Plants-Basel
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2026
·Vol. 15
·期 17
·2654
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IF 4.7
Feiran Hu,Wenzhao Zhou,Nong Zhou,Lanlan Wan,Linyun Pu,Caiyun Fu,Hua Zhang,Junsheng Qi
Lycopus lucidusTurcz. var.hirtusRegel (L. lucidusvar.hirtus) is a medicinal herb traditionally used in Chinese folk medicine for the treatment of inflammatory disorders, joint pain, and rheumatoid arthritis (RA)-like symptoms. However, systematic research on the bioactive flavonoids of this herb in RA-related cellular models is limited. The aim of this study was to isolate the main flavonoid from this herb and evaluate its in vitro anti-inhibitory effects in TNF-α-induced human RA fibroblast-like synoviocytes (HFLS-RA). Flavonoids were extracted, purified, and isolated using chromatographic techniques. The structure was elucidated by spectroscopic analysis. The effects of the isolated compound were assessed in a TNF-α-induced HFLS-RA cell model by evaluating pro-inflammatory cytokine secretion and cell proliferation/metabolic activity. A main flavonoid was identified as formononetin. Formononetin exhibited antioxidant activity and inhibited TNF-α-provoked inflammatory responses in HFLS-RA cells under cell-safe concentrations, as evidenced by reduced secretion of IL-6, IL-8, and IL-1β and suppression of TNF-α-induced hyperproliferation. In conclusion, formononetin is a major flavonoid constituent ofL. lucidusvar.hirtus, and these findings provide preliminary in vitro cellular evidence that formononetin exerts in vitro anti-inflammatory inhibitory activity on TNF-α-activated human RA fibroblast-like synoviocytes. Further in vivo and mechanistic studies are required to explore its potential for anti-RA-related pharmacological application.
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高影响因子
Nano Today
·
2024
·
IF 13.2
Hui Yan,Danping Wang,Chengyin Tian,Long Zhao,Yong Wang,Guoqing Long,Bingjun Sun,Jingming Jia,Anhua Wang
Darutigenol (DL) is an active diterpenoid extracted from the traditional Chinese medicine Sigesbeckia glabrescens (Makino) Makino, widely employed in the treatment of rheumatoid arthritis (RA) for centuries in China. However, the anti-inflammatory mechanism of DL requires further exploration. In this study, we discovered that DL could scavenge reactive oxygen species (ROS) and nitric oxide (NO), and reduce the secretion of proinflammatory cytokines, inducing the M1-to-M2 polarization of macrophages in vitro . In vivo , DL was demonstrated to exert an anti-inflammatory effect via the JAK1, 3/STAT3 and MAPK pathways. It also showed efficacy in repairing cartilage damage via downregulating the proteins MMP2/MMP9 and inhibiting angiogenesis through the CXCL12/CXCR7 system in synovial tissues. However, the application and therapeutic effect of DL was constrained by its poor water solubility and low bioavailability. To address these limitations, ROS-responsive prodrug nanoassemblies were employed, which could be passively transported to the joint inflammation site and decomposed in the inflammatory environment to release DL. The therapeutic effect of prodrug nanoassemblies was superior to that of DL, with negligible toxicity to organs. In summary, we clarified the anti-RA mechanism of DL and constructed an efficient and safe drug delivery system, which provided a strategy for the further application and development of active compounds in traditional Chinese medicine.
研究领域:
药理学
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纳米技术
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免疫学
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传统中药
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药物递送系统
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炎症
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ANALYTICAL CHEMISTRY
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2022
·
IF 8.008
Suya Zhang,Lulu Ning,Zhihui Song,Xinyue Zhao,Feng Guan,Xiao-Feng Yang,Jianjian Zhang
Early diagnosis of rheumatoid arthritis (RA) is crucial to prevent deterioration and improve the prognosis of disease outcome. However, current clinical diagnostic methods are unable to achieve accurate and early detection of RA. In this work, we designed an activatable organic nanoprobe (ONP-CySe) capable of specific and real-time imaging of ClO– in early RA. ONP-CySe comprises a near-infrared fluorescent selenomorpholine-caged cyanine dye as the sensing component and an amphiphilic triblock copolymer triphenyl phosphine derivative for mitochondria targeting. Our results showed that ONP-CySe successfully detected elevated levels of ClO– in the mitochondria of macrophages with high selectivity, low limit of detection (31.5 nM), excellent photostability, and good biocompatibility. Furthermore, ONP-CySe can also be used to monitor anti-inflammatory responses and efficacies of RA therapeutics, such as selenocysteine and methotrexate, in BALB/c mouse models. Therefore, our research proposes a universal molecular design strategy for the detection of ClO–, which holds potential for early diagnosis and drug screening for RA.
