CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Siyu Zhao,Yue Li,Lin Dai,Bo Cheng
The development of artificial biomaterials that simulate the extracellular matrix of bone tissue is a promising strategy for bone regeneration. Hydrogel has become a feasible alternative, yet its lack of biological activity still needs to be improved. Herein, a piezoelectric composite hydrogel (TBP) based on tripolyglycerol monostearate (TM) and loaded with barium titanate (BTO) nanoparticles through hydrogen bonding provided by polydopamine has been developed to promote osteogenesis. In vitro , TBP exhibits excellent injectability, shape adaptability and biodegradability, ensuring the feasibility of its biological applications. Moreover, by virtue of the piezoelectric conversion capability of BTO, TBP has the response ability to low-intensity pulsed ultrasound (LIPUS) and can generate local electrical signals. Meanwhile, TBP performs outstandingly in promoting the proliferation, migration, adhesion and osteogenic differentiation of MC-3 T3-E1 cells. More importantly, TBP combined with LIPUS stimulation can regulate mitochondrial oxidative phosphorylation (OXPHOS) through the AKT/GSK3β/β-catenin signaling cascade, thereby accelerating osteogenesis. In vivo , the application of TBP hydrogel to the bone defect site of rats, combined with LIPUS stimulation, shows satisfactory effects in promoting bone regeneration. To sum up, this piezoelectric composite hydrogel is expected to become a promising candidate for bone tissue engineering.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
纳米技术
·
细胞生物学
·
再生医学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yujuan Gao,Yunhao Li,Zian Pan,Chenlu Xu,Xiaoyu Zhang,Mingjun Li,Weifeng Wang,Fan Jia,Yan Wu
Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors.
研究领域:
生物医学工程
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肿瘤学
·
药剂学
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DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2025
·
IF 21.7
Muhammad Zubair Saleem,Ruyi Huang,Yingying Huang,Xin Guo,Yang Liu,Miao Gao,Yinjuan Fan,Zhe-Sheng Chen,Zun-Fu Ke,Shengnan Ye,Jianhua Xu
Aims TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1. Methods Breast cancer cells were induced to quiescence by hypoxia and low glucose. The relationship of cell metabolism with HSP90 and TRAP1 was investigated by Western blotting, ECAR, OCR, mitochondrial complex activity, and proteomic analysis. The targets of C210 and their functions were analyzed by SPR and immunoprecipitation. The antitumor effect in vivo was investigated with mouse tumor model. Results In hypoxia and glucose deprivation, breast cancer cells exhibited elevated TRAP1 and an OXPHOS-enhanced quiescent phenotype. These cells were highly resistant to DOX but more sensitive to C210. C210 disrupted TRAP1's interaction with OXPHOS-associated client proteins, prompting proteasome-dependent degradation of these proteins, thereby reducing OCR, mitochondrial ATP production and resulting in selective elimination of the quiescent cancer cells by inducing mitochondrial apoptosis which could be reversed by exogenous ATP. Moreover, C210 targeted glycolytic, amino acid, and β-oxidation-associated proteome. C210 demonstrated promising in vivo anticancer efficacy which was particularly related to OXPHOS inhibition. Conclusions C210 eliminates DOX-resistant quiescent breast cancer cells by targeting TRAP1-dependent bioenergetics.
