JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Yaru Li,Qian Yang,Lanlan Fan,Fang Liu,Yaqi Shang,Baoxin Zhang,Zheng Wang,Yanjun Zhao
Ovarian cancers (OC) often resist current standard chemotherapy because of the cancer heterogeneity and over-expression of an anti-apoptotic protein, myeloid cell leukemia-1 (MCL-1). The heterogeneous OC shows impaired redox homeostasis and relies heavily on glutathione peroxidase 4 to eliminate toxic lipid peroxides. Therefore, integrated apoptosis and ferroptosis therapy is promising for OC management. The current work reports a liposomal nanosystem for apoptotic and ferroptotic OC therapy. Simvastatin (Sim) and vorinostat (Saha) were selected as the pleiotropic model drugs. The successive release of Saha and Sim from liposomes enabled the sequential amplification of MCL-1 by Saha, and then MCL-1 inhibition by Sim. Such a strategy could potently induce apoptosis in a human OC cell line (SKOV3), as indicated by increased intracellular cytochrome c concentration, caspase 3/9 activity, and the extent of apoptosis. Besides, Saha played multiple roles in cell death. It could induce cell cycle arrest at the G 2 /M phase and apoptosis. Saha also inhibited the glutamate-cystine transporter (SLC7A11) and provoked ferroptosis, which was corroborated by the depletion of glutathione, reduced nicotinamide adenine dinucleotide phosphate, and boost of lipid peroxides and malondialdehyde in SKOV3 cells. The current work integrated the “sequential amplification and inhibition of MCL-1 target” concept with combinational apoptosis and ferroptosis OC therapy, which might offer a new approach for managing resistant OC and other malignant diseases.
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MedComm
·
2024
·Vol. 5
·期 5
·e555
·
IF 10.7
Heng Liang,Jiani Zhan,Yunqiu Chen,Zikang Xing,Zhen Ning Tony He,Yuying Liu,Xuewen Li,Yijia Chen,Zhiyao Li,Chunxiang Kuang,Dan Yang,Qing Yang
Indoleamine 2,3-dioxygenase 1 (IDO1), the key enzyme in the catabolism of the essential amino acid tryptophan (Trp) through kynurenine pathway, induces immune tolerance and is considered as a critical immune checkpoint, but its impacts as a metabolism enzyme on glucose and lipid metabolism are overlooked. We aim to clarify the potential role of IDO1 in aerobic glycolysis in pancreatic cancer (PC). Analysis of database revealed the positive correlation in PC between the expressions of IDO1 and genes encoding important glycolytic enzyme hexokinase 2 (HK2) , pyruvate kinase (PK) , lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) . It was found that IDO1 could modulate glycolysis and glucose uptake in PC cells, Trp deficiency caused by IDO1 overexpression enhanced glucose uptake by stimulating GLUT1 translocation to the plasma membrane of PC cells. Besides, Trp deficiency caused by IDO1 overexpression suppressed the apoptosis of PC cells via promoting glycolysis, which reveals the presence of IDO1–glycolysis–apoptosis axis in PC. IDO1 inhibitors could inhibit glycolysis, promote apoptosis, and exhibit robust therapeutic efficacy when combined with GLUT1 inhibitor in PC mice. Our study reveals the function of IDO1 in the glucose metabolism of PC and provides new insights into the therapeutic strategy for PC.
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ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES
·
2023
·Vol. 238
·期 6
·1069-1070
·
IF 0.3
Yan-Qing Wang,Wen-Qing Yan,Li-Xue Nie,Ping-Ping Luan,Chao-Qun Li
C 20 H 22 Cu 3 N 8 O 10 , monoclinic, C 2/ c (no. 15), a = 12.0766(11) Å, b = 16.2778(14) Å, c = 14.7605(13) Å, β = 97.8580(10) ∘ , V = 2874.4(4) Å 3 , Z = 4, R
gt ( F ) = 0.0420, wR
ref ( F
2 ) = 0.0988, T = 298.15 K.
