INFLAMMATION RESEARCH
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2026
·Vol. 75
·期 1
·165
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IF 6.2
Wang Bing,Song Yingqiu,Xu Wenbo,Chen Jiaqing,Huang Yurong,Zhou Xinyue,Cai Yikang,Xia Aixin,Li Yanping,Jiang Liwei,Liao Faxue,Huang Jian,Miao Chenggui
Background Our previous research has shown that lipopolysaccharide (LPS) derived from Gram-negative bacteria in the intestine promoted rheumatoid arthritis (RA) after entering peripheral blood, but the specific molecular mechanism was unclear. Method This study used transcriptome and proteomic sequencing, western blotting, co-immunoprecipitation (Co-IP), cell co-culture, and other related methods to investigate whether LPS entering peripheral blood activated the Wnt7b secretion in macrophages, and used the Wnt7b as a messenger molecule to promote the communication between macrophage-fibroblast-like synoviocyte (FLSs), ultimately leading to the onset of RA. Result The results showed that LPS significantly promoted the pathology of collagen induced arthritis (CIA) mice. Transcriptome and proteomic sequencing, as well as experimental validation, confirmed that the target of LPS may be the Wnt7b. Knocking down the Wnt7b in CIA mice could effectively alleviate the LPS induced pathology. Furthermore, in the M 0 macrophage-FLS co-culture system, overexpression of Wnt7b in M 0 macrophages promoted the expression of RA pathological factors in FLSs and activated the WNT/CTNNB1 signaling pathway of FLSs. However, knocking down the Wnt7b in M 1 macrophages resulted in the opposite effects. Interestingly, in the M 0 macrophage-FLS co-culture system, overexpression of Wnt7b in M 0 macrophages could enhance the expression of frizzled class receptor 8 (FZD8) on FLSs, activating the Wnt/β-catenin signaling pathway of FLSs. However, knocking down the FZD8 in FLSs after overexpression of Wnt7b could interfere with the effects of overexpression of Wnt7b. In addition, adding LPS to M 0 macrophages promoted the FZD8 expression of co-cultured FLSs and activated the Wnt/β-catenin signaling pathway. Knocking down FZD8 in FLSs after adding LPS to M0 macrophages could interfere with the effects of LPS. Conclusion This study suggested that circulating LPS stimulated macrophages to secrete Wnt7b, which acted as a messenger molecule and bound to the FZD8 receptor on the FLSs cell membrane in the synovial microenvironment, promoting the activation of the Wnt/β-catenin signaling pathway in FLSs and leading to RA.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2022
·Vol. 103
·期 4
·2014-2022
·
IF 4.125
Wenping Peng,Nan Wang,Shunmin Wang,Junzhen Wang,Zixiu Bian
BACKGROUND Tartary buckwheat is rich in flavonoids. The application of physical processing technology and exogenous materials treatment can effectively promote grain germination and the accumulation of bioactive secondary metabolites. The content of four flavonoids, the activities of key enzymes (phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), flavonol synthase (FLS)) and the expression of key enzyme genes ( FtPAL , FtCHI , FtFLS1 , FtFLS2 ) in Tartary buckwheat sprouts treated with microwave and l -phenylalanine ( l -Phe) were investigated, and the relationship between them was analyzed to explore the mechanism of promoting flavonoid accumulation, and to provide a theoretical basis for the development of functional Tartary buckwheat sprout food. RESULTS Germination can promote the synthesis of flavonoids. The contents of chlorogenic acid and rutin in 7-day sprouts increased by 13 420.63% and 225.12% compared with seeds, respectively. Under the best treatment condition T 3 (microwave 250 W, 90 s, 2.9 mmol L −1 L-Phe), the specific activities of PAL, CHI and FLS in 5-day-old sprouts increased by 47.84%, 53.04% and 28.02% compared with control check (CK), respectively; and the expression of FtPAL , FtCHI and FtFlS1 increased by 39.84%, 24.78% and 33.72% compared with CK, respectively. Correlation analysis showed that the content of flavonoids in Tartary buckwheat sprouts was significantly positively correlated with the specific activities of key enzymes ( P < 0.01) and dynamically correlated with genes related to the synthesis of three enzymes. CONCLUSION It suggested that microwave and l -Phe treatment may promote the synthesis of flavonoids by promoting the expression of key enzymes genes in phenylpropane metabolism and controlling the activity of key enzymes in phenylpropane metabolism. © 2022 Society of Chemical Industry.
研究领域:
食品科学
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植物生理学
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生物化学
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Chinese Journal of Integrative Medicine
·
2024
·
IF 2.2
Liu Xiao-rong,Li Shuo-fu,Mei Wen-ya,Liu Xiang-dan,Zhou Ri-bao
Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table ( n =5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion ( P <0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS ( P <0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β ( P <0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB ( P <0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 ( P <0.05). In in vivo studies, isorhamnetin decreased arthritis index scores ( P <0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue ( P <0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations ( P <0.05). Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.
研究领域:
药理学
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免疫学
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风湿病学
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分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Yan Zhao,Qianqian Yu,Miaolin Duan,Qi Zhang,Zhishang Li,Yan Zhang,Yana Liu,Han Wang,Xingmin Li,Ruitong Dai,Fei Jia
The efficient, sensitive, and rapid detection of Salmonella typhimurium (S. typhimurium) in food and food products is important to ensure food safety and health. This study developed a fluorescence biosensing assay that integrated recombinase-aided amplification (RAA) and CRISPR/Cas12a with a zeolitic imidazolate framework-8@fluorescein sodium (ZIF-8@FLS) nanocomposite for the sensitive detection of S. typhimurium. In this approach, using RAA as a preamplification module, CRISPR/Cas12a-AChE as a target recognition and dual-enzyme cascade amplification module, and the prepared ZIF-8@FLS with high porosity and rapid pH responsiveness as a fluorescence signal explosive amplification module, the RAA-CRISPR/Cas12a-ZIF-8@FLS biosensor was constructed. Under optimal conditions, it exhibited an excellent linear relationship for S. Typhimurium, with a sensitive detection limit as low as 1.3 × 102 CFU/mL and could complete sample detection within 2 h relying on the RAA and ZIF-8@FLS explosive fluorescence rapid response, demonstrating its significant advantages in specificity, sensitivity, and reliability in food-borne pathogens detection.
研究领域:
食品科学
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生物传感器
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分子生物学
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分析化学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Lang Yi,Yan-jun Lyn,Chong Peng,Rui-li Zhu,Sha-sha Bai,Liang Liu,Pei-xun Wang,Hua Zhou,Yan Dong
Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum , has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium , but its role is still unclear. Here we investigated the association between the aggressive proliferation of FLS and α7nAChR expression and the effect of sinomenine. FLS was isolated from synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis factor(TNF)-α was used to induce the aggressive proliferation of FLS. MTT assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA) and protein levels of α7nAChR and early growth response gene-1 (Egr-1) were measured. The results showed that TNF-α induced FLS proliferation in vitro (P < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1 and α7nAChR (P < .05 or P < .01). U0126 , the inhibitor of ERK1/2 inhibited α7nAChR expression and FLS proliferation significantly (P < .05 or P < .01). Specific short interference RNA(siRNA) of α7nAChR decreased α7nAChR expression and inhibited FLS proliferation as well. SIN inhibited the proliferation of FLS and decreased the phosphorylation of ERK1/2, and the expression of Egr-1 and α7nAChR induced by TNF-α (P < .05). In conclusion, the expression of α7nAChR involved in the aggressive proliferation of FLS induced by TNF-α and was regulated by ERK/Egr-1 signal pathway . SIN inhibited FLS proliferation and α7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN.
研究领域:
免疫学
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药理学
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风湿病学
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细胞生物学
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Advanced Healthcare Materials
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2024
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IF 10
Saisai Ge,Xinyue Wang,Xinru Zhao,Lingling Yuan,Xuewei Bao,Caidie Sun,Zehua Gong,Jun Guo,Siyu Yuan,Danyou Hu,Jing Yang,Bin Yuan,Guiyang Zhang
Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.
研究领域:
纳米技术
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药学
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免疫学
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生物医学工程
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治疗学
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JOURNAL OF MOLECULAR LIQUIDS
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2020
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IF 5.065
Fu Li,Bin Li,Ying Zhang,Yaoping Wang,Xiaoqian Jia,Qiang Li,Jianbin Zhang
For liquid and liquid mixtures, density (ρ), viscosity (η) and surface tension (γ) are seen as important basic data. This research reported the data of ρ, η and γ for the binary mixture of tri-ethylene glycol (TEG) + 1,3-propanediamine (PDA) at p = .1 MPa and T = (293.15 to 318.15) K within the whole molar fraction range, finding the maximum of η and γ values when the mole fraction of TEG was x 1 ≈ 0.65. After that, excess molar volume ( V m E ), viscosity deviation (Δη), and surface tension deviation (Δγ) were carefully calculated, and the minimum V m E values and the maximum Δγ values were obtained when the molar fraction of TEG was at x 1 ≈ 0.50; however, the maximum Δη values shifted from x 1 ≈ 0.60 to x 1 ≈ 0.66. And then, the Redlich-Kister (R-K) equation fitting was performed on above parameters to evaluate the coefficient and standard deviation, apparent molar volumes ( V φ , 1 and V φ , 2 ) and partial molar volumes ( V 1 ¯ and V 2 ¯ ). Meanwhile, Gaussian 09 software was used to further analyze the intermolecular force and to calculate the dissociation energy and bond length of the mixture, and the interaction of PDA with TEG were discussed on the basis of FTIR, UV–Vis and FLS spectral technologies. The results showed that there were hydrogen-bond interactions between the nitrogen atoms in PDA and the hydroxyl hydrogen atoms in TEG.
研究领域:
物理化学
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计算化学
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光谱学
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Bioactive Materials
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2024
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IF 18
Peng Hua,Ruifeng Liang,Suleixin Yang,Yanbei Tu,Meiwan Chen
Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K ( TK PF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer ( TK PF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.
研究领域:
药理学
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风湿病学
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纳米技术
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基因治疗
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炎症研究
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高影响因子
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