iScience
·
2023
·
IF 5.8
Sirui Tan,Shaila Afroj,Daiqi Li,Md Rashedul Islam,Jihong Wu,Guangming Cai,Nazmul Karim,Zhong Zhao
Summary Electroconductive textile yarns are of particular interest for their use as flexible and wearable sensors without compromising the properties and comfort of usual textiles. However, the detection of fine actions of the human body is quite challenging since it requires both the relatively higher sensitivity and stability of the sensor. Herein, highly sensitive, ultra-stable, and extremely durable piezoresistive wearable sensors were prepared by loading N-doped rGO and polydopamine-coated carbon nanotubes into silicon rubber tube. The wearable sensors thus produced show an excellent ability to sense subtle movement or stimuli with good sensitivity and repeatability. Furthermore, by bending the straight conductive silicon rubber tube (CSRT) into three different patterns, its sensitivity was then dramatically increased. Finally, the CSRT was found capable of sensing cardiorespiratory signals, indicating that the sensor would be an important step toward realizing bio-signal sensing for next-generation personalized health care applications.
研究领域:
材料科学
·
生物医学工程
·
可穿戴技术
·
医疗保健
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Yangfan Zheng,Jiali Deng,Lewei Li,Jing Cao,QinYan Xie,Yangfen Fu
Malignant neoplasms, which are related closely to epithelial-mesenchymal transition (EMT) pathway, are one of the greatest risks threatening human health today. Magnolol (MAG), a traditional Chinese herbal extract, which has been proved to inhibit EMT pathway of solid tumors in previous studies. In this study, we first verified that MAG reduced metastasis and enhanced chemosensitivity to doxorubicin (DOX) in A549 cells, a non-small cell lung cancer (NSCLC) cell. An adenosine monophosphate (AMP) modified nanomicelles (APD@MAG NMs) was further prepared using the appropriate feeding ratio, loading with synergistic DOX and MAG. APD@MAG NMs with high positive charged surface reduced drug release of negative charged MAG, and achieved continuous cellular uptake. APD@MAG NMs significantly reduced the cell viability and enhanced the cell apoptosis of A549 cells. Moreover, the APD@MAG NMs significantly inhibited the mRNA levels and the protein expression of EMT related pathway. Overall, these APD@MAG NMs provide an effective therapeutic strategy for clinical chemo-therapy in NSCLC.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 3
·
IF 9.043
Meng Wang,Yujiao Tian,Li Xu,Fusheng Zhang,Huigai Lu,Moran Li,Bei Li
Klebsiella pneumoniae is a pathogen known for its high frequency of antimicrobial resistance. Responses to various environmental stresses during its life can influence the resistance to antibiotics. Here, we demonstrate the role and mechanism of KbvR regulator in the response to environmental osmotic stress and in the effect of osmotic stress on antimicrobial resistance. The kbvR mutant strain exhibited increasing tolerance to high osmotic stress and certain antibiotics, including β-lactams. The expression levels of KbvR and outer membrane porin OmpK36 were upregulated in response to high osmotic stress in the wild type (WT), and the deletion of kbvR decreased the expression level of ompK36. The membrane permeability of the kbvR mutant strain was decreased, which was partly restored through the upregulated expression of OmpK36. The DNA affinity purification sequencing (DAP-seq) and microscale thermophoresis (MST) assay disclosed the binding of KbvR to the promoter of the ompK36 gene, indicating that KbvR directly and positively regulated the expression of OmpK36. The high osmotic stress increased the susceptibility to β-lactams and the expression of ompK36 in the WT strain. However, the increased ompK36 expression and the susceptibility to β-lactams in the kbvR mutant strain under high osmotic stress were lower than those of WT. In conclusion, our study has identified that high osmotic stress in the environment influenced the resistance of K. pneumoniae to antibiotics and that the regulation of KbvR with OmpR on the expression of OmpK36 was involved in countering high osmotic stress to change the antimicrobial resistance.IMPORTANCE Klebsiella pneumoniae is considered a global threat because of the rising prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. The sensing and adaption abilities of bacteria to the environmental osmotic stress can change the expression of their outer membrane porins, membrane permeability, and resistance to antibiotics. This study reports that KbvR is a newly found regulator that can be upregulated under high osmotic stress and directly regulate the expression of OmpK36 to change the resistance of K. pneumoniae to β-lactam antibiotics. The results demonstrate how adaptation to high osmotic stress changes the sensitivity of K. pneumoniae to antibiotics. The mechanism can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints in governing adaptation to diverse environmental challenges.
