Small
·
2021
·Vol. 17
·期 36
·2102879
·
IF 13.281
Nanzhu Nie,Dan Zhang,Zuochao Wang,Yingnan Qin,Xuejun Zhai,Bo Yang,Jianping Lai,Lei Wang
At present, it is still a great challenge to synthesize refractory Pt-based electrocatalysts with excellent active specific surface area, specific activity, and stability by a simple method. Here, a superfast and solvent-free microwave strategy is reported to synthesize refractory ultrafine (≈3 nm) Pt–lanthanide@Ketjen Black (PtM@KB, M = La, Gd, Tb, Er, Tm, and Yb) alloy with densely packed as efficient hydrogen evolution electrocatalysts in a domestic microwave oven for the first time. The optimized Pt 61 La 39 @KB delivers excellent hydrogen evolution reaction (HER) activity with a low overpotential of 38 mV (10 mA cm −2 ) and a high TOF value of 44.13 s −1 (100 mV) in 0.5 m H 2 SO 4 , and performs well in 1.0 m KOH. This method can also be used to grow catalysts on carbon cloth (CC) directly. PtLa@CC shows an overpotential of 99 mV (1000 mA cm −2 ) in 0.5 m H 2 SO 4 and can maintain activity after 500 h. Theoretical calculations reveal the enhanced stability and activity owing to the higher vacancy formation energy of Pt atoms and the optimized value of Δ G H* . Solvent-free microwave strategy constitutes a significant insight into the development of refractory electrocatalyst with ultrafine size and highly dense, which can also work well at high current densities.
研究领域:
材料科学
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电化学
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能源催化
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-22
·
IF 10.6
Jiang Hua,Qin Hongyu,Yang Qinghua,Huang Longao,Liang Xiao,Wang Congyang,Moro Abu,Xu Sheng,Wei Qingjun
Background The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. Methods The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. Results We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. Conclusions NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD. Graphical Abstract
研究领域:
骨科
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基因治疗
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Peng Zhang,Xinfang Li,Qinan Xu,Youxiang Wang,Jian Ji
The combination of photothermal therapy and gene therapy has received increasing attention in tumor treatment. However, how to improve synergistic efficacy has become a new challenge. NIR light has a great potential in tumor treatment because of its considerable penetration depth and spatiotemporal controllability. Polydopamine is a popular photothermal conversion agent, which has desirable photothermal conversion ability and good biocompatibility. In this research, polydopamine-polyethyleneimine nanoparticles with diameters of 13 nm (SPPNPs) and 236 nm (LPPNPs) were prepared as gene carriers. The size of polydopamine nanoparticles had great effect on the complexes formation, photothermal conversion ability and gene transfection efficiency. After loading gene, the SPPNPs/gene and LPPNPs/gene complexes were about 60–80 nm and 240 nm respectively, indicating different styles of complexes formation. Both SPPNPs/gene and LPPNPs/gene complexes without NIR irradiation could achieve similar gene transfection efficiency as commercial lipofectamine 2000, while with lower cytotoxicity. Due to better photothermal conversion ability, the transfection level of LPPNPs/pGL-3 complexes increased to 4.5 times after NIR irradiation (2.6 W/cm 2 , 15 min), which ascribed to the quick escape of gene complexes from the endosome. The produced heat under NIR irradiation could also ablate tumor cells. So LPPNPs were chosen to deliver tumor suppressor gene p53 DNA to investigate the synergistic efficacy of gene/photothermal therapy. The tumor in KB tumor-bearing mice was almost eliminated after intratumoral injection, and the tumor inhibition efficacy of gene/photothermal synergistic therapy achieved to 99%. By combining NIR-promoted gene transfection and gene/photothermal synergistic therapy, the LPPNPs hold great promise in practical tumor treatment.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yujie Chen,Zhaode Mu,Jianli Zuo,Min Qing,Jing Zhou,Lijuan Bai
A novel aptasensor for the detection of kanamycin (KNM) was developed based on dual signal amplification through nanomaterials and DNA rolling machines. Firstly, a composite consisting of the covalent organic framework (COF), ketjen black (KB) and toluidine blue (Tb), was synthesized for signal generation. Tb molecules were loaded into the composite and combined with AuNPs to serve as tracer label. Secondly, the wDNA-loaded Fe 3 O 4 magnetic beads (wDNA@MBs) as the DNA walking legs, with cleavage by Mg 2+ -driven DNAzyme, the DNA walking legs can move along the sDNA-decorated MBs surface, converting the target KNM into numerous output DNA strand, achieving sensitive amplification. With a low detection limit of 0.66 fM and a wide linear dynamic range from 10 fM to 100 nM, this aptasensor showed good results in the detection of KNM in real samples. Therefore, we envision it can provide a useful method for KNM detection in actual samples.
