ACS Applied Materials & Interfaces
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2025
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IF 8.2
Yifan Gao,Yuening Qiu,Hongyang Zhao,Yilei Yu,Mingwei Wang,Xuhong Guo,Martien A. Cohen Stuart,Junyou Wang
Cationic polymers have been applied widely for siRNA delivery, yet most of the conventional linear or branched polymers make RNA polyplexes with poor serum stability and low delivery efficacy. We here propose cationic nanogels as a better alternative and demonstrate their advantages for siRNA delivery. Using a recently developed electrostatic-templated polymerization method, we synthesized a series of cationic nanogels with precisely controlled chemical composition, size, and cross-linking degree, enabling the systematic exploration of structure–performance relationships for nanogel-mediated siRNA delivery. We show that the nanogels, with their stable 3D structure, offer both surface and interior sites for siRNA loading depending on the N/P ratio. At high N/P ratios, siRNA binds primarily to the interior sites of the nanogels, which provide enhanced protection against competing serum proteins and facilitate efficient cellular uptake. Furthermore, the chemical composition, size, and degree of cross-linking of the nanogels cooperatively influence siRNA loading and cellular uptake. The optimal formulation, poly(vinylbenzyl trimethylammonium chloride) (PVBTMA) nanogel, incorporates a strong charge group and a hydrophobic phenyl spacer that facilitate siRNA loading and cellular uptake, respectively. With an optimal size of 107 nm and 5% cross-linking, PVBTMA nanogel achieves superior siRNA internalization compared to widely used transfection agents like Lipofectamine 3000 and branched PEI25k. Finally, when loaded with tumor-specific gene silencer siPLK1, the PVBTMA nanogel facilitates superior gene silencing in vitro and effectively inhibits tumor growth in vivo. Our findings clarify the distinct advantages of cationic nanogels as carriers for siRNA delivery and highlight their promising potential for therapeutic applications.
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ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Kai Zheng,Zhaomiao Liu,Siyu Zhao,Nan Zheng,Chenchen Zhang,Yan Pang,Xiang Wang
Precise control of cell lateral positions in microchannels is critical for high-accuracy cell isolation, with such positioning primarily governed by lateral migration. Among the various factors influencing lateral migration, interphase forces play a key but underexplored role. In this study, a simulation model was developed to resolve the evolution of interphase interaction during cell–cell collisions. Using this model, we systematically analyze cell migration under the combined influence of lateral lift forces and interphase force. The results show that under low Reynolds number (Re) conditions, lateral lift forces dominate, and cells gradually reach equilibrium positions through repeated collision and separation. As Re increases, however, collisions occur with greater relative velocity, generating stronger interphase forces that drive rapid separation and induce transient but pronounced shifts in lateral cell position, typically persisting for only a few milliseconds, with peak displacements of about 25% of the equilibrium position. Experimental validation of the simulation results is achieved through microcapillary flow tests with blood cells and particles, supporting the simulation model’s predictive accuracy. Notably, we observe the formation of transient secondary rings under high Re conditions, which are attributed to interphase interactions. This study delivers mechanistic insights into intercellular dynamics in confined microflows and establishes a rigorous modeling framework for the design of high-throughput, high-purity cell isolation systems.
