RESUMO
BACKGROUND: Pediatric emergence delirium is a psychomotor disorder occurring in the early postanesthetic stage. There is no clear consensus regarding its treatment; however, dexmedetomidine and propofol have both been shown to be effective. AIM: In this single-center, randomized, double-blind prospective study, we compared the efficacy of dexmedetomidine against that of propofol in the treatment of established emergence delirium in pediatric patients undergoing general anesthesia. METHODS: Patients aged 1-14 years, with ASA I or II and severe emergence delirium (Pediatric Anesthesia Emergence Delirium score of ≥15) during the postoperative period following general anesthesia, were randomized to receive intravenous bolus injection of 0.5 µg.kg-1 dexmedetomidine or 1 mg.kg-1 propofol. The primary outcome was the pediatric anesthesia emergence delirium (PAED) score after treatment, and the secondary outcome was the recovery time in the postanesthetic care unit. RESULTS: Of the 53 patients who participated in the study, 26 (49%) were treated with dexmedetomidine and 27 (51%) with propofol. In the dexmedetomidine group, a single-dose intervention was effective for all patients (100%); whereas in the propofol group, 19 patients (70.4%) had PAED score of <12 after the first dose (p = .004; relative risk [95% confidence interval] = 0.1422 [0.113-1.815]). No significant difference in recovery time (median [IQR (range)]) was observed between the dexmedetomidine (20[14-30(10-45)]) and propofol groups (25 [20-40 (10-50)]; p = .056; 95% confidence interval = 0.113-1.815). CONCLUSIONS: A single bolus of 0.5 µg.kg-1 of dexmedetomidine was more effective than a single bolus of 1 mg.kg-1 of propofol in treating emergence delirium during the early postanesthetic stage.
Assuntos
Dexmedetomidina , Delírio do Despertar , Propofol , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Criança , Dexmedetomidina/uso terapêutico , Método Duplo-Cego , Delírio do Despertar/tratamento farmacológico , Delírio do Despertar/etiologia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Propofol/uso terapêutico , Estudos ProspectivosRESUMO
Chronic postsurgical pain (CPSP) is a common complication after surgery; however, the underlying mechanisms of CPSP are poorly understood. As one of the most important inflammatory pathways, the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway plays an important role in chronic pain. However, the precise role of the TLR4/NF-κB signaling pathway in CPSP remains unclear. In the present study, we established a rat model of CPSP induced by skin/muscle incision and retraction (SMIR) and verified the effects and mechanisms of central and peripheral TLR4 and NF-κB on hyperalgesia in SMIR rats. The results showed that TLR4 expression was increased in both the spinal dorsal horn and dorsal root ganglia (DRGs) of SMIR rats. However, the TLR4 expression pattern in the spinal cord was different from that in DRGs. In the spinal cord, TLR4 was expressed in both neurons and microglia, whereas it was expressed in neurons but not in satellite glial cells in DRGs. Further results demonstrate that the central and peripheral TLR4/NF-κB signaling pathway is involved in the SMIR-induced CPSP by different mechanisms. In the peripheral nervous system, we revealed that the TLR4/NF-κB signaling pathway induced upregulation of voltage-gated sodium channel 1.7 (Nav1.7) in DRGs, triggering peripheral hyperalgesia in SMIR-induced CPSP. In the central nervous system, the TLR4/NF-κB signaling pathway participated in SMIR-induced CPSP by activating microglia in the spinal cord. Ultimately, our findings demonstrated that activation of the peripheral and central TLR4/NF-κB signaling pathway involved in the development of SMIR-induced CPSP.
