PHYTOMEDICINE
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2025
·
IF 8.3
Jie Gao,Jin Yan,Xingwang Zu,Yanyan Xu,Shilong Wang,Yue Li,Zhenying Zhao,Yuanyuan Hou,Gang Bai
Background In the innate immune system, damage-associated molecular patterns (DAMPs) released by damaged cells, such as peroxiredoxin 1 (PRDX1), interact with Toll-like receptor 4 (TLR4), exacerbating inflammation and tissue injury. Ferulic acid (FA), a dietary and herbal phenolic compound, exhibits notable anti-inflammatory properties. However, the precise anti-inflammatory mechanisms of FA are not fully understood. Purpose The objective of this study was to elucidate mechanisms underlying the anti-inflammatory effects of FA. Methods Lipopolysaccharide (LPS) was intratracheally instilled to establish a mouse model of LPS-induced pneumonia. Different doses of FA were injected intraperitoneally, and their anti-inflammatory effects were evaluated. An alkynyl-modified FA probe was used in conjunction with various chemobiological strategies to explore the localization, capture, and identification of FA targets. The pharmacophore of FA and its mechanisms of interaction with its target or pathway were further validated using rigorous biochemical assays and comprehensive transcriptomic profiling. The proposed mechanism of FA against systemic inflammation was validated in mice administered LPS intraperitoneally. Results FA alleviated LPS-induced pulmonary inflammation in mice by selectively targeting macrophages. Subsequently, PRDX1 was identified as an irreversible FA-binding target. Mechanistic investigations revealed that α,β-unsaturated ketone in FA serves as a critical pharmacophore that covalently binds to the Cys173 residue of PRDX1. This covalent binding event effectively suppressed PRDX1 dimerization, resulting in reduced PRDX1 secretion. The co-localization assay demonstrated that FA reduced TLR4-binding PRDX1 in LPS-treated RAW264.7 cells. Transcriptomic analysis indicated that NF-κB and TNF signaling pathways, downstream of TLR4 signaling, were involved in the FA-mediated anti-inflammatory effects. Reduction of TLR4 activation caused by FA treatment decreased levels of downstream inflammatory cytokines in LPS-treated RAW264.7 cells. Finally, reduced co-localization of TLR4 and PRDX1 by FA was confirmed in the lung slices of mice with LPS-induced intratracheal inflammation. FA also reduced PRDX1 dimerization and mitigated inflammation in mice administered LPS intraperitoneally. Conclusion Our study elucidated a novel mechanism in which FA covalently binds to the Cys173 residue of PRDX1, suppressing its dimerization and secretion and thereby alleviating inflammation by modulating the PRDX1/TLR4 signaling pathway. Our findings redefine plant phenylacrylic acids as covalent modulators of DAMPs, with therapeutic potential for ameliorating inflammation beyond conventional antioxidants.
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高影响因子
Materials
·
2025
·Vol. 18
·期 16
·3780
·
IF 3.2
Lei Yang,Anbang Duan,Zhanyin Liu,Tingying Wei,Chunzhao Liu
Aiming to address the key challenges of poor enzyme stability, difficult recovery, and difficult synergistic optimization of catalytic efficiency in high-value conversion of biomass, this study utilizes mineralization self-assembly technology to combine laccase with Fe3O4@SiO2-PMIDA-Cu2+composite, constructing magnetic laccase nanoflower (MLac-NFs) materials with a porous structure and superparamagnetism. This synthetic material can efficiently catalyze the selective oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). The characterization results indicated that MLac-NFs exhibit optimal catalytic activity (63.4 U mg−1) under conditions of pH 6.0 and 40 °C, with significantly enhanced storage stability (retaining 94.26% of activity after 30 days of storage at 4 °C). Apparent kinetic analysis reveals that the substrate affinity and maximum reaction rate of MLac-NFs were increased by 38.3% and 439.6%, respectively. In the laccase–mediator system (LMS), MLac-NFs mediated by 30 mM TEMPO could achieve complete conversion of HMF to FDCA within 24 h. Moreover, due to the introduction of magnetic nanoparticles, the MLac-NFs could be recovered and reused via an external magnetic field, maintaining 53.26% of the initial FDCA yield after six cycles.
