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Journal of Translational Medicine · 2024 ·Vol. 22 ·期 1 ·1-19 · IF 6.1

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway

Qin Qian,Shan Zhiyan,Xing Lei,Jiang Yutong,Li Mengyue,Fan Linlin,Zeng Xin,Ma Xinrui,Zheng Danyang,Wang Han,Wang Hui,Liu Hao,Liang Shengjun,Wu Lijie,Liang Shuang

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

CAS / MDL: 100068-60-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Inflammation Research · 2025 · IF 4.1

Subchronic Chlorpyrifos Exposure Induces Thyroid Follicular Cell Pyroptosis to Exacerbate Thyroid Toxicity by Modulating Nrf2/Keap1/NF-κB Pathway in Male Mice

Bingyan Gu,Yuying Chen,Huifang Xu,Kunyu Zhan,Keying Zhu,Huan Luo,Yanqun Huang,Hanbing Zeng,Wenbiao Zheng,Kun Tian,Hongfeng Ruan

Purpose Chlorpyrifos (CPF), a widely used organophosphate pesticide in agriculture, particularly in China, has raised significant environmental and health concerns due to its persistence and bioaccumulation. While CPF-induced toxicity in multiple organ systems has been documented, its long-term impact on thyroid homeostasis and the underlying mechanisms remain poorly understood. This study aimed to investigate the subchronic effects of CPF on thyroid function and elucidate the underlying mechanisms of CPF-induced thyroid toxicity.Methods The study utilized 4-week-old male C57BL/6J mice as experimental subjects. These mice were exposed to CPF via intragastric gavage at doses of 3 or 6 mg/kg for a duration of 8 weeks. Throughout the study period, various parameters were assessed, including body weight, serum antioxidant capacity, thyroid endocrine function and structure, apoptosis markers, inflammatory cytokines, and relevant molecular pathways.Results The study revealed that CPF exposure resulted in significant systemic toxicity, manifested through reduced body weight and impaired serum antioxidant capacity. Examination of thyroid-specific effects showed disrupted thyroid endocrine function and structure, accompanied by increased apoptosis and elevated inflammatory cytokines. At the molecular level, CPF significantly stimulated thyroid follicle cell pyroptosis by upregulating the expression of Nlrp3, Caspase-1, and Gsdmd. Further mechanistic analysis demonstrated that CPF activated thyroid follicular cell pyroptosis by modulating the Nrf2/Keap1 antioxidative pathway and enhancing phosphorylation of p65 via NF-κB signaling.Conclusion This comprehensive investigation provides novel insights into the mechanisms of CPF-induced thyroid toxicity. The findings demonstrate that CPF exposure compromises thyroid homeostasis through the induction of follicular cell pyroptosis and modulation of the Nrf2/Keap1/NF-κB signaling axis, highlighting the potential health risks associated with CPF exposure and its impact on thyroid function.

CAS / MDL: 2921-88-2
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2025 ·Vol. 29 ·期 14 ·e70659 · IF 4.2

P-Coumaric Acid Improves Skeletal Muscle Atrophy in Chronic Kidney Disease by Modulating TLR4/MyD88/NF-κB-Mediated Inflammation and Oxidative Stress

Hao Wang,Chi Zhang,Jinyue He,Zhuoen He,Shihua Yan,Yuan Zhang,Shiyin Huang,Yangtian Yan,Yuchi Chen,Zhiqiang Xian,Rong Hu,Yanjing Wang,Wei Xiao,Mingqing Wang

Skeletal muscle atrophy is a prevalent complication in chronic kidney disease (CKD), and its pathogenesis is closely related to inflammation and oxidative stress. P-Coumaric acid (PCA) is a phenolic acid with anti-inflammatory and antioxidant pharmacological actions. This research aims to investigate the effect of PCA on CKD-induced muscle atrophy and its underlying mechanism. In our study, in vivo and in vitro models were established by using 5/6 nephrectomized rats and LPS-induced C2C12 myoblasts. The experimental results showed that PCA ameliorated kidney injury in CKD rats and increased skeletal muscle weight and the cross-sectional area of muscle fibres. In both CKD rats and LPS-induced C2C12 myoblasts, PCA also exhibited anti-inflammatory and antioxidant effects, reduced the levels of pro-inflammatory cytokines and enhanced the activity of antioxidant enzymes. Network pharmacology studies have identified 165 common targets between PCA and skeletal muscle atrophy. Furthermore, the experimental results also demonstrated that PCA decreased the expression of TLR4, MyD88, NF-κB p65, MurF1 and MAFbx at both the protein and mRNA levels. Additionally, in vitro experiments showed that the use of TLR4 agonists could reverse the muscle-protective effect of PCA. In summary, this study illustrated that PCA ameliorated skeletal muscle atrophy in CKD rats by inhibiting the TLR4/MyD88/NF-κB pathway.

