Bioengineering-Basel
·
2026
·Vol. 13
·期 8
·908
·
IF 4.4
Dandan Zhang,Zhigang Zhang,Dingxing Huang,Zhuoran Sun,Jiamin Huang,Chi Zhang,Qingyang Zeng,Qiling Liu,Wenzhuo Chen
Osteoarthritis is an irreversible degenerative joint disease driven by sustained NF-κB-mediated inflammatory responses, and conventional intra-articular hyaluronic acid or small-molecule NF-κB inhibitors cannot achieve targeted on-demand treatment due to poor solubility, rapid clearance and lack of lesion microenvironment responsiveness. OA with inherent anti-chondrolytic activity can self-assemble into nanocarriers in water, yet it lacks stimuli-responsive capacity. Herein, we rationally designed and synthesized an OA-Der by covalently conjugating o-phenylenediamine fragments to the OA backbone.1H NMR and HRESI-MS spectra fully verified the accurate chemical structures of intermediate and final OA-Der. Blank OA-Der micelles exhibited uniform spherical core–shell nanostructures (50–150 nm) under TEM and AFM, while pathological high NO triggered complete disassembly of micellar assemblies. We further co-assembled OA-Der with NF-κB inhibitor BAY 11-7082 to construct NO-responsive BAY@OA-Der supramolecular micelles. In vitro experiments using human C28/I2 chondrocytes with LPS-induced inflammatory injury demonstrated that BAY@OA-Der significantly improved cell viability and reduced apoptotic chondrocyte proportion. At mRNA and protein levels, the supramolecular micelle formulation remarkably suppressed NF-κB p65 phosphorylation, downregulated cartilage-degrading ADAMTS5, and upregulated ACAN compared with free BAY or blank OA-Der. Collectively, this natural bioactive self-assembled NO-responsive delivery platform achieves synergistic anti-inflammatory and matrix-protective effects by precisely releasing drugs at NO-overexpressed osteoarthritis inflammatory sites and offers an in vitro design strategy for osteoarthritis responsive delivery systems.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2016
·
IF 5.091
Shan Liu,Lingxin Zhu,Jie Zhang,Jingjing Yu,Xue Cheng,Bin Peng
Previous studies, including those from our laboratory, have demonstrated that the natural flavonoid isoliquiritigenin (ISL) is a promising agent for bone destructive diseases. However, the mechanisms underlying its anti-osteoclastogenic effects are still far from clear. Here, we evaluated the potential alterations of autophagy and nuclear factor-κB (NF-κB) during anti-osteoclastogenic effects by ISL in vitro and in vivo . We observed that ISL inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed autophagic microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 accumulation. ISL treatment resulted in the interruption of several specific features for autophagy in osteoclast precursors, including acidic vesicular organelle formation, LC3-II accumulation, and appearance of autophagic vacuoles. The RANKL-stimulated expression levels of autophagy-related genes and proteins also diminished in ISL-treated osteoclast precursors. The reactivation of autophagy by rapamycin almost reversed the ISL-elicited anti-osteoclastogenic effects. Interestingly, ISL inhibited the RANKL-stimulated NF-κB expression and nuclear translocation, whereas the NF-κB inhibitor Bay 11-7082 markedly suppressed the RANKL-induced autophagic activation. Consistent with the in vitro results, the administration of ISL could attenuate osteoclastogenic cathepsin K , autophagic LC3, and NF-κB expression to protect against inflammatory calvarial bone erosion in vivo . Our findings highlight the inhibition of NF-κB-dependent autophagy as an important mechanism of ISL-mediated anti-osteoclastogenic activity.
