Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 31
·6912-6924
·
IF 5.344
Lei Liu,Xianling Gao,Xiaoyu Li,Guanglin Zhu,Nanying Li,Xuetao Shi,Yingjun Wang
Bioceramic–biopolymer composites have been used extensively as bone tissue engineering scaffolds due to their bioactive properties. However, composite scaffolds are insufficient in inducing osteogenic differentiation of stem cells. In this study, a strategy for the local delivery of bioactive factors by coating calcium alendronate (ALC) on the surface of composite scaffolds was systematically evaluated for the first time. The coated ALC not only displayed excellent cytocompatibility and cell adhesion properties but also resulted in the significant upregulation of osteogenic related gene expression, osteogenic related protein levels, alkaline phosphatase (ALP) activity and calcium deposition of ADSCs. Furthermore, our results suggested that the molecular mechanism of ADSC osteogenic differentiation induced by the constructed ALC may be related to the integrin binding and the activation of FAK/ERK signalling pathways. These findings suggested that ALC-coated composite scaffolds can serve as bone tissue engineering scaffolds, providing a simple and universal method to improve the osteogenic differentiation of ADSCs by calcium phosphate-containing composite materials.
研究领域:
组织工程
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生物材料
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干细胞生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·Vol. 74
·期 29
·22784-22797
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IF 6.7
Cheng Xin,Wang Jiaxing,Tan Haoyang,Ji Yaxin,Yu Xiaoqing,Hu Jiahuan,Li Siyao,Kang Huijie,Zhang Shuai,Xuanpan Ding,Jiao Wenjing,Fan Honggang,Zhao Yuan
Chronic
stress (CS) represents a pivotal environmental trigger
for depression. It induces depression-like behaviors primarily by
disrupting hypothalamic–pituitary–adrenal (HPA) axis
homeostasis and impairing hippocampal synaptic plasticity. Flavonoids
are abundant in human diet and possess significant neuroprotective
potential. We screened a library of 339 flavonoid compounds. Daidzein
(DAI) was identified as the lead compound. Subsequently, in rats subjected
to chronic restraint stress (CRS), DAI administration effectively
ameliorated depression-like behaviors, and attenuated hippocampal
histopathological damage. Network pharmacology and molecular docking
analyses suggested that ERK-related signaling may be involved in the
protective effects of DAI, and molecular dynamics simulations supported
the stability of the DAI-ERK2 complex. Furthermore, DAI activated
the ERK/CREB/BDNF signaling cascade, an effect that was partially
reversed by ERK inhibitor intervention. Notably, DAI also enhanced
dendritic complexity and spine density in hippocampus. In summary,
our study demonstrates that DAI alleviates stress-induced synaptic
plasticity damage through the ERK/CREB/BDNF signaling pathway.
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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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MOLECULAR CARCINOGENESIS
·
2026
·
IF 3.5
Ningyi Xian,Ziwei Wang,Bingqing Wang,Xiaofei Wang,Yan Zheng
Cutaneous squamous cell carcinoma (cSCC) is a malignant skin cancer which is derived from epidermal keratinocytes, and long-term exposure to ultraviolet rays is its main risk factor. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a crucial gene for the formation and stability of collagen intermolecular cross-links, being vital in the development of cancer. Nevertheless, the interaction between cSCC and PLOD2 has not been elucidated. Here, we found PLOD2 upregulated in human cSCC. Its knockdown in cSCC cells suppressed proliferation, migration, invasion, and angiogenesis while inducing apoptosis and cell cycle arrest; overexpression promoted these malignant phenotypes. In mouse xenografts, PLOD2 knockdown inhibited tumor growth and collagen deposition. Furthermore, in a DMBA/TPA-induced carcinogenesis model, topical PLOD2 inhibition by minoxidil suppressed tumor development as well. Mechanistically, our studies revealed that PLOD2 acts as a key downstream effector of STAT3 to activate ERK and AKT signaling evidenced by rescue experiments. As a result, our study not only establishes the STAT3/PLOD2/ERK-AKT axis as a key driver of cSCC but also identifies the clinically approved drug minoxidil as a potent PLOD2 inhibitor, demonstrating immediate promise as a repurposed therapeutic agent.
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BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
·
IF 3.5
Lu Liu,Zhendong Song,Guangjin Fan,Linlin Lou,Yuanxiang Wang,Xiaolei Zhang,Xiao-Feng Xiong
KRAS serves as a vital regulator for cellular signaling and drives tumor pathogenesis after mutation. Despite extensive research efforts spanning several decades, targeting KRAS is still challenging due to the multiple KRAS mutations and the emergence of drug resistance. Interfering the interactions between KRAS and SOS1 is one of the promising approaches for modulating KRAS functions. Herein, we discovered small-molecule SOS1 agonists with novel indazole scaffold. Through structure-based optimization, compound 11 was identified with high SOS1 activation potency (p-ERK EC 50 = 1.53 μM). In HeLa cells, compound 11 enhances cellular RAS-GTP levels and exhibits biphasic modulation of ERK1/2 phosphorylation through an on-target mechanism and presents the therapeutic potential to modulate RAS signaling by activating SOS1.
研究领域:
肿瘤学
·
分子生物学
·
药物化学
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Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Xiangdong Qu,Jirong Xie,Youyang Zhang,Zhimin Wang
Solamargine has unique antitumor efficacy in a variety of cancers. The study is to explore the role of solamargine in cervical cancer. HeLa and SiHa cells were exposed to solamargine treatment at divergent concentrations (0, 5, 10, and 20 μ M). The antitumor role of solamargine in cervical cancer cells was determined by cell counting kit 8 (CCK-8), colony formation, scratch test, transwell assay, and western blot. The expression of mRNAs regulating the extracellular regulated protein kinases (Erk) pathway in solamargine-treated cells was detected by qRT-PCR. Rescue experiments were conducted to explore the effect of C-X-C motif chemokine ligand 3 (CXCL3). Following that, we inhibited Erk1/2 by PD98059 to investigate the interplay between CXCL3 and Erk pathway in solamargine-treated cells by measuring migration, invasion, and related matrix metalloproteinase (MMP) expressions. Solamargine inhibited the viability, proliferation, migration, and invasion of cervical cancer cells in a dose-dependent manner. The expression of p-Erk1/2 was downregulated by solamargine. CXCL3 overexpression abrogated the antitumor effect of solamargine on cervical cancer cells. The inhibition of the Erk signaling pathway restored the inhibiting role of solamargine which interfered with CXCL3 overexpression, in invasion, migration, and expressions of MMP-2 and MMP-9 in cervical cancer cells. Moreover, solamargine inhibited the growth of tumor in vivo xenograft model. Solamargine alleviated proliferation and metastasis of cervical cancer cells by blocking the CXCL3-mediated Erk signaling pathway.
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
·
药理学
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2026
·Vol. 78
·期 2
·
IF 3.7
Wang Baoying,Liu Hui,Zhang Changjing,Yan Xiangli,Xu Erping,Bai Ming,Li Yucheng
ObjectivesFormononetin (FMN) is known for its significant neuroprotective effects, this study aims to investigate the antidepressant potential and underlying mechanisms of FMN.MethodsAntidepressant efficacy was evaluated in corticosterone (CORT)-induced depression models. In vivo, CORT-exposed mice received FMN to assess behavioral and hippocampal changes (dendritic spine density, synaptic markers: MAP-2/GAP-43). In silico, network pharmacology and molecular docking predicted FMN’s binding affinity and enriched pathways. In vitro, HT22 cells pretreated with FMN (10 μM, 6 h) were subjected to CORT injury, with mechanistic validation via ERα antagonist (MPP) and ERK inhibitor (PD98059).Key findingsFMN alleviated depressive-like behaviors and preserved hippocampal integrity in mice. Bioinformatics analysis revealed FMN’s strong binding to ER subtypes and enrichment in estrogen/MAPK pathways. In vitro, FMN pretreatment activated the ERK-CREB-BDNF axis in CORT-injured HT22 cells, enhancing neuronal survival and synaptic function. The activation was ERα/ERK-dependent, as evidenced by the abolition of protective effects following pharmacological inhibition with MPP (ERα antagonist) or PD98059 (ERK inhibitor). Concomitantly, in vivo FMN treatment restored hippocampal p-ERK/ERK ratios in mice, directly corroborating the ERK-CREB-BDNF pathway activation and highlighting its efficacy in reversing CORT-induced signaling deficits.ConclusionFMN exerts antidepressant effects via ERα-mediated neurotrophic signaling (ERK-CREB-BDNF), offering a mechanistic foundation for natural antidepressant development.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Junhui Yu,Ningning Shao,Jianming Yang,Long Yang,Kaiwen Hong,Yuzhu Chen,Xiaoming Zhao,Hongzhi Yu,Tao Zhang,Jinrui Dong
Introduction Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with oxidative stress and ferroptosis, leading to liver injury and fibrosis. Garlic, renowned for its antioxidant and hepatoprotective properties, is commonly used in traditional medicine. Ultrafine powder technology enhances the physicochemical properties of natural products, improving their bioavailability and efficacy. This study explores the protective effects of ultrafine garlic powder (UGP) on NASH and its underlying mechanisms. Methods In this study, UGP was prepared by high-speed particle collision technology and compared with traditional garlic powder (TGP). Results UGP exhibited a particle size (d(0.5) of approximately 4 μm) that is 30 times smaller than TGP, showing significantly smaller particle size and lower contact angle (UGP=59.775°vs TGP=83.545°). UGP also demonstrated improved solubility and dispersibility, along with an enrichment of key organosulfur compounds such as allicinAllicin, Alliin, SAC, and GSAC. In vitro, UGP significantly reduced palmitic acid-induced ROS production (n=4, p< 0.0001), prevented mitochondrial dysfunction (n=4, p=0.0035), and thereby reduced hepatic stellate cell activation. UGP lowered intracellular Fe2+ levels in hepatocytes from 68.72% to 34.48% (n=4) and significantly protected hepatocytes from erastin-induced ferroptosis (cell viability: UGP treatment 23.46% vs erastin stimulation 53.91%, n = 4, p <0.0001).In the acute liver fibrosis model induced by methionine- and choline-deficient diet supplemented with 60 kcal% fat (CDHF), UGP significantly improved liver histology. Compared to the model group, the liver/body weight ratio of mice was significantly restored (n=4, p<0.0001), and histopathological staining showed a substantial improvement in liver damage. Biochemically, UGP significantly reduced the levels of liver collagen, triglycerides, and cholesterol (n = 6, p < 0.0001). Fibrosis-related mRNA and pro-inflammatory mRNA expression were significantly decreased. Western blot results showed that UGP significantly inhibited the activation of p-ERK signaling. In the chronic liver fibrosis model induced by a diet with 60 kcal% fat (HFD), UGP demonstrated similar therapeutic effects. RNA-seq analysis revealed that UGP modulated key pathways, including fatty acid metabolism and the MAPK signaling pathway, and suppressed ROS production, further highlighting its therapeutic potential in NASH treatment. Discussion Taken together, these data suggest that UGP alleviates NASH by inhibiting hepatocyte ferroptosis and modulating ERK-dependent oxidative stress, supporting its potential as a therapeutic agent.
研究领域:
药理学
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肝病学
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营养科学
·
氧化应激研究
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天然产物
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分子生物学
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Cancer Cell International
·
2026
·
IF 7
Ni Jie,Gao Aidi,Chen Ying,He Chao,Wang Xixi,Savelyeva Natalia,Dong Xin,Wang Yiqiang,Wang Mu
Background Despite significant advances in the treatment of clear cell renal cell carcinoma (ccRCC) over the past two decades, therapeutic intervention for patients at advanced or metastatic stages remains a clinical hurdle. Emerging evidence highlights aberrant CD70 expression during tumor progression, supporting its potential as a therapeutic target in advanced ccRCC. However, the molecular mechanisms underlying CD70-mediated metastatic processes remain poorly defined. Methods CD70 was knocked out or overexpressed in three ccRCC cell lines, and its role in tumor progression was assessed using in vitro migration and invasion assays, as well as in vivo tumorigenesis and metastasis models . Mass spectrometry-based proteomics was performed to identify differentially expressed proteins and potential pathway dysregulation following CD70 depletion. Co-immunoprecipitation (Co-IP) assays confirmed the CD70-NF1 interaction, and NF1 knockdown in CD70-knockout cells was conducted to reverse the effects of CD70 depletion on Ras/ERK signaling, migration, invasion, and epithelial-mesenchymal transition (EMT)-related features. Expression of EMT-related marks were evaluated by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). Results CD70 was significantly upregulated in ccRCC tissues and correlated with poor survival outcomes. CD70 knockout markedly inhibited in vitro cell migration and invasion, as well as in vivo tumor growth and metastasis. Mechanistically, CD70 depletion was associated with increased neurofibromin 1 (NF1) expression in ccRCC cells; CD70 knockout resulted in robust NF1 induction, which in turn suppressed Ras/ERK signaling and downstream EMT-related molecular alterations. Notably, NF1 knockdown largely reversed the inhibitory effects of CD70 knockout on these key molecular and functional phenotype changes. Conclusions Our findings uncover a novel CD70-NF1-Ras/ERK axis that contributes to ccRCC progression and metastasis, involving suppression of NF1 and subsequent activation of the Ras/ERK signaling pathway, which further promotes EMT and enhances metastatic capacity. These insights provide a mechanistic foundation for targeting CD70 as a potential therapeutic strategy in advanced ccRCC. Notably, we propose that CD70-targeted therapy may be more effective when combined with agents blocking adaptive escape pathways (e.g., Ras/ERK inhibitors), a hypothesis generated by mechanistic rescue and pharmacologic inhibition in vitro, which require further preclinical validation to confirm synergistic efficacy and clinical viability.
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PHYTOMEDICINE
·
2020
·
IF 4.268
Xiaotian Qi,Jing Liu,Xiaoyu Li,Mengyue Fan,Nana Huang,Rong Sun
Background Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical, cancer chemotherapy induced neutropenia (CCIN) infection and infection-related mortality is high for lack of functionally mature neutrophils . Generating functional neutrophils is new therapeutic approaches to reduce CCIN-associated infection and mortality. Saikosaponin a (SSA) is one of the major bioactive components of Radix Bupleuri (RB) and exerts immunoregulatory effects. Purpose The present study aims to investigate the efficacy and mechanism of SSA in CCIN therapy. Methods SSA was applied both in vitro and in vivo to assess the efficacy of CCIN therapy. The differentiation of neutrophils was measured by Nitroblue tetrazolium (NBT) reduction assay and Giemsa staining assay. The neutrophil differentiation related real-time transcription factors were detected by quantitative PCR (RT-qPCR) and Western Blot . Bacteria killing assay was used to assess the ability of fighting infection. Network pharmacology was employed to explore the mechanism network, and the predicted pathways were validated by Western Blot. Results We found that SSA contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo . Network pharmacology prediction showed 55 pathways were predicted involved in SSA against CCIN. Further validation showed that CBL-ERK1/2 pathway was activated by SSA, which could upregulate PU.1 and CEBPβ expression leading to neutrophil differentiation. Conclusions Our findings suggest a natural regimen SSA regenerates microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2 pathway, providing a rationale for future therapeutic approaches.
研究领域:
药理学
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肿瘤学
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免疫学
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分子生物学
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细胞生物学
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BEHAVIOURAL BRAIN RESEARCH
·
2024
·
IF 2.6
Chenjie Ge,Shiliang Wang,Xuqi Wu,Lilei Lei
Background Depression is a common psychiatric disorder with limited effective treatments. Research suggests that depression involves apoptosis mechanisms. Quercetin (QUE) has been reported to have anti-apoptotic activities. In this study, we aimed to investigate the effects and mechanisms of QUE in chronic unpredictable mild stress (CUMS)-induced depression. Methods After establishing mouse models of CUMS-induced depression, the mice were randomly assigned into four groups: control, CUMS, CUMS+QUE, and CUMS+Fluoxetine (FLX). The body weight of the mice was measured during the study. Then, depression-associated behaviors were evaluated using the sucrose preference test (SPT), novelty suppressed feeding test (NSFT), forced swim test (FST) and tail suspension test (TST). Apoptosis in the hippocampus and prefrontal cortex was determined using flow cytometry. Bcl-2 and Nrf2 protein expressions in the hippocampus and prefrontal cortex were also detected. Furthermore, Western blot was used to measure the protein levels of p-ERK, ERK, p-CREB, CREB, and Nrf2 in brain tissues. Results QUE or FLX administration increased the body weight of the CUMS mice. Behavioral tests indicated that CUMS mice developed a state of depression, but QUE or FLX treatment improved their depression-associated behaviors. Meanwhile, QUE or FLX treatment decreased apoptosis in the hippocampus and prefrontal cortex. Furthermore, the decreased Nrf2 protein expression, ERK and CREB phosphorylation in CUMS group were enhanced by QUE or FLX administration. Conclusion QUE could attenuate brain apoptosis in mice with CUMS-induced depression, and the mechanism may be related to the ERK/Nrf2 pathway, indicating that QUE could be a potential treatment for depression.
研究领域:
神经科学
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药理学
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EXPERIMENTAL DERMATOLOGY
·
2020
·Vol. 30
·期 7
·932-942
·
IF 3.368
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory disease characterized by abnormal hyperproliferation and differentiation. The object of this study is to explore the role of microRNA-215-5p in psoriasis-like inflammation. The expression of miR-215-5p was found to be down-regulated in pro-inflammatory factor-stimulated HaCaT cells and imiquimod (IMQ)-treated skin tissues. Overexpression of miR-215-5p suppressed the proliferation and cell cycle progression of HaCaT cells. Further, miR-215-5p agomir alleviated the disease severity, pathological features and Ki67 positive cells in IMQ-treated mice. Luciferase assay confirmed that miR-215-5p could bind to the 3′UTR of DYRK1A. The in vitro and in vivo results showed that miR-215-5p negatively regulates DYRK1A, which further inhibited EGFR and its downstream signalling pathways, AKT and ERK. Collectively, our results provide evidence that overexpression of miR-215-5p inhibits the proliferation of HaCaT cells and alleviates psoriasis-like inflammation partly by DYRK1A mediated inhibition of the EGFR signalling pathway. miR-215-5p may serve as a novel small molecule for therapeutic intervention in psoriasis.
研究领域:
分子生物学
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皮肤科
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炎症性疾病
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微小RNA研究
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高影响因子
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