Genes & Genomics
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2022
·Vol. 44
·期 11
·1375-1384
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IF 2.164
Wang Yazhuo,Ren Yanan,Li Na,Zhao Jing,Zhao Sufen
Background Rab11a is a novel identified tumorigenic factor involved in different cancers. Objective This study aimed to assess the biological function of Rab11a in ovarian cancer (OC). Methods GEPIA database and real-time PCR were used to determine Rab11a expression in OC tissues and normal ovarian tissues. CCK-8, cell cycle, wound healing, transwell, and enzyme linked immunosorbent assay were used to detect the effects of Rab11a knockdown or overexpression on the proliferation, migration, and invasion of OC cells. Western blot analysis of autophagy-related markers and immunofluorescence staining of LC3 were performed to determine autophagy induction in Rab11a-silenced or overexpressed OC cells. Moreover, autophagy inhibitor 3-MA was employed to clarify the effects of Rab11a-regulated autophagy on the malignant phenotypes of OC cells. Results The mRNA level of Rab11a was increased in tumor tissues from OC patients as compared to the normal ovarian tissues. Knockdown of Rab11a in OVCAR-3 cells inhibited the growth of OC cells and led to cell cycle arrest, accompanied by reduced expression of PCNA and Cyclin D1. Rab11a deficiency suppressed migration and invasion of OC cells, accompanied by decreased secretion of MMP-2 and MMP-9. Silence of Rab11a impeded autophagy induction, as evidenced by decreased LC3 puncta formation, reduced abundance of LC3II and Beclin1, and increased p62 protein expression. In contrast, the ectopic expression of Rab11a in A2780 cells exerted opposite effects. Interestingly, autophagy inhibitor 3-MA abolished the effects of Rab11a overexpression on autophagy, proliferation, migration, and invasion. Conclusions Rab11a promotes the malignant phenotypes of OC cells by inducing autophagy.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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PubMed
高影响因子
International Journal of Medical Sciences
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2025
·Vol. 22
·期 15
·3839-3853
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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
JOURNAL OF IMMUNOLOGY
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2025
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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
TISSUE & CELL
·
2022
·
IF 2.586
Xiaoping Wu,Qiujie Pang,Fuxiang Zhi,Xiaohong Mao,Yingbin Hu
The role of long non-coding RNA ACTA2 antisense RNA 1 (LncRNA ACTA2-AS1) in colorectal cancer (CRC) was awaited to be elucidated. Clinical specimen and data on ACTA2-AS1 expression in colon adenocarcinoma (COAD) were collected, followed by in situ hybridization . Transfected CRC cell viability, proliferation, migration, and invasion were determined with Cell Counting Kit-8, colony formation, Scratch, and Transwell assays, respectively. Relative expressions of ACTA2-AS1, PCNA, Bcl-2, MMP-2 and MMP-9 were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot . ACTA2-AS1 expression was downregulated in CRC. Overexpressed ACTA2-AS1 repressed the cell viability, proliferation, migration and invasion, increased cleaved caspase-3 level yet decreased PCNA, Bcl-2, MMP-2 and MMP-9 levels. ACTA2-AS1 silencing, however, did oppositely. Collectively, ACTA2-AS1 inhibits the viability, proliferation, migration and invasion of CRC cells to effectively suppress the progression of CRC.
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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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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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
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药剂学
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伤口愈合
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糖尿病研究
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生物工程
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纳米医学
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PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
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2018
·Vol. 120
·期 6
·9648-9655
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IF 2.959
Chaozhi Ma,Liyuan Zou,Yu Xia,Yijun Tu,Daquan Xue,Yanfang Yang,Dan Liu,Yanwen Liu,Hezhen Wu,Hanxiong Dan,Pengtao You
Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.
研究领域:
药理学
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免疫学
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呼吸医学
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PubMed
高影响因子
Food & Function
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2026
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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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Communications Biology
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2025
·Vol. 8
·期 1
·1-15
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IF 5.1
Fan Zhan,Xu Yilun,Lu Yafang,Li Xinlin,Xu Mengli,Liu Jinxin,Cai Zhenzhen,Liu Jiayang,Su Jingping,Wang Jialu,Luo Qingming,Zhang Zhihong,Liu Zheng
The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1 GFP/+ Lyz2 RFP/+ mice as bone marrow donors and Krt14 YFP/+ mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.
