Advanced Healthcare Materials
·
2013
·Vol. 3
·期 2
·261-272
·
IF 0
Chun-Yang Sun,Shuang Dou,Jin-Zhi Du,Xian-Zhu Yang,Ya-Ping Li,Jun Wang
Polyphosphoesters with repeating phosphoester linkages in the backbone can be easily functionalized, are biodegradable and potentially biocompatible, and may be potential candidates as polymer carriers of drug conjugates. Here, the efficacy of a polyphosphoester drug conjugate as an anticancer agent in vivo is assessed for the first time. With controlled synthesis, doxorubicin conjugated to poly(ethylene glycol)- block -polyphosphoester (PPEH–DOX) via labile hydrazone bonds form spherical nanoparticles in aqueous solution with an average diameter of ≈60 nm. These nanoparticles are effectively internalized by MDA-MB-231 breast cancer cells and release the conjugated doxorubicin in response to the intracellular pH of endosomes and lysosomes, resulting in significant antiproliferative activity in cancer cells. Compared with free doxorubicin injection, PPEH–DOX injection exhibits much longer circulation behavior in the plasma of mice and leads to enhanced drug accumulation in tumor cells. In an MDA-MB-231 xenograft murine model, inhibition of tumor growth with systemic delivery of PPEH–DOX nanoparticles is more pronounced compared with free doxorubicin injection, suggesting the potential of polyphosphoesters as carriers of drug conjugates in cancer therapy.
研究领域:
药学
·
生物医学工程
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癌症研究
·
聚合物科学
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产品关联
DOI
PubMed
NANOTECHNOLOGY
·
2022
·Vol. 33
·期 27
·275604
·
IF 3.953
Kai Cheng,Jie Zhou,Yujie Zhao,Yu Chen,Lan Ming,Da Huang,Rui Yang,Zhenyu Lin,Daozhen Chen
Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.
研究领域:
纳米技术
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药学
·
癌症研究
·
高分子化学
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产品关联
DOI
PubMed
高影响因子
Food Science and Technology
·
2023
·
IF 2.602
HU Hao,LI Chengsheng,LYU Chunmao,MENG Xianjun,LI Bin,SHU Chi
The oxidation and structural properties of hazelnut protein prepared from a low-temperature cold-pressed hazelnut meal were evaluated using three oxidative modification methods: AAPH (2,2'-azo(2-methylpropionamidine)dihydrochloride), MDA (malondialdehyde), and H2O2. The three different oxidants gradually increased the carbonyl content of the proteins, MDA from 1.91 to 8.87 nmol/m, AAPH (from 2.13 to 12.18 nmol/mg, and H2O2 from 2.28 to 13.72 nmol/mg, indicating that the hazelnut protein was oxidized. The carbonyl content of H2O2-modified hazelnut proteins was the highest, implying that the proteins were more susceptible to oxidation by hydroxyl radicals. FT-IR, intrinsic fluorescence spectra, surface hydrophobicity, and protein electrophoresis implied that oxidative modifications altered the secondary structure of hazelnut proteins, and promoted protein aggregation and cross-linking. In addition, the oxidative modification resulted in a larger particle size distribution of hazelnut proteins and a decrease in the zeta potential absolute value, indicating a decrease in the hazelnut proteins stability and the formation of soluble aggregates. Overall, incubation with AAPH, MDA, and H2O2 significantly affected the structure of hazelnut proteins, demonstrating that hazelnut proteins in food processing systems are susceptible to structural and property changes due to different oxidation products.
研究领域:
食品科学
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蛋白质化学
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生物化学
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Chenlu Huo,Shuang Li,Anting Liu,Yujie Hong,Yan Zhu
It has been reported that the symptoms of rheumatoid arthritis (RA) can be ameliorated by acupuncture, an external treatment of traditional Chinese medicine. However, the immune mechanism underlying its action is elusive. Accordingly, this study investigated the role and mechanism of manual acupuncture (MA) in collagen-induced arthritis (CIA) in mice. The results demonstrated that MA or NaB treatment reduced Articular Index scores and right paw thickness and alleviated synovial inflammation and cartilage damage. MA or NaB treatment altered the content and relative abundance of short-chain fatty acids, particularly butyric and propionic acids, in feces. Additionally, MA or NaB treatment elevated SCD1, SREBP1, and GPX4 protein expression in synovial tissues and GSH-px contents in serum while decreasing ROS fluorescence intensity and MDA contents in peripheral blood. A linear correlation was found between the relative expression of SCD1 and SREBP1 in synovial tissues and the contents of propionic acids and butyric acids in feces, as well as between the contents of propionic acids and butyric acids. In summary, MA regulates butyric acids to inhibit ferroptosis, therefore suppressing inflammation in RA.
