Cell Reports
·
2024
·
IF 7.5
Sijia Ren,Feng Bai,Viviane Schnell,Clara Stanko,Muriel Ritsch,Tino Schenk,Emanuel Barth,Manja Marz,Bin Wang,Xin-Hai Pei,Holger Bierhoff
Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3' end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 5
·1305-1313
·
IF 4.58
Zhou Lili,Wang Jian,Chen Zhongping,Li Junlong,Wang Ting,Zhang Zhang,Xie Guoming
MicroRNAs (miRNAs) play a considerable role in cancer occurrence and development, and have been identified as promising noninvasive biomarkers. The authors describe a voltammetric method for the determination of the cancer biomarker microRNA-21 (miRNA). It is based on a combination of a universal DNA signal transducer and isothermal target recycling amplification. A hairpin capture probe is bound to the target miRNA to form a duplex structure and to create a toehold in the transducer for initiating the target recycling amplification reaction. In contrast to traditional capture probes, a mismatched site is introduced to improve its ability to capture the target. In order to reduce the complex design procedures of the sequence and widen the applicability of this method, a signal transducer is introduced. Under optimal conditions, response to target miRNA is linear in the 0.5 to 2000 pM concentration range, with a 56 fM. detection limit (at an S/N ratio of 3). In order to characterize the process of target recycling and the stepwise modification of the electrode, real-time fluorescence, agarose gel electrophoresis, cyclic voltammetry, electrochemical impedance spectroscopy and chronocoulometry were used. The results indicate that this isothermal target recycling amplification results in an electrochemical biosensing scheme with wide potential for sensing other bioanalytes.
Schematic illustration of the electrochemical biosensing platform for miRNA-21 detection based on isothermal target recycling amplification and DNA signal transducer triggered strategy.
研究领域:
生物化学
·
分析化学
·
生物传感器
·
癌症研究
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DOI
高影响因子
TALANTA
·
2024
·
IF 5.6
Yuanxun Gong,Danlei Tong,Ping Qiu,Rilian Song,Zhidan Li,Yanlin He,Qisheng Luo,Qianli Tang,Kai Zhang,Xianjiu Liao
B-type natriuretic peptide (BNP) is a biomarker for heart failure, a serious and prevalent disease that requires rapid and accurate diagnosis. In this study, we developed a novel electrochemical biosensor for BNP detection based on CRISPR/Cas13a and chain substitution reaction. The biosensor consists of a DNA aptamer that specifically binds to BNP, a T7 RNA polymerase that amplifies the signal, a CRISPR/Cas13a system that cleaves the target RNA, and a two-dimensional DNA nanoprobe that generates an electrochemical signal. The biosensor exhibits high sensitivity, specificity, and stability, with a detection limit of 0.74 aM. The biosensor can also detect BNP in human serum samples with negligible interference, demonstrating its potential for clinical and point-of-care applications. This study presents a novel strategy for integrating CRISPR/Cas13a and chain substitution reaction into biosensor design, offering a versatile and effective platform for biomolecule detection.
研究领域:
生物技术
·
生物化学
·
分子生物学
·
电化学
·
医学诊断
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DOI
PubMed
高影响因子
iScience
·
2023
·Vol. 26
·期 10
·107943-107943
·
IF 5.8
Nan Xiang,Hao Xu,Zhou Zhou,Junyu Wang,Pengfei Cai,Li Wang,Zhen Tan,Yingbo Zhou,Tianping Zhang,Jiayuan Zhou,Ke Liu,Songwen Luo,Minghao Fang,Guosheng Wang,Zhuo Chen,Chuang Guo,Xiaomei Li
Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by lymphocytic infiltration and exocrine dysfunction, particularly affecting the salivary gland (SG). We employed single-cell RNA sequencing to investigate cellular heterogeneity in 11 patients with pSS and 5 non-SS controls. Notably, patients with pSS exhibited downregulated SOX9 in myoepithelial cells, potentially associated with impaired epithelial regeneration. An expanded ACKR1 + endothelial subpopulation in patients with pSS suggested a role in facilitating lymphocyte transendothelial migration. Our analysis of immune cells revealed expanded IGHD + naive B cells in peripheral blood from patients with pSS. Pseudotime trajectory analysis outlined a bifurcated differentiation pathway for peripheral B cells, enriching three subtypes (VPREB3 + B, BANK1 + B, CD83 + B cells) within SGs in patients with pSS. Fibroblasts emerged as pivotal components in a stromal-immune interaction network, potentially driving extracellular matrix disruption, epithelial regeneration impairment, and inflammation. Our study illuminates immune and stromal cell heterogeneity in patients with pSS, offering insights into therapeutic strategies.
研究领域:
免疫学
·
转录组学
·
自身免疫疾病
·
细胞异质性
·
基质细胞
·
B细胞分化
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yi He,Lejia Zhang,Siyuan Huang,Yuquan Tang,Yiming Li,Hongyu Li,Guanhui Chen,Xun Chen,Xiliu Zhang,Wei Zhao,Feilong Deng,Dongsheng Yu
Background The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.
