BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Lin Lv,Keying Yuan,Jiahao Li,Jing Lu,Qi Zhao,Hongyan Wang,Qiuyu Chen,Xinyu Dong,Siqi Sheng,Mingyu Liu,Yuanqi Shi,Hongquan Jiang,Zengxiang Dong
Myocardial fibroblasts transform into myofibroblasts during the progression of cardiac fibrosis, together with excessive cardiac fibroblast proliferation. Hence, the prevention and treatment of cardiac fibrosis are significant factors for inhibiting the development of heart failure. P-element Induced WImpy testis-interacting RNAs (PiRNA) are widely expressed in the heart, but their involvement in cardiac fibrosis has not yet been confirmed. We identified differentially expressed PiRNAs using Arraystar PiRNA expression profiling in Angiotensin II models of cardiac fibrosis in vivo and in vitro. We then explored cardiac-fibrosis-associated PiRNA-related proteins, RNA-protein interactomes, immunoprecipitation, and pulldown. We detected fibrosis markers and pathway-related proteins using immunofluorescence, qRT-PCR, and Western blot. We uncovered cardiac fibrosis associated PiRNA (CFAPIR) that was obviously dysregulated during cardiac fibrosis, whereas its overexpression reversed fibrosis in vivo and in vitro. Mechanistically, CFAPIR competitively bound muscleblind like protein 2 (MBNL2) and the cyclin-dependent kinase inhibitor P21 to regulate the TGF-β1/SMAD3 signaling pathway.
研究领域:
心脏病学
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
Interdisciplinary Medicine
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2025
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IF 13.6
Qin-Xin Gao,Qian-Qian Wu,Zhi-Ying Dong,Xiao-Yuan Qin,Lin-Yan Zhai,Bao-Ping Xie,Wen-Jun Duan
Increasing studies have demonstrated that PIWI-interacting RNAs (piRNAs) in circulating exosomes can serve as novel molecular biomarkers for tumor liquid biopsy. However, methods for in situ detection of piRNAs encased in exosomes are limited. In this study, we designed a spherical nucleic acid probe named piR-651, which can enter exosomes simply by incubating with them for 2 h and in situ detect piR-651 with a detection limit of 5 × 10 7 particles/μL. Based on this probe, we established a liquid biopsy method for the in situ detection of piR-651 in plasma exosomes. The assay could distinguish the expression levels of piR-651 between 21 breast cancer patients and 22 healthy individuals. The receiver operating characteristic curve shows an area under the curve as 0.9931 and the diagnostic sensitivity and specificity at the best cutoff are 85.7% and 100%, respectively. The probe can also easily perform in situ imaging of piR-651 in living cells. To avoid low sensitivity and kinetics in detecting large-sized PIWI-interacting RNA complexes, we rationally designed the structure and detection scheme of piR-651 probe, which was synthesized by modifying 13-nm gold particles with high-density Anchor-Report DNA duplexes through the butanol dehydration method. The new design of the gold nanoparticle nucleic acid probe can be applied to the fabrication of nucleic acid probes targeting other large-volume nucleic acids for developing more molecular biomarker-based liquid biopsy for cancer diagnosis.
研究领域:
分子生物学
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肿瘤学
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生物医学工程
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遗传学
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2026
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IF 7.7
Yuhan He,Haien Fan,Jianxiu Wang,Hailin Tang,Xinyao Yi
PiRNAs have emerged as promising biomarkers for cancer diagnosis, however, their sensitive detection remains challenging due to the reliance on enzymatic amplification, complex labeling procedures. Herein, we report an integrated sensing strategy that combines a structure-switching ratiometric nano-converter with an enzyme-free entropy-driven catalytic (EDC) DNA circuit for highly sensitive and reliable piRNA detection. A hairpin DNA templated silver nanocluster (HP-DNA-AgNCs) that functions as a programmable nano-converter. In its closed hairpin state, the probe exhibits strong green fluorescence (530 nm). Upon hybridization with the target piRNA, the hairpin undergoes a structural transformation, triggering AgNC redistribution and a pronounced fluorescence shift to red emission (620 nm), thereby generating a ratiometric signal (F 620 nm / F 530 nm ). Notably, this structural transition is rationally coupled to an EDC amplification circuit, enabling each target piRNA to catalytically activate multiple nano-converters under isothermal conditions. Current method allows ultrasensitive piRNA detection with a limit of detection as low as 0.146 pM and a wide dynamic range. The clinical applicability of the platform was further validated using breast cancer tissue samples, yielding an area under the ROC curve (AUC) of 0.951, in excellent agreement with qRT-PCR analysis. By unifying ratiometric self-calibration, enzyme-free amplification, and label-free design, this work establishes a robust and versatile sensing paradigm with strong potential for clinical diagnostics and point-of-care testing.
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产品关联
DOI
高影响因子
ENVIRONMENT INTERNATIONAL
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2024
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IF 10.3
Bingli Zhang,Yizhou Zhong,Jiaxin Du,Rongyi Ye,Bingchi Fan,Yanhong Deng,Ruobing Bai,Yu Feng,Xiaohong Yang,Yuji Huang,Boxuan Liang,Jiewei Zheng,Weifeng Rong,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.
研究领域:
环境毒理学
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生殖生物学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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