MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Wanjun Han,Zheyue Bo,Ting Liang,Han Liu,Lanjing Li,Zhening Guo,Ru Huan,Bruno Hagenbuch,Chunshan Gui
Organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 are two highly homologous transport proteins. However, OATP1B1- and 1B3-mediated estradiol-17β-glucuronide (E17βG) uptake can be differentially affected by clotrimazole. In this study, by functional characterization on chimeric transporters and single mutants, we find that G45 in transmembrane domain 1 (TM1) and V386 in TM8 are critical for the activation of OATP1B3-mediated E17βG uptake by clotrimazole. However, the effect of clotrimazole on the function of OATP1B3 is substrate-dependent as clotrimazole does not stimulate OATP1B3-mediated uptake of 4′,5′-dibromofluorescein (DBF) and rosuvastatin. In addition, clotrimazole is not transported by OATP1B3, but it can efficiently permeate the plasma membrane due to its lipophilic properties. Homology modeling and molecular docking indicate that E17βG binds in a substrate binding pocket of OATP1B3 through hydrogen bonding and hydrophobic interactions, among which its sterol scaffold forms hydrophobic contacts with V386. In addition, a flexible glycine residue at position 45 is essential for the activation of OATP1B3. Finally, clotrimazole is predicted to bind at an allosteric site, which mainly consists of hydrophobic residues located at the cytoplasmic halves of TMs 4, 5, 10, and 11.
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2021
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IF 7.514
Peng Wang,Xinxin Xu,Shanshan Song,Aihong,Wu,Liqiang Liu,Hua Kuang,Chuanlai Xu
In this study, an ultrasensitive monoclonal antibody (mAb) was produced and used to develop a gold nanoparticle-based lateral flow immunochromatographic (ICA) strip for screening of clomazone (CLO) in potato and pumpkin samples. With assayed by indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) method, the mAb belonging of IgG2 subclass showed a half-maximal inhibitory concentration (IC50) of 3.47 ng/mL and a linear range of detection of 0.43–28.09 ng/mL. A cross-reactivity test revealed that the mAb had good specificity for CLO. The strip assay had a visual limit of detection (LOD) of 5 µg/kg and a cut-off value of 50 µg/kg for CLO pumpkin samples (potato samples was 100 µg/kg) when evaluated with the naked eye. The results were consistent with ic-ELISA and high performance liquid chromatography tandem mass spectrometry (HPLC-MS). Thus, this ICA strip assay represents a potentially tool for on-site and rapid initial detection of CLO in potato and pumpkin samples.
研究领域:
分析化学
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免疫学
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DOI
PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-12
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IF 3.8
Song Yang,Zhang Hui,Geng Jie,Chen Haoran,Bo Yang,Lu Xuechun
Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2023
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IF 2.6
Miao Ma,Jidong Wang,Xiaotong Yang,Yixin Qu
In this paper, the solubility of clotrimazole, an antifungal drug, in 10 alcohols (n-propanol, iso-propanol, n-butanol, iso-butanol, sec-butanol, n-pentanol, iso-pentanol, n-hexanol, n-heptanol, and n-octanol) and 6 esters (methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, isopropyl acetate, and methyl propionate) was experimentally determined using a laser dynamic solubility-monitoring device in a temperature range of 283.15 to 323.15 K at atmospheric pressure. The functions of solubility versus temperature were regressed using three semi-empirical models (modified Apelblat, three-parameter van’t Hoff, and λh) and two activity coefficient models (Wilson and NRTL). The results show that all the five models can be used to correlate the solubility of clotrimazole with temperature in these solvents satisfactorily. Furthermore, the thermodynamic mixing properties (ΔmixG, ΔmixH, ΔmixS, ln(γ1∞), and H1E, ∞) were evaluated using the measured solubility values and Wilson model parameters.
研究领域:
药物化学
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物理化学
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热力学
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DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
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IF 7.129
Xiaolei Wang,Hong Lu,Qiansheng Li,Yang Zhou,Jiti Zhou
Anthraquinone compounds (ACs) could be efficiently degraded and detoxified by bacteria. However, the molecular mechanism of bacterial degradation and detoxification of ACs remains unclear. In this study, 1-aminoanthraquinone-2-sulfonate (ASA-2) was used as a model anthraquinone compound, the response mechanism of Rhodococcus pyridinivorans GF3 to ASA-2 using genomics and transcriptomics techniques was investigated. Comparative genome analysis showed that strain GF3 owned an especial gene region (Genes 1337–1399) containing the genes encoding cytochrome P450, monooxygenase, dehydrogenase and oxidoreductase, which did not commonly exist in Rhodococcus genus. The amino acid sequences of these genes were similar to those of the cleavage enzymes of anthraquinone ring in Aspergillus genus. Moreover, the transcriptions of Genes 1392–1394 (cytochrome 450 gene cluster) displayed 1.8–3.1-fold up-regulation under ASA-2 exposure. Meanwhile, as an intermediate product of ASA-2, catechol was degraded to acetyl-CoA, succinyl-CoA and pyruvate, resulting in the enhanced tricarboxylic acid cycle and ATP generation. This process also promoted the up-regulation of the genes encoding resistance, efflux, transporter and anti-oxidation pressure proteins, which were involved in resisting ASA-2 and maintaining the homeostasis of cells. These results provided us with a further understanding of the molecular mechanism of degradation and detoxification of ACs.
研究领域:
微生物学
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环境科学
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分子生物学
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基因组学
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转录组学
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PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Guowei Li,Kai Lv,Xiangjun Pan,Siting Zhou,Hui Xing,Jun Xu,Dong Ma,Yunfeng Hu,Hao Xu
The low permeability of antifungal agents to fungal biofilms , which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine , herein, a dynamic delivery system [email protected] /NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles , in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction , while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system [email protected] /NONOate could efficiently and synergistically eliminate planktonic Candida albicans ( C. albicans ) in a safe and no toxic side effect manner, and effectively cured C. albicans -induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans -induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. Statement of significance A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans , but did not show significant cytotoxicity to normal somatic cells .
研究领域:
药学
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微生物学
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纳米医学
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DOI
PubMed
高影响因子
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