JOURNAL OF CELLULAR PHYSIOLOGY
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2017
·Vol. 233
·期 9
·6714-6721
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IF 4.08
Haihong Zhou,Congli Jin,Lili Cui,Huaijie Xing,Jun Liu,Wang Liao,Haojie Liao,Yangsheng Yu
This study aimed to investigate whether HMGB1 (high mobility group box-1 protein) and receptor for advanced glycation end products (RAGE) were involved in the irradiation-induced endothelial barrier damage and their mechanism. We constructed the damage model of endothelium barrier model with bEnd.3 cells. The permeability of endothelial barrier was detected by sodium fluorescein (Na-F) permeation test, and the irradiation dose which could induce permeability transition was determined by being exposed to different irradiation doses (5, 10, 15, 20 Gy). MTT assay was applied to detect cell viability under different concentrations of HMGB1 , glycyrrhizic acid (GA, a specific inhibitor of HMGB1 ), and FPS-ZM1 (a blood-brain-barrier permeant blocker of RAGE V domain-mediated ligand binding). The expression of HMGB1 , RAGE, and related molecules involved in MAPK signaling pathway, MMP-2, MMP-9, ZO-1, and claudin 5 of differently treated groups were measured by qRT-PCR, western blot, and immunofluorescence. Cells possessed stable endothelial barrier function on 4–7 days after seeded on transwell plates. The permeability of endothelial barrier would change under at least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the permeability. After irradiation, the expressions of HMGB1 and RAGE increased and MAPK signal pathway was activated. Meanwhile, MMP-2 and MMP-9 were overexpressed, while the expression of tight junction proteins ZO-1 and claudin 5 was decreased. Radiation could activate MAPK signaling pathway through promoting the expression of HMGB1 and RAGE, which further led to endothelial barrier injury and changed its permeability.
研究领域:
细胞生物学
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分子生物学
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医学研究
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DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2021
·
IF 2.319
Jianhua Wu,Lizhen Wu,Li Zhang,Huanhuan Xu,Min Wang,Lin Wang,Jie Chen,Kaiyue Sun
Inflammatory allergic reaction is the main cause of allergic rhinitis (AR). Previous studies indicated that miR-224-5p was downregulated in the nasal mucosa of patients with AR, while the function of miR-224-5p in AR remains unclear. To explore this issue, AR mouse model was established using ovalbumin (OVA). For treatment group, lentivirus (LV)-miR-224-5p or its control was intranasally administrated to AR mice. miR-224-5p expression was detected by reverse transcription-quantitative PCR, followed by assessing the immunoglobulin E (IgE) level. Pathological alterations in nasal mucosa were detected using Hematoxylin-Eosin staining and Sirius red staining, followed by assessing the levels of inflammatory cells and factors. The NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway were measured by Western blot, and then the relationship between miR-224-5p and toll-like receptor 4 (TLR4) was verified. The results showed that miR-224-5p was significantly decreased in nasal mucosa of AR mice. AR mice exhibited increased sneezing and nasal rubbing events, IgE level in serum, and pathological alterations in nasal mucosa, while overexpression of miR-224-5p markedly attenuated these changes. The levels of inflammatory cells in nasal lavage fluid and pro-inflammatory factors in serum and nasal mucosa were significantly increased in AR mice, which were reduced by miR-224-5p overexpression. Of note, LV-miR-224-5p treatment remarkably suppressed the activations of NLRP3 inflammasome and the TLR4/MyD88/NF-κB pathway in AR mice. Furthermore, miR-224-5p could bind to 3’-untranslated region (3’-UTR) of TLR4 and negatively regulate TLR4 level. Overall, we conclude that miR-224-5p may relieve AR by negatively regulating TLR4/MyD88/NF-κB pathway, indicating that miR-224-5p may be a promising target for AR treatment.