研究领域:
生物化学
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食品科学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Chen Lexian,Lv Qianqian,Cai Jianghong,Liang Jiajie,Liang Ziyan,Lin Jiahui,Xiao Ying,Chen Ruiyao,Zhang Zhiling,Hong Yue,Ji Hong
Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.
研究领域:
药理学
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肿瘤学
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化学
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细胞生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Hongyan Li,Yiying Fu,Wangbao Gong,Guangjun Wang,Zhifei Li,Jingjing Tian,Kai Zhang,Ermeng Yu,Yun Xia,Wenping Xie,Jun Xie
The pregnane X receptor (PXR) / nuclear factor-kB (NF-kB) signaling pathway plays a critical role in regulating toxin-induced inflammation and apoptosis in mammals. Whether dietary curcumin (CUR) can prevent copper (Cu)-induced liver injury via this signaling pathway remains to be established in aquatic animals. Juvenile largemouth bass ( Micropterus salmoides ) were exposed to dietary Cu and CUR treatments for 8 weeks. The results showed that chronic Cu exposure induced oxidative stress, causing liver function damage and liver injury. Cu exposure stimulated inflammation by regulating nf-kb and pro-inflammatory genes such as tnfα and il-1β and promoted apoptotic signals in the liver by modulating bcl2 and casp3 mRNA levels. In addition, Pearson correlation analysis verified that inflammatory and apoptotic responses were important indicators of Cu-induced liver injury. CUR attenuated stress responses by enhancing the antioxidant system. Importantly, CUR significantly stimulated PXR mRNA and protein levels in the Cu + CUR group and suppressed NF-κB activation to inhibit the inflammatory and apoptotic signaling cascade. These results suggest that CUR may be an effective activator of PXR in teleost fishes, exerting cytoprotective effects on Cu-induced liver injury via a PXR-mediated NF-κB repression mechanism. In conclusion, this study is the first to demonstrate that CUR may act as a potent PXR ligand that exerts hepatoprotective effects against Cu-induced liver injury. The findings shed light on the specific regulatory role of the PXR/NF-κB signaling pathway in liver pathogenesis and its potential as a therapeutic target in teleost fishes.
研究领域:
水生毒理学
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分子生物学
·
营养学
✓ 已验证
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2016
·
IF 3.584
Chongshan Dai,Bin Li,Yan Zhou,Daowen Li,Shen Zhang,Hui Li,Xilong Xiao,Shusheng Tang
The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress , mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX , a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.
研究领域:
药理学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2022
·
IF 4.369
Dandan Wang,Yixin Zhang,Liangyi Cui,Qing Yang,Jiao Wang
Endometriosis , defined as the abnormal growth of functional endometrium outside the uterus , is characterized by the abnormal phenotype of endometrial cells. This study aimed to investigate the role of latent transforming growth factor beta binding protein 2 (LTBP2), an extracellular matrix protein , in the occurrence and development of endometriosis. Elevated LTBP2 expression levels were observed in endometrial tissues and serum of endometriosis patients and their area under the ROC curve (AUC) values for distinguishing endometriosis were 0.9044 and 0.9534, respectively. Overexpressing-LTBP2 could promote proliferation, migration, and invasion, whereas suppressing apoptosis of endometrial stromal cells (ESCs). Moreover, LTBP2 downregulation induced the opposite effect. The supernatant from ESCs overexpressing LTBP2 promoted the tube formation of human umbilical vein endothelial cells (HUVECs), thus indicating an angiogenic effect. Furthermore, overexpression of LTBP2 facilitated the inflammation and might promote endometriosis progression through the NF- k B signaling pathway . Conclusively, LTBP2 might be a potential target in the diagnosis and treatment of endometriosis.
