ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Bin Zhao,Chong Wang,Xinjie Qiu,Xinyue Zeng,Xin Yin,Lina Zhang,Xuedan Yan,Shaobang Wu,Xiuyun Ren
Oral ulcer is a common oral mucosal injury disease that causes significant inconvenience and discomfort for patients. Traditional treatments, such as drugs, ointments, and patches, have limitations, including low local drug utilization, short residence time on the affected area, and the risk of secondary injury from manual application. To address these issues, this study developed a sprayable temperature-sensitive hydrogel (PEI/PAA/PF127-CHO/AA2G@MSN-NH2 hydrogel, PMAG) without manual contact on injuryed mucosa by combining aldehyde-modified Pluronic F-127 (PF127-CHO), ascorbic acid 2-glucoside-loaded amino-mesoporous silica (AA2G@MSN-NH2), polyethylenimine (PEI), and polyacrylic acid (PAA) through Schiff base reaction and physical crosslinking. When sprayed onto an oral ulcer, PMAG exhibits excellent temperature sensitivity and adhesion, rapidly adapting to oral temperature and forming a protective film that closely adheres to the ulcer surface. This creates a stable healing environment by isolating the wound from external stimuli. PMAG has demonstrated significant abilities in promoting epithelial cell proliferation and migration, as well as antioxidant, anti-inflammatory, and antibacterial properties. RNA sequencing revealed that the tissue repair-promoting effects of PMAG are primarily mediated by activating the nerve growth factor receptor/extracellular signal-regulated kinase (NGFR/ERK) signaling pathway. In summary, PMAG represents a significant advancement in improving the treatment of oral ulcers and offers a more convenient option for patients.
研究领域:
药学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2021
·
IF 3.636
Wei Liu,Ling Zhang,Shuo Sun,Long-sheng Tang,Shi-min He,An-qi Chen,Li-na Yao,Da-Long Ren
As a natural extract, cordycepin has been shown to play important regulatory roles in many life activities. In the study, the effects of cordycepin on inflammatory responses and the underlying mechanisms was explored using a zebrafish model. In the model of LPS-induced inflammation, cordycepin was found to significantly inhibited the expression of pro-inflammatory cytokines such as tnf-α, il-1β, il-6, and il-8 . Using in vivo imaging model, cordycepin significantly inhibited fluorescent-labeled neutrophils migrating towards injury sites. Furthermore, results showed that the phosphorylation level of ERK protein dramatically decreased after cordycepin treatment. Meanwhile, the ERK inhibitor, PD0325901, significantly inhibited the expression of pro-inflammatory cytokines in LPS-induced inflammatory model and neutrophils migration in the caudal fin injury model. This study indicated the important roles of cordycepin in inhibiting LPS and injury-induced inflammation and preliminarily explained the role of ERK protein in this process.
研究领域:
免疫学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Current Molecular Pharmacology
·
2024
·Vol. 17
·期 1
·e150923221164
·
IF 2.4
Yejiao Ruan,Guangrong Lu,Yaojun Yu,Yue Luo,Hao Wu,Yating Shen,Zejun Gao,Yao Shen,Zhenzhai Cai,Liyi Li
Introduction Colorectal cancer remains a life-threatening malignancy with increasing morbidity and mortality worldwide. Therefore, new and effective anti-colorectal cancer therapeutics are urgently needed. Methods In this study, we have studied the anti-tumor properties and potential mechanisms of PF-04449913. Colorectal cancer cell viability was reduced by PF-04449913 in a dose-dependent manner. The migration and invasion ability of malignant colon cells were attenuated by the drug, as demonstrated by the Transwell test. Moreover, PF-04449913 repressed the phosphorylation levels of ERK and other proteins, and the expression levels of MMP9. The anti-tumor effects of the drug in vivo were demonstrated in BALB/c-nude mice models, and PF-04449913 inhibited the malignant phenotype of colorectal cancer cells, including reduction of tumor size and promotion of apoptosis. At the molecular level, PF-04449913 induced a significant decrease in ERK and p65 protein phosphorylation levels and inhibited MMP9 protein expression. Results Both in vivo and in vitro results showed PF-04449913 to demonstrate antitumor effects, which have been proposed to be mediated through blockade of the ERK/p65 signaling pathway, and subsequent repression of MMP9 expression. Conclusion Our study provides a new perspective on the potential clinical application of PF-04449913 in the treatment of colorectal cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-20
·
IF 16.6
Yan Hao,Wu Wentong,Hu Yuhuai,Li Jinjin,Xu Jiangxin,Chen Xueqin,Xu Zhifei,Yang Xiaochun,Yang Bo,He Qiaojun,Luo Peihua
The hepatotoxicity of regorafenib is one of the most noteworthy concerns for patients, however the mechanism is poorly understood. Hence, there is a lack of effective intervention strategies. Here, by comparing the target with sorafenib, we show that regorafenib-induced liver injury is mainly due to its nontherapeutic target Eph receptor A2 (EphA2). EphA2 deficiency attenuated liver damage and cell apoptosis under regorafenib treatment in male mice. Mechanistically, regorafenib inhibits EphA2 Ser897 phosphorylation and reduces ubiquitination of p53 by altering the intracellular localization of mouse double minute 2 (MDM2) by affecting the extracellular signal-regulated kinase (ERK)/MDM2 axis. Meanwhile, we found that schisandrin C, which can upregulate the phosphorylation of EphA2 at Ser897 also has protective effect against the toxicity in vivo. Collectively, our findings identify the inhibition of EphA2 Ser897 phosphorylation as a key cause of regorafenib-induced hepatotoxicity, and chemical activation of EphA2 Ser897 represents a potential therapeutic strategy to prevent regorafenib-induced hepatotoxicity.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2018
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IF 3.382
T.H. Wang,S.Y. Wang,X.D. Wang,H.Q. Jiang,Y.Q. Yang,Y. Wang,J.L. Cheng,C.T. Zhang,W.W. Liang,H.L. Feng
Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro , as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
研究领域:
神经科学
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药理学
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分子生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Oral Science
·
2024
·Vol. 16
·期 1
·1-11
·
IF 10.8
Wang Wen,Wang Qian,Sun Shiying,Zhang Pengfei,Li Yuyu,Lin Weimin,Li Qiwen,Zhang Xiao,Ma Zhe,Lu Haiyan
Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.
研究领域:
牙科学
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正畸学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Yasi Mo,Yong Wu,Xin Li,Hui Rao,Xianxiang Tian,Danni Wu,Zhenpeng Qiu,Guohua Zheng,Junjie Hu
Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies worldwide. Inhibition of the lipogenic enzymes involved in hepatic de novo lipogenesis can both effectively restrain proliferation of HCC cells in vitro and reduce the risk of hepatocarcinogenesis in vivo . Although a natural coumarin derivative osthole shows efficacy in suppressing cell proliferation and inducing apoptosis in cultured hepatoma cells and HCC xenograft tumors, the molecular mechanism by which osthole delays hepatocellular malignant transformation during lipogenesis-driven hepatocarcinogenesis remains unknown. Here, we evaluate the efficacy of osthole in a rapid HCC mouse model featuring excessive levels of hepatic steatosis established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Moreover, human hepatoma cell lines were employed for in vitro assessment. Hematoxylin and eosin staining , immunoblotting and immunohistochemistry were applied for mechanistic investigations. The results revealed that if osthole was administered in the early stage of AKT/c-Met-driven HCC, it led to disease stabilization. Moreover, osthole alleviated hepatic steatosis in the AKT/c-Met mice. Further evidence at the molecular level suggested that osthole reduced the expression of phosphor-extracellular signal-regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA) and Ki67 in livers of the AKT/c-Met mice. Mechanically, osthole efficiently repressed the phospho-AKT (Thr308) / ribosomal protein S6 (RPS6) / fatty acid synthase (FASN) signaling both in mice and in vitro . Altogether, this study suggests that osthole exerts its antilipogenic and antiproliferative efficacy by suppressing the AKT/FASN axis and ERK phosphorylation, which contributes to its capacity to delay hepatocarcinogenesis.
研究领域:
癌症研究
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分子生物学
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药理学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2022
·
IF 3.578
Qingxin Song,Shanxin Peng,Fengyuan Che,Xiaosong Zhu
Ferroptosis is implicated in various tumors, including glioblastoma. Artesunate (ART), an anti-malarial drug, exerted antitumor properties in several cancer types. However, the role of ferroptosis in the inhibiting effect of artesunate on glioblastoma remains unclear. The purpose of this study was to investigate the effects of ART on the ferroptosis of glioblastoma and to elucidate the underlying mechanisms. We found that ART inhibited the proliferation of glioblastoma cells in vitro and glioblastoma tumorigenesis in vivo . Characteristic changes of ferroptosis were observed in ART group, including GSH depletion, lipid peroxidation and iron overload. Meanwhile, the protein level of GPX4 were lower in ART group than that in control group. Ferrostatin-1, a ferroptosis inhibitor, could rescue the cell death induced by ART in U251 cells. Further examination of the mechanism revealed that the effect of ART on ferroptosis was partially governed by regulating iron homeostasis and p38 and ERK signaling pathway. These findings support that ART triggers ferroptosis in glioblastoma and might be a potential therapeutic agent for glioblastoma treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2018
·
IF 3.234
Shuli Fan,Xiang Gao,Peng Chen,Xu Li
Myricetin has been reported to promote osteogenic differentiation and inhibit osteoclastogenesis. The aim of this study was to investigate the potential effects of myricetin on glucocorticoid-induced osteoporosis (GIOP) both in vivo and in vitro . Male Sprague-Dawley (SD) rats were given dexamethasone (DEX, 0.1 mg/kg, s.c.) once daily and myricetin (1 mg/kg or 2.5 mg/kg, i.p.) once every other day for a total of five weeks. Body weight was recorded once a week. Bone mineral density (BMD), the activities or levels of bone turnover markers, and histological changes were assessed. MC3T3-E1 cells were incubated with DEX (1 μM) and myricetin (20 μM). Osteoblast proliferation, differentiation and mineralization were evaluated. U0126 was added to evaluate the involvement of the ERK signaling pathway. The results showed that myricetin increased body weight gain and inhibited DEX-induced reduction in BMD, enhanced alkaline phosphatase (ALP) activity, and upregulated osteocalcin (OCN), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) levels, whereas reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen (CTx) level. In addition, myricetin ameliorated histological changes in the femurs. In our in vitro studies, myricetin promoted osteoblast differentiation and mineralization in DEX-treated MC3T3-E1 cells, accompanied by increases in BMP2, Runx2, ALP, OCN, collagen type I alpha 1 (COL1A1) and osteopontin (OPN) levels. The promotion effects of myricetin on osteogenic differentiation and matrix mineralization were reversed by U0126. These results suggest that myricetin may alleviate DEX-induced osteoporosis by promoting osteogenic differentiation and matrix mineralization via the ERK signaling pathway.
研究领域:
药理学
·
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Zheng Zhao,Xue Yang
Paraquat (PQ) poisoning leads to irreversible fibrosis in the lungs with high mortality and no known antidote. In this study, we investigated the effect of the SET and MYND domain containing 2 (SMYD2) on PQ-induced pulmonary fibrosis (PF) and its potential mechanisms. We established an in vivo PQ-induced PF mouse model by intraperitoneal injection of PQ (20 mg/kg) and in vitro PQ (25 μM)-injured MLE-12 cell model. On the 15th day of administration, tissue injury, inflammation, and fibrosis in mice were evaluated using various methods including routine blood counts, blood biochemistry, blood gas analysis, western blotting, H&E staining, ELISA, Masson staining, and immunofluorescence. The findings indicated that AZ505 administration mitigated tissue damage, inflammation, and collagen deposition in PQ-poisoned mice. Mechanistically, both in vivo and in vitro experiments revealed that AZ505 treatment suppressed the PQ-induced epithelial-mesenchymal transition (EMT) process by downregulating GLI pathogenesis related 2 (GLIPR2) and ERK/p38 pathway. Further investigations demonstrated that SMYD2 inhibition decreased GLIPR2 methylation and facilitated GLIPR2 ubiquitination, leading to GLIPR2 destabilization in PQ-exposed MLE-12 cells. Moreover, rescue experiments conducted in vitro demonstrated that GLIPR2 overexpression eliminated the inhibitory effect of AZ505 on the ERK/p38 pathway and EMT. Our results reveal that the SMYD2 inhibitor AZ505 may act as a novel therapeutic candidate to suppress the EMT process by modulating the GLIPR2/ERK/p38 axis in PQ-induced PF.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2023
·Vol. 124
·期 4
·557-572
·
IF 4
Juan Gu,Xu Chu,Yujia Huo,Chaoyi Liu,Qingge Chen,Shengnan Hu,Yanyan Pei,Pu Ding,Sen Pang,Ming Wang
Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2021
·
IF 3.636
Ling Zhang,Li-na Yao,Wei Liu,An-qi Chen,Shi-min He,Mei-li Wei,Zi-xuan Fan,Da-long Ren
N-acetylcholine receptors (AChRs) are mainly distributed in the postsynaptic membrane and have been widely studied for their control of muscle contraction by regulating neural action potentials. However, the influences of AChRs on immune responses and potential mechanisms remain unclear. Here, we used the advantages of live imaging of zebrafish to explore the regulation process of AChRs on inflammatory responses. Pharmacologically activating of the receptor, we found that the expression of pro-inflammatory cytokines il-1β, il-6, tnf-α and il-8 was significantly up-regulated and neutrophil migration to injury sites was also significantly increased. However, these phenomena were reversed under antagonism of the receptor activity. Results showed that interfering with nAChRs functions did not significantly affect zebrafish motion behavior. Results also showed that activation and antagonism of nAChRs function could regulate the phosphorylation of ERK protein respectively. We further demonstrated that ERK participated in the regulation of AChRs in cytokines expression and neutrophils migration in zebrafish. This study preliminarily revealed the roles of AChRs in inflammatory processes and their potential mechanism, providing additional evidence of peripheral immune regulation by cholinergic receptors.
研究领域:
免疫学
·
神经科学
·
斑马鱼生物学
✓ 已验证
DOI
PubMed
高影响因子
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