FASEB JOURNAL
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2025
·Vol. 39
·期 3
·e70379
·
IF 4.2
Jiancheng Yang,Qinghua Tang,Siyu Li,Lei Yang,Ming Yang,Qingmei Li,Yan Feng,Mingming Pan,Yuhong Zeng
The accumulation of intracellular reactive oxygen species (ROS) is widely recognized to stimulate the development of osteoclasts, a crucial factor in the onset of osteoporosis. The ROS scavenging capability of Prussian blue nanoparticles (PBNPs) is exceptional, and they possess excellent biocompatibility. However, the effects of PBNPs on osteoporosis remain unknown. Present study aimed to investigate whether PBNPs could inhibit osteoclast differentiation and prevent ovariectomy (OVX)-induced bone loss by suppressing ROS. In vitro experiments demonstrated that PBNPs attenuated osteoclastogenesis and downregulated the expression of osteoclast-related genes. Mechanistically, PBNPs reduce cellular ROS by blocking RANKL-induced ROS generation and increasing the expression of ROS scavenging enzymes, which in turn block the NF-κB, ERK, JNK, and p38 pathways, thereby reducing NFATc1 signaling. According to in vivo experimental results, OVX caused a significant rise in ROS in the bone marrow, an increase in osteoclastic number on the bone surface, and substantial bone loss; however, PBNPs significantly reduced ROS and successfully protected OVX-induced bone damages. In conclusion, this study showed for the first time that PBNPs prevented OVX-induced bone loss and attenuate osteoclastogenesis, indicating that PBNPs may be a viable alternative therapy for the management of osteoclast-associated bone disorders. Graphical Once RANKL binds to RANK on the cell membrane of BMMs, the NF-κB and MAPK pathways become activated, resulting in the amplification of NFATc1, which upregulates the expression of osteoclast-specific genes such as CTSK , Integrin αV , Atp6v0d2 , and MMP9 . These signaling events are mediated by the RANKL-induced ROS signaling. PBNPs decreased levels of ROS and mitigated these signaling pathways by decreasing ROS production and enhancing the expression of antioxidant enzymes. Consequently, PBNPs prevented osteoclastogenesis.
研究领域:
骨生物学
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纳米医学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Pingping Tuo,Risheng Zhao,Ning Li,Shuang Yan,Gege Yang,Chunmei Wang,Jinghui Sun,Haiming Sun,Mengyang Wang
Background Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. Methods Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. Results LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. Conclusion Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.
研究领域:
心脏病学
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药理学
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分子生物学
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炎症研究
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DOI
PubMed
高影响因子
Veterinary Sciences
·
2025
·Vol. 12
·期 8
·762
·
IF 2.3
Jinwu Zhang,Bo Zhang,Shiqi Huang,Jianhao Deng,Yiying Liang,Jiakang He,Tingjun Hu,Liji Xie,Hailan Chen,Meiling Yu
Simple SummaryImmunosuppressive diseases are frequently encountered in animal husbandry, including porcine reproductive and respiratory syndrome, swine fever, and infectious bursal disease in chickens. Due to their high mortality rates, these diseases pose a significant threat to the healthy development of animal husbandry. The total flavonoids ofSpatholobus suberectus Dunn(TFSD) exhibit significant immunomodulatory properties, demonstrating their therapeutic potential against immunosuppressive conditions. The study results indicate that TFSD administration significantly mitigates cyclophosphamide-induced immunotoxicity by preserving splenic and thymic architecture while restoring immune competence in treated subjects. Additionally, network pharmacology, molecular docking, and in vivo experiments demonstrated that TFSD can reduce immunosuppression-induced damage by regulating the NF-κB signaling pathway. These findings suggest that TFSD is a promising immunotherapeutic candidate for managing immunosuppression-related immune dysfunction in veterinary medicine.This study investigated the immunomodulatory effects and underlying mechanisms of total flavonoid ofSpatholobus suberectus Dunn(TFSD) and its primary constituent formononetin (FMN) in immunosuppressed mouse models.Spatholobus suberectus Dunn(S. suberectus Dunn) was first analyzed qualitatively and quantitatively by broadly targeted metabolomics using Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Integrated network pharmacology and molecular docking approaches were used to investigate the potential mechanisms underlyingS. suberectus Dunn’s immunomodulatory effects. Subsequently, mice were pretreated with TFSD and FMN for seven days before constructing an immunosuppression model through intraperitoneal injection of 200 mg/kg.bw cyclophosphamide (CTX). In vivo experiments validated the findings and investigated the mechanisms underlying the effects of TFSD and FMN on immunosuppression. Metabolomic analysis identified 501 distinct flavonoids inS. suberectus Dunn, with FMN exhibiting the highest relative abundance among all detected compounds. The primary active components ofS. suberectus Dunnagainst immunosuppression are flavonoids, including FMN and vestitol. The core targets of these components were identified as NF-κB and IKKβ, with the NF-κB signaling pathway being suggested as the most probable mechanism of action. FMN exhibited strong binding affinity to the core targets, NF-κB p65 and IKKβ. In vivo experiments indicated that pretreatment with TFSD and FMN prevented CTX-induced pathological damage in the spleen and thymus and increased immune cell counts and immunoglobulin levels. Additionally, it significantly upregulated the secretion and expression of key cytokines and the mRNA expression of NF-κB p65, IKKα, and IKKβ (p< 0.05 orp< 0.01). In conclusion, TFSD and FMN can protect mice from CTX-induced immunosuppression by regulating the NF-κB signaling pathway, making them promising drug candidates for preventing and treating immunosuppression-related diseases.
