JOURNAL OF GENE MEDICINE
·
2017
·Vol. 19
·期 12
·e2998
·
IF 2.524
Yunna Chen,Li Sun,Dongdong Guo,Ziteng Wu,Weidong Chen
Background Drug resistance cancer cells have become a major problem in chemotherapy. To solve this problem, the co-delivery of small interefering RNA (siRNA) and 5-fluorouracil chitosan nanoparticles was employed, aiming to reverse the multidrug resistance of gastric cancer SGC-7901 cells in vitro . Methods Chitosan nanoparticles were prepared using an ionic gel method. siRNA nanoparticles were characterized by gel retardation assays. Particle size and zeta potential were measured to confirm nanoparticle formation. The transfection efficiency of siRNA was determined by flow cytometry and high-content screening. Western blotting and a quantitative real-time-polymerase chain reaction were used to assess the silencing efficiency of siRNA. Accumulation and efflux experiments for rhodamine-123, cell migration experiments, cell sensitivity analyses and cell apoptosis assays were used to determine whether siRNA could reverse multidrug resistance. A systemic toxicity assay was used to evaluate the safety of nanoparticles. Results Compared to naked siRNA, the co-delivery system demonstrated a higher transfection efficiency and gene silencing efficiency by inhibiting the efflux of P-glycoprotein and cell migration. Moreover, the combination treatment with siRNA and 5-fluorouracil co-delivered by chitosan nanoparticles can increase the sensitivity of drug resistance cells and cell apoptosis. Finally, the safety of nanoparticles was evaluated in vivo and the results obtained suggested that nanoparticles did not have any obvious toxicity. Conclusions Co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles is an attractive strategy for overcoming multidrug resistance.
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高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Yuqing Zhang,Wenying Zhang,Yanmin Jian,Shujing Zhang,Dongwu Liu,Kang Zheng,Xungang Tan,Feng You,Qiuxiang Pang,Shuang Jiao
Olive flounder ( Paralichthys olivaceus ) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 ( fzd3 ) and prolactin ( prl ) in brains/pituitaries, and growth hormone receptor ( ghr ), estrogen receptor ( esr1 ), insulin-like growth factor binding protein-3 ( igfbp3 ), bone morphogenetic protein 8A-like ( bmp8a ), leptin receptor ( lepr ), and lipoprotein lipase-like ( lpl ) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2024
·
IF 3.4
Yong Zhang,Zhiling Shen,Xiaodong Han,Yachao Wu,Tianchen Huang
Background Oxaliplatin is a first-line chemotherapy drug for colorectal cancer (CRC), but many patients eventually lose treatment efficacy due to acquired resistance. AC105118.1 is a long non-coding RNA with unknown biological function. This research attempts to probe into the molecular regulatory mechanism of AC105118.1 in CRC oxaliplatin resistance. Methods The expression level of AC105118.1 in CRC tissues and cells was measured based on The Cancer Genome Atlas (TCGA) data and quantitative reverse transcription polymerase chain reaction (qRT-PCR). We utilized dual-luciferase assay and RNA immunoprecipitation to analyze the interaction between AC105118.1, miR-378a-3p, and their downstream target KIF26B. CCK-8, colony formation assay, and flow cytometry were employed to assess the half inhibitory concentration (IC 50 ), cell proliferation, and apoptosis rate of HCT116/L-OHP cells treated with oxaliplatin. The glycolysis evaluation was completed by measuring the extracellular acidification rate (ECAR), glucose consumption, lactate production, and glycolysis-related proteins (HK2, GLUT1, and LDHA). TUNEL staining was used to detect the level of apoptosis. Results AC105118.1 was specifically upregulated in CRC tissues and cells. AC105118.1 indirectly facilitated the expression of miRNA target gene KIF26B by sequestering miR-378a-3p. In HCT116/L-OHP cells, transfection with si-AC105118.1 resulted in a decrease in glycolysis level, a lower maximum IC 50 required for oxaliplatin-treated cells, inhibited cell proliferation, and an increase in apoptosis rate. All of these effects were alleviated when simultaneously transfecting miR-378a-3p inhibitor or oe-KIF26B. Knockdown of AC105118.1 significantly inhibited oxaliplatin resistance to CRC in mice. Conclusion AC105118.1 facilitates glycolysis and increases CRC cells’ resistance to oxaliplatin by targeting the miR-378a-3p/KIF26B axis. The present work shed new insights into the function and mechanism of AC105118.1 in molecular function and suggested that the AC105118.1/miR-378a-3p/KIF26B axis is a promising target for intervening CRC oxaliplatin resistance.