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ACS Applied Polymer Materials
·
2025
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IF 4.7
Jianjun Guo,Liang Yao,Hang Li,Xianqing Wang,Mingzhi Yu,Guohua Wu
Free radicals, generated in the living system through diverse biochemical pathways, can damage biomolecules, thereby causing oxidative stress, impairing tissue function, and delaying wound healing. This has stimulated increasing interest in antioxidant-based strategies to neutralize free radicals and protect biological structures. Gallic acid (GA), a plant-derived polyphenol, is well-known for its potent free-radical scavenging activity. However, its poor solubility and instability under physiological conditions limit its practical applications. In this work, GA was coordinated with ferric ions to form ultrasmall Fe-GA nanoscale coordination polymers (Fe-GA NCPs), designed to enhance its stability and maintain antioxidant activity. To provide a biocompatible and mechanically stable carrier, silk fibroin (SF) from silkworm cocoons, an FDA-approved biomaterial widely used in medical applications, was selected as the carrier. The resulting RSF/Fe-GA NCPs exhibited strong hydroxyl and DPPH radical scavenging abilities, improved mechanical strength and flexibility, and excellent biocompatibility. In vivo studies confirmed accelerated wound closure, enhanced tissue regeneration, and reduced inflammatory marker expression, demonstrating the potential of these antioxidant fibers as multifunctional materials for wound healing and other bio-based applications.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2025
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IF 3.5
Teng Wang,Cong Li,Xiao Dong Lu,Xue Ying Ma,Li Ji,Jian Ling Zhang,Geng Li Huang,Xiao Xie,Ying Ying Liu,Jie Xiao,Hai Feng Li,Zhou Ping Wang
BACKGROUND Asini Corii Colla (ACC) and fish maw (FM) are established bioactive compounds with antioxidant and anti-aging properties, although their combinatorial effects remain uncharacterized. The present study systematically evaluated ACC-FM formulations (low-dose: LAF; high-dose: HAF) through in vitro antioxidant assessments and in vivo aging models, focusing on dermal fibroblast functionality and cutaneous tissue integrity. RESULTS The LAF formulation demonstrated superior in vitro antioxidant activity, achieving 77.60% ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging ( P < 0.05) and 1.47 U mL –1 total antioxidant capacity ( P < 0.05). It enhanced human dermal fibroblasts (HFF-1) migration by 38.50% and stimulated maximal collagen secretion (641.58 ± 64.70 ng mL –1 at 5 mg mL –1 ). In vivo studies revealed that LAF significantly increased skin antioxidant enzyme activity (35.23 ± 1.65 U mg –1 protein, P < 0.05), reduced lipid peroxidation (3.15 ± 0.29 m m mg –1 protein) and improved skin elasticity and thickness compared to controls. CONCLUSION This study provides the first evidence of synergistic anti-aging effects between ACC and FM, with the low-dose formulation (LAF) exhibiting optimal efficacy in enhancing antioxidant defense and tissue repair. These findings position LAF as a viable bioactive agent for anti-aging applications in cosmeceuticals and functional foods, supporting further translational investigation. © 2025 Society of Chemical Industry.
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PHYTOTHERAPY RESEARCH
·
2025
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IF 6.3
Min Zhan,Qin Yi,Liang Yu,Qiankun Li,Murong Jiang,Dongsheng Wu,Mintao Jian,Hui Cao,Donghua Bin
Colitis-associated colon cancer (CAC) is a malignant tumor caused by long-term inflammation. Isopimpinellin, known for its anti-inflammatory and anti-tumor properties in areas beyond CAC, may target arachidonate 5-lipoxygenase (ALOX5). This study aims to investigate the regulation of the isopimpinellin/ALOX5 axis in CAC. CAC mouse model was induced through intraperitoneal injection of 10 mg/kg azoxymethane and administration of 2% dextran sulfate sodium salt in drinking water. Oral isopimpinellin (50 or 100 mg/kg) was administered. ALOX5 expression was upregulated via adenovirus delivery. Non-targeted metabolomics was employed to analyze the influence of isopimpinellin on metabolic profiles. The 100 mg/kg isopimpinellin demonstrated promising therapeutic effects, as evidenced by protected colon tissue and the inhibition of inflammation and tumor. Pro-inflammatory factors were elevated in para-carcinoma tissues, while anti-inflammatory cytokines were upregulated in cancer tissues. M2 macrophages were increased in cancer tissues, whereas M1 macrophages were elevated in para-carcinoma tissues. Oral administration of isopimpinellin suppressed M2 polarization and M1 polarization in macrophages of cancer and para-carcinoma tissues, respectively. The overexpression of ALOX5, which was expressed in macrophages in the colon, abolished the effects of isopimpinellin. Finally, isopimpinellin altered metabolism in CAC mice, involving cancer-related metabolic processes and signaling pathways in cancer tissues, and amino acid metabolic pathways in para-carcinoma tissues. Isopimpinellin inhibits macrophage M1 polarization in cancer tissues and M2 polarization in para-carcinoma tissues by targeting ALOX5, thereby inhibiting tumor growth and inflammatory response in CAC mice. This study provides strategies for the treatment of CAC.
