Biomaterials Science
·
2021
·Vol. 9
·期 16
·5519-5532
·
IF 6.843
Qiyuan Dai,Qingtao Li,Huichang Gao,Longtao Yao,Zefeng Lin,Dingguo Li,Shuangli Zhu,Cong Liu,Zhen Yang,Gang Wang,Dafu Chen,Xiaofeng Chen,Xiaodong Cao
The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol–gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.
研究领域:
生物医学工程
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组织工程
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骨科
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材料科学
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PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Longqing Hu,Zhongyuan Yin,Songwei Tan,Yu Deng,Xincai Qu,Ting Hu,Qiong Wang
Triple-negative breast cancer (TNBC) derives only limited clinical benefit from radiotherapy (RT), partly due to abnormalities in the tumor microenvironment and dysregulated signaling pathways. By integrating TNBC cases from the METABRIC and TCGA cohorts, we implemented an analysis framework centered on RT-by-gene interaction terms, implicating TNF-α–NF-κB signaling and inflammatory response as potential effect modifiers of RT benefit. Based on a pathway-guided polyphenol–gene interaction screen, curcumin (Cur) was prioritized as a modulator of TNF-α–NF-κB/inflammation-related programs. We then engineered a multifunctional nanoplatform (TCC) that couples catalytic modulation of the tumor microenvironment with suppression of adaptive pro-survival programs. TCC was built on pH-responsive nanoceria (CeO 2 nanozymes) to modulate redox homeostasis and alleviate hypoxia, loaded with Cur, and coated with D-α-tocopherol polyethylene glycol succinate (TPGS) to improve stability and cellular uptake; cRGD was further introduced to generate cRGD-TCC for enhanced tumor targeting. In vitro and in vivo, TCC promoted G 2 /M-phase arrest, amplified RT-induced reactive oxygen species generation and DNA damage, and attenuated TNF-α–NF-κB/inflammatory programs and markers of inflammation, survival, and invasion. Collectively, TCC provides an integrated radiosensitization strategy that addresses microenvironmental barriers and adaptive tumor signaling, thereby potentially enhancing RT response in TNBC.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2014
·
IF 5.71
Simin Yan,Xu Zhang,Haili Zheng,Danhong Hu,Yongtian Zhang,Qinghua Guan,Lifang Liu,Qilong Ding,Yunman Li
Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis . Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck , was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes–endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα , suppressed IκB kinase-β (IKK-β) activity, lowered O 2 ∙− and H 2 O 2 levels, tackled p47 phox translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-β that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-β activity was also inhibited by (polyethylene glycol) PEG–catalase, N -acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte–HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis.
研究领域:
药理学
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免疫学
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心血管研究
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分子生物学
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高影响因子
Environmental Science-Nano
·
2022
·Vol. 9
·期 8
·2653-2664
·
IF 9.473
Guofang Zhang,Guoli Cao,Rong-Hua Luo,Qingle Song,Yanqiao Zeng,Ke Liu,Jing Qu,Xian Lin,Feng-Liang Liu,Guocheng Wang,Hongchang Li,Liang Li,Yong-Tang Zheng,Diana Boraschi,Lidong Wu,Yan-Zhong Chang,Yang Li
Microplastics (MP) pollution is a global issue that raises concerns about potential toxicity for environmental and human health. The notion that SARS-CoV-2 is more stable when adsorbed on plastic surfaces urged us to examine whether the virus can attach to MP, which may facilitate infection upon inhalation or ingestion. Here, we describe that MP can bind SARS-CoV-2 pseudovirus on their surface and enhance infection of human cells in vitro. This enhanced in vitro infectivity was confirmed with authentic SARS-CoV-2, in parallel with increased expression of inflammation-related caspase-3, IL-8 and TNF-α genes. These results suggest that the presence of MP in the environment or in our respiratory or gastrointestinal tracts has the potential to interact with SARS-CoV-2, and potentially increase viral infectivity and spreading.
