TOXICOLOGY AND APPLIED PHARMACOLOGY
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2023
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IF 3.8
Yixin Sun,Danyang Guo,Saiding Yue,Mingyan Zhou,Dongxu Wang,Fengjiao Chen,Lingling Wang
Background Doxorubicin (DOX), a chemotherapeutic drug, could relieve the progressions of various diseases. However, its clinical application is limited due to its cardiotoxicity. This study aimed to investigate the effects of afzelin (a flavonol glycoside found in Houttuynia cordata ) on the cardiotoxicity induced by DOX. Methods In ex-vivo, H9C2 cells were incubated with 20, 40, or 80 μM afzelin for 12 h, followed by the treatment with 1 μM DOX for 12 h. In vivo, C57BL/6 J mice were intraperitoneally injected with 4 mg/kg/day DOX on days 1, 7, and 14. Meanwhile, starting from day 1, mice were intragastrically administrated with 5 mg/kg/day or 10 mg/kg/day afzelin for 20 days. The cardiac function of mice was evaluated by detecting hemodynamic parameters using the M-mode echocardiography. Results DOX decreased the cell survival rate, and elevated apoptotic rate, as well as induced the oxidative stress and mitochondrial dysfunction in H9C2 cells. All these changes were alleviated by afzelin treatment in a concentration-dependent manner. The results were further proven by the mitigation of cardiac injury in vivo, as evidenced by the elevation of fractional shortening, heart weight/tibia length, and the rate of the increase/decrease of left ventricular pressure in mice subjected to DOX-induced cardiotoxicity. Furthermore, afzelin upregulated the expression of p-AMP-activated protein kinase alpha (AMPKα) and sirtuin1 (SIRT1). Dorsomorphin (an AMPKα inhibitor) abrogated the anti-cardiotoxicity effects of afzelin in H9C2 cells induced by DOX. Conclusion Afzelin protected against DOX-induced cardiotoxicity by promoting the AMPKα/SIRT1 signaling pathway.
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2023
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IF 5
Yang Xiaoling,Zhao Shunan,Deng Yong,Xu Weidong,Wang Zonghan,Wang Wenjun,Lv Ruiling,Liu Donghong
Abstract This study aimed to evaluate the antibacterial activities of α-terpineol against common foodborne pathogenic bacteria by agar well diffusion, broth microdilution, and colony counting assay. Propulsive research was conducted to reveal the antibacterial mechanisms, including morphology, infrared spectroscopy, membrane fluidity, membrane permeability, proton motive force, and oxidative phosphorylation. Results indicated that the antibacterial activity of α-terpineol decreased in the following order: Escherichia coli O157:H7, Salmonella typhimurium , Listeria monocytogenes , and Staphylococcus aureus . With an initial cell count of 8 log CFU/mL, α-terpineol at 0.8% (v/v) reduced E. coli O157:H7 and S. aureus by approximately 5.6 and 3.9 log CFU/mL within 1 h, respectively. Remarkable destruction in cell envelopes and intracellular organizations was observed. The hydroxyl of α-terpineol might form glycosidic bonds with carbohydrates and hydrogen bonds with PO 2 − and COO − via infrared spectroscopy analysis. Generalized polarization of Laurdan revealed that the polar head groups of phospholipids transformed into close packed. The anisotropy variations of trimethyl amino-diphenylhexatriene (TMA-DPH) and DPH suggested membrane fluidity decreased. The N-phenyl-1-naphthylamine intake assay indicated that α-terpineol impaired the cell wall. Propidium iodide staining was indicative of damaged plasma membranes. Electron transport in the cytoplasmic membrane was impaired, inducing reactive oxygen species accumulation. Both membrane electrical potential and membrane pH gradient collapsed. The disruption of proton motive force and the leakage of ATP resulted in a deficit of intracellular ATP. Our research revealed the interaction between the hydroxyl group of α-terpineol and bacteria affects membrane function contributing to the bacteria’s death. Key points • α-Terpineol hydroxy formed glycosidic bonds and hydrogen bonds with bacteria • α-Terpineol increased the membrane gelation and reduced the membrane fluidity • Proton motive force and oxidative phosphorylation were impaired Graphical abstract
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ACS Applied Nano Materials
·
2023
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IF 5.9
Guangli Li,Xuan Wan,Yonghui Xia,Du Tuo,Xiaoman Qi,Tianyu Wang,Mohammad Mehmandoust,Nevin Erk,Quanguo He,Qing Li
