PHYTOMEDICINE
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2025
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IF 8.3
Qiyue Sun,Ronghua Zhao,Shuran Li,Weiqin Zhou,Jingsheng Zhang,Bo Pang,Shilan Ding,Lei Bao,Zihan Geng,Rui Xie,Dan Xie,Xiaolan Cui,Shanshan Guo,Jing Sun
Background Coronavirus has caused high-mortality viral pneumonia worldwide. The pathogenesis is characterized by hyperinflammatory reactions resulting from immune homeostasis dysregulation. Verbenalin, an iridoid glucoside derived from Verbena officinalis L ., is widely used in Traditional Chinese Medicine (TCM) clinical practice for its antioxidant, anti-inflammatory and antiviral properties. Purpose This study aimed to investigate the pharmacological effects and underlying mechanisms of verbenalin on coronavirus pneumonia both in vivo and in vitro. Methods A coronavirus pneumonia mouse model and macrophage injury models, including mouse alveolar macrophage cell line (MH-S) cells and primary macrophages, were established to initially confirm the antiviral effects of verbenalin. Time-resolved proteomic were then employed to uncover proteomic changes and identify potential therapeutic targets for coronavirus treatment. Subsequently, flow cytometry and Western blot were employed to investigate verbenalin's effects on NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway. Additionally, the targeting regulation of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) / E3 ubiquitin ligase Parkin (Parkin) pathway by verbenalin was validated through molecular docking, surface plasmon resonance (SPR), immunofluorescent staining, RNA interference (RNAi), and mitophagy inhibition both in vivo and in vitro. Results Verbenalin reduced cell injury and inflammation in Human coronavirus 229E (HCoV-229E)-infected macrophages and improved lung inflammation in mice. Proteomics analysis highlighted the roles of nucleotide-binding oligomerization domain (NOD)-like receptor signaling and mitophagy pathways in coronavirus pneumonia. Verbenalin bound strongly to PINK1 and Parkin proteins, increased mitochondrial membrane potential (MMP), decreased mitochondrial reactive oxygen species (mtROS) levels, reduced the opening of mitochondrial permeability transition pore (MPTP), maintained mitochondrial mass, promoted mitophagy flux, upregulated the expression of PINK1, Parkin, and microtubule-associated protein 1A/1B-light chain 3BII (LC3BII). Additionally, verbenalin inhibited the activation of the NLRP3 inflammasome and downregulated the expression of Interleukin-1 beta (IL-1β), cysteine aspartate-specific protease 1 (caspase-1), and gasdermin D (GSDMD) both in vivo and in vitro. Furthermore, treatment with a mitophagy inhibitor and RNAi attenuated the inhibitory effects of verbenalin on NLRP3 activation, confirming the involvement of the PINK1/Parkin/NLRP3 pathway in verbenalin's protective effects. Conclusion Verbenalin enhances PINK1/Parkin-mediated mitophagy to suppress NLRP3 activation, thereby promoting immune homeostasis and mitigating HCoV-229E-induced inflammation.
研究领域:
药理学
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免疫学
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病毒学
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DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Jia Mutian,Wang Yuanyuan,Wang Jie,Qin Danhui,Wang Mengge,Chai Li,Fu Yue,Zhao Chunyuan,Gao Chengjiang,Jia Jihui,Zhao Wei
Stimulator of interferon gene (STING)-triggered autophagy is crucial for the host to eliminate invading pathogens and serves as a self-limiting mechanism of STING-induced interferon (IFN) responses. Thus, the mechanisms that ensure the beneficial effects of STING activation are of particular importance. Herein, we show that myristic acid, a type of long-chain saturated fatty acid (SFA), specifically attenuates cGAS-STING-induced IFN responses in macrophages, while enhancing STING-dependent autophagy. Myristic acid inhibits HSV-1 infection-induced innate antiviral immune responses and promotes HSV-1 replication in mice in vivo. Mechanistically, myristic acid enhances N-myristoylation of ARF1, a master regulator that controls STING membrane trafficking. Consequently, myristic acid facilitates STING activation-triggered autophagy degradation of the STING complex. Thus, our work identifies myristic acid as a metabolic checkpoint that contributes to immune homeostasis by balancing STING-dependent autophagy and IFN responses. This suggests that myristic acid and N-myristoylation are promising targets for the treatment of diseases caused by aberrant STING activation.