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LANGMUIR
·
2013
·
IF 4.187
Xiu-Juan Shi,Gao-Jian Chen,Yan-Wei Wang,Lin Yuan,Qiang Zhang,David M. Haddleton,Hong Chen
Surface-initiated SET-LRP was used to synthesize polymer brush containing N-isopropylacrylamide and adamantyl acrylate using Cu(I)Cl/Me6-TREN as precursor catalyst and isopropanol/H2O as solvent. Different reaction conditions were explored to investigate the influence of different parameters (reaction time, catalyst concentration, monomer concentration) on the polymerization. Copolymers with variable 1-adamantan-1-ylmethyl acrylate (Ada) content and comparable thickness were synthesized onto silicon surfaces. Furthermore, the hydrophilic and bioactive molecule β-cyclodextrin-(mannose)7 (CDm) was synthesized and complexed with adamantane via host–guest interaction. The effect of adamantane alone and the effect of CDm together with adamantane on the wettability and thermoresponsive property of surface were investigated in detail. Experimental and molecular structure analysis showed that Ada at certain content together with CDm has the greatest impact on surface wettability. When Ada content was high (20%), copolymer–CDm surfaces showed almost no CDm complexed with Ada as the result of steric hindrance.
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JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2018
·
IF 2.196
Bing Jia,Liping Wang,Mengmeng Yan,Hai Liu,Yingmin Yu,Qingsong Li
Liquid–liquid equilibrium (LLE) data for ternary systems of water + 2,2,3,3-tetrafluoro-1-propanol + anisole/1-octanol were determined at temperatures of 298.2, 308.2, and 318.2 K under 101.3 kPa. The distribution coefficients and separation factors were calculated from experimental LLE data, which indicated that anisole/1-octanol extracted 2,2,3,3-tetrafluoro-1-propanol from aqueous solution with high efficiency. The consistency of the experimental LLE data was assessed by the Othmer–Tobias and Hand equations. Meanwhile, the NRTL and UNIQUAC models were successfully applied to regress and correlate the experimental data, presenting the root-mean-square deviations (RMSD) less than 1.0%. The relevant binary interaction parameters of these two models were also regressed.
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Bioengineered
·
2021
·
IF 3.269
Yunxin Zhang,Jianlong Liu,Wei Jia,Xuan Tian,Peng Jiang,Zhiyuan Cheng,Jinyong Li
This study is aimed at identifying the roles of AGE/RAGE and ET-1 in deep vein thrombosis (DVT). Advanced glycation end products (AGEs) in glycated human serum albumin (M-HSA) were detected by ELISA. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis, followed by ELISA for the detection of inflammatory cytokine level and oxidative stress level in HUVECs. Immunofluorescence was performed to detect ET-1 and eNOS expression. The expression of specific proteins was assayed by western blot. As a result, decreased HUVEC viability was observed after stimulation with M-HSA, whereas RAGE inhibitor improved it. Cell apoptosis showed the opposite trend. Additionally, M-HSA-induced inflammatory cytokine release and oxidative stress of HUVECs were both alleviated by RAGE inhibitor. RAGE inhibitor also increased the levels of NO and eNOS while decreasing the level of ET-1 in M-HSA-stimulated HUVECs. Furthermore, decreased protein expression of Bax, cleaved-caspase3, RAGE, p65, ET-1 and iNOS was observed after treatment with RAGE inhibitor, in addition to increased protein expression of Bcl-2 and eNOS. In conclusion, blocking AGE/RAGE pathway downregulates ET-1, thereby mitigating HUVEC damage in DVT.
