INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wei Xiong,YuYi Li,Yilin Yan,Tianci Wen,Jingkun Li,Chaoyi Liang,Zechen Zhang,Cijun Shuai,Xiaolin Shi,Zhikui Zeng
Osteoporosis is characterized by disrupted bone metabolism, iron overload, and chronic inflammation, which collectively impair bone regeneration. Ferroptosis, an iron-dependent form of cell death, exacerbates bone loss by inducing oxidative stress and disrupting the immune microenvironment. To address these challenges, we developed a DFO-MS-NG/PLLA scaffold using selective laser sintering. This scaffold integrates deferoxamine (DFO) for iron chelation and naringin (NG) for immunomodulation within a mesoporous silica (MS) matrix. In vitro experiments demonstrated that the scaffold effectively inhibits ferroptosis by reducing intracellular iron and reactive oxygen species (ROS) levels, promotes osteogenic differentiation of mesenchymal stem cells (mBMSCs), and modulates macrophage polarization towards the anti-inflammatory M2 phenotype. A co-culture system with mBMSCs and macrophages under iron-overloaded conditions further confirmed the scaffold's ability to enhance bone formation by mitigating ferroptosis and reprogramming the immune microenvironment. This innovative scaffold design offers a promising strategy for osteoporotic bone defects treatment by simultaneously addressing iron overload, inflammation, and impaired osteogenesis.
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THERAPEUTIC DRUG MONITORING
·
2025
·
IF 2.4
Yu Hengyi,Hu Qun,Liu Lu,Xiang Dong,Yang Guangjie,Wang Yaqin,Wang Zhen,Liu Dong,Liu Aiguo,Gong Xuepeng
Background: Acute lymphoblastic leukemia (ALL) is the predominant malignancy in pediatric patients. As a crucial constituent of ALL chemotherapy, l -asparaginase is recognized as an integral element of treatment with a threshold concentration of 0.1 IU/mL used in treatment protocols. This study presents a novel liquid chromatography–tandem mass spectrometry method for evaluating plasma l -asparaginase activity in pediatric patients with ALL undergoing pegaspargase therapy. Methods: Initially, an enzyme incubation was conducted using 20 μL of plasma and 100 μL of l -asparagine (0.1 mol/L) at 37°C for 15 minutes. The reaction was stopped by adding sulfosalicylic acid and methanol. After the addition of isotope internal standard l -aspartic 13 C 4 acid, subsequent centrifugation, and dilution, the plasma samples underwent analysis by liquid chromatography–tandem mass spectrometry on a hydrophilic interaction liquid chromatography analytical column. A flow rate of 0.3 mL/min was used during isocratic elution using a mobile phase consisting of methanol–water (95:5, vol/vol) with 0.2% formic acid within a 5-minute run. Results: The calibration curves exhibited excellent linearity ranging from 0.1 to 15 IU/mL, with determination coefficients ( r 2 ) exceeding 0.99. The precision and accuracy ranged from 1% to 7% and from 93% to 110%, respectively. The relative recovery fell within the range of 98%–100%, and the internal standard–normalized matrix effect ranged from 95% to 101%. The stability was satisfactory across various conditions. Conclusions: This method was fully validated and successfully applied to quantify l -asparaginase activity in plasma samples of 15 children with ALL, enabling the monitoring of l -asparaginase activity with mass spectrometry.
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Food Bioscience
·
2025
·
IF 5.9
Haotian Zhao,Wenlong Sun,Wenfei Cai,Chang Liu,Wei Wang,Naiyan Lu
This study investigated the effects of Arctium lappa L. polysaccharides (ALP) on exercise performance and gut microbiota composition in mice subjected to acute sleep deprivation (SD) with a focus on the gut-muscle axis. The results revealed that ALP significantly enhanced the forelimb grip strength and muscle endurance in SD mice, thereby improving their overall exercise capacity. Additionally, ALP regulated the energy metabolism by increasing blood glucose, liver glycogen, and muscle glycogen levels, while simultaneously reducing oxidative stress and inflammation. Histological analysis revealed that ALP strengthened intestinal barrier function by promoting the expression of tight junction proteins ZO-1 and Occludin. In terms of gut microbiota, ALP increased the Alpha diversity of the gut microbiota and optimized its structure. Notably, ALP significantly elevated the abundance of beneficial bacteria such as Akkermansia and Muribaculaceae, while inhibiting the proliferation of harmful bacteria like Colidextribacter and Lachnoclostridium. These findings suggest that ALP improves the exercise capacity and overall health of SD mice by modulating the gut microbiota and intestinal barrier function, providing new insights into the use of dietary interventions to alleviate health issues caused by sleep deprivation.
