ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Yi Zhang,Junkun Duan,Lingguang Cai,Dong Ma,Wei Xue
For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.
研究领域:
生物化学
·
分子生物学
·
药学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2024
·
IF 4.5
Liu Yadong,Zhang Guiqi,Wu Jiani,Meng Yi,Hu Jianyu,Fu Hao,Yang Dongfang
Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBα Ser32/36 and p-p65 Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.
研究领域:
骨科
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分子生物学
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细胞生物学
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病理学
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DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 3
·1507-1513
·
IF 4.6
Wei Li,Yan Wang,Hongkun Miao,Maohui Yan,Chen Liu,Yu Wang,Jianjun Zhang,Zhiguang Fu
Oral squamous cell carcinoma is one of the most common types of cancer. Surgical resection is one of the most important treatments at present. However, patients often suffer from regional recurrence after surgery. Therefore, new strategies for combination therapy need to be investigated. This work identified a smart injectable hydrogel system co-delivering DOX and sunitinib nanoparticles. The nano drugs are continuously released from the hydrogels and effectively taken up by cells. The nano drugs in the hydrogel can inhibit tumor cell viability and induce cancer cell apoptosis in vitro. The drug-loaded hydrogel could control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. These findings suggest that this smart injectable hydrogel system may provide new ideas for the comprehensive treatment of oral squamous cell carcinoma.
研究领域:
肿瘤学
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药剂学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Hanchun Yan,Wei Wang,Xinhua Song,Yaqi Wang,Zhaowen Nie,Honghan Zhang,Hao Duan,Ningyuan Li,Yuqi Feng,Yuhui Zhang,Chao Wang,Zhongchun Liu
Background The underlying mechanisms of major depressive disorder (MDD) remain unclear; however, increasing evidence has linked MDD to blood–brain barrier (BBB) dysfunction. This study aimed to determine whether BBB impairment represents an early pathological change during chronic stress and whether preservation of BBB integrity is associated with attenuation of neuroinflammatory and behavioral abnormalities. Methods We employed a time-course (1, 2, and 4 weeks) chronic unpredictable mild stress (CUMS) model in C57BL/6 J mice. Depressive-like behaviors (SPT, FST, TST, OFT), BBB permeability (Evans blue), tight junction (TJ) protein expression (qPCR, Western Blot), ultrastructure (TEM, IF), peripheral and central inflammatory responses (ELISA, qPCR, IF), and transcytosis-related changes (Western Blot, TEM) were systematically assessed at each time point. In separate intervention experiments, the PDGFRβ inhibitor Imatinib (50 mg/kg/d) or an MMP-9 inhibitor (20 mg/kg/d) was administered throughout the 4-week CUMS procedure. Results Depressive-like behaviors became robustly established by week 4. In contrast, BBB disruption occurred earlier: molecular changes (e.g., Claudin-5 protein loss) were significant at week 1, followed by functional permeability, TJ structural disruption, increased endothelial vesicle density, and inflammatory alterations at week 2. This pathology worsened by week 4. The 4-week Imatinib co-treatment attenuated the development of depressive-like behaviors, alleviated BBB disruption, and reduced neuroinflammatory abnormalities. At the molecular level, CUMS induced a time-dependent upregulation of MMP-9. Imatinib treatment attenuated activation of the PDGFRβ/MMP-9 pathway, whereas MMP-9 inhibition preserved BBB integrity and attenuated central inflammatory abnormalities despite persistently elevated peripheral cytokine levels. Conclusion BBB dysfunction is an early pathological event during chronic stress and is associated with both tight junction disruption and transcytosis-related alterations. Pharmacological preservation of BBB integrity was accompanied by reduced neuroinflammation, consistent with BBB integrity being an important modulator of chronic stress-associated central inflammatory abnormalities. The PDGFRβ/MMP-9 pathway may represent a promising mechanism associated with stress-related BBB injury and a potential therapeutic target.
