JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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2022
·Vol. 381
·期 3
·257-265
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IF 4.402
Jian-Li Qiu,Guo-Feng Zhang,Yu-Na Chai,Xiao-Yan Han,Hai-Tao Zheng,Xiang-Feng Li,Fei Duan,Ling-Yan Chen
To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-β (TGF-β) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-β/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-β1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-β/smads pathway–related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-β/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-β/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis.
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JOURNAL OF CHROMATOGRAPHY A
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2022
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IF 4.601
Qianying Sheng,Ling Wang,Leyuan Zhang,Xue Wang,Shengxu Qian,Minbo Lan,Guangyan Qing,Xinmiao Liang
Natural products are rather complex samples containing a large number of compounds ranging from polar to nonpolar, small molecules to macromolecules , as well as numerous homologs/analogs with quite similar structures, which create great opportunities and treasures for discovery of bioactive drugs. For the purpose of better understanding the complex natural products and controlling their qualities, powerful analytical techniques for adequately separating chemical constituents and tracking potentially bioactive components are quite essential. Here, a design concept of bidirectional β-cyclodextrin (β-CD)–modified chromatographic stationary phase toward separation of bufadienolides extracted from toad is proposed. Bufadienolides could be divided into two classes: toad venom ligand (AAUBs) and toad toxin (AACBs) with remarkable differences in structures and polarity. The hydrophobic cavity of β-CD can encapsulate the steroid part of AACBs while the hydroxyls exposed on the β-CD surface have strong hydrophilic interactions with the arginine part of AACBs. Isothermal titration calorimetry and hydrogen nuclear magnetic resonance titration experiment further validate the rationality of this design. Furthermore, the β-CD-based stationary phase can be used as a hydrophilic material to construct a HILIC × RPLC 2D separation mode for the separation of AACBs, also works as a reverse phase material to construct a RPLC × RPLC 2D separation mode for the separation of AAUBs with good orthogonality. This study will open an avenue and provide a novel insight for high-efficiency two-dimensional separation of natural products.
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TALANTA
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2022
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IF 6.556
Xiaobin Zhou,Mengjun Wang,Junyang Chen,Xingguang Su
Developing high-performance nanozyme for the construction of high-sensitivity biosensor platform is of great significance. Herein, we have designed and synthesized a Cu/N co-doped carbon-based nanozyme by anchoring Cu atoms on two-dimensional carbon nanosheet (Cu/NC NS). The Cu/NC NS possessed ultra-high Cu loading, superior peroxidase-like catalytic activity, great stability and reusability. Significantly, the Cu/NC NS exhibited high affinity towards H 2 O 2 and 3,3′,5,5′-tetramethylbenzidine (TMB) under acidic condition, which could induce obvious color changes of TMB in the presence of low H 2 O 2 concentration. By integrating the Cu/NC NS with β-galactosidase (β-Gal) and galactose oxidase (Gal Ox), a multienzyme cascade colorimetric sensing system was established for the detection of lactose and β-Gal, which realizing the assay of lactose and β-Gal in the linear ranges of 0.1–1.4 mM and 0.025–0.2 U/mL, respectively. And the limit of detection for lactose and β-Gal were 0.03 mM and 0.01 U/mL, respectively. Furthermore, this work achieved the accurate detection of the content of lactose in milk and the activity of β-Gal in human serum, exploiting a novel application for nanozyme in biosensing.
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SEPARATION AND PURIFICATION TECHNOLOGY
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2022
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IF 9.136
Dongli Li,Zhaoqiang Zhang,Liqin Zhou,Youquan Zhang,Zhenxia Zhao,Fang Shen,Xingzhen Qin,Kungang Chai,Hongbing Ji
To efficiently separate acetophenone (AP) and 1-phenyethanol (PE) from petrochemical by-product, we herein report a novel feasible strategy to fabricate β-cyclodextrin (β-CD) based core–shell microsphere, which retains the cage-type crystal structure of β-CD and superior affinity to AP over PE. Using triphenylmethane-4,4′,4′'-triisocyanate (TTI) as monomer, the polymeric TTI shell can grow in-situ on the surface of β-CD particles, giving the core–shell structured CD@PTTI. The unique β-CD core and polymeric TTI shell structure was verified by a series of characterization methods. CD@PTTI-3 exhibits both high AP uptake (ca. 2.07 mmol·g −1 ) and AP/PE selectivity (ca. 7.2), outperforming the conventional TTI cross-linked amorphous β-CD polymer (TTI-CDP). The adsorption behavior of CD@PTTI-3 on AP and PE single-component solutions was investigated by batch adsorption experiments. Based on the experimental and theoretical results, a mechanism of competitive adsorption of AP and PE on CD@PTTI-3 involving host–guest inclusion, hydrogen bonding and π-π stacking is proposed. Furthermore, intense competition between AP and PE on CD@PTTI-3 was observed in column breakthrough experiments, and CD@PTTI-3 could purify AP from 77.16% to 93.6% by a single adsorption–desorption process.
