FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Dongjing Cai,Xia Xu,Weiqian Zeng,Zheng Wang,Cheng Chen,Yunan Mo,Piyanat Meekrathok,Dandan Wang,Pengwei Peng,Zhigang Peng,Jian Qiu
Cellular senescence is a natural barrier of the transition from premalignant cells to invasive cancer. Pharmacological induction of senescence has been proposed as a possible anticancer strategy. In this study, we found that deoxyarbutin inhibited the growth of glioblastoma (GBM) cells by inducing cellular senescence, independent of tyrosinase expression. Instead, deoxyarbutin induced mitochondrial oxidative stress and damage. These aberrant mitochondria were key to the p53-dependent senescence of GBM cells. Facilitating autophagy or mitigating mitochondrial oxidative stress both suppressed p53 expression and alleviated cellular senescence induced by deoxyarbutin. Thus, our study reveals that deoxyarbutin induces mitochondrial oxidative stress to trigger the p53-dependent senescence of GBM cells. Importantly, deoxyarbutin treatment resulted in accumulation of p53, induction of cellular senescence, and inhibition of tumor growth in a subcutaneous tumor model of mouse. In conclusion, our study reveals that deoxyarbutin has therapeutic potential for GBM by inducing mitochondrial oxidative stress for p53-dependent senescence of GBM cells.
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高影响因子
BioTech
·
2025
·Vol. 14
·期 1
·18
·
IF 3.1
Yao Lu,Qiang Jiang,Yamin Dong,Runzhen Ji,Yiwen Xiao,Du Zhu,Boliang Gao
The GH43 family of glycosidases represents an important class of industrial enzymes that are widely utilized across the food, pharmaceutical, and various other sectors. In this study, we identified a GH43 family glycoside hydrolytic enzyme,Xyaf313, derived from the plant endophytic fungusChaetomium globosumDX-THS3, which is capable of transforming several common ginsenosides. The enzyme function analysis reveals that Xyaf313 exhibits dual functionality, displaying both α-L-arabinofuranosidase and β-D-xylosidase activity. When acting as an α-L-arabinofuranosidase, Xyaf313 achieves optimal enzyme activity of 23.96 U/mg at a temperature of 50 °C and a pH of 7. In contrast, its β-D-xylosidase activity results in a slight reduction in enzyme activity to 23.24 U/mg, with similar optimal temperature and pH conditions to those observed for the α-L-arabinofuranosidase activity. Furthermore, Xyaf313 demonstrates considerable resistance to most metal ions and common chemical reagents. Notably, while the maximum enzyme activity of Xyaf313 occurs at 50 °C, it maintains high activity at room temperature (30 °C), with relative enzyme activity exceeding 90%. Measurements of ginsenoside transformation show that Xyaf313 can convert common ginsenosides Rc, Rb1, Rb2, and Rb3into Rd, underscoring its potential for pharmaceutical applications. Overall, our findings contribute to the identification of a new class of bifunctional GH43 glycoside hydrolases, highlight the significance of plant endophytic fungi as a promising resource for the screening of carbohydrate-decomposing enzymes, and present new candidate enzymes for the biotransformation of ginsenosides.
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高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2017
·Vol. 40
·期 22
·4311-4319
·
IF 2.557
Nani Wang,Qiaoyan Zhang,Hailiang Xin,Dan Shou,Luping Qin
A method using osteoblast membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time-of-flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases.
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Discover Oncology
·
2024
·Vol. 15
·期 1
·1-13
·
IF 2.8
Deng Chunmin,Zhang Hao,Song Li
Nanoparticle-based photothermal therapy (PTT) has emerged as a promising approach in tumor treatment due to its high selectivity and low invasiveness. However, the penetration of near-infrared light (NIR) is limited, leading it fails to induce damage to the deep-seated tumor cells within the tumor tissue. Additionally, inefficient uptake of photothermal nanoparticles by tumor cells results in suboptimal outcomes for PTT. In this study, we utilized the adhesive properties of photothermal material, polydopamine (PDA), which can successfully load the photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) to achieve photothermal and chemotherapy synergy treatment (PDA/DOX&ICG), aiming to compensate the defects of single tumor treatment. To extending the blood circulation time of PDA/DOX&ICG nanoparticles, evading clearance by the body immune system and achieving targeted delivery to tumor tissues, a protective envelopment was created using erythrocyte membranes modified with folate acid (FA-EM). After reaching the tumor tissue, the obtained FA-EM@PDA/DOX&ICG nanoparticles can specific bind with folate acid receptors on the surface of tumor cells, which can improve the uptake behavior of FA-EM@PDA/DOX&ICG nanoparticles by tumor cells, and leading to the release of loaded DOX and ICG in response to the unique tumor microenvironment. ICG, as a typical photosensitizer, significantly enhances the photothermal conversion performance of FA-EM@PDA/DOX&ICG nanoparticles, thus inducing tumor cells damage. In vitro and in vivo experimental results demonstrated that the coordinated NIR treatment with FA-EM@PDA/DOX&ICG not only effectively inhibits tumor growth, but also exhibits superior biocompatibility, effectively mitigating DOX-induced tissue damage.
