TOXICOLOGY LETTERS
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2025
·
IF 2.9
Sili Chen,Liqin Xiong,Xinlan Wu,Lu Chen,Junwei Zhang,Guanqing Jiang,Xin Li,Qiaoyuan Yang
We investigated the toxicity of benzo[ghi]perylene (BghiP), a prevalent polycyclic aromatic hydrocarbon (PAH). Transcriptome analysis of control and BghiP-exposed human bronchial epithelial cells (BEAS-2B) led to the identification of a novel chimeric RNA (chRNA), TVP23C-CDRT4, whose expression is significantly downregulated by BghiP in vitro and in vivo. Funcionally, overexpression of TVP23C-CDRT4 inhibited BghiP-induced cell proliferation and DNA damage, whereas its knockdown exacerbated these detrimental effects. Mechanistically, TVP23C-CDRT4 acts as a molecular decoy for miR-24-3p. Thus, BghiP-induced suppression of TVP23C-CDRT4 unveils a novel mechanism of PAH toxicity, highlighting its anti-proliferative and genome-protective roles relevant to the early stages of carcinogenesis.
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高影响因子
Bioengineered
·
2021
·
IF 3.269
Haibo Xie,Hanfei Chai,Xiaohong Du,Rongna Cui,Yinan Dong
Sepsis, resulting from infections, is a systemic inflammatory response syndrome with a high fatality rate. The present study revolves around probing into the function and molecular mechanism of long non-coding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) in modulating acute lung injury (ALI) mediated by sepsis. Here, a sepsis model was constructed using cecal ligation and puncture (CLP) surgery in vivo. The alveolar macrophage cell line NR8383 and the alveolar type II cell line RLE-6TN were dealt with lipopolysaccharide (LPS) for in-vitro experiments. We discovered that OIP5-AS1 and Sirtuin1 (SIRT1) were markedly down-regulated in sepsis models elicited by CLP or LPS, while miR-128-3p experienced a dramatic up-regulation. OIP5-AS1 overexpression attenuated NR8383 and RLE-6TN cell apoptosis triggered by LPS and suppressed the expressions of nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in NR8383 and RLE-6TN cells, whereas miR-128-3p overexpression resulted in the opposite phenomenon. Moreover, OIP5-AS1 overexpression relieved lung edema, lung epithelial cell apoptosis, infiltration of myeloperoxidase (MPO)-labeled polymorphonuclear neutrophils (PMN), inflammatory responses triggered by CLP in vivo. Mechanistically, miR-128-3p, which targeted SIRT1, was hobbled by OIP5-AS1. All in all, OIP5-AS1 overexpression enhanced sepsis-induced ALI by modulating the miR-128-3p/SIRT1 pathway, which helps create new insights into sepsis treatment.
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PubMed
高影响因子
Journal of Cancer
·
2021
·
IF 4.207
Yong-Zhi Lun,Jie Sun,Ben Liu,Wen Dong,Ling-Hong Pan,Jian Lin,Jing-Xia Zhang
Objective: As targeted drugs, exogenous serpins could be introduced to patients to restore body balance. This study aimed to observe further the inhibitory effects of recombinant Hespintor (a Kazal-type serpin) combined with Sorafenib on transplanted human hepatoma tumors in nude mice specimens and to explore the possible transcriptional regulation by Hespintor. Methods: A model of human hepatoma tumors transplanted in nude mice was established, and the medication was administrated to observe the growth of the tumors. Four weeks after the drug administration, the tumors were removed to evaluate the inhibition effects of Hespintor on in-situ tumor growth and liver metastasis. The expression levels of MMP2, MMP9, Bax, Bcl-2, and caspase-3 in the tumor organizations were detected with Western blot. The target genes of the Hespintor were screened based on tissue RNA-Seq, and the regulatory network was constructed. Results: It was found that the recombinant Hespintor displayed a significant antitumor effect on the subcutaneous growth of MHCC97-H cells. Moreover, the therapeutic effects of the combination therapy were significantly better than those of single therapy. 10 target genes with significantly different expression by Hespintoron tumor tissue were identified. Finally, a visual regulatory networkwas constructed for target mRNA-pathway. Conclusions: The antitumor effect of Hespintor combined with Sorafenib in treating the subcutaneously implanted hepatocellular carcinoma tumors in nude mice was significant. The possible transcriptional regulation by Hespintor involved multiple signaling pathways, and it was not just the antitumor effect of uPA via its extracellular inhibitions.