研究领域:
环境科学
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病毒学
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毒理学
·
细胞生物学
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DOI
高影响因子
Foods
·
2022
·Vol. 11
·期 21
·3538
·
IF 5.561
Kaiying Jia,Min Wei,Yao He,Yujie Wang,Hua Wei,Xueying Tao
Exopolysaccharide (EPS) from probioticEnterococcus hiraeWEHI01 was isolated and purified by anion exchange chromatography and gel chromatography, the results of which show that the EPS consists of four fractions, namely I01-1, I01-2, I01-3, and I01-4. As the main purification components, I01-2 and I01-4 were preliminarily characterized for their structure and their immunomodulatory activity was explored. The molecular weight of I01-2 was 2.28 × 104Da, which consists mainly of galactose, and a few other sugars including glucose, arabinose, mannose, xylose, fucose, and rhamnose, while the I01-4 was composed of galactose only and has a molecular weight of 2.59 × 104Da. Furthermore, the results of an evaluation of immunomodulatory activity revealed that I01-2 and I01-4 could improve the viability of macrophage cells, improve phagocytosis, boost NO generation, and encourage the release of cytokines including TNF-α and IL-6 in RAW 264.7 macrophages. These results imply that I01-2 and I01-4 could improve macrophage-mediated immune responses and might be useful in the production of functional food and medications.Keywords:Enterococcus hiraeWEHI01;exopolysaccharide;immunomodulatory properties
研究领域:
微生物学
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免疫学
·
药学
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食品科学
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PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 10
·1560
·
IF 5.1
Sisi Huang,Wei Cai,Yan Wang,Xiaoliang Xing,Zaiqi Zhang
Objective:This study aimed to investigate whether pomolic acid (PA), a predicted bioactive metabolite of the Dong botanical drug Madeng’ai (MDA), suppresses inflammatory cytokine expression by inhibiting nuclear factor-κB (NF-κB) pathway activation in a tumor necrosis factor-α (TNF-α)-induced human rheumatoid arthritis fibroblast-like synoviocyte (RA-HFLS) model.Methods:PA content in MDA from different regions and harvest years was quantified via High-Performance Liquid Chromatography (HPLC). Network analysis was employed as a hypothesis-generating tool to predict potential targets and pathways, followed by molecular docking to validate the binding affinity of PA to core targets of the NF-κB pathway, and ADMET prediction to evaluate its pharmacokinetic properties and safety profile. The RA-HFLS inflammatory model was induced by TNF-α. Cell viability and inflammatory cytokine secretion were assessed using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). NF-κB signaling pathway activation and downstream gene expression were examined by Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively.Results:HPLC analysis revealed that MDA samples from Guizhou harvested in 2019 contained the highest PA content (0.1117 mg/g). Network analysis predicted the NF-κB signaling pathway as a candidate mechanism underlying PA’s potential anti-inflammatory effects. Molecular docking showed that PA stably bound to IKKβ, p65, and IκBα, while ADMET prediction indicated favorable intestinal absorption, low drug–drug interaction risk, and good genetic safety, albeit with potential hepatotoxicity and reproductive toxicity risks. In the TNF-α-induced RA-HFLS model, PA dose-dependently inhibited abnormal cell proliferation and significantly reduced the secretion of pro-inflammatory cytokines TNF-α and interleukin-6 (IL-6). Mechanistic studies indicated that PA suppressed the activation of the NF-κB signaling pathway, thereby downregulating the mRNA expression of inflammatory genes such as IL-6, TNF-α, and interleukin-1β (IL-1β).Conclusions:PA, a bioactive metabolite of the Dong botanical drug MDA, may inhibit NF-κB signaling pathway activation, thereby downregulating TNF-α-induced inflammatory cytokine expression in RA-HFLS, demonstrating its in vitro anti-inflammatory potential.
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高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Shuifang Mao,Bin Wang,Lin Yue,Wenshui Xia
In order to improve the anti-inflammatory activity of chitosan oligosaccharide (COS), chitosan oligosaccharide graft citronellol derivatives (COS-g-Cit1-3) were successfully synthesized via grafting citronellol (Cit) onto COS backbone. The degrees of substitution (DS) of COS-g-Cit1-3 were 0.165, 0.199 and 0.182, respectively. The structure of COS-g-Cit1-3 was confirmed by UV–vis, FT-IR, 1 H NMR and elemental analysis. The in vivo anti-inflammatory activity evaluation results displayed that COS-g-Cit1-3 drastically reduced the paw swelling, and the oedema inhibitions were 22.58 %, 29.03 % and 25.81 %, respectively. The results indicated that the anti-inflammatory effects of COS-g-Cit1-3 were significantly higher than COS and COS-g-Cit2 exhibited the highest anti-inflammatory ability. The results also presented that COS-g-Cit1-3 reduced the expression levels of TNF-α by promoting the secretion of IL-4 and IL-10. Moreover, western blot analysis data proved that COS-g-Cit1-3 inactivated the NF-κB signaling pathway via inhibiting the phosphorylation of p65, IKBα and IKKβ.