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高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 4
·e23470
·
IF 4.4
Guangyu Zhou,Pai Liu,Chen Zhang,Qun Huang,Zixia Zhao,Si Wu,Detian Li,Hongbo Liu
Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with β-glycerophosphate (β-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and β-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that β-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in β-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hongwei Li,Le Kang,Shirong Dou,Yiming Zhang,Yumei Zhang,Ning Li,Yangang Cao,Mengyun Liu,Deen Han,Kai Li,Weisheng Feng
Background Gleditsiae Sinensis Fructus (GSF) is commonly used in traditional medicine to treat respiratory diseases such as bronchial asthma. However, there is a lack of research on the chemical composition of GSF and the pharmacological substance and mechanism of action for GSF in treating bronchial asthma. Purpose The chemical constituents of GSF were analyzed using ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In this study, we combined network pharmacology, molecular docking techniques, and experimental validation to explore the therapeutic efficacy and underlying mechanism of GSF in the treatment of bronchial asthma. Methods Characterization of the chemical constituents of GSF was conducted using UHPLC-Q-Orbitrap HRMS. The identified chemical components were subjected to screening for active ingredients in the Swiss Absorption, Distribution, Metabolism, and Excretion (ADME) database. Relevant databases were utilized to retrieve target proteins for the active ingredients and targets associated with bronchial asthma disease, and the common targets between the two were selected. Subsequently, the protein-protein interaction (PPI) network was constructed using the String database and Cytoscape software to identify key targets. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database. The "component-common target" network was constructed using Cytoscape to identify the primary active ingredients. Molecular docking validation was conducted using AutoDock software. The bronchial asthma mouse model was established using ovalbumin (OVA), and the lung organ index of the mice was measured. Lung tissue pathological changes were observed using hematoxylin and eosin (HE), Periodic Acid-Schiff (PAS), and Masson staining. The respiratory resistance (Penh) of the mice was assessed using a pulmonary function test instrument. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IgE, IL-4, IL-5, and IL-13 in the mouse serum. Immunofluorescence staining was performed to detect the protein expression levels of AKT and PI3K in the lung tissues. An in vitro experiment was performed to observe the effects of echinocystic acid (EA) on IL-4 stimulated Human ASMCs (hASMCs). Cell viability was measured using a CCK-8 assay to calculate the IC50 value of the EA. A wound healing test was conducted to observe the effect of EA on degree of healing. RT-qPCR was performed to detect the influence of EA on the mRNA expression levels of ALB, SRC, TNF-α, AKT1, and IL6 in the cells. Results A total of 95 chemical constituents were identified from the GSF. Of these, 37 were identified as active ingredients. There were 169 overlapping targets between the active ingredients and the disease targets. A topological analysis of the protein-protein interaction (PPI) network identified the core targets as IL6, TNF, ALB, AKT1, and SRC. An enrichment analysis revealed that the treatment of bronchial asthma with GSF primarily involved the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway, among others. The primary active ingredients included 13(s)-HOTRE, linolenic acid, and acacetin. The molecular docking results demonstrated a favorable binding activity between the critical components of GSF and the core targets. Animal experimental studies indicated that GSF effectively improved symptoms, lung function, and lung tissue pathological changes in the OVA-induced asthmatic mice, while alleviating inflammatory responses. GSF decreased the fluorescent intensity of the AKT and PI3K proteins. The IC50 value of EA was 30.02μg/ml. EA (30) significantly promoted the proliferation of IL4-stimulated hASMCs cells. EA (30) significantly increased the expression of ALB and SRC mRNA and decreased the expressions of TNF-α, AKT, and IL6 mRNA. Conclusion The multiple active ingredients found in GSF exerted their anti-inflammatory effects through multiple targets and pathways. This preliminary study revealed the core target and the mechanism of action underlying its treatment of bronchial asthma. These findings provided valuable insights for further research on the pharmacological substances and quality control of GSF.