研究领域:
免疫学
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风湿病学
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中医
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Mengzhen Gu,Xiaoqing Xu,Xiaoping Wang,Yun Wang,Yu Zhao,Xiaoxian Hu,Lu Zhu,Zhenzhong Deng,Chao Han
Histone lysine-specific demethylase 1 (LSD1) is hyperactive in breast cancer, which is associated with the metastasis of the tumor. Current irreversible LSD1 inhibitors are all synthesized by covalently binding to the flavin adenine dinucleotide cofactor, which often have side effects due to the high affinity for a variety of targets. Here, we identified isoforsythiaside (IFA), a natural phenylpropanoid glycoside isolated from Forsythia suspensa, as a novel covalent inhibitor of LSD1. The target ligand fishing technique and LC–MS/MS analysis identified that IFA could covalently bind to the Ser817 residue of LSD1 by α,β-unsaturated ketone moiety to block the amine oxidase-like domain of LSD1. Moreover, RBMS3/Twist1/MMP2, the downstream signaling pathway of LSD1, was activated after IFA treatment to inhibit the metastasis of MDA-MB-231 cells in vitro and in vivo. This study provided novel molecular templates for development of LSD1 covalence-binding inhibitor and laid a foundation for developing agents against breast carcinoma metastasis for targeting LSD1.
研究领域:
癌症生物学
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药理学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Li Zhang,Hui-Xia Li,Wu-Si Pan,Farhan Ullah Khan,Cheng Qian,Feng-Rong Qi-Li,Xiaojun Xu
Background and aims Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and is characterized by steatosis, inflammation, and fibrosis. We aim to characterize the hepatoprotective effects of Leonurine hydrochloride (LH) and the possible pathway in a cell and rodent model of diet-induced steatohepatitis (NASH). Methods For in vitro studies, Palmitic acid (PA) and free fatty acid (FFA) induced HepG2 and HL7702 steatosis cell models were used. For in vivo studies, NASH was induced by feeding mice MCD diet. These mice received either placebo or LH at three different doses (50、100、200 mg/kg/day) for 6 weeks. Histological staining’s, and commercially available kits for ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. Results After establishing NASH models, LH treatment improved lipid accumulation, hepatic contents of TG, TC, and expression levels of ALT and AST in dose-dependent manner. Also, LH improved MDA, SOD, and GSH expression levels. The results of RT-PCR and Western blotting showed that LH upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes expression level. Conclusions Our data reveal the promising role of Leonurine hydrochloride in the prevention and treatment of NASH, in vitro and in vivo . This effect may be partially mediated by the AMPK/SREBP1 pathway. These findings provide a novel therapeutic target for the clinical treatment of NASH.
研究领域:
药理学
·
肝病学
·
代谢性疾病
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 44
·27496-27505
·
IF 3.108
Lyulin Hu,Sijie Ren,Qing Shen,Jianchu Chen,Xingqian Ye,Jiangang Ling
The effect of different cooking methods on protein and lipid oxidation of farmed sturgeon (Acipenser gueldenstaedtii) was investigated. In this study, the fish fillets were cooked using five different methods (boiling, steaming, microwaving, roasting and deep-frying), to an internal temperature of approximately 85 °C. General indexes for protein oxidation (carbonyls, free thiols and Schiff bases) and lipid oxidation were evaluated by spectrophotometric and fluorimetric methods. Side-chain modifications of amino acid residues were pinpointed by gel- and MS-based proteomic technology. The results are as follows: (1) cooking, especially roasting and frying, significantly increased the levels of carbonyls and Schiff bases and decreased the amounts of free thiols. (2) Oxidation of aromatic amino acids and extensive oxidation of lysine to carbonyl-containing compounds were characterized in all the cooked samples. (3) Indirect protein oxidation caused by interacting with lipid-derived aldehydes like malondialdehyde (MDA) and 4-hydroxynonenal (HNE) was also observed and much more pronounced in roasted and fried samples, giving a footprint of lipid–protein interaction during cooking. In summary, cooking treatment can induce protein oxidation in sturgeon fillets with a variety of modifications occurring at the protein primary structure. Molecular mapping of protein oxidation is conducive to understand the mechanism of cooking-induced protein oxidation and allows better control of the nutritional properties of protein-based products.