CAS / MDL: 501-98-4
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PHYTOMEDICINE · 2025 · IF 8.3

Royal jelly acid inhibits NF-κB signaling by regulating H3 histone lactylation to alleviate IgE-mediated mast cell activation and allergic inflammation

Xue-Ting Xu,Jun-Kai Fan,Xi Chen,Si-Yi Que,Run-Xin Zhang,Yu-Yan Xie,Tian-Ci Zhou,Kunmei Ji,Zhen-Fu Zhao,Jia-Jie Chen

Background Mast cells (MCs) mediate high-affinity IgE Fc receptor (FcεRI)-mediated allergic reactions. Royal jelly acid (RJA), the major lipid constituent of royal jelly, has anti-inflammatory, anti-tumor, antibacterial, and immunomodulatory properties. Purpose This study aimed to investigate how RJA affects IgE-mediated MC activation and to elucidate mechanisms underlying anti-allergic effects. Methods Mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells-2H3 (RBLs) were stimulated with IgE-antigen (Ag). β-hexosaminidase (β-hex) and histamine (HA) release, inflammatory cytokines expression, and cellular morphology changes were examined in stimulated cells. Transcriptome changes associated with RJA-treated activated-MCs were analyzed. Network pharmacology, gene expression, and western blot analyses were employed to explore the relationship between H3 lactylation and anti-allergic effects of RJA on MC. In vivo studies were conducted in IgE-mediated passive cutaneous anaphylaxis (PCA), ovalbumin (OVA)-induced active systemic anaphylaxis (ASA), and HA-induced passive systemic anaphylaxis (PSA) mouse models. Results RJA inhibited IgE-dependent MC activation as evidenced by reduced β-hex and HA release. RJA inhibited MAPK and NF-κB signaling, down-regulated RELA and NFκB1 transcripts, and decreased NF-κB reporter activity. RJA inhibited cellular H3 lactylation and H3K9 lactylation (H3K9la), leading to reduced histone lactyllysine enrichment in RELA or NFκB1 promoter loci. RJA alleviated allergic symptoms in PCA and ASA mice by intraperitoneal injection or oral administration, but did not affect HA-induced hypothermia. Conclusion RJA inhibits IgE-dependent MC activation by reducing cellular H3K9la and suppressing NF-κB signaling via reduced histone lactyllysine enrichment in RELA or NFκB1 promoter sites. RJA may support MC inhibition in the prevention and treatment of allergic diseases.

CAS / MDL: 51-45-6
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FASEB JOURNAL · 2025 ·Vol. 39 ·期 16 ·e70906 · IF 4.2

Ma-Xing-Shi-Gan Decoction Modulates the Gut-Lung Axis in Pediatric Bacterial Pneumonia via HDAC3/NF-κB Signaling and SCFA Restoration

Lina Wei,Lei Wang,Yang Yu,Xiaozhou Sun,Liang Liu,Jing Han,Yongji Wang,Yinan Guo

Pediatric bacterial pneumonia continues to pose a significant global health burden, often resulting in serious complications. Recent studies have emphasized the pivotal role of the gut-lung axis in the progression of respiratory diseases, wherein disruptions in gut microbiota can aggravate pulmonary inflammation. This research investigates the underlying mechanisms by which Ma-Xing-Shi-Gan Decoction (MXSG), a classical formula in traditional Chinese medicine, influences the gut-lung axis in the context of childhood bacterial pneumonia. Clinical data indicated pronounced alterations in intestinal microbial composition and a marked decline in short-chain fatty acid (SCFA) levels among affected pediatric patients—changes that coincided with dysfunctional gut-lung signaling. In a murine model of bacterial pneumonia, MXSG administration restored microbial diversity, elevated SCFA production, and attenuated inflammatory responses by suppressing the HDAC3/NF-κB signaling cascade. Key bioactive constituents of MXSG—namely, quercetin, osajin, nobiletin, and solasodine—were identified as critical regulators, modulating lipid metabolism and promoting SCFA biosynthesis. These results highlight the therapeutic promise of MXSG in reestablishing gut-lung homeostasis and shed light on its mechanistic potential in the treatment of pediatric bacterial pneumonia. Graphical This schematic illustrates how MXSG restores gut microbiota diversity and SCFA levels, suppresses HDAC3/NF-κB signaling, and alleviates lung inflammation in pediatric bacterial pneumonia. Integrated multi-omics and mouse model experiments reveal that MXSG modulates the gut-lung axis and provides a novel mechanism for its clinical efficacy.

