RSC Advances
·
2020
·Vol. 10
·期 25
·14915-14927
·
IF 3.119
Yiqiang Yu,Kai Liu,Zhuo Wen,Weicai Liu,Lei Zhang,Jiansheng Su
Zinc-incorporated biomaterials show promoting effects on osteogenesis; however, excessive zinc ions lead to cytotoxic reactions and also have other adverse effects. Therefore, the double-edged effects of Zn2+ microenvironments on osteogenesis may become critical issues for new material development. This study systematically investigated the bidirectional influences of diverse Zn2+ microenvironments on the cell adhesion, proliferation, osteogenic differentiation and apoptosis of rBMSCs. Furthermore, the mechanisms of zinc-induced osteogenic differentiation of rBMSCs and of cell apoptosis induced by high concentration of Zn2+ were both discussed in detail. The results indicated that the Zn2+ microenvironments of 2 μg mL−1 and 5 μg mL−1 effectively improved the initial adhesion and proliferation of rBMSCs, while that of 15 μg mL−1 had exactly the opposite effect. More importantly, the suitable Zn2+ microenvironments (2 μg mL−1 and 5 μg mL−1) moderately increased the intracellular Zn2+ concentration by regulating zinc transportation, and then activated the MAPK/ERK signaling pathway to induce the osteogenic differentiation of rBMSCs. In contrast, the high Zn2+ concentration (15 μg mL−1) not only inhibited the osteogenic differentiation of rBMSCs by damaging intracellular zinc homeostasis, but also induced rBMSC apoptosis by enhancing intracellular ROS generation. The current study clarified the double-edged effects of Zn2+ microenvironments on the osteogenic properties of rBMSCs and the related mechanisms, and may provide valuable guidance for optimizing the design of zinc-doped biomaterials and zinc-based alloys.
研究领域:
生物材料
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细胞生物学
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组织工程
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 8
·e71071
·
IF 3.73
Bo-xin Zhao,Ya-bin Sun,Sheng-qi Wang,Lian Duan,Qi-lu Huo,Fei Ren,Guo-feng Li
The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.
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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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Lujuan Han,Xiaohan Xiang,Yuhui Fu,Sisi Wei,Cong Zhang,Lei Li,Yueping Liu,Huilai Lv,Lianmei Zhao,Baoen Shan
Background Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer (EC) in China, and demonstrates varying levels of resistance to multiple chemotherapeutic agents. Our previous studies have proved that periplocin (CPP), derived from the extract of cortex periplocae, exhibiting the capacity to hinder proliferation and induce apoptosis in ESCC cells. Several studies have identified additional anti-cancer constituents in the extract of cortex periplocae, named periplcymarin (PPM), sharing similar compound structure with CPP. Nevertheless, the inhibitory effects of PPM on ESCC and their underlying mechanisms remain to be further elucidated. Purpose The aim of this study was to investigate function of PPM inhibiting the growth of ESCC in vivo and in vitro and to explore its underlying mechanism, providing the potential anti-tumor drug for ESCC. Methods Initially, a comparative analysis was conducted on the inhibitory activity of three naturally compounds obtained from the extract of cortex periplocae on ESCC cells. Among these compounds, PPM was chosen for subsequent investigation owing to its comparatively structure and anti-tumor activity simultaneously. Subsequently, a series of biological functional experiments were carried out to assess the impact of PPM on the proliferation, apoptosis and cell cycle arrest of ESCC cells in vitro . In order to elucidate the molecular mechanism of PPM, various methodologies were employed, including bioinformatics analyses and mechanistic experiments such as high-performance liquid chromatography combined with mass spectrometry (HPLC-MS), cell glycolysis pressure and mitochondrial pressure test. Additionally, the anti-tumor effects of PPM on ESCC cells and potential toxic side effects were evaluated in vivo using the nude mice xenograft