TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2022
·
IF 4.46
Wei Liu,Zechang Li,Xiaoyu Cui,Fang Luo,Chunyan Zhou,Jiangyu Zhang,Liguo Xing
Despite of the global contamination and ubiquitous exposure to nitenpyram (NIT), little knowledge is available on the adverse effects to human health, with some evidence referring to its genotoxic potency to non-target organisms and esophageal squamous papilloma in rats. Human bone marrow mesenchymal stem cells (hBMSCs) was employed as an in vitro model more relevant to humans to assess the potential genotoxicity of NIT and to understand the underlying mechanisms at cellular and molecular levels. Noncytotoxic concentrations of NIT, 50–2500 μg/mL, dose-dependently elevated micronucleus (MN) and nuclear bud (NB) frequencies to 8.7–29‰ and 15–35‰, respectively. Additional metabolism by rat liver S9 fraction decreased chromosome impairment by 27–52% on MN frequencies and 63–76% on NB frequencies. A commercial NIT product, containing 20% of NIT and 60% of pymetrozine , caused higher cytotoxicity and chromosome impairment in comparison with NIT alone. Expressions of genes responses to DNA damage, ATM , ATR , p53 , p21 , Bax, H2AX , and GADD45A were disturbed by NIT treatment. Reactive oxygen species (ROS) amount and superoxide dismutase (SOD) activity were enhanced by NIT. Comet assay showed that lower concentrations of NIT, 12.5–100 μg/mL, induced the DNA damage. Transcriptomic analysis identified 468 differentially expressed genes ( p < 0.05, |log2(Foldchange)| ≥ 1), from which 22 pathways were enriched. Multiple affected pathways were related to cancer including viral carcinogenesis and bladder cancer . NIT may produce genotoxicity via inducing oxidative stress and deregulating PI3K/Akt, AMPK and mTOR signaling pathways, associated with carcinogenetic potency. While environmental levels of NIT alone may pose little risk to human health, attention should be paid to the health risk arose from the synergistic or additive effects that may exist among NEOs and other types of pesticides.
研究领域:
毒理学
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细胞生物学
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分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Jinjin Lu,Rui Li,Shilei Ni,Yuandong Xie,Xinchen Liu,Kai Zhang,Yi Li
Human dental pulp stem cells (hDPSCs) have been a focus of pulp regeneration research because of their excellent odontogenic potential and availability. Applying the odontoblastic differentiation of hDPSCs to tooth regeneration has been challenging. Metformin-based carbon nanodots (MCDs) were synthesized and characterized to investigate their effects in vitro on odontoblastic hDPSC differentiation and the underlying mechanism. MCDs were synthesized by a hydrothermal treatment method and characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The biocompatibility and fluorescence properties of the MCDs in Dulbecco’s modified Eagle’s medium high-glucose culture medium and the in vitro odontogenic potential and related mechanism of the bioactive nanomaterial was explored. TEM images showed that MCDs were spherical in shape with a size of approximately 5.9 nm. MCDs showed biological safety in cell viability, apoptosis, and fluorescence labelling ability at a concentration up to 200 μg/ml in vitro . The presence of MCDs facilitated high-efficiency odontogenic differentiation of hDPSCs by promoting odontogenic gene and protein expression. Moreover, MCDs promoted odontoblastic hDPSC differentiation via autophagy. MCDs are capable of activating autophagy and enhancing the odontogenic differentiation of hDPSCs by upregulating odontoblast gene marker (DMP1, DSPP, RUNX2, and SP7) and protein (DSPP and DMP1) expression.
研究领域:
牙齿再生
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纳米技术
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干细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2022
·Vol. 17
·期 1
·1-10
·
IF 2.677
Bin-bin Zhang,Da-wa Zha Xi,Chao Li,Lan-tao Zhang,Tao Wu,Chuan Lu,Chao-zheng Liu,De-chun Li,Chang Feng,Shu-qing Wei,Zu-nan Dong,Xian-wei Pei,Zhang Zhi-xia,Ke-wen Li
Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public.Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins.Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation.Conclusion sThe present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.