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Dor Crônica/metabolismo , Microglia/metabolismo , Dor Pós-Operatória/metabolismo , Medula Espinal/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Antígeno CD11b/metabolismo , Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Masculino , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Regulação para CimaRESUMO
A common assumption in comparative genomics is that orthologous genes are functionally more similar than paralogous genes. However, the validity of this assumption needs to be assessed using robust experimental data. We conducted tissue-specific gene expression and protein function analyses of orthologous groups within the glutathione S-transferase (GST) gene family in three closely related Populus species: Populus trichocarpa, Populus euphratica and Populus yatungensis. This study identified 21 GST orthologous groups in the three Populus species. Although the sequences of the GST orthologous groups were highly conserved, the divergence in enzymatic functions was prevalent. Through site-directed mutagenesis of orthologous proteins, this study revealed that nonsynonymous substitutions at key amino acid sites played an important role in the divergence of enzymatic functions. In particular, a single amino acid mutation (Arg39âTrp39) contributed to P. euphratica PeGSTU30 possessing high enzymatic activity via increasing the hydrophobicity of the active cavity. This study provided experimental evidence showing that orthologues belonging to the gene family have functional divergences. The nonsynonymous substitutions at a few amino acid sites resulted in functional divergence of the orthologous genes. Our findings provide new insights into the evolution of orthologous genes in closely related species.
Assuntos
Glutationa Transferase/metabolismo , Populus/enzimologia , Substituição de Aminoácidos , Glutationa Transferase/química , Glutationa Transferase/genética , Modelos Moleculares , Família Multigênica , Mutagênese Sítio-Dirigida , Mutação , Especificidade de Órgãos , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Populus/genéticaRESUMO
Evolutionary mechanisms of substrate specificities of enzyme families remain poorly understood. Plant SABATH methyltransferases catalyze methylation of the carboxyl group of various low molecular weight metabolites. Investigation of the functional diversification of the SABATH family in plants could shed light on the evolution of substrate specificities in this enzyme family. Previous studies identified 28 SABATH genes from the Populus trichocarpa genome. In this study, we re-annotated the Populus SABATH gene family, and performed molecular evolution, gene expression and biochemical analyses of this large gene family. Twenty-eight Populus SABATH genes were divided into three classes with distinct divergences in their gene structure, expression responses to abiotic stressors and enzymatic properties of encoded proteins. Populus class I SABATH proteins converted IAA to methyl-IAA, class II SABATH proteins converted benzoic acid (BA) and salicylic acid (SA) to methyl-BA and methyl-SA, while class III SABATH proteins converted farnesoic acid (FA) to methyl-FA. For Populus class II SABATH proteins, both forward and reverse mutagenesis studies showed that a single amino acid switch between PtSABATH4 and PtSABATH24 resulted in substrate switch. Our findings provide new insights into the evolution of substrate specificities of enzyme families.
Assuntos
Aminoácidos/genética , Evolução Molecular , Metiltransferases/genética , Família Multigênica , Populus/enzimologia , Populus/genética , Sequência de Aminoácidos , Cromossomos de Plantas/genética , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Metiltransferases/química , Metiltransferases/metabolismo , Mutagênese Sítio-Dirigida , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Seleção Genética , Estresse Fisiológico/genética , Especificidade por SubstratoRESUMO
BACKGROUND: Persistent post-surgical pain is a difficult clinical problem. In this study, we intend to explore the mechanism underlying the persistent post-surgical pain in SMIR (skin/muscle incision and retraction) rats. METHODS: First of all, the expression of membrane protein Nav1.7 and p-p65 (Phosphorylation of p65) were detected in ipsilateral L4-6 DRGs of SMIR rats by western-blot and immunostaining. Then with ProTx-II (Nav1.7 blocker) or PDTC (p65 inhibitor) were intrathecally injected while the change of Nav1.7 expression and mechanical withdrawal threshold were detected. Finally chromatin immunoprecipitation assay method was used to detect whether could p-p65 bind in the Nav1.7 gene promoter region directly. RESULTS: The results shows that mechanical hyperalgesia occurs following SMIR model, from 5 day (d) and lasted more than 20d after surgery. Meanwhile, the expression of Nav1.7 was up-regulated at 10d, 15d and 20d after surgery compared with naïve group. The expression of p-p65 was up-regulated at 10d and 15d compared with incision group. The mechanical hyperalgesia induced by SMIR was reversed after blocking Nav1.7 or inhibiting p65. Furthermore, Nav1.7 expression was down-regulated when p-p65 was inhibited and p-p65 could combine with the Nav1.7 gene promoter region directly. CONCLUSION: Membrane protein Nav1.7 could participate in the peripheral sensitization of persistent post-surgical pain, which may be regulated by p-p65.
