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Atherosclerosis is marked with the accumulation of low-density lipoproteins and chronic inflammation. The anti-inflammatory therapies exert protective effects on atherosclerosis. Vasicine is a bioactive alkaloid with anti-inflammatory activity from a medicinal plant in Ayurveda and Unani. In this study, the effects of vasicine were evaluated on atherosclerosis in vivo and in vitro. The results showed that vasicine alleviated atherosclerotic lesions and regulated the lipid synthesis by reducing the levels of TC, TG, LDL-C and inhibiting the expresses of scavenger receptors (SR-A, CD36 and LOX-1) to inhibit foam cell formations. And vasicine decreased the levels of IL-1ß, IL-6, MCP-1, and TNF-α to modulate inflammatory response. Besides, vasicine downregulated MAPK and PI3K/AKT/mTOR pathway to activated autophagy, which inhibited the procession of atherosclerosis.
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Pyroptosis signifies a significant form of programmed neuronal demise subsequent to ischemic stroke. In our prior investigations, we demonstrated that the Elabela (ELA)-Apelin receptor (APJ) axis alleviated neuronal death by improving collateral circulation and mitigating ferroptosis in a murine model of middle cerebral artery occlusion (MCAO). However, the connection between ELA and neuronal pyroptosis remains further elucidation. Here, we observed an upregulation of ELA and APJ expression in both murine brain specimens and cultured HT-22 hippocampal neurons exposed to experimental ischemic stroke. ELA administration markedly diminished the infarct size in comparison to controls. ELA treatment ameliorated neurological deficits and anxiety-like symptoms in mice with stroke, concurrently inhibiting pyroptosis and mitochondria fission in neurons. Conversely, ELA knockdown yielded the opposite effects. Utilizing RNA-sequencing analysis, we identified a candidate for pyroptosis priming, Z-DNA-binding protein 1 (ZBP1), which was suppressed in ELA-treated HT-22 neurons during oxygen-glucose deprivation/reperfusion (OGD/R). Subsequent co-immunoprecipitation analyses demonstrated the binding between APJ and ZBP1. Specifically, APJ suppressed ZBP1 to inhibit NLRP3 inflammasome activation and dynamin-related protein 1-mediated mitochondrial fission in neurons. In summary, our findings suggest that ELA functions as a stroke-induced signal limiting neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling, thereby underscoring ELA as a potential therapeutic target for ischemic stroke treatment.
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AVC Isquêmico , Dinâmica Mitocondrial , Neurônios , Piroptose , Transdução de Sinais , Animais , Masculino , Camundongos , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , Dinâmica Mitocondrial/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Piroptose/fisiologia , Piroptose/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/fisiologiaRESUMO
Developing sensitive and accurate Ochratoxin A (OTA) detection methods is essential for food safety. Herein, a simple and reliable strategy for regulating interenzyme distance based on a rigid DNA quadrangular prism as a scaffold was proposed to establish a new electrochemical biosensor for ultrasensitive detection of OTA. The interenzyme distances were precisely adjusted by changing the sequences of the hybridized portions of hairpins SH1 and SH2 to the DNA quadrangular prism, avoiding the complexity and instability of the previous DNA scaffold-based enzyme spacing adjustment strategies. The electrochemical biosensor constructed at the optimal interenzyme distance (10.4 nm) achieved sensitive detection of OTA in a dynamic concentration range from 10 fg/mL to 250 ng/mL with a detection limit of 3.1 fg/mL. In addition, the biosensor was applied to quantify OTA in real samples, exhibiting great application potential in food safety.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Ocratoxinas , DNA , Ocratoxinas/análise , Técnicas Biossensoriais/métodos , Limite de Detecção , Técnicas Eletroquímicas/métodosRESUMO
Long interspersed element type 1 (LINE-1, L1) is an active autonomous transposable element (TE) in the human genome. The first step of L1 replication is transcription, which is controlled by an internal RNA polymerase II promoter in the 5' untranslated region (UTR) of a full-length L1. It has been shown that transcription factor YY1 binds to a conserved sequence motif at the 5' end of the human L1 5'UTR and dictates where transcription initiates but not the level of transcription. Putative YY1-binding motifs have been predicted in the 5'UTRs of two distinct mouse L1 subfamilies, Tf and Gf. Using site-directed mutagenesis, in vitro binding, and gene knockdown assays, we experimentally tested the role of YY1 in mouse L1 transcription. Our results indicate that Tf, but not Gf subfamily, harbors functional YY1-binding sites in its 5'UTR monomers. In contrast to its role in human L1, YY1 functions as a transcriptional activator for the mouse Tf subfamily. Furthermore, YY1-binding motifs are solely responsible for the synergistic interaction between monomers, consistent with a model wherein distant monomers act as enhancers for mouse L1 transcription. The abundance of YY1-binding sites in Tf elements also raise important implications for gene regulation at the genomic level.
