Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Wang Huirui,You Xiaona,Wang Jingcheng,Chen Xinyi,Gao Yinghui,Wang Mengmeng,Zhang Wenru,Zhang Jiaozhen,Yu Yang,Han Bo,Qi Mei,Liu Xiaohui,Lou Hongxiang,Dong Ting
Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C −/− mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.
研究领域:
分子生物学
·
细胞生物学
·
药理学
·
病理学
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DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Yang Zhang,Fangqiu Fu,Qiao Zhang,Lingling Li,Hui Liu,Chaoqiang Deng,Qianqian Xue,Yue Zhao,Wenrui Sun,Han Han,Zhendong Gao,Chunmei Guo,Qiang Zheng,Hong Hu,Yihua Sun,Yuan Li,Chen Ding,Haiquan Chen
Summary Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.
研究领域:
肿瘤学
·
基因组学
·
蛋白质组学
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癌症生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Qiang Shi,Jian-Gang Ju
Circular RNA (circRNA) is considered an important regulator of cancer. Circ_0001998 is a newly discovered circRNA and its role in lung adenocarcinoma (LUAD) remains obscure and requires further study. The expression levels of circ_0001998 and miR-145 in LUAD were predicted by bioinformatics analysis and then verified by qRT-PCR in the LUAD cell lines. CCK-8, clone formation, EdU assay, and flow cytometry were applied to determine the effects of silencing circ_0001998 on the viability, proliferation, and apoptosis of LUAD cells. The target relationship between circ_0001998 and miR-145 was predicted by bioinformatics analysis and verified by a luciferase activity experiment. The effect of circ_0001998/miR-145 axis on the viability, proliferation, and apoptosis of LUAD cells was verified by the rescue experiment. Circ_0001998 was upregulated in LUAD, and silencing circ_0001998 suppressed viability, proliferation, and invasion of LUAD cells. The target gene of circ_0001998, miR-145, was downregulated in LUAD, and the low expression of miR-145 indicated a poor prognosis. The effect of silencing circ_0001998 on the biological function of LUAD cells was reversed by the miR-145 inhibitor. Circ_0001998 regulates the proliferation, invasion, and apoptosis of LUAD via sponging miR-145.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
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DOI
PubMed
高影响因子
Nanoscale
·
2016
·Vol. 9
·期 1
·334-340
·
IF 7.76
Meng Yang,Yanlei Liu,Wenxiu Hou,Xiao Zhi,Chunlei Zhang,Xinquan Jiang,Fei Pan,Yuming Yang,Jian Ni,Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer. Our results showed that the tumor cells were efficiently killed by the heat generated from the gold nanorods, and the iPS cells ultimately died due to the action of MMC seven days after the photothermal treatment. This suggested that pre-treated iPS cells with MMC can be used as a novel and safe approach for targeted tumor therapy. This paves the road for clinical translation in the future.
研究领域:
生物医学工程
·
癌症研究
·
纳米技术
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Biomedical Materials
·
2025
·Vol. 20
·期 5
·055009
·
IF 3.7
Yunguo Liao,Hong Hu,Ziyu Tang,Dan Deng,Chao Li
This study presents a novel electrochemical aptasensor utilizing polydopamine–graphene (PDA–G) nanocomposite for VEGF165 detection. The PDA–G nanocomposite was synthesized through a one-step self-polymerization process and characterized by SEM, XPS, and FTIR, confirming successful PDA coating on graphene sheets with 22.3% C–N bond incorporation. Electrochemical characterization confirmed stepwise increases in charge transfer resistance (Rct), and quantitative detection was based on ΔRct (the change in Rct before vs. after VEGF165 binding). Under optimized conditions (pH 7.4, 37 °C, 30 min incubation), the sensor demonstrated dual-linear response regions with high sensitivity. Analysis of clinical samples showed minimal matrix effects with a 1:4 dilution ratio, and endogenous VEGF165 levels in healthy donor serum were determined to be 28.4 ± 3.2 pg ml−1. The method’s practicality was validated through comprehensive interference studies, with common serum proteins generating relative responses below 5.2% compared to the target.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Tao-Tao Fu,Zhao-Qing Cong,Yun Zhao,Wei-Ya Chen,Chun-Yu Liu,Ying Zheng,Fei-Fei Yang,Yong-Hong Liao
This study intended to investigate the in vivo pulmonary fate of intratracheally dosed nanosuspensions of fluticasone propionate (FP). Three FP suspensions, including a microsuspension and two nanosuspensions with different dissolution profiles, were prepared and they exhibited comparable aerodynamic performances after nebulization via a jet nebulizer . Following intratracheal administration to rats, the microsuspension underwent extensive mucociliary clearance, leading to a limited absorption time whereas the nanosuspensions decreased the mucociliary clearance and allowed dissolution rate-limiting and extended pulmonary absorption, resulting in prolonged pulmonary retention and long-acting anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model. Delaying the FP dissolution of a nanosuspension by phospholipid coating increased AUC value in lung tissues to 1.72-fold of a conventional nanosuspension, but led to a decreased pharmacological efficacy. This study demonstrated that inhalable nanosuspensions were a feasible means for the sustained pulmonary delivery of FP and the local anti-inflammatory efficacy was highly dependent on the dissolution profiles.