研究领域:
药理学
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免疫学
·
骨骼生物学
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PubMed
高影响因子
STEM CELLS
·
2014
·Vol. 32
·期 7
·1943-1955
·
IF 7.133
Sun Hualing,Wu Yanru,Fu Dongjie,Liu Yinchen,Huang Cui
Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase involved in lifespan regulation. To evaluate the effect of SIRT6 on osteogenesis, rat bone marrow mesenchymal stem cells (rBMSCs) with enhanced or reduced SIRT6 function were developed. We observed that SIRT6 knockdown significantly reduced the mRNA levels of several key osteogenic markers in vitro, including alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin, while overexpression of SIRT6 enhanced their expression. Additionally, SIRT6 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of acetyl-NF-κB p65 (Lys310). The decreased osteogenic differentiation ability of rBMSCs could be partially rescued by the addition of NF-κB inhibitor BAY 11–7082. Furthermore, SIRT6 overexpression in rBMSCs combined with the use of collagen/chitosan/hydroxyapatite scaffold could significantly boost new bone formation in rat cranial critical-sized defects, as determined by microcomputed tomography and histological examination. These data confirm that SIRT6 is mainly located in the nuclei of rBMSCs and plays an essential role in their normal osteogenic differentiation, partly by suppressing NF-κB signaling. Stem Cells 2014;32:1943–1955
研究领域:
干细胞生物学
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骨再生
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分子生物学
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Jinzhao Zhou,Yanwei Zhang,Ling Zeng,Xiaofei Wang,Wenpei Xiang,Ping Su
Cadmium (Cd) is a harmful metal that seriously affects the male reproductive system, but the mechanism of how Cd exposure damages Sertoli cells is not fully understood. This study used TM4 cells to explore the mechanism of Cd damage to Sertoli cells. We found that Cd was concentration- and time-dependent on TM4 cell viability. Cd exposure increased intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH), and Interleukin-1β (IL-1β) release in TM4 cells, decreased mitochondrial function, and increased pyroptosis. N-acetylcysteine (NAC), MCC950 and BAY 11–7082 (BAY) alleviate the release of IL-1β and LDH induced by Cd. NAC reduced Cd induced increases in ROS, NLRP3, Caspase-1, Heme oxygenase-1(HO-1), superoxide dismutase (SOD2), and increased mitochondrial function. The activation of GSDMD is the main causes of pyroptosis, and NAC significantly inhibit its activation and formation. Our results suggest that Cd exposure induces a toxic mechanism of GSDMD-mediated pyroptosis in TM4 cells by increasing ROS levels and activating the inflammasome.
研究领域:
毒理学
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细胞生物学
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生殖健康
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高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 15
·3839-3853
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IF 3.2
Wen Weijia,Li Jiaying,Yuan Li,Liao Yan,Shao Caixia,Xu Dingze,Jiang Hongye,Liao Yuandong,Liu Pan,Zhang Chunyu,Yao Shuzhong,Wang Wei
Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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信号转导
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2025
·
IF 2.5
Shao-Qian Wang,Hui Yuan,Hao-Qiang Qin,Ming-Yue Peng,Ming-Xiao Cui,Ke-Hai Liu
This research emphasized the extraction and separation of polysaccharides derived from Syzygium jambos (L.) Alston (PSJAP-5), as well as analyses of their structural characteristics and immunomodulatory activities. This study initially employed response surface methodology to determine the extraction conditions of polysaccharides. The average molecular weight of PSJAP-5 was 58 102 Da, and its monosaccharide composition was galactose, arabinose, galacturonic acid, glucuronic acid, and rhamnose (39.84:29.13:21.97:6.02:4.17). In vitro studies showed that PSJAP-5 promoted the proliferation and phagocytosis of macrophages. Meanwhile, PSJAP-5 (25–200 µg/mL) promoted the release of NO and ROS, and increased the levels of IL-6, TNF-α, and IL-1β. After pretreating macrophages with TLR4, NF-κB, and MAPK inhibitors, the immunoenhancing effects of PSJAP-5 on macrophages treated with the inhibitors were decreased. Similarly, PSJAP-5 promoted the phosphorylation of p38 in the MAPK signaling pathway and reduced the phosphorylation of IκBα in the NF-κB signaling pathway in RAW264.7 cells. PSJAP-5 might serve as a potential immunomodulator for the treatment of diseases characterized by impaired immune function. Graphical This study focused on extracting and purifying a polysaccharide (PSJAP-5) from Syzygium jambos (L.) Alston, analyzing its structural properties, and evaluating its immunomodulatory effects.
研究领域:
免疫学
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天然产物化学
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药用植物学
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分子生物学
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糖生物学
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中药学
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PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Yu Shan,Yang Jinghui,Zhang Rui,Guo Qian,Wang Lu
Systemic inflammatory stimulus is a risk factor for the incidence of ischemic stroke and contributes to poorer clinical outcomes. Solute carrier 15A3 (SLC15A3) is a peptide/histidine transporter that is implicated in regulating inflammatory responses. However, whether SLC15A3 affects the progression of ischemic stroke associated with systemic inflammation is unclear. The transient middle cerebral artery occlusion (tMCAO) mice with LPS administration (LPS/tMCAO) were prepared as an in vivo model, and LPS-induced BV2 cells under oxygen–glucose deprivation (OGD) exposure were utilized as an in vitro model. We found that SLC15A3 was highly expressed in the ischemic penumbra of LPS/tMCAO mice, and its inhibition reduced infarct area, attenuated neurological deficit, recovered motor function, and mitigated apoptotic neurons. Knockdown of SLC15A3 suppressed the proinflammatory M1-type markers and promoted the levels of M2-associated genes. The in vitro results confirmed that SLC15A3 overexpression promoted microglia polarizing towards M1 subtypes, while SLC15A3 inhibition exerted an opposite effect. In addition, we demonstrated that the p65 signaling pathway and HIF1α were activated by LPS/OGD. Luciferase reporter assay showed that inhibiting p65 using its specific inhibitor BAY 11–7082 or silencing HIF1α using siRNAs reduced the transcriptional activity of SLC15A3 in LPS/OGD-induced BV2 cells. Results in NIH 3T3 cells also confirmed that p65 and HIF1α directly bound to the SLC15A3 promoter to activate SLC15A3 transcription. In conclusion, this work shows that SLC15A3 , transcriptionally activated by p65 and HIF1α, contributes to poor outcomes in ischemic stroke associated with systemic inflammation by promoting microglial cells polarizing towards M1 types.
