Acta Biomaterialia
·
2019
·
IF 6.638
Na Li,Liqun Yang,Chenglin Pan,Phei Er Saw,Meng Ren,Biyun Lan,Junfeng Wu,Xiaoyi Wang,Tingting Zeng,Liyan Zhou,Li-Ming Zhang,Chuan Yang,Li Yan
s The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro , while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. Statement of significance In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.
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PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Tong Shanshi,Yu Zhilong,Yin Fang,Yang Qilin,Chu Juhang,Huang Luyao,Gao Wenxue,Qian Mingping
Pancreatic cancer (PC) is one of the deadliest gastrointestinal malignancies. Advances in molecular biology and surgery have significantly improved survival rates for other tumors in recent decades, but clinical outcomes for PC remained relatively unchanged. Chemodynamic therapy (CDT) and Photothermal therapy (PTT) represent an efficient and relatively safe cancer treatment modality. Here, we synthesized Mn-doped Prussian blue nanoparticles (MnPB NPs) through a simple and mild method, which have a high loading capacity for drugs and excellent CDT/PTT effect. Cell line experiments in vitro and animal experiments in vivo proved the safety of MnPB NPs. We stimulated the PC cells with MnPB NPs and performed transwell migration assays. The migration of PC cells was reduced company with the decrease of two classical proteins: matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Moreover, MnPB NPs induced ferroptosis, which mediated the MAPK pathway and achieved tumor elimination in nude mice. This effective and safe strategy controlled by irradiation represents a promising strategy for pancreatic cancer.
研究领域:
肿瘤学
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纳米技术
·
癌症治疗
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PubMed
高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 15
·3839-3853
·
IF 3.2
Wen Weijia,Li Jiaying,Yuan Li,Liao Yan,Shao Caixia,Xu Dingze,Jiang Hongye,Liao Yuandong,Liu Pan,Zhang Chunyu,Yao Shuzhong,Wang Wei
Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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信号转导
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PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Wanyi Zhou,Zhiguang Duan,Jing Zhao,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/ [email protected] &INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib ( [email protected] ). Temperature-sensitive self-adaptive CBP/ [email protected] &INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ [email protected] &INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/ [email protected] &INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.
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JOURNAL OF IMMUNOLOGY
·
2025
·
IF 3.4
Huang Saiping,Wu Guoyuan,Xu Tianfu,Lin Dong,Zhan Zhijian
This study investigates the diagnostic potential of matrix metalloproteinase-9 (MMP-9), IL-8, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) as combined biomarkers for post-infectious bronchiolitis obliterans (PIBO) in children. BALF samples from children with PIBO were analyzed using ELISA to quantify MMP-9, IL-8, and MPO levels. Receiver operating characteristic (ROC) curves were used to assess their diagnostic values, while Pearson correlation analysis examined their associations with lung function and inflammation markers. A PIBO mouse model was established via nebulized nitric acid inhalation, and targeted inhibition of MMP-9, IL-8, and MPO using small interfering RNAs (siRNAs) was performed given via intratracheal administration. The effects on airway inflammation and pathological lung changes were evaluated. Bioinformatics analysis identified upstream microRNAs (miRNAs) regulating MMP-9, IL-8, and MPO, which were validated using dual-luciferase assay and Western blotting. Results revealed significant upregulation of MMP-9, IL-8, and MPO in the BALF of children with PIBO. Combined detection of these biomarkers demonstrated high diagnostic accuracy. MMP-9, IL-8, and MPO levels in BALF were negatively correlated with lung function indicators but positively correlated with inflammatory factors. Targeted inhibition of these molecules reduced airway hyperresponsiveness and inflammation in PIBO mice. miR-766-3p was downregulated in the lung tissues of PIBO mice and in the BALF of affected children, showing a negative correlation with MMP-9, IL-8, and MPO. Functional assays confirmed that miR-766-3p directly targeted MMP-9, IL-8, and MPO. In conclusion, MMP-9, IL-8, and MPO serve as reliable combined biomarkers for PIBO diagnosis and may aid in early clinical identification. miR-766-3p is an upstream miRNA for MMP-9, IL-8, and MPO.
研究领域:
呼吸病学
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分子生物学
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儿科医学
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PubMed
高影响因子
ANALYTICAL LETTERS
·
2024
·
IF 1.6
Dapeng Sun,Chenglong Ye,Zhuo Chen
Matrix metalloproteinase-2 (MMP-2) is a key biomarker involved in various pathological processes, so its sensitive and selective detection is of great clinical significance. A fluorescent sensor for the detection of MMP-2 was successfully designed based on the inner filter effect (IFE) between carbon dots (CDs) and gold nanoparticles (AuNPs). In the presence of MMP-2, peptide chains are hydrolyzed, releasing short peptides that contain thiol groups and positive charges, thereby inducing the aggregation of AuNPs. This aggregation disrupts the IFE between AuNPs and CDs, leading to a significant enhancement of the fluorescence. By monitoring the change in fluorescence intensity of CDs, the concentration of MMP-2 was accurately determined. The sensor exhibited a linear response across the concentration range from 1.0 to 150 ng/mL, with a detection limit as low as 0.23 ng/mL, which is lower than those of previously reported methods. Furthermore, the sensor demonstrated minimal interference from coexisting biochemical substances for MMP-2 in human serum. Notably, the sensor was successfully applied to determine MMP-2 in human serum, showing satisfactory recovery rates ranging from 98.8 to 1106.0%. In conclusion, this fluorescent sensor offers high selectivity and sensitivity for MMP-2 detection, making it a promising tool for clinical diagnosis of related diseases.
