CELL BIOLOGY AND TOXICOLOGY
·
2025
·Vol. 41
·期 1
·1-29
·
IF 5.9
Tian Sirui,Yu Haiyang,Yang Ruoxuan,Wang Heshi,Zhao Baohong,Wang Danning
Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies. Graphical 1. IGFBP3 enhances ADSC function in STI repair by activating ITGB1 and ERK pathways. 2. High IGFBP3 expression promotes ADSC differentiation into epithelial cells, improving tissue regeneration. 3. Single-cell multiomics and 3D bioprinting validate IGFBP3’s role in advancing STI treatment. 4. Findings present IGFBP3 as a promising molecular target for clinical STI therapy.
研究领域:
再生医学
·
分子生物学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acupuncture in Medicine
·
2017
·
IF 2.156
Chunxiao Wu,Chun Li,Guoping Zhou,Lu Yang,Guimei Jiang,Jing Chen,Qiushi Li,Zhulian Zhan,Xiuhong Xu,Xin Zhang
ObjectiveTo explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R).Methods160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group. Eight rats from each group were sacrificed at the following time points: 2 hours, 6 hours, 1 day, 3 days and 1 week. Neurological function was assessed using neurological deficit scores, morphological examination was performed following haematoxylin-eosin staining of cortical tissues, and apoptotic indices were calculated after terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling. Cortical protein and mRNA expression of p-ERK and ERK were measured by immunohistochemistry and real-time quantitative PCR, respectively.ResultsCompared with the I/R group, neurological deficit scores and apoptotic indices were lower in the I/R+EA group at 1 and 3 days, whereas mRNA/protein expression of ERK/p-ERK was higher in the EA group at all time points studied.ConclusionOur results suggest that EA can alleviate neurological deficits and reduce cortical apoptosis in rats with I/R injury. These anti-apoptotic effects may be due to upregulation of p-ERK. Moreover, apoptosis appeared to peak at 1 day after I/R injury, which might therefore represent the optimal time point for targeting of EA.
研究领域:
神经科学
·
分子生物学
·
中医学
✓ 已验证
DOI
高影响因子
Cancer Management and Research
·
2020
·
IF 2.886
Yanshi Wang,Shaojie Yang,Shanshan Zhang,Xin Wu
Purpose To evaluate the anti-tumor effects of oxymatrine in vulvar squamous cell carcinoma (VSCC) cells and to explore the underlying mechanisms. Methods We selected SW962 and A431 VSCC cell lines. Cell proliferation was examined using MTT assay. Cell cycle and apoptosis were detected using flow cytometry. Migration and invasion were evaluated using transwell and wound-healing assays. The relevant protein expression and signaling pathways were analyzed using Western blotting. Results Oxymatrine inhibited the proliferation of SW962 and A431 VSCC cells in a time- and dose-dependent manner. Oxymatrine induced cell cycle arrest in the G2/M phase by increasing the protein expression of P21 and decreasing levels of cyclin B1 and CDC2. Oxymatrine upregulated the expression of cleaved-caspase 3 and BAX and downregulated the expression of BCL2, which led to an increase in apoptosis. Oxymatrine also suppressed the migration and invasion of SW962 and A431 cells by reducing levels of MMP2 and MMP9. After treatment with oxymatrine or a RAS inhibitor (salirasib), expression levels of RAS, p-RAF, p-MEK, p-ERK, C-MYC, and MMP2 were reduced. When TGF-β1 was used to stimulate SW962 and A431 cells, the expression of the above proteins increased; this increase was reversed by using oxymatrine or salirasib again. Conclusion Oxymatrine inhibits proliferation and migration of VSCC cells by blocking the RAS/RAF/MEK/ERK pathway.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
研究领域:
分子生物学
·
细胞生物学
·
儿科
·
肠道生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Can Liu,Lei Fan,Zhenming Tian,Huiquan Wen,Lei Zhou,Pengfei Guan,Yian Luo,Chuncheung Chan,Guoxin Tan,Chengyun Ning,Limin Rong,Bin Liu
Conductive scaffolds have been shown to exert a therapeutic effect on patients suffering from peripheral nerve injuries (PNIs). However, conventional conductive conduits are made of rigid structures and have limited applications for impaired diabetic patients due to their mechanical mismatch with neural tissues and poor plasticity. We propose the development of biocompatible electroconductive hydrogels (ECHs) that are identical to a surgical dressing in this study. Based on excellent adhesive and self-healing properties, the thin film-like dressing can be easily attached to the injured nerve fibers, automatically warps a tubular structure without requiring any invasive techniques. The ECH offers an intimate and stable electrical bridge coupling with the electrogenic nerve tissues. The in vitro experiments indicated that the ECH promoted the migration and adhesion of the Schwann cells. Furthermore, the ECH facilitated axonal regeneration and remyelination in vitro and in vivo through the MEK/ERK pathway, thus preventing muscle denervation atrophy while retaining functional recovery. The results of this study are likely to facilitate the development of non-invasive treatment techniques for PNIs in diabetic patients utilizing electroconductive hydrogels.