研究领域:
药剂学
·
药理学
·
纳米技术
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Shang Liu,Zhenzhen Wang,Xinbang Jiang,Jingjing Gan,Xuejiao Tian,Zhen Xing,Yiqing Yan,Jiahui Chen,Junfeng Zhang,Chunming Wang,Lei Dong
Biomolecular corona formed on nanoparticles (NPs) influences the latter's in vivo biological effects. Nanomaterials with different physicochemical properties exert similar adverse effects, such as cytotoxicity, suggesting the existence of ubiquitous signals during various corona formations that mediate common and fundamental cellular events. Here, we discover the involvement of the unfolded protein response (UPR) and recruited chaperones in the corona. Specially, heat shock protein 90 kDa α class B member 1 (Hsp90ab1) is abundantly enriched in the corona, accompanied by substantial aggregation of misfolded protein on particles intracellularly. Further analysis reveals the particulate matter 2.5 (PM2.5) and metal-containing particles are more capable of denaturing proteins. The recruited Hsp90ab1 activates diverse NPs' pathological behaviour by heat stress response (HSR), which were significantly reversed by geldanamycin (GA), the inhibitor of Hsp90ab1. Murine lung inflammation induced by PM2.5 and iron oxide NPs (Fe 3 O 4 NPs) is suppressed by GA, highlighting that Hsp90ab1-mediated UPR is a potential target for the treatment of environmental pollution-related illnesses. Based on our findings, the UPR and Hsp90ab1 presented in the corona of particles initiate fundamental intracellular reactions that lead to common pathological outcomes, which may provide new insights for understanding nanotoxicity and designing therapeutic approaches for diseases associated with environmental pollution.
研究领域:
纳米技术
·
毒理学
·
环境科学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Tingting Lv,Ziying Li,Liang Xu,Yingying Zhang,Haijun Chen,Yu Gao
Although novel molecular targeted drugs have been recognized as an effective therapy for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, their efficacy fails to meet the expectation due to the acquired resistance in tumors. Up-regulation of the anti-apoptotic protein Survivin was shown to contribute to the resistance to EGFR tyrosine kinase inhibitors (TKI) in EGFR mutation–positive NSCLC. However, the unorganized tumor blood vessels impeded drug penetration into tumor tissue. The resulting insufficient intracellular drug/gene delivery in drug-resistant cancer cells remarkably weakened the drug efficacy in NSCLC. In this work, a multi-functional drug delivery system AP/ES was developed by using anti-EGFR aptamer (Apt)-modified polyamidoamine to co-deliver erlotinib and Survivin-shRNA. Chloroquine (CQ) was used in combination with AP/ES to normalize tumor vessels for sufficient drug/gene delivery to overcome drug resistance in NSCLC cells. The obtained AP/ES possessed desired physicochemical properties, good biostability , controlled drug release profiles, and strong selectivity to EGFR-mutated NSCLC mediated by Apt. CQ not only enhanced endosomal escape ability of AP/ES for efficient gene transfection to inhibit Survivin, but also showed strong vessel-normalization ability to improve tumor microcirculation , which further promoted drug delivery and enhanced drug efficacy in erlotinib-resistant NSCLC cells. Our innovative gene/drug co-delivery system in combination with CQ showed a promising outcome in fighting against erlotinib resistance both in vitro and in vivo . This work indicates that normalization of tumor vessels could help intracellular erlotinib/Survivin-shRNA delivery and the down-regulation of Survivin could act synergistically with erlotinib for reversal of erlotinib resistance in EGFR mutation-positive NSCLC. Statement of Significance NSCLC patients who benefited from EGFR-TKIs inevitably developed acquired resistance. Previous research focused on synthesis of new generation of molecular targeted drugs that could irreversibly inhibit EGFR with a particular gene mutation to overcome drug resistance. However, they failed to inhibit EGFR with other gene mutations. Activation of bypass signaling pathway and the changes of tumor microenvironment are identified as two of the mechanisms of acquired resistance to EGFR-TKIs. We therefore constructed multifunctional gene/drug co-delivery nanocomplexes AP/ES co-formulated with chloroquine that could target the both two mechanisms. We found that chloroquine not only enhanced endosomal escape ability of AP/ES for efficient gene transfection to inhibit Survivin, but also showed strong vessel-normalization ability to improve tumor microcirculation, which further promoted drug delivery into tumor tissue and enhanced drug efficacy in erlotinib-resistant NSCLC.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weikang Yu,Yu Sun,Wenyu Li,Xu Guo,Xuesheng Liu,Wanpeng Wu,Wanqi Yu,Jiajun Wang,Anshan Shan
