BRAIN RESEARCH BULLETIN
·
2024
·
IF 3.5
Yu Bi,Ziyi Xie,Xiang Cao,Huanyu Ni,Shengnan Xia,Xinyu Bao,Qinyue Huang,Yun Xu,Qingxiu Zhang
Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.
研究领域:
神经科学
·
药理学
·
分子生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hao Xu,Ning Ning Guo,Chen Ying Zhu,Lin Yan Ye,Xing Yi Yan,Yong Qin Liu,Ze Yan Zhang,Guangji Zhang,Liaqat Hussain
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
研究领域:
肿瘤学
·
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yuyan Sun,Ziyu Luo,Haiqi Zhou,Sha Wu,Hongwei Shen,Yuanyuan Fu,Thai Namanh Ngo,Wen Wang,Yuanrong Wang,Ying Kong
Chondrocyte mechanotransduction dysfunction is a key feature of osteoarthritis (OA). Previous studies have demonstrated that primary cilia play a crucial role in chondrocyte mechanosensation and signal transduction. Transient Receptor Potential Vanilloid 4(TRPV4), which is highly expressed on primary cilia, is a critical mechanotransduction protein and one of the most important Ca 2+ channels. However, the interplay between the mechanism of primary cilia-mediated signaling and that of TRPV4 channel regulation remains poorly understood. Here, we demonstrate that OA chondrocytes and Intraflagellar Transport Protein 88(Ift88) conditional knockout (cKO) mice exhibit reduced ciliary incidence. This results in cartilage degeneration. TRPV4 expression inversely correlated with ciliary integrity, increasing as cilia were lost. In cilia-intact healthy chondrocytes, TRPV4 antagonism inhibited Ca 2+ -dependent NF-κB activation while promoting type II collagen(COL2) synthesis. These effects were abolished by Interleukin-1 beta(IL-1β)-induced ciliary defect or IFT88 deficiency. Chromatin immunoprecipitation(ChIP) analysis revealed disrupted p65 binding to the COL2 promoter upon the loss of ciliary integrity. Crucially, Ift88 cKO chondrocytes showed unresponsive of the TRPV4 channel, as confirmed by Ca 2+ flux and changes in the expression levels of NF-κB and COL2. Our findings position primary cilia as indispensable regulators of TRPV4-mediated NF-κB - COL2 signaling, offering mechanistic insights into OA pathogenesis and identifying IFT88 as a therapeutic checkpoint.
研究领域:
分子生物学
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细胞生物学
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骨关节炎病理学
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信号转导
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转化医学
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软骨生物学
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机械生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Sun Honglan,Yang Chao,Yin Xiaoyunqing,Chen Shizhao,Huang Yuqi,Kuang Huifang,Luo Wen
The chronic illness known as oral submucous fibrosis (OSF) results in tissue fibrosis, precancerous lesions, and scarring. It usually manifests itself in the buccal mucosa. It frequently occurs in the buccal mucosa. Von Hippel-Lindau (VHL) is an essential component of E3 ubiquitin ligase complex. The loss of VHL led to reduced fibrotic responses, accompanied by ameliorated fiber deposition. However, the precise impact of VHL on OSF is yet unclear. OSF tissues and normal mucosal tissues were applied to analyze the distinct expression of VHL and histone deacetylase 6 (HDAC6). Oral fibroblasts were treated to arecoline to simulate OSF in vitro, and molecular biological experiments were conducted to identify the role of VHL in buccal mucosa fibroblasts (BMFs). VHL was downregulated and HDAC6 was upregulated in OSF tissues and BMFs. Overexpression of VHL inhibited fibrosis in arecoline-treated BMFs. VHL inhibits the level of HDAC6 by inducing the ubiquitination of HDAC6. Knockdown of HDAC6 reduces the fibrogenic ability of BMFs. Furthermore, overexpression of HDAC6 contributes to the activation of NF-κB signaling in BMFs. HDAC6 selective inhibitor ACY-1215 inhibited the NF-κB signaling pathway. VHL attenuated arecoline-induced OSF by inhibiting the ubiquitination of HDAC6 and blocking NF-κB pathway. As a result, our study offers new perspectives into the discovery of novel tactics that can be employed against OSF.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 3
·e70090
·
IF 4.2