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MOLECULES
·
2023
·Vol. 28
·期 13
·5141
·
IF 4.6
Huining Dai,Xiao Xu,Wannan Li,Xueqi Fu,Weiwei Han,Guodong Li
To explore the anti-hyperuricemia components in sunflower (Helianthus annuusL.) calathide extract (SCE), we identified abietic acid (AA) via liquid chromatography–mass spectrometry and found an excellent inhibitor of xanthine oxidase (IC50= 10.60 µM, Ki = 193.65 nM) without cytotoxicity. Based on the transcriptomics analysis of the human embryonic kidney 293T cell model established using 1 mM uric acid, we evaluated that AA showed opposite modulation of purine metabolism to the UA group and markedly suppressed the intensity of purine nucleoside phosphorylase, ribose phosphate pyrophosphokinase 2, and ribose 5-phosphate isomerase A. Molecular docking also reveals the inhibition of purine nucleoside phosphorylase and ribose phosphate pyrophosphokinase 1. The SCE exhibits similar regulation of these genes, so we conclude that AA was a promising component in SCE against hyperuricemia. This present study provided a novel cell model for screening anti-hyperuricemia natural drugs in vitro and illustrated that AA, a natural diterpenoid, is a potential inhibitor of purine biosynthesis or metabolism.Keywords:sunflower calathide;abietic acid;human embryonic kidney 293T cells;transcriptomics;xanthine oxidase inhibitor;purine metabolism
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ENZYME AND MICROBIAL TECHNOLOGY
·
2021
·
IF 3.493
Siyu Ren,Xinkuan Cheng,Long Ma
Natural fluorinated products are rare and attract great attention. The de novo fluorometabolites biosynthetic pathway in microbes has been studied. It is revealed that the carbon-fluorine (C-F) bond is formed by an exotic enzyme called fluorinase (FLA) when using fluorine ions and S -adenosyl- l -methionine (SAM) as substrates. However, the resource of the precursor SAM is still elusive. To solve this, a novel methionine adenosyltransferase from Streptomyces xinghaiensis (SxMAT) was identified and characterized. We proved that SAM was enzymatically synthesized by SxMAT, an enzyme that mediated the reaction between adenosine triphosphate (ATP) and l -methionine ( l -Met) with 99% diastereoisomeric excess ( d.e. ) and 80% yield. Such high diastereoselectivity had never been reported before. SxMAT was a Co 2+ -dependent metalloenzyme. The results showed that the metal cobalt ion contributes to the activity and selectivity of SxMAT. Molecular docking was performed to reveal its catalytic mechanism. The optimal temperature and pH were 55 °C and 8.5, respectively. Lastly, a two-step tandem enzymatic reaction using SxMAT and FLA both from S . xinghaiensis to generate 5’-fluoro-deoxyadenosine (5’-FDA) was performed. This implied that SxMAT may be present in this fluorometabolites biosynthetic route. These results suggested that SxMAT could be a useful biocatalyst for the synthesis of optically pure ( S )-S-adenosyl- l -methionine, an important nutraceutical. In addition, SxMAT will probably play an important role in the biosynthetic pathway of fluorinated natural products in bacteria.
