Asian Pacific Journal of Tropical Medicine
·
2015
·
IF 1.062
Chong Shi,Guo-Bin Zhang,Shu-Wang Yin
Objective To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results MTT assay indicated bortezomib (2.5 μM, 5 μM, 10 μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Dongqing He,Dongjun Liu,Zhuoyan Wu,Ruiguang Xiao,Wenjie Ruan,Zeqiang Lin,Qiuxia Chen,Chanling Yuan,Qiong Wu,Wenjie Mei
Acne is a chronic inflammatory skin disease that is highly prevalent in adolescents, and its recurrent flare-ups can affect facial aesthetics, severely impacting adolescents' mental health and quality of life. Screening for safer, more effective fruit acid molecules for daily acne treatment is crucial. This work examined potential mandelic acid derivatives. In a zebrafish model, mandelic acid showed a 78.17 % rate of inflammatory cell aggregation, outperforming supramolecular salicylic acid (86.96 % aggregation) at the same concentration. In a P. acnes -induced cell model, MMP9 protein expression was significantly upregulated in the model group. After treatment with mandelic acid, MMP9 expression decreased by 72.84 % compared to the model group, a better effect than that of supramolecular salicylic acid (36.78 %). Further mechanistic investigations indicate that mandelic acid may inhibit the PI3K/AKT signaling pathway activated by P. acnes , thereby blocking MAPK signaling and modulating MMP9 protein production, thereby averting the development of NLRP3 inflammatory vesicles. Mandelic acid has a favourable safety profile and notable anti-inflammatory properties, which can be further harnessed to mitigate acne in sensitive skin demographics, offering a novel approach to acne treatment.
研究领域:
皮肤病学
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炎症研究
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分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
Small
·
2023
·
IF 13.3
Keke Huang,Xin Liu,Ziru Lv,Di Zhang,Yuling Zhou,Zhiqing Lin,Juan Guo
Age-related macular degeneration (AMD), especially wet AMD with choroidal neovascularization (CNV), commonly causes blindness in older patients and disruption of the choroid followed by second-wave injuries, including chronic inflammation, oxidative stress, and excessive matrix metalloproteinase 9 (MMP9) expression. Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti-inflammatory effects and minocycline is a specific macrophage/microglial inhibitor that can suppress both macrophage/microglial activation and MMP9 activity. Herein, an MMP9-responsive GOQD-based minocycline-loaded nano-in-micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl-modified peptide sequence (C18-GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser-induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti-inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the “inflammation-MMP9-angiogenesis” cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Tianyi Xu,Qilei Yang,Yue Peng,Congcong Xie,Huimin Yu
Rheumatoid arthritis (RA) therapy demands agents that are both effective and safe, yet many natural products with promising bioactivity, such as curcumin, face major translational challenges due to poor solubility and bioavailability. To overcome these limitations, we designed and synthesized a series of dual-functional curcumin-borneol prodrugs via a succinate ester linkage, including the parent ester (CBS), its water-soluble sodium salt (CBS-Na), and a disubstituted analog (DCBS), to enhance delivery and synergize therapeutic action. These derivatives markedly improved cellular uptake and nuclear localization, potently scavenged reactive oxygen species, and effectively suppressed the MAPK/AP-1 signaling axis by inhibiting ERK and p38 phosphorylation and c-Fos expression, leading to downregulation of matrix metalloproteinase MMP9 and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In a collagen-induced arthritis rat model, the derivatives demonstrated superior efficacy over native curcumin in alleviating joint inflammation and destruction, while exhibiting an excellent safety profile, thus representing a novel and promising therapeutic strategy for RA.
