Stem Cell Research & Therapy
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2024
·Vol. 15
·期 1
·1-15
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IF 7.1
Wang Ping,Wang Min,Liu Lin,Li Hongyi,Liu Helin,Ren Jiangbo,Liu Tianhui,Cong Min,Zhu Zhijun,Zhao Xinyan,Sun Liying,Jia Jidong
Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription ( P < 0.0001) and inhibited the proliferation ( P = 0.0065) of hepatic progenitor cells by suppressing the mTOR signalling pathway and activating the apoptosis pathway. Furthermore, knocking down NPM1 in hepatic progenitor cells resulted in more apoptotic cells (7.33 ± 0.09% vs. 3.76 ± 0.13%, P < 0.0001) but fewer apoptotic cells in the presence of NSC348884 (47.57 ± 0.49% vs. 63.40 ± 0.05%, P = 0.0008) than in the control cells, suggesting that low-NPM1-expressing cells are more resistant to NSC348884. In addition, NSC348884 induced the apoptosis of BEL-7402 cells with an IC50 of 2.77 μmol/L via the downregulation of the IL-6R and mTOR signalling pathways and inhibited the growth of BEL-7402 cells in a subcutaneous xenograft tumour model ( P = 0.0457). Conclusions Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2021
·
IF 4.242
Xiaoping Tan,Yang Hu,Shenye Qu,Gaoxue Wang,Tianqiang Liu
Noxious pathogens always lead to high rates of mortality, which results in severe economic losses in aquaculture. Currently, gyrodactylosis treatments mainly rely on unapproved chemicals, which are not always satisfactory. According to the previous study, arctigenin is an efficient natural product for controlling gyrodactylosis. For the sake of seeking high-efficiency compounds, a new arctigenin derivative (CCA) was synthesized. Next, we evaluated the anthelmintic activity of CCA in vitro and in vivo , and studied the mechanism of action. The number of Gyrodactylus kobayashii significantly reduced as compared with the control group, the EC 50 value at 24 and 48-h after CCA treatment was 0.616 and 0.451 mg/L, respectively, with EC 100 at CCA concentration of 3 mg/L after 1 h bath treatment. In vitro results showed that CCA can rapidly reduce the amount of G. kobayashii and inhibit its mobility that could normally lead to death. The concentration and duration of CCA were positively correlated with the mortality of G. kobayashii . In addition, CCA displayed 100% efficacy against G. kobayashii at 4.0 mg/L after only 20 min exposure. Acute toxicity assay demonstrated that the LC 50 of CCA against goldfish was 5.012 mg/L, which was 8.13 times higher than that of the EC 50 . Furthermore, the results of confocal microscope study revealed that CCA leaded to the epidermal structure and dissolved muscles of worms. Moreover, the ATP level of worms were decreased sharply after both in vitro and in vivo exposures with CCA. The anthelminthic mechanism of CCA against gyrodactylids was related to epidermal structure damages and energy insufficient. From the previous study, the EC 50 of CCA against G. kobayashii (0.616 mg/L) was much lower than the EC 50 (1.85 mg/L) of arctigenin ( Tu et al., 2018 ). In summary, CCA is more effective than arctigenin and has great potential in control of Gyrodactylus infections.
研究领域:
水产养殖
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寄生虫学
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药理学
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兽医学
✓ 已验证
DOI
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2025
·
IF 6.2
Yu Wang,Yangqing Huang,Yaming Jiang
The rapid growth of the smart wearable device market has driven an increasing demand for advanced materials and sensing technologies that offer high sensitivity and stability. Herein, we report the development of a lightweight, highly sensitive, and wide-range pressure sensor based on a carbonized cellulose acetate (CCA)/thermoplastic polyurethane (TPU) nanofiber membrane, fabricated through high-temperature carbonization and vacuum filtration techniques. By uniformly coating TPU onto the carbonized nanofiber surface, the intrinsic brittleness of the carbonized fibers was effectively mitigated, yielding a flexible and robust hybrid structure. The resulting CCA/TPU pressure sensor exhibits an impressive sensitivity of up to 101.22 kPa⁻¹ across a wide detection range of 0–50 kPa, a rapid response time of 20 ms, a minimal detection limit of 5 Pa, and outstanding durability over 10,000 loading-unloading cycles. This sensor is capable of accurately detecting diverse pressure and strain variations, demonstrating remarkable potential in physiological signal monitoring, motion recognition, emergency signal transmission, and safety protection applications. Notably, the sensor enables real-time recording of impact forces during shock events and provides critical data for evaluating the performance of cushioning materials. Beyond these applications, the conductive carbonized nanofiber membrane offers significant promise in the fields of smart textiles, biomedicine, and environmental monitoring.