研究领域:
药理学
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免疫学
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兽医学
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植物化学
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分子生物学
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生物医学研究
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DOI
PubMed
高影响因子
INFLAMMATION
·
2019
·Vol. 42
·期 4
·1179-1189
·
IF 2.939
Xue Yu-Long,Zhang Sheng-Xiao,Zheng Chao-Feng,Li Yu-Feng,Zhang Li-Hui,Hao Yu-Fei,Wang Shu,Li Xue-Wen
Signal transducer and activator of transcription 4 (STAT4) has been implicated in the progression of myocarditis. The aim of the current study was to investigate the role by which STAT4 influences autoimmune myocarditis in an attempt to identify a theoretical therapeutic perspective for the condition. After successful establishment of an autoimmune myocarditis rat model, the expression patterns of STAT4, NF-κB pathway–related genes, Th1 inflammatory cytokines (IFN-γ and IL-2), and Th2 inflammatory cytokines (IL-6 and IL-10) were subsequently determined. The rats with autoimmune myocarditis were treated with oe-STAT4 or sh-STAT4 lentiviral vectors to evaluate the role of STAT4 in autoimmune myocarditis, or administrated with 1 mL 10 μmol/L of BAY11-7082 (the NF-κB pathway inhibitor) via tail vein to investigate the effect of the NF-κB pathway on autoimmune myocarditis. Finally, cell apoptosis was evaluated. The serum levels of IFN-γ and IL-2, extent of IκBα and P65 phosphorylation, and the expression of STAT4 were elevated, while the serum levels of IL-6 and IL-10 as well as the expression of IκBα were reduced among the rats with autoimmune myocarditis, which was accompanied by an increase in the apoptotic cells. More importantly, the silencing of STAT4 or the inhibition of the NF-κB pathway was detected to result in a decrease in the serum levels of IFN-γ and IL-2 and an elevation of the serum levels of IL-6 and IL-10, and inhibited myocardial cell apoptosis in rats with autoimmune myocarditis. Moreover, STAT4 silencing was also observed to decrease the extent of IκBα and P65 phosphorylation while acting to elevate the expression of IκBα. Taken together, silencing of STAT4 could hinder the progression of autoimmune myocarditis by balancing the expression of Th1/Th2 inflammatory cytokines via the NF-κB pathway, which may provide a novel target for experimental autoimmune myocarditis (EAM) treatment.
研究领域:
免疫学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Jieying Liu,Fuze Liu,Cairong Li,Zhengyao Li,Tianle Li,Yuanhao Wu,Di Wu,Yue Huang,Hui Chen,Hai Wang,Yuxiao Lai,Zhihong Wu
Background Iron oxide nanoparticles (IONPs)-based bone scaffolds have attracted increasing attention because of their potential to enhance osteogenesis and angiogenesis. However, the underlying mechanisms remain incompletely understood. Methods We fabricated a biocompatible bone scaffold by incorporating γ-Fe 2 O 3 magnetic nanoparticles into a PLGA matrix using 3D printing technology. The biosafety and effectiveness of the scaffold was validated through in vitro cell assays and in vivo implantation studies. To evaluate osteogenesis and neovascularization, we employed micro-CT imaging with a vascular contrast agent. In-depth mechanistic investigations were conducted via label-free proteomic profiling and pathway enrichment analysis. Results The PLGA/Fe 2 O 3 scaffolds demonstrated excellent biocompatibility and promoted both bone formation and angiogenesis in vitro and in vivo . Micro-CT analysis revealed enhanced new bone and vessel formation in the presence of magnetic scaffolds. Proteomic analysis revealed that alpha-B crystallin (CRYAB) is a key regulatory protein upregulated under a static magnetic field, thereby activating the PI3K/AKT signaling cascade and promoting osteogenic differentiation. In endothelial cells, we observed the upregulation of nuclear NF-κB and HIF-1α, leading to VEGF expression and angiogenic activation. Conclusion Our findings provide direct evidence that 3D-printed PLGA/Fe 2 O 3 scaffolds promote osteogenesis and angiogenesis both in vitro and in vivo . Importantly, we report for the first time that CRYAB-mediated stabilization of β-catenin plays a central role in magnetic scaffold-induced bone regeneration, offering new insights into the design of functional bone substitutes.