研究领域:
免疫学
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分子生物学
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过敏
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药理学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jingchao Li,Shuqi Dai,Ruixue Qin,Changrong Shi,Jiang Ming,Xinying Zeng,Xuejun Wen,Rongqiang Zhuang,Xiaoyuan Chen,Zhide Guo,Xianzhong Zhang
The therapeutic effect of general photodynamic therapy (PDT) is gravely limited by the poor penetration depth of exogenous light radiation. In recent years, Cerenkov radiation (CR) has been exploringly applied to overcome this critical defect. However, the currently reported type I photosensitizers for CR-induced PDT (CRIT) are only TiO2 nanoparticle-based agents with numerous fatally intrinsic drawbacks. Herein, we developed NH2-Ti32O16 nanocluster (NTOC)-derived ultrasmall nanophotosensitizers (NPSs, denoted as TDPs) via innovate ligand engineering. The introduced dopamine (DA) ligands not only facilitate the water solubility and photocatalytic properties of NPSs but also involve the tumor-targeting behavior through the binding affinity with DA receptors on cancer cells. Under CR irradiation, TDPs enable efficient hydroxyl radical (·OH) generation benefiting from the enhanced separation of hole (h+)–electron (e–) pairs, where the h+ will react with H2O to execute type I PDT and the transferred e– can realize the augmentation of Ti3+ to substantially promote the therapeutic index of chemodynamic therapy. This study provides an easy but feasible strategy for constructing versatile NPSs with an ultrasmall framework structure, propounding a refreshing paradigm for implementing efficient CR-induced combined therapy (CRICT) and spurring the development of CR and titanium-familial nanoplatforms in the fields of photocatalysis and nanocatalytic medicine.
研究领域:
纳米技术
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生物医学工程
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放射治疗
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癌症研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 14
·期 2
·361-372
·
IF 7.79
Ruoxi Zhao,Rui Zhang,Lili Feng,Yushan Dong,Jialing Zhou,Songnan Qu,Shili Gai,Dan Yang,He Ding,Piaoping Yang
The construction of nanoplatforms with combined photothermal properties and cascading enzymatic activities has become an active area of anticancer research. However, the overheating of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiOx/CeO2/VOx (SCV) nanoplatform for 1064 nm near-infrared (NIR) triggered mild-temperature PTT and nanozyme catalytic therapy. Firstly, the virus-like shape of SiOx/CeO2/VOx made it favorable for cell adhesion and improved its phagocytosis in cells, and the SCV generated an effective PTT effect upon 1064 nm laser irradiation. Particularly, the produced VO2+ in TME could be used as a heat shock protein inhibitor to inhibit the expression of heat shock protein 60 (HSP60) to enhance the PTT efficiency. Moreover, the SCV nanozyme exhibited obvious peroxidase-mimic (POD) catalytic activity, which could generate highly toxic free radical ions (˙OH) under acidic conditions. The mild-temperature heat and ˙OH produced by enzymatic catalysis effectively blocked the tumor growth, as verified firmly by in vitro and in vivo tests. Our designed virus-like SCV nanozyme with POD mimic enzyme activity and a mild photothermal effect may provide a new way of thinking about the combination therapy model.
研究领域:
纳米医学
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癌症治疗
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材料科学
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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
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·562-570
·
IF 6.331
Shun Liu,Yun Zhao,Meili Shen,Yujiao Hao,Xiaodong Wu,Yixuan Yao,Yapeng Li,Qingbiao Yang
Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical–photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil–water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical–photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.
研究领域:
纳米技术
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药学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
Nanoscale Advances
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2022
·Vol. 4
·期 5
·1414-1421
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IF 5.598
Hui Zhang,Jianping Zhang,Yi Chen,Tianze Wu,Mingzhu Lu,Zhenxia Chen,Yu Jia,Yongtai Yang,Yun Ling,Yaming Zhou
The size modulation of hollow carbon nanospheres (HCSs) has attracted great interest in the contexts of cellular uptake, drug delivery and bioimaging. In this study, a facile fabrication method was specifically used to minimize all influencing factors except for the particle size. A series of nanoparticles of hollow carbon nanospheres embedded with magnetic resonance imaging (MRI) nanoagent γ-Fe2O3 and GdPO4 nanoparticles (Fe–Gd/HCS), were successfully prepared and applied to in vitro/vivo evaluation with well-defined sizes of ∼100 nm (Fe–Gd/HCS-S), ∼200 nm (Fe–Gd/HCS-M), and ∼300 nm (Fe–Gd/HCS-L), respectively. Then the in vitro size effect of Fe–Gd/HCS was systematically investigated by bio-TEM, CLSM, CCK-8 assay, and flow cytometry revealing that Fe–Gd/HCS could be internalized and the cellular uptake amounts increase with the decrease of size. Furthermore, the in vivo size-effect behavior of Fe–Gd/HCS (∼100 nm, ∼200 nm, ∼300 nm) was tracked by MRI technique, demonstrating that all Fe–Gd/HCS can distinguish the liver, in which Fe–Gd/HCS with the smallest particle size exhibited the best performance among these nanoparticles. By leveraging on these features, Fe–Gd/HCS-S (∼100 nm) was further chosen as a theranostic agent, preliminarily presenting its capability for multi-modal imaging and therapy.
