Journal of Materials Chemistry B
·
2024
·
IF 6.1
Maochang Xu,Dan Ran,Jian Hu,Jingying Mao,Dehui Qiao,Zongquan Zhang,Xiaoya Liang,Li Zhang,Yu Nie,Hong Yang,Xiangyu Zhou,Chunhong Li
Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease characterized by the presence of numerous proinflammatory cytokines, massive reactive oxygen species (ROS) and excess lipids, which together result in an overall inflammatory positive feedback loop in the plaque focus. Due to its excellent enzyme-like activity in ROS scavenging and inflammation inhibition, as well as its photothermal effects in the lipid efflux ability of foam cells, Prussian blue (PB) has greater potential in preventing inflammatory factor loops for enhanced treatment of AS than traditional nanozymes. In this study, the multifunctional nanozyme BSA@PB/Cur was synthesized by self-assembly of bovine serum albumin (BSA) with PB and further encapsulation of the anti-inflammatory drug curcumin (Cur). The in vitro results showed that BSA@PB/Cur could effectively scavenge ROS and inhibit the expression of the inflammatory cytokines TNF-α and IL-1β as well as enhance the expression of ABCA1 and ABCG1 in foam cells, promote cholesterol efflux and inhibit foam cell formation. The in vivo experimental results demonstrated that BSA@PB/Cur could target plaque locations, significantly efflux the lipid content, and decrease the matrix metalloproteinase expression. This research provides a potential strategy for alleviating the persistent inflammatory feedback loop within the plaque microenvironment for AS treatment.
研究领域:
医学
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生物化学
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纳米医学
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DOI
PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2024
·
IF 4.4
Hong Guo,Yuanwei Dong,Danqing Luo,Meng Gong,Jianfeng Sun,Zhipeng Wu,Zhixiang Liu,Lei Zhong,Song Jin
Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo , MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.
研究领域:
神经科学
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分子生物学
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针灸
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中风研究
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DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2025
·Vol. 26
·期 1
·1-15
·
IF 5
Wang Yudong,Liu Jun
Background Epithelial–mesenchymal transition (EMT) is regarded as a key process in repair of airway epithelium after injury. Forkhead Box C2 (FOXC2) is a transcription factor involved in EMT process, whether it is involved in repair of bronchial epithelium remains unknown.Methods C57BL/6 mice were subjected to intraperitoneal injection with naphthalene (NAPH; 200 mg/kg) to induce airway injury model. qPCR, immunoblot and FOXC2 immunohistochemistry assays were conducted to detect the expression of FOXC2 in bronchial epithelium. To explore the function of FOXC2 in NAPH-induced airway injury, the mice were given intratracheal administration of shFOXC2- or shNC-lentivirus particles, followed by NAPH treatment. Hematoxylin-and-eosin staining was used to assess the histopathology of the bronchial epithelium. Immunofluorescence analysis of CCSP, a club cell marker confirmed the CCSP expression in bronchial epithelium. Immunoblot and immunofluorescence assays determined the expression of E-cadherin, vimentin, and N-cadherin. In mouse primary bronchial epithelial cells (PBECs), we overexpressed and silenced FOXC2 by lentivirus particles, respectively. Cell migration was analyzed using wound healing assay. Immunoblot assays determined the E-cadherin, vimentin, FN-EDA expression in TGF-β1-induced PBECs. mRNA sequencing (mRNA-seq) and FOXC2 ChIP sequencing (ChIP-seq) to reveal the downstream genes of FOXC2 in TGF-β1-induced PBECs. Luciferase assay, ChIP-PCR and functional rescue experiments were performed to confirm the interaction of FOXC2/formin binding protein 1 (FNBP1) in TGF-β1-induced PBECs.Results FOXC2 expression was up-regulated in the lung tissues of mice at 2, 3 and 6 days post-NAPH. FOXC2 knockdown in bronchial epithelium of mice delayed CCSP+ club cell regeneration and normal repair of the airway epithelium within 14 days after injury. Knockdown of FOXC2 increased E-cadherin but decreased vimentin and N-cadherin, EMT markers during early phase after injury. In vitro, knockdown of endogenous FOXC2 repressed the migration of cells and increased TGF-β1-induced E-cadherin but decreased vimentin, N-cadherin and FN-EDA. Exogenous FOXC2 addition exerted opposite effects. Furthermore, mRNA-seq and FOXC2 ChIP-seq revealed that FNBP1 might be a downstream target of FOXC2. Overexpression of FNBP1 reversed the inhibitory role of FOXC2 knockdown in EMT.Conclusion sThese data highlight the important function of FOXC2 as a regulator in repair of bronchial epithelium after injury.Graphical
研究领域:
分子生物学
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呼吸系统疾病
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病理学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Shuting Zhang,Hong Zhou,Xuan Chen,Shasha Zhu,Dan Chen,Dan Luo,Siyuan Chen,Wei Liu
Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, β-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.