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JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS
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2024
·
IF 5.8
Yingying Zhang,Yue Zhang,Bo Li,Xinyan Jin,Tong Liu,Ke Zhang,Lili Fu,Wei Qi,Qi Zhang,Bin Li
Two Heated Tobacco Products (HTPs) with different airflow pathways were tested in this study to give insight into the aerosol formation and transfer. One permit the puffing air to flow through the tobacco rod and known as the open-ended system, while the other one sealed the tobacco rod and known as the closed-ended system. Results showed that in both systems, with the heating temperature rising, the aerosol transfer rates of nicotine, 1,2-propylene glycol (PG), and glycerol (VG) increased linearly, meanwhile the residual rates in the tobacco section decreased exponentially. In particular, lower residual rates of nicotine and PG were observed in the closed-ended system compared to open-ended system from 200 to 300 ℃, indicating a higher releasing efficiency in close-ended system. However, higher aerosol transfer rates of nicotine in the closed-ended system were noted merely among 200–260 ℃. Additionally, the transfer rates for PG remained basically the same in both systems. For nicotine, the closed-ended system exhibited lower retention rates between 200 and 240 ℃, but reversed between 260 and 300 ℃. Furthermore, the closed-ended system showed significantly higher retention rates for PG compared to the open-ended system from 200 to 300 ℃. Regarding puff-by-puff aerosol release pattern, both systems showed similar trend of increase-decrease for the same key component at identical temperature. While the single-puff release amount differed between them, for example, 3.8 mg for close-ended and 3.0 mg for open-ended of water at the second puff. Furthermore, apparent release kinetics parameters were obtained based on the first-order reaction kinetic model and the Arrhenius Equation. In the closed-ended system, lower activation energy of nicotine (26.255 KJ·mol −1 compared to 34.896 KJ·mol −1 in open-ended) resulted in lower activation energy barrier, and therefore a more efficient release and transfer rate for nicotine.
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ACS Synthetic Biology
·
2024
·
IF 3.7
Jialing Wang,Jie Chen,Kemin Lv,Zhen Gao,Jiahuang Li,Bin Wu,Bingfang He,Gerhard Schenk
Processive endoglucanases have generated significant interest due to their bifunctionality in the degradation of cellulose and low product inhibition. However, enhancing their catalytic efficiency through engineering remains a formidable challenge. To address this bottleneck, our engineering efforts targeted loop regions located in the substrate channel of processive endoglucanase EG5C-1. Guided by a comparative analysis of characteristic structural features of the substrate channels in cellobiohydrolase, endoglucanase, and processive endoglucanase, a highly active triple mutant CM6 (N105H/T205S/D233L) was generated that had a 5.1- and 4.7-fold increase in catalytic efficiency toward soluble substrate carboxymethyl cellulose-Na and insoluble substrate phosphoric acid-swollen cellulose (PASC), compared with wild-type EG5C-1. Furthermore, this mutant exhibited greater processivity compared to EG5C-1. Molecular dynamics simulations unveiled that the mutations in the loop regions reshaped the substrate channel, leading to a deeper cleft, resembling the closed channel configuration of cellobiohydrolases. The increased compactness of the substrate channel induced changes in the substrate binding mode and substrate deformation, thereby enhancing both binding affinity and catalytic efficiency. Moreover, metadynamics simulations demonstrated that the processive velocity of cellulose chain through the binding channel in mutant CM6 surpassed that observed in EG5C-1.
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ADVANCED FUNCTIONAL MATERIALS
·
2024
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IF 18.5
Pengfei Xu,Kangpeng Jin,Yuan Yu,Ming Huang,Zhenhua Yan,Xiang Li,Xiao Gao,Liangwei Fu,Biao Xu
The untapped potential of sub-nanometric materials (SNMs) in constructing high-performance thermoelectrics (TE) presents a promising yet unexplored avenue. This study investigates the utilization of supertetrahedral CdS clusters, representing SNMs, in conjunction with state-of-the-art Bi 2 Te 3 -based systems. The CdS cluster with size-dependent electronic structure enables selective interface scattering of carriers, while its 1 nm size and size-dependent phonon density of states (DOS) contribute to significant interfacial thermal resistance. Furthermore, interfacial dislocations and significant grain refinement induced by the incorporation of the CdS cluster boost the mechanical properties. Consequently, a remarkable peak figure of merit ( ZT ) value of 1.47 at 350 K and a record-high Vickers hardness of 1.08 GPa is achieved in the Bi 0.5 Sb 1.5 Te 3 /0.1 wt% CdS cluster composite. The robust TE module achieves an excellent conversion efficiency of about 6.1% under a ΔT of 241 K. This work opens up exciting possibilities for utilizing 1 nm clusters in thermoelectrics and even inspires other fields involving size-dependent electrical and thermal transport behaviors.
