SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2019
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IF 2.931
Dongxin Zhao,Kui Lu,Guangbin Liu,Juhong Hou,Libo Yuan,Li Ma,Jie Liu,Juan He
Polypeptides with finger-like structures can often intercalate into the grooves of DNA , thereby affecting DNA repair or activating gene transcription, both of which are crucial for the regulation of physiological processes. Their conserved amino acid sequence and simple structure have provided useful elements for the design and assembly of functional molecules. In this paper, using the C 2 H 2 zinc finger domain and the PEP-FOLD3 online simulation platform 11 polypeptides containing 22 amino acid residues were designed. In addition, the CD spectroscopy was combined with the fluorescence spectroscopy to study the polypeptide structures and their interaction with DNA. Results showed that although addition of zinc ions affected the polypeptide structure, particularly of the polypeptides A4, B1, and B3, zinc ion was not an essential factor for increasing polypeptide-DNA interactions. Our study revealed an increase in the interaction strength between mutated polypeptides and DNA, suggesting that mutations disrupt polypeptide structure, and polypeptides interact with DNA by groove and electrostatic binding. Mutations at the 12th and 15th amino acid residues had the greatest effect. The stronger binding between A2 or B2 and DNA indicates that the polypeptide has a spatial structure that can stably interact with DNA. The structure and characteristics of these polypeptide domains can provide information for the design and development of new polypeptide functional molecules, which could have potential significance and applications. However, this information also suggests that there are many challenges facing polypeptide design due to the synergistic effects between the side chains of amino acid residues.
研究领域:
生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
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2018
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IF 3.075
Xiaoyuan Guo,Guojian Wu,Hong Wang,Lukui Chen
Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol–bifunctionalized carmustine-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting interleukin-13 receptor–overexpressed glioma and penetrating the brain microvascular endothelial cells–associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a diameter of 32.6 ± 1.1 nm and zeta potential of −21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization, and effectively induced the cell apoptosis . Likewise, in human brain microvascular endothelial cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance, and thereby enhanced the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labeled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period, and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.
研究领域:
药理学
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纳米技术
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肿瘤学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
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2024
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IF 5.8
Xinru Kong,Yanxi Yang,Xueli Ren,Yandai Lin,Yu Shi,Zhe Liu
The concept of combining external medical stimuli with internal functional biomaterials to serve cancer-oriented treatments is emergingly developed. Optical and acoustical activations have shown special promises as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage their contributions between optical and acoustical stimuli and find the appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelles (ICG@PEP@HA) containing ICG as photo/sonosensitizers, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting were fabricated. Triggered by external stimuli of laser and US irradiations, their photo/sonothermal performances, in vitro reactive oxygen species (ROS) production capabilities and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser induced more quantity of ROS which resulted in a significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analysis and corresponding rationales have been investigated. In the meanwhile, these hybrid nanomicelles were administered into the MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a PDT prevailing efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical stainings. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatments, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give birth to full accessibility to clinical translations for human cancer treatments by means of as-reported laser/US-nanomicelles combination strategy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
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2024
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IF 4
Chengmeng Jin,Wei Hu,Yuqi Wang,Hao Wu,Siying Zeng,Minfeng Ying,Xun Hu
Most cancer cells exhibit high glycolysis rates under conditions of abundant oxygen. Maintaining a stable glycolytic rate is critical for cancer cell growth as it ensures sufficient conversion of glucose carbons to energy, biosynthesis, and redox balance. Here we deciphered the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway. Knocking down or knocking out PKM2 induced a thermodynamic equilibration in the glycolytic pathway, characterized by the reciprocal changes of the Gibbs free energy (ΔG) of the reactions catalyzed by PFK1 and PK, leading to a less exergonic PFK1-catalyzed reaction and a more exergonic PK-catalyzed reaction. The changes of the ΔGs of the two reactions causes the accumulation of intermediates, including the substrate PEP (the substrate of PK), in the segment between PFK1 and PK. The increased concentration of PEP in turn increased PK activity in the glycolytic pathway. Thus, the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway maintains the reciprocal relationship between PK concentration and its substrate PEP concentration, by which, PK activity in the glycolytic pathway can be stabilized and effectively counteracts the effect of PKM2 KD or KO on glycolytic rate. In line with our previous reports, this study further validates the roles of the thermodynamics of the glycolytic pathway in stabilizing glycolysis in cancer cells. Deciphering the interaction between glycolytic enzymes and the thermodynamics of the glycolytic pathway will promote a better understanding of the flux control of glycolysis in cancer cells.
