JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Chen Yang,Tian Hailong,Zhang Xiaodian,Nice Edouard C.,Huang Canhua,Zhang Haiyuan,Zheng Shaojiang
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu 2+ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy. Graphical
研究领域:
癌症研究
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纳米技术
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免疫学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Yi Chen,Hongjin Qian,Dandan Peng,Yan Jiang,Qiaolin Liu,Yan Tan,Longbao Feng,Biao Cheng,Guilan Li
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
研究领域:
材料科学
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生物医学工程
·
伤口愈合
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Yuecheng Zhao,Chuanshan Zou,Lu Zhang,Chengde Li,Xingpeng Li,Liwen Song
Chlorbenzuron is a kind of benzoylphenylureas (BPUs), which plays a broad role in insect growth regulators (IGRs), with an inhibitory effect on chitin biosynthesis. However, BPUs how to regulate glycolysis and insect growth remains largely unclear. Here, we investigated the effects of chlorbenzuron on growth, nutritional indices, glycolysis, and carbohydrate homeostasis in Hyphantria cunea , a destructive and highly polyphagous forest pest, to elucidate the action mechanism of chlorbenzuron from the perspective of energy metabolism. The results showed that chlorbenzuron dramatically restrained the growth and nutritional indices of H. cunea larvae and resulted in lethality. Meanwhile, we confirmed that chlorbenzuron significantly decreased carbohydrate levels, adenosine triphosphate (ATP), and pyruvic acid (PA) in H. cunea larvae. Further studies indicated that chlorbenzuron caused a significant enhancement in the enzyme activities and mRNA expressions of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK), resulting in increased glycolytic flux. Expressions of genes involved in the AMP-activated protein kinase (AMPK) signaling pathway were also upregulated. Moreover, chlorbenzuron had remarkable impacts on H. cunea larvae from the perspective of metabolite enrichment, including the tricarboxylic acid (TCA) cycle and glycolysis, indicating an energy metabolism disorder in larvae. The findings provide a novel insight into the molecular mechanism by which chlorbenzuron abnormally promotes glycolysis and eventually interferes with insect growth and nutritional indices.
研究领域:
昆虫学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yuhuan Li,Jiayin Lv,Shuchen Liu,Zhuoran Wang,Yu Gao,Zheyuan Fan,Lei Huang,Jing Cui,Boya Zhang,Xinchen Liu,Zhuo Zhang,Te Liu,Daowei Li,Modi Yang
The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.
研究领域:
免疫学
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药理学
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风湿病学
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炎症
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Maowen Chen,Dong Wang,Menghuan Li,Ye He,Tingting He,Maohua Chen,Yan Hu,Zhong Luo,Kaiyong Cai
An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction of bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report the in situ construction of bone microenvironment-responsive biofunctional metal–organic framework (bio-MOF) coating on the titanium surface through the coordination between p-xylylenebisphosphonate (PXBP) and Ce/Sr ions by a hydrothermal method. Taking advantage of the anchored Ce and Sr ions, the AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase and catalase-like catalytic activities to decompose ROS in MSCs and restore their mitochondrial functions. In vitro analysis showed that the AHT-Ce/SrMOF implants substantially activated the AMP-activated protein kinase (AMPK) signaling pathway in MSCs and reduced the ROS levels. Meanwhile, MSCs grown on AHT-Ce/SrMOF implants displayed significantly higher expressions of the mitochondrial fission marker (DRP1), mitochondrial fusion marker (MFN2 and OPA1), and mitophagy marker (PINK1 and LC3) than those of the AHT-CeMOF and AHT-SrMOF groups, which indicated that the bio-MOF could amend mitochondrial function in MSCs to reverse senescence. In vivo evaluations showed that the bio-MOF-coated Ti implants could restore MSC function in the implant site and promote new bone formation, leading to improved osteointegration in osteoporotic rat. This study may improve implant-mediated fracture healing in the clinics.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
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骨科
✓ 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
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组织工程
·
代谢工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2024
·
IF 8.2
Chen Wang,Qiliner Feng,Hongli Lu,Qiubei He,Peng Zhang,Junjie Tang,Zhuoyin Liu,Jie Liu,Baizhu Chen
The mitochondrial energy metabolic reprogramming of tumors leads to the hypoxic, acidic, and immunosuppressive microenvironment. To regulate the reprogrammed mitochondrial energy metabolism and the abnormal tumor microenvironment (TME) intracellularly and extracellularly, herein, we purposely constructed the metabolic regulating and immunological activating nanocomposites (NCs) formed by the manganese dioxide (MnO 2 ) nanoparticles loaded with lactate oxidase (LOX), dichloroacetic acid (DCA) and SR-717, camouflaged by the cell membrane of tumors. After the NCs targeting to the tumors, the loaded DCA inhibited the glycolysis and triggered the produced pyruvate into mitochondria for further degradation. DCA also reduced the amount of CD39 and CD73, thereby promoting the accumulation of ATP intracellularly. The cascade of MnO 2 and LOX catalyzed the lactate to pyruvate together with oxygen for the relief of the hypoxic and immunosuppressive TME. The regulation of the mitochondrial metabolism together with the degradation of lactate contributed to activating the immune cells. Meanwhile, the loaded SR-717 together with the release of Mn 2+ activated the cyclic guanosine monophosphate adenosine monophosphate synthase/interferon gene stimulator signaling pathway for efficient antitumor effects and immunotherapy. Taken together, the designed multifunctional nanocomposites realized an effective tumor immunotherapy by regulating the reprogrammed mitochondrial energy metabolism intracellularly, relieving the abnormal TME and activating the innate antitumor immunological effects extracellularly. Our work established an approach to the enhanced immunotherapy by regulating the reprogrammed metabolism for efficient cancer treatment.