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BIOORGANIC CHEMISTRY
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2024
·
IF 4.5
Ting Wang,Xiufeng Liao,Xiaodi Zhao,Kai Chen,Yangzhonghui Chen,Hui Wen,Dali Yin,Yuchen Wang,Bin Lin,Sen Zhang,Huaqing Cui
Mimicking the transition state of tryptophan (Trp) and O 2 in the enzymatic reaction is an effective approach to design indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors. In this study, we firstly assembled a small library of 2-substituted benzo-fused five membered heterocycles and found 2-sulfinyl-benzoxazoles with interesting IDO1 inhibitory activities. Next the inhibitory activity toward IDO1 was gradually improved. Several benzoxazoles showed potent IDO1 inhibitory activity with IC 50 of 82–91 nM, and exhibited selectivity between IDO1 and tryptophan 2, 3-dioxygenase (TDO2). Enzyme binding studies showed that benzoxazoles are reversible type II IDO1 inhibitors, and modeling studies suggested that the oxygen atom of the sulfoxide in benzoxazoles interacts with the iron atom of the heme group, which mimics the transition state of Fe-O-O-Trp complex. Especially, 10b can effectively inhibit the NO production in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and it also shows good anti-inflammation effect on mice acute inflammation model of croton oil induced ear edema.
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Bioactive Materials
·
2024
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IF 18
Zetao Wang,Qiyuan Dai,Huitong Luo,Xiyuan Han,Qi Feng,Xiaodong Cao
Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Min Zhu,Wen Liu,Shan Su,Meng Gong,Guangneng Liao,Fudong Fu,Gen Chen,Zhiyong Rao,Jingqiu Cheng,Jingping Liu,Yanrong Lu,Younan Chen
Diabetic cardiomyopathy (DC) refers to the abnormal myocardial structure and performance induced by diabetes. Although numerous studies have been carried out, the pathophysiological mechanisms of cardiovascular disorders during diabetes have not been fully clarified. Here, we compared the cardiomyopathy of healthy rhesus monkeys and rhesus monkeys with a history of streptozocin induced type 1 diabetes (T1D) over 7 years. Through comparing the cardiac function using echocardiography, and detecting the serum biochemical indexes, and changes of left ventricle (LV), we found that decreased systolic function, higher blood glycosylated hemoglobin A1c (HbA1 C ) level, hyperglycemia, and hyperlipidemia were early events in diabetic rhesus monkeys. In addition, cardiac histological analysis showed mildly fibrosis and early myocardial hypertrophy, as evidenced by increased Sirius red stained area and cross-sectional area of left ventricle. Transcriptome results revealed that the nutrients metabolism and extracellular matrix related pathways were markedly changed in the left ventricle of diabetic monkeys. Targeted metabolomics and targeted lipid metabolomics further revealed that disturbed amino acid metabolism and lipid accumulation in the LV of diabetic monkeys manifested by accumulated branched chain amino acids (BCAAs) and triglycerides (TAGs), and reduced contents of sphingolipids, glycerophospholipids, cholesteryl esters and carnitines. In conclusion, we reported here for the first time that diabetes lasting for more than 7 years leads to some early pathological changes of myocardium in rhesus monkeys. The cardiac function is mildly compromised and the reprogramming of lipids and amino acids metabolism might play important roles in the progression of DC.
