Journal of Orthopaedic Surgery and Research
·
2026
·Vol. 21
·期 1
·2
·
IF 2.8
Yu Xi,Li Yajie,Chen Xiaping,Cheng Junhua,Yu Xinhua,Xu Xueqin,Xiao Qin,Zhu Xiaohu,Ke Changbin
As a prevalent degenerative condition affecting joints, osteoarthritis (OA) involves the gradual deterioration of articular cartilage. Impaired chondrocyte function is a major driver of osteoarthritis pathogenesis. In this study, we focused on deciphering the mechanistic basis of Tspan5 activity in the absence of the tight junction component Claudin11(Cldn11), utilizing male SD rats as the experimental model, which regulates the process of OA through the Notch signalling pathway. An animal model of OA was successfully established by injecting monosodium iodoacetate (MIA) into the knee joint cavity. The rats in the experimental groups were injected with Cldn11-RNAi lentivirus into the knee joint cavity or orally gavaged with Notch signalling pathway-specific inhibitors. The mechanical pain threshold was monitored dynamically using the von Frey fiber filament method. The OA model group exhibited a significant decrease in Cldn11 levels, as confirmed by qRT-PCR, western blot, and immunohistochemical staining, alongside this, the levels of essential Notch signalling molecules declined. Gene downregulation of Cldn11 significantly inhibited the expression of Tspan5 and further downregulated Notch signalling pathway activity, accelerating the process of cartilage degeneration. The Notch inhibitor intervention group presented a significant reduction in the mechanical pain threshold. The present study demonstrated that Cldn11 knockdown transcriptionally suppresses Tspan5 expression, leading to a Tspan5-dependent attenuation of the Notch pathway, which ultimately exacerbates the pathogenesis of osteoarthritis.
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PubMed
高影响因子
Clinical Epigenetics
·
2025
·Vol. 18
·期 1
·12
·
IF 4.4
Yu Chao,Yao Liyuan,Du Xinyu,Yu Jianjun,Wang Yanjin,Hou Xiying,Shen Fengchen,Liu Na,Zhuang Shougang
Background Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), has been implicated in promoting renal fibrogenesis. Nevertheless, its precise role and underlying mechanisms remain incompletely defined. Methods To investigate the role of EZH2 in partial epithelial-mesenchymal transition (pEMT) and renal fibrosis, we utilized a mouse model with renal tubular cell-specific EZH2 deletion and administered gambogic acid (GA), a selective EZH2 degrader, following unilateral ureteral obstruction (UUO). In vitro, mouse renal epithelial cells were stimulated with TGF-β1 and treated with either EZH2-specific siRNA or GA to assess the effects on EMT and Notch1/3 signaling. In addition, chromatin immunoprecipitation (ChIP) assays were conducted to evaluate the binding of EZH2 and H3K27me3 to the promoters of Notch1 and Notch3. Results Compared with wild-type controls, mice with tubular cell-specific EZH2 deletion exhibited significantly reduced renal fibrosis, characterized by decreased expression of fibronectin, collagen III, vimentin, and Snail, while preserving E-cadherin levels in injured kidneys. Pharmacological degradation of EZH2 with GA produced comparable antifibrotic effects. UUO injury markedly upregulated Notch1, Notch3, the Notch intracellular domain, Hes1, Hey2, and Jagged-1; these increases were significantly suppressed by either EZH2 deletion or GA treatment. Similarly, in vitro, GA or EZH2-specific siRNA inhibited the expression of Notch signaling molecules in TGF-β1–treated renal epithelial cells. Chromatin immunoprecipitation analyses revealed direct binding of EZH2 and H3K27me3 to the Notch1 and Notch3 promoters. UUO injury enhanced EZH2 binding while reducing H3K27me3 enrichment at these sites, effects reversed by GA treatment. Conclusions These findings demonstrate that epithelial EZH2 contributes to pEMT in renal tubular cells and promotes renal fibrosis, at least in part through activation of Notch signaling. Targeting EZH2 may hold potential as a therapeutic approach for chronic kidney disease.
