FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Longyan Yang,Ruili Yin,Ziyu Shan,Anqi Feng,Kun Li,Yan Wang,Ke Yu,Yongsong Xu,Lin Mao,Jianan Lang,Baoyu Zhang,Dong Zhao
Aims Overweight and obesity are closely associated with hyperuricemia (HUA). However, the effect of obesity-induced adipokine on the level of serum uric acid (UA) has not been fully elucidated. This study aimed to determine the role of adipokine in the pathogenesis of HUA. Methods Omental adipose tissues from HUA patients with obesity were collected for data- independent acquisition (DIA) proteomics analysis, and the secreted protein angiopoietin-like protein (ANGPTL2) was identified and further validated via Western blot and ELISA. Angptl2 knockout (ko) and adipocyte-specific ANGPTL2 overexpression mice were generated to establish HUA models. HK2 cells and primary renal tubule epithelial cells (RTECs) were applied to induce HUA cell model and treated with recombinant human ANGPTL2 or supernatants derived from C3H10 cells differentiated into adipocytes. Result ANGPTL2 levels were significantly elevated in the omental adipose tissue from HUA with obesity patients compared to control participants. Circulating ANGPTL2 levels were also increased, and positively correlated with serum UA levels, especially in male participants. Plasma UA levels were significantly decreased in Angptl2 ko mice, coinciding with up-regulated expression of ATP binding cassette subfamily G member 2 (ABCG2) and down-regulated glucose transporter 9 (GLUT9) in renal tissue. However, plasma UA levels were significantly increased, accompanied by decreased ABCG2 expression and enhanced GLUT9 expression after adipocyte-specific ANGPTL2 overexpression. Furthermore, adipocyte- derived ANGPTL2 increased UA level in cell supernatants through the inhibition of protein kinase B (AKT)/ABCG2 signaling in RTECs and HK2 cells. Conclusion Adipokine ANGPTL2 levels were significantly elevated in HUA patients with obesity. Circulating ANGPTL2 concentrations were independently associated with serum UA levels, particularly in obese males. Adipocyte-secreted ANGPTL2 promoted the level of UA through AKT/ABCG2 signaling in renal tubular cells. These findings establish ANGPTL2 as a critical adipokine linking obesity to hyperuricemia and suggest its potential as a novel therapeutic target for HUA.
研究领域:
内分泌学
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代谢研究
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分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 5
·2027
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IF 4.9
Shuangliu Chen,Jiřimutu Xiao,Shijie Zhou,Taxi Wumiti,Zitong Zhao,Ruihua Zhao,Yalan Pan,Qing Wang,Yong Ma,Lan Wu,Yang Guo
Dysregulated iron metabolism-induced ferroptosis is considered a key pathological mechanism in the development of osteoporosis (OP). G protein-coupled receptor 30 (GPR30, also known as Gper1) is an estrogen-binding receptor that has shown therapeutic benefits in patients with certain degenerative diseases. Moreover, several studies have demonstrated the anti-ferroptotic effects of estrogen receptor activation. However, its role in the prevention and treatment of OP remains unclear, and there are currently no reports on the anti-ferroptotic function of GPR30 in OP. Therefore, this study aimed to investigate the ferroptosis-related effects and mechanisms of GPR30 in the context of OP. In vivo and in vitro experiments were conducted using wild-type (WT)C57BL/6female mice and GPR30-knockout (GPR30-KO)C57BL/6Jfemale mice. The microarchitecture of the distal femur was assessed using micro-computed tomography (micro-CT), and histomorphological changes were analyzed via hematoxylin and eosin (H&E) staining. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured to establish an iron overload model using ferric ammonium citrate (FAC). Interventions included GPR30 overexpression via transfection and BMP-6 inhibition using LDN-214117. Cell viability was evaluated with the CCK-8 assay, while osteogenic differentiation and mineralization levels were assessed using ALP and Alizarin Red S (ARS) staining. Iron accumulation was detected via Prussian blue staining, oxidative stress levels were evaluated using ROS staining, and mitochondrial membrane potential changes were analyzed using JC-1 staining. Transmission electron microscopy (TEM) was employed to observe mitochondrial ultrastructural changes. Additionally, key gene and protein expression levels