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Journal of Fungi
·
2022
·Vol. 8
·期 6
·644
·
IF 5.724
Hanghang Lou,Xiayu Liu,Siyu Liu,Qihe Chen
Icariin is the most effective bioactive compound in Herba Epimedii. To enhance the content of icariin in the epimedium water extract, a novel strain,Papiliotrema laurentiiZJU-L07, producing an intracellular α-L-rhamnosidase was isolated from the soil and mutagenized. The specific activity of α-L-rhamnosidase was 29.89 U·mg−1through purification, and the molecular mass of the enzyme was 100 kDa, as assayed by SDS-PAGE. The characterization of the purified enzyme was determined. The optimal temperature and pH were 55 °C and 7.0, respectively. The enzyme was stable in the pH range 5.5–9.0 for 2 h over 80% and the temperature range 30–40 °C for 2 h more than 70%. The enzyme activity was inhibited by Ca2+, Fe2+, Cu2+, and Mg2+, especially Fe2+. The kinetic parameters ofKmandVmaxwere 1.38 mM and 24.64 μmol·mg−1·min−1using pNPR as the substrate, respectively. When epimedin C was used as a nature substrate to determine the kinetic parameters of α-L-rhamnosidase, the values ofKmandVmaxwere 3.28 mM and 0.01 μmol·mg−1·min−1, respectively. The conditions of enzymatic hydrolysis were optimized through single factor experiments and response surface methodology. The icariin yield increased from 61% to over 83% after optimization. The enzymatic hydrolysis method could be used for the industrialized production of icariin. At the same time, this enzyme could also cleave the α-1,2 glycosidic linkage between glucoside and rhamnoside in naringin and neohesperidin, which could be applicable in other biotechnological processes.Keywords:Papiliotrema laurentiiZJU-L07;epimedin C;icariin;α-L-rhamnosidase;enzyme characteristics;optimization
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Nutrients
·
2022
·Vol. 14
·期 13
·2591
·
IF 6.706
Cuicui Zhang,Hai Niu,Chengyu Wan,Xiuxian Yu,Guang Xin,Yuda Zhu,Zeliang Wei,Fan Li,Yilan Wang,Kun Zhang,Shiyi Li,Yuman Dong,Yangying Li,Wen Huang
Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD-/-mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.Keywords:acute pancreatitis;L-arginine;Gasdermin D;endoplasmic reticulum stress;TXNIP
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Frontiers in Pharmacology
·
2019
·
IF 3.845
Zhu Mingfei,Wang Hong,Wang Chenglin,Fang Yanfen,Zhu Tong,Zhao Weili,Dong Xiaochun,Zhang Xiongwen
Inhibition of aberrant Hedgehog (Hh) pathway had been proved to be a promising therapeutic intervention in cancers like basal cell carcinoma (BCC), medulloblastoma (MB), and so on. Two drugs (Vismodegib, Sonidegib) were approved to treat BCC and more inhibitors are in clinical investigation. However, the adverse effects and drug resistance restricted the use of Hh inhibitors. In the present study, 61 synthesized compounds containing central backbone of phthalazine or dimethylpyridazine were screened as candidates of new Hh signaling inhibitors by performing dual luciferase reporter assay. Among the compounds, L-4 exhibited an IC50 value of 2.33 nM in the Shh-Light II assay. L-4 strongly inhibited the Hh pathway in vitro and blocked the Hh pathway by antagonizing the smoothened receptor (Smo). Remarkably, L-4 could significantly suppress the Hh pathway activity provoked by Smo mutant (D473H) which showed strong resistant properties to existing drugs such as Vismodegib. Orally administered L-4 exhibited prominent dose-dependent anti-tumor efficacy in vivo in Ptch+/-; p53-/- MB allograft model. Furthermore, L-4 showed good tolerance in acute toxicity test using ICR mice. These evidences indicated that L-4 was a potent, well-tolerated, orally active inhibitor of Hedgehog pathway, and might be a promising candidate in development of Hh-targeted anti-cancer drugs.
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Biomolecules
·
2025
·Vol. 16
·期 1
·68
·
IF 4.8
Bin-Chun Li,Weijuan Dong,Bingbing Wu,Yanlong Liu,Na Han,Guo-Bin Ding
α-L-Rhamnosidase can specifically hydrolyze plant natural glycosides and holds significant potential for biocatalytic applications in functional foods, healthy products, and pharmaceutical industries. Herein, a novel thermophilic and acidophilic α-L-rhamnosidase TsRha fromThermotogasp. 2812B belonging to glycoside hydrolase family 78 was identified by genome mining and comprehensively characterized by bioinformatics, computer-aided structural analysis, and biochemical characterization. TsRha possesses a domain architecture comprising one catalytic (α/α)6-barrel domain and four β-sheet domains. TsRha displayed optimal activity at 90 °C and pH 5.0, remarkable thermostability at 80 °C, and considerable tolerance to organic solvents. TsRha exhibited broad substrate selectivity and might efficiently hydrolyze a series of natural flavonoid glycosides with various glycosidic bonds (α-1, α-1, 2, α-1, 6) from different aglycone subgroups (flavanone, flavone, flavonol, and dihydrochalcone). Moreover, it demonstrated high conversion efficiencies toward a variety of natural flavonoid diglycosides rutin, naringin, naringin dihydrochalcone, hesperidin, and troxerutin, achieving ≥99.1% conversion within 20~100 min. The excellent properties including high activity, thermophilicity, acidophilicity, good thermostability, broad substrate spectrum will make the α-L-rhamnosidase TsRha a promising biocatalyst for the efficient production of rare and high-value flavonoid glucosides with improved bioavailability and bioactivity.