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高影响因子
ACS Sensors
·
2025
·
IF 9.1
Yu Luo,Bicheng Zhu,Congcong Zhu,Penghui Lai,John Taylor,Claire Honney,Ashley Nutsford,Chaofeng Ma,Hailong Chen,Kean C. Aw,Rui Wu,Erasmus Smit,Peikai Zhang,Jadranka Travas-Sejdic
Herein, a novel and simple electrospray (ES) printing technique was developed for the fabrication of ultrathin graphene layers with precisely controlled nanometer-scale thickness, where graphene oxide (GO) was electrosprayed on wafers and subsequently chemically reduced into reduced GO (rGO). Utilizing that technique, we prepared ultrathin rGO in-plane graphene field-effect transistor (GFET)-based biosensors coupled with a portable prototype measuring system for point-of-care detection of pathogens. We illustrate the use of such prepared GFETs to detect COVID-19, using the SARS-CoV-2 nucleocapsid protein antigen (N-protein) and genomic viral RNA as detection targets. The electrosprayed and chemically reduced rGO films enhance the molecular detection in GFET sensors through significant local gating effects. The device detects the N-protein from the SARS-CoV-2 Omicron variant in a culture medium with an LOD of 1.44 PFU/mL and in clinical oropharyngeal samples with an LOD of 45 genome copies/mL in 5 min. It also successfully detects viral RNA in oropharyngeal swabs within 10 min. The GFET sensor responses were further analyzed using our proprietary wireless, miniaturized, and portable FET analyzer, coupled with a smartphone detecting app. Altogether, we present low-cost and mass-producible GFETs with high-quality graphene channels, enabling a portable, efficient, and accurate solution for point-of-care pathogen detection and in clinical testing. This technology has the potential to become a crucial tool in preventing future global epidemic outbreaks.
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高影响因子
DRUG DEVELOPMENT RESEARCH
·
2019
·Vol. 80
·期 6
·750-757
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IF 1.742
Chang Zheng,Wen Hou,Jun Liu,Xiao-Fang Xu,Jing Lin,Ping-Hua Sun,Wei-Min Chen
The prevalence of multidrug resistance among clinically significant bacterial pathogens underlines a critical need for the development of new classes of antibacterial agents with novel structural scaffolds. Cajaninstilbene acid (CSA), which is isolated from pigeonpea leaves, has shown potent antibacterial activity. In this study, a series of 2-hydroxyl-4-methoxyl-3-(3-methylbut-2-en-1-yl)-6-(4-phenylbenzoylamino)benzoic acid derivatives derived from CSA were designed and synthesized, and their antibacterial activities were evaluated. Several synthesized compounds exhibit better antibacterial activity than CSA against Staphylococcus aureus , Staphylococcus epidermidis , and two strains of methicillin-resistant S. aureus . Meanwhile, the results of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays illustrate the good selectivity between bacteria and normal cells of the most active compounds 6u and 6v . Furthermore, well combinations with bacterial RNA polymerase of 6u arising from docking study imply the possible mechanism of antibacterial activity of these synthetic compounds.