were measured using immunofluorescence and Western blotting. The micro-CT analysis revealed significant bone microarchitecture deterioration and bone loss in the GPR30-KO mouse model. At the cellular level, GPR30 overexpression markedly reduced iron accumulation and oxidative stress in BMSCs, restored the mitochondrial membrane potential, and improved the mitochondrial ultrastructure. Furthermore, GPR30 enhanced osteogenic differentiation in BMSCs by promoting the activation of the BMP-6/HEP/FPN signaling pathway, leading to increased expression of osteogenic markers. The protective effects of GPR30 were reversed by the BMP-6 inhibitor LDN-214117, indicating that BMP-6 is a critical mediator in GPR30-regulated iron metabolism and ferroptosis inhibition. GPR30 inhibits ferroptosis in BMSCs and enhances osteogenic differentiation by activating the BMP-6/HEP/FPN signaling pathway. This provides new insights and potential therapeutic targets for the treatment of osteoporosis OP.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Wenyu Luo,Binhua Huang,Minzhen Lei,Zhijian Wu,Qian Yu,Dawei Zhang,Chunyan Yan
Throughout the history of traditional Chinese medicine, Angelica pubescens has been extensively employed to treat inflammatory arthritis. However, little is known about the anti-rheumatoid arthritis (RA) effects of A. pubescens polysaccharides. In this study, four crude polysaccharides (APR50, APR70, APR90, and APRB) were isolated from A. pubescens radix, and the rat model of collagen-induced arthritis (CIA) was established to evaluate the anti-RA effects of A. pubescens polysaccharides. A. pubescens polysaccharides could effectively reduce the degree of paw swelling in CIA rats, among which the effect of APR50 was comparable to that of methotrexate. A homogenous polysaccharide APRP50-2-1 was purified from APR50. Structural characterization indicated that APRP50-2-1 was primarily composed of glucose, mannose, galactose, and arabinose. The main skeleton of APRP50-2-1 consisted of →4)- α - d -Glc p -(1→, →6)- α - d -Glc p -(1→, and →6,4)- α - d -Gal p -(1→ residues. The branched chains of →4)- α - d -Glc p -(1→ and →3)- β - d -Man p -(1→ were substituted at O -4 of →4,6)- α - d -Gal p -(1→. APRP50-2-1 inhibited the proliferation and promoted the apoptosis of MH7A cells by down-regulating the expression of the anti-apoptotic protein B-cell lymphoma-2 (BCL-2) and up-regulating the expression of the pro-apoptotic protein BCL2-associated X (BAX). In conclusion, A. pubescens polysaccharides had significant anti-RA effects in rat CIA model, among which APR50 and APRP50-2-1 possessed the promising prospects of ameliorating RA.
研究领域:
中药学
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免疫学
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结构生物学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2025
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IF 2.8
Zhi-Peng Li,Chen-Ri Su,Long-Xin Yang,Han-Yue Li,Han Zhang,Ji-Fei Yang,Xian-Hua Wang,Yun-Chao Liu,Rui-Xue Ran
Glucocorticoids play a key role in a variety of physiological processes, but their extensive use in the environment has brought potential health hazards. Herein, it is of great necessity to develop a rapid and efficient method for the detection of glucocorticoids. In this work, a hydrophilic core-shell structured magnetic covalent organic framework (HMCOF) was fabricated via a post-modification strategy for the efficient magnetic solid-phase extraction (MSPE) of five glucocorticoids from tap water and milk samples. The HMCOF featured a Fe₃O₄@SiO₂ magnetic core encapsulated by a porous COF shell modified with polyethylene glycol, endowing it with a hydrophilic outer layer, porous structure and sufficient paramagnetism. The adsorption studies showed that HMCOF exhibited high adsorption capacities (50.77–80.25 mg g −1 ) for glucocorticoids. Notably, HMCOF retained 80 % of its adsorption capacity after 5 cycles, confirming its reusability. Under the optimal conditions of MSPE, the HMCOF-based MSPE-UPLC method was developed to test five glucocorticoids, which demonstrated good linearity (5–150 ng mL −1 , R 2 ≥ 0.9991), low detection limits (0.2–1.4 ng mL −1 ) and satisfactory spiked recovery rates (89.5–114.2 %) with intra-day variability below 4.3 % and inter-day precision within 6.3 %. The method underscores the potential of HMCOF serving as an adsorbent for MSPE, providing a promising approach for the analysis of glucocorticoids within food products.
