) and raspberry (R) in dextran sulfate sodium (DSS)-induced colitis mice. D mainly contained rhamnogalacturonan (RG) backbone; L had high amount of arabinan sidechains; P was a high-esterified homogalacturonan (HG) pectic polysaccharide; the primary domain in T was galactan sidechains; R and G had the composition of arabinan: galactan: RG: HG = 19: 28: 15: 22 and 36: 17: 21: 14. Our results suggested that G and R were the most effective in alleviating colitis via alleviating tissue damage, promoting the index of immune organs, suppressing the production of TNF-α, IL-1β and IL-17, improving antioxidant status and promoting the total amount of SCFAs. Similarly, the administration of L alleviated colitis mainly by increasing the fermentation products without changes in the composition pattern of SCFAs. The secretion of IL-6 might be suppressed by pectic polysaccharides containing high amount of arabinan sidechains, while anti-inflammatory cytokines and intestinal barrier function tend to be regulated by pectic polysaccharides rich in galactan. In conclusion, pectic polysaccharide containing diversified structural domains (homogeneous proportion of HG, RG, arabinan, and galactan) might be the most effective in alleviating gut inflammation. This unprecedented report revealed the anti-inflammatory effects of different pectic polysaccharides, which was critical for the reasonable selection of dietary fiber to prevent gut inflammation.
研究领域:
营养学
·
免疫学
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胃肠病学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Zhihui Cai,Jinjin He,Jun Jiang,Zihan Zhao,Ye Shu
Background Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis . Yet, its material basis and relevant mechanisms are still vague. Purpose Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. Methods Linear-Trap-LC/MS n was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers’ range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC–MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. Results The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. Conclusions Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.
研究领域:
药理学
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中医药
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感染性疾病
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分子生物学
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代谢组学
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系统生物学
✓ 已验证
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）