JOURNAL OF APPLIED TOXICOLOGY
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2024
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IF 2.7
Hongmei Chang,Siqi Zhao,Yuzhu Lei,Yunhua Hu,Yizhong Yan,Guanling Song
Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.
研究领域:
生殖生物学
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细胞生物学
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纳米技术
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Dong Guo,Hui Liu,Sheng Zhao,Xinya Lu,Haoyu Wan,Yitao Zhao,Xinzhi Liang,Anbiao Zhang,Mengyuan Wu,Zhisheng Xiao,Ning Hu,Zhong Li,Denghui Xie
A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.
研究领域:
药理学
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免疫学
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纳米技术
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Yahong Li,Junjin Zhu,Xin Zhang,Yuanyuan Li,Shu Zhang,Linxin Yang,Ruyi Li,Qianbing Wan,Xibo Pei,Junyu Chen,Jian Wang
It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the half-life of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis–osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO@ZIF-8. Additionally, due to the sustained release of DFO and Zn2+, DFO@ZIF-8 NPs were able to promote angiogenesis in human umbilical vein endothelial cells (HUVECs) culture and osteogenesis in bone marrow stem cells (BMSCs) in vitro. Furthermore, the DFO@ZIF-8 NPs promoted vascularization by enhancing the expression of type H vessels and a vascular network. The DFO@ZIF-8 NPs promoted bone regeneration in vivo by increasing the expression of OCN and BMP-2. RNA sequencing analysis revealed that the PI3K-AKT-MMP-2/9 and HIF-1α pathways were upregulated by DFO@ZIF-8 NPs in HUVECs, ultimately leading to the formation of new blood vessels. In addition, the mechanism by which DFO@ZIF-8 NPs promoted bone regeneration was potentially related to the synergistic effect of angiogenesis–osteogenesis coupling and Zn2+-mediation of the MAPK pathway. Taken together, DFO@ZIF-8 NPs, which were demonstrated to have low cytotoxicity and excellent coupling of angiogenesis and osteogenesis, represent a promising strategy for the reconstruction of critical-sized bone defects.
研究领域:
骨组织工程
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纳米技术
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药学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Baixi Shan,Haoyan Zhou,Congying Guo,Xiaolu Liu,Mingyu Wu,Rao Zhai,Jun Chen
Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U- 13 C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of TGF-β1- dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro . We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan ⅡA in treating PF using 13 C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.
研究领域:
药理学
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代谢组学
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肺医学
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细胞生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Yan Chen,Ming Zhang,Yanqin He,Suying Li,Shuaiqi Feng,Zhifang Liu,Ning Zhang,Meifeng Liu,Qingpeng Wang
Epithelial–mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/β-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.
研究领域:
癌症生物学
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药理学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
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2024
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IF 7.2
Xiuhong Huang,Liqin Zheng,Pengfei Li,Ziling Lin,Shaohong Huang,Changren Zhou
Bone defects have been a tough clinical challenge. The natural trabecular tissue reflects a balance between the minimal metabolic cost of maintenance and maximal network stability, with mitochondria being the energy suppliers for osteogenesis. Herein, a 3D printed trabecular bone-templated scaffold composed of polylactide (PLA) modified with europium (III)-organic ligands (polydopamine and chitooligosaccharide, PDA/COS@Eu) was fabricated (denoted as Tra-PLA/PDA/COS@Eu) to augment bone repair by facilitating mitochondrial function. First, the trabecular bone templated-scaffold provides superior mechanical performance and permeability in contrast to a computer aided designed (CAD) scaffold under a same volume fraction. Tra-PLA/PDA/COS@Eu scaffold up regulated PI3K/AKT/S6K/HIF-1α pathway and significantly promoted BMSCs proliferation and osteogenic differentiation. In addition, Tra-PLA/PDA/COS@Eu scaffold provided anti-inflammatory environment by promoting macrophages M2 polarization through COS, and significantly stimulated BMSCs osteogenesis with enhanced mitochondrial function and biosynthesis. Remarkably, Eu ions are the key ingredient in enhancing mitochondrial function and biosynthesis in BMSCs. Further studies showed that the above-mentioned facilitations in a rabbit bone defect model were found to be more significant with trabecular bone-templated scaffolds, as opposed to CAD scaffolds. In summary, this novel trabecular bone-templated scaffold targeting mitochondrial function has the potential to become an effective method in the treatment of large bone defects.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）