Assuntos
Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.7/biossíntese , Proteínas de Neoplasias/fisiologia , Proteínas de Transporte Nucleocitoplasmático/fisiologia , Dor Pós-Operatória/metabolismo , Ferida Cirúrgica/metabolismo , Animais , Gânglios Espinais/patologia , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Medição da Dor/tendências , Dor Pós-Operatória/patologia , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Ferida Cirúrgica/patologiaRESUMO
Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.
Assuntos
Genes Duplicados , Glutationa Transferase/genética , Glycine max/enzimologia , Glycine max/genética , Evolução Biológica , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genoma de Planta , Glutationa Transferase/metabolismo , Modelos Genéticos , Mutagênese Sítio-Dirigida , Filogenia , PoliploidiaRESUMO
Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants.
Assuntos
Bryopsida/genética , Citosol , Evolução Molecular , Glutationa Transferase/genética , Família Multigênica , Proteínas de Plantas/genética , Sequência de Aminoácidos , Bryopsida/enzimologia , Núcleo Celular/metabolismo , Citosol/metabolismo , Embriófitas/enzimologia , Embriófitas/genética , Duplicação Gênica , Variação Genética , Glutationa Transferase/classificação , Glutationa Transferase/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Isoenzimas/classificação , Isoenzimas/genética , Isoenzimas/metabolismo , Microscopia Confocal , Modelos Genéticos , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Especificidade por SubstratoRESUMO
Plant enzymes significantly contribute to the rapidly diversified metabolic repertoire since the colonization of land by plants. Carboxylesterase is just one of the ubiquitous, multifunctional and ancient enzymes that has particularly diversified during plant evolution. This study provided a status on the carboxylesterase landscape within Viridiplantae. A total of 784 carboxylesterases were identified from the genome of 31 plant species representing nine major lineages of sequenced Viridiplantae and divided into five clades based on phylogenetic analysis. Clade I carboxylesterase genes may be of bacterial origin and then expanded and diversified during plant evolution. Clade II was first gained in the ancestor of bryophytes after colonization of land by plants, Clade III and Clade IV in ferns which were considered the most advanced seedless vascular plants, while Clade V was gained in seed plants. To date, the functions of carboxylesterase genes in woody plants remain unclear. In this study, 51 carboxylesterase genes were identified from the genome of Populus trichocarpa and further divided into eight classes. Tandem and segmental duplication events both contributed to the expansion of carboxylesterase genes in Populus. Although carboxylesterase genes were proven to enhance resistance to pathogens in many herbaceous species, relevant researches on forest trees are still needed. In this study, pathogen incubation assays showed that overexpressing of six Class VI carboxylesterases in Populus tomentosa, to a greater or lesser degree, reduced colonization of detached leaves by fungus Cytospora chrysosperma. A significant difference was also found in functional divergence patterns for genes derived from different gene duplication events. Functional differentiation of duplicated carboxylesterase genes in Populus was proved for the first time by in vivo physiological analysis. The identification of the potentially anti-fungal PtoCXE06 gene also laid a theoretical foundation for promoting the genetic improvement of disease-resistance traits in forest trees.