研究领域:
药学
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生物技术
·
生物化学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Shangping Xing,Xue Cheng,Shiyu Hou,Lidan Qin,Juan Wang,Yue Ding,Zhangyang Shen,Ziteng Dai,Xiaoming Huang,Yanying Liu,Dan Zhu
Novel therapeutic agents with improved safety and efficacy are urgently required for ulcerative colitis (UC), a refractory inflammatory bowel disease. Mangrove-derived natural products represent a promising reservoir for drug discovery. Monomethylsulochrin (MMSC) is a type II polyketide isolated from the endophytic fungus Aspergillus fumigatus of the mangrove plant Aegiceras corniculatum . However, its therapeutic effects on UC and the underlying mechanisms remain unclear. Herein, we evaluated the efficacy of MMSC by using a dextran sodium sulfate (DSS)-induced colitis mouse model and elucidated the underlying mechanisms by proteomics analyses, molecular biology techniques, and 16S rDNA gene sequencing. Our results demonstrated that MMSC significantly ameliorated DSS-induced colitis, as evidenced by reduced disease activity index, preserved colon length, and attenuated histopathological damage. Mechanistically, proteomics profiling and subsequent validation confirmed that MMSC concurrently suppressed the interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways by downregulating key nodes (matrix metalloproteinase [MMP]-9, S100 calcium-binding protein A8 [S100a8], CCAAT/enhancer-binding protein beta [Cebpb], cAMP responsive element binding protein 1 [Creb1], and Fas) and related pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-17, TNF-α) in both colonic tissues and lipopolysaccharide (LPS)-stimulated NCM460 cells. Furthermore, MMSC restored gut microbial diversity and composition in mice with colitis, reversing DSS-induced dysbiosis. Spearman correlation analysis revealed that the IL-17/TNF pathway exhibited a notable correlation with MMSC-mediated restoration of the gut microbiota. In conclusion, MMSC alleviates UC through a dual mechanism integrating suppression of IL-17/TNF signaling and restoration of gut microbiota homeostasis, highlighting it as a promising candidate for developing novel therapies against UC.
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Materials Today Bio
·
2026
·
IF 11
Chao Song,Yang Zhou,Yinjing Luo,Liquan Wang,Tao Liu,Daqian Zhou,Fei Liu,Jingwen Chen,Zhijiang Fu,Feng Chen,Guoyou Wang,Zongchao Liu
Background Infected bone defects are difficult to treat due to bacterial biofilms and chronic inflammation. Systemic antibiotics often fail and cause severe side effects. A dual-drug delivery system that combines antibacterial and osteo-immunomodulatory actions may offer a synergistic solution. Methods A gelatin-based microfluidic microsphere (GM@RES@VAN) co-loading vancomycin (VAN) and resveratrol (RES) was developed. The microspheres were characterized for morphology, drug release, and elemental composition. Antibacterial and biofilm-degrading effects were assessed in vitro against MRSA. A rat infected bone defect model was used to evaluate in vivo healing via micro-CT, histology, and immunofluorescence. Network pharmacology, molecular docking, and cellular assays (qPCR, Western blot, TEM, HIF inhibition) explored the molecular mechanism. Results GM@RES@VAN microspheres showed uniform size, smooth surface, and sustained dual-drug release. In vitro, the microspheres exhibited potent bactericidal activity and biofilm degradation (∗∗∗p < 0.001). In vivo, the GM@RES@VAN group significantly reduced local bacterial load, decreased inflammatory infiltration, and promoted collagen deposition and new bone formation, with increased bone mineral density and bone volume/tissue volume (∗p < 0.05). Mechanistically, resveratrol suppressed pro-inflammatory factors (IL6, TNF, IL1B), reduced HIF1A, MMP9, and PTGS2 expression, preserved mitochondrial ultrastructure, upregulated osteogenic markers (ALP, OCN, COL I) and the anti-apoptotic protein BCL2. Vancomycin primarily cleared the infection, while resveratrol acted through the TNF/HIF-1 axis to reshape the inflammatory microenvironment and promote osteogenesis—their synergy was confirmed by HIF inhibition tests. Conclusion The GM@RES@VAN dual-drug microspheres achieve programmed antibacterial and osteo-immunomodulatory effects via vancomycin-mediated infection clearance and resveratrol-driven TNF/HIF-1 pathway regulation. This combination offers a promising strategy for treating refractory infected bone defects.