研究领域:
生物医学
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纳米技术
·
临床诊断
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高影响因子
ADVANCED MATERIALS
·
2023
·Vol. 35
·期 42
·2303718
·
IF 29.4
Shuangquan Gou,Gangyang Wang,Yanan Zou,Wenbo Geng,Tingting He,Zizhen Qin,Lingbin Che,Qian Feng,Kaiyong Cai
Developing a drug delivery platform that possesses universal drug loading capacity to meet various requirements of cancer treatment is a challenging yet interesting task. Herein, a self-assembled gelatin/silk fibroin composite (GSC) particle based drug delivery system is developed via microphase separation followed by desolvation process. Thanks to its preassembled microphase stage, this GSC system is suitable for varying types of drugs. The desolvation process fix drugs inside GSC rapidly and densify the GSC structure, thereby achieving efficient drug loading and providing comprehensive protection for loaded drugs. Actually, the size of this brand-new non-pore dependent drug delivery system can be easily adjusted from 100 nm to 20 µm to fit different scenarios. This work selects GSC with 3 µm diameter as the universal inhaled drug delivery platform, which shows an excellent transmucosal penetration and lung retention ability. Additionally, the MMP-9 sensitive degradation property of GSC enhances the targeted efficiency of drugs and reduces side effects. Intestinally, GSC can self-amplify the regulation of innate immunity to reverse the cancerous microenvironment into an antitumor niche, significantly improving the therapeutic effect of drugs. This study of GSC universal drug platform provides a new direction to develop the next-generation of drug delivery system for lung cancer.
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MOLECULAR NEUROBIOLOGY
·
2023
·Vol. 60
·期 7
·3824-3838
·
IF 5.1
Deng Ling,Zhang Jiyu,Chen Sha,Wu Yu,Fan Xiaomei,Zuo Tianrui,Hu Qingwen,Jiang Lu,Yang Shaonan,Dong Zhi
Blood-brain barrier (BBB) disruption can induce further hemorrhagic transformation in ischemic stroke (IS). miR-671-5p, a micro-RNA, is abundant in the cortex of mammalian brains. Herein, we investigated the roles and potential mechanisms for the effects of miR-671-5p on BBB permeability in IS. Results showed that miR-671-5p levels were significantly downregulated in the cerebral cortex of middle cerebral artery occlusion/reperfusion (MCAO/R) C57/BL6 mice in vivo . miR-671-5p agomir administration via right intracerebroventricular injection significantly reduced infarct volume, improved neurological deficits, the axon of neurons and nerve fiber, attenuated cell injury and apoptosis, as well as reduced BBB permeability in MCAO/R mice. Treatment with miR-671-5p agomir alleviated tight junction proteins degradation, including claudin, occludin, and ZO-1 in MCAO/R mice, and these effects were reversed following NF-κB overexpression. Bend.3 brain endothelial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) treatment in vivo , and then miR-671-5p agomir was transfected into the cells. This resulted in reduction of cytotoxicity, improved cell viability, trans-endothelial electrical resistance, reduced fluorescein sodium permeability, and inhibited tight junction degradation in Bend.3 OGD/R cells. However, these effects were reversed following NF-κB overexpression. These results demonstrated that upregulation of miR-671-5p in IS models in vivo and i n vitro alleviated BBB permeability by targeting NF-κB/MMP-9. In summary, miR-671-5p is a potential therapeutic target for protecting BBB permeability in IS to minimize cerebral hemorrhage transformation.
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Food & Function
·
2026
·
IF 6.3
Yang Liu,Xin Zhang,Jiaying Yu,Wangge Xiong,Yaqi Li,Jinsheng Zhang,Jing Guo
This study utilized scanning electron microscopy (SEM), enzymatic kinetics, multispectral analysis, and molecular simulations to explore the effects of theaflavins (TFs) on Streptococcus mutans (S. mutans) biofilms and matrix metalloproteinase-9 (MMP-9) and the TF–MMP-9 interaction mechanism. The results demonstrated that TFs can disrupt the biofilms of S. mutans and reversibly and competitively inhibit MMP-9. TFs can spontaneously bind to MMP-9, with hydrogen bonds being the primary driving forces. Furthermore, fluorescence spectroscopy revealed that the fluorescence quenching mechanism of TFs on MMP-9 is static quenching, and this interaction alters the microenvironmental characteristics of tyrosine and tryptophan residues within MMP-9. Importantly, TFs induce a transformation of the secondary structure of MMP-9 into a more ordered and compact conformation. Interestingly, the inhibitory activity followed the order: theaflavin (TF1) < theaflavin-3-gallate (TF2A) ≈ theaflavin-3′-gallate (TF2B) < theaflavin-3,3′-digallate (TF3), suggesting that the number of galloyl groups positively correlates with the inhibitory effect. These findings indicate that TFs have great potential for application in preventing and slowing down the progression of dental caries.