研究领域:
肿瘤学
·
分子生物学
·
药物研发
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Wei Li,Xiao Wang,Xiaoli Liu,Luoyang Wang,Jie Liang,Yu Cui,Yi Liu,Mengting Zhou,Zijie Yang,Meiying Song,Yanyan Yang,Li Zhang,Bei Zhang
Persistent inflammation impedes peripheral nerve regeneration, in which infiltrating macrophages play pivotal roles by regulating the M1/M2 phenotypic balance. M2 macrophages facilitate repair, yet factors driving M1-to-M2 transition remain unclear. Lactate, a key metabolic byproduct in injured tissue, dynamically regulates microenvironmental signaling. Here, we observed a correlation between M2 macrophage accumulation and lactate elevation within 5 days post-sciatic nerve injury. In vitro, both Schwann cells and macrophages were identified as important lactate producers. In vivo, low-dose lactate (10–20 mM) enhanced M2 polarization and accelerated regeneration, whereas high-dose lactate (50 mM) showed no benefit. Transcriptomic analysis revealed that 10 mM lactate upregulated M2 markers (arginase 1 (Arg1), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β)) and oxidative phosphorylation (OXPHOS)-related genes in M1 macrophages. Seahorse analysis and adenosine triphosphate (ATP) quantification confirmed lactate-driven OXPHOS activation. Conversely, 50 mM lactate induced excessive reactive oxygen species (ROS) and reduced mitochondrial membrane potential which may explain its lack of regenerative efficacy. Furthermore, CCAAT/enhancer-binding protein beta (Cebpb), a transcription factor can promote Arg1 and VEGF expression in M1 cells under 20 mM lactate. Our findings demonstrate that low-dose lactate promotes M1-to-M2 transition via OXPHOS metabolic reprogramming and Cebpb upregulation, whereas excessive lactate disrupts mitochondrial function. This highlights lactate concentration-dependent modulation of macrophage polarization, a finding that provides insights into metabolic regulation of inflammatory responses during nerve repair. The current data, which focus on macrophage polarization outcomes, support further investigation into whether targeting metabolic rewiring could optimize regenerative microenvironments for functional nerve regeneration.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR CELL
·
2026
·Vol. 86
·期 8
·1511-1528
·
IF 16
Lvxin Xie,Shuchao Ren,Li Zhang,Ziqing Wang,Tong Wu,Qing Dai,Shikun Xiang,Zhihua Qian,Yufan Xian,Shutong Xu,Xiao-Lin Chen,Chuan He,Yi Liu,Zhipeng Zhou
Mitochondria generate ATP through oxidative phosphorylation (OXPHOS), with core structural subunits encoded by mitochondrial DNA (mtDNA) and translated by mitochondrial ribosomes. However, how mitochondrial translation elongation influences OXPHOS biogenesis remains unclear. Here, we show that in Neurospora crassa , the mitochondrial ribosomal RNA (rRNA) methyltransferase 1 (MRM1) promotes OXPHOS biogenesis by repressing translation elongation independently of its catalytic activity. The N-terminal intrinsically disordered region (IDR) of MRM1 binds simultaneously to mitochondrial ribosomes and mRNAs. Disrupting either interaction accelerates elongation and enhances synthesis of mtDNA-encoded OXPHOS subunits but impairs their co-translational folding and membrane insertion. Pharmacological slowing of mitochondrial translation partially alleviates these defects. The MRM1 IDR is conserved in Ascomycete fungi and is essential for plant infection by Magnaporthe oryzae . Together, our findings identify translation elongation control as a mechanism coordinating mitochondrial protein synthesis and folding during OXPHOS biogenesis and MRM1 as a potential target for broad-spectrum antifungal strategies.
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Si Yao,Jie Yin,Wen Liu,Yang Li,Jianzheng Huang,Changxing Qi,Zhengxi Hu,Qingyi Tong,Lianghu Gu,Yonghui Zhang
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell non-Hodgkin's lymphoma. Currently, moderate efficacy and limitations of approved drugs still exist, and it is necessary to develop newer and more effective drugs. Gboxin is a promising inhibitor of OXPHOS, which specifically inhibits the growth of many kinds of cancer cell lines. In the present study, 21 Gboxin analogs incorporating amide and ester moieties were designed and synthesized. Preliminary screening results show that 5d also has specific selectivity for cancer cells, particularly on the DLBCL cells, which is weaker than that of Gboxin but still good. Thus, the effect and underlying mechanism of 5d on DLBCL cells were further studied. The results showed that 5d exhibits potent proliferation inhibition and cell cycle arrest effects, and its IC 50 to DLBCL cells is below 1 µM. In addition, 5d induces apoptosis of DLBCL cells in a time- and dose-dependent manner, and this effect is stronger than that of Gboxin and VP16. Mechanistically, 5d plays its role mainly through the stimulation of metabolic stress in DLBCL cell lines, which induces OXPHOS inhibition, inflammation, DNA damage and mitochondrial dysfunction. These data suggest that 5d has potential as a candidate agent for DLBCL alternative drug development.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Wen Zhou,Yuwan Chen,Wenxin Fu,Xinwei Li,Yufei Xia,Qun Zhao,Baofeng Zhao,Yukui Zhang,Kaiguang Yang,Lihua Zhang
The study of in situ conformations and interactions of mitochondrial proteins plays a crucial role in understanding their biological functions. Current chemical cross-linking mass spectrometry (CX-MS) has difficulty in achieving in-depth analysis of mitochondrial proteins for cells without genetic modification. Herein, this work develops the reactive oxygen species (ROS)-responsive cross-linker delivery nanoparticles (R-CDNP) targeting mitochondria. R-CDNP contains mitochondria-targeting module triphenylphosphine, ROS-responsive module thioketal, loading module poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), and cross-linker module disuccinimidyl suberate (DSS). After targeting mitochondria, ROS-triggered cross-linker release improves the cross-linking coverage of mitochondria in situ. In total, this work identifies 2103 cross-linked sites of 572 mitochondrial proteins in HepG2 cells. 1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions.