The excessive use of levofloxacin (LEV) can lead to significant environmental pollution, while also damaging human health. The accurate detection of its concentration is therefore essential to protect both the environment and human health. Herein, we report the simple synthesis of α-zirconium phosphate supported on nitrogen-doped graphene nanosheets (α-ZrP/NG) and its application in the voltammetric determination of trace LEV in real samples. The surface morphology, microstructure, and electrochemical properties of α-ZrP/NG were investigated by microscopic and spectroscopic techniques. The analytical parameters, including the accumulation potential, accumulation time, loading volume, and buffer pH, were optimized to improve the electrocatalytic sensing performance of α-ZrP/NG. Owing to the synergetic interaction between α-ZrP and NG, the proposed sensor exhibited an excellent electrocatalytic activity for the electrical oxidation of LEV. In the range of 0.01–5.0 μM, the anodic peak current of LEV increased linearly with an increase in the LEV concentration, and the limit of detection was 2.6 nmol L–1. Finally, the LEV levels in wastewater, human serum, milk, and eye drop samples were determined by using the α-ZrP/NG system combined with a glassy carbon electrode to give satisfactory recoveries (98.48–103.2%), indicating that the prepared sensor demonstrates promise for use in environmental, food, and drug monitoring applications.
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MICROCHEMICAL JOURNAL
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2023
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IF 4.8
Huanan Guan,Bolin Han,Bo Peng,Hua Ye,Qi Zhang,Dongxu Wang
Herein, the turn-off colorimetric system based on magnetic supported gold-copper bimetallic organic framework (Fe 3 O 4 @Au/Cu-MOF) nanozyme catalytic reaction has developed for the high sensitivity spectrophotometric determination of glutathione (GSH). Fe 3 O 4 is embedded into Cu-MOF to reduse aggregation, exposing more active metal sites. The uniform size, high dispersity of Au and the 2D Cu-MOF structure with coordinatively unsaturated metal sites enhances the host–guest electron transfer. The intrinsic catalytic activity of each site was enhanced due to the synergistic interaction between the three metals. Meanwhile, the Fe 3 O 4 @Au/Cu-MOF was recyclable, maintaining a relative activity of more than 87.4% after 10 cycles, and the catalytic activity remained stable at pH 3–11 and temperature ranging from 5 to 70 °C. Fe 3 O 4 @Au/Cu-MOF nanocomposites displayed higher peroxidase activity than their individual components, which can be utilized in catalysis to oxidise the peroxidase substrate 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) into a green-colored product in the presence of H 2 O 2. After the introduction of GSH, the green color ABTS •+ was gradually fading owing to the free radical scavenging effect. The novel colorimetric sensing platform demonstrated excellent performance for GSH detection in real samples with a detection limits of 0.033 μmol/L, the detection time of only 3 min. The suggested bioassay is user-friendly, economical, and applicable to both food analysis and medical diagnostics.
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Journal of Translational Internal Medicine
·
2023
·Vol. 11
·期 3
·294-308
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IF 4.9
Naiquan Liu,Dongyang Li,Dajun Liu,Ying Liu,Jing Lei
Background
Fos-related antigen 2 ( FOSL2 ) plays a facilitative role in fibrotic disease; however, its role in renal fibrosis remains unclear. This study aimed to clarify the role and underlying mechanisms of FOSL2 in renal fibrosis.
Methods
Upregulated genes in unilateral ureteral obstruction (UUO)-injured kidneys were screened in Gene Expression Omnibus (GEO) databases, and overlapping genes were identified using Venn diagram software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for these genes. The UUO-induced mouse model and transforming growth factor-β1 (TGF-β1)-induced cell model were used for the in vivo and in vitro studies.
Results
A total of 43 commonly upregulated genes were identified. GO and KEGG pathway analyses indicated that FOSL2 may be involved in fibrosis. Furthermore, FOSL2 was confirmed to be upregulated in UUO-injured kidneys and TGF-β1–induced cells. Knockdown of FOSL2 ameliorated interstitial fibrosis, extracellular matrix deposition, and epithelial-mesenchymal transition via the downregulation of fibronectin, α-smooth muscle actin (α-SMA), collagen type I ( Col1a1 and Col1a2 ), and Col5a1 and upregulation of E-cadherin . Bioinformatics analysis revealed that serum/glucocorticoid regulated kinase 1 ( SGK1 ) may be regulated by FOSL2 and involved in renal fibrosis. Further experiments confirmed that TGF-β1 enhanced SGK1 expression and transcription, which were reversed by FOSL2 silencing. Moreover, FOSL2 was bound to the SGK1 promoter, and SGK1 overexpression reversed the effects of FOSL2 silencing in TGF-β1–induced cells.