研究领域:
肾脏病学
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分子生物学
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表观遗传学
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信号转导
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纤维化研究
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高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Mingshu Xie,Yimeng Wang,Zeyu Zhang,Tingrui Lin,Yicheng Wang,Lang Sheng,Jiuqiang Li,Jing Peng,Maolin Zhai
A novel double-network conductive hydrogel based on lithium acetate/gelatin/polyacrylamide (PAAM) was synthesized by heating–cooling and subsequent γ-ray radiation-induced polymerization and cross-linking. Owing to the hydrogen bonding interaction between lithium acetate, physical cross-linked gelatin, and chemical cross-linked PAAM, the resultant hydrogel exhibited high tensile strength (1260 kPa), high ionic conductivity (35.2 mS cm–1), notch-insensitivity (tensile strength 415 kPa, elongation at break 872% with transverse notch), and extensive strain monitoring range (0.15–800%) under optimum conditions. The lithium acetate/gelatin/polyacrylamide hydrogel strain sensor attached to the skin can sensitively monitor the subtle movements of the human body. The strain sensor based on the resultant hydrogel with transverse notch can still work for 1200 cycles, due to that the covalent-cross-linked PAAm chain bridges the cracks and stabilizes the deformation, while the physical-cross-linked gelatin was unzipped to make the blunting of notch. The conductive hydrogel with high-sensitivity and high stability is expected to be used as materials for the preparation of flexible strain sensors in the future.
研究领域:
材料科学
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生物医学工程
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高影响因子
Polymer Chemistry
·
2020
·Vol. 12
·期 5
·660-669
·
IF 5.342
Lun Zhang,Dong Wang,Liqiang Xu,Aimin Zhang
Supramolecular elastomers, possessing excellent mechanical, reusable adhesivity, and rapid self-healing properties, are essential for use in various applications. Herein, we developed a novel polyamide-urea elastomer with metal–ligand interactions and hydrogen bonds forming synergetic double dynamic bonds. Physical crosslinking endows the polyamide-urea elastomer with extreme stretchability and rapid self-healing ability at room temperature. The representative polyamide-urea elastomer, DPPy1–Fe2, can be stretched to 40× its original length without breaking, and has extraordinary notch-insensitive elongation of up to 3500%. Meanwhile, DPPy1–Fe2 can fully restore its elasticity modulus within 5 min at room temperature, and the elongation also reaches 3000% after 30 min of healing. In addition, the unique dynamic bonds of the supramolecule enable it to repeatedly and firmly adhere to different surfaces. The shear strength of DPPy1–Fe2 is restored to an appreciable 80% after the first detachment–reattachment cycle, with it still possessing excellent adhesive strength after multiple cycles. As a result, the supramolecular elastomer shows outstanding stretchability, tear-resistance, quick self-repairing, and reusable adhesivity, which will facilitate the progress of intelligent adhesivity and flexible electronics.