研究领域:
干细胞生物学
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骨组织工程
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外泌体研究
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微小RNA功能
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
QiuShi Wei,MinCong He,MeiHui Chen,ZhenQiu Chen,Fan Yang,HaiBin Wang,Jin Zhang,Wei He
Icariin, the major ingredient of Herba Epimedii, promotes the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and exerts protective effects against bone loss and increases bone regeneration, but the underlying signaling pathway by which icariin affects osteogenic differentiation remain unclear. Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional modulator of the Hippo signaling pathway, which plays an important role in the osteogenic differentiation of BMSCs by activating Runx2 gene during the terminal osteogenic differentiation. In this study, we found that 0.1 μM icariin markedly promoted the proliferation, calcium depositions, and osteogenic genes expression of rBMSCs. Icariin (0.1 μM) upregulated TAZ, Runx2, β-catenin, Osteopotin, and Dlx5 expression mainly at the early stage of osteogenic differentiation, and increased osteocalcin expression at the late stage. Our result further demonstrated that knockdown TAZ expression by lentivirus-mediated TAZ shRNA inhibited the icariin-induced osteogenic differentiation. Moreover, ICI 182780 (the estrogen receptor alpha inhibitor) or DKK1 (the Wnt/β-catenin pathway inhibitor), inhibited the icariin-induced increase in TAZ expression. Furthermore, icariin stimulated the activation of TAZ as evidenced by increased total TAZ protein and nuclear translocation, but these effects of icariin were blocked by ICI 182780 or DKK1. Taken together, our results demonstrate that icariin promotes the osteogenic differentiation of rBMSCs by increasing TAZ expression, and that the increased TAZ expression induced by icariin is mostly mediated by the ERα and Wnt/β-catenin pathway.
研究领域:
药理学
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细胞生物学
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分子生物学
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骨再生
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2019
·Vol. 304
·期 4
·1800630
·
IF 3.038
Yuanhao Zhang,Yudong Tong,Xiuwei Pan,Haibo Cai,Yun Gao,Weian Zhang
Reactive oxygen species (ROS) level is closely associated with the physiological function of hematopoietic stem cells (HSCs) in ex vivo culture systems. Previously developed hydrogels in use of HSCs culture have generally failed in considering their antioxidant property. In the present work, antioxidant hydrogels are constructed to evaluate the biological effect of ROS on HSCs proliferation by suppressing oxidative stress damage. Functionalized carbon nanotubes (CNTs), which act as potential antioxidants, are physically encapsulated in biocompatible hyaluronic acid (HA) hydrogels to achieve long-term antioxidant activity. Consequently, these hybrid hydrogels exhibit enhanced physical properties and superior scavenging capability on oxides and peroxides compared to the pure HA hydrogel. The results indicate that ROS significantly inhibit the biological characteristics of HSCs. Nevertheless, the proliferation ability and pluripotency are dramatically improved when the culture system is supplied with the antioxidant hydrogel, revealing that the CNT-incorporated hydrogel can effectively relieve oxidative stress response in HSCs and reduce apoptosis from ROS. Therefore, the HA/CNT hydrogel can provide a novel strategy to establish an artificial microenvironment with a low ROS level for HSCs proliferation.
研究领域:
生物材料学
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细胞生物学
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再生医学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Wenjing Li,Haiwei Liang,Yanxiao Ao,Baixue Tang,Junyang Li,Ning Li,Jianwei Wang,Yanan Du
Hematopoietic stem cells (HSCs) are adult multipotential stem cells with the capacity to differentiate into all blood cells and immune cells , which are essential for maintaining hematopoietic homeostasis throughout the lifespan and reconstituting damaged hematopoietic system after myeloablation. However, the clinical application of HSCs is hindered by the imbalance of its self-renewal and differentiation during in vitro culture. Considering the fact that HSC fate is uniquely determined by natural bone marrow microenvironment , various elaborate cues in this hematopoietic micro-niche provide an excellent reference for the regulation of HSCs. Inspired by the bone marrow extracellular matrix (ECM) network, we designed degradable scaffolds by orchestrating the physical parameters to investigate the decoupling effects of Young's modulus and pore size of three-dimensional (3D) matrix materials on the fate of hematopoietic stem and progenitor cells (HSPCs). We ascertained that the scaffold with larger pore size (80 μm) and higher Young's modulus (70 kPa) was more favorable for HSPCs proliferation and the maintenance of stemness related phenotypes. Through in vivo transplantation, we further validated that scaffolds with higher Young's modulus were more propitious in maintaining the hematopoietic function of HSPCs. We systematically screened an optimized scaffold for HSPC culture which could significantly improve the cell function and self-renewal ability compared with traditional two-dimensional (2D) culture. Together, these results indicate the important role of biophysical cues in regulating HSC fate and pave the way for the parameter design of 3D HSC culture system.