研究领域:
癌症生物学
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代谢途径
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热力学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2025
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IF 15.7
Haopeng Lin,Xin Liu,Feng Zhang,Deqi Chen,Xiaoxiao Xie,Qifei Dong,Jiawei Yan,Jiaxiang Yin,Zirong Bi,Zhihua Dou,Yingling Jiang,Kuo Jiang,Tongran Zhang,Peng Xue,Wei Peng,Lihua Chen,Tao Xu,Zonghong Li,Yanying Guo,Huisheng Liu
Human stem cell-derived β (SC-β) cells still exhibit limited glucose response required for insulin secretion due to glycolytic bottlenecks, yet how these metabolic abnormalities impact glucose response and functional maturation of SC-β cells remains unclear. In this study, we identify a metabolic checkpoint located at PEP accumulation that impedes the functional maturation, which is rescued by restoration of pyruvate kinase M1 ( PKM1 ). Glucose-tracing metabolomics in human stem cell-derived islets reveal abnormal glycolytic PEP accumulation at resting condition, associated with impaired calcium response and insulin secretion upon high glucose or glycolytic metabolite stimulation. Mechanistically, elevated PEP significantly raises intracellular basal calcium levels and downregulates expression of genes involved in TCA cycle as elucidated by single cell transcriptomics. Furthermore, the activity of pyruvate kinase, which metabolizes PEP, is notably reduced due to low PKM1 expression. Overexpression of PKM1 alleviates PEP accumulation, restores TCA-related gene expression, and enhances glucose-stimulated calcium responses and insulin secretion. Together, our findings reveal a critical role of PKM1-regulated PEP metabolism in SC-β cell functional maturation and highlight the importance of metabolic reprogramming for advancing stem cell-based therapies for diabetes. Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation of stem cell–derived islets for diabetes therapy.
研究领域:
糖尿病研究
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干细胞生物学
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代谢学
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再生医学
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细胞生理学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
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IF 7.145
Yan Jiang,Xiuzhen Wang,Xin Liu,Wei Lv,Hongjuan Zhang,Mingwan Zhang,Xinrui Li,Hongliang Xin,Qunwei Xu
Glioblastoma multiforme (GBM) presents one of the most lethal brain tumor with a dismal prognosis. And nanodrug delivery system (nano-DDS) have raised a lot of concern, while the conventional nanoformulations addressed many limitations, especially the low drug loading capacity and poor stability in vivo. Herein, we proposed PTX prodrug (PTX-SS-C18) conjugate self-assembled nanoparticles (PSNPs) functionalized with Pep-1, glioma homing peptide, to overcome the blood brain tumor barrier (BBTB) via interleukin 13 receptor α2 (IL-13Rα2)-mediated endocytosis for targeting GMB. This nanocarrier was with ultrahigh drug loading capacity (56.03%) and redox-sensitivity to the up-expression of glutathione in glioma tumors. And compared with PEG-PSNPs, Pep-PSNPs could significantly enhance cellular uptake in U87MG cells via IL-13Rα2-mediated endocytosis. Enhanced cytotoxicity of Pep-PSNPs against U87MG cells and BCEC cells pretreated with glutathione monoester (GSH-OEt) confirmed that this nanosystem was sensitive to reduction environment, and there was significant difference between targeting and nontargeting groups in MTT assay. Real-time fluorescence image of intracranialU87MG glioma-bearing mice revealed that Pep-PSNPs could more efficiently accumulate at tumor site and improve the penetration. Furthermore, the ex vivo fluorescence imaging and corresponding semiquantitative results displayed that the glioma fluorescence intensity of Pep-PSNPs group was 1.74-fold higher than that of nontargeting group. Pep-PSNPs exhibited remarkable antiglioblastoma efficacy with an extended median survival time. In conclusion, Pep-PSNPs had a promising perspective as a targeting drug delivery system of PTX for glioma treatment.
