COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Xiaotong Yu,Mengying Xia,Yuanhong Li,Geyun Chen,Chenhao Yu,Qianming Chen,Qiang Peng
Developing the delivery systems with high therapeutic efficacy and low side effects is of great interest and significance for anticancer therapy. Compared to the high cost in synthesizing new chemotherapeutic drugs, exploring the anticancer potentials of existing chemicals is more convenient and efficient. Sodium bicarbonate (BC), a simple inorganic salt, has shown its tumor inhibition capacity via regulating the acidity of tumor microenvironment. However, the effects of intracytoplasmic BC on tumor growth and the potentials of BC to serve as an anticancer agent are still unknown. Herein, we developed a BC-loaded cationic liposome system (BC-CLP) to deliver BC into the cytosol of cancer cells. The in vitro studies showed that the BC-CLP containing 1% BC (w/v) had a size of 112.9 nm and a zeta potential of 19.1 mV, which reduced the viability of the model cancer cells (human oral squamous cell carcinoma HSC-3 cells) to 13.7%. In contrast, the neutral BC-LP caused less than 50% viability reduction. We further found that BC-CLP released BC directly into cytoplasm via membrane fusion pathway rather than endocytosis, leading to the remarkable increase of cytosolic pH, which may contribute to the anticancer effect of BC-CLP. Our findings indicate that BC-CLP is a potential system for high-efficiency cancer therapy without causing drug-related side effects or resistance.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2020
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IF 2.985
Ruixue Wang,Lianyun Lin,Yiqiang Zheng,Peng Cao,Zhiguang Yuchi,Hui-Yuan Wu
Cytosolic carboxypeptidases (CCPs) comprise a unique subfamily of M14 carboxypeptidases and are erasers of the reversible protein posttranslational modification– polyglutamylation . Potent inhibitors for CCPs may serve as leading compounds targeting imbalanced polyglutamylation. However, no efficient CCP inhibitor has yet been reported. Here, we showed that 2-phosphonomethylpentanedioic acid (2-PMPA), a potent inhibitor of the distant M28 family member glutamate carboxypeptidase II (GCPII), rather than the typical M14 inhibitor 2-benzylsuccinic acid, could efficiently inhibit CCP activities. 2-PMPA inhibited the recombinant Nna1 (a.k.a. CCP1) for hydrolyzing a synthetic peptide in a mixed manner, with Ki and Ki’ being 0.11 μM and 0.24 μM respectively. It inhibited Nna1 for deglutamylating tubulin, the best-known polyglutamylated protein, with an IC 50 of 0.21 mM. Homology modeling predicted that the R-form of 2-PMPA is more favorable to bind Nna1, unlike that GCPII prefers to S-form. This work for the first time identified a potent inhibitor for CCP family.
研究领域:
生物化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Lixia Guo,Xueyun Zhang,Danning Wen,Lei Ding,Yan Niu,Lihong Li,Wen Liu,Haipeng Diao,Liheng Feng
Accurate measurement of pH is of great significance in the research of biology and medicine sciences. Cell is the basic unit of living organism and the proper pH of cytoplasm and organelles such as lysosome is the precondition to maintain its function. Alteration of pH may impair the normal process of cells and lead to occurrence of diseases. Sensitively sensing the pH of cytoplasm and organelles is of great value for biomedical research. Due to the complexity of biological microenvironment , it is still challenging to simultaneously detect the pH changes of cytoplasm and lysosome. Here, we reported a ratiometric pH probe with NIR fluorescence termed as PCHC, which realized sensitive cytoplasmic and lysosome pH detection. The probe was prepared by connecting coumarin with dicyanmethylene-4H-pyran via amidation reaction, and displays large Stoke-shift, good biosafety and pH selectivity. After entering the cell, the probe shows blue in cytoplasm and NIR fluorescence in lysosome due to respective pH. The ratio of blue and NIR fluorescence signal can be served as indicator to monitor pH change of cytoplasm and lysosome simultaneously, which has potential application for investigation of pH alteration related diseases.