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Herein, a giant-sized DNA nanoarray was subtly assembled by two kinds of independent tetrahedral DNA structures as the DNA track for a multi-armed three-dimensional (3D) DNA nanomachine to perform signal transduction and amplification efficiently, which was developed as an electrochemical biosensor for the rapid and ultrasensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, in contrast to conventional DNA walkers with inefficiency, which walked on random DNA tracks composed of a two-dimensional (2D) probe or a one-dimensional (1D) single-stranded (ss)DNA probe, the multi-armed 3D DNA nanomachine from exonuclease III (Exo III) enzyme-assisted target recycling amplification would be endowed with faster reaction speed and better walking efficiency because of the excellent rigidity and orderliness of the tetrahedral DNA nanoarray structure. Once the hairpin H3-label with the signal substance ferrocene (Fc) was added to the modified electrode surface, the multi-armed 3D DNA nanomachine would be driven to move along the well-designed nanoarray tracks by toehold-mediated DNA strand displacement, resulting in most of the ferrocene (Fc) binding to the electrode surface and a remarkable increase in electrochemical signals within 60 min. As a proof of concept, the prepared biosensor attained a low detection limit of 11.4 fg/mL for the sensitive detection of the target MMP-2 and was applied in Hela and MCF-7 cancer cell lysates. As a result, this strategy provided a high-performance sensing platform for protein detection in tumor diagnosis.
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DNA , Metaloproteinase 2 da Matriz , Humanos , Metalocenos , DNA de Cadeia SimplesRESUMO
BACKGROUND: Ischaemia-evoked neuroinflammation is a critical pathogenic event following ischaemic stroke. Gasdermin D (GSDMD)-associated pyroptosis represents a type of inflammation-associated programmed cell death, which can exacerbate neuroinflammatory responses and brain damage. Stimulator of interferon genes (STING) was recently described as a vital innate immune adaptor protein associated with neuroinflammation. Nevertheless, the regulatory effects of STING on microglial pyroptosis post-stroke have not been well elaborated. METHODS: STING-knockout and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO). STING small interfering RNA (siRNA) was transfected into BV2 cells before oxygen-glucose deprivation/reoxygenation (OGD/R). STING-overexpressing adeno-associated virus (AAV) and NOD-like receptor family pyrin domain containing 3 (NLRP3) siRNA were administered by stereotaxic injection. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, TdT-mediated dUTP nick end labeling (TUNEL) staining, Fluoro-Jade C (FJC) staining, neurobehavioural tests, immunohistochemistry, cytokine antibody array assay, transmission electron microscopy, immunoblot, Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) were carried out. Co-immunoprecipitation assays were used to investigate the interplay between STING and NLRP3. RESULTS: STING expression was increased after MCAO and mainly detected on microglia. STING deletion alleviated brain infarction, neuronal damage and neurobehavioural impairment in mice subjected to MCAO. STING knockout suppressed microglial activation and the secretion of inflammatory chemokines, accompanied by mitigation of microglial pyroptosis. Specific upregulation of microglial STING by AAV-F4/80-STING aggravated brain injury and microglial pyroptosis. Mechanistically, co-immunoprecipitation showed that STING bound to NLRP3 in microglia. Supplementation of NLRP3 siRNA reversed AAV-F4/80-STING-induced deterioration of microglial pyroptosis. CONCLUSIONS: The current findings indicate that STING modulates NLRP3-mediated microglial pyroptosis following MCAO. STING may serve as a therapeutic target in neuroinflammation induced by cerebral ischaemic/reperfusion (I/R) injury.