研究领域:
食品科学
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蛋白质组学
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营养学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 12
·1834-1843
·
IF 4.776
Chan Feng,Kun Wang,Yun Lin,Zhiwang Song,Yonglin Lu,Jie Liu,Donglei Zhu,Yongyong Li,Chunyan Dong
Compared with intracellular drug delivery, drugs with extracellular targeting sites are rarely considered. As one of these drugs, cyclopamine (CYC) is a promising anticancer drug that functions by targeting the cell membrane receptor. For improving therapeutic effect, an albumin-based nano-system (ABN) with the capacity for extracellular retention was developed. The ABN was formulated by incorporating bovine serum albumin (BSA) into nanoparticles at the denaturing temperature of BSA, with CYC acting as a hydrophobic nucleation site, followed by stabilization upon heat-induced disulfide cross-linking. The resultant ABNs are negatively charged with a nanoparticle size that can be delicately regulated by varying the reaction time. In MDA-MB-231 cells, the size and charge of ABNs significantly affected the extracellular retention capacity, with ABN-300 nm exhibiting an enhanced cytotoxic effect. In vivo fluorescence imaging revealed obvious and persistent tumor accumulation of ABNs. A therapeutic study in an orthotopic mammary fat pad tumor model shows that ABN-300 nm possesses the most remarkable antitumor effect compared with the control groups. These results provide a new strategy for improving the efficacy of drug targeting at extracellular sites.
研究领域:
药学
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纳米技术
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肿瘤学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Jing Wang,Lifei Xie,Tao Wang,Fengxin Wu,Jie Meng,Jian Liu,Haiyan Xu
Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes . To address this challenge, we designed an amphiphilic fullerene derivative (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery. To synthesize C 60 -Dex-NH 2 , terminally aminated dextran was conjugated to C 60 . The conjugate was further cationized by covalently introducing ethylenediamine to the dextran. The physicochemical characteristics of C 60 -Dex-NH 2 was examined with elemental analyses, gel permeation chromatography , solid-state nuclear magnetic resonance ( 13 C, HPDEC), agarose gel electrophoresis , and dynamic light scattering . The cytotoxicity, cellular uptake, intracellular distribution , and in vitro RNA interference (RNAi) of siRNA/C 60 -Dex-NH 2 complex was evaluated in the human breast cancer cell line MDA-MB-231. The RNAi efficiencies mediated by C 60 -Dex-NH 2 in vivo was evaluated in subcutaneous tumor-bearing mice. The results showed that C 60 -Dex-NH 2 has a specific amphiphilic skeleton and could form micelle-like aggregate structures in water, which could prevent siRNA from destroying by reactive oxygen species (ROS). When exposed to visible light, C 60 -Dex-NH 2 could trigger controllable ROS generation which could destroy the lysosome membrane, promote the lysosomal escape, and enhance the gene silencing efficiency of siRNA in vitro and in vivo . The gene silencing efficiency could reach a maximum of 53% in the MDA-MB-231-EGFP cells and 69% in the 4T1-GFP-Luc2 tumor-bearing mice. Statement of Significance We designed a novel photosensitive amphiphilic carrier (C 60 -Dex-NH 2 ) for efficient and controllable siRNA delivery, which can be used in gene therapy. We showed that C 60 -Dex-NH 2 could destroy lysosome membrane via controllable generation of ROS when exposed to light, which can help siRNA to escape from lysosome before degradation. This can enhance the gene silencing efficiency significantly and provides a useful way to regulate RNAi efficiency by light. One advantage for C 60 -Dex-NH 2 system is C 60 has broad absorbance spectrum and can be activated by weak visible light; Furthermore, C 60 -Dex-NH 2 has a specific amphiphilic structure, which may prevent siRNA from degrading and allows C 60 -Dex-NH 2 to embed into the lipid membrane of lysosome to improve the ROS induced lysosomal disturbance after internalization .