研究领域:
生物医学
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细胞生物学
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DOI
高影响因子
RSC Advances
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2017
·Vol. 7
·期 27
·16730-16736
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IF 3.108
Ruiqing Feng,Longlong Li,Bing Li,Jinhui Li,Dan Peng,Yitao Yu,Qiuhong Mu,Ning Zhao,Xiaoqiang Yu,Zhenhua Wang
We have synthesized two-photon organic molecule probes (IMT-E and IMT-M), which selectively stain endogenous RNA in the nucleolus and cytoplasm of living cells in a short incubation time. Using these probes, bright two-photon excitation fluorescence (TPEF) images of living cells have been developed. Titrations and digest tests of ribonuclease indicate the markedly higher affinity of these probes for RNA, especially when using IMT-E. Upon binding to RNA, the fluorescence intensity of IMT-E increases by about 15-fold, showing that IMT-E is a turn-on probe for the detection of RNAs. MTT assays demonstrate that the mitochondria of cells maintain their electron mediating ability after being stained with the probes. These results demonstrate that IMT-E is an attractive two-photon turn-on fluorescent probe for visualizing RNA in living cells.
研究领域:
生物化学
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分子生物学
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细胞生物学
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DOI
高影响因子
mSystems
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2024
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IF 5
Jiaming Zhang,Xiaoxia Yu,Weidong Li,Yunjing Jiang,Liangran Zhang,Shunxin Wang
A good quality egg is essential for a successful pregnancy and early embryo development. Oocyte development is vulnerable to environmental exposures. Bisphenol S (BPS) is widely used as a replacement for its analog bisphenol A, but the reproductive toxicity of BPS has been of great concern. In this study, we showed that BPS exposure induces dysbiosis of the gut microbiota, which further leads to intestinal permeability and inflammation, and ultimately impairs oocyte quality. More importantly, we found that alginate oligosaccharide reshapes the gut microbiota to improve gut homeostasis, thereby preventing the deleterious effects of BPS on the gut and oocytes. Overall, this study not only demonstrates that BPS exposure impairs the intestine and oocytes by inducing dysbiosis of the gut microbiota but also develops a preventive strategy.
研究领域:
生殖生物学
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环境毒理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
HELICOBACTER
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2023
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IF 4.4
Zelin Zhang,Xingchi Chen,Bin Li,Tingting Xia,Xiaobin Wu,Chao Wu
Background Urease subunit B (UreB), a conserved and key virulence factor of Helicobacter pylori ( H. pylori ), can induce the host CD4 + T cell immune responses to provide protection, but less is known regarding CD8 + T cell responses. The characteristics of H. pylori -specific CD8 + T cell responses and the mechanism underlying antigen processing and presentation pathways remain unclear. This study was focus on protective antigen recombinant UreB (rUreb) to detect specific CD8 + T cell responses in vitro and elucidate the mechanism of UreB antigen processing and presentation. Methods The peripheral blood mononuclear cells (PBMCs) collected from H. pylori -infected individuals were stimulated with rUreB in vitro to detect specific CD8 + T cell responses after co-culture with rUreB-pulsed autologous hMDCs. Through blocking assay, we investigated the potential pathway of UreB antigen processing and presentation via the cytosolic pathway or vacuolar pathway. The cytokines production of UreB specific CD8 + T cell were evaluated as well. Results We demonstrated UreB can induce specific CD8 + T cell immune responses in H. pylori infected individuals. Importantly, we characterized that UreB were mainly processed by proteasome instead of lysosomal proteases and presented through cytosolic pathway of cross-presentation, which requires endoplasmic reticulum–Golgi transport and newly synthesized MHC-I molecules, to induce functional-specific CD8 + T cell (IFN-γ + TNF-α + Grz A+ Grz B+) responses. Conclusions These results suggest that H. pylori UreB induces specific CD8 + T cell responses through cytosolic pathway of cross-presentation in infected individuals.