研究领域:
血液学
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干细胞生物学
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组织工程
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Xia Lin,Shang Yixuan,Chen Xiangbo,Li He,Xu Xiaochen,Liu Wei,Yang Guang,Wang Tian,Gao Xia,Chai Renjie
Isotropic inverse opal structures have been extensively studied for the ability to manipulate cell behaviors such as attachment, migration, and spheroid formation. However, their use in regulate the behaviors of neural stem cells has not been fully explored, besides, the isotropic inverse opal structures usually lack the ability to induce the oriented cell growth which is fundamental in neural regeneration based on neural stem cell therapy. In this paper, the anisotropic inverse opal substrates were obtained by mechanically stretching the poly (vinylidene fluoride) (PVDF) inverse opal films. The anisotropic inverse opal substrates possessed good biocompatibility, optical properties and anisotropy, provided well guidance for the formation of neural spheroids, the alignment of neural stem cells, the differentiation of neural stem cells, the oriented growth of derived neurons and the dendritic complexity of the newborn neurons. Thus, we conclude that the anisotropic inverse opal substrates possess great potential in neural regeneration applications.
研究领域:
材料科学
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神经科学
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细胞生物学
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组织工程
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 47
·期 1
·75-85
·
IF 4.473
Yanhua Mao,Yuan Yang,Congcong Sun,Yulong Zou,Yingfeng Zhang,Benyuan Wu,Changjiang Li,Jinglin Huang,Wenwen Zhang,Jia Wang
Human amniotic transplantation has been proposed to improve the therapeutic efficacy of intrauterine adhesions (IUAs). Human amniotic mesenchymal stem stromal cells (hAMSCs) can differentiate into multiple tissue types. This study aimed to investigate the mechanism by which hAMSCs transplantation promotes endometrial regeneration. The rat models with IUA were established through mechanical and infective methods, and PKH26-labeled hAMSCs were transplanted through the tail vein (combined with/without estrogen). Under three different conditions, hAMSCs differentiated into endometrium-like cells. HE and Mason staining assays, and immunohistochemistry were used to compare the changes in rat models treated with hAMSCs and/or estrogen transplantation. To define the induction of hAMSCs to endometrium-like cells in vitro, an induction medium (cytokines, estrogen) was used to investigate the differentiation of hAMSCs into endometrium-like cells. qRT-polymerase chain reaction (PCR) and western blotting were performed to detect the differentiation of hAMSCs into endometrium-like cells. A greater number of glands, fewer endometrial fibrotic areas, and stronger expression of vascular endothelial growth factor and cytokeratin in the combined group (hAMSCs transplantation combined with estrogen) than in the other treatment groups were observed. hAMSCs could be induced into endometrium-like cells by cytokine treatment (TGF-β1, EGF, and PDGF-BB). Transplantation of hAMSCs is an effective alternative for endometrial regeneration after injury in rats. The differentiation protocol for hAMSCs will be useful for further studies on human endometrial regeneration.
