Oncotarget
·
2017
·
IF 5.168
Lu Yang,Yuling Wei,Ying Luo,Qunfang Yang,Huan Li,Congli Hu,Yang Yang,Junqing Yang
To observe the characteristic changes of PGE 2 -EP s pathway and divergent functions of PGE 2 receptor subtypes on neuronal injury. The primary cultured rat hippocampus neuron injury model was established via aluminum maltolate (100 μM). The aluminum-overload neurons were treated with the agonists of EP1 (17-phenyl trinor Prostaglandin E2 ethyl amide), EP2 (Butaprost), EP3 (Sulprostone) and EP4 (CAY10598) and antagonists of EP1 (SC-19220), EP2 (AH6809) and EP4 (L-161982) at different concentrations, respectively. The neuronal viability, lactate dehydrogenase leakage rate and PGE2 content were detected by MTT assay, lactate dehydrogenase assay kit and enzyme-linked immunosorbent assay, respectively. The mRNA and protein expressions of mPGES-1 and EPs were determined by RT-PCR and western blot, respectively. The pathomorphology was identified by hematoxylin-eosin staining. In the model group, neuronal viability significantly decreased, while lactate dehydrogenase leakage rate and PGE2 content increased. The mPGES-1, EP1, EP2 and EP4 mRNA expression, and the mPGES-1, EP1 and EP2 protein expression increased, while EP 3 level decreased. EP3 agonist exerted protective function in neuronal viability and lactate dehydrogenase leakage rate, while EP1 agonist, EP2 and EP4 antagonist exerted an opposite effect. In conclusion, aluminum-overload caused an imbalance of PGE 2 -EP 1-4 pathway and activation of EP receptor may provide a viable therapeutic target in neuronal injury.
研究领域:
神经科学
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药理学
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毒理学
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Tingting Zhang,Congcong Zhang,Xue Li,Dongfang Ren,Mingshuang Zheng,Shuo Zhang,Fangping Yuan,Xin Du,Zhenguo Zhang
Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB–Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10 −5 –10 6 fg/mL and a detection limit (LOD) of 10 −5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.
研究领域:
分析化学
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生物化学
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免疫学
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药理学
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再生医学
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DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Shiying Xu,Lina Wu,Boxin Chen,Xiaoliang Deng,Zhihui Zheng,Fei Wu,Lingjun Zeng,Changqing Zheng,Xiaomu Hu,Aiwen Huang,Xin Zhou,Xianquan Feng,Zhihong Liu
Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment due to its selective tumor ablation and excellent safety characteristics. However, its efficacy is limited by tumor hypoxia and excessive inflammation. In this study, we fabricated human serum albumin-based nanoparticles (CAI NPs) encapsulating celecoxib (CXB), atovaquone (ATO), and IR820 via sonication. The CAI NPs exhibited favorable physicochemical properties, including a uniform size distribution (<200 nm), high encapsulation efficiency and excellent colloidal stability. Initially, ATO acts as a mitochondrial complex III inhibitor, suppressing oxidative phosphorylation to ameliorate tumor hypoxia. This hypoxia alleviation potentiates PDT efficacy by enhancing tumor cell ROS generation. Furthermore, concomitant COX-2/PGE2 inhibition by CXB attenuates the excessive inflammatory cascade triggered during PDT, resulting in enhanced therapeutic outcomes through microenvironment modulation. Eventually, the dual-enhanced CAI NPs demonstrate potent antitumor activity in both in vivo and ex vivo models, while maintaining excellent biocompatibility under physiological conditions. In summary, the integrated three-drug regimen conclusively enhances photodynamic therapeutic outcomes through multimodal mechanisms, establishing a viable treatment approach for esophageal cancer.
