Nutrients
·
2024
·Vol. 16
·期 13
·2052
·
IF 4.8
Haidong Wang,Ji Qiu,Minyao Zhou,Yanqiu Luo,Xinyu Li,Minqi Wang
In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.
研究领域:
微生物学
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免疫学
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营养学
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动物科学
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产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1395-1405
·
IF 2.693
Dan Wang,Zikun Zhang,Zekun Si,Yanlin Yang,Shuangshuang Li,Yaoming Xue
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
研究领域:
药理学
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免疫学
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糖尿病学
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肾病学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Liu Lisha,Deng Dashi,Li Chenchen,Huang Guixiao,Zhang Wenjuan,Liang Ting,Liang Rui,Liang Mingkang,Su Yilin,Lin Chongyang,Li Guangzhi,Wu Song
Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (β-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1β), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment. Graphical abstract
研究领域:
风湿病学
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生物医学工程
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药学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Jingjing Li,Suiyuan Ren,Meng Li,Jingai Bi,Guang Yang,Erguang Li
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2018
·
IF 2.064
Peng Pang,Ke Zheng,Sizhi Wu,Huachong Xu,Li Deng,Yucong Shi,Xiaoyin Chen
The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes.
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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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 16
·7375-7386
·
IF 6.1
Cheng Li,Yang Tian,Jiahuan Pei,Yuyang Zhang,Daokuan Hao,Tianjiao Han,Xiaoqin Wang,Shuang Song,Linjuan Huang,Zhongfu Wang
Previous research studies have shown that sulfated polysaccharides can inhibit food allergy, but the detailed mechanism remains largely unknown. In this study, RBL-2H3 cells were used to compare the anti-allergic activities of four sulfated polysaccharides, and an ovalbumin (OVA)-sensitized allergic mouse experiment was used to explore their desensitization effect, with regard to the alteration in gut microbiota and immune cell differentiation. Compared with the shark, bovine and porcine chondroitin sulfate, sea cucumber chondroitin sulfate (SCCS) significantly inhibited the degranulation of RBL-2H3 cells. SCCS reduced allergic symptoms and protected the jejunum from injury in mice. Furthermore, SCCS increased the relative abundance of Lachnospiraceae NK4A136, decreased the relative proportion of Prevotellaceae NK3B31, and up-regulated the secretion of short chain fatty acids such as butyric acid in the feces, resulting in an increase in the mucin 2 (MUC2) secretion by goblet cells HT-29. Meanwhile, SCCS induced the differentiation of regulatory T cells in the mesenteric lymph nodes of mice. This study provides a deeper understanding of the functioning mechanism of SCCS in alleviating food allergy and may guide the development and production of anti-allergy active ingredients.
研究领域:
免疫学
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营养学
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微生物学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2026
·
IF 4
Zhang Xiaojuan,Song Yingying,Han Xinyan,Wang Mengxue,Chen Yufeng,Weng Yue,Li Yaxin,Huang Fei,Shi Hailian,Wu Hui,Wu Xiaojun
White peony root ( Paeonia lactiflora Pall.) is the dried root of peony. White peony root has a long history in Traditional Chinese Medicine (TCM) and is primarily used to treat various conditions, including pain, inflammation, and immune system disorders. Paeoniflorin (PF) is one of the main active components of white peony root, and it has multiple functions such as anti-inflammation, immune regulation, and neuroprotection. However, the impact of PF on multiple sclerosis (MS) remains to be fully elucidated. In this study, we observed that PF treatment markedly attenuated neurological symptoms in experimental autoimmune encephalomyelitis (EAE) mice, reduced disease severity, and alleviated spinal cord inflammation and demyelination, indicating a significant neuroprotective effect. PF administration was accompanied by reduced CD4 + T cell infiltration, decreased Th17 cell proportions, and increased Treg cell frequency in vivo. It also balanced Th17/Treg-associated cytokine secretion by suppressing IL-17 and promoting IL-10 expression. In addition, PF modulated the expression of differentiation-related proteins in lymphoid tissues and inhibited inflammatory gene and protein levels. In primary murine CD4 + T cells, PF enhanced Treg differentiation under Treg-polarizing conditions. In Jurkat cells, PF induced phosphorylation of Raf, MEK 1/2 , and ERK 1/2 , together with increased expression of Egr-1 and Foxp3. These findings indicate that PF treatment is associated with modulation of the Treg/Th17 balance in EAE mice and with changes in Raf/MEK 1/2 /ERK 1/2 /Egr-1 signaling in Jurkat cells. In summary, PF treatment ameliorated EAE manifestations, together with restoration of Treg/Th17 homeostasis and activation of the Raf/MEK 1/2 /ERK 1/2 /Egr-1 pathway. However, whether the Raf/MEK 1/2 /ERK 1/2 /Egr-1 signaling axis directly contributes to PF-induced Treg differentiation in primary T cells or to the therapeutic effects of PF in vivo remains to be determined. Graphical abstract PF treatment ameliorated EAE manifestations and was associated with reduced CD4 + T-cell infiltration, restoration of the Th17/Treg balance, and attenuation of CNS inflammation and demyelination in EAE mice. PF also enhanced Treg differentiation in primary murine CD4 + T cells and was associated with the activation of the Raf/MEK 1/2 /ERK 1/2 /Egr-1 signaling axis in Jurkat cells. The causal contribution of this signaling axis to Treg differentiation and the therapeutic effects of PF remains to be determined.
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DOI
高影响因子
Science Bulletin
·
2023
·
IF 18.9
Zheng-Meng Jiang,Su-Ling Zeng,Tian-Qing Huang,Yang Lin,Fang-Fang Wang,Xing-Jiao Gao,Jing Li,Ping Li,E-Hu Liu
Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus , and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.
研究领域:
免疫学
·
药理学
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微生物学
·
代谢组学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Junjie Chen,Yixian Cheng,Rui Fu,Xinyu Chen,Peng Zhang,Yixiao Lu,Bingsheng Liu,Peng Chen,Jiahao Wang,Haikun Cao,Jinghua Gu,Haosong Chen,Zilong Jiang,Ting Li,Jiawei Zhang,Bo Chen,Guodong Cao
Microplastics (MPs), as emerging global environmental pollutants, exhibit intestinal toxicity mechanisms that are closely associated with the particle size. Nonphagocytosable MPs (NPMs), though incapable of being internalized by intestinal epithelial cells, still provoke colonic inflammatory damage. However, the exact mechanisms remain elusive. This study established a BALB/c mouse model subjected to long-term oral exposure to 10 μm polystyrene MPs (PS MPs) to comprehensively explore how NPMs induce colonic inflammation and injury. The results demonstrate that prolonged PS MPs exposure disrupts the colonic redox balance, leading to oxidative stress. Simultaneously, it disturbs intestinal immune homeostasis by elevating the Th17/Treg cell ratio and upregulating pro-inflammatory cytokines. Additionally, PS MPs notably compromise intestinal mechanical barrier function, diminishing mucin secretion and downregulating tight junction protein expression. Multiomics analysis further uncovered that PS MPs induce bile acid (BA) metabolic dysregulation by interfering with liver function and gut microbiota, causing a marked accumulation of total bile acids in the colon, especially conjugated BAs. Both in vitro and in vivo experiments confirmed that specific concentrations of taurochenodeoxycholic acid (TCDCA) activate the reactive oxygen species-mitochondrial pathway, triggering apoptosis in colonic epithelial cells and exacerbating PS MPs-induced colonic inflammatory injury. This study provides the first evidence of a cross-organ regulatory mechanism in which NPMs mediate intestinal toxicity via the “liver-BA-gut axis,” offering novel theoretical insights for assessing the intestinal toxicity of MPs.
研究领域:
环境毒理学
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免疫学
·
胃肠病学
·
微生物学
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代谢组学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Luoyingzi Xie,Jie Gong,Zhiqiang He,Weinan Zhang,Haoyu Wang,Shitao Wu,Xianxing Wang,Pijiang Sun,Lei Cai,Zhongjun Wu,Huaizhi Wang
Cancer is one of the most important challenges worldwide with an increasing incidence. However, most of patients with malignant cancer receiving traditional therapies have tumor recurrence and short-term 5-year survival. Herein, a novel Cu 2 O-MnO@PEG (CMP) nanomaterial is developed to treat tumors. CMP directly mediates cuproptosis in tumor cells. Meanwhile, CMP potentiates anti-tumor immune responses in the tumor microenvironment (TME) to induce tumor regression. CMP improves the tumor antigen processing and presentation of dendritic cells and tumor-associated macrophages, and further promotes CD8 + T cell responses, especially for cytotoxic CD8 + T cells and transitory exhausted CD8 + T cells. Additionally, CMP downregulates the proportion of Treg cells and CTLA-4 expression on Treg cells. Notably, CMP induces systemic immune responses against distant tumors and long-term immune memory. Furthermore, CMP synergized with PD-L1 mAb promotes tumor inhibition and sustains the anti-tumor efficacy post PD-L1 mAb treatment. Collectively, this strategy has the clinically therapeutic potential for tumors by facilitating cuproptosis in tumor cells and anti-tumor immune responses.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-12
·
IF 4.546
Wang Li,Shao Li,Chen Man-Yun,Wang Lin,Zhang Wei,Tan Feng-Bo,Huang Wei-Hua
Background Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota. Methods DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota. Results GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis. Conclusion GC-K alleviated colitis via the modulation of gut microbiota. Graphical Abstract
研究领域:
药理学
·
免疫学
·
微生物学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
ACTA PAEDIATRICA
·
2021
·Vol. 110
·期 7
·2221-2229
·
IF 2.299
Jing Li,Meixue Chen,Jinfeng Wang,Lingling Lu,Xiang Li,Yuan Le
Aim This study aimed to profile the microRNA levels in Chinese Henoch-Schonlein purpura (HSP) children and to explore their association with inflammatory factors and T helper 17 (Th17)/regulatory T (Treg). Methods Forty-five HSP children and 27 healthy controls were enrolled in this study, and microRNA levels were profiled with a microRNA microarray. The levels of selected microRNAs were determined by quantitative real-time PCR, and the levels of serum IgA, interleukin-6, interleukin-10 and interleukin-17A were detected by enzyme-linked immunosorbent assay. Additionally, Th17 and Treg cells were analysed by flow cytometry. Results There were 9 up-regulated and 27 down-regulated microRNAs in the PBMCs of Chinese HSP children. Among them, miR-1-3p, miR-19b-1-5p and miR-29b-1-5p were up-regulated, while miR-483-5p and miR-1246 were down-regulated. Additionally, these selected microRNAs could differentiate HSP patients from healthy controls. Interestingly, miR-29b-1-5p was correlated with IgA, miR-19b-1-5p, miR-483-5p and miR-1246 were correlated with interleukin-6, while miR-1-3p and miR-1246 were correlated with Th17/Treg. Conclusion This study reveals that the altered microRNAs could differentiate HSP from the healthy, and were associated with inflammatory factors or Th17/Treg. It is indicated that alteration in these microRNAs may contribute to the HSP pathogenesis and may become therapeutic targets or diagnostic biomarkers for HSP.
研究领域:
儿科
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
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