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Food Science & Nutrition
·
2025
·Vol. 13
·期 11
·e71153
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IF 3.8
Jinjia Liu,Yuning Zhang,Furong Lv,Chengming Wang,Jixiang Wang,Lijuan Li,Jinqiang Wu,Lina Lai
In this study, we aimed to investigate the hepatoprotective effects of plantagoside (PLA) against D-galactose (D-gal)-induced liver injury in aged mice. PLA treatment significantly alleviated the D-gal-induced body weight loss and the elevated liver index in mice, and effectively reduced oxidative stress, inflammatory response, and liver tissue damage in vivo. Transcriptomic analysis identified 513 differentially expressed genes (DEGs) regulated by PLA, and enrichment analysis revealed that these genes were primarily associated with the PI3K-Akt signaling pathway and purine metabolism. Metabolomic analysis revealed that PLA regulates purine metabolism by modulating key metabolites, such as hypoxanthine and cAMP. Integrated omics analysis suggested that PLA exerts protective effects by regulating purine metabolism, thereby enhancing antioxidant capacity and suppressing inflammation. In conclusion, PLA significantly alleviated D-gal-induced liver injury, reduced oxidative stress, and attenuated inflammation by regulating purine metabolism, thereby demonstrating its potential as an anti-aging and hepatoprotective drug and providing a new theoretical basis for the treatment of age-associated liver diseases.
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Small
·
2025
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IF 12.1
Lan Li,Tingting Huang,Xianglei Mo,Siyi Huang,Shuiquan Deng,Zhuoling Jiang,Jinxin Lin
Octacalcium phosphate (OCP) is a biodegradable material with excellent biocompatibility and osteoinductive activity, showing great promise in bone repair applications. Although silk fibroin (SF) demonstrates osteogenic potential and SF-modified OCP has shown enhanced mineralization and osteogenesis in vitro, the underlying regulatory mechanism remains unclear. In this study, by combining cryo-transmission electron microscopy analysis and density functional theory (DFT) calculations, the SF-modified OCP is revealed that possesses a higher density of dislocations. The hydrophobic amino acid sequence of SF induced the formation of edge dislocations via an “adsorption-epitaxy-extrusion” mechanism, accompanied by changes in adsorption energy, which facilitated the transformation of OCP into hydroxyapatite (HAp) and enhanced osteoinduction. In vitro experiments further confirmed that SF-modified OCP enhanced cytocompatibility, promoted ALP and ARS activity, upregulated osteogenic gene expression, and strengthened osteogenic protein expression. This work proposed a novel strategy for modulating defect structures in bioceramics through organic molecules and demonstrated the potential of dislocation-engineered SF-OCP for bone defect repair.