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Current Pharmaceutical Analysis
·
2021
·Vol. 17
·期 9
·1197-1205
·
IF 0.89
Wang Jie,Lu Ping,Zhang Shengting,Li Wanwan,Ji Xiuling,Li Jing,Zhang Hui,Wei Yunlin,Liang Chenggang
Background: Current methods for assaying bioactivity of GLP-1 analogues are costly and time consuming, mainly dependent on AlphaScreen luminous beads, based on fluorescent resonance energy transfer technology, and cAMP-GloTM Max assay kit, and on ATP to generate a negative- association
curve. Objective: To establish a sensitive, stable, and low-cost method for the determination of biological activity of therapeutic glucagon-like peptide-1(GLP-1) and their analogous drugs in vitro in quality control. Methods: An applicable fluorescent high-content system (fHCS)
method was developed in U2OS cell, which was stably transfected with green fluorescent protein (GFP) labeled at the C-terminal of glucagon-like peptide-1 receptor (GLP-1R). HCS was firstly used to measure per unit area of fluorescent intensity changes as a result of drug-stimulated receptor
endocytosis. Results: The detection sensitivity improved at least 30 folds than the other reported methods. This method showed a wide detection range with a good linear regression of R2>0.98. In five scgs from 50~150% SCG, the accuracy achieved the standard of the 41st United States
Pharmacopoeia with all biases being less than 7.5%. The precision attained the 9.0th European Pharmacopoeia standard with all relative standard deviations (RSDs) below 10%. This assay result can be kept stable over 100 h at room temperature. Furthermore, the U2OS/GLP-1R cells showed a sharp
specificity towards GLP-1 analogues during detecting activities in a mixture of different ligands. Conclusion: These results suggested that the GLP-1R/fHCS method can be employed broadly in the bioactivity determination of GLP-1 analogous drugs and as a platform for screening GLP-1 similar
active ingredients in natural products.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Hongji Liu,Jinju Nie,H.C. Stephen Chan,Hailu Zhang,Liang Li,Hongqing Lin,Henry H.Y. Tong,Ande Ma,Zhengzheng Zhou
Herein, we reported a new bergenin : 4-aminobenzamide ( BGN-4AM ) cocrystal with significantly enhanced solubility and low hygroscopicity probed from two aspects such as phase solubility diagrams and theoretical calculations. Compared with anhydrous BGN , BGN-4AM solubilities in water and different buffer solutions (pH = 1.2, 4.5, 6.8) increase significantly. It is noted that BGN-4AM solubility in pH = 6.8 buffer solution presents 32.7 times higher than anhydrous BGN . Interestingly, BGN-4AM (0.31 ± 0.07%) showcases lower hygroscopicity than anhydrous BGN (9.31 ± 0.16%). The predicted and experimental solubilities agree with each other when considering solubility product ( K sp ) and solution binding constant ( K 11 ) in phase solubility diagrams, indicating the solution complexes formation occurs. Further crystal surface-water interactions and Bravais, Friedel, Donnay-Harker (BFDH) analyses based on Density Functional Theory with dispersion correction (DFT- d ) methods support the enhanced solubility. The water probe demonstrates an average interaction energy of −6.48 kcal/mol on the 002 plane of BGN-4AM , and only −5.47 kcal/mol on the 011 plane of BGN monohydrate. The lower lattice energy of BGN-4AM guarantees its lower hygroscopicity than BGN monohydrate. BGN-4AM with enhanced solubility and low hygroscopicity can be a potential candidate for further formulation development.
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IMMUNITY
·
2025
·Vol. 58
·期 7
·1811-1829
·
IF 26.3
Ding Qiu,Shuishen Zhang,Chanyan Huang,Xinying Wang,Jianping Deng,Haiyang Sun,Bingbing Feng,Ying Tan,Kaile Ji,Shaoting Xu,Xiaoqi Ye,Chao Cheng,Shigeru Kakuta,Yoshiyuki Adachi,Yoichiro Iwakura,Shuai Wang,Shaowei Dong,Ce Tang
Dectin-1 ( Clec7a ), a C-type lectin receptor for β-glucans, is critical in host defense against fungal infections and has been implicated in allergic responses, yet its role in pulmonary fibrosis remains unclear. In this study, we reveal that bleomycin-induced pulmonary fibrosis was suppressed in Dectin-1-deficient mice, mediated by interactions with the commensal lung fungus Engyodontium . Dectin-1 was predominantly expressed on alveolar macrophages (AMs), correlating with fibrosis severity in both humans and mice. Dectin-1 deficiency reduced Arginase-1 and TGF-β-producing AMs and profibrotic factor expression. Mechanistically, Dectin-1 signaling promoted quiescent AM differentiation into profibrotic AMs via the Raf1-dependent pathway, bypassing CARD9 signaling and mono-macrophage chemotactic recruitment. Therapeutic targeting of Dectin-1 with laminarin or Raf1 inhibitors attenuated fibrosis in mice and reduced profibrotic factors in human AMs and fibroblasts. These findings highlight the Dectin-1-Raf1 axis as a key regulator of pulmonary fibrosis and a promising therapeutic target for fibrotic diseases.