研究领域:
肿瘤学
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纳米医学
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光动力治疗
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分子药理学
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肿瘤微环境
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转化医学
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药物递送系统
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PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
Qi-Rui Hu,Qing-Xin Huang,Huan Hong,Yao Pan,Ting Luo,Jing Li,Ze-Yuan Deng,Fang Chen
s Background Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis . Purpose The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma , and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. Study Design The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. Method In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. Results The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner ( p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT ( p < 0.05). Conclusion Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
研究领域:
肿瘤学
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药理学
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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
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 11
·311
·
IF 3.1
Qing Zhu,Yuanshan Han,Ying He,Yilan Fu,Hui Yang,Yun Chen,Yingrui Shi
Background: Breast cancer-related depression (BCRD) is strongly associated with BC and increases recurrence and mortality. This study investigated the role of kaempferol in the pathogenesis of BCRD and its underlying mechanism. Methods: 4T1 mouse BC cells were treated with corticosterone (Cort) in vitro to develop a neuronal injury model, and a BCRD mouse model was established by injecting 4T1 cells and Cort. The effects of kaempferol on 4T1 cells and BCRD models were measured by behavioral tests, Cell Counting Kit-8 assay, wound healing assay, colony formation assay, Western blot analysis, quantitative real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay, and immunofluorescence. BCRD cells were transfected with the cyclo-oxygenase-2 (COX-2) overexpression plasmid to study the role of the COX-2/prostaglandin E2 (PGE2) axis in the anti-BCRD activity of kaempferol. The connection between kaempferol and COX-2 was analyzed by molecular docking. Results: Kaempferol reduced the viability, migration, and clones of 4T1 cells and inhibited BC growth and depression-like behavior in mice. Kaempferol alleviated inflammation in BCRD, decreased interleukin 1 beta (IL-1β) and IL-6 levels, and increased transforming growth factor beta 1 (TGF-β1) and IL-10 levels. In addition, kaempferol elevated the levels of serotonin, dopamine, and norepinephrine and the amount of 5-Bromo-2′-deoxyuridine/neuronal nuclei-positive cells. Kaempferol downregulated COX-2 and PGE2, and kaempferol could dock with the protein structure of COX-2. Overexpression of COX-2 reduced BCRD viability, upregulated IL-1β and IL-6 levels, and downregulated TGF-β1 and IL-10 expression. Overexpression of COX-2 reversed the protective effects of kaempferol. Conclusion: Kaempferol exerted anti-BCRD effects, at least in part by inhibiting the COX-2/PGE2 pathway, which regulates neuroinflammation, neurotransmitter imbalance, and defective neurogenesis. Therefore, kaempferol may be a promising candidate active ingredient for treating BCRD.
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高影响因子
EMBO REPORTS
·
2021
·Vol. 22
·期 3
·e51329
·
IF 8.807
Ziqing Chen,Ying Yang,Shi Y Neo,Hao Shi,Yi Chen,Arnika K Wagner,Karin Larsson,Le Tong,Per-Johan Jakobsson,Evren Alici,Jing Wu,Yihai Cao,Kai Wang,Lisa L Liu,Yumeng Mao,Dhifaf Sarhan,Andreas Lundqvist
Inadequate persistence of tumor-infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL-2 or IL-15 renders NK cells resistant to suppression by PGE2. Analyzing Cancer Genome Atlas (TCGA) data, we found that high NK cell gene signatures correlate with significantly improved overall survival in patients with high levels of the prostaglandin E synthase (PTGES). In vitro, IL-15, in contrast to IL-2, enriches for CD25+/CD54+ NK cells with superior mTOR activity and increased expression of the cAMP hydrolyzing enzyme phosphodiesterase 4A (PDE4A). Consequently, this distinct population of NK cells maintains their function in the presence of PGE2 and shows an increased ability to infiltrate lung adenocarcinoma tumors in vitro and in vivo. Thus, strategies to enrich CD25+/CD54+ NK cells for adoptive cell therapy should be considered.
研究领域:
免疫学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2013
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IF 1.722
Huiqing Lv,Xiaoping Zhang,XueZhi Chen,Zhijun Xie,Changfeng Hu,Chengping Wen,Kezhi Jiang
Background. Ficus pandurata H. (Moraceae) is widely used in traditional Chinese medicine as a healthy food condiment or a medicine for treatment of various diseases including inflammation. Objective. The purpose of the present study is to investigate the phytochemical compositions and antioxidant and anti-inflammatory activities of crude water (FPW) and ethanolic extracts (FPE) from Ficus pandurata H. Methods. Phytochemical compositions were identified by a high-performance liquid chromatography-electrospray ionization-mass spectrometry method (HPLC-ESI-MS). The antioxidant activities were evaluated by diphenylpicrylhydrazyl (DPPH) and hydroxyl radical assays, and the anti-inflammatory activities were evaluated by paw edema and levels of inflammatory mediator TNF-α and PGE2 in monosodium urate (MSU) crystal-induced rats. Results. Six compounds were identified by HPLC-MS method, and abundance of phenolics was found in FPE. The FPE showed concentration-dependent-significant scavenging of DPPH and hydroxyl radicals with IC50 values 118.4 and 192.9 μg/mL, respectively. The FPE treatment significantly inhibited the paw edema and the production of TNF-α and PGE2 in MSU crystal-induced rats. Conclusion. The FPE exerted stronger antioxidant and anti-inflammatory activities which may be attributed to its high phenolic content.
