JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
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IF 10.6
Xu Wenhao,Ye Shiqi,Liu Wangrui,Guo Huaqi,Zhang Linhui,Wei Shiyin,Anwaier Aihetaimujiang,Chang Kun,Malafaia Guilherme,Zhang Hailiang,Ye Dingwei,Wei Gang
In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8 + effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4 + macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4 + macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4 + macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals. Graphical Abstract
研究领域:
环境健康
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分子生物学
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免疫学
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肾病学
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癌症研究
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DOI
PubMed
高影响因子
Stem Cells International
·
2024
·Vol. 2024
·期 1
·7419270
·
IF 3.8
Rui Zhai,Fumin Tai,Kexin Ding,Xin Tan,Hujie Li,Zhengyue Cao,Changhui Ge,Xiaofei Zheng,Hanjiang Fu
Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.
研究领域:
肿瘤学
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干细胞生物学
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放射生物学
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肺科学
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分子生物学
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DOI
PubMed
高影响因子
TALANTA
·
2026
·
IF 6.1
Xuting Liu,Yi Zhen,Xin Ren,Yuhong Xiang,Nengsheng Ye,Lu Zhang
The circular RNAs (circRNAs) and their homologous linear RNAs are involved in various cellular functions and disease development. The simultaneous detection of them can correctly reflect the changes in the gene transcription process, thereby facilitating the studies of RNA-related mechanisms and biomarker discovery. The high sequence homology between circular RNAs and their linear counterparts has always been a challenge for their specific detection. Herein, a two-type RNA detection platform based on DNA-stabilized silver nanoclusters (DNA-AgNCs) is designed for the simultaneous detection of circRNAs and homologous linear RNAs. The decreased fluorescence induced by the open of the hairpin structure of DNA-AgNCs can indicate the whole amount of the two-type RNAs. When G-rich DNA is present in the system, its bind with the back splice junction site in circRNAs results in a fluorescence redshift and enhancement, which can indicate the presence and amount of the circRNA. The concentrations of the circRNA and the two-type RNAs were quantified by the change in fluorescence intensity, with the limits of detection of 1.10 pM and 3.46 pM, respectively. The homologous linear RNA concentration can be quantified by subtracting the concentration of circRNA from the total concentration of the two-type RNAs. The platform was successfully applied for the detection of circABCB10 and its homologous linear RNA in cells and showed high selectivity and great potential for the detection of disease-related circRNAs and linear RNAs in biomedical research.
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PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
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DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 30
·2201425
·
IF 17.521
Huan Lei,Daidi Fan
In addition to oxidative stress and impaired angiogenesis, the overexpression of metalloproteinases (MMPs) and proinflammatory cytokines, which are promoted by hyperglycemia, causes chronic inflammation in diabetic wounds. Herein, TA-siRNA nanogels are prepared for the first time on the basis of the self-assembling interaction between tannic acid (TA) and short interfering RNA (siRNA). The efficient, biodegradable nanogels are cross-linked with poly(vinyl alcohol) (PVA), human-like collagen (HLC), TA, and borax to prepare adaptive, conductive PHTB (TA-siRNA) hydrogels. In response to high levels of reactive oxygen species (ROS), the ROS-responsive borate ester bonds in the hydrogels are oxidized and broken, and TA-siRNA nanogels are released into cells to reduce the expression of the MMP-9. Moreover, the TA and HLC promote collagen expression, reduce inflammation, and ROS level. It is found that electrical stimulation (ES) promotes the in vivo release of TA-siRNA nanogels from PHTB (TA-siRNA) hydrogels and endocytosis of the nanogels. The combination therapy using ES and PHTB (TA-siRNA) hydrogels accelerates the healing of diabetic wounds by reducing the levels of ROS and MMP-9 and promoting the polarization of macrophages, production of collagen, and angiogenesis. This study provides insights on the design of functional gene-delivery and efficient therapeutic strategies to promote the repair of diabetic chronic wounds.