研究领域:
药物化学
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微生物学
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合成化学
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PubMed
高影响因子
Molecular Medicine Reports
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2016
·Vol. 14
·期 3
·2143-2149
·
IF 1.559
Shaofeng Wang,Wenhua Liu
Multiple myeloma (MM) is a type of cancer characterized by the excessive proliferation of malignant plasma cells. In China, the incidence of MM has been increasing annually. Paeoniflorin exerts numerous functions, including coronary vessel expansion, and anti‑inflammation and anticancer activities. The present study aimed to investigate the effects of paeoniflorin on the proliferation and apoptosis of SKO‑007 MM cells, via its effects on the regulation of matrix metalloproteinase‑2 (MMP‑2) and microRNA (miR)‑29b. In the present study, an MTT assay was used to analyze the proliferation of SKO‑007 cells treated with paeoniflorin. Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis and caspase‑3 activation assays were used to detect the levels of cellular apoptosis. The expression levels of MMP‑2 and miR‑29b were detected using gelatin zymography and quantitative‑polymerase chain reaction, respectively. In addition, miR‑29b and anti‑miR‑29b plasmids were transfected into SKO‑007 cells, and the effects of paeoniflorin on cell proliferation and apoptosis were subsequently detected. The results of the present in vitro studies demonstrated that paeoniflorin was able to inhibit the proliferation of SKO‑007 cells in a dose‑ and time‑dependent manner. Furthermore, paeoniflorin effectively increased cell apoptosis, and augmented the activation of caspase‑3 and caspase‑9 in the SKO‑007 cells. The expression levels of MMP‑2 were suppressed following treatment of the SKO‑007 cells with paeoniflorin. In addition, paeoniflorin was able to induce the expression of miR‑29b. Notably, the results of the present study indicated that miR‑29b expression may control the expression of MMP‑2 in SKO‑007 cells. In conclusion, the present study demonstrated that paeoniflorin was able to inhibit cell proliferation and promote apoptosis of MM cells by suppressing the expression of MMP‑2, via the upregulation of miR‑29b.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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高影响因子
TALANTA
·
2022
·
IF 6.556
Qiujun Lu,Lingling Xie,Shuhang Yin,Feng Chen,Cuiyan Wu,Meiling Liu,Haitao Li,Youyu Zhang
The overexpression of microRNA-10b (miRNA-10b) is closely associated with hepatocellular carcinoma (HCC), which may act as an advance biomarker to diagnose HCC early. Here, a novel luminescent nanosensor for the ultrasensitive detection of miRNA-10b was firstly developed by target-triggered catalytic hairpin assembly ( CHA ) and upconversion nanoparticles (UCNPs)-based luminescence resonance energy transfer (LRET). The hybridization process of DNA1-modified UCNPs with DNA2-modified gold nanoparticles (AuNPs) makes the energy donor (UCNPs) and acceptor (AuNPs) into close proximity, resulting in luminescence quenching of UCNPs. The miRNA-10b can hybridize with the hairpin structure of DNA2, releasing the recognition domain site and activate the CHA reaction with its signal amplification chain (H3). At the same time, the LRET was inhibited accompany with the AuNPs moved away from the UCNPs, which resulted in the luminescence recovery of UCNPs. The miRNA-10b can be quantified by measurement of the luminescence recovery rate of UCNPs. The sensor has high sensitivity with a detection limit of 8.96 fM. In addition, the sensor can be used to the discrimination of miRNA-10b expression levels in human hepatocarcinoma and hepatocyte cell lines with satisfactory results. The technique shows great promise for early diagnosis of HCC because of its high sensitivity and selectivity .
研究领域:
生物化学
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分子生物学
·
医学诊断
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2020
·
IF 9.038
Chang-Mei Li,Hai-Zhen Wu,Yu-Xiao Wang,Shuang Zhu,Chao-Hai Wei
The aim of this work is to study the synergistic effect of Stenotrophomonas sp. N5 and Advenella sp. B9 co-culture (COC) on enhancement of phenol biodegradation. These two strains utilizing phenol as sole carbon and energy source were isolated from phenol-containing coking wastewater. The results of biodegradation experiment showed the COC of N5 and B9 has stronger capability to degrade phenol than either of mono-culture (MOC). Growth kinetics studies indicated inhibitory effect of phenol on COC was reduced by the interaction of N5 and B9 in COC. The RNA-Seq results demonstrated that phenol biodegradation was enhanced by metabolic division of labor (DOL) in COC based on the expression of key genes for phenol degradation. GO enrichment analysis of differentially expressed genes (DEGs) indicated DEGs between COC and MOC degradation systems are mainly concentrated in the synthesis of cell components, microbial growth and metabolism, and catalytic activity. The expression of 3 transcriptional factors (LysR, Two-component system response regulator, and TetR families) which can regulate degradation of aromatic compounds, was identified beneficial to phenol degradation.
研究领域:
环境微生物学
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生物降解
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基因组学
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高影响因子
Heliyon
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2023
·
IF 4
Hang-fei Chen,Zhang-ping Li,Qi Wu,Chun Yu,Jing-Yi Yan,Yong-feng Bai,Sheng-mei Zhu,Mao-xiang Qian,Ming Liu,Li-feng Xu,Zheng Peng,Feng Zhang
Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B , a major component of selectivity factor 1 ( SL1 ), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B , in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.
