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Etomidate (ETO), a hypnotic agent used for anesthesia induction, has been shown to induce long-lasting cognitive deficits. In the present study, we investigated whether ETO could activate the HIF1A/PGK1 pathway to antagonize oxidative damage in mice with postoperative cognitive dysfunction (POCD). A mouse model of ETO-mediated POCD was established, and pathological changes, apoptosis, and inflammatory factors in mouse hippocampal tissues were analyzed by HE staining, TUNEL assay, and ELISA. ETO was revealed to cause cognitive dysfunction in mice. Integrated database mining was conducted to screen out transcription factors that are both related to ETO and POCD. Hypoxia-inducible factor 1-alpha (HIF1A) was overexpressed in mice with POCD, and downregulation of HIF1A alleviated cognitive dysfunction in mice. HIF1A downregulation inhibited the transcription of phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 abated the alleviating effects of HIF1A knockdown on oxidative stress in mice with POCD. In addition, HIF1A activation of PGK1 induced oxidative stress and apoptosis in HT-22 cells while inhibiting cell viability. Taken together, we demonstrated that HIF1A activation of PGK1 induced oxidative stress in ETO-mediated POCD.
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Etomidato , Subunidad alfa del Factor 1 Inducible por Hipoxia , Estrés Oxidativo , Fosfoglicerato Quinasa , Complicaciones Cognitivas Postoperatorias , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Fosfoglicerato Quinasa/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Complicaciones Cognitivas Postoperatorias/metabolismo , Etomidato/farmacología , Masculino , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Disfunción Cognitiva/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Baolia H.W.Kung & G.L.Chu is a monotypic genus only known in Diebu County, Gansu Province, China. Its systematic position is contradictory, and its morphoanatomical characters deviate from all other Chenopodiaceae. Recent study has regarded Baolia as a sister group to Corispermoideae. We therefore sequenced and compared the chloroplast genomes of this species, and resolved its phylogenetic position based on both chloroplast genomes and marker sequences. RESULTS: We sequenced 18 chloroplast genomes of 16 samples from two populations of Baolia bracteata and two Corispermum species. These genomes of Baolia ranged in size from 152,499 to 152,508 bp. Simple sequence repeats (SSRs) were primarily located in the LSC region of Baolia chloroplast genomes, and most of them consisted of single nucleotide A/T repeat sequences. Notably, there were differences in the types and numbers of SSRs between the two populations of B. bracteata. Our phylogenetic analysis, based on both complete chloroplast genomes from 33 species and a combination of three markers (ITS, rbcL, and matK) from 91 species, revealed that Baolia and Corispermoideae (Agriophyllum, Anthochlamys, and Corispermum) form a well-supported clade and sister to Acroglochin. According to our molecular dating results, a major divergence event between Acroglochin, Baolia, and Corispermeae occurred during the Middle Eocene, approximately 44.49 mya. Ancestral state reconstruction analysis showed that Baolia exhibited symplesiomorphies with those found in core Corispermoideae characteristics including pericarp and seed coat. CONCLUSIONS: Comparing the chloroplast genomes of B. bracteata with those of eleven typical Chenopodioideae and Corispermoideae species, we observed a high overall similarity and a one notable noteworthy case of inversion of approximately 3,100 bp. of DNA segments only in two Atriplex and four Chenopodium species. We suggest that Corispermoideae should be considered in a broader sense, it includes Corispermeae (core Corispermoideae: Agriophyllum, Anthochlamys, and Corispermum), as well as two new monotypic tribes, Acroglochineae (Acroglochin) and Baolieae (Baolia).