Assuntos
Plantas Geneticamente Modificadas , Populus , Populus/genética , Populus/microbiologia , Plantas Geneticamente Modificadas/genética , Filogenia , Evolução Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Família Multigênica , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismoRESUMO
The SABATH methyltransferases catalyze methylation of small-molecule metabolites, which participate in plant growth, development and defense response. Given lack of genome-wide studies on gymnosperms SABATH family, the formation and functional differentiation mechanism of the Larix kaempferi SABATH gene family was systematically and exhaustively explored by analyzing gene sequence characteristics, phylogenetic relationship, expression pattern, and enzyme activities. Phylogenetic analysis showed that 247 SABATH genes from 14 land plants were divided into 4 clades, and lineage-specific gene duplication events were important factors that contributed to the evolution of the SABATH gene family in gymnosperms and angiosperms. Substrate specificity analysis of 18 Larix SABATH proteins showed that LaSABATHs could catalyze O-methylation of indole-3-acetic acid (IAA) and farnesic acid (FA), N-methylation of theobromine, and S-methylation of thiobenzoic acid. Furthermore, only LaSABATH2 and LaSABATH29 could catalyze O-methylation of FA, and only LaSABATH30 could catalyze O-methylation of IAA. Homology modeling and molecular docking studies showed the hydrogen bond formed between the His188 of LaSABATH30 and IAA and the noticeable hydrophobic IAA-binding pocket may be helpful for IAA methylation. In this study, identification of proteins with significant specific catalytic activity toward FA and IAA provided high-quality candidate genes for forest genetics and breeding.
Assuntos
Larix , Filogenia , Larix/genética , Simulação de Acoplamento Molecular , Melhoramento Vegetal , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Abies ferreana Bordères & Gaussen 1947 is endemic to China, where it is distributed at 3300-4000 meters in the mountains of Southwest Sichuan and Northwest Yunnan. In this study, the complete chloroplast genome of A. ferreana was reconstructed by de novo assembly using whole-genome sequencing data. The complete chloroplast genome of A. ferreana was 120,049 bp in length with a GC content of 37.9%. A total of 113 genes were identified, including 4 rRNA genes, 35 tRNA genes, and 74 protein-coding genes. Among these, 14 genes contain introns. In the phylogenetic tree with 12 other species of Abies, A. ferreana and Abies fanjingshanensis W. L. Huang et al. 1984 were grouped into the same branch, with a bootstrap value of 100%. The complete chloroplast genome of A. ferreana provides potential genetic resources for further Abies evolutionary and genomic studies.
RESUMO
Upconversion nanoparticles (UCNPs) and MnO2 composite materials have broad prospects in biological applications due to their near-infrared (NIR) imaging capability and tumor microenvironment-responsive features. Nevertheless, the synthesis of such composite nanoplatforms still faces many hurdles such as redundant processing and uneven coatings. Here, we explored a simple, rapid, and universal method for precisely controlled coating of mesoporous MnO2 (mMnO2) using poly(ethylene imine) as a reducing agent and potassium permanganate as a manganese source. Using this strategy, a mMnO2 shell was successfully coated on UCNPs. We further modified the mMnO2-coated UCNPs (UCNP@mMnO2) with a photosensitizer (Ce6), cisplatin drug (DSP), and tumor targeting pentapeptide (TFA) to obtain a nanoplatform UCNP/Ce6@mMnO2/DSP-TFA for treating spinal metastasis of nonsmall cell lung cancer (NSCLC-SM). The utilization of both upconversion and downconversion luminescence of UCNPs with different NIR wavelengths can avoid the simultaneous initiation of NIR-II in vivo imaging and tumor photodynamic therapy, thus reducing damage to normal tissues. This platform achieved a high synergistic effect of photodynamic therapy and chemotherapy. This leads to beneficial antitumor effects on the therapy of NSCLC-SM.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Neoplasias da Coluna Vertebral , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Raios Infravermelhos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Manganês/farmacologia , Óxidos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Coluna Vertebral/tratamento farmacológico , Microambiente TumoralRESUMO
Surface ozone pollution has attracted extensive attention with the decreasing of haze pollution, especially in China. However, it is still difficult to efficiently control the pollution in time despite numbers of reports on mechanism of ozone pollution. Here we report a method for implementing effective control of ozone pollution through power big data. Combining the observation of surface ozone, NO2, meteorological parameters together with hourly electricity consumption data from volatile organic compounds (VOCs) emitting companies, a generalized additive model (GAM) is established for quantifying the influencing factors on the temporal and spatial distribution of surface ozone pollution from 2020 to 2021 in Anhui province, central China. The average R2 value for the modelling results of 16 cities is 0.82, indicating that the GAM model effectively captures the characteristics of ozone. The model quantifies the contribution of input variables to ozone, with both NO2 and industrial VOCs being the main contributors to ozone, contributing 33.72% and 21.12% to ozone formation respectively. Further analysis suggested the negative correlation between ozone and NO2, revealing VOCs primarily control the increase in ozone. Under scenarios controlling for a 10% and 20% reduction in electricity use in VOC-electricity sensitive industries that can be identified by power big data, ozone concentrations decreased by 9.7% and 19.1% during the pollution period. This study suggests a huge potential for controlling ozone pollution through power big data and offers specific control pathways. Supplementary Information: The online version contains supplementary material available at 10.1007/s42452-022-05045-5.