研究领域:
免疫学
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病原生物学
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医学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Hong Chen,Peng Lei,Tianming Wang,Ting Li,Minjuan Zhong,Lili Zhang,Xianting Sun,Hao Zhou,Yue Liu,Weihua Liao,Yanlan Liu
Manipulating metabolic rewiring in cancer cells has become a central focus in cancer treatment. However, the intricate, yet not fully elucidated, adaptability of cancer metabolism frequently undermines the effectiveness of such interventions. Here, a novel cascade metabolic regulation system is presented by manipulating the mitochondria-cytosol metabolic networks to disrupt multipath energy replenishment in cancer. Specifically, multienzymatic Mn-LDH nanodiscs are synthesized, which not only impair energy metabolism in mitochondria by triggering mitochondrial dysfunction via self-cascade catalysis, but also show the activity of blocking the compensatory energy metabolism from cellular glycogen. Concurrently, vessel embolization is combined to obstruct the carbon sources essential for both glycolysis in cytosol and the tricarboxylic acid (TCA) cycle in mitochondria, while simultaneously fostering an environment conducive to Mn-LDH catalysis. This dual-pronged regulation strategy induced ATP exhaustion and apoptosis in cancer cells, leading to remarkably enhanced antitumor efficacy in orthotopic liver tumor rabbit models compared to a standard clinical embolization formulation for advanced liver tumors. Moreover, comprehensive mechanism studies across cellular and animal models confirmed that this strategy effectively blocked multifaceted metabolic adaptations within the mitochondria and cytosol of cancer cells. Overall, this work offers a promising platform for metabolic intervention and provides important insights into cancer biology and management.
研究领域:
生物化学
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分子生物学
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肿瘤学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2022
·
IF 9.965
Lijuan Yang,Shaochi Liu,Tian Quan,Yongqing Tao,Meng Tian,Luchun Wang,Junji Wang,Dandan Wang,Die Gao
Aggregation-induced emission fluorescent carbon dots (AIE-CDs) have applications in the fields of multi-colour anti-counterfeiting, information encryption, and imaging. In this study, four AIE-CDs (B-AIE-CDs, G-AIE-CDs, Y-AIE-CDs, and O-AIE-CDs) with blue, green, yellow, and orange fluorescence at high concentrations were fabricated using crystal violet as a precursor, solutions with different sulfuric acid concentrations as solvents under different temperatures and reaction times for the first time. The structural properties and fluorescence behaviour of the AIE-CDs were investigated. The results revealed that the sulfuric acid concentration had a significant effect on the fluorescence colour of the AIE-CDs because sulfuric acid can affect the degree of carbonisation, the type and content of nitrogen. Moreover, the reaction temperature and time affected the surface-defect state and the degree of carbonisation of the AIE-CDs, which affected the emission wavelength and quantum yield (QY) of the AIE-CDs. Furthermore, to exploit the unique characteristics (polychromatic aggregation fluorescence and acid-sensitive properties) of the obtained-AIE-CDs, anti-counterfeiting and information encryption methodologies (i.e., acid-stimuli-response producing multi-colour fluorescence) were preliminarily developed. Finally, B-AIE-CDs with a high QY of 43.5% were successfully used for rapid cytoplasmic imaging, demonstrating their applicability in biological fields.