CAS / MDL: 64-19-7 73384-59-5
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FISH & SHELLFISH IMMUNOLOGY · 2021 · IF 4.581

Effects of glutamine on the IKK/IκB/NF-кB system in the enterocytes of turbot Scophthalmus maximus L. stimulated with soya-saponins

Min Gu,Shihui Pan,Wanzhen Deng,Qing Li,Zezheng Qi,Chuwen Chen,Nan Bai

Soya-saponins represent key anti-nutritional factors that contribute to soybean meal-induced enteritis , and glutamine is an effective fish intestine protectant that combats the negative effects of soya-saponins. Nuclear transcription factor-kappa B (NF-кB) systems are involved in the interactions between soya-saponins and glutamine, and the goal of the present work was to clarify the related molecular mechanisms used by the NF-кB kinase (IKK)/inhibitor of NF-κB (IκB)/NF-кB system. Primary cultured turbot ( Scophthalmus maximus L.) intestinal epithelial cells were concurrently administrated with 1 mg/mL of soya-saponins and several levels of glutamine (0, 0.5, 1.0 and 2.0 mM) for 12 h and then subjected to real-time PCR and Western blot assays. Compared with cells treated with soya-saponins alone, glutamine significantly decreased the expression of interleukin-1 beta, interleukin 8 and tumor necrosis factor α genes, significantly reduced nuclear and cytosolic NF-κB p65 abundance levels in a dose-dependent manner, increased the IκBα protein level but decreased its phosphorylation, and down-regulated the IKKα/β and phosphorylated IKKα/β levels. In conclusion, this in vitro work confirmed that glutamine attenuated soya-saponin-induced inflammatory responses in turbot intestines. Moreover, it identified molecular pathways in which glutamine first decreased the p65 level and then prevented its nuclear translocation. In addition, glutamine reduced IκBα phosphorylation and maintained its level. Finally, glutamine decreased IKK expression and phosphorylation.

✓ 已验证 DOI PubMed 高影响因子
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INFLAMMOPHARMACOLOGY · 2025 · IF 5.3

Camellia nitidissima Chi extract ameliorates dextran sulfate sodium-induced acute ulcerative colitis in mice by inhibiting TLR4/NF-κB-mediated inflammatory activation

Li Lirong,Huang Rui,Li Wenwen,Yao Dengjie,Zhang Beibei,Li Mengna,Luo Shunan,Qin Yu,Zhang Wenwen

Camellia nitidissima Chi (CNC), whose main composition was gallic acid, catechin, procyanidin-gallate, apigenin-pentosyl-glucoside, vitexin, cyanidin-3-o-glucoside, myricitrin-glucoside, gallocatechin-gallate, epicatechin and rutin, posses sound anti-inflammatory and antioxidant effects. This study aimed to explore the protective effects and mechanisms of the alcoholic extract of CNC on dextran sulfate sodium-induced ulcerative colitis. CNC effectively maintained weight and colon length, and significantly ameliorated colonic histopathological damage. Furthermore, CNC mitigated colitis-induced oxidative stress and exhibited anti-inflammatory properties in UC mice by reducing levels of myeloperoxidase (MPO) and malondialdehyde (MDA), decreasing the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, CNC downregulated the protein expression levels of TLR4, p-NF-κBP65, and p-IκBα of the inflammation-related TLR4/NF-κB signaling pathways. Validation of the molecular docking results also revealed that rutin, the most abundant compound in CNC, interacts with TLR4 and NF-κB protein mainly through hydrogen bonds. CNC also promoted the proliferation of Lactobacillus and Bifidobacterium while reducing the number of Enterococcus , E. coli , Bacteroides, and Peptococcus in mice to improve the intestinal environment and alleviate colitis. CNC inhibited TLR4/NF-κB signaling pathways to relieve inflammation and oxidative damage on UC, is a potential development of natural medicine for UC.