研究领域:
癌症生物学
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免疫学
·
纳米技术
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Hengte Xing,Chuancai Liang,Chenyu Wang,Xiongfeng Xu,Yong Hu,Bo Qiu
In this study, we aim to investigate the effect of metformin on cholesterol synthesis and efflux-related genes in chondrocytes during osteoarthritis (OA) and explore the underlying mechanisms. Primary chondrocytes were harvested from Wistar rat cartilage and divided into control and treatment groups. Chondrocytes in the treatment group were treated with interleukin-1β (IL-1β) mimicking the inflammatory environment of osteoarthritis. Subsequently, RT-qPCR, Western blotting, immunofluorescence staining, and Cell Counting Kit-8 (CCK-8) were conducted. Significant reductions in phosphorylated AMP-activated protein kinase (p-AMPK) and silent information regulator 1 (SIRT1) protein expression were observed in both human OA chondrocytes and cultured primary murine chondrocytes treated with IL-1β, while AMP-activated protein kinase (AMPK) was not inhibited. Moreover, in the presence of IL-1β, metformin significantly increased the expression of p-AMPK and SIRT1 at the protein and mRNA level. Meanwhile, metformin could reverse IL-1β-induced cartilage extracellular matrix degradation in chondrocytes from the rat model of OA (treated by IL-β) by activating the AMPK/SIRT1 pathway. Moreover, metformin activated AMPK and SIRT1, mediated by the activation of SREBP-2 and HMGCR in OA chondrocytes. Inhibiting AMPK/SIRT1 activity by its specific inhibitor could suppress IL-1β-induced expression of LXRα, ABCA1 and ApoA1 and cholesterol efflux. Thus, metformin inhibits cholesterol synthesis and promotes cholesterol efflux by activating the AMPK/SIRT1 pathway in OA chondrocytes. This study improves our understanding of the effect of metformin on cholesterol accumulation in OA chondrocytes.
研究领域:
药理学
·
风湿病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2024
·Vol. 9
·期 1
·1-17
·
IF 40.8
Peng Fu,Liao Minru,Jin Wenke,Liu Wei,Li Zixiang,Fan Zhichao,Zou Ling,Chen Siwei,Zhu Lingjuan,Zhao Qian,Zhan Gu,Ouyang Liang,Peng Cheng,Han Bo,Zhang Jin,Fu Leilei
Sirtuin 3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide + (NAD + )-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis, myocardial fibrosis and even heart failure (HF), through its deacetylation modifications. Accordingly, discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed. Herein, we identified a new small-molecule activator of SIRT3 (named 2-APQC) by the structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models. Importantly, in SIRT3 knockout mice, 2-APQC could not relieve HF, suggesting that 2-APQC is dependent on SIRT3 for its protective role. Mechanically, 2-APQC was found to inhibit the mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal kinase (JNK) and transforming growth factor-β (TGF-β)/ small mother against decapentaplegic 3 (Smad3) pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis. Based upon RNA-seq analyses, we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis was closely assoiated with HF. By activating PYCR1, 2-APQC was shown to enhance mitochondrial proline metabolism, inhibited reactive oxygen species (ROS)-p38 mitogen activated protein kinase (p38MAPK) pathway and thereby protecting against ISO-induced mitochondrialoxidative damage. Moreover, activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase (AMPK)-Parkin axis to inhibit ISO-induced necrosis. Together, our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis, which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.
研究领域:
心血管药理学
·
分子生物学
·
细胞生理学
✓ 已验证
DOI
高影响因子
Frontiers in Nutrition
·
2023
·
IF 5
Cao Feiwei,Ding Qinchao,Zhuge Hui,Lai Shanglei,Chang Kaixin,Le Chunyan,Yang Guorong,Valencak Teresa G.,Li Songtao,Ren Daxi
This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (109 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG-014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.
研究领域:
微生物学
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营养学
·
分子生物学
·
胃肠病学
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMB Express
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.5
Yan Yan,Yuan Haisheng,Yang Fan,Na Heiya,Yu Xiuling,Liu Jingran,Wang Yuzhen
Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn ( Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 ( B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold ( P < 0.05) and 2.3 folds ( P < 0.05), respectively, while the CPT1α and PPARα mRNA levels was significantly increased by 2.3 fold ( P < 0.05) and 1.6 fold ( P < 0.05), respectively, after SP administration. SP activated phosphorylated-AMPK and inhibited PPARγ protein expression, improved serum oxidative stress and inflammation ( P < 0.05). SP supplementation leads to increased hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and Superoxide dismutase-2 (SOD-2). Furthermore, SP treatment improved HFD-induced intestinal dysbiosis. Lentisphaerae , Firmicutes , Tenericutes and Peptococcus sp., RC9_gut_group sp., and Parabacteroides sp. of the gut microbiota were significantly associated with hepatic steatosis and indicators related to oxidative stress and inflammation. Therefore, SP can mitigate hepatic lipid accumulation by regulating Nrf-2/HO-1 signaling pathways and gut microbiota. This study offers new evidence supporting the use of SP as a prebiotic treatment for NAFLD.
研究领域:
药理学
·
肝病学
·
营养学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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