研究领域:
神经科学
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免疫学
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分子生物学
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病理生理学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Fang-Fang Liu,Hai-Yan Ren,Feng Liu,Wen-Xuan Qi,Chao-Peng Liang,Bang-Xian Zhang,Xiang-Jun Rao
Insects mount robust immune responses to reduce the efficacy of biopesticides. Identification of critical immune targets for biocontrol strategies is thus essential. However, immune targets in the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), a major pest of corn, remain largely unexplored. Here, we investigated the immune response of S. frugiperda to the entomopathogen Beauveria bassiana (Hypocreales: Cordycipitaceae). Time-series RNA sequencing revealed 863, 717, and 165 differentially expressed genes (DEGs) at 24, 48, and 60 h post-infection, respectively. GO and KEGG enrichment analyses revealed that DEGs were significantly enriched in immune-related terms and pathways. Among the DEGs, the gene encoding immulectin SfIML-1 , a C-type lectin with dual carbohydrate recognition domains, was significantly upregulated during the early and intermediate stages of infection. Genome-wide analysis identified nine IML genes, with SfIML-1 as the only one highly responsive to B. bassiana . Recombinant SfIML-1 binds pathogen-associated molecular patterns and pathogens, enhancing cellular responses. RNAi of SfIML-1 decreased survival after fungal infection, while injection of recombinant SfIML-1 increased survival. Suppression of the NF-κB and JAK-STAT pathways diminished SfIML-1 expression in both fat body and Sf9 cells. These results identify SfIML-1 as a key pattern recognition receptor and a promising target for developing novel biocontrol strategies.
研究领域:
昆虫学
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分子生物学
·
生物防治
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PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Ruobing Wang,Dan Su,Yueze Liu,Hua Huang,Jiangdong Qiu,Zhe Cao,Gang Yang,Hao Chen,Wenhao Luo,Jinxin Tao,Guihu Weng,Taiping Zhang
Summary Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2’s role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p -SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
Discover Oncology
·
2023
·Vol. 14
·期 1
·1-14
·
IF 2.2
Yu Zhong,Ouyang Ling
Background Odd-skipped related 1 (OSR1) has been reported as a tumor suppressor gene in various malignant tumors. The mechanism through which OSR1 regulates ovarian cancer (OC) progression remains unclear. Materials and methods Immunohistochemistry was utilized to evaluate OSR1 expression in patients with ovarian cancer. We investigated the association between clinicopathological parameters and OSR1 expression in OC patients and the influence of OSR1 expression on patient survival and prognosis. OC cells with OSR1 overexpression or knockdown were established and validated using Western blot and Quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The influence of OSR1 on the NF-κB pathway was examined by analyzing the p-IκBα, IκBα, p65, and p-p65 protein expression. In vitro assays, such as cell cycle assay, Cell Counting Kit-8 (CCK-8), transwell invasion assay, wound healing migration assay, enzyme-linked immunoassay (ELISA), and Annexin V/PI flow cytometry apoptosis assay, were conducted to explore the effect of OSR1 knockdown or dual inhibition of OSR1 and the NF-κB pathway on OC malignant biological behavior. Results OSR1 expression was downregulated in OC tissues, with significant associations observed between its expression and The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue differentiation. Low OSR1 expression in OC patients correlated with reduced overall survival (OS) rates and poor prognosis . In vitro , experiments confirmed a negative correlation between OSR1 expression and NF-κB pathway activity. OSR1 knockdown facilitated OC cell malignant biological behavior, while the NF-κB pathway inhibitor (Bay 11-0782) reversed the impacts of OSR1 knockdown on cell proliferation, migration, invasion, and apoptosis. Conclusion Our findings indicate that OSR1 is downregulated and associated with OC prognosis. OSR1 suppresses NF-κB pathway activity and inhibits OC progression by targeting the NF-κB pathway.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
·
癌症研究
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PubMed
高影响因子
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