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PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Yang Wenyan,Ma Lu,Hu Ting,Zhang Lei,Wu Kewei,Chen Hualin,Zhang Dandan,Luo Peng
Geochemical fluoride pollution is a global public health issue affecting a wide range and large population. The major health hazard from long-term fluoride exposure is skeletal fluorosis, a highly disabling and irreversible bone damage disease with no effective early interventions available to date. Given reactive oxygen species (ROS) accumulation is a key event in fluoride-induced bone damage, we established a sodium fluoride-exposed rat model. During the phase when fluoride induced ROS accumulation and mild bone damage in rat bone tissue, we administered Rosa roxburghii Tratt juice (RRTJ)—a natural food-medicinal homologous plant with antioxidant properties—to explore its intervention effect and potential mechanism against fluoride-induced bone damage. Results showed RRTJ inhibited fluoride-induced decreases in bone mineral density and trabecular number in male rats. Since enhanced bone resorption mediated by osteoclast overactivation is the initiating link of these fluoride-induced pathological changes, this study further found RRTJ suppressed fluoride-induced increases in osteoclast activity in male rat bone tissue, specifically reducing osteoclast numbers in bone tissue and lowering serum levels of bone resorption markers CTX and TRAP-5b. This effect is achieved by RRTJ scavenging fluoride-induced ROS accumulation in bone tissue, restoring ROS/TNF-α/NF-κB pathway homeostasis, and thereby inhibiting the overexpression of osteoclast activation-related genes tartrate-resistant acid phosphatase and cathepsin K. In conclusion, this study confirms RRT inhibits fluoride exposure-induced bone damage in male rats by regulating ROS/TNF-α/NF-κB pathway homeostasis. These findings provide new perspectives on the mechanism of fluoride-induced bone damage and, more importantly, reveal a potential novel intervention strategy.
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高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 11
·1-15
·
IF 2.6
Shen Wei,Wang Meng,Han Ting,Yao Yan,Ying Xinyi,Cui Yuyue,Du Peng
Previous research has indicated that the exopolysaccharide galactosaminogalactan (GAG) from Aspergillus fumigatus plays a pivotal role in the pathogenesis of experimental invasive aspergillosis by promoting virulence. However, it remains unclear whether the exopolysaccharide is directly virulent to host cells. In this study, we established a co-incubation system using human THP-1-derived macrophages and GAG extracted from A. fumigatus ATCC 1022 to assess the capacity of GAG to induce necroptosis in THP-1 cells, as well as to elucidate the underlying mechanisms of this process. Our findings indicate that the proportion of N-acetylgalactosamine in the GAG fraction derived from strain ATCC 1022 was lower, while GAG demonstrated a significantly greater ability to induce the production of the pro-inflammatory cytokines TNF-α and IL-1β, which was accompanied by the induction of necroptosis. Western blotting analysis revealed a significant increase in the phosphorylation of RIP1, RIP3, and MLKL proteins in GAG-treated THP-1 cells, and RIP1-RIP3-MLKL signaling activation and GAG-induced caspase activity-independent cell death were effectively inhibited by the TNF-α receptor-1 (TNFR1) inhibitor R-7050, the neutralizing antibody against TNF-α or necroptosis inhibitor Necrostatin-1. It's worth noting that the expression of CLEC4E, the gene encoding the Mincle receptor in macrophages, was elevated in the co-incubation system, potentially enhancing TNF-α-mediated necroptotic cell death. In addition to the RIP1-RIP3-MLKL axis, BAX, cleaved PARP, and JNK were also activated following GAG treatment, warranting further investigation into their roles in the regulation of necroptosis. Our findings demonstrate that GAG produced by A. fumigatus conidia during germination triggers necroptotic cell death in human THP-1 cells via TNF-α-mediated RIP1-RIP3-MLKL signaling.
研究领域:
微生物学
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免疫学
·
分子生物学
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感染性疾病
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真菌病理学
·
细胞死亡机制
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Foods
·
2024
·Vol. 13
·期 24
·4019
·
IF 4.7
Zhou Xu,Yanxia Xiong,Pei Hu,Long Chen,Jianhua Wan,Chenggang Huang,Wenjun Liu
Alpinia officinarumHance has a medicinal history of thousands of years in treating cough, diabetes, and gastrointestinal system diseases, and it is also a medicine food homology (MFH) plant in China. To evaluate the pharmacological activities of polysaccharides from the rhizomes ofA. officinarum, polysaccharides were initially obtained by hot-water extraction and the ethanol precipitation method. A homogenous polysaccharide designated as AOP-w was isolated by a DE-52 column. The proposed structure was elucidated and the immunoregulatory effects on RAW 264.7 macrophage cells were evaluated. The results showed that AOP-w had a molecular weight of 5.26 kDa, and mainly consisted of galactose and glucose (molar ratio of 0.12:0.88). Its backbone comprised α-(1→4)-Glcp, α-(1→4,6)-Glcpand β-(1→3,4)-Galpresidues, terminated by α-(1→6)-Glcpand T-Glcpresidues. AOP-w was nontoxic to RAW 264.7 cells, but demonstrated promotion in cell proliferation within a 100 μg/mL concentration. The immunostimulatory effects of AOP-w were confirmed by the elevated NO production of AOP-w-treated cells. Moreover, the RNAseq was conducted and the results showed that AOP-w may activate the TNF and NF-κB signaling pathways by binding to Toll-like receptors, thereby affecting the immune modulatory activity of RAW264.7 cells. These results suggest a high potential of AOP-w fromA. officinarumfor immunotherapeutic applications.
研究领域:
药理学
·
分子生物学
·
免疫学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）