Frontiers in Pharmacology
·
2018
·
IF 3.831
Tsai Hsiang-I,Jiang Lijuan,Zeng Xiaowei,Chen Hongbo,Li Zihuang,Cheng Wei,Zhang Jinxie,Pan Jie,Wan Dong,Gao Li,Xie Zhenhua,Huang Laiqiang,Mei Lin,Liu Gan
The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-b-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.
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Scientific Reports
·
2024
·Vol. 14
·期 1
·1-9
·
IF 3.8
Yuan Fang-Fang,Wang Pei,Han Xiao-Jie,Qin Ting-Ting,Lu Xin,Bai Hai-Jiao
The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.
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Nanoscale
·
2015
·Vol. 8
·期 5
·3100-3118
·
IF 7.394
Di Jiang,Xiaoling Gao,Ting Kang,Xingye Feng,Jianhui Yao,Mengshi Yang,Yixian Jing,Qianqian Zhu,Jingxian Feng,Jun Chen
Drug resistance is the major reason for therapeutic failure during cancer treatment. Chemo-photodynamic combination therapy has potential to improve the treatment efficiency in drug-resistant cancers, but is limited by the incompatible physical properties of the photosensitizer with a chemo-drug and poor accumulation of both drugs into the inner areas of the tumor. Herein, a novel drug delivery system was designed by incorporating the photosensitizer, chlorine 6, chemically in the shell and the chemo-drug, doxorubicin, physically in the core of D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactic acid) (TPGS-PLA) nanoparticles with a targeting ligand, tLyp-1 peptide, decorated over the surface (tLyp-1-NP). This nanoparticle with a high drug loading capacity of both the photosensitizer and chemo-drug is expected to realize chemo-photodynamic combination therapy of drug-resistant cancer and simultaneously achieve the specific deep penetration and accumulation of drugs into the inner areas of tumor. tLyp-1-NP was prepared via a nanoprecipitation method and it exhibited a uniformly spherical morphology with a size of approximately 130 nm. After appropriate irradiation, tLyp-1-NP showed high cellular uptake and strong cytotoxicity in both human umbilical vein endothelial cells (HUVEC cells) and doxorubicin-resistant human breast adenocarcinoma cells (MCF-7/ADR cells) in vitro. After intravenous administration, compared with the unmodified NPs, tLyp-1-NP was found to have superior tumor targeting ability and more potent reversion of doxorubicin-resistant cancer. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and the hematoxylin and eosin staining of the treated tumors further demonstrated the anti-tumor efficacy of tLyp-1-NP in the presence of a laser. These observations collectively suggest the potential of tLyp-1-NP for the actively targeting chemo-photodynamic combination therapy of drug-resistant cancer.
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Materials Today Chemistry
·
2025
·
IF 6.7
Minghao Zhai,Wanan Cai,Jingtao An,Chunli Ma,Tingting Zhou,Haijun Niu,Wen Wang
A highly efficient, stable electrochromic (EC) material with high photoluminiscent (PL) intensity contrast is crucial in EC/electrofluorochromic (EC/EFC) bifunctional devices (EC/EFCD) which play important role in display and camouflage. To solve this issue, we utilized non-planar triphenylamine (TPA) with electron-accepting triphenyltriazine (TPT) to construct novel electron-rich donor-electron-deficient acceptor (D-A) type diamine monomer, which was polymerized with three different diacid monomers to form three non-conjugated polyamides (PAs). TPT-TPA-CA film exhibits strong solid-state emission ( φ PL = 74 %), suitable for highly integrated EC/EFCD, maintaining not only high optical transmittance change ( ΔT = 46 %) after cycling for 3000 s but also high PL intensity contrast ( ΔPL = 70 %). Furthermore, these PAs are yellow in the neutral (bleached) state and green in the oxidized (colored) state during the EC process, demonstrating their potential for display and military camouflage. Especially, TPT-TPA-OA film exhibits good cycle stability (more than 15000 s), high ΔT (72 %), and fast response times (3.5 s/4.1 s for t c / t b ) . Moreover, due to strong emission, TPT-TPA-CA exhibits promising in the application of chemical sensors which has low limit of detection ( LOD ) for the explosive 2,4,6-Trinitrophenol (TNP) ( LOD = 76 nM in solution and LOD = 304 nM in film). In summary, this research provides a novel approach for the field of EC/EFC displays and chemical sensors.