研究领域:
生物材料学
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组织工程
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分子生物学
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转化医学
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骨骼系统生物学
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血管生物学
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纳米医学
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再生医学
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DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2021
·Vol. 170
·期 3
·349-362
·
IF 3.387
Liu Xiaoyu,Guo Bingyan,Zhang Wei,Ma Bocong,Li Yongjun
Diabetic cardiomyopathy (DCM) is a common cardiovascular disease. A declined miR-20a-5p was observed in hearts of diabetic mice, while its effect on DCM remains unknown. Herein, we established streptozotocin-induced DCM rat model and high glucose-stimulated H9C2 model of DCM. Then they were treated with adenovirus expressing miR-20a-5p to explore the function of miR-20a-5p. Insulin tolerance test and intraperitoneal glucose tolerance test assay revealed that miR-20a-5p reduced blood glucose level. Besides, miR-20a-5p improved cardiac dysfunction reflected by reduced heart weight/body weight and left ventricular diastolic pressure, and increased left ventricular systolic pressure and ±LV dp/dt max. MiR-20a-5p prevented cardiomyocyte apoptosis, along with the upregulated c-caspase-3, bax and downregulated bcl-2. Moreover, miR-20a-5p alleviated cardiac hypertrophy as the parameters of atrial natriuretic peptide, B-type natriuretic peptide and MyHC-β decreased. Also, miR-20a-5p attenuated the cardiac fibrosis demonstrated by decreased transforming growth factor-β1, collagen I levels and the inflammatory response manifested by reduced interleukin-6, tumour necrosis factor-α and IL-1β production. Furthermore, miR-20a-5p prevented Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) p65nuclear translocation. Similarly, the effects of miR-20a-5p on DCM were confirmed in our in vitro experiments. Additionally, ROCK2 is a possible target gene of miR-20a-5p. ROCK2 overexpression reversed the protective effect of miR-20a-5p on DCM. Overall, miR-20a-5p may effectively ameliorate DCM through improving cardiac metabolism, and subsequently inhibiting inflammation, apoptosis, hypertrophy, fibrosis and JNK/NF-κB pathway via modulating ROCK2.
研究领域:
心脏病学
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分子生物学
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糖尿病
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病理生理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-14
·
IF 6
Gao Weilu,Liu Rui,Huang Keke,Fu Wenhan,Wang Anquan,Du Gongwen,Tang Hao,Yin Li,Yin Zongsheng S.
Background Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear.Methods In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1β) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1β-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays.Results Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway.Conclusion sThis study demonstrated that CHMP5 repressed IL-1β-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.
研究领域:
骨科
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR DRUGS AND THERAPY
·
2025
·
IF 3.1
Ba Lina,Wu Nan,Feng Xiang,Wang Ruixuan,Zhao Zhichao,Wang Rui,Liu Renling,Shi Pilong,Sun Hongli,Qi Hanping
Purpose The purpose of this study was to investigate the protective effects of biochanin A (BCA) on cardiac hypertrophy and to elucidate the underlying molecular mechanisms. The research question was whether BCA can reverse heart dysfunction and attenuate cardiomyocyte hypertrophy induced by pressure overload and AngII, respectively, and how it interacts with the NLRP3 pyroptosis pathway to achieve these effects. Methods We employed an animal model of pressure overload-induced cardiac hypertrophy and an in vitro model of AngII-induced cardiomyocyte hypertrophy to assess the effects of BCA. The expression of NLRP3 and its related signaling molecules was analyzed by western blotting, and the activity of the NLRP3 pathway was measured using pyroptosis assays. The role of Cbl-b, an E3 ubiquitin ligase, in BCA-mediated NLRP3 inhibition was also investigated. Results BCA was found to reverse heart dysfunction and attenuate cardiomyocyte hypertrophy induced by pressure overload and AngII. Mechanistically, BCA mitigated cardiac hypertrophy by targeting the NLRP3 pyroptosis pathway. The reduction in NLRP3 expression by BCA was predominantly mediated through the upregulation of Cbl-b, which enhanced the ubiquitination and subsequent degradation of NLRP3. Additionally, BCA facilitated the upregulation of Cbl-b expression by interacting with NF-κB, preventing NF-κB binding to the promoter region of Cbl-b and reversing its suppressive action on Cbl-b expression. Conclusion This study provides initial evidence that BCA can protect against cardiac hypertrophy. Its mechanism of action involves interacting with NF-κB to promote the expression of Cbl-b, which facilitates the ubiquitination and degradation of NLRP3, ultimately inhibiting pyroptosis. This finding suggests that BCA may be a potential therapeutic agent for the treatment of cardiac hypertrophy.