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ACS Applied Nano Materials
·
2022
·
IF 6.14
Qiang Chen,Chunjing Guo,Huimin Guo,Yanguo Su,Zhongxin Liu,Min Cao,Daquan Chen
With the improvement of people’s living standards, obesity has become a health threat, but an effective drug treatment for obesity has not been found yet. Here, we suggest the use of celastrol, a pentacyclic triterpenoid from the traditional Chinese medicine Tripterygium wilfordii, which has a powerful antiobesity effect. Increasing studies have discovered that obesity is closely related to inflammation. In addition, MMP-2 enzyme is highly expressed in inflammatory sites. According to the principle of the prodrug, celastrol was used as a hydrophobic group, PVGLIG as a link, and dextran sulfate as a hydrophilic group to form a micelle (DS-PVGLIG-Cel). Celastrol was then loaded for the effective treatment of high-fat-diet (HFD)-induced obesity. MMP-2-sensitive assays confirmed that PVGLIG cleavage by MMP-2 enzymes favors the synchronous release of celastrol. A series of animal experiments tested that the preparation group has a strong weight loss effect. Our results suggest that this will shed light on a strategy for the subsequent effective treatment of HFD obesity.
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Materials Horizons
·
2024
·
IF 12.2
Weikai Chen,Shihao Sheng,Kai Tan,Sicheng Wang,Xiang Wu,Jiayi Yang,Yan Hu,Liehu Cao,Ke Xu,Fengjin Zhou,Jiacan Su,Qin Zhang,Lei Yang
The degradability of hydrogels plays a pivotal role in bone regeneration, yet its precise effects on the bone repair process remain poorly understood. Traditional studies have been limited by the use of hydrogels with insufficient variation in degradation properties for thorough comparative analysis. Addressing this gap, our study introduces the development of matrix metalloproteinase (MMP)-responsive hydrogels engineered with a tunable degradation rate, specifically designed for bone regeneration applications. These innovative hydrogels are synthesized by integrating MMP-sensitive peptides, which exhibit chirality-transferred amino acids, with norbornene (NB)-modified 8-arm polyethylene glycol (PEG) macromers to form the hydrogel network. The degradation behavior of these hydrogels is manipulated through the chirality of the incorporated peptides, resulting in the classification into L, LD, and D hydrogels. Remarkably, the L hydrogel variant shows a significantly enhanced degradation rate, both in vitro and in vivo, which in turn fosters bone regeneration by promoting cell migration and upregulating osteogenic gene expression. This research highlights the fundamental role of hydrogel degradability in bone repair and lays the groundwork for the advancement of degradable hydrogel technologies for bone regeneration, offering new insights and potential for future biomaterials development.
研究领域:
生物材料
·
组织工程
·
生物医学工程
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhixiang Mu,Yan Yang,Guanyao Zhang,Xiaobin Yang,Qingqing Dong,Jiaying Ma,Anlin Li,Ke Li,Jiajun Hu,Xuanxin Yang,Qiuqiu Mu,Xiaojie Wang
Diabetic wound healing remains challenging due to persistent hyperglycemia-driven reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. To address this, we engineered a photocurable hydrogel ( [email protected] ) composed of gelatin methacryloyl (GelMA) and bovine serum albumin methacryloyl (BSAMA) to encapsulate aucubin (Auc). Systematic evaluation of GelMA/BSAMA ratios identified the 1:1 formulation as optimal, exhibiting superior mechanical strength. The binding ability of BSAMA to Auc could realize sustained release. Furthermore, GelMA's MMP-9-responsive domains enabled accelerated Auc release in inflammatory microenvironments. The design integrates BSAMA's drug-binding capacity with GelMA's MMP-9 responsiveness to achieve spatiotemporal drug release. In vitro studies demonstrated that the hydrogel effectively scavenges ROS and restores mitochondrial membrane potential, thereby disrupting the ROS storm cycle. This antioxidative effect further suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6) and the overexpression of MMP-9. In a type 2 diabetic rat model, the hydrogel accelerated full-thickness wound closure, with histological analysis revealing dense collagen deposition and enhanced angiogenesis. By synergistically integrating GelMA's MMP-9-triggered drug release with BSAMA's Auc-binding capacity, the hydrogel establishes a multifunctional platform that couples microenvironment-responsive drug delivery with anti-oxidative, anti-inflammatory, and pro-angiogenic functions, offering a promising solution for diabetic wound management.
研究领域:
生物材料
·
药剂学
·
伤口愈合
·
糖尿病研究
·
生物工程
·
纳米医学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）