assay. Results Our study revealed that PPM possesses the ability to impede the proliferation of ESCC cells, induce apoptosis, and arrest the cell cycle of ESCC cells in the G2/M phase in vitro . Mechanistically, PPM exerted its effects by modulating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as confirmed by glycolysis pressure and mitochondrial pressure tests. Moreover, rescue assays demonstrated that PPM inhibits glycolysis and OXPHOS in ESCC cells through the PI3K/AKT and MAPK/ERK signaling pathways. Additionally, we substantiated that PPM effectively suppresses the growth of ESCC cells in vivo , with only modest potential toxic side effects. Conclusion Our study provides novel evidence that PPM has the potential to simultaneously target glycolysis and mitochondrial OXPHOS in ESCC cells. This finding highlights the need for further investigation into PPM as a promising therapeutic agent that targets the tumor glucose metabolism pathway in ESCC.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Qiangfei Su,Jian Wang,Yu Song,Zhaowenbin Zhang,Bo Cai,Xiakeerzhati Xiaohalati,Jingwei Liu,Haozhe Li,Zheng Wang,Jiang Chang,Lin Wang
Schwann cells are pivotal in generating a pro-regenerative microenvironment for long-gap peripheral nerve injury (PNI) repair via their orchestrated behaviors, including cell migration, proliferation, and secretion. Bioceramics can release bioactive ions to regulate “repair” cells for regenerating damaged tissues. Herein, bioceramic akermanite (AT) is screened and found to significantly enhance Schwann cell proliferation, migration, and secretion by activating the PI3K/AKT and MAPK/ERK signaling pathways. Integration with silk sericin (SS), a natural biomaterial possessing excellent bioactivity, promotes the release of Ca and Mg from AT, synergistically enhancing Schwann cell pro-regenerative behaviors and accelerating axon elongation. The AT-SS composite conduit effectively restores nerve structure and function in a 13 mm transected PNI. Compared with commercial eton conduit, AT-SS conduit promotes axons and myelin sheaths regeneration, improves nerve conduction, and effectively alleviates gastrocnemius muscle atrophy. The AT-SS conduit achieves autograft-comparable behavioral recovery as evidenced by the paw withdrawal latency, hind limb grip force, and sciatic function index. The excellent degradation and biosafety of AT-SS conduit indicate its potential for clinical translation. This study introduces an ion-based therapeutic approach for enhancing the pro-regenerative functions of Schwann cells, and provides novel insights and strategies for clinically managing long-gap PNI and other nerve tissue injuries.
研究领域:
生物材料
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神经再生
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组织工程
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生物医学工程
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细胞信号传导
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Yu Wang,Ye Wu,Bo Zhang,Cheng Zheng,Cheng Hu,Chuan Guo,Qingquan Kong,Yunbing Wang
Intervertebral disc degeneration (IDD) progresses due to local inflammatory response, gradually unbalanced anabolic/catabolic activity, and progressive functional impairment within the nucleus pulposus. Antagomir-21, a cholesterol-modified miRNA-21 inhibitor, has potential extracellular matrix (ECM) regenerative ability , but its application for IDD is limited by inadequate local delivery systems. An injectable hydrogel gene delivery system encapsulating a modified tannic acid nanoparticles (TA NPs) vector was engineered for on-demand and sustained delivery of antagomir-21 into the nucleus pulposus. After nucleus pulposus cell uptake, antagomir-21 was released from TA NPs and regulated the ECM metabolic balance by inhibiting the MAPK/ERK signaling pathway . TA NPs scavenged intracellular ROS and reduced inflammation by downregulating TNF-α expression. In vivo , synergistic anti-inflammatory effects and ECM regeneration effectively promoted therapeutic efficacy against IDD. This hydrogel gene delivery system represents a creative, promising strategy for IDD repair.