研究领域:
免疫学
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细胞生物学
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病毒学
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代谢
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
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IF 5.9
Yu Li,Hailiang Wang,Hongtao Bi,Jingyue Feng,Tingting Gao,Dai Dong,Guoqiang Li,Boxuan Liu,Hongyan Yuan,Weihua Ni
Hirsutella sinensis ( H. sinensis ), a substitute for a valuable edible and medicinal fungus, Cordyceps sinensis , is well known for its various of beneficial pharmacological properties. However, research on the effects of H. sinensis on colitis in mice is limited. In our previous studies, we carried out a systematic classification and structural identification of the polysaccharides in H. sinensis . Here, we utilized a murine model of colitis induced by a 3% dextran sulfate sodium (DSS) administration to investigate the protective effects of the H. sinensis mycelium-derived starch-like polysaccharide (HSWP-1a) on colitis. Our findings demonstrate that HSWP-1a effectively mitigates DSS-induced weight loss, reduces colon tissue damage, increases tight junction protein expression, and restores intestinal barrier function. Notably, during this process, HSWP-1a reversed the DSS-induced increase in M1/M2 macrophage polarization and the Th17/Treg cell balance, ameliorating the DSS-induced decrease in anti-inflammatory cytokine expression while inhibiting the DSS-induced increase in proinflammatory cytokine levels and mediating immune tolerance to maintain local intestinal immune homeostasis. Furthermore, HSWP-1a is capable of regulating the intestinal microbiota, enhancing the abundance of beneficial bacteria such as Lachnospiraceae_NK4A136_group , and reducing the abundance of harmful bacteria like Proteobacteria and Cyanobacteria. HSWP-1a also restores the levels of short-chain fatty acids (SCFA) to maintain the balanced intestinal microenvironment. Overall, HSWP-1a achieves its colitis-protective effects through its ability to strengthen the intestinal barrier, regulate the immune system, and restore gut microbiota interactions. These findings suggest that HSWP-1a has potential as a valuable food supplement or nutritional health product for alleviating colitis.
研究领域:
药理学
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免疫学
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微生物学
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营养学
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产品关联
DOI
高影响因子
Microbiology Spectrum
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2022
·Vol. 10
·期 3
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IF 9.043
Xiaojun Li,Yu Ren,Jie Zhang,Chunhui Ouyang,Chunlian Wang,Fanggen Lu,Yani Yin
Early-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases.IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.
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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营养学
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转化医学
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DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 66
·期 24
·2200455
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IF 6.575
Yuanjie Guo,Yu Ma,Liyuan Ma,Zixin Guo,Yingliang Xiao,Yunjun Liu,Jie Li,Shengnan Wang,Yixiang Liu
Scope This study assesses whether oleuropein prevents ovalbumin (OVA)-induced food allergy (FA) and investigates the underlying mechanisms. Methods and results A Balb/c FA mouse model is established and maintained for 7 weeks. The subjects are administered OVA by oral gavage to induce FA and supplemented with different oleuropein doses (1.00–20.00 mg kg −1 per day) to evaluate its preventative efficacy. The results indicate that oleuropein effectively alleviates OVA-induced allergy symptoms and promotes temperature elevation in sensitized mice. The secretion of serology-specific OVA-immunoglobulin (Ig)E, OVA-IgG, and histamine is inhibited in the sensitized mice. Oleuropein dramatically upregulates the expression of intestinal tight junction (TJ) proteins, regenerating gene (Reg) IIIγ, and interleukin (IL)-22, enhancing the physical and biochemical barrier function of the intestinal epithelium. Additionally, oleuropein improves the immune homeostasis of the intestinal epithelium by affecting the function of mucosal mast cells and regulatory T (Treg) cells. The disordered intestinal flora of the sensitized mice also improves after oleuropein administration. Conclusions These findings suggest that oleuropein prevents FA by enhancing intestinal epithelial barrier function and improving immune homeostasis and intestinal flora in sensitized mice. Therefore, diets rich in oleuropein should be recommended for people with FA.