研究领域:
生物医学工程
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伤口愈合
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纳米技术
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基因治疗
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糖尿病研究
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2022
·
IF 14.026
Liang Qi,Jiayun Zhang,Ying Gao,Pin Gong,Chengyuan Liang,Yao Su,Qiao Zeng,Yafeng Zhang
The regulator of expression of virion (Rev) protein binds specifically to the Rev-responsive element (RRE) RNA in order to regulate the expression of the human immunodeficiency virus (HIV)-1 genes. Fluorescence indicator displacement assays have been used to identify ligands that can inhibit the Rev–RRE interaction; however, the small fluorescence indicators cannot fully replace the Rev peptide or protein. As a result, a single rhodamine B labeled Rev (RB-Rev) model peptide was utilized in this study to develop a direct and efficient Rev–RRE inhibitor screening model. Due to photon-induced electron transfer quenching of the tryptophan residue on the RB fluorophore, the fluorescence of RB in Rev was weakened and could be dramatically reactivated by interaction with RRE RNA in ammonium acetate buffer (approximately six times). The interaction could reduce the electron transfer between tryptophan and RB, and RRE could also increase RB fluorescence. The inhibitor screening model was evaluated using three known positive Rev–RRE inhibitors, namely, proflavin, 6-chloro-9-[3-(2-chloroethylamino)propylamino]-2-methoxyacridine (ICR 191), and neomycin, as well as a negative drug, arginine. With the addition of the positive drugs, the fluorescence of the Rev–RRE decreased, indicating the displacement of RB-Rev. This was confirmed using atomic force microscopy (AFM) and the fluorescence was essentially unaffected by the addition of arginine. The results demonstrated that RB-Rev can be used as a fluorescent probe for recognizing small ligands that target RRE RNA. The Rev–RRE inhibitor screening model offers a novel approach to evaluating and identifying long-acting Rev inhibitors.
研究领域:
病毒学
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生物化学
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分子生物学
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药学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF ANAESTHESIA
·
2026
·
IF 10.3
Xiaoyu Hu,Qingsheng Meng,Sai Chen,Jinjin Yang,Mingming Zhao,Yangyang Shan,Jian-jun Yang,Lei Lei
Background Perioperative exposures such as general anaesthesia can induce long-term neurodevelopmental changes with potential intergenerational effects, but the paternal epigenetic mechanisms remain unclear. We investigated whether neonatal sevoflurane exposure in male rats drives intergenerational anxiety through DNA methyltransferase 2 (DNMT2)-dependent remodelling of sperm transfer RNA–derived small RNAs (tsRNAs). Methods Anxiety-like behaviours and hypothalamic-pituitary-adrenal (HPA) axis function were assessed in F0 males (sevoflurane-exposed or control generation), their offspring (F1), and grand-offspring (F2). Glucocorticoid receptor (GR)–mediated DNMT2 regulation was verified using chromatin immunoprecipitation quantitative polymerase chain reaction and primary cell assays. Sperm tsRNA profiles and 5-methylcytosine (m 5 C) methylation were analysed using small RNA sequencing and liquid chromatography–tandem mass spectrometry. Epididymal exosomes were isolated, and their role in tsRNA transfer was evaluated. Pharmacological and genetic interventions (GR blockade, DNMT2 knockdown, exosome inhibition) were used for validation of the pathway. Results Paternal neonatal sevoflurane exposure induced anxiety-like behaviours in F0 males (open-field test, P =0.041; elevated plus maze, P =0.005) and F1 (not F2) offspring. Sevoflurane-induced HPA axis sensitisation, sustained corticosterone elevation ( P =0.004), and GR-mediated DNMT2 upregulation in the cauda epididymis ( P =0.014) of F0 males, with increased sperm m 5 C methylation ( P =0.019) and aberrant tsRNA profiles. Epididymal exosomes mediated tsRNA transfer; DNMT2 knockdown or exosome blockade prevented tsRNA remodelling and intergenerational anxiety. Similar alleviating effects were observed after paternal treatment with the DNMT inhibitor decitabine. Conclusions Neonatal sevoflurane exposure triggers a paternal GR-DNMT2 pathway in the epididymis, reprogramming sperm tsRNA profiles and driving intergenerational anxiety in a rat model. Epididymal DNMT2 is a key epigenetic mediator of anaesthesia-induced inheritance, and the alleviating effects of decitabine suggest additional mediating mechanisms.