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TISSUE & CELL
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2022
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IF 2.586
Yuan Xu,Jian He,Jun He
Purpose The treatment of intervertebral disc degeneration is limited, cyanidin can protect chondrocytes from degeneration. This research investigated the effect of cyanidin on human nucleus pulposus cells (HNPC) metabolism and its mechanism. Methods HNPC were treated with cyanidin, XAV-939 (inhibitor of Wnt/β-catenin signaling) and SKL2001 (activator of Wnt/β-catenin signaling), and pressurized at 1, 3, and 30 atm. Quantitative real-time PCR and Western blot were used to assess the expressions of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), Collagen-II, Aggrecan , Wnt-3a and β-catenin in treated HNPC. Cell counting kit-8 was used to detect the HNPC cell viability . Radioisotope incorporation method was used to assess the proteoglycan synthesis rate of HNPC. The level of cell matrix was detected by toluidine blue staining. Results Proper hydrostatic pressure of 3 atm could elevate cell viability, proteoglycan synthesis and the level of cell matrix of HNPC, while high hydrostatic pressure of 30 atm reduced the above effects. Cyanidin and XAV-939 reversed the promoting effect of 30 atm pressure on Wnt/β-catenin signaling pathway and the inhibiting effect on cell viability, proteoglycan synthesis and the level of cell matrix. Subsequently, SKL2001 further reversed the function of cyanidin on HNPC. Conclusion Cyanidin attenuated the high hydrostatic pressure-induced degradation of cellular matrix of HNPC via blocking the Wnt/β-catenin signaling pathway. Our findings in this research provided a basis for in vitro experiment of cyanidin and a theoretical fundament on this disease.
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
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2023
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IF 5.7
Binwei Huang,Pingzhan Si,Quanxing Ren,Zhuang Qian,Ziqiang Yin,Zhengren Huang,Qing Huang,Yinsheng Li
SiC ceramic was fabricated by spark plasma sintering of β-SiC powder and Y 2 O 3 -MgO additives in argon. The effects of β→α phase transformation of SiC on microstructure and thermal conductivity of densified bulks were systematically investigated, in comparison to the counterparts using α-SiC as starting powder. The β→α phase transformation led to a “unimodal to bimodal” transition in grain size distribution. After sintering at 1850 o C, the incomplete β→α phase transformation induced the appearance of β/α heterophase boundary with strong effect of phonon-scattering. After sintering at 2050 o C, the completion of β→α phase transformation resulted in enlarged grains and disappearance of β/α heterophase boundary in SiC ceramic. The lattice oxygen content was decreased primarily by enhanced grain growth and oxygen picking-up of sintering additives, and possibly some contribution from β→α phase transformation. The optimized microstructure enabled SiC ceramic to obtain a remarkable increase in thermal conductivity from 126 to 204 W/mK after the replacement of α-SiC by β-SiC as starting powder and the accomplishment of β→α phase transformation.
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JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Hang Li,Qing-Sheng Zhao,Sen-Lin Chang,Tan-Ran Chang,Ming-Hui Tan,Bing Zhao
Industrial hemp is an important economic crop. The ethanol extract of its leaf is also known as cannabidiol full-spectrum oil (CFSO) and has a lot of health benefits. But its applications in many fields are limited owing to the poor thermal stability and low aqueous solubility. In this study, 2, 6-di-O-methyl-β-cyclodextrin (DM-β-CD) was used to prepare inclusion complex (IC) of CFSO to enhance its thermal stability and water solubility. Phase solubility study indicated that CFSO formed ICs with DM-β-CD at a 1:1 stoichiometric ratio. The complexation rate of CFSO/DM-β-CD IC was 91.5%. The results of SEM, FT-IR, DSC, PXRD, NMR, and molecular docking revealed that the bioactive components of CFSO were embedded into DM-β-CD cavities. After complexation, the aqueous solubility of CFSO in CFSO/DM-β-CD IC was increased from 0.046 to 12.4 μg/mL. The DPPH and ABTS EC 50 values of CFSO/DM-β-CD IC were 130.5 and 12.0 μg/mL respectively, which indicated that the antioxidant ability of CFSO/DM-β-CD IC was stronger than that of CFSO. The MICs of CFSO/DM-β-CD IC were around 6.25–12.5 μg/mL for Escherichia coli and 12.5–25 μg/mL for Bacillus subtilis . The data showed that the antibacterial activity of CFSO was nearly not influenced by complexation. The thermal stability of CFSO was also improved after inclusion. The findings could promote the use of CFSO and the development of the industrial hemp industry.
