DENTAL MATERIALS
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2026
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IF 6.3
Tianjia Huang,Huan Chen,Shuwei Qiao,Boyu Sun,Shuyao Zheng,Haiya Liao,Zuosen Shi,Song Zhu
A multifunctional Myr@ZIF-8 nanoplatform was developed for dentin bonding. • Myr@ZIF-8 exhibited pH-responsive release of myricetin and Zn²⁺. • Myr@ZIF-8 enhanced antibiofilm activity against Streptococcus mutans . • Myr@ZIF-8 stabilized dentin collagen and suppressed MMP activity. • The modified adhesive significantly improved dentin bonding durability. Objectives This study aimed to develop a myricetin-loaded ZIF-8 (Myr@ZIF-8)-modified universal adhesive with antibacterial, collagen-stabilizing, and matrix metalloproteinase (MMP)-inhibitory properties to improve bonding durability. Methods Myr@ZIF-8 nanoparticles were synthesized and characterized. Myr loading efficiency, drug loading, and pH-responsive release were evaluated. Myr@ZIF-8 was incorporated into a universal adhesive at 2.5–10 wt%, and the optimal concentration was selected according to degree of conversion, dentin wettability, and antibiofilm activity. Dentin collagen stability, MMP-mediated gelatinolytic activity, microtensile bond strength (μTBS), interfacial nanoleakage, interfacial mechanical properties, and in vitro cytocompatibility were evaluated. Short-term systemic toxicity was preliminarily assessed by oral gavage of cured adhesive extracts. Molecular docking was performed to investigate potential interactions between myricetin and collagen, MMP-2, and MMP-9. Results Myr@ZIF-8 exhibited a Myr loading efficiency of 50.72%, drug loading of 50.36%, and pH-responsive release. The adhesive containing 5 wt% Myr@ZIF-8 showed the best overall performance, including enhanced antibiofilm activity, improved collagen stability, and reduced MMP-mediated gelatinolytic activity. Incorporation of 5 wt% Myr@ZIF-8 increased immediate μTBS from 22.79 MPa to 32.07 MPa and aged μTBS after 10,000 thermocycles from 13.91 MPa to 27.99 MPa. Molecular docking predicted potential interactions between myricetin and collagen, MMP-2, and MMP-9. The modified adhesive showed acceptable in vitro cytocompatibility, with no obvious short-term systemic toxicity after oral gavage of cured adhesive extracts. Significance These findings demonstrate that Myr@ZIF-8 functions as a multifunctional bioactive nanoplatform and represents a promising strategy for improving bonding durability. Download: Download high-res image (189KB) Download: Download full-size image Schematic diagram of the experimental process.
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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2025
·Vol. 122
·期 13
·e2416771122
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IF 9.1
Badri Narayanan Narasimhan,Stephanie I. Fraley
In native extracellular matrices (ECM), cells utilize matrix metalloproteinases (MMPs) to degrade and remodel their microenvironment. Accordingly, synthetic matrices have been engineered to permit MMP-mediated cleavage, facilitating cell spreading, migration, and interactions. However, the interplay between matrix degradability and mechanical properties remains underexplored. We hypothesized that MMP activity induces immediate mechanical alterations in the ECM, which are subsequently detected by cells. We observed that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation following MMP exposure. Cells responded to these variations in relaxation by modulating their spreading and focal adhesions. Furthermore, we demonstrated that stress relaxation and cell spreading can be precisely controlled through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, with potential implications for a broad spectrum of biological applications.
研究领域:
生物材料学
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细胞生物学
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生物力学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Xiuru Zhang,Zhuangzhuang Liu,Yuna Li,Jingqin He,Lulu Yang,Yulin Yan,Shanshan Tong,Yeqi Wang,Tao Zhang
Lead (Pb), a persistent heavy metal, has caused widespread environmental contamination due to its extensive industrial use. Among its compounds, lead acetate (PbAc) is particularly hazardous in aqueous form, exhibiting neurotoxic potential. However, its toxic effects on the integrity of the blood-brain barrier (BBB) and the underlying mechanisms remain poorly understood. This study demonstrates that zebrafish embryos exposed to varying concentrations of PbAc exhibit dose-dependent morphological abnormalities, including growth retardation, delayed hatching, and cardiovascular dysfunction, along with pronounced neurobehavioral deficits in both embryonic and adult zebrafish. Live imaging analysis revealed that both acute and chronic exposure to different concentrations of PbAc can induce cerebral hemorrhage and BBB dysfunction. Additionally, PbAc selectively disrupted cerebral angiogenesis without affecting trunk intersegmental vessels and significantly reduced pericyte coverage within both cerebral and trunk vessels. Mechanistically, RNA sequencing and qPCR validation revealed significant upregulation of MMP-9 and MMP-13 in PbAc-exposed embryos. Pharmacological inhibition of MMP-9/13 using polygalacic acid significantly reduced cerebral hemorrhage and restored pericyte coverage, suggesting that these proteases mediate PbAc-induced cerebrovascular damage. Overall, our findings underscore the ecological and public health risks associated with lead contamination and provide a basis for future therapeutic strategies targeting MMPs to mitigate heavy metal toxicity.