研究领域:
免疫学
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胃肠病学
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营养学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Shuo Wang,Yuequan Wang,Yantong Li,Xiaoxue Lai,Miao Hu,Meng Chen,Cong Li,Xinrong Liu,Yanzhi Song,Yihui Deng
Inflammation-related immune cell subsets with abnormal activation, impaired tolerance, and complex intercellular interactions drive the progression and incurability of autoimmune diseases (AIDs). Here, we present an antigen-free nanovaccine-enabled holo-immunotherapy that comprehensively modulates inflammation, innate immunity, and adaptive immunity. The nanovaccine, composed of dual NF-κB inhibitors (budesonide and bortezomib) and comodified with sialic acid (SA) and enzyme-cleavable polyethylene glycol (PEG), leverages the SA-Siglec axis for targeted delivery to inflammation-related macrophage, dendritic cell, and CD4+ T cell subsets. By bridging innate and adaptive immunity, this multitargeted strategy synergistically reshapes the inflammatory microenvironment, establishes robust memory immune tolerance, and promotes immune homeostasis restoration, leading to sustained efficacy and delayed relapse in the collagen-induced arthritis (CIA) mouse model. Unlike traditional vaccines, the antigen-free design eliminates reliance on exogenous antigens, minimizes off-target immune risks, and holds promise for broader clinical applicability. The nanovaccine outperforms anti-TNF-α antibodies in treating models of CIA, adjuvant-induced arthritis, and chronic ulcerative colitis, highlighting its potential as a universal vaccine platform for AID therapy. Overall, this work provides a strategy to address AID challenges through precise immune regulation and durable therapeutic benefits.
研究领域:
免疫学
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纳米医学
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转化医学
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自身免疫病治疗
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分子药理学
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2025
·Vol. 15
·期 10
·4465
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IF 13.3
Yu-Yue Zhao,Qian-Fang Meng,Hao Cui,Wei Liu,Yan Chen,Zhou Lan,Hao Chen,Dan-Dan Ma,Lang Rao,Guang-Tao Yu
Rationale: Immune homeostasis microenvironment of bone regeneration is especially important for inflammatory-derived bone defect repair. The two key influencing factors for achieving ideal bone regeneration are the balance between inflammatory cells represented by T cells and anti-inflammatory cells represented by MDSCs, and the dynamic balance between osteoblasts and osteoclasts. Methods: Herein, an injectable thermosensitive bone meal was designed with Pluronic F127 hydrogel loading myeloid-derived suppressive cells (MDSCs) membrane vesicles coated nano-hydroxyapatite (F127/nHA/MDSCs-MV, abbreviated as F127/nHAM) for periodontitis-derived bone defect repair. Results: The proteomics revealed F127/nHAM were able to catalyze the production of adenosine from ATP depend on CD73 and CD39. In vitro and in vivo assays further showed that F127/nHAM inhibited the proliferation and function of T cells by component MDSCs-MV, exerting an anti-inflammatory role. Subsequently, the RNA-sequencing and confirmation experiments revealed that F127/nHAM inhibiting the differentiation of macrophages into osteoclasts through down-regulating the secretion of CCL2 and CCL5. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that F127/nHAM had an outstanding anti-inflammatory and bone regeneration promoting properties, restoring immune homeostasis. Conclusion: This biomimetic and multifunctional bone meal opens new avenues for inflammatory-derived bone defect repair and future clinical application.