研究领域:
妇科学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INVESTIGATIVE DERMATOLOGY
·
2023
·
IF 6.5
Qinqin Meng,Mei Bai,Meiliang Guo,Zhengxiao Li,Wanwen Liu,Xiaojing Fan,Rui Sun,Xinrong Yang,Dingfen Yuan,Yuling Shi,Hui Deng
Although the anti-inflammatory effect of serum- and glucocorticoid-regulated protein kinase 1 (SGK1) has been established in other diseases, the possible regulatory role of SGK1 in psoriasis and the underlying molecular mechanisms remain largely unknown. In this study, we found that SGK1 expression was decreased in macrophages from patients with psoriasis. Moreover, a specific pharmacological SGK1 inhibitor, EMD638683, significantly enhanced imiquimod-mediated toll-like receptor 7/8 activity and proinflammatory cytokine production in RAW264.7 cells, and this result was confirmed by Sgk1 small interfering RNA . Further mechanistic data showed that SGK1 inhibition increased the phosphorylation of Bruton’s agammaglobulinemia tyrosine kinase ; moreover, Bruton’s agammaglobulinemia tyrosine kinase inhibition abrogated the proinflammatory effects of the SGK1 inhibitor on toll-like receptor 7/8 activation, thereby validating that SGK1 inhibition enhances the toll-like receptor 7/8 pathway by increasing Bruton’s agammaglobulinemia tyrosine kinase phosphorylation. In addition, our in vivo results showed that SGK1 inhibition significantly increased the secretion of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the infiltration of T helper 17 cells in an imiquimod-induced psoriasis mouse model. Altogether, these results show that SGK1 plays a critical role in the pathogenesis of psoriasis by modulating inflammatory responses in skin lesions , indicating that SGK1‒Bruton’s agammaglobulinemia tyrosine kinase signaling could be a novel therapeutic target for the control of psoriasis.
研究领域:
免疫学
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皮肤病学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Jun Ma,Peng Yang,Zhibin Zhou,Tengfei Song,Liang Jia,Xiaofei Ye,Wei Yan,Jiuyi Sun,Tianwen Ye,Lei Zhu
Introduction Osteoarthritis (OA) is the most common arthritis that is characterized by the progressive synovial inflammation and loss of articular cartilage. Although GYY4137 is a novel and slow-releasing hydrogen sulfide (H 2 S) donor with potent anti-inflammatory properties that may modulate the progression of OA, its underlying mechanism remains unclear. Objectives In this study, we validated the protective role of GYY4137 against OA pathological courses and elucidated its underlying regulatory mechanisms. Methods Cell transfection, immunofluorescence staining, EdU assay, transmission electron microscopy, mitochondrial membrane potential measurement, electrophoretic mobility shift assay, sulfhydration assay, qPCR and western blot assays were performed in the primary mouse chondrocytes or the mouse macrophage cell line raw 264.7 for in vitro study. DMM-induced OA mice model and Macrophage-specific p65 knockout (p65 f/f LysM-CreER T2 ) mice on the C57BL/6 background were used for in vivo study. Results We found that GYY4137 can alleviate OA progress by suppressing synovium pyroptosis in vivo. Moreover, our in vitro data revealed that GYY4137 attenuates inflammation-induced NLRP3 and caspase-1 activation and results in a decrease of IL-1β production in macrophages. Mechanistically, GYY4137 increased persulfidation of NF-kB p65 in response to inflammatory stimuli that results in a decrease of cellular reactive oxygen species (ROS) accumulation and ameliorates mitochondrial dysfunctions. Using site-directed mutagenesis, we showed that H 2 S persulfidates cysteine38 in p65 protein and hampers p65 transcriptional activity, and p65 mutant impaired macrophage responses to GYY4137. Conclusion These findings suggest a mechanism by which GYY4137 through redox modification of p65 participates in inhibiting NLRP3 activation by OA to regulate inflammatory responses. Thus, we propose that GYY4137 represents a promising novel therapeutic strategy for the treatment of OA.