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Soybean oil produces harmful substances after long durations of frying. A rapid and nondestructive identification approach for soybean oil was proposed based on photoacoustic spectroscopy and stacking integrated learning. Firstly, a self-designed photoacoustic spectrometer was built for spectral data collection of soybean oil with various frying times. At the same time, the actual free fatty acid content and acid value in soybean oil were measured by the traditional titration experiment, which were the basis for soybean oil quality detection. Next, to eliminate the influence of noise, the spectrum from 1150 cm-1 to 3450 cm-1 was selected to remove noise by ensemble empirical mode decomposition. Then three dimensionality reduction methods of principal component analysis, successive projection algorithm, and competitive adaptive reweighting algorithm were used to reduce the dimension of spectral information to extract the characteristic wavelength. Finally, an integrated model with three weak classifications was used for soybean oil detection by stacking integrated learning. The results showed that three obvious absorption peaks existed at 1747 cm-1, 2858 cm-1, and 2927 cm-1 for soluble sugars and unsaturated oils, and the model based on stacking integrated learning could improve the classification accuracy from 0.9499 to 0.9846. The results prove that photoacoustic spectroscopy has a good detection ability for edible oil quality detection.
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Óleos de Plantas , Óleo de Soja , Óleo de Soja/análise , Óleo de Soja/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Óleos de Plantas/análiseRESUMO
Transforming the task of information extraction into a machine reading comprehension (MRC) framework has shown promising results. The MRC model takes the context and query as the inputs to the encoder, and the decoder extracts one or more text spans as answers (entities and relationships) from the text. Existing approaches typically use multi-layer encoders, such as Transformers, to generate hidden features of the source sequence. However, increasing the number of encoder layers can lead to the granularity of the representation becoming coarser and the hidden features of different words becoming more similar, potentially leading to the model's misjudgment. To address this issue, a new method called the multi-granularity attention multi-scale self-learning network (MAML-NET) is proposed, which enhances the model's understanding ability by utilizing different granularity representations of the source sequence. Additionally, MAML-NET can independently learn task-related information from both global and local dimensions based on the learned multi-granularity features through the proposed multi-scale self-learning attention mechanism. The experimental results on two information extraction tasks, named entity recognition and entity relationship extraction, demonstrated that the method was superior to the method based on machine reading comprehension and achieved the best performance on the five benchmark tests.
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Angiogenesis helps to improve neurological recovery by repairing damaged brain tissue and restoring cerebral blood flow (CBF). The role of the Elabela (ELA)-Apelin receptor (APJ) system in angiogenesis has gained much attention. We aimed to investigate the function of endothelial ELA on post-ischemic cerebral angiogenesis. Here, we demonstrated that the endothelial ELA expression was upregulated in the ischemic brain and treatment with ELA-32 mitigated brain injury and enhanced the restoration of CBF and newly formed functional vessels following cerebral ischemia/reperfusion (I/R) injury. Furthermore, ELA-32 incubation potentiated proliferation, migration, and tube formation abilities of the mouse brain endothelial cells (bEnd.3 cells) under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. RNA sequencing analysis indicated that ELA-32 incubation had a role in the Hippo signaling pathway, and improved angiogenesis-related gene expression in OGD/R-exposed bEnd.3 cells. Mechanistically, we depicted that ELA could bind to APJ and subsequently activate YAP/TAZ signaling pathway. Silence of APJ or pharmacological blockade of YAP abolished the pro-angiogenesis effects of ELA-32. Together, these findings highlight the ELA-APJ axis as a potential therapeutic strategy for ischemic stroke by showing how activation of this pathway promotes post-stroke angiogenesis.
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Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Camundongos , Células Endoteliais/metabolismo , Transdução de Sinais , Encéfalo/metabolismoRESUMO
Herein, by directly limiting the reaction space, an ingenious three-dimensional (3D) DNA walker (IDW) with high walking efficiency is developed for rapid and sensitive detection of miRNA. Compared with the traditional DNA walker, the IDW immobilized by the DNA tetrahedral nanostructure (DTN) brings stronger kinetic and thermodynamic favorability resulting from its improved local concentration and space confinement effect, accompanied by a quite faster reaction speed and much better walking efficiency. Once traces of target miRNA-21 react with the prelocked IDW, the IDW could be largely activated and walk on the interface of the electrode to trigger the cleavage of H2 with the assistance of Mg2+, resulting in the release of amounts of methylene blue (MB) labeled on H2 from the electrode surface and the obvious decrease of the electrode signal. Impressively, the IDW reveals a conversion efficiency as high as 9.33 × 108 in 30 min with a much fast reaction speed, which is at least five times beyond that of typical DNA walkers. Therefore, the IDW could address the inherent challenges of the traditional DNA walker easily: slow walking speed and low efficiency. Notably, the IDW as a DNA nanomachine was utilized to construct a sensitive sensing platform for rapid miRNA-21 detection with a limit of detection (LOD) of 19.8 aM and realize the highly sensitive assay of biomarker miRNA-21 in the total RNA lysates of cancer cell. The strategy thus helps in the design of a versatile nucleic acid conversion and signal amplification approach for practical applications in the areas of biosensing assay, DNA nanotechnology, and clinical diagnosis.