研究领域:
生物化学
·
细胞生物学
·
分子生物学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 4
·3422-3433
·
IF 10.269
Dong Fudan,Jiang Qikun,Li Lingxiao,Liu Tian,Zuo Shiyi,Gao Lin,Fang Mengna,Gao Yanlin,Sun Bingjun,Luo Cong,He Zhonggui,Sun Jin
Mitochondrial bioenergy plays a vital role in the occurrence and development of cancer. Although strategies to impede mitochondrial energy supply have been rapidly developed, the anticancer efficacy is still far from satisfactory, mainly attributed to the hybrid metabolic pathways of mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. Herein, we construct a cancer cell membrane camouflaged nano-inhibitor, mTPPa-Sy nanoparticle (NP), which co-encapsulates OXPHOS inhibitor (mitochondrial-targeting photosensitizers: TPPa) and glycolysis inhibitor (syrosingopine (Sy)) for synergistically blocking the two different energy pathways. The mTPPa-Sy NPs exhibit precision tumor-targeting due to the high affinity between the biomimic membrane and the homotypic cancer cells. Under laser irradiation, the mitochondrial-targeting TPPa, which is synthesized by conjugating pyropheophorbide a (PPa) with triphenylphosphin, produces excessive reactive oxygen species (ROS) and further disrupts the OXPHOS. Interestingly, OXPHOS inhibition reduces O 2 consumption and improves ROS production, further constructing a closed-loop OXPHOS inhibition system. Moreover, TPPa-initiated OXPHOS inhibition in combination with the Sy-triggered glycolysis inhibition results in lethal energy depletion, significantly suppressing tumor growth even after a single treatment. Our findings highlight the necessity and effectiveness of synergetic lethal energy depletion, providing a prospective strategy for efficient cancer therapy.
研究领域:
癌症生物学
·
纳米技术
·
治疗学
·
生物化学
·
药理学
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产品关联
DOI
高影响因子
iMeta
·
2025
·Vol. 4
·期 6
·e70100
·
IF 33.2
Sen-Lin Zhu,Yu-Nan Yan,Ming-Hui Jia,Hou-Cheng Li,Bo Han,Tao Shi,Lian-Bin Xu,Xiao-Wen Wang,Qi Zhang,Wei-Jie Zheng,Jing-Hong Xu,Liang Chen,Wenlingli Qi,Sheng-Jun Cai,Xin-Peng Chen,Feng-Fei Gu,Jian-Xin Liu,George E. Liu,Yu Jiang,Dong-Xiao Sun,Ling-Zhao Fang,Hui-Zeng Sun
Oxygen signaling is essential for cellular homeostasis and tightly linked to metabolism, growth, and survival. In dairy cows, oxidative stress, arising from an imbalance between reactive oxygen species and antioxidants, is a major postpartum challenge that contributes to disease susceptibility. Using single-cell transcriptomes from 1,793,854 cells across 59 tissues, we analyzed oxygen signaling states within 1006 cellular clusters. The gastrointestinal tract (GIT) epithelium, particularly the forestomach, exhibits the strongest antioxidant activity, closely coupled to oxidative phosphorylation (OXPHOS) and glycolysis, with OXPHOS levels surpassing those of cardiomyocytes and hepatocytes (Cohen's d > 3.9, p < 0.001). Pseudotime and spatial transcriptomics demonstrated that both OXPHOS and antioxidant capacity increase progressively along the basal-to-luminal differentiation axis. Functional experiments in primary rumen epithelial cells showed that antioxidant supplementation or GPX1 modulation enhances mitochondrial respiration, boosts intracellular glutathione, and accelerates epithelial differentiation. Limited proteolysis-mass spectrometry (LiP-MS) analysis identified GPX1 , GSTP1 , COX7A2 , and COX6B1 as candidate targets mediating antioxidant-driven metabolic remodeling. Together, these results reveal a redox-governed metabolic program in the forestomach epithelium and highlight antioxidant