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Amaranthaceae , Genoma del Cloroplasto , Filogenia , Amaranthaceae/genética , Amaranthaceae/anatomía & histología , Amaranthaceae/clasificación , Repeticiones de Microsatélite , China , ADN de Cloroplastos/genética , Análisis de Secuencia de ADN , Marcadores GenéticosRESUMEN
BACKGROUND: Salsola laricifolia is a typical C3-C4 typical desert plant, belonging to the family Amaranthaceae. An efficient single-cell system is crucial to study the gene function of this plant. In this study, we optimized the experimental conditions by using Box-Behnken experimental design and Response Surface Methodology (RSM)-Artificial Neural Network (ANN) model based on the previous studies. RESULTS: Among the 17 experiment groups designed by Box-Behnken experimental design, the maximum yield (1.566 × 106/100 mg) and the maximum number of viable cells (1.367 × 106/100 mg) were obtained in group 12, and the maximum viability (90.81%) was obtained in group 5. Based on these results, both the RSM and ANN models were employed for evaluating the impact of experimental factors. By RSM model, cellulase R-10 content was the most influential factor on protoplast yield, followed by macerozyme R-10 content and mannitol concentration. For protoplast viability, the macerozyme R-10 content had the highest influence, followed by cellulase R-10 content and mannitol concentration. The RSM model performed better than the ANN model in predicting yield and viability. However, the ANN model showed significant improvement in predicting the number of viable cells. After comprehensive evaluation of the protoplast yield, the viability and number of viable cells, the optimal results was predicted by ANN yield model and tested. The amount of protoplast yield was 1.550 × 106/100 mg, with viability of 90.65% and the number of viable cells of 1.405 × 106/100 mg. The corresponding conditions were 1.98% cellulase R-10, 1.00% macerozyme R-10, and 0.50 mol L-1 mannitol. Using the obtained protoplasts, the reference genes (18SrRNA, ß-actin and EF1-α) were screened for expression, and transformed with PEG-mediated pBI121-SaNADP-ME2-GFP plasmid vector. There was no significant difference in the expression of ß-actin and EF1-α before and after treatment, suggesting that they can be used as internal reference genes in protoplast experiments. And SaNADP-ME2 localized in chloroplasts. CONCLUSION: The current study validated and evaluated the effectiveness and results of RSM and ANN in optimizing the conditions for protoplast preparation using S. laricifolia as materials. These two methods can be used independently of experimental materials, making them suitable for isolating protoplasts from other plant materials. The selection of the number of viable cells as an evaluation index for protoplast experiments is based on its ability to consider both protoplast yield and viability. The findings of this study provide an efficient single-cell system for future genetic experiments in S. laricifolia and can serve as a reference method for preparing protoplasts from other materials.
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In recent years, DNA origami-based nanocarriers have been extensively utilized for efficient cancer therapy. However, developing a nanocarrier capable of effectively protecting cargos such as RNA remains a challenge. In this study, we designed a compact and controllable DNA tubular origami (DTO) measuring 120 nm in length and 18 nm in width. The DTO exhibited appropriate structural characteristics for encapsulating and safeguarding cargo. Inside the DTO, we incorporated 20 connecting points to facilitate the delivery of cargoes to various ovarian and normal epithelial cell lines. Specifically, fluorescent-labeled DNA strands were attached to these sites as cargoes. The DTO was engineered to open upon encountering miR-21 through RNA/DNA strand displacement. Significantly, for the first time, we inhibited fluorescence using the compact DNA nanotube and observed dynamic fluorescent signals, indicating the controllable opening of DTO through live-cell imaging. Our results demonstrated that the DTO remained properly closed, exhibited effective internalization in ovarian cancer cells in vitro, showcasing marked differential expression of miR-21, and efficiently opened with short-term exposure to miR-21. Leveraging its autonomous behavior and compact design, the DTO emerges as a promising nanocarrier for various clinically relevant materials. It holds significant application prospects in anti-cancer therapy and the development of flexible biosensors.
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Artemisiaqingheensis (Asteraceae, Anthemideae), a new species from Qinghe County, Xinjiang, China, is described and illustrated. We investigated its phylogenetic position and relationships with 35 other species of Artemisia using whole chloroplast DNA sequence data. The molecular phylogenetic results and morphological evidence (multi-layered involucral bracts and homogamous capitula with bisexual flowers) showed that the new species belongs to ArtemisiasubgenusSeriphidium. A diagnostic table and discussion of morphological characters are provided to distinguish the new species from A.amoena, A.gracilescens, A.lessingiana and A.terrae-albae.