研究领域:
纳米医学
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生物材料
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医学影像学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2022
·
IF 3.708
Hanshu Zhao,Yushuang Liu,Nan Chen,Hongyi Yu,Sihan Liu,Meihe Qian,Zhongling Zhang
Cerebral ischemia/reperfusion injury is the main cause of neurological deficit following stroke. Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is increasingly recognized as a critical determinant in immunological regulation and cell apoptosis, but its role in neuroinflammation during cerebral ischemia/reperfusion injury remains to be elucidated. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in C57BL/6 mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in BV-2 cells were used as models in vivo and in vitro , respectively. MACO/R mice and OGD/R cells were treated with scramble or PHLDA1 small interfering RNAs (siRNAs) to achieve the goal of PHLDA1 knockdown. The results showed that the expression of PHLDA1 was significantly increased in MCAO/R mice and OGD/R cells compared to their normal controls, respectively. Mice treated with PHLDA1 siRNA exhibited a lower degree of infarct volume and brain water content compared to the NC siRNA-treated mice. Notably, PHLDA1 knockdown switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by decreasing the expression of M1 markers (i.e., CD16, TNF-α, IL-6 and IFN-γ, and iNOS) and elevating the expression of M2 markers (i.e., CD206, IL-4, IL-10, and Arg-1). Moreover, PHLDA1 knockdown suppressed the NLRP3 inflammasome activation by reducing NLRP3, ASC, cleaved caspase 1 and cleaved IL-1β expression. In summary, these results suggest that PHLDA1 blockade effectively alleviates the ischemia/reperfusion-induced cerebral injury by switching microglial M1/M2 polarization and inhibiting NLRP3 inflammasome activation. Targeting PHLDA1 could be considered as a novel strategy in the treatment against post-ischemic brain injury.
研究领域:
神经科学
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免疫学
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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
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
·
IF 3.712
Yunting Zhang,Yuxi Liu,Jianguang Wang,Zongying Jiang,Lin Zhang,Yong Cui,Danyu Zhao,Yanjie Wang
Objective M2-like tumor-associated macrophages (TAMs) play a crucial role in promoting tumor proliferation, angiogenesis, and metastasis. In the current study, we investigated the relationship between macrophage polarization and the antitumor effect of Atractylenolide II (AT-II) in lung cancer cells.Materials and methods Cell viability, migration, and invasion were determined by MTT assay, wound healing assay, and transwell assay, respectively. Flow cytometry analysis showed the percentage of CD206+ cells. Gene expression was determined by real-time PCR, western blotting, and immunofluorescence staining. Lewis lung carcinoma mouse xenograft and metastasis models were used to examine the effects of AT-II on lung cancer in vivo.Results AT-II (2.5 and 5 µM) did not cause significant inhibition of A549 cell viability but markedly inhibited IL-4/IL-13-induced M2-like polarization, evidenced by the decreased expression of the M2 surface marker CD206, down-regulation of specific M2-marker genes (Arg-1, IL-10 and TGF-β) as well as inhibition of M2 macrophages-mediated invasion and migration of A549 cells. In addition, AT-II inhibited IL-4/IL-13-induced activation of the STAT6 signaling pathway that is vital in the M2-like polarization of macrophages. In animal models, administration of AT-II (50 mg kg−1, i.g., QD for 21 days) significantly inhibited tumor growth, reduced pulmonary metastatic nodules, and down-regulated the percentages of M2 macrophages (F4/80+ and CD206+) in total macrophages (F4/80+) in tumor tissues and pulmonary metastatic nodules.Conclusions AT-II effectively inhibits M2-like polarization, thereby inhibiting lung cancer cell metastasis both in vivo and in vitro, revealing a novel potential strategy for the antitumor effect of AT-II.
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 14
·7529-7539
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IF 6.317
Hongxia Xiu,Yajie Liu,Huihui Yang,Haibin Ren,Bowen Luo,Zhipeng Wang,Hong Shao,Fengzhong Wang,Jingjian Zhang,Yutang Wang
Umami substances can increase the overall taste of food and bring pleasure to people. However, it is still challenging to identify the umami molecules through virtual screening due to the crystal structure of the umami receptor being undefined. Herein, based on the hypothesis that the molecules with bitter and sweet taste characteristics may be umami molecules, this study proposed an in silico method to identify novel umami-tasting molecules in batch from SWEET-DB and BitterDB databases via the QSAR models, PCA, molecular docking and electronic tongue analysis. In total, 169 potential umami molecules were identified through QSAR modeling, PCA, and molecular docking. Of the 169 molecules, 18 were randomly selected, and all were identified as umami molecules via electronic tongue analysis. Among the 18 chosen molecules, 10 molecules could be traced back to their concentration range in food, and finally, 8 molecules were predicted to be nontoxic. This work provides a simple and efficient strategy to identify novel umami molecules, holding an excellent promise for demonstrating the crystal structure of umami receptors and taste-sensing mechanisms. Furthermore, this study opens the possibility for the practical application of new umami molecules in food.