interventions as a potential strategy to support epithelial development and mitigate oxidative stress-related disorders in dairy cattle. Graphical Single-cell and transcriptomics from 1.79 million cells identify the forestomach epithelium as the dominant site of antioxidant activity and oxidative phosphorylation (OXPHOS) in the bovine gastrointestinal tract. Along the basal-to-luminal differentiation axis, antioxidant capacity and OXPHOS rise in a coordinated metabolic–redox gradient. Primary rumen cell assays show that this gradient is strengthened by Cys-Cys-Cys supplementation or modulation of GPX1 expression, demonstrating a direct causal influence on epithelial metabolism. Key redox-metabolic regulators, including GPX1 and GSTP1 , mediate these responses. Overall, antioxidants actively drive metabolic remodeling and promote epithelial differentiation in the cattle forestomach epithelium. Highlights A single-cell transcriptomic atlas of 1.79 million bovine cells revealed the forestomach epithelium as one of the most antioxidant-active tissues. As the forestomach epithelium differentiates from the basal layer towards the luminal surface, both mitochondrial respiration and antioxidant capacity progressively intensify, establishing a coupled metabolic–redox gradient. Functional assays identified GPX1 as a key antioxidant target mediating OXPHOS and cell differentiation.
研究领域:
动物科学
·
反刍动物生理学
·
转录组学
·
氧化还原生物学
·
代谢
·
单细胞分析
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 12
·2202907
·
IF 10
Xinghua Yu,Ming Lyu,Xupei Ou,Wenquan Liu,Xing Yang,Xiaoxi Ma,Tianfu Zhang,Longnan Wang,Ying-Chuan Zhang,Sijie Chen,Ryan T. K. Kwok,Zheng Zheng,Hong-Liang Cui,Lintao Cai,Pengfei Zhang,Ben Zhong Tang
Aggregation-induced emission luminogens (AIEgens) are widely used as photosensitizers for image-guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep-seated tumors by visible-light-sensitized aggregation-induced emission (AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial-targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep-seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物物理学
·
细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Zhuo Li,Boguang Yang,Zhengmeng Yang,Xian Xie,Zhengnan Guo,Jianyang Zhao,Ruinan Wang,Hao Fu,Pengchao Zhao,Xin Zhao,Guosong Chen,Gang Li,Fuxin Wei,Liming Bian
Cellular energetics plays an important role in tissue regeneration, and the enhanced metabolic activity of delivered stem cells can accelerate tissue repair and regeneration. However, conventional hydrogels with limited network cell adaptability restrict cell–cell interactions and cell metabolic activities. In this work, it is shown that a cell-adaptable hydrogel with high network dynamics enhances the glucose uptake and fatty acid β -oxidation of encapsulated human mesenchymal stem cells (hMSCs) compared with a hydrogel with low network dynamics. It is further shown that the hMSCs encapsulated in the high dynamic hydrogels exhibit increased tricarboxylic acid (TCA) cycle activity, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) biosynthesis via an E-cadherin- and AMP-activated protein kinase (AMPK)-dependent mechanism. The in vivo evaluation further showed that the delivery of MSCs by the dynamic hydrogel enhanced in situ bone regeneration in an animal model. It is believed that the findings provide critical insights into the impact of stem cell–biomaterial interactions on cellular metabolic energetics and the underlying mechanisms.
研究领域:
生物材料
·
干细胞生物学
·
组织工程
·
代谢工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）