GENOMICS
·
2023
·
IF 4.4
Dan Chen,Li Shi,Dingfu Zhong,Ying Nie,Yi Yang,Dong Liu
Background Gastric cancer (GC) is a common cancer with a high incidence and mortality rate. Herein, the role of hsa_circ_0002019 (circ_0002019) in GC was investigated. Methods The molecular structure and stability of circ_0002019 were identified by RNase R, and Actinomycin D treatment. Molecular associations were verified by RIP. Proliferation, migration, and invasion were detected by CCK-8, EdU, and Transwell, respectively. The effect of circ_0002019 on tumor growth was analyzed in vivo. Results Circ_0002019 was elevated in GC tissues and cells. Circ_0002019 knockdown inhibited the proliferation, migration, and invasion. Mechanically, circ_0002019 activated NF-κB signaling by increasing TNFAIP6 mRNA stability by PTBP1. Activation of NF-κB signaling limited the antitumor effect of circ_0002019 silencing in GC. Circ_0002019 knockdown inhibited tumor growth in vivo by reducing TNFAIP6 expression. Conclusions Circ_0002019 accelerated the proliferation, migration, and invasion by regulating TNFAIP6/NF-κB pathway, suggesting circ_0002019 could be a key regulatory factor in GC progression.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2018
·
IF 3.549
Yiyi Jin,Jianchang Qian,Xin Ju,Xiaodong Bao,Li Li,Suqing Zheng,Xiong Chen,Zhongxiang Xiao,Xuemei Chen,Weiwei Zhu,Weixin Li,Wencan Wu,Guang Liang
Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.
研究领域:
药理学
·
免疫学
·
病理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROTOXICOLOGY AND TERATOLOGY
·
2025
·
IF 2.8
Fangfei Li,Jie Zhang,Xiaoli Ma,Hao Chen,Guiqiang Liang,Yunfeng Zou
Excessive accumulation of manganese (Mn) can cause neuroinflammation, impairing cognitive function. SPON1, a secreted glycoprotein in the extracellular matrix, is implicated in neuroinflammation, but its role in activating pro-inflammatory pathways in Mn-induced neuroinflammation remains unclear. This study employed in vivo and in vitro models to investigate Mn neuroinflammation. The expression levels of SPON1 and the ERK1/2/NF-κB pathway associated with inflammation were measured in male C57BL/6 mice after gavage of Mn at different doses (0, 25, 50, 100 mg/kg) for 12 weeks. SPON1 levels were measured after primary hippocampal neurons, primary cortical neurons, neuroblastoma cells (N2a), and microglial cells (BV2) were exposed to various concentrations of Mn for 24 h. We observed that in vivo Mn exposure significantly decreased SPON1 expression in the cortex but not in the hippocampus. Similarly, in vitro experiments demonstrated that Mn exposure significantly reduced SPON1 levels in primary cortical neurons, N2a, and BV2. In addition, Mn exposure increased the expression levels of ERK1/2 and NF-κB pathway proteins in the mouse cortex. Because BV2 cells are susceptible to inflammatory signals, they were chosen to elucidate how SPON1 induces neuroinflammation during Mn exposure. SPON1 knockdown increases the expression of inflammatory factors, whereas SPON1 overexpression inhibits the activation of the ERK1/2/NF-κB pathway and reduces inflammatory factor levels. In summary, these results suggest that Mn may affect the activation of ERK1/2/NF-κB pathway and the expression of inflammatory factors by inhibiting SPON1, ultimately promoting neuroinflammation.
研究领域:
神经科学
·
毒理学
·
分子生物学
·
免疫学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Xiaoli Qin,Yan Lu,Yawen Luo,Yafang Cui,Kai Zhao,Yang He,Muhammad Aziz ur Rahman,Shengnan Min,Wenfang Wang,Fuyu Yang,Binghai Cao,Huawei Su
Alfalfa is rich in flavonoid compounds, which are known for their antioxidative and anti-inflammatory properties, suggesting therapeutic potential for alfalfa flavonoids (AF) in inflammation-related diseases. This study investigated the effects of AF on Salmonella -induced colitis, a severe inflammatory bowel disorder characterized by oxidative damage and inflammatory response. In vitro, antioxidant assays revealed AF's concentration-dependent radical scavenging, significantly reducing electron paramagnetic resonance (EPR) signals for HO • and O 2 •− by 42% and 54%, respectively. In vivo, AF treatment significantly mitigated body weight (BW) loss by 6%, increased colon length by 11%, and reduced liver and spleen weights by 19% and 81%, respectively, compared to the colitis group. Mechanistically, AF suppressed inflammation by downregulating the Toll-like receptor 4 (TLR4)/IκB/nuclear factor-κB (NF-κB)/cyclooxygenase-2 (COX-2) pathway and inhibiting nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby lowering levels of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β]). Concurrently, AF enhanced antioxidant defense via the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing catalase (CAT) (69%), glutathione peroxidase (GPx) (83%), and superoxide dismutase (SOD) (21%) activities. Moreover, AF preserved epithelial and mucosal barriers by reducing apoptosis and upregulating tight junction proteins (Claudin1, ZO-1, E-cadherin) and goblet cell marker Ulex europaeus (Gorse) Agglutinin I (UEA-1). Microbiota analysis revealed that AF significantly enriched beneficial bacteria, including Akkermansia , Oscillibacter , and butyrate-producing taxa, thereby counteracting Salmonella -induced dysbiosis. Furthermore, AF restored the disrupted profile of short-chain fatty acids (SCFAs), strengthening the relationship between symbiotic microbiota and mucosal defense. Overall, AF exerted multifaced protection against Salmonella -induced colitis by alleviating oxidative stress, stabilizing intestinal homeostasis, and thus attenuating inflammation. These findings make AF a promising phytopharmaceutical for the prevention and treatment of inflammatory diseases.
研究领域:
药理学
·
微生物学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Mijia Li,Wei Yuan,Shiyi Duan,Yang Li,Sijie Zhang,Yan Zhao,Shimei Xiao,Keyuan Zhong
The large-scale mining and utilization of rare earth elements have significantly increased their concentration in the environment, especially in regions surrounding mining areas. These environmentally-enriched rare earth elements accumulate in agricultural products and organisms through soil and water, potentially impacting in human health through the food chain. Erbium (Er), a rare earth element of the lanthanide series (Group IIIB), plays a crucial role in various modern technological applications. It is primarily utilized in ceramics, glass coloring, optical fibers, laser technology, and the nuclear industry, among others. However, a paucity of information on the health effects and ecotoxicity of erbium is currently available. In this study, we used the zebrafish as experimental animal to investigate the potential impact of the rare earth element erbium on the immune system. We exposed fertilized zebrafish embryos to different concentrations of erbium (0, 4, 8 and 16 mg/L) from 6 hours post-fertilization (hpf) until 72 hpf. We found that with increasing concentrations of erbium exposure, there was an increasing and dispersing trend in the number of zebrafish neutrophils; a decreasing trend in the number of macrophages. Exposure to erbium was demonstrated to impair the phagocytic capability of macrophages, reduce the recruitment of neutrophils to the wound site, and lower the resistance of zebrafish to Escherichia coli infection. Erbium exposure led to macrophage apoptosis and upregulation of oxidative stress in the zebrafish. The individual application of the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine, the IKBKB inhibitor resveratrol and the NF-κB inhibitor andrographolide was demonstrated to alleviate erbium-induced immune toxicity, as confirmed by assays including acridine orange staining, neutrophil enumeration and recruitment, and real-time quantitative PCR. Therefore, the rare earth element erbium induced immune toxicity in zebrafish through the ROS/NF-κB pathway. The findings of this study provide information for assessing the impact of rare earth elements on human health and ecosystems.
研究领域:
环境毒理学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
ENVIRONMENT INTERNATIONAL
·
2020
·
IF 7.577
Wenhui Qiu,Jiaqi Hu,Jason T. Magnuson,Justin Greer,Ming Yang,Qiqing Chen,Meijuan Fang,Chunmiao Zheng,Daniel Schlenk
Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01–100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway.
研究领域:
水生毒理学
·
免疫学
·
环境科学
✓ 已验证
产品关联
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
·
细胞生物学
·
骨关节炎病理学
·
信号转导
·
转化医学
·
软骨生物学
·
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
Materials
·
2024
·Vol. 17
·期 10
·2195
·
IF 3.1
Yu Liu,Panpan Li,Zegao Wang,Liangjuan Gao
This study reported a multi–functional Co0.45Fe0.45Ni0.9–MOF/NF catalyst for oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and overall water splitting, which was synthesized via a novel shape–preserving two–step hydrothermal method. The resulting bowknot flake structure on NF enhanced the exposure of active sites, fostering a superior electrocatalytic surface, and the synergistic effect between Co, Fe, and Ni enhanced the catalytic activity of the active site. In an alkaline environment, the catalyst exhibited impressive overpotentials of 244 mV and 287 mV at current densities of 50 mA cm−2and 100 mA cm−2, respectively. Transitioning to a neutral environment, an overpotential of 505 mV at a current density of 10 mA cm−2was achieved with the same catalyst, showing a superior property compared to similar catalysts. Furthermore, it was demonstrated that Co0.45Fe0.45Ni0.9–MOF/NF shows versatility as a bifunctional catalyst, excelling in both OER and HER, as well as overall water splitting. The innovative shape–preserving synthesis method presented in this study offers a facile method to develop an efficient electrocatalyst for OER under both alkaline and neutral conditions, which makes it a promising catalyst for hydrogen production by water splitting.
研究领域:
材料科学
·
电化学
·
能源转换
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2022
·
IF 7.139
Yekai Zhang,Shuai Wang,Hong Zhong,Xin Ma,Zhanfang Cao
Exploring low-cost and high-efficiency OER catalysts is still a challenge. In this paper, self-supporting catalyst-Ni 3 S 2 @FeCrMoS x /NF was prepared using metal organic frameworks as templates. The morphology of the pre-catalyst has been deeply restructured after the sulfidation reaction, which significantly changes the composition and catalytic performance of the catalyst. The overpotential of Ni 3 S 2 @FeCrMoS x /NF is only 144 mV and 241 mV at a current density of 10 and 50 mA cm −2 respectively, the Tafel slope is as low as 45 mV dec −1 . And it can maintain good electrochemical stability at a high current density of 100 mA cm −2 . The outstanding OER performance of Ni 3 S 2 @FeCrMoS x /NF can be attributed to the increase of electrochemical surface area after sulfidation, the synergistic effect among multi-metals and the synergistic effect of polymetallic sulfides generated by sulfidation.
研究领域:
材料科学
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）