研究领域:
食品科学
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计算生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Ju Liang,Runfa Guo,Maosong Xuan,Qiankun Sun,Wenlan Wu
Purpose This study aimed to construct a DOX conjugate with liver tumor targeting and acid sensitivity based on a short aromatic peptide FFYEE, which could amplify the tumor inhibition efficacy of DOX and alleviate tissue toxicity. Methods A novel DOX-peptide conjugate, D-gal-FFYEE-hyd-DOX, was constructed by linking DOX to the side chain of FFYEE with acid-sensitive hydrazone bond and by modifying the C-terminal of peptide with α-D-galactosamine (D-gal) as targeting ligand. The structure of D-gal-FFYEE-hyd-DOX was characterized by mass spectrometry, infrared spectroscopy (IR), and UV-Vis spectroscopy (UV-Vis). The assembly characteristics of pentapeptide FFYEE and D-gal-FFYEE-hyd-DOX were observed by transmission electron microscope (TEM). In vitro drug release, cytotoxicity, endocytosis, in vivo antitumor experiment and histopathology analysis were investigated. Results Peptide FFYEE endowed the D-gal-FFYEE-hyd-DOX with self-assembly performance and improved biocompatibility. D-gal-FFYEE-hyd-DOX can self-assemble into nanofibers with a diameter of ~ 40 nm in neutral aqueous solution and significantly reduced the cytotoxicity of free DOX to L02 cells. In vitro drug release results showed that D-gal-FFYEE-hyd-DOX had acid sensitivity and controlled release characteristics. The cytotoxicity and endocytosis investigations confirmed that D-gal-FFYEE-hyd-DOX enhanced the cellular uptake of DOX and inhibition effect on HepG2 cells. In vivo antitumor experiment indicated that D-gal-FFYEE-hyd-DOX could significantly inhibit the growth of liver tumor in mice and reduce the side effects of DOX. Conclusion The conjugate D-gal-FFYEE-hyd-DOX with liver tumor targeting and acid sensitivity has the characteristics of strong tumor inhibition and low toxicity, hinting the great clinical application potential for targeted delivery of DOX in cancer treatment.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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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
EXPERIMENTAL EYE RESEARCH
·
2022
·
IF 3.77
Jun Chen,Yizhou Sun,Lei Chen,Yun Zhou
Diabetic retinopathy (DR) is a progressive vascular complication of diabetes mellitus (DM) and is related to retinal vascular abnormalities. NADH-Cytochrome B5 Reductase 2 (CBR2) has been implicated in angiogenesis , but the effect of CBR2 on angiogenesis and endothelial cell biological behavior in DR remains unclear. Here, we aimed to explore the effect of CBR2 on retinal vascular dysfunction under diabetic conditions. The histological analyses were performed to explore the effect of CBR2 on pathological change in streptozotocin (STZ)-induced diabetic rat retinas . The effect of CBR2 on endothelial cell function was explored by CCK-8, scratch wound, transwell, tube formation, and immunofluorescence assays in high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). CBR2 expression was significantly downregulated in DM rat retinas and HG-stimulated HRMECs. Intravitreal injection of CBR2-expressing lentivirus under diabetic conditions reduced retinal angiogenesis, acellular capillary formation, and pericyte loss, along with decreased expression of hypoxia-inducible factor-1α (HIF-1α), cluster of differentiation 31 (CD31), and vascular endothelial growth factor A (VEGFA) in vivo . Moreover, CBR2 overexpression inhibited cell growth and tube formation and led to decreased expression of HIF-1α and VEGFA in HG-induced HRMECs. Interestingly, the repressive effects of CBR2 on cell proliferation , migration, and tube formation under HG conditions were strongly reversed when VEGFA was overexpressed. Overall, the key findings of our study suggested that CBR2 might alleviate retinal vascular dysfunction and abnormal endothelial proliferation during the process of DR by regulating VEGFA, providing a piece of potent evidence for DR therapy.
研究领域:
眼科学
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糖尿病
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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
ACS Applied Bio Materials
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2022
·
IF 0
Tianxing Zhou,Shuangcong Xie,Chunze Zhou,Yiyu Chen,Hong Li,Ping Liu,Rongjian Jiang,Lifeng Hang,Guihua Jiang
Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 μg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.
研究领域:
生物医学工程
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纳米医学
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肿瘤治疗
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产品关联
DOI
PubMed
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