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Técnicas Biossensoriais , MicroRNAs , Nanoestruturas , MicroRNAs/genética , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , DNA/química , Nanoestruturas/química , Limite de DetecçãoRESUMO
Ferroptosis is a form of non-apoptotic cell death caused by iron-dependent peroxidation of lipids. It contributes to ischemic stroke-induced neuronal damage. Elabela (ELA), a novel endogenous ligand for Apelin receptor (APJ), regulates oxidative stress and exerts a protective role in cardiovascular disease. However, the effect of ELA-APJ axis on cellular ferroptosis in cerebral ischemia/reperfusion (I/R) remains elusive. The present study showed that ELA and APJ were expressed on neurons and increased after cerebral I/R injury. The I/R insult triggered typical molecular and morphological features of neuronal ferroptosis, including iron and MDA accumulation, mitochondrial shrink and membrane rupture, upregulation of positive ferroptosis regulators and downregulation of negative regulators. ELA-32 treatment reduced brain infarction and ameliorated neurobehavioral deficits and cognitive dysfunction. Moreover, ELA-32 administration alleviated neuronal ferroptosis, accompanied by reduced iron deposition, decreased mitochondrial damage, relived lipid peroxidation and glutathione reduction. Such effects of ELA-32 were abolished by AAV-APJ-RNAi or nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385. Mechanistically, ELA was shown to bind to APJ and activate NRF2/ARE anti-oxidative signaling pathway via Gα13. Together, these findings suggested that ELA-APJ axis mitigates neuronal ferroptosis after ischemic stroke and that the ELA-32 peptide may be a putative therapeutic avenue for ischemic stroke.
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Isquemia Encefálica , Ferroptose , AVC Isquêmico , Traumatismo por Reperfusão , Humanos , Ferroptose/genética , Fator 2 Relacionado a NF-E2/genética , Neurônios , Traumatismo por Reperfusão/genética , Isquemia Encefálica/genéticaRESUMO
Herein, by introducing mismatches, a high-efficiency mismatch-fueled catalytic multiple-arm DNA junction assembly (M-CMDJA) with high-reactivity and a high-threshold is developed as a programmable DNA signal amplifier for rapid detection and ultrasensitive intracellular imaging of miRNA. Compared with traditional nucleic acid signal amplification (NASA) with a perfect complement, the M-CMDJA possesses larger kinetic and thermodynamic favorability owing to the more negative reaction standard free energy (ΔG) as driving force, resulting in much higher efficiency and rates. Once traces of the input initiator react with the mismatched substrate DNA, it could be converted into amounts of output multiple-arm DNA junctions via the M-CMDJA as the functional DNA conversion nanodevice. Impressively, the mismatch-fueled catalytic four-arm DNA junction assembly (M-CFDJA) exhibits high conversion efficiency up to 1.05 × 108 in 30 min, which is almost ten times more than those of conventional methods. Therefore, the M-CMDJA could easily address the challenges of traditional methods: slow rates and low efficiency. In application, the M-CFDJA as a DNA signal amplifier was successfully used to develop a biosensing platform for rapid miRNA detection with a LOD of 6.11 aM and the ultrasensitive intracellular imaging of miRNA, providing a basis for the next-generation of versatile DNA signal amplification methods for ultimate applications in DNA nanobiotechnology, biosensing assay, and clinical diagnoses.
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Potent antioxidative drugs are urgently needed to treat ischemia-reperfusion (I/R) induced reactive oxygen species (ROS)-mediated cerebrovascular and neural injury during ischemia strokes. However, current antioxidative agents have limited application in such disease due to low blood-brain barrier (BBB) penetration. We herein designed a "neutrophil piggybacking" strategy based on albumin opsonized nanoparticles co-encapsulated with antioxidases catalase (CAT) and superoxide dismutase 1 (SOD1). The system utilized the natural potential of neutrophils to target inflamed tissues to deliver antioxidases to injured sites in the brain. In addition, the system was integrated with a selenium (Se)-containing crosslinker to inhibit ferroptosis. We showed that the nanoparticles opsonized in the hybrid form rather than with an albumin-shell structure exhibited enhanced neutrophil targeting and efficient BBB penetration in vitro and in vivo. We further showed that the neutrophil-mediated delivery of antioxidases effectively reduced oxidative damage and apoptosis of neurons in brain tissue in a transient middle cerebral artery occlusion (tMCAO) mouse model. Moreover, the successful delivery of Se with the nanoparticles increased the expression of glutathione peroxidase 4 (GPX4) and effectively inhibited neuronal ferroptosis, achieving a satisfactory neuroprotective effect in I/R injury mice. Our study demonstrated that the rationally designed nanomedicines using the "neutrophil piggybacking" strategy can efficiently penetrate the BBB, greatly expanding the application of nanomedicines in the treatment of central nervous system (CNS) diseases.