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JOURNAL OF BIOTECHNOLOGY
·
2015
·
IF 2.871
Yu-Cai He,Zhi-Cheng Tao,Yun Ding,Dan-Ping Zhang,Yin-Qin Wu,Yun Lu,Feng Liu,Yu-Feng Xue,Cheng Wang,Jian-He Xu
To avoid adding NAD + and effectively transform ethyl 4-chloro-3-oxobutanoate, the mixture of l -glutamine (200 mM) and d -xylose (250 mM) was added into in n -butyl acetate–water (10:90, v/v) biphasic system instead of NAD + for increasing the biocatalytic efficiency. To further improve the synthesis of optically pure ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ), β-cyclodextrin was also added into this reaction media, and ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ) could be effectively synthesized from 800 mM ethyl 4-chloro-3-oxobutanoate in the yield of 100% by whole-cells of recombinant E. coli CCZU-A13. Finally, the possible mechanism for improving the reductase activity by supplementation of l -glutamine, d -xylose and β-CD was proposed. In conclusion, this strategy has high potential for the effective biosynthesis of ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ).
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Journal of Macromolecular Science Part B-Physics
·
2020
·
IF 0.911
Dan Wang,Jianjun Fang,Wenjuan Liu,Tianlong Huang,Yanmin Zhao,Jianglong Duan,Hailin Xie,Ping Chen,Ziwei Zhou,Zhihua Zhou
Poly(L-lactide-co-glycolide-co-ε-caprolactone) (PLLGC) and 1,4-butanediamine modified maleated poly(D,L-lactide-co-glycolide) (BMPLGA) were both synthesized by ring-opening polymerization with stannous octoate as catalyst. Then PLLGC/BMPLGA blend porous films were prepared by using NaCl particles as a porogen through a solvent casting/particle leaching method. The PLLGC/BMPLGA blend porous films were characterized by Fourier transform infrared spectroscopy, gel permeation chromatography and scanning electron microscopy. The tensile properties of the PLLGC/BMPLGA porous films were also studied. The results showed that the content and size of the NaCl porogens had significant effects on the porosity of the PLLGC/BMPLGA porous films. The tensile strength and elongation percentage of the porous films decreased with increasing porogen content. Thus, both the pore structure and mechanical properties of the porous PLLGC/BMPLGA blend films can be controlled by changing the amount and size of the porogen.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Xia Liu,Hui Li,Ningning Shan,Bingxin Guan,Yang Jiang,Chengyun Zheng,Leisheng Zhang,Dexiao Kong
Aplastic anemia (AA) is a debilitating disorder marked by bone marrow failure, frequently associated with dysregulated T cell activity. The present study explored the therapeutic potential of anti-CD3 antibody-modified calcium silicate nanoparticles loaded with novel 7H-pyrrolo[2,3-d]pyrimidine derivatives (antiCD3-pCaSiNP@NPDP) for AA treatment. Whole-transcriptome sequencing and bioinformatics analysis identified interleukin-2-inducible T-cell kinase (ITK) as a critical regulator of T cell function in AA. In vitro experiments demonstrated that ITK enhances T cell proliferation and promotes differentiation toward inflammatory subsets, thereby contributing to disease progression. The newly developed NPDP derivatives effectively inhibited ITK activity. Targeted delivery of NPDP via antiCD3-pCaSiNP nanoparticles selectively suppressed ITK expression in T cells, resulting in reduced inflammatory T cell proliferation and increased regulatory T cell populations. In an AA mouse model, administration of antiCD3-pCaSiNP@NPDP nanoparticles markedly improved hematopoietic recovery and immune balance. The findings indicate that nanoparticle-mediated ITK inhibition represents a promising therapeutic strategy for restoring immune and bone marrow function in AA.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Tong Zhou,Xue Xia,Heping Cui,Yun Zhai,Foxin Zhang,Khizar Hayat,Xiaoming Zhang,Chi-Tang Ho
The influence of pH was studied on volatile flavor formation during thermal treatment of an Amadori rearrangement product (ARP) with or without the addition of cysteine (Cys). The formation of thiols and sulfides or 2-acetylthiazole and pyrazines induced by Cys during thermal degradation of ARP was pH-dependent. At low pH levels, the hydrolysis of Cys to hydrogen sulfide (H2S) was promoted, giving rise to the increase of thiols and sulfides with an obvious meaty aroma. However, alkaline conditions were beneficial for enhancing the cyclization or transformation of imine to the enol structure, which strengthened the formation of 2-acetylthiazole and pyrazines with a roasted and nutty aroma. The imine was derived from the nucleophilic addition of Cys and methylglyoxal (MGO) and subsequent decarboxylation. At pH 8, Cys-induced variation of the flavor profile was weakened during thermal degradation of ARP. Accordingly, the combinational effect of pH and added Cys could be beneficial for achieving the desirable flavors during thermal processing of ARP.
