npj Biofilms and Microbiomes
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2026
·
IF 11.4
Huang Yue,Hu Yu,Zhao Yifei,Li Yuerui,Liu Yunkun,Wang Miao,Wang Qian,Hu Huan
Ulcerative colitis (UC) and periodontitis, both microbial dysbiosis-driven chronic inflammatory disorders, coexist and mutually exacerbate, but the causal mechanisms remain unclear. Using ligature-induced periodontitis plus DSS-colitis mice, we found UC doubles alveolar bone loss, heightens systemic inflammation, oxidative stress, and osteoclastogenesis. 16S rRNA and LC–MS metabolomics showed UC enriches oral pathogens, depletes gut Firmicutes, expands Bacteroides, and correlates with suppressed amino-acid/bile-acid biosynthesis. Fecal microbiota transplantation (FMT) from DSS donors into antibiotic-pretreated periodontitis-prone mice replicated aggravated bone loss, systemic inflammation, gut-barrier leakage, and Th17/Treg imbalance, while healthy-donor FMT protected. GC–MS revealed 35–60% reductions in acetate, propionate, and butyrate; keystone taxa Parabacteroides and Muribaculum inversely correlated with SCFAs and host inflammatory genes. Collectively, UC-driven gut dysbiosis is a transmissible causal factor that simultaneously remodels oral and intestinal biofilms, erodes epithelial barriers, and amplifies osteoclastic bone resorption. SCFAs-producing microbes or supplementation may be potential therapeutics for UC-associated periodontitis patients. The alternative text for this image may have been generated using AI.
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Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Xiufeng Wang,Yunqing Zhong,Rongzhen Zhang,Yueqiao Chen,Minggang Wang,Chao Lv,Dewen Mao
Objective. Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods. The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-β were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results. Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion. This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.
研究领域:
肝病学
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免疫学
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药理学
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病理学
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高影响因子
ACS Applied Materials & Interfaces
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2026
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IF 7.8
Tianqi Dai,Su Zhao,Yufei Qiu,Fei He,Tao Jia,Shuming Li,Jiangai Piao,Yanli Wang,Yanping Zhao,Xutong Wu,Hai Xu,Xiaoyu Zheng
Postoperative immunosuppression, which is closely associated with the oxidative-stress-driven expansion of regulatory T cells (Tregs), increases susceptibility to severe postoperative outcomes, including infectious complications, multiple organ dysfunction syndrome (MODS), and tumor progression. Here, we report a zirconium-based metal–organic framework (MOF) cascade nanozyme, designated “Pt@PCN-224-Fe”, coated with poly(ethylene glycol) (Pt@FeMOF–PEG) that simultaneously mimics superoxide dismutase (SOD) and catalase (CAT) to neutralize excessive reactive oxygen species (ROS). Mechanistically, scavenging ROS reactivates the PI3K–AKT–mTOR signaling axis, suppresses Foxp3 expression, and thereby inhibits both the differentiation of naı̈ve CD4+ T cells into Tregs under Treg-polarizing conditions and their TGF-β1 secretion in vitro. In a murine model of surgical trauma, the single intraperitoneal administration of Pt@FeMOF–PEG reversed immunosuppression within 72 h, evident as a reduced frequency of Tregs, expanded Th17 cells, normalized CD4+/CD8+ ratio, and suppressed M2 macrophage polarization (all p < 0.05). Concurrently, proinflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) increased, whereas anti-inflammatory cytokines (IL-4, IL-10) decreased, indicating the systemic reinvigoration of the innate and adaptive immunity. The nanozyme showed excellent biocompatibility, with negligible hemolysis (<5%), no histological organ damage, and minimal systemic toxicity. In this work, we have developed a dual-enzyme-mimicking nanozyme (Pt@FeMOF–PEG) that precisely targets the ROS–PI3K–Treg axis in a single-dose strategy to reverse postoperative immune dysfunction, thus addressing a long-unmet clinical requirement for surgical recovery.