研究领域:
医学诊断
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纳米技术
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药理学
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炎症性疾病
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高影响因子
INFLAMMATION RESEARCH
·
2024
·
IF 4.8
Tan Min,Mao Jing,Zheng Jianxiong,Meng Yu,Li Jun,Hao Jiayao,Shen Haili
Background Mammalian STE20-like kinase 1 (MST1) is involved in the occurrence of cancer and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis and other functions. However, its role and downstream targets in rheumatoid arthritis (RA) remain unclear. Methods The model of RA fibroblast-like synoviocytes (RA-FLSs) overexpressing MST1 was constructed by lentiviral transfection in vitro and analyzed the effects of MST1 on apoptosis, migration, invasion, and inflammation of RA-FLSs. The effect of MST1 on joint synovial membrane inflammation and bone destruction was observed in vivo by establishing a rat model of arthritis with complete Freund’s adjuvant. Results MST1 is down-regulated in RA-FLSs, and up-regulation of MST1 inhibits the survival, migration, invasion and inflammation of RA-FLSs. Mechanistically, MST1 inhibits SIRT3/mTOR-signaling pathway, inducing decreased mitochondrial autophagy and increased mitochondrial fission, resulting in mitochondrial morphological abnormalities and dysfunction, and ultimately increased apoptosis. We have observed that activation of MST1 alleviates synovial inflammation and bone erosion in vivo. Conclusions MST1 reduces the survival, migration, invasion and inflammation of FLSs by inhibiting the SIRT3/mTOR axis to reduce mitochondrial autophagy and promote mitochondrial division, thereby achieving the potential role of relieving rheumatoid arthritis.
研究领域:
免疫学
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风湿病学
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细胞生物学
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分子生物学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Kaili Wang,Hao Chen,Jiani Zheng,Jiali Chen,Yixuan Chen,Yue Yuan
Dual pathological barriers, including capillarized liver sinusoidal endothelial cells (LSECs) and deposited extracellular matrix (ECM), result in insufficient drug delivery, significantly compromising the anti-fibrosis efficacy. Additionally, excessive reactive oxygen species (ROS) in the hepatic microenvironment are crucial factors contributing to the progression of liver fibrosis. Hence, hyaluronic acid (HA) modified liposomes co-delivering all-trans retinoic acid (RA) and L-arginine (L-arg) were constructed to reverse hepatic fibrosis. By exhibiting exceptional responsiveness to the fibrotic microenvironment, our cleverly constructed liposomes efficiently disrupted the hepatic sinus pathological barrier, leading to enhanced accumulation of liposomes in activated hepatic stellate cells (HSCs) and subsequent induction of HSCs quiescence. Specially, excessive ROS in liver fibrosis promotes the conversion of loaded L-arg to nitric oxide (NO). The ensuing NO serves to reestablish the fenestrae structure of capillarized LSECs, thereby augmenting the likelihood of liposomes reaching the hepatic sinus space. Furthermore, subsequent oxidation of NO by ROS into peroxynitrite activates pro-matrix metalloproteinases into matrix metalloproteinases, which further disrupts the deposited ECM barrier. Consequently, this NO-induced cascade process greatly amplifies the accumulation of liposomes within activated HSCs. More importantly, the released RA could induce quiescence of activated HSCs by significantly downregulating the expression of myosin light chain-2, thereby effectively mitigating excessive collagen synthesis and ultimately leading to the reversal of liver fibrosis. Overall, this integrated systemic strategy has taken a significant step forward in advancing the treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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药物递送系统
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病理生理学
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 19
·2213465
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IF 19
Huiyi Liang,Yibo Du,Lixin Liu,Junqiu Liu,Yongming Chen
Excessive self-DNAs recognized by intracellular DNA sensors can initiate innate immunity to express disordered TNF-α or type I IFN resulting in several autoimmune diseases. Cationic polymers have been profoundly proved to alleviate the inflammatory symptoms by removing the debris of cell-free DNA (cfDNA). However, clinical applications of cationic materials have been impeded by concerns of their toxicity and the fate of cfDNA in polymer-cfDNA complex. Herein, it is showed that PEGylated polyimidazoles as a biomimetic DNase potently alleviate pathologic symptoms of self-DNA-associated rheumatoid arthritis (RA) rats and Trex1 (DNase III) deficient Aicardi-Goutiéres syndrome (AGS) mice. The mechanism studies demonstrate that the polyimidazole efficiently attacks the phosphodiester linkages of NAs and cleavages them into small pieces. As imidazole unit is a much weaker organic base that occurs in natural proteins, the polyimidazoles are less toxic to cells and tissues, as manifested by the IC50 values larger than 1000 µg mL −1 . This work suggests that synthetic tailored DNase can be a new and safe therapeutic agent to treat chronic autoimmune and refractory inflammatory diseases by degradation of excessive nucleic acids.