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FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Jingjie Hou,Guixin Tan,Shihui Hua,Huajiang Zhang,Jing Wang,Ning Xia,Sijie Zhou,Dong An
The work aimed to develop the multi-protein mixture of egg yolk as natural particles to stabilize high internal phase Pickering emulsions (HIPPEs) to improve the bioaccessibility of β-carotene in the elderly. The results showed that the depletion attraction drove the adsorption of egg yolk protein particles at the oil–water interface and the formation of osmotic droplet clusters due to the attachment of particle-coated droplets in the dispersed phase, leading to kinetic blocking and stable gelation of HIPPEs. Rheological measurements showed that HIPPEs had shear thinning, low shear stress, viscoelastic properties, and structural recovery properties, which facilitated easy consumption for the elderly. The stability of HIPPEs was verified by ionic and centrifugal stability tests, demonstrating their potential for application to complex gastric environments. HIPPEs have been applied to the International Dysphagia Dietary Standardization Initiative (IDDSI) test and simulated in vitro digestion in older adults, demonstrating their safe swallowability and high β-carotene bioaccessibility. Our findings suggest solutions for food practitioners facing the aging problem and provide new insights for preparing age-friendly foods.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Yanli Wang,Siwei Zhong,Ke Yang,Ruifeng Luo,Linxin Dai,Wenzhen Zhong,Yan Ye,Chaomei Fu,Dasheng Lin,Nan Li,Jianping Chen,Chuan Zheng,Shu Fu,Fei Gao
Herein, a β-1,3- D -glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral “nano-in-micro” advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the “nests”-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of β-1,3- D -glucan by β-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.
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Diabetology & Metabolic Syndrome
·
2023
·Vol. 15
·期 1
·1-13
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IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2021
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IF 6.514
Fangfang Chen,Mengmeng Bai,Wentian Liu,Hongtao Kong,Tingting Zhang,Hong Yao,En Zhang,Juan Du,Shangshang Qin
The emergence and dissemination of metallo-β-lactamases (MBLs) producing Enterobacterales is a great concern for public health due to the limited therapeutic options. No MBL inhibitors are currently available in clinical practice. Herein, we synthesized a series of H 2 dpa derivatives containing pentadentate-chelating ligands and evaluated their inhibitory activity against MBLs. Related compounds inhibited clinically relevant MBLs (Imipenemase, New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase) with IC 50 values of 1–4.9 μM. In vitro , the most promising compounds, 5b and 5c , which had a chiral methyl at the acid adjacent to 5a , demonstrated potent synergistic activity against engineered strains, with fractional inhibitory concentration index values as low as 0.07–0.18. The addition of 5b and 5c restored meropenem efficacy against 42 MBL-producing Enterobacterales and Pseudomonas aeruginosa to satisfactory clinical levels. In addition, safety tests revealed that 5b/5c showed no toxicity in red blood cells, cell lines or mouse model. Further studies demonstrated that compounds 5b and 5c were non-competitive MBL inhibitors. In vivo compounds 5b and 5c potentiated meropenem efficacy and increased the survival rate from 0 to at least 83% in mice with sepsis caused by an NDM-1-positive clinical strain. The activity of the compounds exhibited consistency at the molecular, cellular, and in vivo levels. These data indicated that H 2 dpa derivatives 5b and 5c containing pentadentate-chelating ligands may be worthy of further study.
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JOURNAL OF MEDICINAL CHEMISTRY
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2019
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IF 6.054
Yao-Ling Wang,Sha Liu,Zhu-Jun Yu,Yuan Lei,Meng-Yi Huang,Yu-Hang Yan,Qiang Ma,Yang Zheng,Hui Deng,Ying Sun,Chengyong Wu,Yamei Yu,Qiang Chen,Zhenling Wang,Yong Wu,Guo-Bo Li
The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.
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