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ORAL DISEASES
·
2025
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IF 2.9
Yidan Zhang,Luxuan Cai,Shengjie Cui,Yanning Guo,Ning Hu,Yuan Zhang,Yehua Gan,Jieni Zhang,Xuedong Wang
Objective Elucidate the mechanism underlying chondrocyte apoptosis induced by abnormal glycometabolism in the early stages of temporomandibular joint osteoarthritis (TMJOA) and identify potential therapeutic targets. Design Established TMJOA model by monosodium iodoacetate(MIA), a direct inhibitor of glyceraldehyde 3-phosphate dehydrogenase(GAPDH). Assessed the relationship between chondrocyte apoptosis and the levels of advanced glycation end products (AGEs) and their receptor (RAGE). Confirmed the apoptosis-inhibitory effect of AGEs by RAGE inhibitor FPS-ZM1. Verified the role of p38 in the up-regulation of cleaved caspase-3. Investigated the effect of glyceraldehyde 3-phosphate (G3P) in AGEs-RAGE pathway. verified the universality of the AGEs-RAGE pathway in occlusal interference-induced TMJOA. Results In the early stages of TMJOA, chondrocyte apoptosis was associated with an upregulation of AGEs and RAGE. AGEs induced chondrocyte apoptosis by activating p38 through a RAGE-dependent pathway. Inhibition of GAPDH led to the accumulation of G3P, resulting in an upregulation of AGEs and RAGE. Inhibition of RAGE reversed chondrocyte apoptosis following GAPDH inhibition. Local joint injection of FPS-ZM1 alleviated TMJOA induced by both MIA and OI. Conclusions Altered glycometabolism can induce chondrocyte apoptosis through the AGEs-RAGE axis, suggesting that RAGE may serve as a therapeutic target for TMJOA.
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CHEMBIOCHEM
·
2025
·Vol. 26
·期 20
·e202500271
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IF 2.8
Yanan Wei,Yanying Sun,Xinyue Zhou,Doyoun Kim,Jihyeon Lee,Jeong Kyu Bang,Woo Jae Kim
Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics in combating multidrug-resistant pathogens, yet their clinical translation is hindered by proteolytic instability, cytotoxicity, and poor bioavailability. Herein, it is demonstrated that glycosylphosphatidylinositol-mediated membrane tethering of honeybee defensin1 (Def1) in Drosophila melanogaster enhances its antimicrobial efficacy by 100-fold compared to secreted or untethered forms, while preserving physiological and behavioral integrity under baseline conditions. Using a genetically engineered Drosophila model, three Def1 variants are expressed: native (Def1), secreted (s-Def1), and membrane-tethered (t-Def1). Flies expressing t-Def1 exhibit superior bacterial clearance of Pseudomonas aeruginosa and show improved survival postinfection, with no adverse effects on locomotion, courtship, or sleep architecture. However, under stress paradigms—including sleep deprivation and dextran sulfate sodium (DSS)-induced gut injury—t-Def1 exacerbates intestinal barrier dysfunction, as evidenced by elevated Smurf phenotype incidence, highlighting a trade-off between antimicrobial potency and epithelial vulnerability. This work establishes Drosophila as a powerful platform for dissecting AMP mechanisms and engineering spatially targeted therapies, offering translational insights for pollinator health and human infectious disease management. These results advocate for iterative refinement of membrane-anchoring strategies to balance therapeutic efficacy with host safety, advancing the development of next-generation AMPs with minimized off-target effects. Graphical Confocal images showing bacterial proliferation in the Drosophila gut reveal antimicrobial activity of t-Def1(tethered defensin1) against Pseudomonas aeruginosa.