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Numerous biological systems in nature provide much inspiration for humanity to master diverse coloration strategies for creating stimuli-responsive materials and display devices, such as to access gorgeous structural colors from well-defined photonic structures. Cholesteric liquid crystals (CLCs) are a fascinating genre of photonic materials displaying iridescent colors responsive to circumstance changes; however, it is still a big challenge to design materials with broadband color variation as well as good flexibility and freestanding capacity. Herein, we report a feasible and flexible strategy to fabricate cholesteric liquid-crystal networks (CLCNs) with precise colors across the entire visible spectrum through molecular structure tailoring and topology engineering and demonstrate their application as smart displays and rewritable photonic paper. Influences of chiral and achiral LC monomers on the thermochromic behaviors of CLC precursors as well as on the topology of the polymerized CLCNs are systematically investigated, demonstrating that the monoacrylate achiral LC facilitated the formation of a smectic phase-chiral phase (Sm-Ch) pretransitional phase in the CLC mixture and improved the flexibility of the photopolymerized CLCNs. High-resolution multicolor patterns in one CLCN film are generated through photomask polymerization. In addition, the freestanding CLCN films show perceivable mechanochromic behaviors and repeated erasing-rewriting performances. This work opens avenues toward the realization of pixelated colorful patterns and rewritable CLCN films promising in technology fields ranging from information storage and smart camouflage to anti-counterfeiting and smart display.
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BACKGROUND: Artemisia subg. Seriphidium, one of the most species-diverse groups within Artemisia, grows mainly in arid or semi-arid regions in temperate climates. Some members have considerable medicinal, ecological, and economic value. Previous studies on this subgenus have been limited by a dearth of genetic information and inadequate sampling, hampering our understanding of their phylogenetics and evolutionary history. We therefore sequenced and compared the chloroplast genomes of this subgenus, and evaluated their phylogenetic relationships. RESULTS: We newly sequenced 18 chloroplast genomes of 16 subg. Seriphidium species and compared them with one previously published taxon. The chloroplast genomes, at 150,586-151,256 bp in length, comprised 133 genes, including 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and one pseudogene, with GC content of 37.40-37.46%. Comparative analysis showed that genomic structures and gene order were relatively conserved, with only some variation in IR borders. A total of 2203 repeats (1385 SSRs and 818 LDRs) and 8 highly variable loci (trnK - rps16, trnE - ropB, trnT, ndhC - trnV, ndhF, rpl32 - trnL, ndhG - ndhI and ycf1) were detected in subg. Seriphidium chloroplast genomes. Phylogenetic analysis of the whole chloroplast genomes based on maximum likelihood and Bayesian inference analyses resolved subg. Seriphidium as polyphyletic, and segregated into two main clades, with the monospecific sect. Minchunensa embedded within sect. Seriphidium, suggesting that the whole chloroplast genomes can be used as molecular markers to infer the interspecific relationship of subg. Seriphidium taxa. CONCLUSION: Our findings reveal inconsistencies between the molecular phylogeny and traditional taxonomy of the subg. Seriphidium and provide new insights into the evolutionary development of this complex taxon. Meanwhile, the whole chloroplast genomes with sufficiently polymorphic can be used as superbarcodes to resolve interspecific relationships in subg. Seriphidium.
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Artemisia , Genoma del Cloroplasto , Artemisia/genética , Filogenia , Teorema de Bayes , GenómicaRESUMEN
DNA computing has become the focus of computing research due to its excellent parallel processing capability, data storage capacity, and low energy consumption characteristics. DNA computational units can be precisely programmed through the sequence specificity and base pair principle. Then, computational units can be cascaded and integrated to form large DNA computing systems. Among them, DNA strand displacement (DSD) is the simplest but most efficient method for constructing DNA computing systems. The inputs and outputs of DSD are signal strands that can be transferred to the next unit. DSD has been used to construct logic gates, integrated circuits, artificial neural networks, etc. This review introduced the recent development of DSD-based computational systems and their applications. Some DSD-related tools and issues are also discussed.
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Most elastomers suffer from poor thermal conductivity, which limits their further applications in various fields, especially for electronic devices. A common method to enhance thermal conductivity is to introduce thermally conductive fillers into elastomers. Unfortunately, thermal conductivity and compliance are often correlated and coupled: large amounts of fillers are required to increase thermal conductivity while damaging the compliance dramatically. In this study, we report thermally conductive and compliant polyurethane elastomer composites by constructing a tri-branched polymer network. The resultant polyurethane elastomer composites exhibit excellent superhigh stretchability (2000%), low Young's modulus (640 kPa), and low thermal resistance (0.11 K cm2 W-1). Experimental rheology and a theoretical tube model are employed to study the nature of the high compliant tri-branched polymer network. Furthermore, the remarkable flexibility of our elastomer composite and heat dissipation act as thermal interface materials in the thermal management of flexible electronics. These findings advance our understanding on the rational design of the polymer frameworks of thermal composites, improving our ability to predict, design, and leverage their unique properties for future applications.
