International Journal of Nanomedicine
·
2023
·
IF 8
Dawei Deng,Yang Li,Jianpeng Xue,Jie Wang,Guanhua Ai,Xin Li,Yueqing Gu
Messenger RNA (mRNA), a single-strand ribonucleic acid with functional gene information is usually abnormally expressed in cancer cells and has become a promising biomarker for the study of tumor progress. Hairpin DNA-coated gold nanoparticle (hDAuNP) beacon containing a bare gold nanoparticle (AuNP) as fluorescence quencher and thiol-terminated fluorescently labeled stem–loop–stem oligonucleotide sequences attached by Au–S bond is currently a new nanoscale biodiagnostic platform capable of mRNA detection, in which the design of the loop region sequence is crucial for hybridizing with the target mRNA. Hence, in this study, to improve the sensitivity and selectivity of hDAuNP beacon simultaneously, the loop region of hairpin DNA was screened by bioinformatics strategy. Here, signal transducer and activator of transcription 5b (STAT5b) mRNA was selected and used as a practical example. The results from the combined characterizations using optical techniques, flow cytometry assay, and cell microscopic imaging showed that after optimization, the as-prepared hDAuNP beacon had higher selectivity and sensitivity for the detection of STAT5b mRNA in living cells, as compared with our previous beacon. Thus, the bioinformatics method may be a promising new strategy for assisting in the designing of the hDAuNP beacon, extending its application in the detection of mRNA expression and the resultant mRNA-based biological processes and disease pathogenesis.
研究领域:
纳米技术
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分子生物学
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生物信息学
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癌症研究
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DOI
PubMed
高影响因子
BIOLOGIA PLANTARUM
·
2011
·Vol. 55
·期 4
·669-674
·
IF 1.582
Zeng Q. -P.,Zeng X. -M.,Yang R. -Y.,Yang X. -Q.
Although crosstalk between cytosolic and plastidic terpenoid pathways has been validated in many plant species, we report here for the first time a striking elevation of the nucleus-encoded artemisinin biosynthesis relevant DBR2 mRNA following the incubation of plants with fosmidomycin (FM). FM decreased singlet oxygen ( 1 O 2 ) scavengers such as β-carotene and α-tocopherol and subsequently invoked 1 O 2 burst. The treatment of plants with fluridone (FD) neither decreased α-tocopherol content nor triggered 1 O 2 emission. In conclusion, FM can up-regulate 1 O 2 -sensitive nuclear genes responsible for artemisinin biogenesis by mitigating the accumulation of plastidic scavenging terpenoids, thereby eliciting 1 O 2 generation and initiating 1 O 2 retrograde signaling.
研究领域:
植物生物化学
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分子遗传学
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植物化学
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产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2025
·
IF 4.2
Jingran Yang,Ruirui Ding,Ling Qi,Haoran Bi,Jianan Li
Cypermethrin (CMN) is a synthetic pyrethroid insecticide known for its neurotoxic effects, particularly in the hippocampus. To investigate the underlying molecular mechanisms, we conducted integrated microRNA (miRNA) and messenger RNA (mRNA) sequencing in HT22 hippocampal cells treated with 400 μM CMN. We identified 36 differentially expressed miRNAs and 170 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant involvement in cell adhesion, extracellular matrix organization, and signaling pathways such as phosphoinositide 3-kinase–protein kinase B signaling pathway (PI3K-Akt), mitogen-activated protein kinase (MAPK), and extracellular matrix (ECM)–receptor interaction. Using six topological algorithms, three hub genes (Col1a2, Fn1, and Pdgfrb) were finally identified. In addition, a miRNA–mRNA regulatory network was constructed, and expression patterns of key miRNAs and mRNAs were validated via reverse transcription polymerase chain reaction (RT-PCR). These findings highlight the critical role of the miRNA–mRNA regulatory network in CMN-induced neurotoxicity. The study provides valuable insights into potential therapeutic targets and preventive strategies for CMN-associated hippocampal damage.