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Food Bioscience
·
2022
·
IF 5.318
Caixing Pan,Heping Cui,Khizar Hayat,Xiaoming Zhang,Chi-Tang Ho
This research elucidated the reason of flavor deficiency during the thermal degradation of glutamic acid (Glu)-galactose (Gal) Amadori rearrangement product (GG-ARP) and the solution. The flavor formation from GG-ARP during the thermal degradation was investigated. Compared to the volatile compounds in Glu-Gal Maillard reaction products (GG-MRP), pyrazines in the volatile compounds derived from GG-ARP were restrained. The disadvantage in evolution asynchrony and content sufficiency of α -dicarbonyl compounds and Glu in the GG-ARP model limited the pyrazines formation. With the addition of Gal, the asynchronous effect was further exacerbated, and the furans in the GG-ARP-Gal model (956.81 μg/L, 120 °C, 60 min) were more significantly dominant among the volatile flavor compounds than in the GG-ARP model (454.98 μg/L, 120 °C, 60 min), while the pyrazines were still missing. Whereas, the extra-added Glu in the GG-ARP model could offset the deficiency of amino acids growth after α -dicarbonyl formation and promote the formation of pyrazines (74.47 μg/L, 120 °C, 60 min). Meanwhile, the formation of diketones (92.96 μg/L, 120 °C, 60 min) was promoted. The addition of Glu enhanced both milk-like and baking flavor of the GG-ARP system simultaneously. Formulated GG-ARP-Glu mixture was proposed to promisingly achieve the controlled formation of process flavors for baked foods with both desirable milk-like and baking scent.
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BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 6
·e5866
·
IF 1.8
Zhijian Zha,Ruihua Wang,Qian Wang,Fahui Chen,Ziyang Ye,Yafeng Li
Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC–tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l - and d -amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d -amino acids and 20 l -amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l - and d -amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l -amino acids and lower concentrations of d -amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Lunhe Wang,Jun Lu,Pengcheng Zhang,Juanjuan Su,Jian Han
In high molecular weight poly(L-lactic acid)/poly(D-lactic acid) (HMW PLLA/PDLA) blends, the construction of exclusive stereocomplex crystals (SC) with high crystallinity and strong melt memory remains a great challenge. In the present study, various norbornene dicarboxylate complexes (TMX Na, Mg, Al, or Ca) were employed as the stereo-selective nucleating agents (NAs), and their effect on the crystallization characteristics, rheological behavior, and heat resistance of PLLA/PDLA blends were thoroughly studied. Strikingly, TMX-Al facilitated the construction of exclusive SC with over 50 % crystallinity and excellent melt memory. The dense SC crystals network structure boosted the heat resistance of L/D-xAl blends with a VST as high as 145 °C. The strengthened intermolecular interaction fostered the generation of pre-ordered structure in the melt and enhanced chain interdiffusion, which contributed to intermolecular nucleation and SC crystallization in L/D-xAl blend. This study opens up a new avenue for melt processing and application development of SC-PLA materials.
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JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 9
·1600-1609
·
IF 3.614
An Kang,Jialu Jiang,Qin Li,Xianjie Sheng,Yan Chen,Jiani Tan,Liu Li,Weixing Shen,DongXin Tang,Haibo Cheng,Dongdong Sun
Scutellaria barbata D. Don ( S. barbata ) is one of the most frequently used anticancer herb medicine in China. Mechanistic understanding of the biological activities of S. barbata is hindered by limited knowledge regarding its components and metabolic profile. In this study, ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (quadrupole time-of-flight mass spectrometry) was used to identify the chemical constituents in S. barbata and their metabolic profiles in rats. By applying cleavage rules and comparison with reference substances, 89 components were identified in S. barbata , which included 45 flavonoids, 28 diterpenoids, 10 phenolics, and 6 others. A total of 110 compounds, including 32 prototype compounds and 78 metabolites, were identified or tentatively characterized in vivo. Methylation, sulfonation, and glucuronidation were the main metabolic pathways, which could be attributed to the fact that several of the compounds in S. barbata have phenolic hydroxyl groups. This is the first systematic study on the chemical constituents and in vivo metabolic profile of S. barbata . The analytical method features a quick and comprehensive dissection of the chemical composition and metabolic profile of S. barbata and provides a basis for exploring its various biological activities.
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