研究领域:
材料科学
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纳米技术
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光学
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化学
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生物技术
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2017
·Vol. 27
·期 14
·1604620
·
IF 12.124
Tingjie Yin,Jiyong Liu,Zekai Zhao,Yuanyuan Zhao,Lihui Dong,Meng Yang,Jianping Zhou,Meirong Huo
Nanocarriers capable of circumventing various biological barriers between the site of administration and the therapeutic target hold great potential for cancer treatment. Herein, a redox-sensitive, hyaluronic acid-decorated graphene oxide nanosheet (HSG) is developed for tumor cytoplasm-specific rapid delivery using near-infrared (NIR) irradiation controlled endo/lysosome disruption and redox-triggered cytoplasmic drug release. Hyaluronic acid (HA) modification through redox-sensitive linkages permits HSG a range of advantages over the standard graphene oxide, including high biological stability, enhanced drug-loading capacity for aromatic molecules, HA receptor-mediated active tumor targeting, greater NIR absorption and thermal energy translation, and a sharp redox-dependent response for accelerated cargo release. Results of in vivo and in vitro testing indicate a high loading of doxorubicin (DOX) onto HSG. Selective delivery to HA-receptor overexpressing tumors is achieved through passive and active targeting with minimized unfavorable interactions with blood components. Cytoplasm-specific DOX delivery is then achieved through NIR controlled endo/lysosome disruption along with redox-triggered release of DOX in glutathione rich areas. HSG's specificity is resulted in enhanced cytotoxicity of chemotherapeutics with minimal collateral damage to healthy tissues in a xenograft animal tumor model. HSG is validated the programmed delivery of therapeutic agents in a spatiotemporally controlled manner to overcome multiple biological barriers results in specific and enhanced cancer treatment.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2016
·Vol. 17
·期 8
·1374
·
IF 3.257
Ou Yun,Xin-An Zeng,Charles S. Brennan,Zhong Han
Salmonella typhimuriumcells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0–4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity ofSalmonella typhimurium(S. typhimuriumi), possibly due to the alterations of fatty acid biosynthesis-associated gene expressions (down-regulation ofcfaandfabAgene expressions and the up-regulation offabDgene expression), which, in turn, modified the composition of membrane lipid (decrease in the content ratio of unsaturated fatty acids to saturated fatty acids). In addition, oxidative injury induced by PEF treatment was associated with an increase in the content of malondialdehyde. The up-regulation of cytochrome bo oxidase gene expressions (cyoA,cyoB, andcyoC) indicated that membrane damage was induced by PEF treatment, which was related to the repairing mechanism of alleviating the oxidative injury caused by PEF treatment. Based on these results, we achieved better understanding of microbial injury induced by PEF, suggesting that micro-organisms tend to decrease membrane fluidity in response to PEF treatment and, thus, a greater membrane fluidity might improve the efficiency of PEF treatment to inactivate micro-organisms.Keywords:pulsed electric fields;Salmonella typhimurium;membrane lipids;cytoplasmic membrane fluidity;oxidative injury
研究领域:
微生物学
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食品科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2021
·
IF 0
Yunjing Wang,Qian Gong,Fan Huang,Linfang He,Yule Liu
Summary Wounding evokes transient increases in cytosolic calcium (Ca 2+ ) concentration. Visualizing real-time Ca 2+ flux provides new insights into Ca 2+ -signaling pathways. Here, we outline a protocol to detect insect feeding-induced Ca 2+ flux elevation in Nicotiana benthamiana leaves based on the GCaMP3 reporter system by Leica fluorescence stereo microscopes (LFSM). LFSM combines super-fast manual screening with high-end imaging capabilities. Through this protocol, we can clearly observe the calcium flow after aphid’s piercing-sucking. Additionally, we describe a protocol to quantify Ca 2+ level using LFSM. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021) .
研究领域:
植物生物学
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分子生物学
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昆虫学
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DOI
PubMed
STAR Protocols
·
2023
·
IF 0
Jiaqi Shi,Caiqi Liu,Shengnan Luo,Yingying Zhang,Mingwei Li,Meng Zhou,Mingjiao Weng,Xiaobo Li,Tongsen Zheng
Summary Here, we present a protocol for the detection of the two STING isoforms (erSTING and pmSTING) in human peripheral blood mononuclear cells or mouse splenocytes using Western blot and PCR. We detail steps to construct plasmids encoding each isoform and transfer them into mouse and human cell lines. Finally, we describe how to detect cell membrane localization of pmSTING using flow cytometry, immunoprecipitation, and immunofluorescence. This protocol is applicable for proteins with well-predicted topological structures. For complete details on the use and execution of this protocol, please refer to Li et al. 1 .
研究领域:
分子生物学
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细胞生物学
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免疫学
✓ 已验证
DOI
PubMed
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