BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Xi Luo,Yi Zheng,Yong-rui Bao,Shuai Wang,Tian-jiao Li,Jia-peng Leng,Xian-sheng Meng
Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including anti-inflammatory and anti-cancer properties, but the potential effects on the colitis-associated carcinogenesis have not been thoroughly investigated. Recent clinical data show that, as yet, few agents clearly inhibited CRC development in long-standing inflammatory bowel diseases. Here, we identified that FAE showed significant efficiency to inhibit HT-29 cell proliferation. The potential of FAE in vivo was further evaluated in an AOM/DSS-induced CAC mouse model. Intriguingly, FAE diminished the number of polyps in mice. Furthermore, FAE inhibited CAC by regulating the gene expression of Notch/ NF-κB/IL-1 signaling pathways. Collectively, these results were indicative of FAE has great potential in CAC prevention and treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2018
·
IF 4.427
Haiyang Zhang,Peiyan Wang,Hongyan Yu,Kaiyuan Yu,Zheng Cao,Feibo Xu,Xu Yang,Miao Song,Yanfei Li
Aluminum (Al) is a recognized environmental pollutant that causes neuroinflammatory lesions, leading to neurodegenerative diseases. Interleukin-1 (IL-1) signaling pathway is responsible for regulating inflammatory lesions. However, it remains unclear whether IL-1 signaling pathway is involved in neuroinflammatory lesions induced by Al exposure. In the present study, one hundred and twenty Wistar rats were orally exposed to 0, 50, 150 and 450 mg/kg BW/d aluminum trichloride (AlCl 3 ) for 90 days, respectively. We found that AlCl 3 exposure increased hippocampal Al concentration, reduced hippocampus coefficient, impaired cognitive ability, deteriorated microstructure of hippocampal CA1 and CA3 regions, increased reactive oxygen species (ROS) level, activated astrocytes and microglia, increased pro-inflammatory cytokines contents and mRNA expressions, and decreased anti-inflammatory cytokines contents and mRNA expressions in the hippocampus. These results indicated that AlCl 3 induced the hippocampal inflammatory lesion (HIL). Moreover, AlCl 3 exposure increased the mRNA and protein expression of IL-1 signaling pathway core components in the hippocampus, demonstrating that AlCl 3 activated IL-1 signaling pathway. Furthermore, the correlation between interleukin-1β (IL-1β) content and HIL and activation of the IL-1 signaling pathway was analyzed. Results showed that IL-1β content was positively correlated with pro-inflammatory cytokines contents and mRNA expressions and activation of IL-1 signaling pathway, and was negatively correlated with hippocampus coefficient, anti-inflammatory cytokines contents and mRNA expressions, and the number of hippocampal neurons. The above results demonstrate that AlCl 3 -induced HIL is associated with IL-1 signaling pathway, in which IL-1β is a link.
研究领域:
神经科学
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药理学
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毒理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2023
·
IF 8.8
Qianyu Yang,Huaxing Dai,Ying Cheng,Beilei Wang,Jialu Xu,Yue Zhang,Yitong Chen,Fang Xu,Qingle Ma,Fang Lin,Chao Wang
Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 μm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.
研究领域:
免疫学
·
神经科学
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毒理学
·
环境科学
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DOI
PubMed
高影响因子
GLYCOCONJUGATE JOURNAL
·
2022
·Vol. 39
·期 1
·131-141
·
IF 3.009
Pan Hao-Yu,Zhang Chun-Qian,Zhang Xiu-Qi,Zeng Hui,Dong Chun-hong,Chen Xia,Ding Kan
Abstract Antibiotic-associated diarrhea (AAD) is a common side-effect of antibiotic treatment resulting from an imbalance in the colonic bacteria. The hypothesis of this study is to ask whether polysaccharide from the rhizome of Dioscorea opposita which is recorded as conventional herbs and food for diarrhea treatment in Southeast Asia, may be an active compound against diarrhea induced by antibiotics. To address, firstly, a homogenous polysaccharide, DOP0.2-S-3 was characterized as a homogalacturonan containing linear repeating units of → 4)-α- D -GalA p (1 → 4)-α- D -GalA p (1 → with the average molecular weight of 14 kDa. DOP0.2-S-3 significantly reduced the water content and defecation times caused by AAD in mice, while it also remarkably attenuated the cytokines of IL-1β and IL-6 expression in mice colon tissues. DOP0.2-S-3 decreased potential pathogen and increased Bacteroidetes in the mice gut. These results suggested DOP0.2-S-3 might be a new leading compound for the functional foods or drug candidate development against AAD partially through regulating gut flora. Graphical abstract
研究领域:
药理学
·
微生物学
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免疫学
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营养学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2020
·Vol. 236
·期 5
·3660-3674
·
IF 5.546
Xinxuan Cheng,Danxue He,Chunyan Liao,Sijie Lin,Liying Tang,Yuan-Liang Wang,Jiaoyue Hu,Wei Li,Zuguo Liu,Yalin Wu,Yi Liao
The underlying mechanisms of complement activation in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD) are not fully understood. Overaccumulation of all- trans -retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b-9 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin-1β production was provoked in both atRAL-treated RPE cells and microglia/macrophages. Coincubation of RPE cells with interleukin-1 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine/paracrine IL-1/IL-1R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.