研究领域:
生物医学工程
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骨科
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基因治疗
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纳米技术
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Shengwen Cheng,Chen Zhao,Senrui Liu,Bowen Chen,Hong Chen,Xuefeng Luo,Li Wei,Chengcheng Du,Pengcheng Xiao,Yiting Lei,Yonggang Yan,Wei Huang
Bone defects, especially large ones, are clinically difficult to treat. The development of new bone repair materials exhibits broad application prospects in the clinical treatment of trauma. Bioceramics are considered to be one of the most promising biomaterials owing to their good biocompatibility and bone conductivity. In this study, a self-curing bone repair material having a controlled degradation rate was prepared by mixing calcium citrate, calcium hydrogen phosphate, and semi-hydrated calcium sulfate in varying proportions, and its properties were comprehensively evaluated. In vitro cell experiments and RNA sequencing showed that the composite cement activated PI3K/Akt and MAPK/Erk signaling pathways to promote osteogenesis by promoting the proliferation and osteoblastic differentiation of mesenchymal stem cells. In a rat model with femoral condyle defects, the composite bone cement showed excellent bone repair effect and promoted bone regeneration. The injectable properties of the composite cement further improved its practical applicability, and it can be applied in bone repair, especially in the repair of irregular bone defects, to achieve superior healing.
研究领域:
生物材料
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组织工程
·
骨科
·
再生医学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CANCER LETTERS
·
2024
·
IF 9.1
Ying Ning,Yu Chen,Tian Tian,Xinyan Gao,Xiaolan Liu,Jia Wang,Huijun Chu,Chenyang Zhao,Yufei Yang,Ke Lei,He Ren,Zhumei Cui
Neutrophil extracellular traps (NETs) have been shown to promote the metastatic potential of many kinds of tumors. Our study aimed to investigate the role and mechanisms of NETs in lymph node metastasis (LNM) of cervical cancer (CCa), and evaluated the therapeutic value of targeting NETs in CCa. Immunohistochemistry demonstrated that neutrophil infiltration and NETs formation were increased in CCa patients with LNM, as well as confirming a positive correlation between S100A7 expression and neutrophil infiltration in CCa. NETs enhanced the migratory capability of CCa by activating the P38-MAPK/ERK/NFκB pathway through interaction with TLR2. Digesting NETs with deoxyribonuclease 1 (DNase 1) or inhibiting TLR2 with chloroquine eliminated the NETs-induced metastatic potential of CCa. Additionally, NETs promoted lymphangiogenesis and increased the permeability of lymphatic vessels, thus facilitating translymphatic movement of CCa. CCa-derived S100A7 exhibited a chemotactic effect on neutrophils and promoted NETs generation by elevating ROS levels rather than activating autophagy in neutrophils. The mouse model with footpad implantation illustrated that DNase 1 effectively reduced LNM in LPS-induced mice and in mice seeded with S100A7-overexpressing CCa cells. In conclusion, our study reveals a new tumor-promoting mechanism of S100A7, clarifies the crucial role and mechanism of NETs in LNM of CCa, and indicates that the NETs-targeted therapy emerges as a promising anti-metastasis therapy in CCa.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Lu Yang,Zijin Lin,Ruijing Mu,Wenhan Wu,Hao Zhi,Xiaodong Liu,Hanyu Yang,Li Liu
Blood–brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs’ BBB permeability.
研究领域:
神经科学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 6
·1-10
·
IF 4.101
Xinyan Ma,Ying Zhang,Mingyang Guan,Weidong Zhang,Huifang Tian,Caixiao Jiang,Xiaoxin Tan,Weijun Kang
The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2‑ethyl‑6‑methyl-2-chloroacetanilide (CMEPA) and 6‑ethyl‑o‑toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co‑treatment with anti‑reactive oxygen species (ROS) reagent N‑acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co‑treatment with N‑acetylcysteine alleviated the pro‑apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N‑acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.
研究领域:
毒理学
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分子生物学
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发育生物学
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环境科学
✓ 已验证
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2023
·
IF 3.3
Xiaoying Mo,Xiaochun Chen,Xiaojiao Pan,Yantong Lu,Guangjuan Pan,Jielan Xie,Zhenzhen Pan,Li Li,Hui Tian,Yaohua Li
Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1β, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.