研究领域:
药学
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纳米技术
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 10
·3068
·
IF 4.927
Wenyun Wang,Song Liu,Mingyan Yan
Salinity is one of the major abiotic stresses limiting crop growth and productivity worldwide. Salt stress during germination degenerates crop establishment and declines yield in wheat, therefore alleviating the damage of salt stress to wheat seedlings is crucial. Chitooligosaccharide (COS) was grafted with γ-aminobutyric acid based on the idea of bioactive molecular splicing, and the differences in salt resistance before and after grafting were compared. The expected derivative was successfully synthesized and exhibited better salt resistance-inducing activity than the raw materials. By activating antioxidant enzymes such as superoxide dismutases (SOD), catalase (CAT) and phenylalanine ammonia-lyase (PAL) and subsequently eliminating reactive oxygen species (ROS) in a timely manner, the rate of O−2production and H2O2content of wheat seedlings were reduced, and the dynamic balance of free radical metabolism in the plant body was maintained. A significantly reduced MDA content, reduced relative permeability of the cell membrane, and decreased degree of damage to the cell membrane were observed. A significant increase in the content of soluble sugar, maintenance of osmotic regulation and the stability of the cell membrane structure, effective reduction in the salt stress-induced damage to wheat, and the induction of wheat seedling growth were also observed, thereby improving the salt tolerance of wheat seedlings.Keywords:chitooligosaccharide;γ-aminobutyric;salt stress
研究领域:
植物科学
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农业生物技术
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逆境生理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Han Mengyao,Zhang Zhongshan,Li Xinyue,Tong Haibin,Xu Zhiguo,Ding Zikang,Yang Anquan,Xie Min,Wang Xiaomei
To investigate the protective effect of collagen peptide from Micropterus salmoides skin (CPMs) on oxidative damage induced by cyclophosphamide in mice. Balb/c female mice were divided into blank, model (cyclophosphamide, CTX), positive control (levamisole hydrochloride), and collagen peptide low-, medium-, and high-dose groups. The results showed that CPMs increase the body mass and immune-related organ indexes, such as liver and kidneys of immunosuppressed mice. The activities of ALT, AST, UA, BUN, and MDA in the liver and kidney tissues decreased significantly, while those of SOD and GSH-Px increased significantly. CPMs can relieve the pathological damage to immune organs. CPMs significantly increase the activities of IL-2, IgG, and TNF-α in serum and SOD activity, while the MDA content was decreased compared to the model group. CPMs can exert a protective effect on cyclophosphamide-induced oxidative damage and have application prospects in the field of health food.
研究领域:
药理学
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免疫学
·
毒理学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-11
·
IF 4.6
Fengchao Chen,Siya Zhang,Tongtong Yan,Hongquan Wang,Jie Li,Qiang Wang,Danish Subhan,Kun Li
Recently, natural photosensitizers, such as berberine, curcumin, riboflavin, and emodin, have received more and more attention in photodynamic therapy. Tanshinone I (TanI) is extracted from a traditional Chinese herb Danshen, and exhibits many physiological functions including antitumor. TanI is a photoactive phytocompounds, but no work was tried to investigate its potential photodynamic effect. This study evaluated the cytotoxicity induced by the photodynamic effect of TanI. The photochemical reactions of TanI were firstly investigated by laser flash photolysis. Then breast cancer cell line MDA-MB-231 was chosen as a model and the photodynamic effect of TanI on cancer cell was evaluated by MTT assay and flow cytometry. The results showed that TanI could be photoexcited by its UV–Vis absorption light to produce 3 TanI* which was quickly quenched by O 2 . MTT assay showed that the photodynamic effect of TanI resulted in more obvious inhibitive effect on cell survival and cell migration. Besides, the photodynamic effect of TanI could induce cell apoptosis and necrosis, lead to cell cycle arrest in G2, increase intracellular ROS, and decrease the cellular Δψm. It can be concluded that the photodynamic effect of TanI can obviously enhance the cytotoxicity of TanI on MDA-MB-231 cells in vitro, which indicated that TanI might serve as a natural photosensitizer.
研究领域:
药理学
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肿瘤学
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光动力疗法
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）