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Diabetology & Metabolic Syndrome
·
2025
·Vol. 17
·期 1
·427
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IF 3.9
Wang Wenyan,Yang Shurui,Liu Jing,Huang Shang,Li Yong,Liang Fengxia
Background The prevalence of obesity and its associated complications poses a significant threat to human health. The application of electroacupuncture (EA) in the treatment of obesity has been extensively studied. This study aims to investigate the immunological mechanisms underlying the beneficial effects of EA on obesity-related inflammation. Methods In the present study, obesity was induced in rats through a high-fat diet (HFD), followed by the implementation of EA treatment for a duration of 8 weeks. Additionally, the obese rats were subjected to treatment with both an agonist (Resveratrol) and inhibitor (Sirtinol) of silent information regulator 1 (SIRT1). The body weight, fasting blood glucose, and 2-hour postprandial blood glucose levels were regularly monitored throughout the treatment of obese rats. Insulin sensitivity was evaluated through intraperitoneal insulin tolerance test and intraperitoneal glucose tolerance test upon completion of the treatment. The weight of perirenal adipose of obese rats was measured, and the size of adipocytes was observed using HE staining. The quantification of helper T 17 (Th17) cells and regulatory T (Treg) cells in peripheral blood and perirenal adipose tissue was performed using flow cytometry. The expression levels of SIRT1 and acetylated NF-κB in perirenal adipose tissue of rats were observed using immunofluorescence staining and Western blotting analysis. Results Compared to rats on a normal diet, HFD-induced obese rats exhibited insulin resistance (IR), pronounced accumulation of perirenal adipose, an imbalance between Th17 and Treg cells, as well as down-regulated expression of SIRT1. The administration of Resveratrol resulted in the alleviation of the aforementioned symptoms in obese rats. The EA treatment also ameliorated body weight gain, adipose accumulation, IR, and adipose tissue inflammation in rats. Additionally, it was found to enhance SIRT1 expression and reduce acetylation of NF-κB protein. However, the effects of EA treatment on HFD-induced obese rats were partially attenuated by Sirtinol. Conclusion EA exhibits a favorable therapeutic effect on IR and adipose inflammation in obese rats. The underlying mechanism is associated with the promotion of the SIRT1-mediated anti-inflammatory pathway, which regulates the balance between Th17 and Treg cells.
研究领域:
内分泌学
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免疫学
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代谢性疾病
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补充与替代医学
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分子生物学
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Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Yuhong Wang,Lin Hu,Lei Wang,Chonghai Zhang,Wenhao Shen,Hongli Yang,Min Li,Xin Zhang,Mengmeng Xu,Muxing Zhang,Kai Yang,Xiaopeng Tian
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ pMUT1/2 -ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro , and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo . Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides . This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.
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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胃肠病学
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合成生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shiru Huang,Han He,Hanxi Li,Chongyang Li,Fu Wang,Yuan Hu,Youping Liu,Lin Chen,Hongping Chen
Atractylodis macrocephalae Rhizoma (AM), a widely used Chinese herb for treating spleen deficiency diarrhea (SDD), is rich in polysaccharides. However, the precise mechanism underlying the antidiarrheal effects of Atractylodis macrocephalae Rhizoma polysaccharide (AMP) remains unclear. In this study, AMP, with a molecular weight of 69 kDa, is isolated from AM and consists of Glc, Gal, and Ara in a molar ratio of 84.16:6.51:9.33. FTIR and NMR analyses indicate that AMP features a linear backbone of →4,6)-α-D-Glc p -(1→ with branches of →3)-β-D-Glc p -(1→, terminating in →2,4)-β-D-Gal p -(1→. Animal models of SDD induced by Folium sennae demonstrate that AMP alleviates diarrhea symptoms, mitigates colon damage, and enhances spleen index, thymus index, and the expression of CD4 + CD25 + Foxp3 + Treg cells. Further, the potential mechanisms for AMP's antidiarrheal action are explored through the comprehensive approach integrating intestinal flora, polysaccharide utilization loci, short-chain fatty acids (SCFAs), and metabolomics. AMP reduces the abundance of pathogenic c_ Clostridia while promoting beneficial o_Bacteroidales and f_Muribaculaceae, influencing SCFAs production via its strong binding affinities with SusD, GH2, and GH43. This modulation is linked to alterations in linoleic acid metabolism, alpha-linolenic acid metabolism, and primary bile acid biosynthesis. In conclusion, AMP demonstrates significant potential as a therapeutic agent for SDD.