研究领域:
微生物学
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分子生物学
·
细菌遗传学
·
抗菌素耐药性
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DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Liangping Li,Wenqing Du,Hui Wang,Yufei Zhao,Zetian Huang,Yan Peng,Shulan Zeng,Guohai Zhang
p53 inactivation is a common feature in non-small cell lung cancer (NSCLC) resulting in NSCLC malignant transformation . Targeting serine 392 phosphorylation to restore p53 anticancer activity has proven to be an effective therapeutic strategy against NSCLC. A synthetic p53 activator, NA-17, has been developed that shows promise in preclinical models of NSCLC. However, NA-17 exhibits limited therapeutic efficacy in oncogene-driven tumors as well as relatively high toxicity to normal cells. It is possible that high efficiency and low toxicity p53 activators can be obtained by optimizing the leading molecule. Here, we performed high-throughput screening of compounds optimized based on NA-17 to identify new p53 activators. Two promising candidates named MX-C2 and MX-C3 were identified, both exhibited considerable therapeutic efficacy in oncogene-driven tumor models. Similar to NA-17, MX-C2/3 induced p53 activation via phosphorylating serine-392 without DNA damage. Both compounds showed broad antitumor activity in NSCLC cells and limited toxicity in normal cell lines. Moreover, MX-C2/3 suppressed tumor progression by arresting the cell cycle at G2/M phase, exhibiting a different mechanism of cell cycle arrest than NA-17. In addition, MX-C2/3 promoted the enrichment of p-p53 (s392) in mitochondria, leading to the conformational activation of Bak for cell apoptosis, which is consistent with NA-17. Finally, we demonstrated that MX-C2 significantly inhibited tumor growth without obvious systemic toxicity in oncogene-driven HCC-827 xenograft models. Collectively, we report two p53 activators with high-efficiency and low-toxicity that target p53 serine 392 phosphorylation for anticancer translational investigation.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
癌症研究
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DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Gan Xin,Xie Jingwen,Dong Zhaojun,Wu Yuna,Zeng Xiaoqing,Yang Zhenzhen,Liu Bo,Zhu Min,Wang Bozhen,Li Wulan,Wang Ledan,Zhang Huajie,Wu Jianzhang,Hu Yue
Background: Pyroptosis, a cell death process triggered by chemotherapy drugs, has
emerged as a highly promising mechanism for combating tumors in recent years. As the lead of
new drugs, natural products play an important role in the discovery of anticancer drugs. Compared
to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior
safety profile. Among a series of MFHNP molecular skeletons, this study found that only
benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity
of 1 remains to be improved.
Aims: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by
modifying the chalcone structure.
Methods: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis,
several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer
activity was tested by MTT assay, and morphological indications of pyroptosis were observed
in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore,
to improve the activity of the chalcone skeleton, the anticancer group 3,4,5-
trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed,
synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally,
a quantitative structure-activity relationship (QSAR) model was established using the
eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore.
Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular
mechanisms of pyroptosis induced by the active compound.
Results: α, β-unsaturated ketone was the functional group of the chalcone skeleton and played a
pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients
(R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these
compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was
found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing
the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft
tumors.
Conclusion: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis
axis and is a kind of promising pyroptosis inducer.