研究领域:
药理学
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皮肤病学
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植物科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 2
·1-15
·
IF 2.2
Hou Huailong,Qiu Zhengjun,Che Jingyi,Li Yanping,Sun Jingxuan,Zhang Weiwei,Ma Jinjie,Zhang Shuang,Li Mengdi,Niu Yumei,He Lina
Dental pulp stem cells (DPSCs), a subset of tooth-derived mesenchymal stem cells (MSCs), demonstrate significant promise in clinical stem cell therapy. However, prolonged in vitro expansion commonly results in compromised stemness, limiting therapeutic efficacy. Thus, maintaining the stemness of DPSCs during expansion and culture is a key challenge for regenerative medicine. In the current study, the impact of simulated microgravity (SMG) on DPSC stemness was investigated using the three-dimensional clinostat Cellspace-3D. After SMG treatment for 3 days, DPSCs demonstrated markedly enhanced replicative activity, proliferation efficiency, self-renewal capacity, and effective inhibition of the senescence process. Under specific differentiation induction conditions, DPSCs in the SMG group exhibited superior osteogenic, adipogenic, chondrogenic, and neural differentiation potentials. Additionally, DPSCs exhibited higher expression levels of the MSC surface markers Stro-1 and CD146 and stemness maintenance-related genes Oct4, Nanog, and Sox2 in the SMG group compared to those from the normal gravity (NG) group. To elucidate the potential molecular mechanisms by which SMG influences the stemness of DPSCs, transcriptome sequencing of total RNA was performed, and identified that differentially expressed genes (DEGs) are closely associated with the MAPK signaling pathway. Further verification experiments demonstrated that the MAPK/ERK signaling pathway was activated in the SMG group. In conclusion, SMG effectively maintains the stemness of DPSCs cultivated in vitro, and its mechanism of action may be associated with the activation of the MAPK/ERK signaling pathway.
研究领域:
干细胞生物学
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再生医学
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细胞生理学
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分子生物学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yuan Xu,Xin An,Lei Liu,Xinran Cao,Zhanfeng Wu,Wang Jia,Jiacheng Sun,Haoyu Wang,Jiawei Huo,Zihao Sun,Mingming Zhen,Chunru Wang,Chunli Bai
Endotoxemia is a life-threatening multiple organ failure disease caused by bacterial endotoxin infection. Unfortunately, current single-target therapy strategies have failed to prevent the progression of endotoxemia. Here, we reported that alanine fullerene redox modulator (AFRM) remodeled the intestinal microenvironment for multiple targets endotoxemia mitigation by suppressing inflammatory macrophages, inhibiting macrophage pyroptosis, and repairing epithelial cell barrier integrity. Specifically, AFRM exhibited broad-spectrum and self-cascade redox regulation properties with superoxide dismutase (SOD)-like enzyme, peroxidase (POD)-like enzyme activity, and hydroxyl radical (•OH) scavenging ability. Guided by proteomics, we demonstrated that AFRM regulated macrophage redox homeostasis and down-regulated LPS/TLR4/NF-κB and MAPK/ERK signaling pathways to suppress inflammatory hyperactivation. Of note, AFRM could attenuate inflammation-induced macrophage pyroptosis via inhibiting the activation of gasdermin D (GSDMD). In addition, our results revealed that AFRM could restore extracellular matrix and cell-tight junction proteins and protect the epithelial cell barrier integrity by regulating extracellular redox homeostasis. Consequently, AFRM inhibited systemic inflammation and potentiated intestinal epithelial barrier damage repair during endotoxemia in mice. Together, our work suggested that fullerene based self-cascade redox modulator has the potential in the management of endotoxemia through synergistically remodeling the inflammation and epithelial barriers in the intestinal microenvironment.
研究领域:
药理学
·
免疫学
·
病理学
·
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）