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 11
·期 3
·1177-1194
·
IF 7.233
Chenfeng Xu,Yu Sun,Yulin Yu,Mei Hu,Conglian Yang,Zhiping Zhang
An intravenously administered drug delivery system should undergo a five-step ‘CAPIR’ cascade (circulation, accumulation, penetration, internalization and release), and the maximal efficiency of each step is of great importance to obtain the improved final therapeutic benefits and overall survival rate. Here, a pH/matrix metalloproteinase-9 (MMP9) sequentially responsive and continuously structure-transformable nanoparticle assembled from a doxorubicin (DOX)-conjugated peptide was exploited for comprehensively improving the ‘CAPIR cascade’ and eventually enhancing the therapeutic efficacy. The chimeric peptide can self-assemble into spherical nanoparticles (RGD-sNPs) at pH 7.4 with a particle size of 45.7 ± 5.4 nm. By a combination of passive and active targeting mechanisms, RGD-sNPs achieved efficient accumulation at the tumor site (∼15.1% ID g−1 within 24 h). Both in vitro and in vivo experiments revealed that RGD-sNPs can be transformed into rod-like nanoparticles (S-NFs) triggered by MMP9 that overexpressed in the tumor microenvironment, demonstrating remarkable advantages of deep tumor penetration, prolonged drug retention with ∼3.7% ID g−1 at 96 h, and 2-fold enhanced internalization. Subsequently, S-NFs would respond to the intracellular weakly acidic stimuli to rapidly release DOX for induction of cytotoxicity and apoptosis. Meanwhile, the remaining peptide was further converted into long fibers (length >5 μm) with significant cytotoxicity, thereby exerting a synergistic antitumor effect. Thus RGD-sNPs displayed superior antitumor efficacy and extended the median survival period to 55 days. This provides a new horizon for the exploration of high-performance antitumor nanomedicines.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
·
IF 5.3
Chuanxi Tian,Jinyue Zhao,Qian Wang,Keke Luo,Shuang Zhao,Li Wan,Jiarui Li,Kaile Ma,Yanyan Zhou,Min Li
Background Huashi Baidu granule (HSBD), an approved herbal formula for treating COVID-19, demonstrates safety and efficacy. Despite its market approval, the detailed methodology and identification of its active components remain unexplored, leaving its bioactive constituents and action mechanisms unclear. Methods This study investigated the potential mechanisms of HSBD’s active ingredient in treating COVID-19. Our approach integrated various techniques, including the UHPLC-QqQ-MS/MS method, analysis of the GEO database, network pharmacology, surface plasmon resonance, molecular docking and molecular dynamics simulations, to formulate a comprehensive research strategy. Results The UHPLC-QqQ-MS/MS method employed for HSBD analysis proved stable, reliable, and reproducible. We identified 25 principal components in HSBD, with 7 compounds detected in plasma, namely Pogostone, P-Hydroxybenzoic acid, Paeoniflorin, Rhein, Emodin, Ephedrine hydrochloride, and Pseudoephedrine hydrochloride. Protein-Protein Interaction (PPI) network analysis identified MMP9 as a pivotal target. Surface plasmon resonance analysis revealed that Paeoniflorin and Rhein exert their antiviral effects by interacting with RBD and ACE2. In contrast, Emodin’s antiviral mechanism predominantly involves binding to MMP9. Molecular docking results indicated strong binding affinities of Rhein and Paeoniflorin to the hACE2 protein, and high binding affinities of Emodin to the MMP9 protein, all of which were corroborated by molecular dynamics simulations. Conclusion We investigated the methodology and identified the active components of HSBD, focusing on those absorbed into the plasma, to elucidate the effective material basis of HSBD in the treatment of COVID-19, our research offered insightful exploration into its mechanisms of action against COVID-19.