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Artemisia borotalensis Poljakov is an endemic and endangered herb in China. In this study, we sequenced and analyzed the complete chloroplast genome of this species. Sequencing revealed the genome to be 151,179 bp in length, containing a large single copy region (82,862 bp), a small single copy region (18,377 bp), and a pair of inverted repeat regions (24,970 bp each). Our analyses demonstrated that it contained 133 genes, including 87 protein-coding genes, 37 transfer RNA genes, eight ribosomal RNA genes, and one pseudogene (ycf1). Furthermore, we found the genome to have an overall GC content of 37.4%. A phylogenetic analysis indicated that A. borotalensis and A. maritima clustered together as sister group to A. annua and A. fukudo clade.
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Although noble metal nanocrystals have been studied extensively in the past decades, the shape-controlled synthesis of non-noble metal nanocrystals has remained challenging with limited success, which is a grand obstacle to their wide applications. Herein, a novel lattice mismatch-involved shape-control mechanism of Cu nanocrystals in a seed-mediated synthesis is reported, which can produce Cu nanoplates in high yield with tailored sizes (28-130 nm), holding great potential in optical and catalytic applications. The lattice mismatch between Cu and the seed is found effective in inducing crystallographic defects for symmetry breaking toward anisotropic nanocrystals. While a too-large lattice mismatch (11.7% for Au seeds) leads to multiple twin defects to form quasi-spherical Cu nanocrystals, an appropriately large lattice mismatch (7.7% for Pt and 6.9% for Pd seeds) successfully induces planar defects for the formation of Cu nanoplates. The size of the Cu nanoplates is customizable by controlling the concentration of the seeds, leading to tunable optical properties. A prototype of a colorimetric indicator with Cu nanoplates, potentially applicable to the safety control of foods and drugs is demonstrated. This mechanism paves a new way for the shape-controlled synthesis of Cu and other metal nanocrystals for a broad range of applications.
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Land degradation caused by soil salinization and wind erosion is the major obstruction to sustainable agriculture in the arid region. Salsola species have the potential to prevent land degradation. However, there is limited information about seed germination requirements and tolerance to salinity and drought for representative Salsola species. This study aimed to assess the effects of the winged perianth (seed structural features) and abiotic factors (light, temperature, salinity, and drought) on the seed germination of these species. These Salsola species varied considerably in seed germination characteristics. Compared with naked seeds, winged seeds had lower germination percentages for S. heptapotamica S. rosacea, and S. nitraria species. Darkness decreased the germination percentage of winged and naked seeds of S. rosacea, however, for S. heptapotamica and S. nitraria, decreased seed germination was only when the winged perianth existed. Germination of S. heptapotamica, S. rosacea, and S. nitraria seeds depended on the perianth and light conditions. The naked seeds of these three species could germinate at a wide range of temperatures, especially in light. The presence of perianth, light, and temperature did not significantly influence the germination of S. ruthenica seeds. When cultivating these species, it is beneficial to remove the winged perianth of seeds and sow it on the soil surface when the temperature is above 5/15°C. In addition, seed germination of Salsola displayed high tolerance to salinity and drought. Compared with winged seeds, naked seeds showed lower recovery germination under high salinity but had a similar recovery of germination under high PEG concentration. Our study provides detailed germination information for the cultivation of these four representative Salsola species in degraded saline soils of the arid zone.
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Water conditions directly affect plant growth and thus modify reproduction allocation. However, little is known about the transgenerational effects of water conditions on xerophytes. The desert annual Atriplex aucheri produces three types of seeds (A: dormant, ebracteate black seeds; B: dormant, bracteolate black seeds; C: non-dormant, bracteolate brown seeds) on a single plant. The aim of this study was to investigate the effects of low/high water treatment (thereafter progeny water treatment) on aboveground biomass, C:N stoichiometry, and offspring seed characteristics of A. aucheri grown from brown seeds whose mother plants were under low/high water treatment (thereafter maternal water treatment). Progeny water only affected shoot dry weight and seed allocation of type A. Under low progeny water treatment, plants from parents with low maternal water treatment had the lowest biomass. Maternal water did not significantly influence the C and N content, however high maternal water increased the C:N ratio. Maternal water treatment did not significantly affect seed number. However, plants under low maternal and progeny water treatments had the lowest weight for type B seeds. When progeny plants were under low water treatment, seed allocation of type A, type B, and total seed allocation of plants under high maternal water were significantly lower than those of plants under low maternal water. These results indicate that water conditions during the maternal generation can dramatically contribute to progeny seed variation, but the transgenerational effects depend on the water conditions of progeny plants.
