CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Yu Zhang,Yan Liu,Yinxing Zhou,Ziming Zheng,Wenqi Tang,Mengzi Song,Jinglin Wang,Kaiping Wang
Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro . SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.
研究领域:
肿瘤学
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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
Biochemistry and Cell Biology
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2023
·Vol. 102
·期 1
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IF 2.9
Bin Zhang,Ruowen Sun,Min Gu,Zehui Jiang,Ye Wang,Linlin Zhang,Xiaoyang Liu,Zuofei Chi
Acute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with NOVA1, and RNA immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. The knockdown of NOVA1 had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function might be achieved by binding to and stabilizing USP44 mRNA.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
CRYOBIOLOGY
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2018
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IF 2.05
Hao Xu,Wenyue Cao,Liang Huang,Min Xiao,Yang Cao,Lei Zhao,Na Wang,Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative “drug” for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved. After one month, the cells were resuscitated, and their transduction rates, apoptosis rates and cell subsets were examined via flow cytometry. The results indicated no significant changes in transduction rates or cell subsets, and the survival rate of the resuscitated cells was approximately 90% Furthermore, similar tumoricidal effects and degranulation functions of the resuscitated cells compared with normally cultured cells were verified by calcein release and CD107a assays. A NOD/SCID mouse model was used to estimate the differences in the in vivo antitumor effects of the cryopreserved and normally cultured T cells, but no significant differences were observed. Following co-culture with several target cell types, the cytokines released by the cryopreserved and normally cultured T cells were measured via enzyme-linked immunosorbent assays (ELISAs). The results revealed that the release of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly decreased. These data demonstrated that with the exception of a decrease in cytokine release , the cryopreserved CART cells retained their antitumor functions.
研究领域:
肿瘤学
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免疫治疗
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2019
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IF 6.054
Ran Zhang,Xue-Qing Song,Rui-Ping Liu,Zhong-Ying Ma,Jing-Yuan Xu
As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of “dual-prodrug” by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10–17, named Fuplatin, exhibited much higher cytotoxicity against the tested cancer cells while lower cytotoxicity toward the human normal lung cells than free drugs or their combinations. Among them, 14 enhanced cellular accumulation with 62- and 825-fold amount of oxaliplatin and 8 at 9 h, respectively, significantly induced DNA damage and cell apoptosis, and inhibited migration and invasion in HCT-116 cells. Compound 14 arrested the cell cycle at S and G2 phases and up-regulated thymidylate synthase and p53, consistent with the results of the combination, suggesting 14 adopted a collaborative mode of 5-FU and oxaliplatin to kill cancer cells. In vivo, compound 14 showed high antitumor effect and no observable toxicity in NOD/SCID mice bearing HCT-116 tumors.
研究领域:
肿瘤学
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药理学
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化疗
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2021
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IF 6.684
Deng Moyuan,Tan Jiulin,Dai Qijie,Luo Fei,Xu Jianzhong
The positive role of macrophages in the osteogenesis of mesenchymal stem cells (MSCs) has been a recent research focus. On the other hand, MSCs could carefully regulate the paracrine molecules derived from macrophages. Human umbilical cord mesenchymal stem cells (hucMSCs) can reduce the secretion of inflammatory factors from macrophages to improve injury healing. hucMSC-derived extracellular matrix (hucMSC-ECM) has the similar effect to hucMSCs, which could combat the inflammatory response of macrophages. Additionally, MSC-derived extracellular matrix also enhanced bone regeneration by inhibiting osteoclastic differentiation of monocyte/macrophage lineage. However, whether hucMSC-ECM could improve bone formation by guiding macrophage-induced osteogenic differentiation of MSCs is unknown. Here, we present decalcified bone scaffolds modified by hucMSC-derived extracellular matrix (DBM-ECM), which maintained multiple soluble cytokines from hucMSCs, including macrophage migration inhibitory factor (MIF). Compared with DBM, the DBM-ECM scaffolds induced bone formation in an improved heterotopic ossification model of severe combined immunodeficiency (SCID) mice in a macrophage-dependent manner. Macrophages cocultured with DBM-ECM expressed four osteoinductive cytokines (BMP2, FGF2, TGFβ3 and OSM), which were screened out by RNA sequencing and measured by qPCR and western blot. The conditioned medium from macrophages cocultured with DBM-ECM improved the osteogenic differentiation of hBMSCs. Furthermore, DBM-ECM activated CD74/CD44 (the typical MIF receptors) signal transduction in macrophages, including phosphorylation of P38 and dephosphorylation of c-jun. On the other side, the inhibitory effects of the DBM-ECM scaffolds with a deficient of MIF on osteogenesis in vitro and in vivo revealed that macrophage-mediated osteogenesis depended on MIF/CD74 signal transduction. The results of this study indicate that the coordinated crosstalk of macrophages and MSCs plays a key role on bone regeneration, with an emphasis on hucMSC-ECM constructing a macrophage-derived osteoinductive microenvironment.
研究领域:
组织工程
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再生医学
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免疫学
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细胞生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
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2020
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IF 6.182
Guomin Wu,Xiao Ma,Yiding Wang,Le Fan,Yining Wang,Hongbing Deng
In order to highly simulate the chondrocyte extracellular matrix, electrospinning and layer-by-layer (LBL) self-assembly techniques were applied in this study. Polycaprolactone (PCL) with good mechanical property was selected as the substrate, while D-glucosamine sulfate (GAS) and collagen type I (COL) with chondroprotective properties were coated on the surfaces of PCL nanofibers. The morphology, chemical and physical investigations suggested the successful deposition of GAS/COL, improved mechanical properties and significantly ameliorated surfaces hydrophilicity after LBL medication. The release of GAS/COL was proved to be slow and sustainable. Besides, CCK-8 assay and cell morphology observation manifested that LBL structured mats were more suitable for rat articular chondrocytes (rACs) adhesion and proliferation, while quantitative Real-Time polymerase chain reaction analysis and glycosaminoglycans (GAG) production measurement indicated the introduction of GAS/COL upregulated glucuronosyltransferase I (GlcAT-I) gene expression and GAG content in rACs. Additionally, LBL structured mats induced GlcAT-I expression and reduced interleukin‐1β (IL‐1β) and Matrix metalloproteinases 13 (MMP13) expression in IL‐1β-induced rACs. Moreover, subcutaneous model in SCID mice further confirmed that GAS/COL modified PCL mat could facilitate the GAG production and collagen type II expression of rACs.
研究领域:
生物医学工程
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组织工程
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材料科学
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生物材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）