研究领域:
眼科学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
Stem Cells International
·
2021
·
IF 5.443
Yuxin Zhao,Bobo Cai,Weijun Zhu,Jue Shi,Yu Wang,Misi Si
Mesenchymal stem cells (MSCs) have been considered to be a future treatment option for periodontitis due to their excellent regenerative capability. However, it is still a challenge to protect MSCs’ biological properties from multiple bacterial toxins in local inflammatory environment. The present study is aimed at investigating the treatment effect of interleukin-1 receptor antagonist (IL-1ra) on cell proliferation, migration, and osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSCs) under an inflammatory microenvironment induced by Porphyromonas gingivalis lipopolysaccharides (P. gingivalis-LPS). GMSCs derived from Sprague-Dawley (SD) rats’ free gingival tissues were treated with P. gingivalis-LPS (10 μg/mL) to create in vitro inflammatory environment. Different concentrations of IL-1ra (0.01-1 μg/mL) were used to antagonize the negative effect of LPS. Cell behaviors including proliferation, cloning formation unit (CFU), cell migration, osteogenic differentiation, mineral deposition, and cytokine production were assessed to investigate the protection effect of IL-1ra on GMSCs under inflammation. The toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway activated by LPS was evaluated by real-time quantitative polymerase chain reaction (RT-PCR) and western blot. In response to P. gingivalis-LPS treatment, cell numbers, cloning formation rate, cell migration rate, proinflammatory cytokine production, and osteogenic differentiation-associated protein/mRNA expressions as well as mineralized nodules were suppressed in a time-dependent manner. These negative effects were effectively attenuated by IL-1ra administration in a time- and dose-dependent manner. In addition, mRNA expressions of TLR4 and IkBα decreased dramatically when IL-1ra was added into LPS-induced medium. IL-1ra also reversed the LPS-induced TLR4/NF-κB activation as indicated by western blot. The present study revealed that IL-1ra decreased inflammatory cytokine production in a supernatant, so as to protect GMSCs’ osteogenesis capacity and other biological properties under P. gingivalis-LPS-induced inflammatory environment. This might be explained by IL-1ra downregulating TLR4-mediated NF-κB signaling pathway activation.
研究领域:
牙科科学
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干细胞生物学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2025
·
IF 2.7
Yarong Yan,Shulei Xing,Jinghua Liu,Xinlin Yan,Yi Guan,Zhixin Jiang,Wei Zhang,Xuan Li
Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties; however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGFβ-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (αSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-κB/NLRP3/IL-1β signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGFβ-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGFβ/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.
研究领域:
药理学
·
眼科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2023
·
IF 3.8
Shun Wang,Xiaodi Jin,Hao Chen,Mingdong Han,Jiaxin Bao,Dong Niu,Yikang Wang,Rui Li,Zhiyong Wu,Jichang Li
Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo . Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.
