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FOOD CHEMISTRY · 2022 · IF 9.231

A cyclodextrin-based reagent for cis/trans-geometrical isomers separation by mobility measurements and chemical calculations

Fangling Wu,Xishi Wu,Zhe Li,Di Zhang,Chuan-Fan Ding

Identification of cis/ trans -carbon–carbon double-bond (C C) isomers remain challenging. Herein, a simple and rapid method for the separation and analysis of cis/ trans -maleic acid (MA) and aconitic acid (AA) using Trapped Ion Mobility Spectrometry (TIMS) was developed. α-, β-, γ-cyclodextrin (CD) were served as the separation reagent, slight difference in mobility separation was obtained by [CD-MA/AA-H] - . Specially, with the addition of divalent metal ion (G 2+ ) as coordination metal ion, the separation effect was much increased by [CD-MA/AA + G-H] + , and α-CD has better mobility separation effect than β-/γ-CD. Moreover, chemical calculations revealed the binary and ternary complexes are in the inclusion forms, and microscopic interactions between cis/ trans -MA/AA, CDs, and G 2+ are somewhat different that making their mobility separation. Finally, quantifications of cis/ trans -isomers were analyzed in food samples, with good linearity (R 2  > 0.99) and recoveries obtained from 87.25 % to 100.73 %.

研究领域: 分析化学 · 计算化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Aconitic acid derived carbon dots: Conjugated interaction for the detection of folic acid and fluorescence targeted imaging of folate receptor overexpressed cancer cells

Jiali Qian,Feifei Quan,Fengjiao Zhao,Chengxin Wu,Zhaoyan Wang,Lei Zhou

Herein, we utilized aconitic acid (AA) as the precursor for preparing carbon dots (AA-CDs) by a facile hydrothermal reaction , and the resulting AA-CDs exhibited bright blue fluorescence with an absolute quantum yield of 56.5% in aqueous solution. Preliminary experiments showed that the prepared AA-CDs without further surface passivation or modification could selectively interact with folic acid (FA), resulting in significant fluorescence quenching. Based on this, a sensitive method for FA analysis was developed with a detection limit of 40 nM (S/N = 3), which was then successfully applied for the detection of FA in food and pharmaceutical samples with the average recoveries of 95.0–105.3%. Furthermore, a weak fluorescent nanoprobe (FA-AA-CDs) was fabricated based on the conjugated interaction of FA and AA-CDs, and its feasibility was evaluated as a fluorescence turn-on nanoprobe for targeted imaging of cancer cells using Hela, SMMC-7721, and A549 cells as models that expressed different levels of folate receptors (FRs) on the cell surface. The results exhibited that the fluorescence intensity of these cells was in accordance with their FRs expression levels, testifying its potential of FA-AA-CDs for targeted imaging of cancer cells. Subsequently, the internalization mechanism of FA-AA-CDs into cells was elucidated via receptor-mediated endocytosis using control experiments.

研究领域: 分析化学 · 纳米医学 · 肿瘤学 · 分子影像 · 药物递送 · 生物传感 · 细胞生物学
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Journal of Inflammation Research · 2025 · IF 4.1

M-CSF Protects Against Ulcerative Colitis via Aconitate: Mendelian Randomization and Experimental Evidence

Yuan Zhang,Longbin Huang,Ningning Yue,Zhiliang Mai,Chen Kong,Chengmei Tian,Dao-ru Wei,Jun Yao,Lisheng Wang,Defeng Li

Background Although cytokines have been implicated in the development of ulcerative colitis (UC), the potential mediating role of metabolite levels in this association remains unclear.Methods Utilizing data from genome-wide association studies (GWAS) encompassing 91 circulating cytokines, 1400 blood metabolites, and 178,689 UC cases, we performed a two-sample Mendelian randomization (MR) analysis to investigate the effect of metabolites mediated cytokines on the development of UC. A two-step MR analysis was conducted to quantitatively evaluate the mediation effect. Additionally, dextran sodium sulfate (DSS)-induced colitis mice were used to further confirm our results.Results Mendelian randomization (MR) analysis indicated that macrophage colony-stimulating factor (M-CSF) had a causal and positive relationship with aconitate (OR: 1.10, 95% CI: 1.00–1.20, p = 0.043, IVW beta 1 = 0.095). Moreover, MR analysis revealed that high level of aconitate were associated with reduced risk of UC (OR: 0.44, 95% CI: 0.24–0.80, p = 0.008, IVW beta 2 = −0.818). In addition, MR analysis showed M-CSF had an inverse correlation with the disease onset of UC (OR: 0.31, 95% CI: 0.15–0.80, p = 0.002, IVW beta all = −1.16). Furthermore, the mediation effect of aconitate mediated M-CSF on the risk of UC was −0.0777 (95% CI: −0.154 to −0.0018, p = 0.045), accounting for 6.69% of the total effect, and indicating a modest contribution to the protective effect of M-CSF against UC. Subsequently, as an in vivo validation model, DSS-induced colitis was employed to demonstrate that M-CSF treatment significantly ameliorated weight loss, disease activity index (DAI) scores, colon shortening, and histological damage. Additionally, M-CSF treatment also significantly reduced M1 macrophage infiltration, elevated levels of aconitate as well as itaconate, and decreased the levels of pro-inflammatory cytokines in colitis. These results demonstrated that aconitate inhibited the expression of pro-inflammatory cytokines through its enzymatic conversion into the immunometabolite itaconate by aconitate decarboxylase 1 (Acod1), and downregulated the levels of M1 macrophages, thereby ameliorating colitis.Conclusion These findings suggest that M-CSF is an important anti-inflammatory cytokine in UC, which may be a promising therapeutic target in the treatment of UC.