研究领域:
毒理学
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神经生物学
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生物信息学
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分子生物学
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DOI
PubMed
高影响因子
Clinical and Translational Medicine
·
2025
·Vol. 15
·期 3
·e70250
·
IF 6.8
Kaixiang Li,Runjiao Luo,Xindi Yu,Wei Dong,Guoliang Hao,Dan Hu,Ziyou Yu,Minglu Liu,Tingting Lu,Xiangying Wang,Xin Tang,Xinjun Lin,Huijing Wang,Wei Wang,Wei Fu
Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases. Key points ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins. Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction. The hADSCs dual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.
研究领域:
干细胞治疗
·
心脏病学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Lei huang,Siyuan Tang,Jiachen Guo,Yixing Tu,Sian Li,Taihua Yang,Dong Zhao,Chao Wang
Localized delivery of mRNA-based therapies has shown promise in cancer treatment, but challenges such as drug leakage and systemic toxicity remain. This study aimed to develop a locally retained lipid nanoparticle (LNP) system for the co-delivery of mRNA and the photosensitizer indocyanine green (ICG) to treat superficial tumors. By systematically optimizing the lipid composition and mRNA-to-ICG ratio, we achieved high encapsulation efficiency and localized protein expression. The LNP system demonstrated robust transfection efficiency and photothermal effects, with minimal off-target distribution. In vivo studies revealed significant tumor growth inhibition, highlighting the potential of this approach for localized cancer therapy. This study provides a novel strategy for the co-delivery of mRNA and photosensitizers, offering a promising avenue for the treatment of superficial tumors with minimal systemic exposure.
研究领域:
癌症研究
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纳米医学
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药剂学
·
分子治疗
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Hai Xiao,Altanzul Altangerel,Gerile Gerile,Yinga Wu,Huricha Baigude
RNA interference (RNAi) is a highly efficient approach for gene silencing. Regulation of gene expression at post-transcriptional level provides great potential for curing diseases caused by abnormal overexpression of disease-related genes. However, the application of RNAi in the clinic has been hindered by the lack of efficient and biocompatible delivery systems. Therefore, the development of a safe and tissue-targeted double-stranded interfering RNA (siRNA) carrier for clinical application is urgently needed. Here we report the discovery of a highly efficient liposomal siRNA delivery agent based on a novel peptidomimetic built from natural amino acids. Fine tuning of the composition of amino acids, the type of amide linkage in the peptidomimetic, as well as the formulation and the physicochemical parameters of the novel lipoplex resulted in a lipid nanoparticle (LNP) that efficiently encapsulates and carries siRNA to mouse liver. In vivo experiments showed that a single injection of unmodified siRNA complexed to one of the peptidomimetics at a clinically feasible dose induced significant RNAi in mouse liver, resulting in a 90% decrease in apolipoprotein B (ApoB) mRNA level, as well as a 60% decrease in serum ApoB protein level. Analysis of mouse serum by ELISA indicated that the novel peptidomimetic based lipoplex did not elevate the level of liver enzymes (ALT, AST) in the serum. Our novel peptidomimetic-based lipoplex demonstrated great potential for the development of a safe and efficient siRNA delivery agent for clinical applications.
研究领域:
药理学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Chemical Science
·
2020
·Vol. 11
·期 7
·1878-1891
·
IF 9.346
Qing-Yun Cheng,Jun Xiong,Cheng-Jie Ma,Yi Dai,Jiang-Hui Ding,Fei-Long Liu,Bi-Feng Yuan,Yu-Qi Feng
The discovery of dynamic and reversible modifications in messenger RNA (mRNA) is opening new directions in RNA modification-mediated regulation of biological processes. Methylation is the most prevalent modification occurring in mRNA and the methyl group is mainly decorated in the adenine, cytosine, and guanine base or in the 2′-hydroxyl group of ribose. However, methylation of the uracil base (5-methyluridine, m5U) has not been discovered in mRNA of eukaryotes. In the current study, we established a method of N-cyclohexyl-N′-β-(4-methylmorpholinium) ethylcarbodiimide p-toluenesulfonate (CMCT) labelling coupled with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) analysis for the sensitive determination of uridine modifications in RNA. Our results demonstrated that the detection sensitivities of uridine modifications in RNA increased up to 1408 fold upon CMCT labelling. Using the developed method, we identified the distinct existence of m5U in mRNA of various mammalian cells and tissues. In addition, the stable isotope tracing monitored by mass spectrometry revealed that the methyl group of m5U originated from S-adenosyl-L-methionine (SAM). Our study expanded the list of modifications occurring in mRNA of mammals. Future work on transcriptome-wide mapping of m5U will further uncover the functional roles of m5U in mRNA of mammals.