Conclusion
FOSL2 plays an essential role in promoting renal fibrosis in an SGK1 -dependent manner, and targeting the FOSL2 / SGK1 signaling axis may offer a potential strategy for the treatment of renal fibrosis.
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ACS Applied Materials & Interfaces
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2023
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IF 9.5
Xiaoxia Wu,Dinghu Zhang,Ting Pan,Jianwei Li,Yujiao Xie,Chenguang Zhang,Chunshu Pan,Zhewei Zhang,Jie Lin,Aiguo Wu,Guoliang Shao
Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol–disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo. These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.
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Food Bioscience
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2023
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IF 5.2
Wenli Shi,Guowen Zhang,Yijing Liao,Xiaoyun Fei,Deming Gong,Xing Hu
Kaempferol , a natural flavonoid compound, was found to suppress the activity of AChE in a reversible mixed-inhibition with an IC 50 value of 12.43 ± 0.19 μM. Fluorescence spectra showed that the fluorescence burst mechanism of kaempferol on AChE was of static burst type, and it was coupled with AChE to form a complex with a moderate binding affinity driven mainly by hydrogen bonding and hydrophobic interactions. The analysis of circular dichroism spectra found that kaempferol induced structural relaxation of AChE with a decrease in α-helix content (from 19.64% to 18.02%). Computer simulation showed that kaempferol was a two-site inhibitor that bound to both the catalytic active site (Trp86, Glu202, Tyr337) and peripheral anionic site (Tyr72, Asp74, Tyr124 and Tyr341) of AChE, inducing the enzyme structure to become more stable, then the substrate was prevented from binding to the active site of AChE, and the catalytic activity of AChE was inhibited. Moreover, kaempferol binding at the PAS-AChE site induced a conformational change of AChE that may increase the binding affinity of galanthamine to the enzyme, and thus kaempferol and galanthamine synergistically inhibited the activity of AChE. This work may offer novel insights into the development of kaempferol as a food functional factor for the cure of AD.
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ACS Applied Nano Materials
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2023
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IF 5.9
Jiaojiao Chen,Yarong Song,Wenqian Yang,Jianhui Guo,Saihui Zhang,Dong Wan,Yonghui Liu,Jie Pan
Chemotherapy remains the primary treatment for cancer; however, conventional chemotherapeutic drugs have several shortcomings, including poor solubility, lack of targeting, low bioavailability, and high toxicity to healthy tissues. In order to overcome these limitations, drug delivery systems (DDS) have emerged as a promising alternative. In this study, we synthesized TPGS3350-PVGLIG-SS-DOX polymeric micelles that incorporate both extracellular MMP2/9 enzyme response and intracellular reduction response at a nanoscale level. The micelles remained stable throughout the blood circulation and only aggregated at the tumor sites, thanks to the enhanced permeability and retention (EPR) effect. Moreover, the tumor tissue showed a high expression of MMP2/9 enzymes, which resulted in the cleavage of the PVGLIG peptide sequence, ultimately leading to an improved phagocytosis efficiency. Under the action of high intracellular GSH concentration, the disulfide bond was broken and DOX was released to induce tumor cell death. The TPSD&D micelles exhibited good tumor inhibitory activity in vivo and significantly reduced toxic side effects on normal tissues. Our work provides a simple method to assemble tumor-targeted prodrug micelles to improve cancer therapy, which holds potential for clinical applications in antitumor therapy.