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Barreira Hematoencefálica , Traumatismo por Reperfusão , Animais , Camundongos , Nanomedicina , Traumatismo por Reperfusão/tratamento farmacológico , Albuminas , IsquemiaRESUMO
In this manuscript, the polysaccharide isolated from Piperis Dahongpao was extracted with the method of water-extraction and alcohol-precipitation. Besides, the homogeneous polysaccharide (PDP-1) with an MW of 2.47 × 103 KDa was purified with the Sephadex G-150 column. The monosaccharide composition analysis showed that PDP-1 consisted of Man, Glc and Gal in a ratio of 1.678:1.784:1, respectively. Besides, the methylation analysis indicated that PDP-1 was composed of six sugar alcohol derivatives, which were â4ï¼6)-D-Galp-(1â, â4)-D-Galp-(1â, â4)-D -Manp-(1â, â4)-D-Glcp-(1â, â6)-D -Glcp-(1â and D-Glcp-(1 â . Otherwise, the microscopic conformation of PDP-1 was flat, dense and porous. In addition, the PDP-1 had a strong scavenging ability for DPPH free radicals, Hydroxyl free radicals and ABTS free radicals. At the same time, PDP-1 could effectively decrease the peroxidation process of kidney and heart in mice with acute alcoholic liver injury, improve its antioxidant capacity, and protect the organ injury caused by alcohol to a certain extent. Therefore, the results of this manuscript showed that Piperis Dahongpao polysaccharides have antioxidant potential, which lays a theoretical foundation for the research of Piperis Dahongpa polysaccharides in medicine.
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Antioxidantes , Traumatismos Cardíacos , Camundongos , Animais , Antioxidantes/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Monossacarídeos/química , Rim/química , Peso MolecularRESUMO
A series of γ-lactone derivatives (E)-4-arylidene-5-oxotetrahydrofuran derivatives were synthesized via a tandem Passerini 3CC/SN cyclization microwave-assisted one-pot method efficiently starting from Baylis Hillman acids, aryl glyoxals and isocyanides, and using ionic liquid as reaction medium. The products were characterized by hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR). Single crystal X-ray analysis of the compound RPDFB clearly confirmed its assigned chemical structures. Meanwhile, the effects of four compounds (RPDFB, RPDFC, RPDFI, RPDFJ) on the growth inhibition activity of Gibberella zeae were detected, and found that the compound RPDFB has significant growth inhibition activity to Gibberella zeae.
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We have synthesized Rhopaladins' analog (2E,4E)-4-chlorobenzylidene-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) via a highly facile, inexpensive and green approach and verified the structural superiority of compound RPDPRH through molecular docking. Moreover, we further detected the anti-proliferation, apoptosis and HPV E6/E7 effects of RPDPRH on CaSki cells. Finally, we confirmed that compared with the previous compound (E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB), RPDPRH could better inhibit proliferation, induce apoptosis, and down-regulate HPV E6/E7 mRNA expression on Caski cells. And preliminary RT-PCR experiments have demonstrated that RPDPRH also could affect the expression of Bcl-2, Bax and Caspase-3 mRNA in Caski cells. In summary, RPDPRH has potential as an effective agent against cervical cancer and will play an important role in our subsequent research.
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Herein, a long period liner DNA tandem (Lr-DNT) was intelligently designed as DNA track for quadruped DNA walker (q-walker) to run in an orderly and efficient manner, which could be applied to construct an electrochemical biosensor for rapid and ultrasensitive detection of microRNA-21 (miRNA-21). Impressively, benefiting from the orderliness and equidistance of Lr-DNT, the q-walker could be endowed with a high controllability, directionality as well as a quite short reaction time down to 20 min compared with those of traditional DNA walkers walked on the stochastic tracks. Once the target miRNA-21 interacted with the locked q-walker, the q-walker could be activated to expeditiously cleave Lr-DNT for releasing amounts of signal probes ferrocene (Fc) with the assistance of the Nt.BbvCI enzyme. This way, the developed q-walker could not only readily overcome the problem of low reaction efficiency but also address the drawback of time consumption in a previous strategy. As a proof of concept, the prepared biosensor could accomplish sensitive detection of target miRNA-21 with a detection limit down to 31 aM. As a result, this tactic gave impetus to design high-performance sensing platform with ultimate application in clinical sample analysis and nucleic acid based cancer diagnostics.