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PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2025
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IF 1.9
Shuhan Yang,Jing Jiang,Dan Zhao
Exopolysaccharide (EPS) from lactic acid bacteria is of interest for its multifunctional properties, but low yield limits industrial application. This study optimized EPS production by Weissella confusa P2 using response surface methodology (RSM). Plackett-Burman (PB) design identified significant factors (sucrose, sodium acetate, and K2HPO4), followed by steepest ascent approach to approximate optimal levels, with final optimization via central composite design (CCD). Under the optimized conditions (77.42 g/L sucrose, 3.42 g/L sodium acetate, 1.76 g/L K2HPO4, 12 g/L peptone, 12 g/L beef extract, 6 g/L yeast extract, 3 g/L ammonium citrate, 0.15%Tween-80, 0.2 g/L MgSO4 and initial pH value 6.5), EPS yield increased 1.60-fold to 49.93 g/L. W. confusa P2 EPS exhibited significant antioxidant activity, with scavenging rates of 40.2 ± 0.02% (DPPH), 30.2 ± 0.01% (ABTS), 45.6 ± 0.03% (·OH), and 40.7 ± 0.03% (H2O2), and a reducing power of 0.24 ± 0.03 (OD700 nm) at 5 mg/mL. Compared to commercial prebiotics, the EPS significantly stimulated the growth of probiotics, including Bifidobacterium lactis Bi-OA 07, Lactobacillus rhamnosus CICC 21773, and Lactobacillus casei HDS-01. Furthermore, the EPS induced a concentration-dependent coagulation in sucrose-supplemented skim milk. These results highlight the potential of W. confusa P2 EPS for food industry applications.
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Current Protocols
·
2025
·Vol. 5
·期 10
·e70241
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IF 2.2
Yiming Zhao,Jingjun Hong
Chromatin remodeling is a process of regulating gene expression levels by altering chromatin structure, facilitated by chromatin remodeling factors. ISWI (Imitation SWItch), a type of chromatin remodeling factor, plays a crucial role in epigenetic regulatory processes, such as cell differentiation and development. It primarily achieves remodeling effects by promoting the direct sliding of nucleosomes and their relocation on DNA. To study the function and structural characteristics of ISWI, this basic protocol describes a simple and rapid procedure for the large-scale expression and purification of soluble Ct ISWI 77-1038 and Ct ATPase 77-722 proteins in Escherichia coli ( E. coli ). The procedure provides high yields (∼20 mg) and is followed by in vitro measurement of ATP hydrolysis activity. © 2025 Wiley Periodicals LLC. Basic Protocol : Expression, purification, and ATP hydrolysis activity measurement of Ct ISWI and Ct ATPase
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PLANT BIOTECHNOLOGY JOURNAL
·
2025
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IF 10.5
Tengfei Zhang,Jie Zang,Boming Yang,Qiuxia Wang,Jijun Yan,Peiyong Xin,Jinfang Chu,Huabang Chen,Zhaogui Zhang
Vitamin B1 (VB1) plays a crucial role in sustaining plant health and enabling adaptive responses to environmental stress. The complex maize genome implies a sophisticated VB1 synthesis pathway, with the mechanisms by which VB1 benefits plants remaining elusive. Here, we identified two VB1 biosynthetic genes, THIAMINE REQUIRING 1 ( ZmTH1 ) and its paralog THIAMINE MONOPHOSPHATE SYNTHASE 1 (ZmTMPS1 ), from a natural mutant pale leaf and depauperate growth 1 ( pldg1 ). We elucidated their specific roles in regulating multiple thiamin diphosphate (TDP)-dependent metabolic pathways and their effects on plant growth and stress tolerance. ZmTH1 encodes a chloroplast-localised, bifunctional enzyme comprising phosphomethylpyrimidine kinase (HMPP-K) and thiamine monophosphate synthase (TMP-S) domains. Functional dissection revealed that these domains functioned synergistically, with disruption of one domain significantly attenuating the other, although both can function independently. A frameshift mutation in ZmTH1 ( Zmth1 ) resulted in reduced biosynthesis of VB1, TMP and TDP. Consequently, the activity of TDP-dependent enzymes was impaired, disrupting multiple TDP-dependent metabolic pathways. Additionally, ZmTMPS1 , localised to the cytosol and nucleus, exhibited limited TMP-S activity that partially compensated for ZmTH1 mutation in pldg1 but cannot fully restore VB1 levels. Overexpression of ZmTH1 or exogenous VB1 application enhanced maize seedling tolerance to cold and drought stresses by increasing TDP-dependent enzyme activity. These findings advance the understanding of VB1 metabolism in maize and provide genetic targets for improving stress resilience and crop performance.
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