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Chitinases, the chitin-degrading enzymes, have been shown to play important role in defense against the chitin-containing fungal pathogens. In this study, we identified 48 chitinase-coding genes from the woody model plant Populus trichocarpa. Based on phylogenetic analysis, the Populus chitinases were classified into seven groups. Different gene structures and protein domain architectures were found among the seven Populus chitinase groups. Selection pressure analysis indicated that all the seven groups are under purifying selection. Phylogenetic analysis combined with chromosome location analysis showed that Populus chitinase gene family mainly expanded through tandem duplication. The Populus chitinase gene family underwent marked expression divergence and is inducibly expressed in response to treatments, such as chitosan, chitin, salicylic acid and methyl jasmonate. Protein enzymatic activity analysis showed that Populus chitinases had activity towards both chitin and chitosan. By integrating sequence characteristic, phylogenetic, selection pressure, gene expression and protein activity analysis, this study shed light on the evolution and function of chitinase family in poplar.
Assuntos
Quitinases/genética , Quitinases/metabolismo , Mapeamento Cromossômico/métodos , Populus/enzimologia , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Folhas de Planta/enzimologia , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Caules de Planta/enzimologia , Caules de Planta/genética , Populus/genética , Seleção GenéticaRESUMO
Mercury is widely used in industry and has caused global environmental pollution. Inorganic mercury accumulates in the body causes damage to many organs, and the kidney is the most susceptible to the toxic effects of mercury. However, the underlying specific molecular mechanism of renal injury induced by inorganic mercury remains unclear at the cellular level. Therefore, in order to understand its molecular mechanism, we used in vitro method. We established experimental models by treating human embryonic kidney epithelial cell line (HEK-293 T) cells with HgCl2 (0, 1.25, 5, and 20 µmol/L). We found that HgCl2 can lead to a decrease in cell viability and oxidative stress of HEK-293 T, which may be mediated by upregulation mitochondrial fission. In addition, HgCl2 exposure resulted in the mitochondrial disorder of HEK-293 T cells, which was mediated by downregulating the expression of silent information regulator two ortholog 1 (Sirt1)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) signaling pathway. In summary, our results suggest that HgCl2 induces HEK-293 T cell toxicity through promoting Sirt1/PGC-1α axis-mediated mitochondrial dynamics disorder and oxidative stress. Sirt1/PGC-1α may be an appealing pharmaceutical target curing HgCl2-induced kidney injury.
Assuntos
Mercúrio , Doenças Mitocondriais , Células Epiteliais/metabolismo , Células HEK293 , Humanos , Rim/metabolismo , Mercúrio/metabolismo , Doenças Mitocondriais/metabolismo , Dinâmica Mitocondrial , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismoRESUMO
Because of the low tissue penetration depth and poor photostability of organic cyanine dye, in addition to environmental interference, it is a great challenge to monitor the degree of drug-induced hepatotoxicity by the in vivo detection of peroxynitrite (ONOO-). Herein, we fabricated heptamethine cyanine dye (P-cy7)-coordinated upconversion nanoparticles (UCNPs), namely UCY7, as a fluorescent nanoprobe for evaluating drug-induced hepatotoxicity. