JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2024
·
IF 11.2
Ce Zhu,Miaomiao He,Juehan Wang,Yong Huang,Wei Deng,Limin Liu,Ganjun Feng,Li Zhang,Yueming Song
Photothermal therapy (PTT) is a desirable way to attain on-demand hyperthermia owing to the heat generated by photothermal materials absorbing near-infrared) light. The mild heat (42 ± 0.5 °C) can not only accelerate bone tissue regeneration but also promote the release of bioactive ions from biomaterials. Based on this one-stone-two-birds strategy, a 3D printed PEEK-graphene composite scaffold (PG) with hydroxyapatite (HA) coating (PGH) for photothermally remote control of bone regeneration was well designed in this study. The results showed that the HA coating on PGH could release Ca 2+ and PO 4 3– ions easily under NIR irradiation, which was ascribed to the mild heat generated from graphene in the composite scaffold. The mild heat and the boosted Ca 2+ /PO 4 3– release could synergistically enhance the bone regeneration ability both in vitro and in vivo . The underlying mechanism was further explored and confirmed to be closely related to the upregulation of HSP 70, by which the MAPK/ERK signaling pathway was activated selectively. The favorable results demonstrate that the 3D-printed PEEK/graphene composite scaffold is promising in the applications of bone defect repair.
研究领域:
生物材料
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组织工程
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生物医学工程
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光热疗法
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骨再生
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产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 9
·3687
·
IF 4.6
Changli Fu,Mingjin Wang,Yuan Lu,Jie Pan,Yueting Li,Yongjun Li,Yonglin Wang,Aimin Wang,Yong Huang,Jia Sun,Chunhua Liu
AlthoughPolygonum orientaleL. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.Keywords:Polygonum orientaleL.;myocardial ischemia;MAPK signaling pathway
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ChemistryOpen
·
2024
·
IF 2.5
Wei Gao,Xiaoju Hua,Shengliang Liao,Zhikai Xiahou,Haikuan Yang,Lifang Hu,Yunyang Chi
Graphical Compound 3h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells.The results show that 3h induces cell-cycle arrest in the S phase. Additionally, 3h exerts a strong pro-apoptotic effect. Specifically, compound 3h reduces the phosphorylation of PI3K, AKT, and ERK, thereby inhibiting both the MAPK/ERK and PI3K/AKT signaling pathways. 2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N -arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC 50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h . Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.
研究领域:
药理学
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肿瘤学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2026
·
IF 4
Chen Xiaohui,Liang Gang,Wang Liangwei,Xie Zhilang,Li Zhongpan,Xiang Yulin,Li Rongzhu,Zhao Fulan,Chen Xiaojun,Huang Rui
This study leverages modern nanotechnology and molecular biological approaches to elucidate the scientific rationale underlying the traditional aqueous decoction practice of Lycopodium japonicum Thunb. (LJT) for knee osteoarthritis (KOA), establishing that the spontaneously formed nanoparticles may contribute to the pharmacologically active material foundation, and demonstrating that they confer therapeutic benefits predominantly through modulation of the MAPK/ERK inflammatory pathway, thereby positioning LJT-NPs as a potentially biocompatible, plant-derived nanotherapeutic candidate. LJT constituents were profiled by ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HR-MS) during aqueous decoction, and their self-assembly into supramolecular nanoparticles was observed by transmission electron microscopy (TEM). After optimization, LJT-derived nanoparticles (LJT-NPs) were prepared and biosafety was assessed in vivo . Systems pharmacology predicted the main pathway, and anti-osteoarthritic efficacy was validated in papain-induced KOA rat models and in vitro cellular assays. UPLC-HR-MS analysis indicated that lycopodium alkaloids were the primary components of LJT-NPs. In vivo profiling suggested that this endogenous nanosystem exhibits preliminary biosafety. Systems pharmacology revealed MAPK/ERK as the primary regulatory pathway, and experiments showed attenuated phosphorylation of RAF, MEK, ERK, and ELK1 in vivo and in vitro . Additionally, LJT-NPs ameliorated KOA at low doses via local joint injection. LJT-NPs showed therapeutic potential in KOA models, associated with attenuation of MAPK/ERK pathway hyperactivation. This positions LJT-NPs as a botanical-origin nanotherapeutic candidate with good safety and efficacy profiles. Graphical
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产品关联
DOI
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Yuan Liang,Qing Wang,Dianwen Zhang,Yiyao Gong,Qiuyan Jiang,Cong Ma,Libo Si,Tiehua Zhang,Jie Zhang,Zheng Ma
In this work, ginsenoside CK was confirmed as an EGFR tyrosine kinase inhibitor, with an IC 50 value of 32.58 ± 0.09 μM. Molecular docking showed that ginsenoside CK could fit into EGFR binding pocket, thereby acting as a ligand for EGFR. Ginsenoside CK inhibited proliferation of A549 cells as well as induced its apoptosis via downregulating anti-apoptotic factors and upregulating apoptosis induction factors. Ginsenoside CK alone and combined with gefitinib inhibited the tumor progression of A549 lung cancer xenografts in BALB/c nude mice. ELISA assay showed that ginsenoside CK combined with gefitinib alleviated the inflammatory response by suppressing the release of pro-inflammatory cytokines, indicating better inhibitory effects than ginsenoside CK or gefitinib alone. This work further confirmed that ginsenoside CK regulated the EGFR/MAPK/ERK signaling both in vitro and in vivo . In conclusion, ginsenoside CK can exhibit the anti-lung cancer effect via acting as an EGFR tyrosine kinase inhibitor.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
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2026
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IF 4.1
QiWei Yang,Lin Yu,Ran Tang,YiShan Peng,Tao Huang,HaoQi Chen,WenFeng Zhu,Qing Yuan,Wei Wang,Xiaojian Jiang,ZhiLi Ma,Lei Yuan,SuMei Wang,XiaoWen Wang,GenShu Wang
Environmental chemical exposure has emerged as an important modulator of cancer progression and therapeutic outcomes. Di-2-ethylhexyl phthalate (DEHP), a ubiquitous environmental plasticizer, has been widely recognized for its endocrine-disrupting effects; however, its impact on intracellular signaling reprogramming and cancer drug responsiveness remains incompletely understood. In this investigation, we aimed to elucidate the toxicological mechanisms by which DEHP alters cellular phenotypes and therapeutic sensitivity in hepatocellular carcinoma (HCC) cells. We demonstrate that DEHP exposure does not primarily promote cancer cell proliferation but instead induces epithelial–mesenchymal transition (EMT), leading to enhanced migratory and invasive capacities and reduced responsiveness to the tyrosine kinase inhibitor lenvatinib. Notably, integrative bioinformatic analyses combined with functional validation identified sperm-associated antigen 4 (SPAG4) as a key DEHP-responsive regulator mediating toxicant-induced cellular reprogramming. Mechanistic studies revealed that DEHP-induced upregulation of SPAG4 activates the MAPK/ERK signaling pathway, thereby driving EMT and attenuating lenvatinib responsiveness. Genetic silencing of SPAG4 or pharmacological inhibition of MAPK/ERK signaling effectively reversed DEHP-induced EMT and drug resistance. In conclusion, we highlight DEHP as a signaling-disrupting environmental toxicant that reprograms cancer cell states and modulates therapeutic responses through a SPAG4-dependent MAPK/ERK pathway. These findings provide mechanistic insight into how environmental chemical exposure can reshape intracellular signaling networks and influence cancer treatment outcomes, underscoring a previously underappreciated aspect of chemical toxicology.
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DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2026
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IF 1.8
Lin Zhang,Guanke Liu,Bingyang Zhang,Shiqing Song,Xiao Liu,Tie Yao,Feng Qiu,Feng Zhao
Two new secoiridoid glycosides, gentscaside A (1) and gentscaside B (2), were isolated along with three known compounds gentiopicroside (3), rindoside (4), gentiotrifloroside (5), from the Rhizomes of Gentiana scabra. The structures of the new compounds were determined by comprehensive NMR analysis, and their absolute configurations were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The five compounds were evaluated for their anti-inflammatory activity (NO inhibitory activity in LPS-stimulated macrophages). Compounds 1, 4 and 5 showed significant inhibitory effects on LPS-induced NO release in RAW 264.7 cells. The IC50 values are 2.15 μM, 3.02 μM and 6.87 μM, respectively. Additionally, the potential anti-inflammatory mechanism of the active new compound 1 was explored.
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产品关联
DOI
PubMed
高影响因子
Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
·
IF 1.3
Hongji Wang,Lisha Chen,Juping Xing,Xiangchao Shi,Changshui Xu
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Marine Drugs
·
2020
·Vol. 18
·期 7
·375
·
IF 4.073
Mi Zhou,Bo-Rong Peng,Wenjing Tian,Jui-Hsin Su,Guanghui Wang,Ting Lin,Dequan Zeng,Jyh-Horng Sheu,Haifeng Chen
12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine spongeHippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77.Keywords:12-deacetyl-12-epi-scalaradial;HeLa cells;apoptosis;Nur77;MAPK/ERK pathway
研究领域:
海洋化学
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癌症研究
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Caihong Wang,Wenhao Huang,Jiebo Lin,Fang Fang,Xuedong Wang,Huili Wang
Triclosan (TCS) is widely used in personal care products, and its chronic exposure leads to severely toxic effects in zebrafish ( Danio rerio ). PKCα, Nrf2 and p53 are three important signaling pathways concerned with cell development. Herein, we speculated on and verified a novel TCS regulatory pathway: (1) TCS acted on GPER (G-protein-coupled estrogen receptor) to activate MAPK/ERK pathway, further resulting in the expression changes of protein kinase C (PKC) family; (2) PKC participated in Nrf2 phosphorylation; (3) The expression of miR-125b was regulated by Nrf2; and (4) The expression changes of related genes in the PKCs-Nrf2-ARE pathway showed the specificity of zebrafish tissue and organ. TCS exposure led to down-regulation of the Nrf2 and phosphorylated Nrf2(Ser40) protein in diencephalon nucleus, stratum marginale and stratum centrale areas in adult zebrafish brain. The phosphorylated Nrf2(Ser40) was mainly expressed in PGz area, while it was not the case for Nrf2. Both Nrf2 and phosphorylated Nrf2 were activated by TCS exposure; however, the changing trend of PKCs was opposite to that of Nrf2 in the liver. Both DAPI staining and Merge images demonstrated that TCS induced oxidative phosphorylation, and phosphorylated Nrf2 is translocated into the nucleus as the transcription factor to regulate gene transcription in liver and brain. Nrf2 over-expression increased accumulation of lipid droplets in yolk, brain and liver, resulting from the upregulation of pri-miR-125b1, pri-miR-125b3, but not pri-miR-125b2. These findings reveal the upstream regulation mechanism of miR-125b for TCS-induced fat-metabolism disorder from the regulatory perspective of the pri-miR-125b promoter region.
研究领域:
毒理学
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分子生物学
·
水生生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Genes
·
2022
·Vol. 13
·期 7
·1113
·
IF 4.141
Biying Jiang,Baolong Cao,Zhichun Zhou,Zejiao Li,Can Lv,Jiannan Zhang,Heyuan Zhang,Yajun Wang,Juan Li
Adrenoceptors are suggested to mediate the functions of norepinephrine (NE) and epinephrine (EPI) in the central nervous system (CNS) and peripheral tissues in vertebrates. Compared to mammals, the functionality and expression of adrenoceptors have not been well characterized in birds. Here, we reported the structure, expression, and functionality of chicken functional α2A-adrenoceptor, namedADRA2A. The cloned chickenADRA2AcDNA is 1335 bp in length, encoding the receptor with 444 amino acids (a.a.), which shows high amino acid sequence identity (63.4%) with its corresponding ortholog in humans. Using cell-based luciferase reporter assays and Western blot, we demonstrated that the ADRA2A could be activated by both NE and EPI through multiple signaling pathways, including MAPK/ERK signaling cascade. In addition, the mRNA expression ofADRA2Ais found to be expressed abundantly in adult chicken tissues including thyroid, lung, ovary and adipose from the reported RNA-Seq data sets. Moreover, the mRNA expression ofADRA2Ais also found to be highly expressed in the granulosa cells of 6–8 mm and F5 chicken ovarian follicles, which thus supports that ADRA2A signaling may play a role in ovarian follicular growth and differentiation. Taken together, our data provide the first proof that the α2A-adrenoceptor is functional in birds involving avian ovarian follicular development.Keywords:chickens;α2-adrenoceptor;ADRA2A
研究领域:
分子生物学
·
内分泌学
·
生殖生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2024
·
IF 2.8
Fang Liang,Cheng Hongyan,Chen Weidong,Peng Can,Liu Yuanxu,Zhang Caiyun
ObjectivesThe aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer’s disease (AD) rats.MethodsThe therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism.Key findingsThe results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats.ConclusionsTSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）