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高影响因子
BIOSENSORS & BIOELECTRONICS
·
2017
·
IF 7.78
Yiyi Tao,Dan Yin,Mingchao Jin,Jie Fang,Tao Dai,Yi Li,Yuxia Li,Qinli Pu,Guoming Xie
An electrochemical microRNA (miRNA) analysis platform by combining double-loop hairpin probe (DHP) and doxorubicin-loaded gold nanoparticles ( [email protected] ) for ultrasensitive miRNA detection is proposed. Firstly, we here report a DHP that is simultaneously engineered to incorporate a miRNA recognition sequence, an output segment and output's complementary fragment. The important aspect of this hairpin probe is that it would not be degraded by duplex specific nuclease (DSN) and circumvents elaborately chemical modification disadvantages encountered by classic molecular beacon . For the DHP-based DSN signal amplification system, DHP hybridizes with target miRNA to form DNA-miRNA heteroduplexes , and the DSN can hydrolyze the DNA in the heteroduplexes structure selectively, while released target miRNA strand can initiate another cycle resulting in a significant signal amplification and the accumulated output segments could be responsible for strand displacement on the electrode directly. Furthermore, a great deal of doxorubicin (Dox) are loaded on the gold nanoparticles (AuNPs) to fabricate the [email protected] biocomposites that could magnify the electrochemical signal and enable the ultrasensitive analysis of miRNA. As a result, the miRNA was capable of being detected in a limit of 0.17 pM and other kinds of miRNA were discriminated facilely by this method. The described DHP as a toolbox and the nano-biocomposites as a novel signal material would not only promote the design of electrochemical biosensors but also open a good way to promote the establishment of test method in malignant tumors.
研究领域:
生物化学
·
分子生物学
·
纳米医学
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Wu Chen,Mengfan Guo,Zeyu Chen,Ying Sun,Yudian Huang,Yushan Chen,Yanyan Ma,Juan Sun,Bin Qiu,Hui Lin
The overexpression of microRNA-21 (miRNA-21) is closely associated with gastric cancer (GC) and may be used as a biomarker to diagnose GC early. Here, a colorimetry and fluorescence dual-mode biosensor for the detection of miRNA-21 was developed from polydopamine-coated magnetic upconversion nanoparticles (Fe 3 O 4 @UCNP@PDA) and aptamer-modified gold nanoparticles (AuNP-apt). The strong adsorption of single-stranded DNA by PDA results in close proximity between the energy donors (UCNPs) and acceptors (AuNPs), resulting in luminescence quenching of the UCNPs. The miRNA-21 can hybridize with the apt-conjugated AuNPs, and the AuNPs move away from the UCNPs, which results in the luminescence recovery of the UCNPs and the catalytic activity of the AuNPs. After H 2 O 2 and tetrapaminophenylethylene were added, the yellow solution turned green and gradually deepened with increasing miRNA-21 concentration. Under optimal conditions, the detection limits of miRNA-21 by fluorescence and colorimetry assays are 8.90 pM and 185 pM, respectively. In addition, the developed approach was utilized to measure miRNA-21 in serum samples, and the recovery rates ranged from 105.4-107.1 % and 98.5–109.3 %, respectively. The above results indicate great promise for the early diagnosis of GC because of its high sensitivity and selectivity.
研究领域:
生物化学
·
分子诊断
·
纳米医学
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BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Weipeng Liu,Minjun Zhu,Hongxing Liu,Jitao Wei,Xiaoming Zhou,Da Xing
Searching for a strategy to enhance the efficiency of nucleic acid amplification and achieve exquisite discrimination of nucleic acids at the single-base level for biological detection has become an exciting research direction in recent years. Here, we have developed a simple and universal primer design strategy which produces a fascinating effect on isothermal strand displacement amplification (iSDA). We refer to the resultant primer as “invading stacking primer (IS-Primer)” which is based on contiguous stacking hybridization and toehold-mediated exchange reaction and function by merely changing the hybridization location of the primer. Using the IS-Primer, the sensitivity in detecting the target miR-21 is improved approximately five fold compared with the traditional iSDA reaction. It was further demonstrated that the IS-Primer acts as an invading strand to initiate branch migration which can increase the efficiency of the untwisting of the hairpin probe. This effect is equivalent to reducing the free energy of the stem, and the technique shows superior selectivity for single-base mismatches. By demonstrating the enhanced effect of the IS-Primer in the iSDA reaction, this work may provide a potentially new avenue for developing more sensitive and selective nucleic acids assays.