研究领域:
药学
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纳米技术
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皮肤科
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
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IF 5.4
Liqin Xie,Xirui Zuo,Beilei Wang,Dan Li,Wenke Chang,Shenglu Ji,Dan Ding
Using the coordination bonds between transition metal atoms and electron-rich functional groups, we synthesized two kinds of micelle-like nanoparticles. Using magnetic Fe3O4 as the core, poly(methyl methacrylate) (PMMA) and poly(acrylic acid) (PAA) brushes were grafted via activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP), which formed micelle-like magnetic nanoparticles Fe3O4/PAA–PMMA with a hydrophobic outer layer and Fe3O4/PMMA–PAA with a hydrophilic outer layer. Both the micelle-like nanoparticles had amphiphilic properties and can be used to load hydrophilic or hydrophobic drugs. Even loaded with hydrophobic drugs, the micelle-like nanoparticles can still be dispersed in aqueous solution, and Fe3O4/PAA–PMMA had a higher loading content. As the drug carrier, these two micelle-like nanoparticles can be used for magnetically targeted drug delivery and magnetic resonance imaging due to superparamagnetic Fe3O4. In addition, due to the magnetic retention effect, the drug-loaded micelle-like nanoparticles remained at the tumor site, increasing the local drug concentration. At the same time, the drug-loaded micelle-like nanoparticles generated a magnetocaloric effect under the alternating magnetic field, which not only killed tumor cells by magnetic hyperthermia but also promoted the rapid release of drugs at the tumor site. In general, magnetically enhanced chemotherapy showed the best therapeutic effect on tumors.
研究领域:
生物材料学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
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2024
·Vol. 30
·期 10
·e70076
·
IF 4.8
Jing An,Lulu Wen,Haiyang Yu,Zhongqi Bu,Juan Feng
Aims Insulin-like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear. Methods PD rat model was established by 6-OHDA injection. After 3 weeks, mRNA-seq was conducted. Rats received rIGFBP2 via intra-MFB injection 6 h prior to 6-OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC-1 staining, and TUNEL analysis. In vitro, PC12 cells were treated with 6-OHDA, and CCK-8, specific kits, Hoechst 33258 staining, Western blotting, and JC-1 staining were performed to assess the IGFBP2's role. Results mRNA-seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, Ψm, ATP level and SOD, GSH-Px activities but increased α-synuclein, ROS, MDA, mitochondrial cytochrome c contents, cell apoptosis in 6-OHDA-lesioned rats, which might be mediated through inactivating IGF-1R/AKT pathway. In 6-OHDA-treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co-treatment with rIGFBP2 and rIGF-1 partially reversed the effect of rIGFBP2 on cell damage. Conclusion IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF-1R/AKT pathway.
研究领域:
神经科学
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分子生物学
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药理学
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病理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Xinxin Si,Quan Zhang,Bo Ning,Lei Qiang,Qiang Li,Yihao Liu,Minjie Fan,Jing Shan,Guanlu Shen,Zichen Lin,Pengfei Zheng
The growth plate is vital for childhood development, and most of the injuries can formation of bone bridges on it, which has negative impact on limb development. Current biomaterial scaffolds often lack essential cartilage matrix components, which hurdles to get an acceptable regeneration. Additionally, stem cell transplantation faces challenges including high apoptosis rates and uncertain differentiation. Then, we designed an injectable composite hydrogel (Exo-AMG) loaded with exosomes (Exo) and composed of methacrylate-modified acellular cartilage matrix (ACMMA) and gelatin methacrylate (GelMA) to repair the growth plate for children and adolescents. The hydrogel is administered via minimally invasive injection and undergoes in-situ photocrosslinking to fill the growth plate defects. It exhibited suitable mechanical properties, biodegradation rates; it also could sustain exosome release. Moreover, it promoted M2 macrophage polarization and secretion of anti-inflammatory factors, and it enhanced bone mesenchymal stem cells (BMSCs) proliferation and chondrogenic differentiation in vitro . In vivo study, this Exo-AMG induced growth plate cartilage regeneration without bone bridge formation. Therefore, this injectable and in-situ photocrosslinkable composite hydrogel is promising on growth plate injury repair by alleviating inflammation and promoting chondrogenic differentiation.
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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骨科
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产品关联
DOI
高影响因子
Human Cell
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2024
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IF 3.4
Cao Yue,Xing Ruixian,Li Qiushi,Bai Yang,Liu Xuewen,Tian Buxian,Li Xin
Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood–brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90 min and reperfusion (R) for 48 h. Then AAV2-shTFPI2 particles (5 × 10 10 vg) were injected into the right lateral ventricle of rats 3 weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6 h and reoxygenation (R) for 18 h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.