研究领域:
免疫学
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生物医学工程
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分子生物学
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药理学
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高影响因子
JOURNAL OF ELECTRONIC MATERIALS
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2022
·Vol. 52
·期 1
·547-558
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IF 2.047
Zhou Jian,Ren Sili
The phosphor-converted white light-emitting diode (WLED) has received tremendous attention as a promising alternative to traditional light sources in lighting and displays. Herein, a novel broadband red emitter Ca 2 Sr(PO 4 ) 2 :Mn 2+ was successfully designed and synthesized based on the Sr-alloying and Mn-doping of Ca 3 (PO 4 ) 2 . The phase purity of the materials was verified by x-ray diffraction (XRD) analyses, while a scanning electron microscope (SEM) coupled with an energy-dispersive spectrometer (EDS) was employed to confirm the uniform dopant distribution. XRD Rietveld refinements were further performed to clarify the site occupation of alloying Sr and the Mn dopants. Effective site engineering confined the Mn dopants in a highly symmetric Ca5 site and excluded the immersion of Sr, leading to an extraordinarily long fluorescence lifetime. Density functional theory (DFT) simulations also revealed the good potential of the materials as host matrices for activators such as Mn 2+ . Finally, Ca 2 Sr(PO 4 ) 2 :Mn 2+ was used to fabricate a WLED prototype based on a near-ultraviolet (n-UV) commercial LED chip, which realized a warm white-light emission and high color rendering index (Ra) of 82.9. This WLED was able to survive the long-term stability test while maintaining high luminous efficacy of ~ 60 lm/W within 20 h, showing its great potential in practical applications.
研究领域:
材料科学
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光电技术
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照明技术
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固体物理
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高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Shanshan Zhao,Xingyu Zhou,Junbo Dang,Yilong Wang,Junhui Jiang,Tianhao Zhao,Dahui Sun,Chen Chen,Xin Dai,Yan Liu,Mei Zhang
Carbon fiber-reinforced polyether ether ketone (CFRPEEK) implants have attracted widespread attention in the field of clinical bone defect repair. However, the surface bioinertness confines the application of CFRPEEK implants. Inspired by the study of rosmarinic acid (RA)-promoted osteogenic differentiation, a self-assembly surface modification method based on electrostatic interactions, involving deposition of sodium carboxymethyl cellulose/chitosan and rosmarinic acid layer by layer on the surface of poly-L-lysine modified hydroxy CFRPEEK (SCPP/CC5@RA), is proposed to introduce RA on the surface of CFRPEEK for bioactivation. After layer-by-layer self-assembly (LBL), the surface of SCPP/CC5@RA exhibits weak electrophoresis (11.43 eV), suitable hydrophilicity, and bioactivity. The results of in vitro studies indicate that the RA release behavior of SCPP/CC5@RA effectively regulates the immune-inflammatory response and promotes the differentiation of osteoblasts. The rapid release of RA (0.17 μg mL−1) in the initial stage can downregulate the secretion of inflammation-related cytokines and significantly reduce oxidative stress levels; the sustained release of RA (0.06 μg mL−1) in the late stage can upregulate the expression of osteogenesis-related genes and induce mineralization of osteoblasts. Moreover, the rabbit tibia defect model demonstrates that the LBL technique can enhance the osseointegration of CFRPEEK implants. Compared with the control group, the bone trabecular thickness of the SCPP/CC5@RA group increases by 1.36 times, and the maximum pushing force increases by 2.67 times. In summary, this study provides a promising LBL based RA delivery system for the development of a dual-functional CFRPEEK implant in the field of bone implant biomaterials.
研究领域:
生物材料
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骨科
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组织工程
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药物递送系统
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生物医学工程
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高影响因子
Foods
·
2021
·Vol. 10
·期 2
·239
·
IF 4.35
Nina Bao,Di Wang,Xizhe Fu,Hujun Xie,Guizhen Gao,Zisheng Luo
LotusReceptaculum Nelumbinishas been sparking wide research interests due to its rich phenolic compounds. In the present work, ultrasonic-assisted extraction coupled with glycerol was employed to extract phenolic compounds fromReceptaculum Nelumbinisand the process was optimized using a response surface methodology with Box-Behnken design (BBD). The optimal conditions for the total phenolic content (TPC) extract were obtained: glycerol concentration of 40%, an extraction temperature of 66 °C, ultrasonic time of 44 min, and the solvent-to-solid ratio of 55 mL/g. Under these optimum extraction conditions, the extraction yield of TPC was 92.84 ± 2.13 mg gallic acid equivalents (GAE) /g. Besides, the antioxidant activities demonstrated the ability of free radical scavenging by four different methods that included 2,2-Diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing activity (RA) were 459.73 ± 7.07, 529.97 ± 7.30, 907.61 ± 20.28, and 983.66 ± 11.80 μmol TE/g, respectively. Six phenolic compounds were identified by ultra-high pressure liquid chromatography combined with triple-time-of-flight mass spectrophotometry (UPLC-Triple-TOF/MS) from the extracts. Meanwhile, Fourier transform infrared (FTIR) was conducted to identify the characteristic functional groups of the extracts and thus reflected the presence of polyphenols and flavonoids. Scanning electron microscopy (SEM) illustrated the microstructure difference of four treatments, which might explain the relationships between antioxidant activities and the structures of phenolic compounds.
研究领域:
植物化学
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分析化学
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食品科学
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天然产物研究
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