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Canadian Journal of Chemistry
·
2021
·Vol. 99
·期 11
·
IF 1.118
Ying Liu,Mengyu Zhu,Yadong Hu,Yijun Zhao,Chengzhu Zhu
The photochemical reactions between 1-naphthol (1-NP) and the superoxide anion radical (O2•–) were investigated in detail by using 365 nm UV irradiation. The results showed that the conversion rate of 1-NP decreased with the increase of the initial concentration of 1-NP, whereas by increasing the pH and riboflavin concentration, the photochemical reaction was accelerated. The second-order reaction rate constant was estimated to be (3.64 ± 0.17) × 108 L mol−1 s−1. The major photolysis products identified by using gas chromatography – mass spectrometry (GC–MS) were 1,4-naphquinone and 2,3-epoxyresin-2,3-dihydro-1,4-naphquinone, and their reaction pathways were also discussed. An atmospheric model showed that both the bulk water reaction and the heterogeneous surface reaction deserve attention in atmospheric aqueous chemistry.
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Frontiers in Chemistry
·
2022
·
IF 5.545
Zhang Changsheng,Chu Shaoqi,Jiang Jie,Zhao Jinchong,Wen Song,Sun Bing,Xu Wei
Synthesis of zeolites in more efficient and greener methods is of great significance in both industrial and academic fields. However, the relative long time for zeolite crystallization and much consumption of water solvent make the target challengeable. Herein, a route for ultrafast synthesis of nano Silicalite-1 zeolites in 10 min with much less water consumption has been developed. Comprehensive characterizations, i.e., X-ray powder diffraction, N2 sorption, scanning electron microscope, and NMR, confirm the high quality of such obtained Silicalite-1 zeolites. In the catalytic deoxygenation of O2-containing ethylene (mixture of O2 and ethylene), these reported Silicalite-1 zeolite samples show the comparable performance with the conventional Silicalite-1 zeolites synthesized under hydrothermal conditions. This research therefore provides a new trial toward the ultrafast synthesis of zeolite materials in an environment-friendly route.
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MOLECULES
·
2021
·Vol. 26
·期 5
·1462
·
IF 4.412
Hao Xu,Jie Zhu,Xiong Wang,Chao Shen,Shengshen Meng,Kai Zheng,Chao Lei,Longfeng Zhu
Developing sustainable routes for the synthesis of zeolites is still a vital and challenging task in zeolite scientific community. One of the typical examples is sustainable synthesis of aluminosilicate EU-1 zeolite, which is not very efficient and environmental-unfriendly under hydrothermal condition due to the use of a large amount of water as solvent. Herein, we report a sustainable synthesis route for aluminosilicate EU-1 zeolite without the use of solvent for the first time. The physicochemical properties of the obtained EU-1 zeolite are characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetry-differential thermal analysis (TG-DTA), N2sorption, inductively coupled plasma (ICP) analysis, and solid nuclear magnetic resonance (NMR), which show the product has high crystallinity, uniform morphology, large BET surface area, and four-coordinated aluminum species. Moreover, the impact of synthesis conditions is investigated in detail. The sustainable synthesis of aluminosilicate EU-1 zeolite under solvent-freeKeywords:zeolite;aluminosilicate EU-1;sustainable route;solvent-free
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