INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Jing Lv,Guangyu Liu,Huimin Gao,Yutao He,Xiaorong Tang,Ziqi Wang,Kaikai Sun,Kulbaram Bayazitova,Zhongliang Jiang
Trehalose, as a food and feed additive, can regulate physiological and pathological processes by activating autophagy, yet the molecular mechanism of trehalose dominated a rise in autophagy has not been elucidated. This study investigated the mechanisms of trehalose-induced autophagy in porcine granulosa cells (PGCs). Trehalose was internalized into PGCs by endocytosis and caused a temporary change of the lysosome pH, ultimately inducing autophagy. Furthermore, miRNA-seq analysis of PGCs indicated that trehalose upregulated the expression of miR-221-5p_R-4, which can target nuclear receptor binding factor 2 (NRBF2) to induce autophagy of PGCs. In summary, this study reveals that miR-221-5p_R-4 targeting NRBF2 was involved in the autophagy of PGCs challenged by trehalose, which was taken up by PGCs through endocytosis.
研究领域:
分子生物学
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细胞生物学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Liwei Ni,Jianhao Xu,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jie Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
MicroRNAs (miRNAs) are involved in the initiation and development of cancer and participate in drug resistance. Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The abnormal miRNA expression in NSCLC and its association with chemotherapy drug resistance remains largely unknown. The study aimed to investigate the aberrant expression of miR-221–3p in NSCLC and to elucidate its molecular mechanisms in relation to PTX resistance. PTX increased miR-221–3p expression and regulated MDM2/P53 expression in the PTX-sensitive NSCLC strain (A549). Meanwhile, miR-221–3p was rarely expressed and not interfered by PTX in PTX-resistant A549 cells (A549/Taxol). Dual-luciferase reporter assay confirmed that miR-221–3p specifically binds to MDM2 messenger RNA and inhibited MDM2 expression. The expression of MDM2 and P53 showed a negative correlation in NSCLC cell lines. MiR-221–3p down-regulation reduced the sensitivity of A549 cells to PTX, whereas its up-regulation partially reversed the A549/Taxol cells resistance to PTX and increased the chemosensitivity of A549/Taxol cells to PTX in xenograft models. Quantitative polymerase chain reaction analysis revealed that miR-221–3p expression increased, whereas the MDM2 level decreased in human NSCLC tumor tissues. Moreover, Western bolt analysis showed that P53 was lowly expressed in tumor tissues with MDM2 overexpression. Low expression of miR-221–3p in NSCLC tissues might indicate a poor T staging. In conclusion, miR-221–3p overexpression could regulate MDM2/p53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.
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
Cell Death Discovery
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2023
·Vol. 9
·期 1
·1-11
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IF 7
Zhang Libo,Ren Zhen,Lü Jinhui,Mo Xinhai,Lin Jie,Li Ya,Ma Wenjing,Liu Pengfei,Shen Yajing,Zhao Qian,Qian Lu,Cheng Xiaoxin,Yu Zuoren,Zhang Bo
Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.
研究领域:
癌症生物学
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药学
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生物医学工程
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纳米技术
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治疗诊断学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-22
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IF 15.7
Wang Wenkai,Cheng Zhuo,Yu Miao,Liu Ke,Duan Hongli,Zhang Yang,Huang Xinle,Li Menghuan,Li Changqing,Hu Yan,Luo Zhong,Liu Minghan
Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.
研究领域:
医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2023
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IF 6.2
Shengjie Ge,Gaoyang Chen,Jialin Deng,Yuexing Gu,Yu Mao,Xinyu Zhou,Guang Li
In this paper, a multiplex signal amplification strategy was developed for the determination of miR-214 and miR-221 on a surface-enhanced Raman scattering (SERS)-enabled lab-on-a-chip (LoC) system to realize the early-stage diagnosis of Parkinson's disease (PD). The gold nanobipyramids (GNBPs) with great monodispersity were functionalized with Raman reporter molecules and hairpin DNA 1, serving as the SERS nanotags. The presence of targets can initial the strand displacement amplification (SDA) reaction and the numerous short-stranded trigger DNA (tDNA) can be released under the action of polymerase and nicking enzyme . Then, the tDNA can trigger the catalytic hairpin assembly (CHA) event between the SERS nanotags and the capture nanoprobes (Magnetic beads (MBs) modified with hairpin DNA 2), resulting in the aggregation of GNBPs on the MBs surface. The multiplex signal amplification contributed by the SDA-CHA strategy and the magnet-induced aggregation effect can ultimately lead to the significant improvement of the detection sensitivity and the limit of detection (LOD) was low to aM level with reproducibility and specificity meanwhile. Furthermore, a MPTP-induced PD mice model was established to verify the practicability and the expression level of miR-214 and miR-221 at different stages analyzed with the LoC system was confirmed by qRT-PCR.
研究领域:
医学诊断
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生物化学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
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2026
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IF 6.2
Lingyun Zhao,Anqi Li,Shijing Chen,Wei Hua,Ru Dai,Lingyu Pan,Meng Hu,Nan Huang,Runke Zhou,Yuanyuan Han,Lidan Xiong,Li Li
Stem cells and their paracrine factors hold promise for alopecia treatment, yet research on human skin-derived precursors (hSKPs), which are closely related to hair follicles in biological positioning and function, remains limited. We demonstrated that extracellular vesicles of human transformed skin-derived precursors (htSKP-EVs), harvested utilizing our directed induction, culture transition and gradient ultracentrifugation technology, exhibited superior efficiency and quality determined by transmission electron microscopy, nanoparticle tracking analysis, and detection of specific markers. Using CCK8, scratch assay, immunofluorescence, H&E staining, immunohistochemistry staining, dermoscope, qRT-PCR and Western blotting, it was found that htSKP-EVs significantly promoted the proliferation of hair follicle stem cells (hHFSCs) by effectively modulating the Wnt signaling pathway, thereby enhancing overall hair follicle growth. Notably, miR-221-3p, highly expressed in htSKP-EVs, suppressed DKK2 expression, activated the Wnt pathway in human dermal papilla cells (hDPCs), and induced hair follicles to enter and sustain the anagen phase, based on the aforementioned similar in vivo and in vitro experiments. These findings, validated in hHFSCs, hDPCs and human hair follicles in vitro and in a murine alopecia model in vivo, revealed the potential mechanism of htSKP-EVs in hair growth and identified a new therapeutic target for alopecia in regenerative medicine.
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Junjun Yang,Xiaoyuan Gong,Tao Li,Zengzilu Xia,Rui He,Xiongbo Song,Xin Wang,Jiangyi Wu,Jiajia Chen,Fangzheng Wang,Ran Xiong,Yangjing Lin,Guangxing Chen,Liu Yang,Kaiyong Cai
In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.
研究领域:
生物材料
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免疫学
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骨生物学
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干细胞研究
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再生医学
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DOI
高影响因子
危险品化学品经营许可证（带存储）