研究领域:
生殖医学
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干细胞生物学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Cell Journal
·
2021
·
IF 2.479
Liping Zhou,Haiwei Ye,Lizhen Liu,Yunhua Chen
Objective Human bone marrow mesenchymal stem cell (hBMSC)-derived exosomes exhibit protective effects againstinflammatory diseases. This study aimed to explore the effects of hBMSC-derived exosomes on osteoarthritis (OA) invitro and its related mechanisms. Materials and Methods In this experimental study, we characterised exosomes derived from hBMSCs by transmissionelectron microscopy, nanoparticle tracking and Western blot analysis. Cellular uptake of exosomes was observed byfluorescent microscopy. Cell viability of chondrocytes exposed to interleukin-1 beta (IL-1β) was determined by theCell Counting Kit-8 (CCK-8). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determineexpression levels of genes related to apoptosis, inflammation, cartilage collagen metabolism and mitogen-activatedprotein kinases. Results Fluorescence microscopy revealed that hBMSC-derived exosomes could be taken up by chondrocytes.hBMSC-derived exosomes could significantly enhance cell viability of chondrocytes in response to IL-1β treatment.RT-qPCR showed significant up-regulation of Survivin, Versican, IL-1β, IL-6, NF-κB, MMP-13, MAPK p38, JNK, ERK,Aggrecan and SOX9 expression levels by IL-1β treatment, while their mRNA expression levels decreased after co-culture with exosomes. The anti-inflammatory gene TGF-β was markedly suppressed by IL-1β treatment; however, weobserved its expression after co-culture with exosomes. Additionally, the pro-inflammatory genes IL-1β, IL-6, NF-κB,TNF-α and TNF-β displayed significantly elevated expression levels in the IL-1β group and reduced expression levelsafter co-culture with exosomes. Conclusion hBMSC-derived exosomes may play a protective role in chondrocytes through inhibiting cell apoptosisand the inflammatory response. These results will provide a novel therapeutic strategy for OA.
研究领域:
干细胞生物学
·
炎症
·
骨科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Regenerative Medicine
·
2022
·
IF 3.21
Enqi Guo,Jianlong Wu,Hongrui Lu,Liang Wang,Qiang Chen
Background: Development of alternative bone tissue graft materials based on tissue engineering technology has gradually become a research focus. Engineered bone composed of biodegradable, biosafe and bioactive materials is attractive, but also challenging. Materials & methods: An adipose-derived stem cell/poly(L-glutamic acid)/chitosan composite scaffold was further developed for construction of biodegradable and bone-promoting tissue-engineered bone. A series of composite scaffold materials with different physical properties such as structure, pore size, porosity and pore diameter was developed. Results: The composite scaffold showed good biodegradability and water absorption, and exhibited an excellent ability to promote bone differentiation. Conclusion: This type of biodegradable scaffold is expected to be applied to the field of bone repair or bone tissue engineering.Plain language summaryIn recent years, the application of bone graft materials in bone defect repair has become a research hotspot. Engineered bone composed of biodegradable, biosafe and bioactive materials is attractive but also challenging. A composite scaffold composed of adipose-derived stem cells and two polymers was developed for construction of biodegradable and bone-promoting tissue-engineered bone. A series of composite scaffold materials with different physical properties was prepared and studied. The composite scaffold showed good biodegradability and water absorption, and exhibited excellent ability to promote bone differentiation – that is, bone defect repair function. This kind of biodegradable scaffold is expected to be applied to the field of bone repair or bone tissue engineering.Graphical abstract
研究领域:
生物医学工程
·
组织工程
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Journal of Neural Engineering
·
2017
·Vol. 14
·期 2
·026005
·
IF 3.465
Chao Yang,Xinghan Li,Liang Sun,Weihua Guo,Weidong Tian
Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.
研究领域:
神经科学
·
干细胞生物学
·
再生医学
·
脊髓损伤研究
✓ 已验证
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2016
·
IF 5.784
Bowen Wu,Hao Yu,Yifan Wang,Zongfu Pan,Yihan Zhang,Tong Li,Lu Li,Weichen Zhang,Lijun Ge,Ying Chen,Choe Kyong Ho,Danyan Zhu,Xin Huang,Yijia Lou
Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S -nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes , Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity , causing transient endogenous hydrogen peroxide (H 2 O 2 ) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis.
研究领域:
干细胞生物学
·
分子生物学
·
心血管生物学
·
蛋白质组学
·
细胞信号传导
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）