研究领域:
生物医学工程
·
神经科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 3
·2847-2856
·
IF 4.522
Jiabing Zhang,Leili Wang,Wei Xie,Shunying Hu,Hao Zhou,Pingjun Zhu,Hang Zhu
Septic cardiomyopathy is associated with mitochondrial damage and endoplasmic reticulum (ER) dysfunction. However, the upstream mediator of mitochondrial injury and ER stress has not been identified and thus little drug is available to treat septic cardiomyopathy. Here, we explored the role of B-cell receptor-associated protein 31 (BAP31) in septic cardiomyopathy and figure out whether melatonin could attenuate sepsis-mediated myocardial depression via modulating BAP31. Lipopolysaccharide (LPS) was used to establish the septic cardiomyopathy model. Pathway analysis was performed via western blot, quantitative polymerase chain reaction and immunofluorescence. Mitochondrial function and ER stress were detected via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. After exposure to LPS, cardiac function was reduced due to excessive inflammation response and extensive cardiomyocyte death. Mechanistically, melatonin treatment could dose-dependently improve cardiomyocyte viability via preserving mitochondrial function and reducing ER stress. Further, we found that BAP31 transcription was repressed by LPS whereas melatonin could restore BAP31 expression; this effect was dependent on the MAPK-ERK pathway. Inhibition of the ERK pathway and/or knockdown of BAP31 could attenuate the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress. Altogether, our results indicate that ERK-BAP31 pathway could be used as a critical mediator for mitochondrial function and ER homeostasis in sepsis-related myocardial injury. Melatonin could stabilize BAP31 via the ERK pathway and thus contribute to the preservation of cardiac function in septic cardiomyopathy.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PeerJ
·
2021
·
IF 2.984
Yufan Zhu,Zhiqiang Yang,Yuanlong Xie,Min Yang,Yufeng Zhang,Zhouming Deng,Lin Cai
Objective This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular mechanism. Material and Methods 143B and U2OS osteosarcoma cells were treated with gradient concentrations of daidzein, and MTT assay was used to determine the cell proliferation capacity and IC 50 . Hoechst 33342 staining and Annexin V-FITC/PI detection were used to determine apoptosis. Cell cycle was analyzed by flow cytometry, and migration ability were detected by transwell assays and scratch wound assay. An osteosarcoma xenograft mice model was applied to investigate the effect of daidzein on osteosarcoma in vivo . Systematic pharmacology and molecular modeling analysis were applied to predict the target of daidzein to osteosarcoma, and the target Src was verified by western blotting. We also observed the effect of daidzein on cell proliferation and apoptosis of Src-overexpressing osteosarcoma cells. Results In vitro , daidzein significantly inhibited 143B and U2OS osteosarcoma cell proliferation and migration, and induced cell cycle arrest. In vivo , daidzein exerts antitumor effects in osteosarcoma xenograft mice. After systematic screening and analysis, Src-MAPK signaling pathway was predicted as the highest-ranked pathway. Western blot demonstrated that daidzein inhibited phosphorylation of the Src-ERK pathway in osteosarcoma cells. Also, overexpression of Src could partially reverse the inhibitory effects of daidzein on osteosarcoma cell proliferation. Conclusion Daidzein exerts an antitumor effect on osteosarcoma, and the mechanism may be through the Src-ERK pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Bai Yang,Chen Jiaqi,Hu Weijian,Wang Lei,Wu Yulian,Yu Shi’an
Background: Silibinin is widely utilized drug in various cancer treatments, though its application in cholangiocarcinoma has not yet been explored. For the first time, we evaluated the anticancer potential and underlying molecular mechanism of silibinin in treatment of cholangiocarcinoma treatment.Methods: HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were exposed to various concentrations of silibinin for indicated times. Cell viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was determined through the use of colony formation and 5-Ethynyl-2′- deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining assay and flow cytometry (FCM). The protein levels of extracellular regulated protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through western blotting (WB). Mitochondrial membrane potential changes were determined via 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1). A cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor activity of silibinin in vivo.Results: Inhibition of the ERK protein by silibinin led to a significant decrease in mitochondrial membrane potential, which, in turn, caused Cytochrome C to be released from the mitochondria. The activation of downstream apoptotic pathways led to apoptosis of cholangiocarcinoma cells. In general, silibinin inhibited the growth of cholangiocarcinoma cell line xenograft tumors.Conclusions: Silibinin is able to inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma treatment.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
·
2016
·
IF 2.135
Wu Li,Minqiang Liu,Jianping Xie
The pathogenesis of tuberculosis, caused by Mycobacterium tuberculosis, is largely because of the pathogen's successful entry and survival within macrophages. We predicted that rv3369, a gene encoding a conserved protein, might play a role in the interactions with host cells. To test this, rv3369 gene was heterologously expressed in a nonpathogenic fast-growing Mycobacterium smegmatis strain. The recombinant strain survives better than the control within macrophages, accompanied by more host cell death and a marked higher secretion of interleukin-1β (IL-1β). Furthermore, pharmacological inhibition experiments showed that the NF-κB and ERK pathways were involved in the Rv3369-triggered IL-1β changes. These results provided evidence for the engagement of Rv3369 in the interaction between mycobacteria and host.
研究领域:
微生物学
·
免疫学
·
感染病学
·
分子生物学
·
细胞生物学
·
病原生物学
✓ 已验证
DOI
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 2
·e70067
·
IF 3.3
Jingting Zeng,Zhenshuo Luo,Tiansheng Zhao,Chunhua Xia,Fanglan Liu,Na Li,Lailiang Qu,Cheng Wang
Aberrant activation of the RAS/RAF/MEK/ERK pathway occurs in more than 30% of human cancers. As part of this pathway, MEK1/2 has crucial roles in tumorigenesis, cell proliferation, and inhibition of apoptosis. At present, a number of MEK1/2 inhibitors are approved for the treatment of melanoma. However, MEK1/2 inhibitors have poor single-drug efficacy in the treatment of solid tumors and are prone to drug resistance. A series of compounds containing a diarylamine skeleton and phenylacrylamide (acrylamide) have been designed and synthesized in this paper. The most promising compound M15 showed good inhibitory activity of MEK1 (IC 50 = 10.29 nM) and good inhibitory effect on three types of solid tumor cells: MDA-MB-231(IC 50 = 2.76 μM), HepG2 (IC 50 = 2.57 μM) and A549 (IC 50 = 5.40 μM). At the same time, M15 was less toxic to human normal cells (MCF-10A IC 50 > 20 μM) and has certain stability of liver microsomes in vitro (human, t 1/2 = 27.9 min; rat, t 1/2 > 60 min). It can induce apoptosis of MDA-MB-231 cells and slow down their migration. Therefore, compound M15 acts as a novel MEK1/2 inhibitor and may be a promising candidate for solid tumor intervention.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Hongliang You,Dao Wang,Linlin Wei,Jiao Chen,Huanhuan Li,Yufeng Liu
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectively decreased the concentration of intracellular iron in ALL cells. DFO inhibited proliferation, induced apoptosis, and obstructed cell cycle of ALL cells, whereas DFO and dextriferron (Dex) used in combination significantly decreased the sensitivity of ALL cells to DFO. Reactive oxygen species (ROS) level was reduced in ALL cells treated with DFO, and the combination of DFO and Dex reversed the effects of DFO. In vivo, DFO inhibited mouse tumor growth. Besides, cyclinD1, β-catenin, c-Myc, hypoxia inducible factor 1 (HIF-1), p-p38MAPK, and p-ERK1/2 protein levels were significantly downregulated, and the levels of prolyl hydroxylase-2 (PHD-2) were upregulated after treated with DFO, whereas Dex treatment reversed those in vivo and in vitro. In conclusion, DFO inhibited the proliferation and ALL xenograft tumor growth, obstructed the cell cycle, and induced apoptosis of ALL cells, probably via inactivating the ROS/HIF-1α, Wnt/β-catenin, and p38MAPK/ERK signaling.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2025
·
IF 2.2
Haipeng Feng,Qianqian Qiao,Jingyan Zhang,Kang Zhang,Lei Wang,Jianxi Li
Duchesnea indica (Andr.) Focke ( DIF ), a medicinal plant from the Rosaceae family, possesses therapeutic properties such as heat-clearing and detoxification, dispersion of stasis detumescence, blood-cooling, and hemostatic effect. The latest research unveiled a diverse array of pharmacologically active compounds from DIF, showcasing a broad spectrum of pharmacological effects. However, there was limited attention given to the comprehensive investigation of its high molecular weight compounds, particularly polysaccharides. In this study, DIF extracts were prepared by water-extraction and alcohol-precipitation method and the pharmacological effect was detected. The results demonstrated that the total polysaccharide content, reducing sugar content, total flavonoid content, and total polyphenol content in DIF extracts were 32.62 ± 0.91 %, 13.41 ± 0.18 %, 1.07 ± 0.07 %, and 12.16 ± 0.27 %, respectively. Although the total antioxidant activity of DIF extracts were significantly low than that of the vitamin C group, its ability to scavenge ABTS, DPPH, and superoxide anion radicals was similar to that of the vitamin C group. Furthermore, DIF extracts demonstrated significant inhibition on NO and MDA levels while simultaneously enhancing SOD activity in LPS-stimulated RAW264.7 cells. Finally, DIF extracts significantly reduced the mRNA level of pro-inflammation cytokines interleukin ( IL )-6, IL-1β, inducible nitric oxide synthase ( iNOS ), cyclooxygenase-2 ( COX-2 ) and tumor necrosis factor ( TNF ) -α , and directly inhibited the phosphorylation level of extracellular regulated kinase and mitogen-activated protein kinase ( ERK-MAPK ) pathway. Taken together, these results indicated that DIF extracts exhibited an anti-inflammatory and antioxidant effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting ERK-MAPK signaling pathway. Based on these findings, DIF extracts provided new insights into the treatment and prevention of diseases related to oxidative stress and inflammation.
研究领域:
药理学
·
免疫学
·
天然产物化学
·
分子生物学
·
炎症与感染
·
抗氧化研究
·
信号转导
✓ 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）