Cailan Wang,Xinyi Lin,Shichun Guan,Qiaoyuan Wu,Shixiong Liang
Dihydroartemisinin (DHA) is a derivative of artemisinin, which affects inflammation, oxidative stress, and immune regulation. However, the mechanism underlying its effects remains largely unknown. This study aims to explore the mechanism by which DHA affects radiation-induced lung injury (RILI), providing new insights for lung radiotherapy. To elucidate its mechanism of action, C57BL/6 J mice were irradiated with 15 Gy whole chest. RILI was evaluated by qRT-PCR, ELISA, histology, Western blot analysis, immunohistochemistry, and RILI signaling cascade studies. In addition, small interfering RNAs were employed to knockdown cGAS proteins in the cGAS-STING signaling pathway in the human bronchial epithelium cell line (BEAS-2B). Both In Vivo and Vitro experiments were conducted to investigate the specific mechanism by which DHA alleviated RILI. We observed the activation of the cGAS-STING pathway, along with the phosphorylation of the downstream target NF-κB and an increase in inflammatory factor levels in the mouse model following radiation exposure. In the cell model, irradiation also triggered the activation of the cGAS-STING signaling pathway and its downstream targets, leading to elevated levels of inflammatory factors. Notably, knocking down the cGAS using small interfering RNA in the BEAS-2B cells significantly alleviated RILI in the cell model. Our study elucidated the mechanism of DHA reducing RILI through the cGAS/STING/NF-κB signaling pathway, and revealed that the GAS/STING/NF-κB axis may be a potential therapeutic target for RILI.
研究领域:
医学
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药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2023
·
IF 2.4
Rui DAI,Yun XIANG,Rui FANG,Hai-Han ZHENG,Qing-Song ZHAO,Yan WANG
Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 μg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18–20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16–P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-ĸB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.
研究领域:
免疫学
·
药理学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Xu Wenting,Zhou Mengjia,Li Linlin,Zhang Yuqing,Zhang Tianya,Zhang Xiangjian
Activated and polarized microglia regulate neuroinflammatory responses and programmed cell death processes in ischemic stroke. Although the inactivation of muscleblind-like 1 (Mbnl1) is known to cause structural defects in the brain, its role in microglial apoptosis and polarization remains unclear. This study aims to explore the mechanism of Mbnl1 in ischemic stroke, particularly its role in the regulation of microglial apoptosis and polarization, as well as its impact on neuroinflammatory responses and cognitive dysfunction. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. Mbnl1 overexpression exerts a protective effect against ischemic stroke by regulating microglia-mediated neuroinflammation through inhibition of the NF-κB signaling pathway. This modulation promotes cognitive recovery in C57BL/6N mice with stroke, highlighting Mbnl1 as a potential therapeutic target for stroke treatment.
研究领域:
神经生物学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2017
·Vol. 41
·期 6
·611-621
·
IF 1.831
Yaojie Niu,Qiumei Dong,Rongheng Li
To investigate the efficacy and mechanisms of matrine, a component derived from Sophora flavescens in treatment of rheumatoid arthritis (RA), a rat model of RA was established. Compared to control rats, matrine significantly mitigated inflammation and severity of RA (paw volume and articular index (AI) score). Using either mice splenic T cells stimulated with PMA/ionomycin or rat splenic T cells, the levels of Th1 and Th2 responses were determined by flow cytometry, quantitative RT-PCR, and ELISA. Furthermore, the levels of NF-κBp65 (RelA), IκBα, and phosphor-IκBα in T cells were determined by Western blot. Our study found that matrine modulated the imbalance of Th1 and Th2 cytokine responses in rats with RA by reducing the levels of Th1 cytokines (IFN-γ, TNF-α, IL-1β), but increasing Th2 cytokine (IL-4 and IL-10) through attenuating the NF-κB signaling in T cells, suggesting matrine as a promising drug for intervention of RA.