研究领域:
肿瘤学
·
药理学
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Hua Fang,Xiumei Wang,Mengyu Li,Mengxian Huang,Yiping Zhang,Taige Zhao,Cuiling Sun,Min Xu,Wenhui Jin,Weizhu Chen,Meijuan Fang
In this study, twenty-five novel carboxylic acid DHA-alkanolamine derivatives were synthesized by the reaction of cis -docosa-4,7,10,13,16,19-hexaenoic acid-alkanolamine (DHA-AA) with various carboxylic acids, including Naproxen (S1), Ibuprofen (S2), Ferulic acid (S3), Mefenamic acid (S4), and Aspirin (S5). Their molecular structures were characterized using 1 H/ 13 C NMR and HRMS techniques. To evaluate the anti-inflammatory activities of synthesized compounds, RAW264.7 macrophage cells pretreated with or without these compounds, were stimulated by LPS, and the levels of pro-inflammatory cytokines (NO, TNF-α, IL-1β, and IL-6) were then measured by ELISA, qPCR, and Western Blot. The cell-based assays showed that compound 11 had marked anti-inflammatory activity. In addition, the molecular docking study and SPR assay demonstrated that compound 11 exhibited good Nur77-binding affinity (K D = 3.61 × 10 −6 M). Moreover, compound 11 was found to inhibit NF-κB activation in a Nur77-dependent manner. Notably, compound 11 could attenuate LPS-induced inflammation in the mouse acute lung injury (ALI) model. In conclusion, these derivatives are potential Nur77-targeting anti-inflammatory agents against versatile inflammatory and autoimmune disorders.
研究领域:
药理学
·
炎症研究
·
药物化学
✓ 已验证
DOI
高影响因子
Nanoscale
·
2025
·
IF 5.1
Yuan Quan,Yan Yuan,Kejin Chen,Ting Li,Jing Li,Mengxing Zhang,Rongying Shi,Shanshan He,Lin Li,Xun Sun,Tao Gong,Ling Zhang,Zhirong Zhang,Qing Lin
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high recurrence rates, limited therapeutic options, and a strong propensity for spontaneous lung metastasis. Increasing evidence indicates that neutrophil extracellular traps (NETs) significantly promote TNBC progression, immune evasion, and metastatic dissemination, highlighting NETs inhibition as a promising therapeutic strategy. Herein, we developed a dual pH/ROS-responsive nanoplatform (pH/ROS@(PTX/SIV)) constructed from acetylated dextran (Ace-DEX) and phenylboronic acid-modified dextran (PBAP-DEX), and further functionalized with the fibronectin-targeting peptide CREKA to achieve tumor-specific accumulation. The nanoplatform enables controlled, microenvironment-responsive release of paclitaxel (PTX) and the neutrophil elastase inhibitor sivelestat (SIV) in acidic and oxidative tumor tissues. The optimized nanoparticles exhibited uniform size, high encapsulation efficiencies, and robust dual-responsive drug release. In vitro, CREKA modification markedly enhanced cellular uptake and tumor-targeting efficiency, while the dualloaded system showed superior cytotoxicity against TNBC cells. In orthotopic TNBC mouse models, pH/ROS@(PTX/SIV) significantly suppressed primary tumor growth, prolonged survival, and critically inhibited spontaneous lung metastasis.Mechanistically, the formulation effectively blocked NETs formation both in isolated primary neutrophils and in tumor tissues, thereby disrupting NETs-mediated prometastatic signaling. Furthermore, the nanoplatform displayed favorable systemic safety with negligible organ toxicity. This dual-responsive, NET-modulating nanoplatform provides a potent and safe therapeutic strategy for combating TNBC and preventing its metastasis, offering strong potential for clinical translation.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
·
2015
·
IF 2.645
Jia Ma,Zhiping Zhang,Zhanjie Zhang,Jing Huang,You Qin,Xu Li,Hongli Liu,Kunyu Yang,Gang Wu
Purpose: Heat generated by magnetic nanoparticle clusters (MNCs) in an alternating magnetic field (AMF) can be used for hyperthermia cancer treatment. Here, we have synthesised polyacrylic acid-coated MNCs according to previous report, with the ability to increase particle stability in suspension. Radiosensitisation effects of the MNCs under an AMF were investigated in vitro and in vivo.Materials and methods: MTT assay, flow cytometry, clone formation assay, Western blotting, and a γ-H2AX experiment were used to explore the biocompatibility and radiosensitisation effect of the MNCs and their putative radiosensitisation mechanism. An NCI-H460 mouse xenograft model was used to investigate the anti-tumour effect under an AMF in vivo.Results: The temperature of MNC fluids at different concentrations (200 μg/mL to 2 mg/mL) increased rapidly. The MNCs were endocytosed by the cells and were found to be biocompatible. Hsp70 and caspase-3 were found to be up-regulated upon MNCs under an AMF, radiation, and combination of both treatments. MNCs under an AMF efficiently radiosensitised both CNE-2 cells and NCI-H460 cells. Finally, the tumour inhibition rate after treatment with MNCs under an AMF and radiation was significantly higher than that after either treatment alone. The mechanism of radiosensitisation putatively involves inhibition of DNA repair and induction of apoptosis.Conclusions: The MNC fluids under an AMF enhanced the radiosensitivity of tumour cells both in vitro and in vivo.