研究领域:
分子生物学
·
核酸化学
·
生物技术
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高影响因子
CELL DEATH AND DIFFERENTIATION
·
2024
·
IF 13.7
Cai Jiangxue,Li Chenxuan,Liu Suyuan,Tan Meiling,Sun Yiran,Sun Xiaoxiao,Yang Miaoxin,He Bin
The cellular stress response system in immune cells plays a crucial role in regulating the development of inflammatory diseases. In response to cellular damage or microbial infection, the assembly of the NLRP3 inflammasome induces pyroptosis and the release of inflammatory cytokines. Meanwhile, Angiogenin (Ang)-mediated transfer RNA-derived small RNAs (tsRNAs) promote cell survival under stressful conditions. While both tsRNAs and inflammasomes are induced under stress conditions, the interplay between these two systems and their implications in regulating inflammatory diseases remains poorly understood. In this study, it was demonstrated that Ang deficiency exacerbated sodium arsenite-induced activation of NLRP3 inflammasome and pyroptosis. Moreover, Ang-induced 5′-tsRNAs inhibited NLRP3 inflammasome activation and pyroptosis. Mechanistically, 5′-tsRNAs recruit DDX3X protein into stress granules (SGs), consequently inhibiting the interaction between DDX3X and NLRP3, thus leading to the suppression of NLRP3 inflammasome activation. Furthermore, in vivo results showed that Ang deficiency led to the downregulation of tsRNAs, ultimately leading to an exacerbation of NLRP3 inflammasome-dependent inflammation, including lipopolysaccharide-induced systemic inflammation and type-2 diabetes-related inflammation. Altogether, our study sheds a new light on the role of Ang-induced 5′-tsRNAs in regulating NLRP3 inflammasome activation via SGs, and highlights tsRNAs as a promising target for the treatment of NLRP3 inflammasome-related diseases.
研究领域:
免疫学
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分子生物学
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炎症
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代谢紊乱
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高影响因子
PLANT CELL AND ENVIRONMENT
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2024
·
IF 6
Linlin Su,Wenyun Li,Xiaohua Chen,Pengcheng Wang,Diqiu Liu
The root rot mainly caused by Fusarium solani is a bottleneck in the cultivation of Panax notoginseng . In this study, we reported a gene encoding a plant cell wall structural protein, P. notoginseng proline-rich protein (PnPRPL1), whose transcription was upregulated by F. solani and induced by some hormone signals. The PnPRPL1 recombinant protein significantly inhibited the growth and conidial germination of the root rot pathogens. Downregulation of PnPRPL1 by RNA interference (RNAi) in P. notoginseng leaves increased the susceptibility to F. solani , whereas overexpression of PnPRPL1 in tobacco ( Nicotiana tabacum ) enhanced the resistance to F. solani . Compared with wild-type tobacco, the PnPRPL1 -overexpressing transgenic tobacco had higher reactive oxygen species (ROS)-scavenging enzyme activities, lower ROS levels, and more lignin and callose deposition. The opposite results were obtained for the P. notoginseng expressing PnPRPL1 RNAi fragments. Furthermore, the PnPRPL1 promoter transcription activity was induced by several plant hormones and multiple stress stimuli. In addition, the transcription factor PnWRKY27 activated the expression of PnPRPL1 by directly binding to the promoter region. Thus, PnPRPL1 , which is positively regulated by a WRKY transcription factor, encodes an antimicrobial protein that also mediates ROS homoeostasis and callose/lignin deposition during the response to F. solani infection.
研究领域:
植物病理学
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分子生物学
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植物遗传学
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高影响因子
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2025
·
IF 3.7
Fuqiang Rao,Jie Yang,Danhao Peng,Xinghao Li,Zhaoqun Li,Deguang Liu
Herbivorous insects rely on olfactory cues to select oviposition sites on host plants, which is a process critical for their reproductive success. The rape stem weevil, Ceutorhynchus asper Roel. (Coleoptera: Curculionidae), is a major pest that causes significant damage to rapeseed and other cruciferous crop production, yet the chemical and molecular mechanisms underlying its oviposition preference remain unknown. Our behavioral assays revealed that C. asper females strongly avoided pre-infested rapeseed plants. Five monoterpenes (p-cymene, 1,8-cineole, ocimene, camphor, and α-pinene) were identified as herbivore-induced plant volatiles of C. asper -infested plants, with their emission levels significantly higher than those in healthy plants. Among these five compounds, subsequent electroantennogram (EAG) screening revealed that only 1,8-cineole triggered significant responses in C. asper and showed a concentration-dependent sensitivity. Behavioral assays showed that female C. asper exhibited significant behavioral and oviposition avoidance when exposed to 1,8-cineole. We identified CaspOR39 as the specific odorant receptor for 1,8-cineole, with molecular docking for prediction of the binding affinity and key residues. RNAi of CaspOR39 abolished female EAG responses, as well as behavioral and oviposition avoidance of 1,8-cineole. These results revealed a sex-specific chemical sensing mechanism: female C. asper can utilize CaspOR39 to detect 1,8-cineole as a key cue of plant infestation, driving adaptive oviposition behaviors of this beetle. Our results provide mechanistic and molecular insights into CaspOR39-mediated oviposition behaviors of C. asper , and a basis for the development of semiochemical-based strategies for management of this weevil.
