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
·
免疫学
·
营养学
·
动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zherui Fu,Yiwen Xu,Fangqi Xu,Haoyu Zhou,Na Lin,Ning Zhang,Feng Lin
The incidence of steroid-induced osteonecrosis of the femoral head (SONFH) is increasing annually; however, the underlying pathological mechanism remains unclear, which is an obstacle to its effective treatment. The negative effect of immune infiltration on the physiological activity of focal stem cells is one potential mechanism that has attracted attention. It is difficult to simulate the complex regulation of the interaction system between immune cells and stem cells using a single regulation method. In this study, we demonstrated that the immune infiltration of T helper 17 (Th17) cells plays an important role in the progression of SONFH. Based on this finding, we developed an injectable hydrogel system with both physical and chemical synergistic regulatory properties to enhance the activity of stem cells using electrical stimulation. This treatment was designed to prevent the infiltration of Th17 cells by regulating the physiological function of stem cells and blocking the negative effect of Th17 cells on stem cells pharmacologically. Thus, the dual synergistic regulation of immune infiltration at the lesion site of SONFH enhanced the physiological activity and function of the stem cells, thereby improving the therapeutic effect of SONFH. This hydrogel system provides insight for the future development of multifactorial regulatory systems and provides a strategy for the treatment of SONFH.
研究领域:
医学
·
生物材料学
·
免疫学
✓ 已验证
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
·
免疫学
·
糖尿病学
·
肾病学
✓ 已验证
DOI
PubMed
高影响因子
Infection and Drug Resistance
·
2023
·
IF 3.9
Lingna Xu,Ren-ai Xu,Dan Zhang,Shanshan Su,Hanyan Xu,Qing Wu,Yuping Li
Background: T helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methods: Six to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.Results: The proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).Conclusion: The expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.
研究领域:
免疫学
·
微生物学
·
分子生物学
·
病理学
✓ 已验证
产品关联
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
·
生物医学工程
·
药学
·
免疫学
✓ 已验证
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
·
免疫学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2026
·
IF 6.1
Qinbiao Chen,Yanli Ma,Yuewu Tang,Ni Du
Sepsis-related acute kidney injury (SA-AKI) represents a severe complication associated with elevated mortality rates, primarily driven by imbalanced Th17 immune responses and mitochondrial dysfunction. Consequently, there is an urgent need for a versatile nanomaterial that can enhance mitochondrial performance while also exerting anti-inflammatory effects. A synthetically produced nanoenzyme has the potential to address this challenge. In this study, we created a biomimetic nanozyme (BPQDs@Raw264.7@Kim-1) by engineering clusters of black phosphorus quantum dots (BPQDs) that are coated with macrophage membranes and functionalized with kidney injury molecule-1 (Kim-1) for targeted delivery. This nanozyme improves its antioxidant and anti-inflammatory properties by clustering black phosphorus quantum dots, while the stability of the drug is maintained through encapsulation within Raw264.7 cell membranes. The system effectively achieves homologous targeting via external Kim-1 molecules. The objective of this nanozyme is to modulate the SIRT3/RORγt/STAT3 pathway to reduce Th17-driven inflammation and alleviate SA-AKI. In vitro experiments demonstrated that the nanozyme possesses excellent biocompatibility, efficient cellular uptake, and the ability to scavenge reactive oxygen species (ROS) in LPS-stimulated HK-2 cells. It mitigated mitochondrial injury, decreased apoptosis, and lowered the levels of pro-inflammatory cytokines. Mechanistically, the nanozyme's overexpression of SIRT3 inhibited RORγt/STAT3 signaling, resulting in reduced Th17 differentiation and inflammatory cytokine release. Importantly, silencing SIRT3 negated these therapeutic benefits, underscoring its critical role. This research introduces a targeted nanozyme approach that alleviates SA-AKI by simultaneously restoring mitochondrial balance and suppressing Th17 inflammation through the SIRT3/RORγt/STAT3 pathway, presenting a promising therapeutic strategy for organ injury caused by sepsis.
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2022
·
IF 5.152
Yan-Lin Chen,Lan Bai,Dilirebati Dilimulati,Shuai Shao,Che Qiu,Ting Liu,Shuo Xu,Xue-Bing Bai,Lin-Juan Du,Lu-Jun Zhou,Wen-Zhen Lin,Xiao-Qian Meng,Yi-Chao Jin,Yan Liu,Xiao-Hua Zhang,Sheng-Zhong Duan,Feng Jia
Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17 + γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4 + T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.
研究领域:
神经科学
·
免疫学
·
微生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
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
·
微生物学
·
代谢组学
·
风湿病学
✓ 已验证
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
·
免疫学
·
胃肠病学
·
微生物学
·
代谢组学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Meng Wang,Jinglan Zhang,Huayan Zhao,Dingming Wan,Zhongxing Jiang
Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.
研究领域:
免疫学
·
药理学
·
血液学
·
移植学
✓ 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
✓ 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）