研究领域:
免疫学
·
药理学
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2025
·Vol. 39
·期 6
·e70303
·
IF 2.8
Hongyu Zhang,Guoshun Lin,Yang Yang,Yifei Wang,Xiushuo Yang,Guige Hou,Zhenbo Wang,Qingguo Meng,Yun Hou
Hydroxytyrosol (HT), a primary phenolic compound in olive oil, exhibits antioxidant and antiapoptotic effects in various cell types, including cardiomyocytes and human umbilical vein endothelial cells. Contrastingly, bisphenol S (BPS) is known to induce apoptosis in myocardial and endothelial cells via oxidative stress. BPS increases reactive oxygen species (ROS) production and reduces the viability of hippocampal HT22 cells. In this study, we explored whether HT could protect neurons from BPS-induced oxidative stress and apoptosis. Our results showed that HT effectively inhibited oxidative stress responses in the brains of BPS-treated mice and significantly decreased ROS production in BPS-treated HT22 and PC12 cells. Additionally, HT reduced BPS-induced neuronal apoptosis in the cortical regions of mice as well as in HT22 and PC12 cells. Further analysis revealed that BPS activates the NF-κB signaling pathway, a key mediator of oxidative stress and neuronal apoptosis, while HT counteracted these effects. In summary, this study demonstrates the antioxidant and antiapoptotic properties of HT in BPS-exposed neurons. These findings provide compelling experimental evidence supporting the potential dietary inclusion of HT-rich compounds to alleviate oxidative stress-related neuronal damage. Summary HT showed neuroprotection in BPS-treated in mice, HT22 and PC12 cells. HT attenuates oxidative stress in BPS-treated in mice, HT22 and PC12 cells. HT inhibits NF-κB activity in BPS-treated in HT22 and PC12 cells.
研究领域:
神经生物学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Inflammation
·
2014
·
IF 0
Hang Yang,Haili Qi,Jingli Ren,Jing Cui,Zhenfeng Li,Helge L. Waldum,Guanglin Cui
Nuclear factor-kappaB (NF-κB)/interleukin (IL-6) pathway links chronic inflammation to colitis associated cancer (CAC). In this study, we examined the dynamic temporal changes of the NF-κB/IL-6 pathway during the procession of experimental CAC mouse model. Mice were sacrificed after induction for 14, 16, 18, and 22 weeks for the examination of tumor burden, inflammation degree, and protein level of NF-κB and IL-6 in bowel tissues. The results showed that tumor burden and inflammation severity in the bowels were gradually increased over the observed time-points. The expressions of IL-6 and NF-κB proteins were gradually increased after induction of dysplastic lesions over times. These data provide new information on the dynamic temporal changes of NF-κB/IL-6 pathway in relation to CAC development that may be relevant in the design of future investigations of therapeutic interventions to effectively target CAC processes.
研究领域:
分子生物学
·
肿瘤学
·
免疫学
✓ 已验证
DOI
PubMed
EXPERIMENTAL ANIMALS
·
2023
·
IF 2.4
Jianqiang WEI,Jing YIN,Ying CUI,Kaijie WANG,Mingyan HONG,Jianzhong CUI
Intracerebral hemorrhage (ICH) is an incurable neurological disease. Microglia activation and its related inflammation contribute to ICH-associated brain damage. FERM domain containing kindlin 1 (FERMT1) is an integrin-binding protein that participates in microglia-associated inflammation, but its role in ICH is unclear. An ICH model was constructed by injecting 50 μl of autologous blood into the bregma of rats. FERMT1 siRNA was injected into the right ventricle of the rat for knockdown of FERMT1. A significant striatal hematoma was observed in ICH rats. FERMT1 knockdown reduced the water content of brain tissue, alleviated brain hematoma and improved behavioral function in ICH rats. FERMT1 knockdown reduced microglia activity, inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and decreased the expression of inflammatory factors including interleukin-1β (IL-1β) and interleukin 18 (IL-18) in the peri-hematoma tissues. BV2 microglial cells were transfected with FERMT1 siRNA and incubated with 60 μM Hemin for 24 h. Activation of NLRP3 inflammasome induced by hemin were reduced in microglia when FERMT1 was knocked down, leading to decreased production of inflammatory factors IL-1β and IL-18. In addition, knockdown of FERMT1 prevented the activation of nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. Our findings suggested that down-regulation of FERMT1 attenuated microglial inflammation and brain damage induced by ICH via NLRP3/NF-κB pathway. FERMT1 is a key regulator of inflammatory damage in rats after ICH.
研究领域:
神经科学
·
分子生物学
·
炎症
·
神经病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMATION RESEARCH
·
2025
·Vol. 74
·期 1
·1-22
·
IF 5.4
Zhang Jingwen,Hayat Muhammad Abid,Si Yu,Guo Tao,Ni Yinying,Wang Qian,Hong Yancheng,Cao Yudie,He Sijia,Weng Zijuan,Li Fengmei,Zuo Hao,Sun Xin,Chen Bo,Hu Jiabo
Objective Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms. Methods C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot. Results IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88. Conclusions IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.
研究领域:
神经科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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