研究领域:
心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·Vol. 396
·期 6
·1247-1255
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IF 3.6
Su Jie,Yin Wei,Huo Mengmeng,Yao Qing,Ding Liqiong
Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC 50 ) values of lycorine on C6 glioma cells at 48 h was 2.85 μM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.
研究领域:
肿瘤学
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药理学
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细胞生物学
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神经科学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Kai Zhang,Zhenqiang Fan,Bo Yao,Tingting Zhang,Yuedi Ding,Sha Zhu,Minhao Xie
2019 novel coronavirus (2019-nCoV) with strong contagion in the crowd, has ravaged worldwide and severely impacts the human health and epidemic prevention system, by producing a series of significant stress reactions in the body to induce further cytokine storm. Transcription factors (TFs) served as essential DNA binding proteins play an integral role in regulating cytokine storm, and the detection of it in the human coronavirus environment provides especially valuable approaches to diagnosis and treatment of 2019-nCoV and development of antiviral drugs. In this work, an entropy-driven electrochemiluminescence (ECL) biosensor was constructed for ultra-sensitive bioassay of NF-κB p50. The strategy primarily capitalizing the splendid double-stranded DNA (dsDNA) binding properties of transcription factors, employing GOAu-Ru composite material as ECL emitter, utilizing entropy-driven reactions for signal amplification method, offered a repeatable proposal for TFs detection. In the absence of TFs, the released DNA1 further went in the entropy-driven reaction, contributing to an “ECL off” state. However, in the presence of TFs, the dsDNA avoided being digested, which blocked DNA1 for participating in the entropy-driven reaction, and the system exhibited an “ECL on” state. Most importantly, the ECL bioanalytical method denoted broad application prospects for NF-κB p50 detection with a lower detection limit (9.1 pM).
研究领域:
分析化学
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生物化学
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分子生物学
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病毒学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
Journal of Immunology Research
·
2021
·
IF 4.818
Lin Zhang,Lukun Yang,Xiaowei Xie,Hongyue Zheng,Hangsheng Zheng,Lizong Zhang,Cuizhe Liu,Ji-Gang Piao,Fanzhu Li
Baicalin (BA) magnesium salt (BA-Mg) is a good water-soluble ingredient extracted from Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine. This study is aimed at investigating whether BA-Mg could exert a better protective effect on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and illuminate the underlying mechanisms in vivo and in vitro. Mice were intraperitoneally administrated with equimolar BA-Mg, BA, and MgSO4 before LPS inducing ALI. Lung tissues and bronchoalveolar lavage fluid were collected for lung wet/dry ratio, histological examinations, cell counts, and biochemical analyses at 48 h post-LPS exposure. Meanwhile, the protein expressions of TLR4/NF-κB signaling pathway and proinflammatory cytokines in lung tissues and lung bronchial epithelial cells (BEAS-2B) were detected. The results showed BA-Mg pronouncedly ameliorated LPS-induced inflammatory response and histopathological damages, elevated antioxidant enzyme activity (SOD), and downregulated myeloperoxidase (MPO) and malonaldehyde (MDA) levels through the inhibition of TLR4/NF-κB signaling pathway activation. Moreover, the effect of BA-Mg was significantly better than that of BA and MgSO4 in ameliorating symptoms. Overall, BA-Mg can effectively relieve inflammatory response and oxidative stress triggered by LPS, indicating it may be a potential therapeutic candidate for treating ALI.
研究领域:
药理学
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免疫学
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肺病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Asian Pacific Journal of Cancer Prevention
·
2021
·
IF 0
Yanjun An,Jiandong Zhao,Yourui Zhang,Wen Wu,Jiangtao Hu,Haosen Hao,Yu Qiao,Ying Tao,Liping An
Background: Rosmarinic acid (RA) is a natural phenolic compound that acts as a Fyn inhibitor by 53 homology modeling of the human Fyn structure. Therefore, the apoptosis mechanism related to NF-κB signaling pathway induced by RA in HepG2 was investigated. Methods: The cell growth, apoptosis, and proliferation of HepG2 regulated by various concentrations of RA were studied. The proteins expression of MMP-2, MMP-9, PI3K, AKT, NF-κB, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were detected. Results: RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expressions of invasion-related factors, such as matrix metalloproteinase (MMP)-2 and MMP-9. TUNEL staining revealed that RA resulted in a dose-dependent increase of HepG2 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl-2 was downregulated and that of the pro-apoptotic proteins Bax and cleaved caspase-3 was increased. In addition, we found that the phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor kappa B (NF-κB) signaling pathway was involved in RA-mediated inhibition of HepG2 cell metastasis. Conclusion: Our study identified that RA as a drug candidate for the treatment of HCC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
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