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高影响因子
AIP Advances
·
2025
·Vol. 15
·期 7
·
IF 1.4
Yu Dong-hua,Wang Yu,Yu Chun-Miao,Zhou Qi,Liu Shu-min,Liu Ting-ting
The aim of this study is to construct a competitive endogenous RNA regulatory network of gouty arthritis through transcriptomics and investigate its underlying pathogenesis. Transcriptomics was performed with the rats’ joints in both the control and model groups. The mRNA, miRNA, lncRNA, and circRNA were analyzed using the R language. The RNA data were visualized as the ceRNA network. Genes were combined, the KEGG pathway was enriched, and the first five pathways were selected. Meanwhile, relationships between genes in the extraction pathway were integrated into a network, and key genes were mapped. mRNA, lncRNA, and circRNA were scored to compare the conservatism of RNA. Finally, lncRNA, circRNA, miRNA, and genes were considered the core, and information about other differential RNAs having a targeted relationship with them (i.e., host genes) was added. Based on ceRNA analysis, the relationship pairs between lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were extracted. A total of 1165 de-mRNAs, 91 de-miRNAs, 456 de-lncRNAs, and 70 de-circRNAs were selected. The key genes were identified for pathway enrichment, such as the phospholipase D signaling pathway and endocytosis. Based on the ceRNA analysis, the networks of lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were constructed. The differentially expressed RNAs between the control and model groups were identified using the transcriptomics of ankle tissue. The findings indicate that mRNA, lncRNA, and circRNA can competitively bind to GA-related miRNAs, leading to mutual regulatory effects. The RNAs identified from the constructed lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks are potential targets for therapeutic drugs and may be involved in the pathogenesis of GA.
研究领域:
分子生物学
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基因组学
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生物信息学
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RNA生物学
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免疫学
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关节炎研究
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DOI
高影响因子
International Journal of Biological Sciences
·
2020
·
IF 4.858
Yiliang Wang,Lianzhou Huang,Yun Wang,Weisheng Luo,Feng Li,Ji Xiao,Shurong Qin,Zhaoyang Wang,Xiaowei Song,Yuan Wang,Fujun Jin,Yifei Wang
Herpes simplex virus (HSV) type 1 (HSV-1) infection exhibited high heterogeneity at individual cells level, including the different gene expression patterns and varying amounts of progeny virus. However, the underlying mechanism of such variability remains obscure. The importance of host long noncoding RNAs (lncRNAs) in virus infection had been recognized, while the contribution of lncRNAs to the heterogeneous infection remains unknown. Herein, a prior single-cell RNA sequencing data using HSV-1 reporter strain expressing ICP4-YFP was re-analyzed to obtain the differentially expressed lncRNA between the successfully initiated viral gene expression (ICP4-YFP + ) cells and the aborted infection cells (ICP4-YFP - ). The ICP4-YFP + population show a higher abundance of MAMDC2 antisense 1 (MAMDC2-AS1) lncRNA than ICP4-YFP - population. MAMDC2-AS1 silencing reduces the expression of HSV-1 immediate early (IE) genes and limit HSV-1 infection in human host cells. Consistently, ectopic expression of MAMDC2-AS1 enhances HSV-1 IE genes transcription and facilitates the formation of HSV-1-induced plaques. Mechanically, both RNA-pull down and RNA immunoprecipitation assays show that MAMDC2-AS1 interacts with the RNA binding protein heat shock protein 90α (Hsp90α), a molecular chaperone involving in the nuclear import of HSV-1. The MAMDC2-AS1-Hsp90α interaction facilitates the nuclear transport of viral tegument protein VP16, the core factor initiating the expression of HSV-1 IE genes. The transcription factor YY1 mediates the induction of MAMDC2-AS1 upon HSV-1 infection. Our study elucidates the contribution of lncRNA to HSV-1 infection susceptibility in human cells and the role of Hsp90α RNA binding activity in HSV-1 infection.
研究领域:
病毒学
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分子生物学
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细胞生物学
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基因组学
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DOI
PubMed
高影响因子
HUMAN MUTATION
·
2026
·
IF 1.8
Xiaomei Nie,Gang Su,Ran Zhang,Han Wang,Mingbo Li,Qian Liang
Background Diabetic retinopathy is caused by chronic hyperglycemia, which damages the retina′s blood vessels and neurons. This study is aimed at identifying potential therapeutic targets for DR. Methods Transcriptomic and proteomic data were obtained from the Gene Expression Omnibus (GEO) and ProteomeXchange databases, respectively. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were intersected. An enrichment analysis of the overlapping genes was performed based on the DAVID database. A protein–protein interaction (PPI) network (STRING) was analyzed via Cytoscape/cytoHubba to identify key genes. Single‐cell RNA‐sequencing (scRNA‐seq) data were processed using Seurat. Gene set enrichment analysis (GSEA) (clusterProfiler) and molecular docking (EnrichR) were performed. High glucose‐induced retinal microvascular endothelial cells (RMECs) were used for functional assays. Results The intersection of DEGs and DEPs yielded shared genes, enriched in the PI3K–Akt signaling pathway, AGE–RAGE signaling pathway in diabetic complications, complement and coagulation cascades, and ECM–receptor interaction; a PPI network incorporating these genes revealed two key DR‐associated highly expressed genes, COL1A1 and SERPINE1. GSEA showed that samples with high expression of these key genes were enriched in pathways such as reactome signaling by TGFB family members, inflammatory response, TGF‐ β signaling, and reactome cell extracellular matrix interactions. Single‐cell and molecular docking analyses revealed high expression of the two key genes in fibroblasts and binding between SERPINE1 and paricalcitol, and HG induction increased their levels in RMECs, whereas knockdown of SERPINE1 repressed RMEC proliferation, migration, and invasion in vitro. Conclusion This study identifies SERPINE1 and COL1A1 as possible DR therapeutic targets, providing new insights into relevant therapeutic development.