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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生物材料
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骨科
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高影响因子
FITOTERAPIA
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2025
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IF 2.6
Jinyuan Yang,Zhaojing Chen,Yikun Ren,Chunlei Yuan,Senhua Hu,Yiyang Liu,Dahong Li,Huiming Hua
Phytochemical investigation of Thalictrum baicalense Turcz. roots, traditionally used for inflammatory conditions, led to the isolation of three novel isoflavones, thalibaicalins A-C ( 1 – 3 ), and a new lignan, (7 R , 8 S , 7′ R , 8′ S )-9 E -feruloylneoolivill ( 6 ), alongside six known compounds ( 4 – 5 , 7 – 10 ). Structural characterization was accomplished by HRESIMS, comprehensive NMR analysis, and quantum chemical calculations. Anti-inflammatory evaluation in lipopolysaccharide-stimulated RAW 264.7 macrophages identified potent NO inhibitors, with lignan 6 exhibiting the highest activity (IC 50 = 9.56 ± 2.03 μM). This study expands the phytochemical diversity of T. baicalense Turcz. and highlights its potential as a source of anti-inflammatory lead compounds, particularly the highly active lignan derivative.
研究领域:
植物化学
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药理学
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药物化学
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天然产物研究
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炎症生物学
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Yu Zhong,An-Yang Li,Jun-Bin Dai,Chen Guo,Shan-Shan Chen,Li-Li Su,Qin-Ying Liu,Yang Sun
Sensitive and rapid quantification of chemotherapeutic drug paclitaxel (PTX) in human serum is crucial for enabling personalized dosing and minimizing severe toxicity. In this approach, an ultrasensitive electrochemical sensor was developed via facile one-step deposition method for rapid determination of PTX. The nitrogen-doped carbon quantum dots-multiwalled carbon nanotubes (NCQDs-MWCNT) nanocomposite, which modified on the screen-printed carbon electrode (SPCE), synergistically enhanced the active surface area, boosted the electrical conductivity and improved the detection sensitivity. Under the optimized conditions, the prepared NCQDs-MWCNT/SPCE exhibited good linearity in both 0.2 M phosphate buffer (pH 7.4) and human serum, and the limit of detection (LOD) reached as low as 1.0 nM and 2.3 nM, respectively. Additionally, the developed sensor possessed satisfactory repeatability, long-term storage property and anti-interference capability. The recovery rates were in the range of 107.73–114.05 % in human serum, indicating its accuracy of PTX measurement. In depth, the electrochemical behaviors of PTX at NCQDs-MWCNT/SPCE were examined. Collectively, the proposed ultrasensitive and facile sensor displays potential applications in therapeutic drug monitoring for PTX, facilitating individualized treatment in precision medicine.