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高影响因子
HEREDITAS
·
2026
·Vol. 163
·期 1
·77
·
IF 2.6
Jian Fanghua,Fu Jun,Li Dan,Bao Weiqiang
Background Severe pneumonia (SP) threatens the quality of life and well-being of children. This study aims to explore the serum NNT-AS1 expression in SP children and its impact on lipopolysaccharide (LPS)-induced injury in human embryonic lung fibroblasts. Methods The study included 69 SP children, 62 mild pneumonia (MP) children and 75 healthy controls. A pneumonia cell model was constructed with LPS-induced MRC-5 cells. Loss-of-function experiments were performed using si-NNT-AS1 and miR-23a-3p inhibitor. The NNT-AS1 and miR-23a-3p expression was detected by real-time quantitative polymerase chain reaction. The diagnostic effect and prognostic value of NNT-AS1 were evaluated by receiver operating characteristics curves and Kaplan-Meier method. Cell viability and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Inflammatory factors were measured by enzyme-linked immunosorbent assay. The interaction between NNT-AS1 and miR-23a-3p was verified by luciferase reporter gene and RNA immunoprecipitation assays. Pearson correlation coefficient was used to analyze the correlation. Results NNT-AS1 was upregulated in SP children and showed good diagnostic efficacy (area under the curve (AUC) = 0.815). High NNT‑AS1 expression predicted a poorer survival. Silencing of NNT-AS1 increased cell viability, decreased apoptosis, and alleviated inflammatory responses. MiR-23a-3p was a target of NNT-AS1. Inhibition of miR-23a-3p partially reversed the protective effects of NNT-AS1 silencing on LPS-induced MRC-5 cell injury. Conclusions Serum NNT-AS1 is upregulated in SP patients, and its expression is correlated with clinical prognosis. NNT-AS1 participates in LPS-induced cellular damage by regulating miR-23a-3p. These findings provide a new theoretical basis for understanding the pathogenesis of SP.
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高影响因子
ANALYTICAL CHEMISTRY
·
2026
·
IF 7.3
Hui Liu,Hang Yin,Tao Yang,Jia Xiang,Tianhui Xue,Baiqi Lu,Yang Wu,Yongmei Liu,Tiantian Deng,Tingting Sun
Circular RNAs (circRNAs) are emerging as promising biomarkers in liquid biopsy, yet their accurate detection in circulating tumor cells remains challenging due to low abundance and interference from linear RNA counterparts. Here, we develop a dCas13a/crRNA-Linked Immunosorbent Mimic Assay (dCLIMA) for sensitive and specific colorimetric detection of circRNAs. The dCas13a/crRNA complex immobilized on a microplate specifically captures target circRNAs via their back-splicing junction (BSJ) region, eliminating linear RNA interference. Upon capture, the circRNA unlocks a hairpin probe and facilitates padlock circularization, triggering rolling circle amplification (RCA) to produce tandem G-rich repeats. Notably, this design enables RCA to recognize and probe dual functional domains on the same circRNA, allowing more comprehensive functional characterization. The G-rich repeats fold into G-quadruplex/hemin DNAzyme that catalyzes TMB oxidation to generate a blue product for label-free final readout. The dCLIMA assay achieves a detection limit of 0.63 fM for circRNA_100876, discriminates single-base mismatches, and exhibits excellent anti-interference capability. We successfully quantify circRNA_100876 in lung cancer-derived cells, cell lysates, and clinical serum samples, with results correlating well with qRT-PCR. This method holds great promise for advancing circRNA-based liquid biopsy and precision oncology.
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Guoni Huang,Jiezhen Pan,Junfang Zhu,Ye Zhang,Xiaohe Zhang,Shihua Luo
In this study, we introduce an ultrasensitive electrochemical RNA biosensor based on hyperbranched primer exchange reaction (HPER) cascade amplification and Au@Pt@UiO-66-NH 2 nanozymes. This strategy employs catalytic hairpin assembly (CHA) for precise target RNA recognition, which trigger the immobilization of HPER products onto the electrode surface, thereby providing binding sites for nanozymes. Then, the sDNA@Au@Pt@UiO-66-NH 2 signal probes (sDAPU probes) attach to the HPER scaffolds through base-pairing interactions, facilitating signal amplification. The nanozymes catalyze the decomposition of hydrogen peroxide into H 2 O and O 2 , producing a significantly amplified electrochemical signal. By combining CHA-HPER cascade amplification with the catalytic activity of sDAPU probes, the established biosensor achieves remarkable sensitivity, with a detection limit as low as 14.68 aM, and high specificity that enables the differentiation of non-target pathogen RNA. Furthermore, the biosensor also demonstrates excellent recovery rates in serum samples. Therefore, this electrochemical strategy shows great potential as a diagnostic tool for ultrasensitive Mycobacterium tuberculosis detection.
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