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The NADP-malic enzyme (NADP-ME) catalyzes the reversible decarboxylation of L-malate to produce pyruvate, CO2, and NADPH in the presence of a bivalent cation. In addition, this enzyme plays crucial roles in plant developmental and environment responses, especially for the plastidic isoform. However, this isoform is less studied in C3-C4 intermediate species under drought and salt stresses than in C3 and C4 species. In the present study, we characterized SaNADP-ME4 from the intermediate woody desert species Salsola laricifolia. SaNADP-ME4 encoded a protein of 646 amino acids, which was found to be located in the chloroplasts based on confocal imaging. Quantitative real-time PCR analysis showed that SaNADP-ME4 was highly expressed in leaves, followed by stems and roots, and SaNADP-ME4 expression was improved and reached its maximum under the 200 mm mannitol and 100 mm NaCl treatments, respectively. Arabidopsis overexpressing SaNADP-ME4 showed increased root length and fresh weight under mannitol and salt stress conditions at the seedling stage. In the adult stage, SaNADP-ME4 could alleviate the decreased in chlorophyll contents and PSII photochemical efficiency, as well as improve the expression of superoxide dismutase, peroxidase, and pyrroline-5-carboxylate synthase genes to enhance reactive oxygen species scavenging capability and proline levels. Our results suggest that SaNADP-ME4 overexpression in Arabidopsis increases drought and salt stress resistance.
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This work details the scalable and solventless synthesis of a potential fully biobased monobenzoxazine resin derived from tyrosol and furfurylamine. The structure of the monomer was studied by nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared (FTIR). The curing of the precursors was characterized by differential scanning calorimetry (DSC), rheological measurements, and thermogravimetric analysis (TGA). The properties of the resulting biobased polybenzoxazine were then determined by thermogravimetric analysis (TGA) and dynamic mechanical thermal analysis (DMA). A thermally stable resin was obtained with 5% and 10% weight-reduction-temperature (T d5 and T d10) values of 349 and 395 °C, respectively, and a char yield of 53%. Moreover, the low melting temperature, low viscosity, and excellent thermomechanical behavior make this fully biobased resin a promising candidate for coating applications.
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Liquid crystal polymers have attracted massive attention as stimuli-responsive shape memory materials due to their unique reversible large-scale and high-speed actuations. These materials can be utilized to fabricate artificial muscles, sensors, and actuators driven by thermal order-disorder phase transition or trans-cis photoisomerization. This review collects most commonly used liquid crystal monomers and techniques to macroscopically order and align liquid crystal materials (monodomain), highlighting the unique materials on the thermal and photo responsive reversible shape memory effects. Challenges and potential future applications are also discussed.
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Cristales Líquidos/química , Polímeros/química , Materiales Inteligentes/química , Materiales Biocompatibles/química , Sustancias Macromoleculares/químicaRESUMEN
Herein, a novel three-dimensional (3D) DNA nanomachine with high walking efficiency via free DNA walker movement on biomimetic lipid bilayers supported by hard silica@CdTe quantum dots (SiO2@CdTe) was constructed for ultrasensitive fluorescence detection of microRNA. The synthesized SiO2@CdTe nanoparticles were adopted as the fluorescence indicator and spherical carrier of lipid bilayers, and then the DNA substrates were anchored on lipid bilayers with biomimetic fluidity through the cholesterol-lipid interaction. Once target microRNA-141 interacted with the 3D DNA nanomachine to release cholesterol labeled arm (Chol-arm), the Chol-arm could generate a series of strand displacement reactions by moving freely on the lipid bilayers, resulting in the releasement of numerous quenchers from the SiO2@CdTe nanoparticles and inducing a strong fluorescence signal. Impressively, compared with traditional 3D DNA nanomachine conjugating DNA substrates on hard surfaces (such as gold or silica) with limited reactivity, the proposed biomimetic 3D DNA nanomachine not only immobilized DNA substrates rapidly and effectively but also kept it with a favorable fluidity, which significantly enhanced the walking efficiency. As expected, the biomimetic 3D DNA nanomachine for fluorescence detection of microRNA-141 exhibited an excellent performance with a detection limit of 0.21 pM and presented promising properties in cell lysate detection and intracellular imaging. Thus, the described biomimetic 3D DNA nanomachine provided a novel avenue for sensitive detection of biomolecules, which could be useful for bioanalysis and early clinical diagnoses of disease.