✓ 已验证 DOI PubMed 高影响因子
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Catalysts · 2022 ·Vol. 12 ·期 11 ·1297 · IF 4.501

Electro-Chemical Degradation of Norfloxacin Using a PbO2-NF Anode Prepared by the Electrodeposition of PbO2 onto the Substrate of Nickel Foam

Jianshe Tang,Zhubin Cheng,Hao Li,Li Xiang

A novel three-dimensional network nickel foam/PbO2combination electrode (PbO2-NF) with high electrochemical degradation efficiency to norfloxacin was successfully fabricated through the electrodeposition of PbO2on the substrate of nickel foam. The characterization of an PbO2-NF electrode, including surface morphology, elemental components, electrochemical performance, and stability was performed. In electrochemical oxidation tests, the removal efficiency of norfloxacin (initial concentration for 50 mg/L) on PbO2-NF reached 88.64% within 60 min of electrolysis, whereas that of pure nickel foam was only 30%. In the presence of PbO2-NF, the optimum current density, solution pH, electrode spacing for norfloxacin degradation were 30 mA/cm2, 11, and 3 cm, respectively. The electric energy consumption for 80% norfloxacin was approximately 5 Wh/L. Therefore, these results provide a new anode to improve the removal of norfloxacin in the wastewater with high efficiency and low energy consumption.

✓ 已验证 DOI 高影响因子
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CHEMOSPHERE · 2019 · IF 5.108

Comparison of the performance of prepared pristine and TiO2 coated UF/NF membranes for two types of oil-in-water emulsion separation

Tong Zhang,Fan-xin Kong,Xi-chen Li,Qian Liu,Jin-fu Chen,Chun-mei Guo

Polysulfone ultrafiltration (UF) and polypiperazine-amide nanofiltration (NF) membranes were first fabricated by phase inversion and interfacial polymerization, and then modified by the commonly used TiO 2 on the membrane surface, respectively. Compared with the pristine UF and NF membranes, pure water flux decreased by 40.66% for modified UF membrane and 12.92% for modified NF membrane, while the contact angle of the modified membranes decreased from 66.5° to 35.3° for UF membrane and from 48.2° to37.7° for NF membrane. However, the membrane modified by TiO 2 nanoparticles for both UF and NF membranes exhibited much better anti-fouling and separation performance for two types of oil-in-water emulsions with different droplet size (i.e., prepared oil-in-water emulsion with low salinity and oil produced water in Shengli oilfield, China). It was obvious that water flux of modified UF only slightly decreased and the stable water flux was 2.2 times and 15.6% higher than that of pristine membranes for the prepared oil-in-water emulsion and produced water, respectively. According to the five fouling models for UF, the TiO 2 modified UF membrane could alleviate the fouling on membrane surface and greatly increase water flux by reducing the adsorption, deposition, blockage of membrane pores and formation of cake layer for two types of oil-in-water emulsion. For NF, water flux of the modified membrane increased by 66.1% and 22.8% for prepared oil-in-water emulsion and produced water, respectively. TiO 2 coating effectively alleviated the oil adhesion and cake layer formation on the membrane surface.

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INTERNATIONAL JOURNAL OF HYDROGEN ENERGY · 2024 · IF 8.1

Eco-friendly and large-scale fabrication of NiMoN/Ni(OH)2/NF as highly efficient and stable alkaline hydrogen evolution reaction electrode

Mengyao Xue,Yuankang Bao,Xun Xu,Luliang Liao,Ping Li,Hao Zhang,Deliang Li,Binbin Wei,Shuwang Duo