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CHEMISTRY & BIODIVERSITY
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2023
·Vol. 20
·期 10
·e202300620
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IF 2.9
Dang-Nan Zhou,Lu Han,Zhan Zhang,Yun-Long Wang,Xiao-Ping Zhang,Yun-Jie Wu,Gao-Lei Xi
Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors ( n ) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of ⋅OH-oxidation of the DNA system, compounds I ~ V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I ~ V could also inhibit Cu 2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS + ⋅), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien- p- tolylox radical (galvinoxyl⋅). The ability of compounds I ~ V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS + ⋅, galvinoxyl, and DPPH radicals, respectively. Graphical
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CHEMISTRY OF MATERIALS
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2023
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IF 8.6
Pengyu Zang,Yaqian Du,Chenghao Yu,Dan Yang,Shili Gai,Lili Feng,Shikai Liu,Piaoping Yang,Jun Lin
The newly developed thermoelectric dynamic therapy (TEDT) may not only solve the problem that photothermal therapy (PTT) is limited by the overexpression of heat shock proteins (HSPs) in tumor cells but also improve the killing effect through a dynamic process. Here, we propose photothermal-driven TEDT based on Ag–Ag2S nanoparticles that integrate Ag2S with Ag+ vacancies (VAg) and Ag in a Janus structure. VAg and Ag optimize the band structure and thermoelectric properties of Ag2S, and additional electrons from the introduction of Ag enhance the PTT effect and facilitates the construction of a significant thermoelectric field for electron–hole migration in the reverse direction, thereby markedly enhancing the TEDT effect. Furthermore, the generated VAg can also serve as a hole trap to suppress electron–hole recombination to promote 1O2 production, which inactivates HSPs to produce positive feedback on PTT, leading to better antitumor efficacy. The combined photothermal–thermoelectric therapeutic properties of Ag–Ag2S were verified from both in vivo and in vitro perspectives using ESR, UV–visible spectroscopy, cellular experiments, simulated tumor models, and other experiments.
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DYES AND PIGMENTS
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2023
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IF 4.5
Ahmed Mohammed Ali Abdulkhaleq,Yixu Zhao,Kun Qian,Xueshi Wang,Zhongfu Zuo,Xibin Zhou
Peroxynitrite (ONOO − ), a highly reactive nitrogen and oxygen species (RNS/ROS), has been associated with a numerous of pathophysiological diseases, including inflammation, cancer, neurodegenerative, and cardiovascular diseases. There are great demands to develop strategies that can detect ONOO − in biological systems. Herein, we developed a novel fluorescent probe based on carbon dots (CDs) for a very sensitive and selective detection and imaging of endogenous and exogenous ONOO − in cells and animal models. Green light-emitting (527 nm) CDs with high quantum yield (QY) was synthesized by hydrothermal method using resorcinol as carbon source. After the phenolic hydroxyl groups of the CDs are combined with the recognition group of ONOO − via covalent ether bond, the fluorescence is quenched and forming the fluorescent probe. Upon the addition of ONOO − to the probe, the ether bond has broken and the CDs fluorescence has recovered. This response has been detailed investigated, including response time, pH values, selectivity and sensitivity, and linearity range, which confirmed the satisfactory detection ability for ONOO − . The probe shows low cytotoxicity and was successfully applied for imaging of ONOO − exogenously and endogenously in cells and in live models of zebrafish and mice.
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Artificial Cells Nanomedicine and Biotechnology
·
2023
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IF 5.8
Yanhai Xi,Wenming Pan,Yanyan Liu,Ji Liu,Guohua Xu,Yanguo Su,Daquan Chen,Xiaojian Ye
Osteoporosis is a common disease among the ageing society. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) is the aetiology of osteoporosis. α-Lipoic acid (ALA) is an antioxidant in the body, which can eliminate excess ROS in the body and inhibits levels of oxidative stress in cells. Herein, we designed PEGylated hollow gold nanoparticles (HGNPs) loaded with ALA (mPEG@HGNPs-ALA) to remove ROS in the treatment of osteoporosis. First, mPEG@HGNPs with a particle size of ∼63 nm has been successfully synthesized. By comparing the drug loading of mPEG@HGNPs, it was concluded that the optimal mass ratio of mPEG@HGNPs (calculated by the amount of gold) to ALA was ∼1:2. ABTS antioxidant assay showed that free radical removal ability. In vitro results revealed that the preparation had good biocompatibility. At the gold concentration of 1–150 μg/mL, the cell viability of mPEG@HGNPs was more than 100%, which indicated that it could promote the proliferation of osteoblasts. What’s more, mPEG@HGNPs-ALA could effectively remove the ROS caused by H2O2 injury and improve the cell viability. According to these results, it can be considered that mPEG@HGNPs-ALA has the potential to treat osteoporosis.
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