研究领域:
生物材料
·
组织工程
·
骨再生
·
分子生物学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zhuangzhuang Chu,Xingdan Liu,Tong Zhao,Dongya Jiang,Jing Zhao,Xiaohua Dong,Kelvin W.K. Yeung,Xuanyong Liu,Yun Liao,Liping Ouyang
Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
·
组织工程
·
材料科学
·
光热治疗
·
感染控制
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Nano Energy
·
2019
·
IF 15.548
Fu-Ting Wang,Yi-Han Wang,Jing Xu,Ke-Jing Huang,Zhen-hua Liu,Yun-fei Lu,Shu-yu Wang,Zi-wei Han
A self-powered microRNA (miRNA) biosensing device is fabricated with high-energy enzymatic biofuel cell (EBFC) and cruciform DNA (cDNA). Sulfur-selenium co-doped graphene/gold nanoparticles (S–Se-GR/AuNPs) is synthesized and used as supporting substrate of biocathode and bioanode . The glucose oxidase (GOD) molecules are bonded to carboxyl-functionalized AuNPs through the condensation reaction between the amino groups in enzyme and carboxyl groups on the AuNPs to form the bioanode. The ultra-thin porous carbon shell/AuNPs-complementary strand of cDNA (UPCS/AuNPs-cDNA) is meticulously designed. The potassium ferricyanides are then inserted in mesoporous UPCS/AuNPs as the biocathode electron acceptor , and the cruciform DNA bioconjugate is synthesized as signal amplifier. When target miRNA is added, the hybridization reaction happens between miRNA and capture probe DNA on the biocathode to open the capture probe DNA chain. Cruciform DNA bioconjugate is immobilized onto the biocathode through base pairing with the capture DNA on the biocathode, which can release electron acceptor [Fe(CN) 6 ] 3- , resulting in the dramatically increase of the open circuit voltage of the EBFCs. The self-powered biosensor responds linearly in the miRNA level range of 0.5–10000 fM with a detection limit of 1.5 × 10 −16 mol L −1 . Detection of miRNA in spiked serum samples is also realized with the self-powered biosensor, demonstrating its great potential in the clinical applications.
研究领域:
生物工程
·
生物医学工程
·
分析化学
·
分子生物学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 29
·23966
·
IF 4.6
Yi Liu,Zheng Zhang,Huyang Du,Xiangjun Chen,Nan Hu,Tingting Yu,Meili Hou,Xiaolin Yu
Chemoresistance poses a critical challenge in cancer therapy across diverse tumor types, including non-small cell lung cancer (NSCLC), where chemotherapy-induced neuroendocrine differentiation (NED) of tumor cells plays a pivotal role in acquiring treatment resistance. This process significantly reduces chemotherapy efficacy, accelerates tumor progression, and ultimately worsens patient survival outcomes. The complex mechanisms underlying chemoresistance involve multiple factors, including enhanced DNA repair pathways, increased drug efflux capacity, and alterations in gene expression. Additionally, the tumor microenvironment, a dynamic ecosystem surrounding cancer cells, fosters a protective niche that exacerbates chemotherapy resistance. To address this challenge, we propose an innovative nanocomposite hydrogel system for the co-delivery of cisplatin and short hairpin RNA (shRNA) targeting protein arginine methyltransferase 5 (PRMT5), a key gene implicated in drug resistance. This system utilizes polyethyleneimine-modified mesoporous silica nanoparticles, which serve as nanocarriers, encapsulating cisplatin within the mesopores and coating the surface with methacryloylated hyaluronic acid (HA-MA). The design enables tumor microenvironment-responsive drug release, triggered by hyaluronidase enzymes abundant within the tumor, resulting in nanoparticle disassembly and the release of cisplatin. Simultaneously, the delivery of shRNA silences PRMT5 expression, enhancing chemosensitivity. By integrating targeted gene therapy with chemotherapy, this system offers a promising strategy for overcoming chemoresistance in NSCLC. Targeting both cancer cells and their microenvironment, this approach holds potential to transform the treatment of chemotherapy-resistant cancers, advancing more effective and personalized oncological therapies. An enzyme-responsive hydrogel to co-deliver cisplatin and shRNA, targeting NED-driven chemoresistance in NSCLC.
研究领域:
肿瘤学
·
纳米医学
·
药物递送
·
分子生物学
·
癌症治疗
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR GENETICS AND GENOMICS
·
2022
·Vol. 297
·期 3
·801-815
·
IF 2.98
Zhang Yonglei,Gao Shanshan,Zhang Ping,Sun Haidi,Lu Ruixue,Yu Runnan,Li Yanxiao,Zhang Kunpeng,Li Bin
Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum ; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2 , Isocitrate dehydrogenase , and Cytochrome b-related protein , might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP , UGT , GST , OBP , CSP , and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7 , detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum , providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum . These results aid eugenol insecticidal mechanisms and provide the basis of insect control.
研究领域:
昆虫学
·
分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Wu Min,Wang Tingting,Ji Nan,Lu Ting,Yuan Ran,Wu Lingxiang,Zhang Junxia,Li Mengyuan,Cao Penghui,Zhao Jiarui,Li Guanzhang,Li Jianyu,Li Yu,Tang Yujie,Gao Zhengliang,Wang Xiuxing,Cheng Wen,Ge Ming,Cui Gang,Li Rui,Wu Anhua,You Yongping,Zhang Wei,Wang Qianghu,Chen Jian
Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.
研究领域:
肿瘤学
·
基因组学
·
药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 33
·2302622
·
IF 15.1
Yifan Ma,Lili Sun,Jingjing Zhang,Chi-ling Chiang,Junjie Pan,Xinyu Wang,Kwang Joo Kwak,Hong Li,Renliang Zhao,Xilal Y. Rima,Chi Zhang,Anan Zhang,Yutong Liu,Zirui He,Derek Hansford,Eduardo Reategui,Changsheng Liu,Andrew S. Lee,Yuan Yuan,Ly James Lee
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.
研究领域:
再生医学
·
组织工程
·
干细胞生物学
·
骨修复
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）