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Materiales Biomiméticos/química , Técnicas Biosensibles , Compuestos de Cadmio/química , Ácidos Nucleicos Inmovilizados/química , Membrana Dobles de Lípidos/química , MicroARNs/análisis , Telurio/química , Línea Celular Tumoral , Colesterol/química , Femenino , Humanos , Límite de Detección , Células MCF-7 , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , MicroARNs/genética , MicroARNs/metabolismo , Microscopía Fluorescente , Nanotecnología/métodos , Puntos Cuánticos/química , Dióxido de Silicio/químicaRESUMEN
Herein, by anchoring cholesterol-labelled DNA probes to silicon-supported lipid bilayers via cholesterol-lipid interaction, a dynamic three-dimensional (3D) DNA nanostructure could be facilely assembled, which is applied as a microRNA (miRNA)-induced self-powered 3D DNA nanomachine with high movement efficiency. Once the self-powered 3D DNA nanomachine is triggered by target miRNA, it achieves autonomous operation without external addition of fuel DNA strands or protein enzymes. Impressively, the biocompatible lipid bilayers not only preserve the biological character of the DNA probes, but also improve the movement efficiency of the DNA nanomachine, which directly solves the key challenge of the steric barrier effect of traditional rigid surfaces (Au or silicon) for DNA probe diffusion. As a proof of concept, our proposed DNA nanomachine is successfully applied in rapid and sensitive detection of miRNAs, which gives a new idea for the construction of highly efficient DNA nanomachines for biosensing and clinic diagnosis.
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Técnicas Biosensibles , ADN/química , Membrana Dobles de Lípidos/química , Nanoestructuras/química , Silicio/química , Colesterol/química , Sondas de ADN/química , Técnicas y Procedimientos Diagnósticos , Células HeLa , Humanos , Células MCF-7 , MicroARNs/análisis , MicroARNs/química , Microscopía Confocal , Imagen Óptica , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Accumulating evidence indicates that angiotensin (1-7) [Ang-(1-7)] protects against idiopathic pulmonary fibrosis (IPF) in animal experiments. However, whether Ang-(1-7) effectively inhibits epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1) remains unclear. The aim of this study is to examine the eï¬ ;ects of Ang-(1-7) on TGF-ß1-induced EMT in human alveolar epithelial cells. We found that angiotensin-converting enzyme 2 (ACE2) /Ang-(1-7)/MasR were decreased in the lungs of mice with IPF induced by bleomycin, and were negatively correlated with Tgfb1 mRNA expression. In vitro, our data showed that exogenous Ang-(1-7) restored the expression of E-cadherin and decreased the expressions of α-SMA and Vimentin induced by TGF-ß1 in A549 cells. Ang-(1-7) also reduced TGF-ß1-induced migration and synthesis of the extracellular matrix, such as collagen â and collagen â ¢. Mechanistically, we observed that Ang-(1-7) directly inhibited TGF-ß1-induced phosphorylation of Smad2 and Smad3, and suppressed the expression of the downstream target gene of TGF-ß1-Smad signaling, including ZEB1, ZEB2, TWIST, and SNAIL1. Additionally, phosphorylation of mTOR induced by TGF-ß1 also been suppressed by Ang-(1-7) treatment in A549 cells. Interestingly, we found that TGF-ß1 strongly suppressed the expression of ACE2 in A549 cells through inhibiting SIRT1. In conclusion, our findings indicate that Ang-(1-7) directly inhibits TGF-ß1-induced EMT in alveolar epithelial cells via disruption of TGF-ß1-Smad signaling pathway, contributing to the protective effect against IPF.
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Células Epiteliales Alveolares/efectos de los fármacos , Angiotensina I/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Células A549 , Células Epiteliales Alveolares/metabolismo , Animales , Línea Celular Tumoral , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Proto-Oncogenes Mas , Transducción de Señal/efectos de los fármacosRESUMEN
In this work, a novel fluorescent assay was proposed for the ultrasensitive detection of microRNA-21 (miRNA-21) based on the efficient immobilization of protoporphyrin IX (PPIX) as signal indicators in massive G-quadruplex structures obtained by target recycling, three-dimensional DNA walker and a rolling circle amplification (RCA) coupled cascade nucleic acid amplification strategy.