Targeting the limitation of antimicrobial peptides (AMPs) application in vivo, self-assembled AMPs library with specific nanostructures is expected to gradually overtake monomer AMPs libraries in the future. Peptide polymers are fascinating self-assembling nanoscale structures that have great advantage in biomedical applications because of their satisfactory biocompatibility and versatile properties. Herein, we describe a strategy for inducing the self-assembly of T9W into nanostructured antimicrobial micelles with evidently improved pharmacological properties, that is, PEGylation at the C-terminal of T9W (CT9W1000), an antibacterial biomaterial that self-assembles in aqueous media without exogenous excipients, has been developed. Compared with parental molecular, the CT9W1000 is more effective against Pseudomonas aeruginosa, and its antibacterial spectrum had also been broadened. Additionally, CT9W1000 micelles had higher stability under salt ion, serum, and acid–base environments. Importantly, the self-assembled structure is highly resistant to trypsin degradation, probably allowing T9W to be applied in clinical settings in the future. Mechanistically, by acting on membranes and through supplementary bactericidal mechanisms, CT9W1000 micelles contribute to the antibacterial process. Collectively, CT9W1000 micelles exhibited good biocompatibility in vitro and in vivo, resulting in highly effective treatment in a mouse acute lung injury model induced by P. aeruginosa PAO1 without drug resistance. These advances may profoundly accelerate the clinical transformation of T9W and promote the development of a combination of peptide-based antibiotics and PEGylated nanotechnology.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
微生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2016
·Vol. 16
·期 6
·5569-5576
·
IF 1.338
Li Qinqin,Li Chenglin,Tong Weijun
Here, a novel poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for magnetic resonance (MR) and fluorescence imaging was developed for cell imaging. PLGA NPs loaded with fluorescent dye Nile red (NR) and surface-coated with poly(ethyleneimine) (PEI) were produced in a single
step nanoprecipitation process. Diethylenetriamine pentaacetic dianhydride (DTPA) was conjugated to PLGA/NR@PEI NPs through amidation reaction between –COOH of DTPA and –NH2 of PEI, which can chelate gadolinium (Gd3+) as an MR imaging contrast agent. The PLGA/NR@PEI-DTPA-Gd
NPs exhibited a uniform particle size of ∼200 nm and were stable in culture medium. These NPs had a high T
1 relaxivity (R
1) of 28.36 mM−1S−1. They did not introduce serious cytotoxicity against A549 lung cancer cells.
Furthermore, fluorescence and MR imaging studies on A549 lung cancer cells in vitro revealed that PLGA/NR@PEI-DTPA-Gd NPs can serve as an efficient fluorescence/MR dual-modality imaging nanoprobe.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
医学成像
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Lei Luo,Fanshu Xu,Huilan Peng,Yonghuang Luo,Xiaohe Tian,Giuseppe Battaglia,Hu Zhang,Qiyong Gong,Zhongwei Gu,Kui Luo
Functionalized drug delivery systems against malignant lung metastasis of breast cancer have been extensively studied, while metastasis remains a challenging issue. We propose a new strategy to achieve eradication of primary breast cancer cells and inhibition of pulmonary metastasis. A cathepsin B/pH dual-sensitive block copolymer with a molecular weight of 92 kDa was synthesized to conjugate with doxorubicin (DOX). The copolymer-DOX was further loaded with nifuroxazide (NFX) to self-assemble co-prodrug-loaded micelles (CLM). CLM displayed a drug release pattern in response to pH/enzyme dual stimuli and was enzymatically biodegradable. CLM was demonstrated to reduce viability and inhibit migration and invasion of 4T1 murine breast cancer cells in vitro. After i.v. injection of CLM, its nanoscale size and stimuli-responsiveness facilitated delivery of drugs to the tumor site in mice. Enhanced anti-tumor efficacy and great anti-metastatic effects were found in both orthotropic and lung metastasis 4T1 breast cancer mice models. Meanwhile, histological immunofluorescence and immunohistochemical analyses revealed a high level of apoptosis, suppressed expression of matrix metalloproteinases and reduction in MDSCs infiltration , and all these contributed to inhibit pulmonary metastasis. CLM may be explored as a potential nanomedicine against breast cancer metastasis.
研究领域:
药学
·
肿瘤学
·
生物材料学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Wenhao Xu,Meiqun Hu,Qihong Zhang,Jingbo Yu,Weike Su
Ethnopharmacological relevance Cassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough (‘pertussis’) and inflammatory diseases . Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma. Aim of the study To explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma. Materials and methods Extraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN- γ ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2 -ΔΔCt method. Results Treatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN- γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. Conclusions These findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.
研究领域:
药理学
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免疫学
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民族药理学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）