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DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 15
·2360
·
IF 5.561
Haiyan Zheng,Yu Pei,Yuan-Lin He,Yi Liu,Minqi Chen,Pengzhi Hong,Chunxia Zhou,Zhong-Ji Qian
Sulfated polysaccharides from red algae have a variety of biological activities, especially antitumor activities. Matrix metalloproteinase-9 (MMP-9) is a proteolytic metalloenzyme that degrades the central part of the extracellular matrix (ECM) and promotes tumor metastasis. In this research, we have investigated the influence and mechanism of GNP (sulfated polysaccharide fromGelidium crinale) on tumor metastasis and MMP-9 expression of human fibrosarcoma (HT1080) cells. The results inflected that the concentration of GNP below 100 μg/mL has no toxicity to HT1080 cells, but showed excellent activity in inhibiting cells migration and invasion. In addition, GNP effectively inhibits the mRNA of MMP-9 and reduces its expression and activity by regulating nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPK) and mTOR/PI3K/Akt signaling pathways. GNP has great potential as MMP-9 inhibitor and could be developed as a functional food or drug to prevent tumor metastasis.Keywords:sulfated polysaccharides;Gelidium crinale;MMP-9;migration;invasion
研究领域:
药理学
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肿瘤学
·
海洋生物学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2026
·
IF 5.9
Wu Rong,Chen Yanyang,Wu Junyu,Ren Kaixuan,Cui Wenguo,Yin Jingbo
Osteoarthritis (OA) is a degenerative joint disease characterized
by the failure of cartilage lubrication and persistent inflammation
induced by friction-generated debris. Therefore, an effective OA treatment
strategy should simultaneously enhance joint long-term lubrication
and suppress inflammation. Toward this goal, we developed durable
Lipo/PADM microgels via multiple cross-linking to integrate sustained
lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone
release. The microgels maintained a low coefficient of friction of
0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation.
In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained,
on-demand drug release, reaching 70% within 14 days. Lipo/PADM microgels
restored type II collagen expression, suppressed MMP-13 in bone marrow
mesenchymal stem cells, and alleviated the OA-associated catabolic
microenvironment. Intra-articular administration significantly reduced
cartilage degeneration and delayed OA progression. These poly(glutamic
acid)-based microgels offer a promising OA therapy through durable
lubrication, responsive drug delivery, and prolonged intra-articular
retention.
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shanmei Lyu,Min Yin,Hongwei Wang,Dingwen Cao,Li Ma,Ting Zhang,Chao Wei,Weiyun Shi
Fungal keratitis (FK) poses a significant threat to vision, with a substantial risk of corneal blindness. This risk is markedly amplified by the inappropriate application of glucocorticoids (GCs), yet the underlying pathogenesis remains unclear, and targeted therapeutic strategies are lacking. Through RNA sequencing (RNA-seq), we revealed profound pathological alterations in corneal tissues from FK mice exposed to dexamethasone (DXMS), mainly characterized by robust inflammatory cascades, disrupted collagen turnover, elevated matrix metalloproteinases (MMPs), and excessive oxidative stress. These factors probably contributed to the observed deterioration in DXMS- treated FK mice, evidenced by significantly increased corneal perforation incidence and fungal burden. Guided by these histopathological insights, we designed an integrated therapeutic nanozyme, termed VDCe-NPs. These nanoparticles combined a cerium oxide (CeO 2 ) nanozyme core (providing reactive oxygen species (ROS) scavenging) with anti-fungal agent voriconazole (VRC) and a pan-inhibitor for MMP doxycycline (Doxy). The formed VDCe-NPs exhibited a quasi-spherical morphology with an average diameter of 9.965 ± 1.947 nm, and displayed excellent biocompatibility, potent ROS scavenging, effective anti-fungal potential, and broad-spectrum MMP inhibition. In vivo studies confirmed that VDCe-NPs significantly mitigated DXMS-associated severe FK, with decreased expression of pro-inflammatory cytokines, lowered MMP levels, reduced expression of oxidative stress-related genes and higher expression of antioxidative-related genes. Collectively, these findings not only addressed the key molecular pathological features of GC- associated severe FK, but also established VDCe-NPs as a promising platform for this challenging condition.
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产品关联
DOI
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
·
纳米技术
·
癌症治疗
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DOI
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
·
分子生物学
·
细胞生物学
·
癌症研究
·
信号转导
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产品关联
DOI
PubMed
高影响因子
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
·
分子生物学
·
儿科医学
✓ 已验证
产品关联
DOI
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
·
纳米技术
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
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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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）