研究领域:
材料科学
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化学工程
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高影响因子
RESEARCH IN VETERINARY SCIENCE
·
2020
·
IF 1.892
Jing Dong,Yuelei Chen,Wenhui Yang,Xi Zhang,Lin Li
Breast cancer is a high incidence disease in humans. Artemisinin is an important extract that is widely used as an antimalarial drug which also serve as effective treatments for cancer. 32 nude mice were injected with 0.2 ml of MDA-MB-231 cell suspension of 2 × 10 7 cells/ml respectively. The nude mice models were randomly divided into four groups of 8 in each group. Each group was given daily gavage, high dose group: 200 mg/kg/0.1 ml, middle dose group 100 mg/kg/0.1 ml, low dose group 50 mg/kg/0.1 ml, control group: 0.1 ml vegetable oil was fed continuously for 21 days. ELISA was used to detect serum vascular endothelial growth the content of factor VEGF and hypoxia-inducible factor HIF-1α were detected. The expression of Notch pathway-related factors in tumor tissue was detected by fluorescence quantitative assay. ELISA results showed that the serum VEGF decreased significantly in the high dose group compared with the control group ( p < .01), while the other dose groups did not have significant ( p > .05). The serum HIF-1α in the high dose group compared with the control group, the decrease in HIF-1α was significant ( p < .05), and the other groups were not significant ( p > .05). The result of fluorescence quantitative section showed that artemisinin could down-regulate the expression of notch signaling related factors notch1, Dll4 and Jagged1, and 200 mg/kg dose group had the most significant effect. It may inhibit the development of tumors by reducing serum angiogenesis-related factors VEGF, HIF-1ɑ and inhibiting the activity of notch1 signaling pathway related factors.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yixin Li,Tiancheng Li,Cheng Zhu,Hairui Li,Runzhe Fang,Ruomei Li,Yu Jin,Zhiyu Zhu,Lunguo Xia,Bing Fang
Cartilage regeneration requires a specialized biomechanical environment. Macroscopically, cartilage repair requires a protracted, stable mechanical environment, whereas microscopically, it involves dynamic interactions between cells and the extracellular matrix. Therefore, this study aims to design a hydrogel that meets the complex biomechanical requirements for cartilage repair. Dynamic hybrid hydrogels with temporal stability at the macroscale and dynamic properties at the microscale are successfully synthesized. The dynamic hybrid hydrogel simulates the stress relaxation and viscoelasticity of the pericellular matrix, facilitating effective interactions between the extracellular matrix and cells. The in vitro and in vivo experiments demonstrated that the hybrid hydrogel significantly promoted cartilage repair. The dynamic hybrid hydrogel alleviates abnormal actin polymerization, reduces intracellular stress, and increases the volume of individual cells. By modulating the cytoskeleton, the hybrid hydrogel inhibits Notch signal transduction in both the receptor and ligand cells, resulting in an improved cartilage phenotype. This study introduces an effective hybrid hydrogel scaffold that modulates the chondrocyte cytoskeleton and Notch signaling pathways by establishing an appropriate biomechanical environment, thus offering a promising material for cartilage repair.
研究领域:
生物材料学
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再生医学
·
细胞生物学
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PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2026
·
IF 4.6
Shi Xiao-Jiao,Zhang Yu-Bin,Li Na,Qiao Yu-Xuan,Liang Ya,Yu Gong-Kuo,Su Ai-Hong,Song Ze-Cheng,Song Dan-Dan,Jiao Ti-Feng,Qin Zhi-Hui
The rapid advancement of wearable sensors necessitates ionically conductive hydrogels that simultaneously exhibit high stretchability, damage tolerance, and reliable adhesion. However, achieving these properties in a single material remains a significant challenge. Herein, we report an ionically conductive polyoxometalate (POM)-based hydrogel (PAA/L-arg@SIW) fabricated by incorporating L-arginine (L-arg)-modified silicotungstic acid nanocomplexes (L-arg@SIW) into a poly(acrylic acid) (PAA) network as a multifunctional dynamic crosslinker. Strong electrostatic interactions and hydrogen bonding between rigid L-arg@SIW nanoclusters and flexible PAA chains generate a three-dimensional hard-soft synergistic network, in which dynamic crosslinks preferentially rupture and re-form under mechanical loading, thereby dissipating energy and suppressing crack propagation. Consequently, the hydrogel exhibits exceptional stretchability (fracture strain >1500%), high toughness (1483 kJ/m 3 ), outstanding crack resistance (fracture energy up to 6.82 kJ/m 2 ), and high ionic conductivity (0.15 S/m), along with robust adhesion to diverse substrates. Hydrogel-based sensors demonstrate high strain sensitivity (gauge factor (GF)=8.06), fast response, and excellent cyclic stability, enabling reliable monitoring of human motion and high-fidelity acquisition of electrocardiogram (ECG) and electromyogram (EMG) signals. This study presents an effective strategy for constructing high-performance ionically conductive hydrogels for wearable sensing applications. The alternative text for this image may have been generated using AI.