研究领域:
药理学
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微生物学
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免疫学
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代谢组学
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中医药学
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ADVANCED MATERIALS
·
2023
·
IF 29.4
Xiaoyu Yin,Lintao Wang,Yiming Niu,Daping Xie,Qingwen Zhang,Jian Xiao,Lei Dong,Chunming Wang
Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, we develop an oligosaccharide biomaterial with “unmasked” specific activity to recruit T reg cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, we obtain a series of oligosaccharide fractions with more specific chemokine-inducing functions. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express T reg -chemoattractant CCL5 through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3 -reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes T reg mobilization around HFs and stimulates de novo regeneration of robust hairs. Our study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety. This article is protected by copyright. All rights reserved
研究领域:
免疫学
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生物材料科学
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皮肤科
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药学
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MOLECULAR IMMUNOLOGY
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2025
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IF 3
Linmao Lyu,Yanfei Ma,Xuyan Sun,Meng Luo,Zhong Wang,Lijun Fang,Wenqiang Li,Yuguo Chen,Shize Liu,Xiaopeng Jia
Background Cord blood mononuclear cells (CB–MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB–MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear. Methods In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB–MNCs, umbilical cord-derived mesenchymal stem cells (UC–MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study. Results Our findings demonstrated that compared with UC–MSCs and mesalazine, CB–MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC–MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB–MNCs were also more effective than UC–MSCs and mesalazine at maintaining Th17/Treg balance than UC–MSC and mesalazine in colitis mice. Conclusions The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.
研究领域:
免疫学
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胃肠病学
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干细胞治疗
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代谢组学
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炎症性疾病
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2020
·
IF 3.943
Simiao Qiao,Xingpan Lian,Mengfan Yue,Qin Zhang,Zhifeng Wei,Li Chen,Yufeng Xia,Yue Dai
Previously, we reported that oral administration of madecassoside, the main active triterpene in Centella asiatica L., exerted anti-arthritis effect by inducing the generation of regulatory T (Treg) cells in small intestine. This study investigates the action site and mechanism of madecassoside to induce Treg cells. In collagen-induced arthritis (CIA) of rats, oral administration of madecassoside significantly alleviated arthritis symptoms, but its main metabolite madecassic acid did not, suggesting that madecassoside functions in the parent form. Madecassoside was shown to increase the number of Treg cells and promote the expression of Foxp3 and IL-10 in rat ileum rather than duodenum and jejunum, as detected using the immunohistochemistry assay and quantitative PCR assay, respectively. Unexpectedly, madecassoside was absent of significant effect on in vitro Treg cell differentiation and the expression of Foxp3 and IL-10. A combined use of broad-spectrum antibiotics resulted in significant reduction of the anti-arthritis effect of madecassoside in CIA rats. The 16S rRNA gene sequence showed that madecassoside could reverse the changes of gut microbiota under arthritis condition, and enrich several bacteria such as Lachnospiraceae, Butyricicoccus, Faecalibacterium, Butyricicoccus pullicaecorum and so on. GC-MS assay showed that madecassoside elevated the levels of acetic acid and butyric acid, but not other short chain fatty acids (SCFAs) in the cecum contents of CIA rats. Butyric acid rather than acetic acid could induce the in vitro differentiation of Treg cells and the expression of Foxp3 and IL-10. Accordingly, when madecassoside was co-administered with heptanoyl CoA, the competitive inhibitor of butyrate synthase, its effect on butyric acid production, Treg cell proportion and arthritis nearly disappeared. These findings indicate that oral madecassoside induces the generation of Treg cells and therefore displays anti-arthritis effect in the parent form but not metabolites, and the ileum is the main action site. The mechanism of madecassoside can be summarized as: expansion of the richness of butyrate-producing bacteria-up-regulation of intestinal butyrate level-induction of Treg cell differentiation and IL-10 expression.