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Materials Today Bio
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2025
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IF 10.2
Yanhui Cui,Xueqin Wang,Caiyang Lu,Liling Ran,Zirui Guo,Jiayu Yao,Tian Yu,Xuanxi Liu,Fang Li,Changqi Li,Yingcai Meng,Wenhu Zhou
Acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition marked by severe inflammatory responses and disruption of the alveolar-capillary barrier, leading to high mortality rates and lack of effective treatments. Recent research has underscored the crucial role of programmed cell death pathways-pyroptosis, apoptosis, and necroptosis-in exacerbating inflammation and barrier dysfunction in ALI/ARDS. However, effective therapeutic agents targeting this process remain scarce. In this study, we reveal that PANoptosis, which integrates these cell death pathways through the PANoptosome complex, plays a central role in the pathogenesis and progression of ALI/ ARDS. The levels of PANoptosis-related molecules were significantly elevated in both the ALI mice and the clinical ARDS patient samples, highlighting it as a novel therapeutic target. Building on this insight, we developed a multifunctional nanomedicine, TPNs/Sal B, which integrates tea polyphenol-based nanoparticles (TPNs), a bioactive nanomaterial with anti-pyroptotic and anti-necroptotic properties, with salvianolic acid B (Sal B), known for its anti-apoptotic effects. Our results demonstrate that the nanomedcine TPNs/Sal B effectively inhibit PANoptosis, thereby attenuating lung tissue pathological damage, reducing inflammation, and improving lung epithelial barrier function in ALI models. Moreover, we identified LIM and SH3 protein 1 (LASP1) which may play an critical role in modulating alveolar epithelial barrier function during ALI/ARDS progression, and treatment with TPNs/Sal B effectively restored LASP1 levels. Our findings underscore the therapeutic potential of TPNs/Sal B as a targeted treatment for ALI/ARDS, offering a promising strategy for modulating PANoptosis and preserving lung function.
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Diabetes & Metabolism Journal
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2025
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IF 8.5
Lei Zhou,Yuwen Jiao,Jiaming Xue,Xiaoqiang Zhan,Dongmei Wang,Liming Tang
Background: To investigate the biological functions of the transcription factor LRR binding FLII interacting protein 1 (LRRFIP1) in white adipocyte differentiation (WAD) and elucidate the underlying molecular regulatory mechanisms involved. Methods: Consensus clustering, differential gene expression screening, and intersection analysis were used to identify transcription factors involved in WAD. Adipogenic differentiation experiments were conducted using C3H10T1/2 cells, and a diet-induced obesity model in C57BL/6J mice was established to investigate the function of LRRFIP1 in WAD in vitro and in vivo. Molecular mechanisms were examined through quantitative real-time polymerase chain reaction, Western blotting, luciferase assays, and chromatin immunoprecipitation. Results: Bioinformatics analyses identified LRRFIP1 as a transcription factor associated with WAD. LRRFIP1 expression was downregulated in white adipose tissues from obese patients and in mature white adipocytes. Silencing LRRFIP1 significantly inhibited WAD in C3H10T1/2 cells and reduced differentiation biomarker expression; in contrast, overexpressing LRRFIP1 had the opposite effects. Mechanistically, LRRFIP1 bound to the E2F transcription factor 6 (E2F6) promoter to suppress E2F6 transcription, thereby downregulating a key differentiation regulator, CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, in a diet-induced obesity model, LRRFIP1 could regulate the differentiation and maturation of inguinal white adipose tissue. Conclusion: Our findings reveal that LRRFIP1 plays a crucial inhibitory role in WAD by negatively regulating the E2F6/C/EBPα axis. This discovery not only enriches our understanding of the molecular networks governing WAD but also holds great promise for creating targeted therapies for obesity and associated metabolic conditions.
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高影响因子
Frontiers in Medicine
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2025
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IF 3
Leidong Lian,Dingli Xu,Chaonan He,Zhe Luo,Han Yu,Botao Liu,Ke Zhou,Liangjie Lu,Kaifeng Gan
Introduction The natural polysaccharide-based injectable hydrogels have showed significant interest to use as 3D scaffolds for critical-sized bone defect repair. Methods Here, we incorporated ZnO nanoparticles (NPs) into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-ZnO) via supramolecular combination between phosphate groups in CSMP and Zinc in ZnO NPs. Results The phosphocreatine in this hydrogel not only provides sites to combine with ZnO NPs form supramolecular binding but also serves as the reservoir to control Zn 2+ release. The results show that the lyophilized CSMP-ZnO hydrogels presented a porous structure with some small holes in the pore wall, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of ZnO NPs. In vitro experiments showed that the CSMP-ZnO hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CSMP hydrogel. The as-released Zn 2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP2/SMAD signaling pathway. In vivo , the as-released Zn 2+ ions promot osteoblastic proliferation and the mineralization of osteoblasts inside the CSMP-ZnO scaffolds. Immunofluorescence for RUNX2, COL-1, and CD31, showed that stable vasculature could be formed inside the CSMP-ZnO scaffolds. Discussion Both the in vitro and in vivo results demonstrate that CSMP-ZnO hydrogel shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.