Bimetallic nickel-molybdenum nitride (NiMoN) catalysts have attracted great attention due to their remarkable similarity to group VIII noble metals in terms of electronic structure, good electron conductivity, and durability for the hydrogen evolution reaction (HER). However, the existing approaches for fabricating NiMoN catalysts usually entail a series of multiple steps and hazardous ammoniated ingredient. As a result, these methods are difficult to be scaled up for large-area fabrication towards industrial water splitting. Herein, a hierarchical composite NiMoN@Ni(OH) 2 @NF composite electrode with a sheet morphology was synthesized based on a rational combination of seawater etching and magnetron sputtering. This method is easily scalable for producing large-area electrodes with minimal pollution. The incorporation of Ni(OH) 2 @NF nanoarray carriers enhances the exposure of additional active sites on the NiMoN layer, thereby augmenting the electrochemically active specific surface area of the electrode.The as-synthesized NiMoN@Ni(OH) 2 @NF electrode demonstrates excellent HER activity, with an overpotential of 57 mV at 10 mA cm −2 , and exhibits remarkable long-term catalytic stability for over 100 h at a current density of 100 mA cm −2 .This study presents an eco-friendly and straightforward method for preparing large-scale transition metal nitride catalysts with high catalytic activity.

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Frontiers in Pharmacology · 2025 · IF 4.8

In vitro and in vivo characterization of oridonin analogs as anti-inflammatory agents that regulate the NF-κB and NLRP3 inflammasome axis

Huiping Ou,Zhanpan Wu,Jinhua Ning,Qiufeng Huang,Wancun Wang,Guochun Yang,Yingxun Zhou,Anguo Hou,Peng Li,Lingyun Chen,Wen Bin Jin

Introduction: A series of oridonin hybrids were synthesized and evaluated for anti-inflammatory potential, focusing on their ability to inhibit NO production in RAW264.7 cells and their therapeutic prospects for NLRP3-driven disorders.Methods: Anti-inflammatory activity was assessed by measuring NO inhibition in LPS-stimulated RAW264.7 cells. The most active compound, 4c, was further analyzed using ELISA and WB to evaluate its effects on inflammatory proteins (p-NF-κB, p-IκB, NLRP3, IL-6, IL-1β, COX-2, iNOS). In vivo efficacy was tested in a murine acute lung injury model, with RT‒qPCR and WB used to assess inflammatory markers in lung tissues. Molecular docking predicted 4c’s binding mode with NLRP3, while RNA-seq and RT‒qPCR identified differentially expressed genes.Results: Compound 4c significantly inhibited NO production and suppressed key inflammatory proteins in vitro. In vivo, it alleviated acute lung injury, reduced IL-6 and TNF-α mRNA levels, and inhibited NLRP3, p-NF-κB, and IL-6 protein expression. Docking suggested covalent binding to NLRP3. RNA-seq revealed 4c upregulated Trdc, Stfa2, and Gsta2 while downregulating Spib, Csf2, and Nr4a1.Discussion: Compound 4c demonstrates potent anti-inflammatory effects via NLRP3 pathway inhibition and modulation of inflammatory genes. These findings highlight oridonin hybrids, particularly 4c, as promising candidates for NLRP3-driven inflammatory disorders, warranting further investigation.

✓ 已验证 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2024 · IF 3.9

Rutin, a natural flavonoid glycoside, ameliorates zearalenone induced liver inflammation via inhibiting lipopolysaccharide gut leakage and NF-κB signaling pathway in mice

Yanan Wang,Qianqian Wang,Gaigai Wang,Qiongqiong Zhang,Yongpeng Guo,Xin Su,Yu Tang,Matthew Koci,Jianyun Zhang,Qiugang Ma,Lihong Zhao

Zearalenone (ZEN) poses a potential threat on human and animal health partly through the nuclear factor (NF)-κB signaling pathway. In silico study suggested that rutin effective against TLR4 and NF-κB. A wetting test was designed to evaluate the effect and underlying mechanism of rutin in alleviating ZEN-induced inflammation in animals. Twenty-four female mice were randomly divided into 4 groups: control (basal diet), ZEN group (basal diet + ZEN), rutin group (basic diet + rutin), Z + R group (basal diet + rutin + ZEN). Results showed that rutin effectively alleviated ZEN-induced inflammation and damage of liver and jejunum in mice. Rutin addition reduced the content of lipopolysaccharide (LPS) in serum and liver mainly by improving the intestinal barrier function resulted from the production increase of short-chain fatty acids (SCFA). In sum, this study showed that rutin alleviated ZEN-induced liver inflammation and injury by modulating the gut microbiota, increasing the production of SCFA and improving intestinal barrier function, leading to the decrease of LPS in liver and the inhibition of MyD88 independent NF-κB signaling pathway in mice. Specifically, these findings may provide useful insights into the screening of functional natural compounds and its action mechanism to alleviate ZEN induced liver inflammation.

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