研究领域:
肿瘤学
·
纳米技术
·
放射治疗
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Niu Kai,Li Nan,Yao Yunming,Guo Chunjie,Ge Yuanyuan,Wang Jianmeng
Two kinds of tumor microenvironment-responsive polypeptide nanogels were developed for intracellular delivery of cytotoxics to enhance the antitumor efficacies and reduce the side effects in the chemotherapy of lung carcinoma. The sizes of both doxorubicin (DOX)-loaded nanogels methoxy poly(ethylene glycol)–poly(L-phenylalanine-co-L-cystine) [mPEG–P(LP-co-LC)] and methoxy poly(ethylene glycol)–poly(L-glutamic acid-co-L-cystine) [mPEG–P(LG-co-LC)] (NGP/DOX and NGG/DOX) were less than 100 nm, which was appropriate for the enhanced permeability and retention (EPR) effect. The bigger and smaller scale of nanoparticle could induce the elimination of reticuloendothelial system (RES) and decrease the in vivo circulating half-life, respectively. The loading nanogels were stable in the neutral environment while quickly degraded in the mimic intracellular microenvironment. Furthermore, the DOX-loaded reduction-responsive nanogels showed significantly higher tumor cell uptake than free DOX⋅HCl as time went on from 2 to 6 h. In addition, these DOX-loaded nanogels showed efficient antitumor effects in vivo, which was verified by the obviously increased necrosis areas in the tumor tissues. Furthermore, these DOX-loaded nanogels efficiently reduced the side effects of DOX. In conclusion, these reduction-responsive polypeptides based nanogels are suitable for the efficient therapy of lung carcinoma.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Liping Yin,Wenhao Duan,Yanai Chen,Danyang Chen,Yong Wang,Shuai Guo,Jianglei Qin
Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo , and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.
研究领域:
药学
·
材料科学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
·
2024
·
IF 4
Yingcai Xiong,Keyu Tao,Tao Li,Yinghui Zhou,Zhaowei Zhang,Weiying Ou,Zhao Wang,Shouchuan Wang,Yayi Hou,Peng Cao,Jianjian Ji
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose–response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.
研究领域:
病毒学
·
药理学
·
分子生物学
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Weili Yang,Hui Liu,Xiaowei Liu,Yuxin Cao,Xuemei Wang,Xinxin Wang,Wenwen Cao,Chunjing Guo,Daquan Chen
Acute lung injury (ALI) is a complex acute respiratory illness with a high mortality rate. Reactive oxygen species (ROS) play a pivotal role in ALI, inducing cellular damage, inflammation, and oxidative stress, thereby exacerbating the severity of the injury. In this study, inspired by the “subtractive” strategy, we developed a fucoidan-based macrophage membrane bio-nanosystem, abbreviated as MF@CB, designed as an anti-inflammatory and antioxidant agent to alleviate lipopolysaccharide (LPS)-induced inflammation in ALI. MF@CB coated with macrophage membrane for effective targeting and accumulation in ALI lesions. In addition, MF@CB activates Nrf2 transcriptional activity in macrophages, inhibiting ROS synthesis at its origin while effectively removing ROS already present in the ALI. This dual-pronged approach demonstrates robust antioxidant properties and restores the macrophage antioxidant defense barrier. In the LPS-induced ALI mouse model, MF@CB significantly mitigated lung inflammatory damage by modulating lung macrophage polarization and inhibiting the over-secretion of pro-inflammatory cytokines by activated immune cells. More importantly, unlike most surface modification strategies because it remove the molecule, this approach is easier to apply and potentially safer and may provide useful insights into the development of more effective therapeutic strategies for ALI.
研究领域:
纳米技术
·
药理学
·
免疫学
·
呼吸医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）