研究领域:
免疫学
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药理学
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微生物学
·
风湿病学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Kunyao Guo,Qianyao Yu,Kaixi Zhu,Yuhui Yang,Tao Chen,Yiping Huang,Weiran Li
Stem cell-derived exosomes from human exfoliated deciduous Teeth (SHED-Exos) show promising treatment effects through immune modulation and angiogenic properties. However, when applied to diabetic wound healing, their inactivation and rapid clearance limit their clinical application. In this study, we aimed to develop a chitosan/dextran-based hydrogel using a biotin-avidin system that showed excellent injectability, adhesiveness, and antibacterial effects and enabled the slow and steady release of SHED-Exos to enhance diabetic wound healing. SHED-Exos were immobilized within a hydrogel through the biotin-avidin interaction and electrostatic forces of chitosan, allowing for slow release over >7 days. Additionally, the hydrogel exhibited excellent cell compatibility and supported cell spheroid growth in a 3D network. In vivo , the hydrogel significantly enhanced wound healing in diabetic rats by reducing inflammation and decreasing the ratio of Th17/Treg cells around wounds. This innovative noncellular hydrogel shows promise in facilitating the healing of diabetic wounds and may serve as a potential clinical therapy using natural bioactive materials delivery of exosomes.
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TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
·
2026
·
IF 1.5
Ting Zhou,Shanshan Xu,Juan Tang,Xiaomei Han,Yu Jiang,Huaying Chen
Diminished ovarian reserve (DOR) is a critical challenge in reproductive health, leading to reduced fertility and hormonal imbalances. Current treatments such as assisted reproductive technologies and hormone replacement therapy often have limited success and adverse effects. Progesterone receptor membrane component 2 (PGRMC2) is a protein essential for various reproductive processes and is involved in ovarian folliculogenesis, with its increased expression associated with DOR. This study investigates the protective mechanisms of total flavonoids from Semen Cuscutae (TFSC) on ovarian reserve through PGRMC2 modulation and T helper 17 cell (Th17)/regulatory T cell (Treg) immune balance in a DOR rat model. DOR was induced in rats by administering 50 mg/kg tripterygium glycosides (TG) via intragastric administration once daily for 15 days. Various analytical techniques were used to assess the effects of TFSC, including immunohistochemistry for ovarian tissue analysis, Western blotting to measure PGRMC2 protein expression, flow cytometry for evaluating Th17/Treg ratio, and Enzyme-linked immunosorbent assay (ELISA) to quantify serum cytokine levels. Results demonstrate that TFSC enhances ovarian function, up-regulates PGRMC2 expression, and restores immune homeostasis, highlighting its potential as an alternative therapeutic strategy. By elucidating TFSC’s role in immune modulation and ovarian function, this study paves the way for developing targeted therapies to improve outcomes for women with DOR.
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2026
·
IF 4.8
Ziyu Wang,Hongyang Wang,Qinghai Wang,Tao Huang,Chen Guo,Jianlei Ji,Zhen Dong,Yanwei Cao
Glycolysis plays a critical role in regulatory T cells (Tregs), which are frequently exploited by tumor cells, as Treg survival depends on glycolytic activity to suppress antitumor immunity. However, the precise effects of glycolysis on Treg proliferation and differentiation remain incompletely understood. Monocarboxylate transporters (MCTs) are pivotal regulators of glycolytic flux. In this study, we investigated how MCT1 inhibition modulates Treg metabolism and function, and the potential implications for tumor immunotherapy. Silencing MCT1 in human primary Tregs using siRNA disrupted glycolysis, leading to G0/G1 cell cycle arrest, increased apoptosis, and ATP depletion. Integrated metabolomic and transcriptomic analyses identified the ABC transporter pathway as the most significantly altered, with coordinated changes in key genes (ABCA1, ABCB10, ABCC9, etc.) and the metabolite adenosine. Validation using The Cancer Genome Atlas (TCGA) acute myeloid leukemia cohort demonstrated that high expression of the ABC transporter gene ABCC9 is associated with improved overall survival (hazard ratio = 0.45, p < 0.001). These findings indicate that MCT1 inhibition is associated with alterations in the ABC transporter pathway, which may correlate with changes in Treg metabolism and the tumor immune microenvironment. Collectively, this work highlights metabolic reprogramming of Tregs as a novel therapeutic target for cancer immunotherapy.
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