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MOLECULAR NEUROBIOLOGY
·
2024
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IF 4.6
Wang Ajun,Li Nan,Zhang Nan,Liu Jian,Yang Tao,Li Dongxue,Li Changwen,Li Rui,Jiang Tongcui,Xia Chengyu
The pathogenesis and development of Moyamoya disease are still unclear. This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease. RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells’ biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overexpression or knockdown of DSG2 were identified in endothelial cells. The expression of DSG2 in the STA tissues of Moyamoya disease was lower than that in normal controls. Overexpression of DSG2 inhibits the proliferation and migration but promotes apoptosis in endothelial cells, and low DSG2 levels result in impaired angiogenesis. In addition, there was an interaction between DSG2 and MMP-9, and DSG2 acted through the PI3K signaling in endothelial cells. Our results indicate that DSG2 affects PI3K signaling in vascular endothelial cells, and MMP-9 is involved in DSG2-mediated vascular changes in Moyamoya disease.
研究领域:
神经病学
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血管生物学
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细胞信号
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分子生物学
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JOURNAL OF FOOD PROCESSING AND PRESERVATION
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2020
·Vol. 44
·期 4
·e14383
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IF 1.405
Zi-qiang Liu,Da-yong Zhou,Yu-xin Liu,Xiao-yang Liu,Yan Liu,Bing Liu,Liang Song,Fereidoon Shahidi
Matrix metalloprotease (MMP) is the key endogenous protease that boosts the autolysis of sea cucumber, while its action and mechanism in vivo are still unclear. MMP inhibitor (1,10-phenanthroline) was injected into coelomic cavity of sea cucumber ( Stichopus japonicus ) and its effects on autolysis and mechanism of action were investigated for the first time by using scanning electron microscopy, multi-functional in vivo imaging system, and confocal laser scanning microscopy. In response to external stimuli, the level of Ca 2+ in live sea cucumber dermis increased, which may activate MMP activity. MMP inhibitor could diffuse from coelomic cavity into body wall and significantly prevented the activation of MMP by chelating Ca 2+ , and thus, retarded the autolysis of fresh sea cucumber by preventing degradation of interfibrillar proteoglycan bridges between adjacent collagen fibrils. This work provides information toward understanding the mechanism behind the sea cucumber autolysis and demonstrate a potential approach to prevent the autolysis. Practical applications Autolysis occurs in sea cucumber in response to external stimulation. Matrix metalloproteinase (MMP) has been found to be the key endogenous protease that boosts the autolysis of sea cucumber body wall (SCBW). However, the role of MMP in the autolysis of SCBW in vivo and the mechanisms involved remain unclear. In this study, MMP inhibitor (1,10-phenanthroline) was injected into the body cavity of live sea cucumber, and its effects on in situ changes in SCBW were studied. Our results indicated that the activity of endogenous MMP in live SCBW was activated in response to external stimulation, which may be responsible for the autolysis. After injection into coelomic cavity, MMP inhibitor could diffuse into SCBW and significantly reduced the progress of typical morphological and microstructural changes of autolytic sea cucumber. Through chelating Ca 2+ , the MMP inhibitor could prevent the activation of MMP, and thus reduced the autolysis of fresh sea cucumber.