研究领域:
药理学
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医学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Yue Xin,Tianyue Guan,Guanglu Wang,Yannan Xiang,Mengxin Li,Yikun Zhao,Panpan Zhao
Sepsis is a severe systemic infection that leads to multiple organ dysfunction and high mortality, making it one of the primary causes of death in ICU patients. Sepsis also induces septic encephalopathy (SAE), resulting in acute and long-term cognitive impairments. Research indicates that inhibiting BBB damage, anti-inflammatory, and antioxidant responses are critical therapeutic directions for SAE. Monotropein (Mon), the main active component of the traditional Chinese medicine Epimedium, possesses various pharmacological effects, including antioxidant properties. This study aims to explore the protective effects and potential targets of Mon in SAE. Firstly, the GEO database was utilized to screen for highly expressed genes, identifying matrix metalloproteinase-9 (MMP9) as a target. Drug target reverse screening using Schrodinger software confirmed MMP9 as a potential therapeutic target for Mon. Subsequently, in vitro experiments using an LPS-stimulated BV-2 and HUVECs co-culture model examined the interaction between Mon and MMP9. A CLP-induced mouse model was employed to investigate Mon's role in SAE. Results indicate that MMP9 is highly expressed in SAE and promotes its progression. Mon targets MMP9, enhancing its protein stability and exerting anti-inflammatory, improved vascular permeability, and barrier protective effects. Mon alleviates brain tissue damage, BBB disruption, and synaptic loss induced by CLP, increases antioxidant enzyme activity to eliminate ROS, and suppresses sepsis-induced oxidative stress, thereby mitigating CLP-induced cognitive impairment in mice. In conclusion, Mon targets MMP9, exerting anti-inflammatory, antioxidant, and barrier protective effects, alleviating SAE. Mon may serve as a potential natural therapeutic agent for treating sepsis-induced brain dysfunction.
研究领域:
药理学
·
神经科学
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免疫学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 7
·2114
·
IF 4.927
Yi Li,Xia-Jin Liu,Shu-Lan Su,Hui Yan,Sheng Guo,Da-Wei Qian,Jin-Ao Duan
Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9.Keywords:Flos Chrysanthemi;chrysanthemum stem and leaf;inflammatory bowel disease (IBD);zebrafish;UPLC-TQ/MS
研究领域:
药理学
·
炎症研究
·
水生毒理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
·
2019
·Vol. 34
·期 5
·297-305
·
IF 1.894
Zhiyuan Li,Xiaohui Sun,Xiaoming Liu,Ziyuan Sun,Jingwei Li
Background: Ruyiping is an effective traditional Chinese herbal medicine formula for preventing postoperative recurrence and metastasis of breast cancer. However, the exact function and underlying mechanism of Ruyiping in breast cancer remain unclear.Materials and Methods: After breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with Ruyiping, the CCK8, colony formation, wound-healing, and transwell invasion assays were used to examine cell proliferation, migration, and invasion, respectively. Flow cytometry was performed to examine the effect of Ruyiping on cell cycle distribution. Western blot was performed to examine the expression of related proteins, and the activity of MMP9 was detected using Gelatin zymography assay.Results: Ruyiping treatment significantly inhibited cell proliferation and viability of MDA-MB-231 and MDA-MB-468 cells. Ruyiping was also revealed to trigger cell cycle arrest at the G2 phase in MDA-MB-231 and MDA-MB-468 cells. Moreover, Ruyiping suppressed the migration and invasion abilities of MDA-MB-231 and MDA-MB-468 cells in vitro. Furthermore, Ruyiping blocked the activity of MMP9 in MDA-MB-231 and MDA-MB-468 cells. Additionally, western blotting showed that Ruyiping attenuated epithelial-to-mesenchymal transition (EMT) of breast cancer through downregulation of N-cadherin, Vimentin, Snail1, and Snail2 and upregulation of E-cadherin. The authors observed that the components of Ruyiping Pseudobulbus Cremastra seu pleiones polysaccharide and curcumol showed significant suppression in the growth and invasion of breast cancer cell.Conclusions: The observations of this study suggest the antitumor properties of Ruyiping in cell growth and invasion of breast cancer, which are modulated by induction of cell cycle arrest and reduction of MMP9 and EMT.