研究领域:
药理学
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植物化学
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传统医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2016
·
IF 2.73
Ming Zong,Dan-Dan Fan,Shan Lin,Yan-Ping Song,Ze-Yu Wang,Xiao-Liang Ma,Wei-Hua Qiu,Yu-Hua Bai,Lei Li,Sen Li
Aspirin has been used in the treatment and chemoprevention of many malignant cancers. The mechanism of its anti-cancer activity mainly involves the inhibition of cyclooxygenase-2 (COX-2). However, the application of aspirin is limited by the serious gastric mucosal damage that accompanies its usage. We have previously reported the preparation of a novel aspirin derivative that we named Ca-Asp, and showed that it causes less damage to gastric mucosa of rat and inhibits the expression of COX-2 to higher degree than Asp. However, the anti-cancer effect and mechanism of Ca-Asp was not demonstrated. In this study, the anti-cancer effect of Ca-Asp was investigated and compared with those of Asp and Hydroxyapatite (Hap) at the cell level. The results showed that treatment of SGC-7901 cells (human gastric cancer cell line) with 200–400 μg/ml Ca-Asp resulted in significant reduction in cell viability , compared to treatment with either Asp or Hap, and at a higher concentration (500 μg/ml). Subsequent investigation into the possible underlying mechanism showed that Ca-Asp induced apoptosis and caused cell cycle arrest at the G1 phase . Ca-Asp also up-regulated the levels of caspase-3 and p53, but down regulated the level of cyclin D1 , NF-κB, COX-2 and PGE 2 . Furthermore, simultaneous treatment of SGC-7901 cells with Ca-Asp and exogenous PGE 2 reduced the anti-proliferative effect of Ca-Asp on the cells. Taken together, the results suggested that Ca-Asp might act as a potential anti-cancer drug, and that its suppression of PGE 2 production might constitute an important part of its anti-cancer activity.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
Chinese Herbal Medicines
·
2025
·
IF 8.9
Fuyun Chi,Wenshuang Wang,Shanshan Zhai,Man Zhang,Yuanyuan Hou,Gang Bai
Objective To explore novel anti-inflammatory strategies by targeting prostaglandin E2 (PGE2) overexpression, aiming to overcome the limitations of conventional cyclooxygenase-1/2 (COX-1/2) inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs). Methods A correlation analysis of the anti-inflammatory activities of 24 exterior- releasing herb medicines, including NF- κ B, COX2, and PGE2 activities, was conducted, and the key active ingredients in the herbs showing significant associations were screened. Using a self-assembly technique, baicalein-2,4-decadienal (BD) were formulated into stable and homogeneous carrier-free nanoparticles to enhance drug solubility and targeting. Subsequently, disease models associated with PGE2 overexpression—fever, pneumonia and rheumatoid arthritis were established to evaluate the antipyretic, analgesic and anti-inflammatory properties of BD nanomedicines. Their targeting capability and drug release profile were also investigated. Results BD nanomedicines exhibited a synergistic inhibitory effect on PGE2 production by concurrently targeting COX2 and microsomal prostaglandin E synthase-1 (mPGES1), thereby producing antipyretic, analgesic, and anti-inflammatory effects superior to those observed with either agent alone. Furthermore, BD nanoparticles demonstrated preferential accumulation in macrophages implicated in the inflammatory response and facilitated pH-responsive drug release within the inflammatory microenvironment. This targeted delivery approach not only enhances therapeutic efficacy but also enables dose reduction and mitigates the risk of adverse effects, representing a promising strategy for the treatment of PGE2-mediated inflammatory diseases. Conclusion The findings provide new insights into drug development for inflammatory diseases caused by PGE2 overexpression, emphasizing the advantages of carrier-free supramolecular bioactive materials derived from natural products in the treatment of such diseases.