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ULTRASONICS SONOCHEMISTRY
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2025
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IF 9.7
Jiarong Su,Peishan Li,Xinrui Tang,Zihao Chen,Qiang Peng,Huilin Li,Qianhua Zhang,Shengjie Lu,Famin Wen,Huaicheng Qin,Yongguang Bi,Juan Guo,Fansheng Kong,Haijie Jin,Canzhao Chen,Huiyan Xu
Plant polyphenols have gained increasing attention due to their abundant and powerful biological activities. However, polyphenols from roots of Ilex asprella (RIAPs) remain largely unexplored, with limited research on their composition and bioactivity, making it necessary to focus on RIAPs. In the present study, single - factor analysis and response surface optimization were performed for the extraction of RIAPs via an ultrasonic bath extraction method. The findings demonstrated that at 50 % ethanol concentration, 30 min of ultrasonic time, and 300 W of ultrasonic power, the maximum extraction content of RIAPs was 30.14 ± 0.41 mg/g. Compound and structural analysis via high-resolution liquid chromatography-mass spectrometry (LC-MS/MS) and a Fourier transform infrared (FT-IR) spectrometer confirmed that polyphenols were the majority of compounds comprising RIAPs, in addition to small amounts of alkaloids and trace amounts of other compounds such as amino acids. Scanning electron microscope (SEM) images revealed that RIAPs exhibited a densely reticulated and fragmented microstructure. In addition, bioactivity experiments demonstrated significant antioxidant, antibacterial, anti-inflammatory, and anti-hyperlipidemic activities of RIAPs, supporting their potential pharmaceutical applications. This study provides an experimental foundation for further pharmacological research and potential drug development of RIAPs.
研究领域:
植物学
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生物化学
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药理学
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高影响因子
Gut Microbes
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2025
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IF 11
Yan Liu,Zhangtie Wang,Yansong Zhang,Tian Zhao,Qingjun Zhang,Weisu Huang,Baiyi Lu
Dietary cholesterol is often found in a high-fat diet (HFD) and excessive intake is harmful to cognitive function. The gut microbiome constitutes an environmental factor influenced by diet, which regulates cognitive function via the gut-brain axis. The present study explored the role of dietary cholesterol in HFD-induced cognitive impairment and the participation of the gut microbiota and metabolites. Here, we found that dietary cholesterol promoted cognitive impairment in HFD-fed mice, which was associated with an increase in gut microbiota containing 7α-dehydroxylase, including Lachnospiraceae bacterium, Dorea sp. Clostridium sp. and elevated levels of deoxycholic acid (DCA) in the hippocampus. Upon dietary cholesterol intake, the activity of gut microbiota in mice to produce DCA is increased. Fecal microbiota transplantation confirmed that the cognitive impairment-promoting process was driven by gut microbiota. Reducing circulating bile acid levels with cholestyramine improved cognitive decline in mice, whereas hippocampal administration of DCA worsened cognitive function. Pharmacological inhibition of hippocampal apical sodium bile acid transporter reduces neuronal DCA accumulation and improves neuronal apoptosis as well as cognitive impairments in mice. Overall, this study revealed that dietary cholesterol promotes HFD-induced cognitive impairment by inducing the production of DCA through gut microbiota metabolism.
研究领域:
神经科学
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微生物学
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营养学
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代谢组学
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药理学
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高影响因子
危险品化学品经营许可证（带存储）