MICROCHIMICA ACTA
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2025
·Vol. 192
·期 9
·1-14
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IF 5.3
Hao Weiyuan,Chen Cheng,Cao Fei,Xu Min,Zheng Jiaping
This study presents an integrated approach combining photoelectrochemical (PEC) biosensing, density functional theory (DFT), and machine learning (ML) to address diagnostic and mechanistic challenges in cholangiocarcinoma (CCA). A novel Bi 4 Ti 3 O 12 /WS 2 heterojunction was engineered as a high-performance PEC platform, exhibiting broad-spectrum absorption extending to 850 nm and a 70% reduction in photoluminescence intensity due to suppressed electron–hole recombination. The optimized biosensor achieved ultrasensitive miR-29a detection with a linear range of 1 fM–200 nM, a detection limit of 0.19 fM, and 98.2–102.5% recovery in spiked serum, alongside robust specificity and reproducibility (1.3% RSD over 16 cycles). DFT calculations revealed interfacial electronic coupling between Bi 4 Ti 3 O 12 and WS 2 , narrowing the bandgap to 1.571 eV and establishing a type-II charge transfer pathway, which synergistically enhanced photocurrent generation compared with pristine WS 2 . Parallel ML analysis of multi-omics datasets uncovered consistent miR-29a upregulation in CCA tumors and identified integrins COL4A1/CDK6 as top discriminative targets. The Random Forest classifier integrating miR-29a and targets achieved 0.890 AUC for tumor diagnosis, revealing pathway-specific regulatory networks. The bridging nanomaterial innovation with computational biology not only advances ultrasensitive miRNA detection but also deciphers miR-29a’s dual role in CCA pathogenesis, offering a novel framework for precision oncology. Graphical
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JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Rui Zhang,Jingyao Guo,Yupeng Wang,Rundong Sun,Guangzhu Dong,Xinru Wang,Guizhen Du
The increased usage of bisphenol S (BPS) results in wide distribution in pregnant women. In this study, pregnant mice were given multiple-dose BPS during gestation. Results showed that prenatal BPS exposure (50 μg/kg/day) induced increased weight gain, dyslipidemia, higher liver triglyceride (TG), adipocyte hypertrophy, and hepatic lipid deposition in male offspring . Exosomes play important roles in regulating lipid metabolism . Here, serum exosomes and adipose miRNA sequencing of male offspring indicated a remarkable decrease in miR-29a-3p expression. To clarify whether adipocyte-derived exosomes mediate hepatic lipid deposition, exosomes were extracted from BPS-treated adipocytes and co-cultured with hepatocytes. These exosomes could be taken up by hepatocytes and promoted lipid deposition, and notably, exosomal miR-29a-3p was downregulated. Furthermore, miR-29a-3p knockdown in adipocyte-derived exosomes promoted hepatocyte lipid deposition, whereas overexpression led to the opposite effect. Also, the role of miR-29a-3p was demonstrated in hepatocytes by overexpressing or knocking it down. Subsequent studies have shown that miR-29a-3p can promote lipid deposition by directly targeting Col4a1 . Taken together, prenatal BPS exposure could lead to lower miR-29a-3p yield in adipocyte-derived exosomes and decrease miR-29a-3p content transported to hepatocytes, which further negatively regulate Col4a1 and promote hepatic lipid deposition. Our findings provided clues to maternal environmental exposure-induced liver metabolic diseases.
研究领域:
毒理学
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分子生物学
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内分泌学
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发育生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Jiakai Xing,Jiaxin Jia,Xiaofeng Cong,Ziling Liu,Quanshun Li
MicroRNAs have been identified as a promising tool in cancer gene therapy, and an efficient and safe gene carrier was significantly required in the clinical application of miRNAs. Herein, a polyethylenimine (PEI) derivative, N -isopropylacrylamide-modified PEI (namely PEN), was constructed through Michael addition and then employed as a carrier for miR-29a transfection. The carrier PEN has been demonstrated to possess favorable ability to condense miR-29a into stable nanoparticles and protect miR-29a against the nuclease degradation, using agarose gel retardation assay. Meanwhile, PEN exhibited excellent efficiency in miR-29a transfection demonstrated by flow cytometry and confocal laser scanning microscope. Further, the PEN-mediated miR-29a transfection could achieve an obvious anti-proliferative effect owing to the activation of cell apoptosis and the cell cycle arrest at G1 phase, using human lung adenocarcinoma cell line A549 as a model. In addition, PEN/miR-29a nanoparticles could suppress the migration and invasion of cancer cells measured by wound healing and Transwell migration assays. Overall, the PEN-mediated miR-29a transfection could be potentially employed as a useful approach to achieve cancer gene therapy.
研究领域:
生物技术
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分子生物学
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肿瘤学
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药学
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TOXICOLOGY LETTERS
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2022
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IF 4.271
Shuhong Guan,Hui Liu,Jun Zhou,Qiudi Zhang,Hui Bi
Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis . Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo , MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro , MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.