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2020
·
IF 6.17
Zhaoyun Zong,Jing Liu,Ning Wang,Changmei Yang,Qingtao Wang,Wenhao Zhang,Yuling Chen,Xiaohui Liu,Haiteng Deng
Liver fibrosis is a reversible wound-healing response to acute or chronic liver injury that can progress to cirrhosis and liver cancer. Finding new strategies for prevention and management of liver fibrosis is urgently needed. It is known that hepatic stellate cell (HSC) is the primary source of extracellular matrix that drives liver fibrosis progression. Herein, we carried out a comprehensive secretome profiling to identify NMN-induced changes in secretory proteins and found that NMN suppressed the secretion of profibrotic protein and oxidoreductase in activated HSC (LX-2) cells, while real-time quantitative PCR analysis revealed that NMN downregulated profibrotic gene expression, resulting in HSC inactivation. Next, we demonstrated that nicotinamide mononucleotide (NMN) reduced the accumulation of liver extracellular matrix in thioacetamide (TAA) and carbon tetrachloride (CCl 4 ) induced mouse models for liver fibrosis. Furthermore, we determined that NMN inhibited oxidation-mediated 15-PGDH degradation to promote prostaglandin E 2 degradation and suppress HSC activation. In summary, our results propose that NMN supplementation is a new therapeutic approach for liver fibrosis prevention.
研究领域:
肝病学
·
药理学
·
分子生物学
·
细胞生物学
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PubMed
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Biao Chen,Qing Chai,Shengmin Xu,Qian Li,Tao Wu,Shaopeng Chen,Lijun Wu
Silver nanoparticles (AgNPs) are widely used as antimicrobial agents and resulted in their accumulation in environment. The purpose of this study was to investigate the detailed molecular mechanisms underlying AgNP-induced lung cellular senescence which has been proposed as a pathogenic driver of chronic lung disease. Herein, we demonstrate that exposure to AgNPs elevates multiple senescence biomarkers in lung cells, with cell cycle arrest in the G2/M phase, and potently activates genes of the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cell line MRC5. Fluorescence-based assay also reveals that apoptosis induced by AgNPs is associated with senescence. Furthermore, we show that AgNPs cause premature senescence through an increase in transcription factor nuclear factor kappa B (NF- κ B), cyclooxygenase-2 (COX2) expression and over-production of prostaglandin E2 (PGE2) in lung cells. Inhibition of COX2 reduces AgNPs-induced senescence to a normal level. Moreover, AgNPs also induce upregulation of COX2 and accelerate lung cellular senescence in vivo and cause mild fibrosis in the lung tissue of mice. Taken together, our studies support a critical role of AgNPs in the induction of lung cellular senescence via the upregulation of the COX2/PGE2 intracrine pathway, and suggest the adverse effects to the human respiratory system.
研究领域:
毒理学
·
呼吸医学
·
分子生物学
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DOI
PubMed
高影响因子
AGING CELL
·
2026
·Vol. 25
·期 2
·e70374
·
IF 7.1
Sainan Zhang,Jiahui Qi,Chuanming Liu,Huidan Zhang,Bichun Guo,Die Wu,Yicen Liu,Xin Zhen,Yang Zhang,Nannan Kang,Jidong Zhou,Guijun Yan,Chaojun Li,Lijun Ding,Haixiang Sun
With the increasing trend of delayed childbearing, the decline in oocyte quality associated with advanced maternal age has emerged as a pressing concern. However, the mechanism remains unclear, and effective strategies for improvement are currently lacking. Previously, we reported that the downregulation of the mevalonate pathway in aged granulosa cells (GCs) contributed to meiotic defects in oocytes, which may implicate farnesyl pyrophosphate-mediated protein farnesylation. Nevertheless, the role of farnesylation in ovarian aging and its impact on oocytes requires further investigation. In this study, using cumulus-oocyte complexes (COCs) from young and aged female mice, we observed impaired cumulus expansion and concurrent meiotic defects during aged oocyte maturation, accompanied by significantly reduced protein farnesylation in aged GCs. Furthermore, inhibiting farnesylation with FTI-277 in young COCs recapitulated the aging phenotype, disrupting cumulus expansion and inducing meiotic defects similar to those in aged COCs. Conversely, restoring farnesylation via farnesol supplementation effectively ameliorated these deficits in both aged COCs (in vitro) and aged mice (in vivo). Proteomic analysis and experimental validation identified prostaglandin E2 synthase 2 (PTGES2) as a farnesylated protein. Mechanistically, age-related decline in PTGES2 farnesylation in GCs reduces its endoplasmic reticulum localization and impairs prostaglandin E2 (PGE2) production, thereby compromising PGE2-dependent cumulus expansion and oocyte maturation. Collectively, our findings highlight the detrimental effects of decreased farnesylation in aged GCs on oocyte quality and propose a potential therapeutic strategy for improving the developmental competence of aged oocytes.
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