研究领域:
风湿病学
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免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 94
·51950-51959
·
IF 3.708
Jie Feng,Di Chang,Zhifei Wang,Bin Shen,Jinjin Yang,Yanyun Jiang,Shenghong Ju,Nongyue He
Dual-modal imaging contrast agents with unique X-ray computed tomography (CT) and optical imaging capabilities have attracted much attention in recent years. Herein, the new silica hybrid nanocomposites containing Au nanoparticles and FITC dyes (FITC–Au@SiO2) were investigated as this kind of contrast agent. TEM characterization showed that the as-synthesized FITC–Au@SiO2 nanoprobes were uniform in morphology with the average size of 90 nm. After the PEGylation, the obtained FITC–Au@SiO2@PEG exhibited good dispersion stability under different conditions. The MTT assay suggested that FITC–Au@SiO2@PEG didn't show appreciable toxicity toward KB cells even at high concentration of up to 1000 μg mL−1. In addition, it was found that FITC–Au@SiO2@PEG could cross the cell membrane and enter into the cytoplasm during the incubation with cells. In vivo dual modal optical/CT imaging of C57BL/6J mice uncovered that within 2 h post-injection FITC–Au@SiO2@PEG nanoprobes preferred to accumulate in the liver and were gradually cleared through the enterohepatic circulation system, which could bring novel opportunities to the next generation of dual-modality contrast agents.
研究领域:
纳米技术
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生物医学工程
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医学成像
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产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Zhiruo Fang,Yu Yao,Liping Cao,Jiancao Gao,Quanjie Li,Zhijuan Nie,Yi Sun,Gangchun Xu,Jinliang Du
This study investigated the toxicological mechanism of deltamethrin on Chinese mitten crab Eriocheir sinensis juveniles in fresh water. We first conducted an acute toxicity test, followed by laboratory methods to detect changes in immune-related indices in terms of antioxidant enzyme markers, lipid metabolism-related genes, and autophagy-related and apoptosis genes. The acute toxicity (96-h LC50) of deltamethrin to E. sinensis was 7.195 μg/L. After 48 h of exposure, serum showed elevated immune-related indices ( P < 0.05) for alkaline phosphatase (AKP), acid phosphatase (ACP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), complement components C3 and C4, and the key pro-inflammatory cytokines interleukin-6, interleukin-1β, and tumor necrosis factor alpha (TNF-α). In hepatopancreas at 48 h, indicators related to the antioxidant system, namely superoxide dismutase (SOD) and glutathione (GSH), were significantly elevated, whereas nitric oxide and total antioxidant capacity (T-AOC) were decreased ( P < 0.05). In contrast, lipid metabolism indices for triglyceride (TG), total cholesterol (TC), and malondialdehyde (MDA) were increased ( P < 0.05). Transcriptomics and metabolomics revealed that exposure to deltamethrin disrupted the lipid metabolic process in the hepatopancreas mainly by altering fatty acid synthesis, amino acid metabolism, immune signaling, and autophagy activation, while the exposure increased the content of phospholipids and cholesterol but decreased the levels of amino acids and palmitoleic acid. Quantitative genetics revealed significantly aberrantly expressed ( P < 0.05) lipid metabolism-related genes, including acc1 , fasn , scd1 , and pnpla2 , all key genes involved in lipid accumulation. Deltamethrin exposure also significantly altered ( P < 0.05) gene expression levels for Toll-like receptor ( tlr ), myeloid differentiation factor 88 ( myd88 ), crustin1 , anti-lipopolysaccharide factor isoform 3 ( alf3 ), tumor necrosis factor alpha ( tnf-α ), and NF-κB transcription factor relish . Furthermore, deltamethrin activated the toll-like receptor/major myeloid differentiation response gene 88/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/MyD88/NF-kB) signaling pathway, which activates a nonspecific immune response in E. sinensis . Additionally, carnitine palmitoyltransferase 1 A ( cpt1a ), cytochrome c ( cyt-c ), adenosine 5′-monophosphate (amp)-activated protein kinase ( ampk ), the autophagosomal protein microtubule-associated protein 1 light chain 3c ( lc3c ), and the autophagy-related proteins beclin1 , atg5 , atg12 were significantly induced ( P < 0.05) in the adenosine monophosphate-activated protein kinase/rapamycin (AMPK/mTOR) signaling pathway. These changes resulted in excess free radicals, causing oxidative stress in the mitochondrial membrane, promoting mitochondrial autophagy. The results confirm that deltamethrin exposure can induce hepatopancreatic injury by promoting mitochondrial autophagy, activating an immune response, and inhibiting lipid metabolism. Overall, this study provides multi-level information to reveal the toxic effects of deltamethrin on E. sinensis .
研究领域:
毒理学
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分子生物学
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环境科学
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水生生物学
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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）