CAS / MDL: 619-27-2 67-56-1
研究领域: 免疫学 · 胃肠病学 · 遗传学 · 代谢组学 · 炎症研究 · 生物医学研究
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JOURNAL OF CONTROLLED RELEASE · 2017 · IF 7.786

Doxorubicin-conjugated Escherichia coli Nissle 1917 swimmers to achieve tumor targeting and responsive drug release

Songzhi Xie,Long Zhao,Xiaojie Song,Maosheng Tang,Chuanfei Mo,Xiaohong Li

The use of bacteria as drug carriers meets several challenges, such as biocompatibility, motility deterioration after drug loading and lack of in vivo verification. Escherichia coli Nissle 1917 (EcN) is one of the best studied probiotic strains, and doxorubicin (DOX) is conjugated onto EcN in the current study via acid-labile linkers of cis -aconitic anhydride (EcN-ca-Dox), realizing the bacteria-directed accumulation and acid-responsive release of anticancer drugs in tumors. The drug conjugation has maintained the bacterial motion profiles of over 9   μm/s and cell viability of over 70%. After 3   h and 3   days of intravenous injection of EcN-ca-Dox, DOX accumulations in tumors are determined as 12.9% and 6.4% of the injected doses per gram of tissue, respectively, which are much higher than the commonly used nanocarriers . Compared with free DOX and DOX-conjugated EcN via stable linkers of succinic anhydride , the EcN-ca-Dox treatment improves the antitumor efficacy with respect to the tumor growth inhibition, prolongation of animal survivals, and apoptosis induction of tumor cells. In addition, EcN has been cleaned off from tumors and other tissues after antimicrobial treatment. Thus, the acid-labile EcN conjugates provide a safe and concise strategy to enhance the temporal and spatial controllability of anticancer drugs.

研究领域: 药理学 · 肿瘤学 · 生物技术 · 药物递送系统
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Biomaterials Science · 2019 ·Vol. 7 ·期 8 ·3307-3319 · IF 5.251

A “self-accelerating endosomal escape” siRNA delivery nanosystem for significantly suppressing hyperplasia via blocking the ERK2 pathway

Bin Gao,Qiaoping Zhang,Xiaoyu Wang,Meiyu Wang,Xiang-kui Ren,Jintang Guo,Shihai Xia,Wencheng Zhang,Yakai Feng

Small interfering RNA (siRNA)-based therapy is an emerging treatment to address serious cardiovascular disease. It is essential to construct highly efficient vehicles for therapeutic siRNA intracellular delivery. Extracellular signal-regulated kinase-2 (ERK2) siRNA (abbreviated as ERK2-siRNA) is known as a type of siRNA to selectively silence the expression of ERK2. Herein, a type of ternary delivery system characterized by an endosome-selective-self-accelerating-escape ability was designed and prepared for the purpose of inhibiting the migration of vascular smooth muscle cells (VSMCs) in vitro. This system was called ternary ERK2-siRNA complexes (abbreviated as TRCs-Aco), which were fabricated via sequential electrostatic self-assembly of a star-shaped cell-penetrating peptide based on polyhedral oligomeric silsesquioxane (POSS-(C-G-R8-G-W)16), ERK2-siRNA and a pH-sensitive anionic polymer of cis-aconitic anhydride grafted ε-poly(L-lysine). Importantly, TRCs-Aco could break down the obstacle of biocompatibility-silencing efficiency. In comparison with the parent binary siRNA complexes (abbreviated as BRCs), which are composed of POSS-(C-G-R8-G-W)16 and ERK2-siRNA, our designed TRCs-Aco revealed more excellent biocompatibility including hemocompatibility and cytocompatibility. Unexpectedly, TRCs-Aco exhibited stronger ERK2 silencing efficiency at the level of mRNA and protein, which was mainly due to its remarkable self-accelerating endosomal escape. Definitive evidence demonstrated that this ternary ERK2-siRNA delivery system significantly prevented the migration of VSMCs and decreased the dermal thickness in bleomycin-treated mice. In brief, this unique structured system could provide a valuable nanoplatform for highly efficient siRNA delivery in VSMCs, and it might hold great potential in guiding ERK2-siRNA-based proliferative disease therapy.

CAS / MDL: 25761-72-2
研究领域: 纳米技术 · 药学 · 心血管疾病 · 分子生物学 · 治疗学
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Nanoscale · 2015 ·Vol. 8 ·期 1 ·104-116 · IF 7.394

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

Wenxiu Hou,Xin Zhao,Xiaoqing Qian,Fei Pan,Chunlei Zhang,Yuming Yang,Jesús Martínez de la Fuente,Daxiang Cui

The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo–photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo–photodynamic system for theranostics of lung cancer, etc. in the near future.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学 · 分子生物学
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