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高影响因子
Theranostics
·
2024
·
IF 12.4
Yitian Shi,Jiayin Peng,Mengfan Liu,Xiling Qi,Siyu Li,Qiangqiang Li,Qing Jiang,Liming Zheng,Jiankun Xu,Yun Zhao,Yifeng Zhang
The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear. Methods : The transverse femoral shaft fracture model was employed to evaluate the potential advantages of NMN administration for overall repair during the initial fracture stages in male mice through micro-CT analysis, histochemistry, and biomechanical testing. The pro-proliferative function of NMN on skeletal stem cells (SSCs) was investigated through flow cytometry, qRT-PCR, NAD content measurement, and cell proliferation assay. Results : In this study, we observed that the administration of NMN during the initial phase of fracture in mice led to a larger callus and corresponding improvement in micro-CT parameters. NMN enhances the cartilaginous component of the callus by elevating the NAD content, consequently accelerating subsequent endochondral ossification and the fracture healing process. Subsequent analyses elucidated that NMN was beneficial in promoting the expansion of diverse stem cells in vivo and in vitro potentially via modulation of the Notch signaling pathway. Moreover, the depletion of macrophages profoundly obstructs the proliferation of SSCs. Conclusion : Our discoveries provide a potential strategy for enhancing fracture healing through stimulation of callus SSC proliferation at an early stage, shedding light on the translational value of NMN as an enhancer for skeletal regeneration and highlighting the pivotal role of macrophage-stem cell interactions in governing the regenerative influence of NMN on stem cells.
研究领域:
再生医学
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干细胞生物学
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骨科
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分子生物学
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PubMed
高影响因子
Journal of Translational Medicine
·
2017
·Vol. 15
·期 1
·1-11
·
IF 3.786
Zang Ming-de,Hu Lei,Fan Zhi-yuan,Wang He-xiao,Zhu Zheng-lun,Cao Shu,Wu Xiong-yan,Li Jian-fang,Su Li-ping,Li Chen,Zhu Zheng-gang,Yan Min,Liu Bing-ya
Background Gastric cancer (GC) is one of the most malignant tumors and the second leading cause of cancer-related deaths in the world. Luteolin, a flavonoid present in many fruits and green plants, suppresses cancer progression. The effects of luteolin on GC cells and their underlying mechanisms remain unclear.Methods Effects of luteolin on cell proliferation, migration, invasion, and apoptosis were examined in vitro and in vivo by cell counting kit-8 (CCK-8), transwell assays, and flow cytometry, respectively. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blots were performed to evaluate Notch1 signaling and activation of epithelial-mesenchymal transition (EMT) in GC cells treated with or without luteolin. Immunohistochemistry was performed to examine proliferation and Notch1 expression in xenograft tumors.Results Luteolin significantly inhibited cell proliferation, invasion, and migration in a dose-dependent and time-dependent manner and promoted cell apoptosis. Luteolin reversed EMT by shrinking the cytoskeleton and by inducing the expression of epithelial biomarker E-cadherin and downregulating the mesenchymal biomarkers N-cadherin, vimentin and Snail. Furthermore, Notch1 signaling was inhibited by luteolin, and downregulation of Notch1 had similar effects as luteolin treatment on cell proliferation, migration, and apoptosis. In addition, luteolin suppressed tumor growth in vivo. A higher expression of Notch1 correlated with a poor overall survival and a poor time to first progression. Furthermore, co-immunoprecipitation analysis revealed that activated Notch1 and β-catenin formed a complex and regulated cell proliferation, migration, and invasion.Conclusion sIn this study, GC progression was inhibited by luteolin through suppressing Notch1 signaling and reversing EMT, suggesting that luteolin may serve as an effective anti-tumor drug in GC treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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PubMed
高影响因子
ChemPlusChem
·
2019
·Vol. 84
·期 4
·432-440
·
IF 3.441
Guangjie Gai,Libin Liu,Cheng-Hui Li,Ranjita K. Bose,Dong Li,Ning Guo,Biao Kong
Graphical Tough and stretchable : A metal-coordinated polyurethane complex was fabricated by complexing a simple pyridine-containing ligand with Fe 2+ ions The strong reversible coordination bond provides mechanical strength and the basis for self-healing. The complex possesses a very high tensile strength, and excellent self-healing efficiency of around 96 % of tensile strength at room temperature. The complex is notch-insensitive and possesses a very high fracture energy of 76186 J/m 2 . Self-healing materials can prolong device life, but their relatively weak mechanical strength limits their applications. Introducing tunable metal-ligand interactions into self-healing systems can improve their mechanical strength. However, applying this concept to solid elastomers is a challenge. To address this need, polyurethane-containing metal complexes were fabricated by introduction of a pyridine-containing ligand into polyurethane, and subsequent coordination with Fe 2+ . The strong reversible coordination bond provides mechanical strength and self-healing ability. By optimizing the monomer ratio and Fe 2+ content, the resulting complex possesses a very high tensile strength of 4.6 MPa at strain of around 498 % and a high Young's modulus (3.2 MPa). Importantly, the metal complex exhibits an extremely high self-healing efficiency of approximately 96 % of tensile strength at room temperature and around 30 % at 5 °C. The complex is notch-insensitive and the fracture energy is 76186 J/m 2 , which is among the highest reported values for self-healing systems.