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
·
2024
·
IF 5.8
Yuan-Bin Chen,Siyi Xiong
This article explores the microwave dielectric properties of (La 1-x Nd x ) 2 (Zr 0.96 Ti 0.04 ) 3 (MoO 4 ) 9 (x=0.1,0.3,0.5, and 0.7) ceramics prepared by solid-state reaction. Utilizing the Rietveld refinement technique in XRD, the sample is identified as a trigonal crystal system belonging to the R 3 ¯ c space group. SEM analysis indicates that relative density has a significant impact on the ε r and Q×f of ceramics. The Q×f values of ceramics are closely related to the FWHM of the Raman spectra. At 750℃, (La 0.5 Nd 0.5 ) 2 (Zr 0.96 Ti 0.04 ) 3 (MoO 4 ) 9 ceramic exhibited excellent dielectric properties: ε r = 10.4 (±0.08), Q×f = 149,300 (±3211) GHz, τ f = −34.8 (±0.7) ppm/℃. To gain a deeper understanding of the intrinsic mechanisms governing the microwave dielectric properties of ceramics, analysis based on the P-V-L theory reveals that the La(Nd)-O bond and Mo-O bond contribute significantly to ε r and Q×f, respectively.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiadong Pang,Leilei Huang,Yating Lian,Zhijie Yuan,Fen Wang,Li-Ming Zhang
Astrocyte elevated gene-1 (AEG-1) oncogene is a notorious and evolving target in a variety of human malignancies including osteosarcoma. The RNA interference (RNAi) has been clinically proven to effectively knock down specific genes. To successfully implement RNAi in vivo, protective vectors are required not only to protect unstable siRNAs from degradation, but also to deliver siRNAs to target cells with controlled release. Here, we synthesized a Zein-poly( l -lysine) dendrons non-viral modular system that enables efficient siRNA-targeted AEG-1 gene silencing in osteosarcoma and encapsulation of antitumor drugs for controlled release. The rational design of the ZDP integrates the non-ionic and low immunogenicity of Zein and the positive charge of the poly( l -lysine) dendrons (DPLL) to encapsulate siRNA and doxorubicin (DOX) payloads via electrostatic complexes and achieve pH-controlled release in a lysosomal acidic microenvironment. Nanocomplexes-directed delivery greatly improves siRNA stability, uptake, and AEG-1 sequence-specific knockdown in 143B cells, with transfection efficiencies comparable to those of commercial lipofectamine but with lower cytotoxicity. This AEG-1-focused RNAi therapy supplemented with chemotherapy inhibited, and was effective in inhibiting the growth in of osteosarcoma xenografts mouse models. The combination therapy is an alternative or combinatorial strategy that can produce durable inhibitory responses in osteosarcoma patients.
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Eco-Environment & Health
·
2025
·
IF 17.6
Chunmei Ran,Meiqi Guo,Yuan Wang,Ye Li,Jiao Wang,Yinqing Zhang,Chunguang Liu,Bridget A. Bergquist,Chu Peng
Evaluating the plant risk of soil pollution by plant physiological indices usually requires a long cycle and has significant uncertainty. In this study, oxidative potential (OP) of the in situ heavy metal contaminated soils was measured by the dithiothreitol method. The oxidative stress response of the model plant ryegrass ( Lolium perenne L. ) induced by heavy metal contaminated soil was evaluated by the biomarkers, including superoxide dismutase and total antioxidant capacity. The comprehensive biomarker response index has a significant exponential correlation with the OP of soil ( r = 0.923, p < 0.01) in ryegrass. Metabolomics analysis also showed a significant relationship of the metabolic effect level index of amino acids and sugars with OP. Random forest was selected from four machine learning models to screen the metabolites most relevant to OP, and Shapley additive explanations analysis was used to explain the contribution and the influence direction of the features on the model. Based on the selected 20 metabolites, the metabolic pathways most related to OP in plants, including alkaloid synthesis and amino acids metabolism, were identified. Compared to the plant physiological indices, OP is a more stable and faster indicator for the plant risk assessment of heavy metals contaminated soil.
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