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高影响因子
SENSORS
·
2024
·Vol. 24
·期 20
·6701
·
IF 3.4
Zhao-Jiang Yu,Ting-Ting Yang,Gang Liu,De-Hua Deng,Lin Liu
This work reported gold nanoparticles (AuNPs)-based colorimetric immunoassay with the Cu-based metal–organic framework (MOF) to load pyrroloquinoline quinone (PQQ) for the catalytic oxidation of cysteine. In this method, both Cu2+and PQQ in the MOF could promote the oxidation of inducer cysteine by redox cycling, thus limiting the cysteine-induced aggregation of AuNPs and achieving dual signal amplification. Specifically, the recombinant carcinoembryonic antigen (CEA) targets were anchored on the MOF through the metal coordination interactions between the hexahistidine (His6) tag in CEA and the unsaturated Cu2+sites in MOF. The CEA/PQQ-loaded MOF could be captured by the antibody-coated ELISA plate to catalyze the oxidation of cysteine. However, once the target CEA in the samples bound to the antibody immobilized on the plate surface, the attachment of CEA/PQQ-loaded MOF would be limited. Cysteine remaining in the solution would trigger the aggregation of AuNPs and cause a color change from red to blue. The target concentration was positively related to the aggregation and color change of AuNPs. The signal-on competitive plasmonic immunoassay exhibited a low detection limit with a linear range of 0.01–1 ng/mL. Note that most of the proteins in commercial ELISA kits are recombinant with a His6tag in the N- or C-terminal, so the work could provide a sensitive plasmonic platform for the detection of biomarkers.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaohong Zhu,Tiantian Feng,Yidan Chen,Yao Xiao,Wei Wen,Xiuhua Zhang,Dong Wang,Shengfu Wang,Jichao Liang,Huayu Xiong
Skin wound healing, particularly diabetic wound healing, is a common clinical challenge. Reducing bacterial infection and promoting angiogenesis are key strategies for diabetic wound healing. In this study, we construct the porphyrin-based Cu-covalent organic frameworks (Cu-COF) through a Schiff base condensation reaction, and then functionalize Cu-COF with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE), denoted as PEG/Cu-COF, for enhancing diabetic wound healing. PEG/Cu-COF exhibits dual enzymatic properties (glutathione (GSH) oxidase-like and peroxidase (POD)-like nanozymes), facilitating the depletion of GSH and the generation of reactive oxygen species (ROS) through a self-cascading enzymatic reaction, thereby leading to chemodynamic therapy (CDT). Density functional theory (DFT) calculations are employed to investigate the catalytic mechanism and the results reveal that Cu-COF exhibits higher catalytic activity for POD. Moreover, porphyrin-based COF generates singlet oxygen and localize heating under white light and near-infrared irradiation, respectively. Both in vitro and in vivo experiments demonstrate that PEG/Cu-COF exhibits multimodal synergistic sterilization and promotes angiogenesis, collagen deposition, and re-epithelialization during diabetic wound healing. This work highlights the potential utilization of PEG/Cu-COF for self-supplying hydrogen peroxide (H 2 O 2 ) and amplifying self-cascade reactions to address the limitations of enzymatic treatment, while the synergistic effect of phototherapy improves sterilization and minimizes side effects in vivo .
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高影响因子
DESALINATION
·
2024
·
IF 8.3
Yumeng Xie,Jing Ren,Peng Liu,Junfeng Zheng,Zhaohuan Mai,Yanyan Liu,Xuewu Zhu,Xin Li,Daliang Xu,Heng Liang
Nanofiltration technology has been widely used in drinking water purification due to its excellent permeance and selectivity properties, especially in small molecular solute separation. However, using oxidizing agents in the pretreatment process for fouling control threatens the nanofiltration membrane structure, leading to the deterioration of the separation performance. Herein, we fabricate a polyester nanofiltration membrane utilizing xylose as an aqueous monomer in the interfacial polymerization process. Due to abundant hydroxyl groups and low reactivity of xylose monomers, the polyester membrane possessed a hydrophilic and thin separation layer, which led to high water permeance with the optimal value of 28.7 L·m −2 ·h −1 ·bar −1 . Possessing highly cross-linking structures and negatively charged surfaces, the fabricated polyester membranes showed an excellent Na 2 SO 4 rejection of up to 95.4 %. In addition, the low electron-donating property of polyester membranes ensured their chemical stability toward active chlorine. This endows relatively stable performance of the polyester membrane after chlorine resistance tests in a wide pH range. This study presents a feasible approach employing green monomers for fabricating nanofiltration membranes with outstanding separation performance and robust chlorine resistance.