研究领域:
材料科学
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化学工程
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Yunhui Shi,Yan Zhang,Limin Jia,Qian Zhang,Xinhua Xu
Next-generation wearable electronics are expected to endure significant deformations and mechanical damage. Therefore, self-healing stretchable electrolytes with high ionic conductivity and robust mechanical strength, which have high tolerance of deformations and spontaneously recover electrochemical properties after external damage, are necessary conditions for the realization of flexible supercapacitors. Here, a new type of zwitterionic supramolecular hydrogel cross-linked through rationally designed ionic associations and hydrogen bonds is reported (PAD/H2SO4). The resultant supramolecular network realizes a high ionic conductivity of 57 mS cm–1 and unprecedented mechanical properties such as a high toughness of 35 000 J m–2, a notch-insensitive of up to 2200% strain, and efficient instantaneous self-healing within 5 min. Acting as an electrolyte, a novel flexible supercapacitor design strategy is proposed by integrating capacitive materials directly onto the PAD/H2SO4 hydrogel to achieve exceptional electrochemical performance, which can be repeatable for at least 50 cutting/healing cycles. The facile and versatile strategy for the construction of the integrated all-gel-state supercapacitors with self-healing stretchable electrolytes will provide new directions for future long-life flexible devices.
研究领域:
材料科学
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能源技术
·
柔性电子
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PubMed
高影响因子
Soft Matter
·
2017
·Vol. 13
·期 48
·9237-9245
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IF 3.889
Rui Niu,Zhihui Qin,Feng Ji,Meng Xu,Xinlu Tian,Junjie Li,Fanglian Yao
The lack of sufficient mechanical properties restricts the application of polysaccharide-based hydrogels in the field of biomedicine, especially load-bearing tissue repair. Nowadays, double network (DN) hydrogels have aroused great interest through special cooperation between two contrasting networks. Inspired by this idea, here, we devised a new strategy to prepare a pectin–Fe3+/polyacrylamide hybrid DN hydrogel using a simple two-step method. The introduction of Fe3+ ions into a pectin network to produce strong reversible ionic complexation, results in excellent toughness. Under optimal conditions, our hybrid DN hydrogels possessed tensile strength as high as 0.9 MPa, corresponding to a high strain of 1300%. Besides, our hybrid DN hydrogels also exhibited superb stiffness (elastic modulus ∼ 1.46 MPa), toughness (fracture energy ∼ 3785 J m−2), and water absorption capacity (85%). Loading–unloading tests showed that the internal fracture process of the hydrogels was continuous. Owing to the reversible structure of Fe3+–pectin complexation, the hybrid DN hydrogels also showed good fatigue resistance, notch-insensitivity and recoverability. This type of polysaccharide-based hydrogel has potential to broaden the application in the load-bearing tissue repair field.
研究领域:
生物材料学
·
组织工程学
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PubMed
高影响因子
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