研究领域:
神经科学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
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2025
·
IF 4.7
Xiaoxuan Liu,Dafei Yu,Yujun Wang,Na Li,Kuo Wang,Yingnan Yang,Na Liu
Some pathogenic microorganisms can survive and spread as bioaerosols which is a serious threat to human health. Hence, a visible light-assisted photocatalytic inactivation system for bioaerosol inactivation was constructed based on the novel P/Ag/Ag 2 O/Ag 3 PO 4 /TiO 2 (PAgT) composite photocatalyst. The highest inactivation efficiency for 10 8 CFU/m 3 Escherichia coli bioaerosol could reach 99.3 % within just 14.1 s under visible light irradiation. The effect of various operational conditions on photocatalytic inactivation efficiency were investigated, including light intensity, bioaerosol concentration and residence time. Furthermore, during the bioaerosol inactivation process, the changes of cell morphology and intracellular reactive oxygen species were clarified. The oxidizing substances h + , O 2 − and OH produced on the surface of the photocatalyst under the irradiation of visible light were the direct cause of cell oxidizing damage. It disrupted cell membrane permeability and cause an increase in intracellular reactive oxygen species, ultimately leading to cell death. The system possessed an irreversible and efficient photocatalytic bioaerosol sterilization ability toward different airborne pathogenic bacteria, including Gram-positive and Gram-negative bacteria. In addition, the PAgT photocatalytic system demonstrated good cyclability and stability for bioaerosol inactivation, providing a promising strategy to reduce the airborne pathogenic microbial contamination, especially for indoor or occupied space.
研究领域:
环境科学
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微生物学
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材料科学
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产品关联
DOI
高影响因子
NEUROSCIENCE
·
2024
·
IF 2.9
Xinyue Zhang,Xiao Wang,Le Yin,Dan Wang,Hong Jiao,Xiaodan Liu,Jiaolin Zheng
HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia–reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. Here, we used the transient middle cerebral artery occlusion-reperfusion (tMCAO/R) model to induce CIRI in rats and found lower HACE1 expression in ischemic rats compared with the control. To explore the exact role of HACE1, the lentivirus vector carrying the HACE1 sequence was administrated to rats by intracerebroventricular injection (1 × 10 9 TU/mL, 9 μL) one week before tMCAO/R operation. HACE1 overexpression alleviated tMCAO/R-induced brain damage in rats. Further studies revealed that it reduced oxidative stress via activating the PI3K/AKT/Nrf2 pathway, thereby inhibiting neuronal apoptosis in the ischemic penumbra of rats with CIRI. Then, differentiated PC12 cells were cultured in oxygen-glucose deprivation-reoxygenation (OGD/R) conditions (OGD: 1 % O 2 , 94 % N2, and 5 % CO 2 ; R: normal atmosphere) to simulate CIRI in vitro . Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.
研究领域:
神经科学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2025
·
IF 3.6
Lei Wei,Zonggang Feng,Qian Dou,Genhong Mao,Hu Zhao,Xinghua Zhao,Bin Hao
Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10 7 TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders in vitro . Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis via the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.
研究领域:
生殖毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Shaofang Ma,Yan Zhang,Zihan Zhu,Deping Wang,Xin Zhou,Jing Wang,Wei Bian,Xinjing Tang
The low cure rate and high mortality associated with cancer pose significant threats to human health. Photodynamic and photothermal therapies have emerged as promising treatment strategies for various types of cancers. In this study, we successfully synthesized a novel type of carbon dot (CD) using 1,2,4-aminobenzene and ethylenediamine as precursors. Surprisingly, these CDs exhibited outstanding nucleolus-targeting capabilities coupled with a remarkable photothermal effect. Through the integration of these nucleolus-targeting CDs with indocyanine green (ICG) and folic acid (FA), we created CDs-ICG-FA nanocomplexes suitable for combined photodynamic and photothermal therapy. In vitro experiments demonstrated that CDs-ICG-FA maintained a robust photothermal ability, achieving a conversion efficiency of up to 34.3%. Furthermore, CDs-ICG-FA generated abundant reactive oxygen species, effectively inducing cancer cell death and demonstrating its potential for photodynamic therapy. In MCF-7 cancer cells, CDs-ICG-FA exhibited a pronounced synergistic photothermal/photodynamic anticancer effect. Subsequent in vivo experiments in mice revealed that CDs-ICG-FA could selectively accumulate at tumor sites, significantly inhibiting tumor growth upon exposure to an 808 nm laser. These findings suggest that the developed nucleolus-targeting CDs-ICG-FA hold promising potential for cancer targeting and the application of combined photothermal/photodynamic therapy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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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）