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高影响因子
DYES AND PIGMENTS
·
2025
·
IF 4.2
Jing Zhu,Songfang zhao,Ruifang Guan,Hao Zhang
Heteroatom doping can achieve specific regulation of carbon dots by changing their nanostructure, electronic structure and band gap. Here, we synthesized nitrogen-sulfur co-doped carbon dots (N, S-CDs) with full-spectrum fluorescence emission capability. Through comprehensive structural analysis using XPS, FTIR, and other characterization techniques, it was revealed that most of the nitrogen atoms were integrated into the carbon core of the N, S-CDs. Meanwhile, sulfur atoms were identified on the surface of the N, S-CDs, incorporated as functional groups. This unique structural configuration provides a foundation for understanding the solvent effect on N, S-CDs. Specifically, as the polarity of the solvent increases, the fluorescence emission of the N, S-CDs experiences a red-shift. The varying hydrogen donor abilities of different solvents contribute to changes in fluorescence emission. Notably, N, S-CDs exhibit near-infrared fluorescence emission when dissolved in acetic acid solvent. Under the synergistic effect of solvent polarity and hydrogen bonding, the fluorescence emission of N, S-CDs achieves full-spectrum luminescence, spanning from blue light to near-infrared. It is particularly interesting to observe that when N, S-CDs are dispersed in polyvinyl alcohol (PVA) films by dissolving them in three different solvents, the red, green, and yellow light emission can be achieved. When coated onto Light Emitting Diode (LED) lamp beads, these films exhibit versatile light emission properties. This provides inspiration for the development and preparation of LED fluorescent materials. Meanwhile, thanks to the excellent luminescent properties of N, S-CDs in water, they can be used for targeted localization of lysosomes in biological cells.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Wenjing Ren,Huiru Zhu,Dongshuai Shang,Xinyu Zhou,Hua Zhang,Juan Zhang,Guangpu Liu,Yunbo Wei,Kaiming Wang,Chengshi Jiang,Ping Sun
In this article, folic acid (FA) modified biodegradable poly (ethylene glycol) (PEG 2K ) was chosen as the polymeric skeleton to conjugate with curcumin (CUR) via a disulfide bond to construct a reduction-responsive drug delivery system (FA-PEG 2K -SS-CUR), aiming at improving the solubility of CUR and providing a targeted, efficient, and low side-effect anti-cancer nano-preparation. The polymers were synthesized through three steps to develop FA-PEG 2K -SS-CUR micelles, with a drug loading capacity of up to 10.9% and good stability. The particle of FA-PEG 2K -SS-CUR micelles determined by Malvern Mastersizer was 79.14±2.2 nm, and a hemolysis assay confirmed their good biocompatibility. The reduction sensitivity of FA-PEG 2K -SS-CUR micelles was verified by adding dithiothreitol (DTT) to the release medium, showing a programmed drug release mode with 60.41% released within 72 h, indicating a certain sustained-release capability. In vitro cytotoxicity assays showed that the FA-PEG 2K -SS-CUR micelles were more cytotoxic than free CUR. Additionally, FA-PEG 2K -SS-CUR micelles exhibited a higher cellular uptake rate than micelles without FA. Hence, the prepared multifunctional FA-PEG 2K -SS-CUR micelles is a promising anti-tumor nano-preparation.
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MOLECULES
·
2024
·Vol. 29
·期 9
·2043
·
IF 4.2
Ju Liu,Wenfeng Li,Lu Jin,Yingchao Wang,Xinjun Xu,Enyao Ma,Depo Yang,Zhimin Zhao
Two unreported heteropolysaccharides, denoted as YCJP–1 and YCJP–2, were isolated from the herbs ofChloranthus japonicus. YCJP–1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475–228,443 Da range. YCJP–2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects ofC. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP–1 and YCJP–2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP–1, and YCJP–2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP–1, and YCJP–2. Moreover, YCJP–2 demonstrated superior anti-gastric cancer effects compared to YCJP–1. This could potentially be attributed to YCJP–2’s higher glucose content and narrower molecular weight distribution.
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高影响因子
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