研究领域:
癌症生物学
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分子生物学
·
细胞生物学
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高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·44359
·
IF 3.9
Zhang Yuepeng,Sun Yuhua,Gong Xueshan,Zhao Shuang,Cao Weiwei,Wang Hongbo,Wang Hao,Zhang Xi,Du Changwei,Chen Zhiguo,Deng Lu
Sequence-specific microRNAs (miRNAs) represent promising biomarkers for tumor diagnosis, while current detection methods are often limited by stringent temperature requirements and excessive protease dependency. Herein, we present an isothermal, protein-free cascaded amplification circuit for the sensitive analysis of miRNA-21. This strategy, termed CHA-DNAzyme, integrates a miRNA-activated catalytic hairpin assembly (CHA) reaction with a deoxyribozymes (DNAzyme) component. Specifically, the target miRNA-21 initiates the CHA process via a toehold-mediated strand displacement reaction. This reaction unveils a previously sequestered DNAzyme sequence embedded within a hairpin structure, forming an active double-stranded complex. Subsequently, in the presence of Mg²⁺ cofactors, the catalytically activated DNAzyme drives the continuous cleavage of fluorescent reporter hairpins, releasing a measurable fluorescent signal. Implemented in a one-pot format, the CHA-DNAzyme strategy demonstrates excellent sensitivity (with a limit of detection of 8.70 pM), high specificity (the capability to discern single-base mismatches), short sample-to-answer time (approximately 60 min), and robust performance in analyzing serum samples. This approach holds significant potential to facilitate the advancement of miRNA detection tools and support their application in tumor diagnosis and prognosis assessment.
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高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·
IF 3.4
Pingge Tian,Lei Xu,Fan Zou,Qian Jia,Yangjian Liu,Jin Chen,Pengzhen Wang
Background: Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease characterized by left ventricular hypertrophy and excessive myocardial contraction. Endothelial cells (ECs) play a key role in the pathogenesis of HCM, and their secreted growth factors regulate the growth and function of cardiomyocytes. However, the specific molecular mechanisms and biomarkers associated with endothelial dysfunction in HCM remain unclear. Methods: Single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database (GSE255296), and bulk RNA sequencing data were obtained from GSE249925 and GSE180313. The scRNA-seq data were processed using the Seurat package for cell type annotation and batch effect removal. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed, and pathway activity was evaluated using the AUCell algorithm. SCENIC was applied to construct transcription factor-specific regulatory networks. Differential gene expression analysis was conducted using the limma package, and key genes were determined by intersecting differentially expressed genes (DEGs) with EC-specific highly expressed genes. The diagnostic efficacy of these key genes was assessed via receiver operating characteristic (ROC) curve analysis. The mRNA expression of genes in HUVECs treated with or without angiotensin II (Ang II) was assessed using qPCR. Cell viability was determined using the CCK-8 assay, and cell invasive ability was evaluated through Transwell assays to investigate the regulatory effect of TMTC1 overexpression on Ang II-induced injury in HUVECs. Results: Seven major cell types were identified, with cardiomyocytes and ECs being the main cell populations in HCM. KEGG enrichment analysis revealed significant activation of pathways such as the transforming growth factor-beta (TGF-β) signaling pathway in ECs. High-activity transcription factors NFIB, MECOM, and FLI1 were identified in ECs, whose target genes were enriched in processes related to cell morphogenesis. Three key genes-TMTC1, RPS6KA2, and F8-were selected based on differential expression and EC specificity. These genes were lowly expressed in HCM and exhibited high diagnostic efficacy, with area under the curve (AUC) values > 0.7. Ultimately, the CCK-8 assay results indicated that Ang II inhibited the viability of HUVECs, and this inhibitory effect could be reversed by the overexpression of TMTC1 (oe-TMTC1). Furthermore, Transwell assays indicated that Ang II impaired cellular migration, and this impairment could be restored by oe-TMTC1. Conclusion: The identified key genes and pathways provide new targets for therapeutic intervention and contribute to a deeper understanding of the pathogenesis of HCM.
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高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Xiaojun Cai,Haofang Zhu,Yanmei Zhang,Zhongwei Gu
RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.
研究领域:
药剂学
·
分子生物学
·
癌症研究
·
纳米医学
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高影响因子
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