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高影响因子
JOURNAL OF MOLECULAR RECOGNITION
·
2024
·Vol. 37
·期 5
·e3100
·
IF 2.3
Jiachen Li,Xiaoting Dong,Yeli Zhang
Metallo-β-lactamases (MβLs) hydrolyze and inactivate β-lactam antibiotics, are a pivotal mechanism conferring resistance against bacterial infections. SMB-1, a novel B3 subclass of MβLs from Serratia marcescens could deactivate almost all β-lactam antibiotics including ampicillin (AMP), which has posed a serious threat to public health. To illuminate the mechanism of recognition and interaction between SMB-1 and AMP, various fluorescence spectroscopy techniques and molecular dynamics simulation were employed. The results of quenching spectroscopy unraveled that AMP could make SMB-1 fluorescence quenching that mechanism was the static quenching; the synchronous and three-dimensional fluorescence spectra validated that the microenvironment and conformation of SMB-1 were altered after interaction with AMP. The molecular dynamics results demonstrated that the whole AMP enters the binding pocket of SMB-1, even though with a relatively bulky R1 side chain. Loop1 and loop2 in SMB-1 undergo significant fluctuations, and α2 (71–73) and local α5 (186–188) were turned into random coils, promoting zinc ion exposure consistent with circular dichroism spectroscopy results. The binding between them was driven by a combination of enthalpy and entropy changes, which was dominated by electrostatic force in agreement with the fluorescence observations. The present study brings structural insights and solid foundations for the design of new substrates for β-lactamases and the development of effective antibiotics that are resistant to superbugs.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang
Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
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JOURNAL OF CHEMICAL NEUROANATOMY
·
2020
·
IF 2.353
Hongqing Liu,Shiqi Li,Cuizhu Yang,Hui Jia,Ziting Gu,Xing Tu,Sumin Tian,Jing Liu,Guoying Li,Yuxin Ma
The senile plaque formed by β-amyloid (Aβ) deposition in the brain is one of the main pathological features of Alzheimer’s disease (AD), and the c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the pathogenesis of AD. This study aimed to investigate that D-serine may ameliorate motor and cognitive impairment in Aβ injected mice by inhibiting JNK signaling pathway. Firstly, Kunming mice were injected intrahippocampally with Aβ 1-42 to build AD model. The mice were injected intraperitoneally with saline, D-serine, D-amino acid oxidase (DAAO), and Sodium benzoate (BE) for 10 consecutive days, respectively. Subsequently, the motor and cognitive functions of mice were detected by behavioral tests. The silver staining and immunohistochemical methods were used to detect the distributions of Aβ in the hippocampus of mice. 18 F-2-Fluro-D-deoxy-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scans were performed to detected glucose metabolism of Aβ 1-42 induced lesions. The expressions of relative JNK factors were detected by immunohistochemistry and Western blot methods. These results showed that Aβ severely impaired the motor and memory abilities of mice. The expressions of glial fibrillary acidic protein (GFAP), tumor necrosis factor (TNF-α), N-methyl-D-aspartate receptor 1 (NMDAR1), phospho-JNK (p-JNK), p-c-Jun and activating transcription factor 2 (ATF2) increased significantly. After D-serine treatment, the abilities of movement and memory of mice were improved, and the clearance rate of Aβ was accelerated. The expressions of GFAP, TNF-α, NMDAR1, p-JNK, p-c-Jun and ATF2 decreased significantly. DAAO and BE were administered to further validate these results. Therefore, this study showed that D-serine could alleviate the cognitive impairment of Aβ 1-42 injected mice by inhibiting JNK signaling pathway. These results provide more evidences for the effect of D-serine on AD and relevant mechanism to treat AD.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Xican Li
Current in vitro antioxidant assays have several limitations, which frequently cause inconsistent results. The study develops a new antioxidant assay using the 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•). After the investigation of various factors, the experimental protocol was briefly recommended as follows: PTIO• and the sample solution were added to phosphate buffer (pH 7.4, 50 mM), incubated at 37 °C for 2 h, and then spectrophotometrically measured at 557 nm. The validation test based on 20 pure compounds and 30 lyophilized aqueous extracts suggested that PTIO• scavenging had a good linear relationship, stability, and reproducibility. In the ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, PTIO• was observed to give m/z 234 when encountering l-ascorbic acid. As an antioxidant assay, PTIO• scavenging possesses four advantages, i.e., oxygen-centered radical, physiological aqueous solution, simple and direct measurement, and less interference from the tested sample. It can also satisfactorily analyze the antioxidant structure–activity relationship. PTIO• scavenging has no stereospecificity and is at least involved in H+ transfer.
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