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ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Yaozhi Zhang,Menglu Jiang,Shiqi Zhang,Aimeng Dong,Fenghua Zhang,Yanju Liu,Huiping Yuan,Jinsong Leng
Traditional hydrogel-based drug delivery systems face critical limitations, including poor toughness and adhesion, and low drug utilization efficiency, which collectively limit their efficacy in glaucoma treatment. Deep eutectic solvents (DESs) can effectively address these limitations because they are structurally tunable and exhibit high rates of drug dissolution. Herein, we apply β-cyclodextrin and phytic acid to prepare a novel DES, which was used to fabricate a deep eutectic smart gel drug delivery system (DSGS). The DES establish multi-hydrogen-bonded shielding networks with polymer chains, endowing the DSGS with an ocular tissue-matched modulus and a high toughness of 5.94 MJ·m − 3 . Notably, the DSGS enables precise drug release in response to dual stimuli: matrix metalloproteinase-2 and temperature. We employ 4D printing technology to engineer a novel glaucoma drainage device (GDD) from the DSGS loaded with an antifibrotic drug for glaucoma treatment. Based on the synergistic effect of DSGS and the drug, the GDD regulates intraocular pressure (IOP), suppresses fibrosis, and restructures the extracellular matrix collagen architecture in vivo. Furthermore, the DSGS is injectable and exhibits strong tissue adhesion. Following minimally invasive implantation into the conjunctiva, a stable IOP was maintained for 30 days. This innovative design represents a promising direction for future drug delivery.
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METHODS
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2025
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IF 4.3
Wensi Li,Zhichao Tang,Xiang Zhu,Beijuan Wang,Xiuqin Zhang,Ze Ji,Suhang Cheng
In this work, an electrochemiluminescence (ECL) biosensor integrating T7 RNA polymerase amplification and CRISPR/Cas13a-mediated signal enhancement was developed for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2), a key biomarker associated with chronic inflammatory diseases such as COPD. A peptide nucleic acid (PNA) probe was designed to respond specifically to MMP-2 cleavage, enabling the release of DNA templates for subsequent T7 RNA polymerase-driven transcription amplification. The generated RNA triggers the collateral cleavage activity of CRISPR/Cas13a, resulting in a significant amplification of the ECL signal. The biosensor’s surface was constructed using a AuNPs/Ti 3 C 2 Tx/Ru(II)-PEI nanocomposite, which enhanced signal transduction and stability. Under optimized conditions, the proposed biosensor achieved a detection limit as low as 62.05 fM, demonstrating superior sensitivity compared to conventional methods, as summarized in Table 1 . The platform also exhibited excellent specificity and anti-interference capability, ensuring reliable detection of MMP-2 in complex biological samples. This study provides a simple yet highly efficient strategy for enzymatic biomarker detection, offering great potential for clinical applications in early disease diagnosis and monitoring.
研究领域:
生物传感器
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分子诊断
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CRISPR技术
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纳米技术
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慢性阻塞性肺疾病
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酶检测
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Journal of Functional Foods
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2020
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IF 3.701
Zhenbang Xiao,Shengtao Yang,Jiali Chen,Chengyong Li,Chunxia Zhou,Pengzhi Hong,Shengli Sun,Zhong-Ji Qian
Ultraviolet radiation B cause photoaging of the skin by enhancing the high expression of matrix metalloproteinases (MMPs) to degrade collagen and inhibit the synthesis of procollagen. Trehalose (TRE), a widely occurring natural disaccharide, has been shown to play a cytoprotective role in many pathological processes. However, few studies have evaluated whether it has anti-photoaging potential. In this study, we investigated the anti-photoaging and mechanism of action of TRE using Human immortalized keratinocytes (HaCaT) cells. The results indicated that TRE pretreatment effectively scavenges reactive oxygen species (ROS) accumulation induced by UVB and increases the content of certain endogenous antioxidant factors in HaCaT cells. TRE suppressed UVB-induced MMP expression by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1) and NF-κB signaling. TRE treatment increased procollagen I synthesis via activating transforming growth factor-β (TGF-β)/Smad pathway and demonstrated that TRE may be a potential natural disaccharide for photoaging therapy in the future.
研究领域:
皮肤科
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细胞生物学
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药理学
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SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Kai Zhang,Meina Yang,Helin Sun,Xueyin Wang,Hao Li,Jinxiang Han,Zhongwen Zhang
Using Peptide nucleic acid (PNA), this work provides a unique approach for controlling CRISPR/Cas13a activity by RNA Inhibitory PNA (RIP). This method reduces the action of CRISPR/Cas13a by inhibiting the binding of crRNA to CRISPR/Cas13a, which was subsequently utilized to detect metalloproteinase-2 (MMP-2) activity. We carefully constructed a PNA sequence that includes a peptide sequence (Gly-Pro-Leu-Gly-Val-Arg-Gly) that is particularly cleaved by MMP-2 in the middle. When MMP-2 is not present in the system, the PNA/crRNA complex reduces crRNA binding to CRISPR/Cas13a, hence inhibiting CRISPR/Cas13a cleavage activity. When MMP-2 is present in the system, it cleaves the peptide sequence (Gly-Pro-Leu-Gly-Val-Arg-Gly) selectively and so prevents PNA from binding to crRNA, enabling crRNA to reach the "free" form. Then, in the presence of an RNA activator, crRNA may bind to CRISPR/Cas13a and stimulate its activity. CRISPR/Cas13a triggered in this manner may precisely cleave the DNA sequence containing modified -UU- bases on the electrode surface . Thus, the ferrocene (Fc) is changed away from the electrode surface at one end of the DNA , enabling for the recovery of the Electrochemiluminescence (ECL) signal from the two-dimensional material transformed on the electrode surface. As a result, MMP-2 activity was detected utilizing this technique of inhibiting crRNA activity with a detection limit of 15.56 fM. Our suggested method of inhibiting CRISPR/Cas13a activity via PNA has a broad variety of potential therapeutic applications in gene editing and the development of CRISPR/Cas13a-based biosensors.