研究领域:
生物材料学
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骨科医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
NATURE CELL BIOLOGY
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2025
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IF 19.1
Wang Bin,Wang Yongqiang,Pan Ting,Zhou Lili,Ran Yu,Zou Jing,Yan Xiaohua,Wen Zhenke,Lin Shixian,Ren Aiming,Wang Fangwei,Liu Zhuang,Liu Ting,Lu Huasong,Yang Bing,Zhou Fangfang,Zhang Long
Maintaining innate immune homeostasis is critical for preventing infections and autoimmune diseases but effective interventions are lacking. Here we identified C864–C869-mediated intermolecular disulfide-linkage formation as a critical step for human RIG-I activation that can be bidirectionally regulated to control innate immune homeostasis. The viral-stimulated C864–C869 disulfide linkage mediates conjugation of an SDS-resistant RIG-I oligomer, which prevents RIG-I degradation by E3 ubiquitin-ligase MIB2 and is necessary for RIG-I to perform liquid–liquid phase separation to compartmentalize downstream signalsome, thereby stimulating type I interferon signalling. The corresponding C865S ‘knock-in’ caused an oligomerization defect and liquid–liquid phase separation in mouse RIG-I, which inhibited innate immunity, resulting in increased viral load and mortality in mice. Using unnatural amino acids to generate covalent C864–C869 linkage and the development of an interfering peptide to block C864–C869 residues, we bidirectionally regulated RIG-I activities in human diseases. These findings provide in-depth insights on mechanism of RIG-I activation, allowing for the development of methodologies that hold promising implications in clinics.
研究领域:
免疫学
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分子生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
IMMUNITY
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2025
·
IF 26.3
Qianzhou Yu,Danlu Jiang,Tianming Zhao,Yuelin Guan,Jian Zhang,Dehang Yang,Ruya Sun,Weiwei Yu,Zhen Wang,Sheng Chen,Mobai Li,Tianyi Hu,Qiqi Deng,Xiaoyang Lu,Yidong Yang,Mengfei Chang,Liheng Du,Xue Zhang,Zhexu Chi,Di Wang
The small intestine (SI) absorbs nutrients and acts as a barrier against pathogens. Diet enables the absorptive function of the SI while maintaining immune homeostasis. But how the SI transmits nutritional signals to the immune response and adapts to dietary intake remains unclear. Here, we demonstrated that epithelial gasdermin D (GSDMD) in the SI facilitated the absorptive function of enterocytes, subsequently empowering an epithelial-immune cooperation to modulate host defense. Unlike its pyroptotic function, GSDMD determines the absorptive versus the defensive zonation of enterocytes and promotes brush border assembly. This diet-induced, GSDMD-mediated adaptation promoted lipid absorption and subsequently rewired enterocyte metabolism to support intraepithelial γδ T lymphocytes (γδ T-IELs), thereby enhancing barrier function. Impairment of this GSDMD-mediated circuit exacerbated barrier-dysfunction-associated enteritis. Our results reveal how epithelial cells and lymphocytes co-adapt to nutrient signals in the SI, thereby adjusting the equilibrium between nutrient uptake and host defense in response to environmental change.