研究领域:
肿瘤学
·
药理学
·
中医药
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Feixiang Luo,Mingqian Li,Yuguo Chen,Shifei Song,Haiyang Yu,Peng Zhang,Chunsheng Xiao,Guoyue Lv,Xuesi Chen
Acute rejection is a life-threatening complication after liver transplantation. Immunosuppressants such as tacrolimus are used to inhibit acute rejection of liver grafts in clinic. However, inefficient intragraft accumulation may reduce the therapeutic outcomes of tacrolimus. Here, an enzyme-responsive nanoparticle is developed to selectively enhance the accumulation of tacrolimus in liver allograft through enzyme-induced aggregation to refine immunotherapeutic efficacy of tacrolimus. The nanoparticles are composed of amphiphilic tacrolimus prodrugs synthesized by covalently conjugating tacrolimus and matrix metalloproteinase 9 (MMP9)-cleavable peptide-containing methoxy poly (ethylene glycol) to poly ( l -glutamic acid). Upon exposure to MMP9, which is overexpressed in rejected liver allografts, the nanoparticles undergo a morphological transition from spherical micellar nanoparticles to microscale aggregate-like scaffolds. Intravenous administration of MMP9-responsive nanoparticles into a rat model of acute liver graft rejection results in enhanced nanoparticle accumulation in allograft as compared to nonresponsive nanoparticles. Consequently, the MMP9-responsive nanoparticles significantly inhibit intragraft inflammatory cell infiltration and proliferation, maintain intragraft immunosuppressive environment, alleviate graft damage, improve liver allograft function, abate weight loss and prolong recipient survival. This work proves that morphology-switchable enzyme-responsive nanoparticles represent an innovative strategy for selectively enhancing intragraft accumulation of immunosuppressive agents to improve treatment of liver allograft rejection.
研究领域:
药学
·
纳米技术
·
移植免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Host & Microbe
·
2024
·
IF 20.6
Zhen He,Jing Yu,Junli Gong,Jinjie Wu,Xuan Zong,Zhanhao Luo,Xiaowen He,Wai Ming Cheng,Yugeng Liu,Chen Liu,Qiang Zhang,Lei Dai,Tao Ding,Beile Gao,Raad Z. Gharaibeh,Jinlin Huang,Christian Jobin,Ping Lan
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni -derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni -infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB ( ΔcdtB ) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni’s pro-metastatic property. In C.-jejuni -colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2023
·
IF 3.9
Hongyang Xie,Junyu Chen,Changyan Ma,Jingjing Zhao,Manhua Cui
Dysregulation of the deubiquitinating protease, UBP43, has been implicated in many human diseases, including cancer. Here, we evaluated the functional significance and mechanism of action of UBP43 in epithelial ovarian cancer. We found that UBP43 was significantly upregulated in the tumor tissues of patients with epithelial ovarian cancer. Similar results were observed in OVCAR-3, Caov-3, TOV-112D, A2780, and SK-OV-3 cells. Furthermore, in vitro functional assays of A2780 and TOV-112D cells demonstrated that UBP43 overexpression promoted cell proliferation, migration, and invasion. Upregulation of UBP43 might result in epithelial–mesenchymal transition by inducing the nuclear transport of β-catenin, which was accompanied by enhanced N-cadherin but decreased E-cadherin expression. These malignant phenotypes were reversed by UBP43 silencing. Further investigation revealed that the knockdown of UBP43 inhibited cell proliferation by inducing a cell cycle arrest at the G2/M phase. The oncogenic characteristics of UBP43 were validated in a subcutaneous xenograft mouse model. In vivo, tumor growth was delayed in the UBP43-silenced group but accelerated after UBP43 overexpression. Finally, we demonstrated that β-catenin is a key protein in the UBP43-mediated malignant development of epithelial ovarian cancer. Specifically, overexpression of UBP43 decreased the ubiquitination degradation of β-catenin and enhanced its protein stability. Also, we observed that the downstream genes of beta-catenin such as cyclin D1, MMP2, and MMP9 were upregulated due to UBP43 overexpression. Thus, we concluded that UBP43 promoted epithelial ovarian cancer tumorigenesis and metastasis through activation of the β-catenin pathway, suggesting that UBP43 may be a potential therapeutic target for this intractable disease.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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