研究领域:
分子生物学
·
生物化学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
·
2020
·Vol. 51
·期 3
·1012-1025
·
IF 1.748
Xiao Yan,Chaobin Qin,Dapeng Deng,Guokun Yang,Junchang Feng,Ronghua Lu,Liping Yang,Xiaolin Meng,Xianglin Cao,Guoxing Nie,Guiqin Wang
Apelin and its receptor apj have a variety of biological functions and are involved in appetite and energy regulation. However, the comparative studies of apelin/apj system in fish are still absent. In this study, the open reading frames of apelin and apja and apjb were obtained. Apelin and apj mRNAs were widely distributed in all tissues detected, with the highest level in the brain, followed by the spleen, kidney and foregut. The mRNA expression of apelin and apj s increased rapidly at mealtime and significantly decreased after 30 min of feeding. In addition, there were obvious circadian rhythms (higher at nighttime and lower at daytime) in the expression of apelin and apja and apjb . Furthermore, fasting elevated the mRNA levels of apelin and apj s in the hypothalamus, foregut and hepatopancreas. When the 8-day fasted fish were refed, apelin and apj s mRNA expression significantly decreased. However, there were differences in the response to fasting and refeeding between apja and apjb . The roles of apelin and its receptor apjs in fish are poorly understood. Herein, we employed molecular and physiological studies to characterize their structures, distribution and mRNA expression responses to periprandial changes and fasting–refeeding in Cyprinus carpio L. for the first time.
研究领域:
分子生物学
·
生理学
·
水产养殖
·
营养学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Lijie Qiao,Na Fan,Yupei Zhang,Yuting Chen,Shugang Qin,Xiangrong Song
Messenger RNA (mRNA) vaccine efficacy requires delivery systems that maximize antigen expression while precisely modulating innate immune activation. However, many conventional adjuvants induce type I interferons that inadvertently suppress mRNA translation, compromising vaccine efficacy. To overcome this limitation, we engineered a multifunctional lipid nanoparticle (LNP) by partially substituting a fraction of the structural lipid cholesterol with SitoC7A - a conjugate of sitosterol and the STING (Stimulator of Interferon Genes) agonist (C7A) linked via a reducible disulfide bond. This single SitoC7A component serves dual roles: its disulfide bond markedly enhances LNP uptake by dendritic cells (DCs) and boosts mRNA translation, while its C7A moiety selectively triggers STING signaling within DCs, avoiding systemic interferon responses. This integrated design yielded robust DC maturation and superior antigen presentation. In murine models, SitoC7A-LNPs encapsulating SARS-CoV-2 mRNA elicited potent protective immunity, while tumor antigen-loaded LNPs significantly suppressed lymphoma progression. We introduce a principle for the novel LNP design wherein a single engineered lipid simultaneously provides structural support, enhances mRNA delivery and expression specifically in key immune cells, and delivers spatially controlled adjuvanticity creating a versatile and potent platform for next-generation mRNA vaccines.
研究领域:
免疫学
·
肿瘤学
·
纳米医学
·
疫苗学
·
分子药剂学
·
转化医学
·
先天免疫
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGY OF REPRODUCTION
·
2024
·
IF 3.1
Shi Heng,Zhao Xin-Hai,Peng Qin,Zhou Xian-Ling,Liu Si-Si,Sun Chuan-Chuan,Cao Qiu-Yu,Zhu Shi-Ping,Sun Sheng-Yun
Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear. Healthy male C57BL/6J mice were divided into five groups: control, DEHP, DEHP + GTP treatment, GTP, and oil groups. Testicular histopathological changes were assessed using hematoxylin–eosin (H&E), periodic acid-Schiff (PAS), and Masson staining. Ultrastructural alterations were examined through transmission electron microscopy. High-throughput sequencing was performed to analyze the expression of mRNA, miRNA, and lncRNA and construct an lncRNA–miRNA–mRNA regulatory network for identifying key regulatory axes. Mice in the DEHP group exhibited significant testicular damage, including reduced sperm count, mitochondrial deformation, and endoplasmic reticulum dilation. GTP treatment notably improved testicular structural integrity, restored sperm count, and alleviated mitochondrial and endoplasmic reticulum damage. Additionally, DEHP significantly increased activated CD8+ T cells, which were reduced with GTP treatment. High-throughput sequencing revealed that GTP treatment exerted protective effects through the regulation of six key lncRNA–miRNA–mRNA axes. GTPs significantly protect against DEHP-induced testicular damage, and the lncRNA–miRNA–mRNA regulatory axes play a potential role in this process.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Nature Chemistry
·
2025
·
IF 20.2
Wen Ping,Huang Hanwei,Zhang Ruizhe,Zheng Hanqi,Liang Tingxizi,Zhuang Chuyue,Wu Qing,Wang Junxia,Liu Feng,Zhang Ke,Wu Wei,He Kaixin,Liu Funan,Li Hongjun,Gu Zhen
Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid–liquid phase separation of cholesterol-modified DNA and histones. Unlike a phospholipid-based membrane-bounded vesicle, a coacervate vesicle lacks a membrane structure on the surface and is organized with a high-density liquid layer and a water-filled cavity. Through a straightforward coacervation process, we demonstrate that various biological agents, including virus particles, mRNA, cytokines and peptides, can be innocuously and directly enriched in the liquid phase. In contrast to the droplet-like coacervates that are prone to aggregation challenges, coacervate vesicles display superior kinetic stability, positioning them as a versatile delivery vehicle for biopharmaceuticals. We validate that incorporating oncolytic viruses into these coacervate vesicles endows them with potent oncolytic efficacy and elicits robust anti-tumour immune responses in mouse models.
研究领域:
生物技术
·
药剂学
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Hui Li,Siyi Pan,Xiaoyun Xu
Flavonoids are natural active components. They distribute widely in edible plants with high activity of anti-inflammation. Inhibition of cyclooxygenase-2(COX-2) was determined by real-time fluorescent quantitative olymerase chain reaction (RTFQ-PCR). And structure characteristics of flavonoids for COX-2 inhibition were mainly analyzed by a quantitative structure activity relationship (QSAR) model. Descriptors such as SMR_VSA5, vsurf_DD12, reactive were the top three important independent variables to COX-2 mRNA inhibiton in RAW264.7. Low SMR_VSA5 value meant a lower molecular refractivity resulting in a lower COX-2 mRNA inhibition. High vsurf_DD12 value related to poor molecular balance and showed profound adverse to COX-2 mRNA inhibition. Reactive group in this paper referred to C2–C3 double bond contributed negatively to COX-2 mRNA inhibition. Glycosidic and C3–OH substitutions may lower SMR_VSA5 value. It indicated that flavanones such as hesperetin , naringenin , liquiritigenin were efficient to repress COX-2 mRNA and they were potential anti-inflammatory natural products. Further, substitution with a glucopyranosyl at C-6 resulted in a poorer molecule balance than that at C-8 and a lower COX-2 mRNA inhibiton accordingly. This may expain why orientin and vitexin exhibited better anti-inflammatory activity than their isomers homoorientin and isovitexin . Also, methoxyl groups at C-4’ may also be a favorable flavonoid structural characteristic for COX-2 mRNA inhibiton. These results provide valuable information on understanding the high anti-inflammatory activity of flavonoids.
研究领域:
药理学
·
分子生物学
·
化学
✓ 已验证
DOI
PubMed
高影响因子
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