研究领域:
材料科学
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生物医学工程
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智能可穿戴设备
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传感器技术
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
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IF 3.887
Aijie Guo,Yun Wang,Shaohui Xu,Xiao Zhang,Min Li,Qing Liu,Yuanyuan Shen,Derong Cui,Shengrong Guo
Because the surface of the cationic polymer gene complex is positively charged, it can result in problems such as poor blood stability and cytotoxicity. Therefore, reducing the positive charge of the cationic gene complex without affecting its transfection efficiency is crucial. To achieve this objective, a pH -responsive charge-convertible ternary complex was developed in this study. Modified plyethylenimine (PEI) with two different degrees of substitution of NH 2 (plyethylenimine-1,2-cyclohexanedicarboxylic anhydride, PEI-CCA, and folic acid-plyethylenimine-1,2-cyclohexanedicarboxylic anhydride, FA-PEI-CCA) were first obtained by a chemical graft reaction. PEI-CCA and FA-PEI-CCA have significantly lower cytotoxicities and much better blood compatibilities than PEI does, and the former have an undifferentiated compression capability of DNA . The zeta potential values of the as-prepared ternary complexes (PEI-CCA/PEI/DNA and FA-PEI-CCA/PEI/DNA) were negative at pH 7.4 and positive at pH 6.5, with particle sizes of approximately 150 nm. MTT assays demonstrated the significantly lower cytotoxicities of the ternary complexes compared to that of PEI/DNA. Moreover, the cytotoxicities of the ternary complexes were lower at pH 7.4 than pH 6.5. Transfection experiments in vitro revealed that the mean fluorescence intensities and transfection efficiencies of the ternary complexes were lower than for PEI/DNA at pH 7.4 but were almost the same at pH 6.5. The ternary complex with a FA group had significantly higher mean fluorescence intensity and transfection efficiency than did the ternary complex without it. In addition, the transfection experiment in 293T cells preliminarily validated the targeting function of the FA group of the ternary complex.
研究领域:
分子生物学
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基因治疗
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药物递送
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
·
2023
·Vol. 90
·期 5
·e13791
·
IF 3.6
Wenzhi Wang,Jianyong Shi,Lei Zheng
The emerging role of microRNA-935 (miR-935) in modulating cancer progression has been recognized. However, its role in regulating choriocarcinoma (CCA) development and progression remains unknown. The present work aims to reveal the effect of miR-935 on CCA cell tumor properties and the related mechanism. The RNA expression of methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3), miR-935, and gap junction protein alpha 1 (GJA1) was detected by quantitative real-time polymerase chain reaction. Protein expression of GJA1, Ki67, and METTL3 was measured by western blotting and immunohistochemistry assays. CCK-8 and colony formation were used to analyze cell proliferation. Transwell assays were performed to assess cell migration and invasion. Angiogenesis was investigated by tube formation assay. Xenograft mouse model assay was used to determine miR-935-mediated effect on tumor formation in vivo. The luciferase reporter assay and RNA pull-down assay were used to verify the relationship between miR-935 and GJA1. MeRIP assay was used to analyze the m6A methylation of pri-miR-935. MiR-935 expression was significantly upregulated in CCA tissues and cells when compared with control groups. MiR-935 overexpression promoted CCA cell proliferation, migration, invasion, and tube formation and tumor tumorigenesis in vitro and in vivo, but miR-935 knockdown showed the opposite effects. In addition, miR-935 targeted GJA1 and mediated CCA cell tumor properties by negatively regulating GJA1 expression. METTL3 promoted miR-935 maturation by inducing m6A methylation of pri-miR-935, and its overexpression contributed to CCA cell tumor properties through the regulation of miR-935. METTL3 promoted choriocarcinoma progression by m6A-dependently activating the miR-935/GJA1 pathway.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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表观遗传学
✓ 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）