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PubMed
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Yunsheng Lu,Yibin Huang,Chenchen Mao,Pengfei Shan,Chenkang Wu,Jiongzhou Zhu,Yujie Lin,Zhongyu Li,Mingdong Lu
Silencing NOP2/Sun RNA methyltransferase family member 2 (NSUN2) effectively inhibits gastric cancer (GC) progression but is limited by RNase degradation, rapid renal clearance, and low uptake. Based on the characteristic high levels of reactive oxygen species (ROS) in the tumor microenvironment, this study designed and synthesized a novel ROS-responsive ferrocene nanoparticle loaded with siNSUN2 (PRPFc@siNSUN2). Under ROS conditions, the nanoparticle disintegrates to release siNSUN2. Characterization by proton nuclear magnetic resonance, transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry revealed that PRPFc@siNSUN2 is spherical, with an average diameter of 88.79 ± 1.14 nm, an encapsulation efficiency of 83.10%, and a drug loading capacity of 13.85%. Moreover, these nanoparticles demonstrated excellent stability and, under hydrogen peroxide conditions, exhibited structural disruption leading to the release of siNSUN2, thereby confirming their high ROS responsiveness. In vitro, PRPFc@siNSUN2 markedly enhanced the inhibition of GC cell proliferation, migration, and invasion, and promoted apoptosis, accompanied by increased intracellular ROS and improved siNSUN2 uptake. In vivo studies further confirmed that PRPFc@siNSUN2 markedly enhanced the therapeutic efficacy of siNSUN2 against GC, while exhibiting low cytotoxicity and good biocompatibility. Overall, our findings indicate that PRPFc@siNSUN2, with its favorable morphology, stability, and ROS-triggered release, substantially improves the anti-GC effects of siNSUN2 by inhibiting GC cell proliferation, migration, and invasion, as well as by promoting apoptosis. These results support NSUN2 as a promising therapeutic target and underscore the potential of PRPFc@siNSUN2 nanoparticles in drug delivery, offering a novel strategy to improve clinical outcomes for GC patients.
研究领域:
肿瘤学
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2026
·
IF 4
Wendan Zheng,Dongke Liu,Hongxu Chen,Jingyang Zhao,Songping Zhang
As the 2.0 version of mRNA technology, circular RNA (circRNA) is advantageous over the linear mRNA in stability, offered by its covalently closed loop structure. In the in vitro circularization (IVC) system for circRNA synthesis, there exist linear precursor RNA and nicked RNA by-product as impurities. Both impurities are highly similar to the target circRNA in size and structure, making high-resolution separation and quantification of circRNA more challenging. In this study, we developed a capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) method, which could precisely separate the circRNA from its impurities in the IVC systems with high resolution (Rs > 5.8) and excellent reproducibility (RSD < 0.04%). We then focused on the different migration behaviors of circRNA in gel environments by systematically exploring the key influencing factors, including sample pretreatment, separation voltage and gel matrix. Our results demonstrated that the circular integrity of circRNA is a critical determinant of its electrophoretic migration behavior. Pretreating the circRNA with denaturant or prolonging the migration time increased the possibility of its digestion into the nicked species. Further mechanistic analysis revealed that circRNA underwent random, rather than sequence-dependent backbone cleavage during electrophoresis. These findings suggested that circRNA stability during electrophoretic separation may be influenced by cumulative mechanical stress arising from the combined effects of electrophoretic force and molecular sieving. The mechanism elucidating the determinants of circRNA mobility in different gel systems lays the foundation for developing more reliable approaches for circRNA purification and characterization.
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PubMed
高影响因子
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