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ACS Applied Materials & Interfaces
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2022
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IF 10.383
Huifang Liu,Dongqin Lei,Jiong Li,Jing Xin,Luwei Zhang,Lei Fu,Jing Wang,Weihui Zeng,Cuiping Yao,Zhenxi Zhang,Sijia Wang
Combining photodynamic therapy (PDT) with natural killer (NK) cell-based immunotherapy has shown great potential against cancers, but the shedding of NK group 2, member D ligands (NKG2DLs) on tumor cells inhibited NK cell activation in the tumor microenvironment. Herein, we assembled microenvironment-/light-responsive bio-nanosystems (MLRNs) consisting of SB-3CT-containing β-cyclodextrins (β-CDs) and photosensitizer-loaded liposomes, in which SB-3CT was considered to remodel the tumor microenvironment. β-CDs and liposomes were linked by metalloproteinase 2 (MMP-2) responsive peptides, enabling sequential release of SB-3CT and chlorin e6 triggered by the MMP-2-abundant tumor microenvironment and 660 nm laser irradiation, respectively. Released SB-3CT blocked tumor immune escape by antagonizing MMP-2 and promoting the NKG2D/NKG2DL pathway, while liposomes were taken up by tumor cells for PDT. MLRN-mediated photo-immunotherapy significantly induced melanoma cell cytotoxicity (83.31%), inhibited tumor growth (relative tumor proliferation rate: 1.13% of that of normal saline) in the xenografted tumor model, and enhanced tumor-infiltrating NK cell (148 times) and NKG2DL expression (9.55 and 16.52 times for MICA and ULBP-1, respectively), achieving a synergistic effect. This study not only provided a simple insight into the development of new nanomedicine for programed release of antitumor drugs and better integration of PDT and immunotherapy but also a novel modality for clinical NK cell-mediated immunotherapy against melanoma.
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ANALYST
·
2022
·Vol. 148
·期 4
·752-761
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IF 5.227
Xintong Lu,Luoyu Ding,Haohan Song,Wenxin Yu,Chaoqing Dong,Jicun Ren
Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor progression. It is of great significance to establish a sensitive in situ assay strategy for MMP-9 activity in single living cells. Here a novel in situ single molecule spectroscopy method based on the fluorescence correlation spectroscopy (FCS) technique was proposed for measuring the MMP-9 activity at different locations within single living cells, using a fluorescent specific peptide and a reference dye as dual probes. The measurement principle is based on the decrease of the ratiometric translational diffusion time of dual probes in the detection volume due to the peptide cleavage caused by MMP-9. The peptide probe was designed to be composed of an MMP-9 cleavage and cell-penetrating peptide sequence that was labeled with a fluorophore and conjugated with a streptavidin (SAV) molecule. The ratiometric translational diffusion time was used as the measurement parameter to eliminate the effect of intracellular uncertain viscosity. The linear relationship between the ratiometric diffusion time and MMP-9 activity was established, and applied to the determination of enzymatic activity in cell lysates as well as the evaluation of the inhibitory effects of different inhibitors on MMP-9. More importantly, the method was successfully used to dynamically determine MMP-9 activity in single living cells or under the stimulation with phorbol 12-myristate 13-acetate (PMA) and inhibitors.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
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IF 10.6
Wu Zhen,Zhang Peng,Yue Jie,Wang Qingshan,Zhuang Peipei,Jehan Shah,Fan Liyuan,Xue Jiarun,Zhou Wenhu,Wang Haiyang
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier’s intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.Graphical Abstract
研究领域:
纳米技术
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基因治疗
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血管生物学
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药学
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生物医学工程
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