研究领域:
免疫学
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皮肤病学
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细胞生物学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 26
·4314-4325
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IF 4.776
Tao Liu,Shaohua Chen,Siyi Zhang,Xidong Wu,Peina Wu,Beiping Miao,Xiang Cai
Transferrin-functionalized chitosan-graft-poly(L-lysine) dendrons (CS–PLLD–Tf) were synthesized in this work and then used to deliver the MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS–PLLD–Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS–PLLD–Tf showed much higher gene transfection efficiency than PEI-25k and CS–PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition of the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS–PLLD–Tf delivered the MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with the PBS control group. Moreover, CS–PLLD–Tf displayed higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy of tumors.
研究领域:
癌症研究
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基因治疗
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生物医学工程
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药剂学
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PubMed
高影响因子
BIOMATERIALS
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2014
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IF 8.312
Dong Ma,Qian-Ming Lin,Li-Ming Zhang,Yuan-Yuan Liang,Wei Xue
The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro , and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays , and also showed a good biocompatibility in vivo . Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy.
研究领域:
药学
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生物医学工程
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癌症研究
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 11
Chengbai Dai,Cheng Chen,Jun Zhu,Minghao Chao,Hanrong Yan,Pengjin Wei,Ming Guan,Bin Pan,Fenglei Gao,Rongze Tang
ZCM2 reprograms redox–inflammatory coupling by activating Nrf2/HO-1 signaling and suppressing NF-κB–driven responses in macrophages. • ZCM2 disrupts macrophage-mediated matrix degradation via downregulation of MMP-9, mitigating pathological bone resorption. • Calcium ion release from ZCM2 instructs osteogenic commitment through activation of the RUNX2-centered transcriptional network. • ZCM2 achieves immune modulation–coupled bone regeneration, enabling systemic restoration of bone homeostasis in osteoporosis. Osteoporosis is a systemic skeletal disorder characterized by bone loss and microstructural deterioration, and its pathogenesis is closely associated with dysregulation of the bone marrow immune microenvironment. In this study, bioinformatic analysis first revealed significant oxidative stress and mitochondrial metabolic dysfunction in macrophages within the osteoporotic microenvironment. Based on this, we constructed a biomimetic nanoplatform (ZCM2) composed of ZIF-8@CaCO 3 core–shell nanoparticles camouflaged with M2 macrophage membranes, designed to achieve comprehensive osteoporosis therapy through a triple synergistic mechanism: the ZIF-8 core scavenges reactive oxygen species to exert antioxidant and anti-inflammatory effects, inhibits MMP-9 secretion to reduce pathological bone resorption, and the CaCO 3 shell releases calcium ions to promote osteogenic differentiation. ZCM2 exhibited favorable biosafety, high cellular uptake efficiency, and excellent bone-targeting capability. Mechanistic studies demonstrated that ZCM2 upregulates the expression of Nrf2 and HO-1, downregulates the expression of NF-κB p65, and significantly reduces the secretion of matrix metalloproteinase-9 (MMP-9) by macrophages, thereby attenuating bone resorption. Meanwhile, calcium ions released from the CaCO 3 shell activate the RUNX2/OSX/OPN signaling axis, promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In an ovariectomized mouse model of osteoporosis, ZCM2 markedly improved bone microarchitecture, promoted new bone formation, and effectively inhibited bone resorption activity. Collectively, this biomimetic nanoplatform integrates anti-inflammatory, anti-resorptive, and pro-osteogenic functions, offering a multifaceted synergistic therapeutic strategy for osteoporosis. M2 macrophage membrane–biomimetic nanoparticles activates the Nrf2/HO-1 antioxidant pathway in macrophages, thereby inhibiting NF-κB activation and MMP-9 secretion, which suppresses pathological bone resorption. Download: Download high-res image (327KB) Download: Download full-size image
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高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Huang Dan,Sun Chaoqun,Chen Min,Bai Shuyou,Zhao Xuanna,Wang Weiming,Geng Kang,Huang Wenbo,Zhao Tingting,Wu Bin,Zhang Guilin,Wu Dong,Xu Youhua
Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.
研究领域:
免疫学
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药理学
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
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