研究领域:
药物递送系统
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癌症治疗
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
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2026
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IF 6.7
Tianlong Huang,Zhen Mu,Yuanxiang Zhang,Maosheng Cui,Xiaoxiao Wang,Yang Zhang,Lingxiu Chen,Xiaolan Xue
Magnesium-metal organic batteries (MMOBs) are promising candidates for large-scale energy storage due to their high theoretical capacity, abundant resource, and cost-effectiveness. However, the high solubility of organic molecules and the commonly used thick glass fiber separators with poor mechanical strength and high cost hinder their further development. Herein, we report a ZIF-8/Carbon composite-modified polypropylene/polyethylene/polypropylene (ZIF-8/C@PEP) separator to overcome these limitations. This ZIF-8/C@PEP separator was fabricated by uniformly coating a mixture of ZIF-8 and carbon black onto a PEP separator via a doctor-blade method. The porous structure of ZIF-8 acts as a molecular sieve, effectively blocking the diffusion of soluble anthraquinone (AQ) species toward the anode while allowing facile Mg 2+ ion transport. Meanwhile, the carbon black enhances the separator’s compactness and provides additional physical confinement and adsorption sites for soluble molecules. Benefiting from these synergistic effects, by implementing the ZIF-8/C@PEP separator, Mg||Mg cells exhibit stabilized Mg plating/stripping behavior with reduced overpotential, while Mg||AQ full cells deliver good cyclability, maintaining a capacity of 104.8 mAh g −1 after 100 cycles at 0.05 A g −1 with a Coulombic efficiency of 98%. The results demonstrate that separator modification represents a promising strategy for enhancing the performance of MMOBs.
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Haipeng Tan,Weiyan Li,Zhiqing Pang,Xueyi Weng,Jinfeng Gao,Jing Chen,Qiaozi Wang,Qiyu Li,Hongbo Yang,Zheng Dong,Zhengmin Wang,Guangrui Zhu,Yiwen Tan,Yuyuan Fu,Chengzhi Han,Shiteng Cai,Juying Qian,Zheyong Huang,Yanan Song,Junbo Ge
Efferocytosis, mediated by the macrophage receptor MerTK (myeloid-epithelial-reproductive tyrosine kinase), is a significant contributor to cardiac repair after myocardial ischemia-reperfusion (MI/R) injury. However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK (main effector receptor), and overexpression of “do not eat me” signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post-MI/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Therefore, we aim to develop a strategy that challenges all three barriers in an integrated manner. Methods : We design a collaborative drug delivery strategy based on genetically modified macrophage therapy. The genetic engineering of exogenous macrophages involves overexpression of C-C chemokine receptor type 2 (CCR2) and cleavage-resistant MerTK (MerTK CR ) by adenovirus. Liposomes loaded with PEP-20 (a CD47 antagonist) are then anchored to the engineered macrophage surface by click chemistry. Results : CCR2 targets exogenous macrophages to the injured heart as a direct supplement to efferocytosis effector cells, while MerTK CR preserves functional intact locally. PEP-20 is responsively released to block the braking effect of CD47 on cardiac efferocytosis. In MI/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. Conclusion : Genetically engineered macrophages co-loaded with CD47 inhibitors synergistically reconstruct efferocytosis and improve cardiac remodeling post MI/R injury. This article is protected by copyright. All rights reserved
研究领域:
心脏病学
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分子生物学
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药理学
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基因工程
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产品关联
DOI
PubMed
高影响因子
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