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Técnicas Biossensoriais , MicroRNAs , DNA/genética , Técnicas Eletroquímicas , Limite de Detecção , MicroRNAs/análiseRESUMO
Herein, an ultrasensitive and versatile electrochemical biosensor was developed through the target-controlled capture and release of signal probe-loaded DNA nanotube for the ultrasensitive detection of two different types of cancer-related biomarkers, microRNA-21 (miRNA-21) and glutathione (GSH). In this system, target 1 (miRNA-21) first triggered duplex-specific nuclease (DSN)-assisted recycle amplification to generate numerous disulfide-linked DNA strands (DL), which could effectively capture DNA nanotube to immobilize methylene blue (MB) to produce remarkable electrochemical signals and achieve the ultrasensitive detection of miRNA-21 with a detection limit down to 32.6 aM. Furthermore, in the presence of target 2 (GSH), the electrochemical signal was significantly reduced by a thiol-disulfide bond exchange reaction on DL to release MB-immobilized DNA nanotubes away from the sensing interface, which enabled the sensitive analysis of GSH with a detection limit of 0.379 nM. Impressively, this strategy could achieve ultrasensitive detection of different types of biomarkers to prominently lessen false-positive responses from the current sensing methods toward a single biomarker or the same type of biomarker and remarkably heighten the accuracy and precision of early cancer diagnosis. Meanwhile, the proposed electrochemical biosensor made it possible to realize the regenerative analysis of targets over four times without extra fuel, which could conspicuously improve the analytical efficiency compared with that of traditional biosensing assays. As a result, this study might open up novel insights to design a versatile and multifunctional sensing platform and encourage deeper exploration for detecting different types of biomarkers in the fields of early disease diagnosis and biochemical research.
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Técnicas Biossensoriais , MicroRNAs , Nanotubos , Neoplasias , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , DNA/química , Sondas de DNA , Dissulfetos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Azul de Metileno , MicroRNAs/análiseRESUMO
Gynecological malignancy seriously threatens the physical and mental health of women. Shikonin is a naphthoquinone compound with a variety of biological activities. Studies have shown that shikonin can inhibit cell proliferation, promote cell apoptosis and induce cell necrosis. And in recent years, shikonin are also being increasingly used for the study of gynecological malignant diseases. Therefore, we reviewed the mechanism of action and structure optimization of shikonin in gynecological malignant tumors, in order to provide some reference for further research and development of related drug.
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Heterocyclic compounds were widely used in many domains; pyrrolidone is a derivative of heterocycles that can be used to synthesize anticancer drugs. A new fluorine-containing rhopaladins' analog(E)-2-(4-bromobenzoyl)-N-(tert-butyl)-4-(4-fluoro benzylidene)-5-oxo-1-propylpyrrolidine-2-carboxamide (RPDPD for short) of 2-aroyl-4-arylidene-5-oxopyrrolidine derivative was synthesized by the one-pot synthesis method and evaluated for its anti-tumor activity in vitro via CCK8 assay and annexin V/propidium iodide (PI) staining of HeLa cells. The results exhibited that compound RPDPD has inhibited the proliferation of HeLa in a dose-dependent manner with an IC50 of 24.23 µmol/L (p < 0.05) and has low hepatotoxicity with an IC50 of 235.6 µmol/L (p < 0.05) to normal hepatocyte LO2 cells. The apoptotic assay demonstrated that compound RPDPD has induced apoptosis in HeLa cells (from 14.26 to 23.4%, p < 0.05). qRT-PCR results showed that the compound RPDPD could inhibit the expression of oncogene E6/E7 mRNA (p < 0.05) of human papillomavirus (HPV). The results of Western blot showed that the compound RPDPD promoted the expression of TIMP3 protein and inhibited the expression of MMP3 (p < 0.05). In conclusion, the compound RPDPD can inhibit the proliferation of cervical cancer cells and induce the apoptosis of cervical cancer cells, and its mechanism may be related to the inhibition of E6 mRNA and E7 mRNA expressions, and the anticancer effect of the compound RPDPD on cervical cancer is closely related to the TIMP3/MMP3 signaling axis.