研究领域:
免疫学
·
细胞生物学
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营养学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Lingwei Kong,Minghui Ye,Xingzi Liang,Wenjing Lai,Jiaxin Liao,Dayan Zhou,Adili Abudu,Yulei Zhang,Chuanhao Pan,Huapu Chen,Changxu Tian
Aquaculture in saline-alkaline waters offers a potential solution to freshwater scarcity while sustaining aquatic production, yet the physiological limits and adaptive mechanisms of cultured species remain insufficiently understood. This study examined the responses of Hong Kong catfish ( Clarias fuscus ), a widely farmed species in southern China, under acute saline-alkaline stress. Fish were exposed for 0, 12, 24, 48, 72, and 96 h to either control water (0 ‰ salinity, 0 mmol/L alkalinity, n = 30) or saline-alkaline water (17 ‰ salinity, 50 mmol/L alkalinity, n = 30). Histological analysis revealed dynamic liver damage, initially characterized by mild vacuolar degeneration and inflammatory infiltration, progressing to a peak at 48 h with marked hepatocellular atrophy and cytoplasmic depletion, followed by partial alleviation during prolonged exposure. Antioxidant enzyme (SOD, CAT, GSH-Px) declined initially, reaching a nadir at 12 h before partially recovering, indicating disruption of redox homeostasis. In contrast, MDA, ALP, ACP, ALT, and AST increased and peaked at 12 h, consistent with lipid peroxidation, and hepatocellular injury. Transcriptome profiling revealed that a total of 6949 DEGs were detected in liver tissue, with functional enrichment pointing to energy metabolism, oxidative phosphorylation, immune response, and protein processing pathways. Notably, thermogenesis and oxidative phosphorylation pathways were predominant at 48 h, while endoplasmic reticulum protein processing pathways were up-regulated at 96 h, indicating a temporal shift from energy metabolism to cellular repair and adaptation. Collectively, these findings demonstrate that acute saline-alkaline stress causes liver injury, perturbs oxidative and immune homeostasis, and reprograms gene expression in C. fuscus , offering critical insights into liver-mediated stress adaptation and metabolic regulation and a basis for optimizing management practices in saline-alkaline aquaculture.
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产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Ju,Shan Hui,Guo Jinglin,Wang Xiaoying,Wang Weiwei
Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized skeletal muscle matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel towards RAW264.7 cells resulted in a significantly higher percentage of CD206+ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism, and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution, and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.
研究领域:
组织工程
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免疫学
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伤口愈合
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肌肉骨骼疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Jianmei Fu,Shuai Li,jing Li,Zhichang Zhao,Jing Li,Xinyang Tan,Shan Yu,Maofeng Jing,Keyan Zhu-Salzman,Jichao Fang,Rui Ji
Plants activate defense machinery when infested by herbivorous insects but avoid such costs in the absence of herbivory. However, the key signaling pathway regulators underlying such flexibility and the mechanisms that insects exploit these components to disarm plant defense systems remain elusive. Here, it is reported that immune repressor 14-3-3e in rice Oryza sativa (OsGF14e) regulates immune homeostasis. Infestation with brown planthopper (BPH) Nilaparvata lugens decreased OsGF14e expression; however, the level of downregulation is limited both by the short duration and the specific feeding location. OsGF14e interacts with Enhanced Disease Resistance 1-like (OsEDR1l), a Raf-like MAP kinase kinase kinase (MAPKKK), and repressed jasmonic acid, jasmonic acid-isoleucine, and H 2 O 2 accumulation by enhancing OsEDR1l abundance and signaling ability. OsGF14e and OsEDR1l overexpression renders rice susceptible to BPH, whereas their knockout increases plant resistance but compromises rice growth and grain yield. Intriguingly, BPH 14-3-3e protein (Nl14) that shares high sequence homology and structural similarity with OsGF14e is identified from BPH saliva and egg-associated secretions. Mediated through BPH feeding and oviposition, Nl14, similar to OsGF14e, interacts with OsEDR1l and triggers the OsEDR1l signaling, thereby suppressing plant defenses and facilitating BPH infestation. Apparently, structural and functional mimicry makes it possible for this newly discovered BPH effector to exploit rice OsGF14e-EDR1l immune suppression module. The results reveal a novel mechanism deployed by herbivorous insects, in a manner similar to certain pathogen effectors, to evade host plant defenses by mimicking host immune regulators.
CAS / MDL:
研究领域:
植物学
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植物病理学
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昆虫学
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分子生物学
✓ 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）