研究领域:
肺科学
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分子生物学
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细胞生物学
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药理学
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2015
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IF 2.297
Shuai Wang,Jie Zan,Mingjie Wu,Wenting Zhao,Zhenwei Li,Yanyun Pan,Zewei Sun,Jianhua Zhu
Monocyte differentiation into macrophages results in upregulation of miR-29a and scavenger receptor A (SRA) expression, while the expression of RNA binding protein , QKI is suppressed. Since SRA is a functionally important protein in atherosclerosis, it is imperative to understand the various mechanisms involved in its regulation specially the mechanism involving miR-29a. There are individual studies linking miR-29a to SRA or QKI to monocyte differentiation but there is no evidence of any linkage among them. Therefore, we intend to investigate the association among these three, if any, in terms of regulation of SRA expression. Hence, in this study, the differentiated macrophages were initially transfected with miR-29a or its inhibitor and it was shown that QKI is a direct target of mir-29a. In addition, it was also observed by bioinformatics analysis that 3′UTR in SRA mRNA has QKI binding site. So, we attempted to further understand the role of QKI in SRA regulation. The macrophages were manipulated either with overexpression of QKI or by its ablation and it was observed that QKI suppressed SRA at the transcriptional level. Moreover, with the help of luciferase reporter vector, it was shown that QKI inhibited SRA transcription by binding to QRE region in its 3′UTR mRNA. Furthermore, to link the QKI mediated regulation of SRA expression with its functional activity; we analyzed lipid uptake capacity of macrophages transfected with either ectopic OKI plasmid or ablated for QKI. It was observed that, indeed, QKI upregulation inhibits lipid uptake by repressing SRA expression. Overall, our study demonstrates that miR-29a inhibits QKI, which in turn results in upregulation of SRA and lipid uptake.
研究领域:
分子生物学
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细胞生物学
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心血管疾病
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ACS Applied Polymer Materials
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2025
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IF 4.7
Yingqi Wei,Hao Wang,Yaxi Zhu,Guancheng Zhan,Lihuan Zhang,Huichang Gao,Longyang Jin,Ruobing Feng
Peripheral nerve injury frequently occurs alongside vascular injury due to the incorporation of vascular tissue within the nerve bundle. During the repair process of peripheral nerve injuries, the concurrent regeneration of capillaries within the nerve bundles is crucial for facilitating nerve regeneration. However, current studies often overlook the regeneration of blood vessels in nerve bundles when designing nerve repair scaffolds, leading to suboptimal nerve regeneration outcomes. To address this limitation, amino-modified Cu-doped mesoporous bioactive glass (Cu-MBG) was developed as a nanodelivery carrier for miR-29a to construct miR-29a@Cu-MBG nanoparticles, which exhibit dual functionality in promoting nerve regeneration and inducing vascular regeneration. Subsequently, miR-29a@Cu-MBG was incorporated into a CS/GelMA hydrogel to create an engineered multifunctional nerve conduit through the ionic cross-linking of chitosan and the optical cross-linking of GelMA, which demonstrated excellent mechanical properties and biocompatibility. In vitro cell experiments indicated that the sustained release of miR-29a@Cu-MBG from the conduit effectively delivered miR-29a into PC12 cells, leading to the upregulation of nerve regeneration-associated genes (GAP-43 and NF-200) and the outgrowth of neurite. Additionally, Cu-MBG was found to enhance the migration of HUVECs and upregulate genes related to angiogenesis (HIF-α, ANG, eNOS, and KDR), promoting the tube formation of HUVECs. These findings offer a perspective for the design of nerve conduits capable of promoting both nerve and vascular regeneration.
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Small
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2023
·
IF 13.3
Shaowei Pan,Zhaowei Yin,Chen Shi,Haonan Xiu,Guanfu Wu,Yongyuan Heng,Zhangyu Zhu,Jing Zhang,Jianchao Gui,Ziyi Yu,Bin Liang
The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.
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Oxidative Medicine and Cellular Longevity
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2022
·
IF 7.31
Xiang Li,Longlong Wu,Xuan Tian,Weiping Zheng,Mengshu Yuan,Xiaorong Tian,Huaiwen Zuo,Hongli Song,Zhongyang Shen
Hepatic ischemia-reperfusion injury (IRI) is an inevitable result of liver surgery. Steatotic livers are extremely sensitive to IRI and have worse tolerance. Ferroptosis is considered to be one of the main factors of organ IRI. This study is aimed at exploring the role of ferroptosis in the effect of heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) on steatotic liver IRI and its mechanism. An IRI model of a steatotic liver and a hypoxia reoxygenation (HR) model of steatotic hepatocytes (SHPs) were established. Rat BMMSCs were extracted and transfected with the Ho1 gene to establish HO-1/BMMSCs, and their exosomes were extracted by ultracentrifugation. Ireb2 was knocked down to verify its role in ferroptosis and cell injury in SHP-HR. Public database screening combined with quantitative real-time reverse transcription PCR identified microRNAs (miRNAs) targeting Ireb2 in HO-1/BMMSCs exosomes. miR-29a-3p mimic and inhibitor were used for functional verification experiments. Liver function, histopathology, terminal deoxynulceotidyl transferase nick-end-labeling staining, cell viability, mitochondrial membrane potential, and cell death were measured to evaluate liver tissue and hepatocyte injury. Ferroptosis was assessed by detecting the levels of IREB2, Fe2+, malondialdehyde, glutathione, lipid reactive oxygen species, glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2 mRNA, and mitochondrial morphology. The results revealed that HO-1/BMMSCs improved liver tissue and hepatocyte injury and suppressed ferroptosis in vivo and in vitro. The expression of IREB2 was increased in steatotic liver IRI and SHP-HR. Knocking down Ireb2 reduced the level of Fe2+ and inhibited ferroptosis. HO-1/BMMSC exosomes reduced the expression of IREB2 and inhibited ferroptosis and cell damage. Furthermore, we confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p.
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