研究领域:
兽医学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2020
·
IF 8.579
Gengyang Shen,Hui Ren,Qi Shang,Zhida Zhang,Wenhua Zhao,Xiang Yu,Jingjing Tang,Zhidong Yang,De Liang,Xiaobing Jiang
Postmenopausal osteoporosis (PMOP) is a severe health issue faced by postmenopausal women. microRNA-128 (miR-128) is associated with aging, inflammatory signaling, and inflammatory diseases, such as PMOP. It has also been reported to modulate in vitro osteogenic/adipogenic differentiation. However, its function in osteoclast formation is unknown. Methods : First, the expression of miR-128 and nuclear factor of activated T cells 1 ( Nfatc1, bone resorption master marker) was investigated in bone tissues derived from PMOP patients, while their correlation to each other was also investigated. The levels of miR-128 and Nfatc1 in bone specimens and bone marrow-derived macrophages (BMMs) from mice subjected to ovariectomy (OVX) were also assayed. Next, we employed mice BMMs modified for overexpression and inhibition of miR-128 levels to determine its effect on osteoclast differentiation. Moreover, we generated osteoclastic miR-128 conditional knockout ( miR-128 Oc-/- ) mice and isolated miR-128 deletion-BMMs to observe its biological function on bone phenotype and osteoclastogenesis in vivo , respectively. The miR-128 Oc-/- BMMs were used to explore the downstream regulatory mechanisms using pull-down, luciferase reporter, and western-blotting assays. Finally, the impact of miR-128 deficiency on OVX-induced bone loss in mice was evaluated. Results : The miR-128 level was found to be positively correlated with the increase in Nfatc1 level in mouse/human bone specimens and mouse primary BMMs. In vitro experiments demonstrated miR-128 levels that were dependent on activity of osteoclast differentiation and miR-128 overexpression or inhibition in BMMs significantly increased or decreased osteoclastogenesis, respectively. In vivo , we revealed that osteoclastic miR-128 deletion remarkedly increased bone mass through the inhibition of osteoclastogenesis. Mechanistically, we identified sirtuin 1 (SIRT1) as the direct target of miR-128 at the post-transcriptional level during osteoclast differentiation. Increased levels of SIRT1 reduced nuclear factor κB (NF-κB) activity by decreasing the level of acetylation of Lysine 310, as well as inhibiting tumor necrosis factor-α (Tnf-α) and interleukin 1 (IL-1) expressions. Lastly, osteoclastic deletion of miR-128 significantly suppressed OVX-triggered osteoclastogenesis and exerted a protective effect against bone loss in mice. Conclusions : Our findings reveal a critical mechanism for osteoclastogenesis that is mediated by the miR-128/SIRT1/NF-κB signaling axis, highlighting a possible avenue for the further exploration of diagnostic and therapeutic target molecules in PMOP.
研究领域:
分子生物学
·
骨骼生物学
·
内分泌学
·
老年医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FLAVOUR AND FRAGRANCE JOURNAL
·
2025
·
IF 2
Zhi Wu,Jiahui Zheng,Yang Xu,Dairong Wang,Qingbin Han,Ping Liu,Xiaorong Liu,Lanyue Zhang
Discomfort caused by inflammation leads to stress and anxiety in patients and seriously decreases the patients' quality of life. People prefer to use natural products instead of anti-inflammatory drugs because of their low toxicity and side effects. Studies have shown that Sphagnum palustre L. ( S. palustre ) can be used as medicinal plant, but few studies have focused on its anti-inflammatory effects. This study explored the mechanism of action of the ethanol extract of the peat moss plant S. palustre on lipopolysaccharide-induced inflammation in macrophage RAW264.7 cells. Components in S. palustre ethanol extracts (SPE) were identified by HPLC-MS, which mainly included 4-methoxybenzaldehyde, 4-methoxycinnamaldehyde and oleanolic acid. The effects of different concentrations (6.25–100 μg/mL) of SPE after 24 h administration were evaluated to establish a cellular inflammation model. Three biological replicates were performed based on each experiment, the MTT assay results showed that a low concentration of SPE promoted cell proliferation marked by Formazan. In a neutral red uptake assay, the SPE group was effectively inhibited the cell phagocytosis rate. With the increase of SPE concentration, intracellular ROS release decreased, which detected by DCFH-DA. Immunofluorescence assay result showed that SPE inhibited the release of reactive oxygen species from macrophages with fluorescent markers and DAPI. SPE inhibited the release of nitric oxide from macrophages as well. What's more, SPE significantly decreased the protein expression of interleukin (IL)-1, IL-6, and nuclear factor (NF)-κB according to enzyme-linked immunosorbent and immunocytochemical assays. SPE reduces inflammation in macrophage RAW264.7 cells and thus is a promising natural anti-inflammatory plant.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
药用植物研究
✓ 已验证
DOI
高影响因子
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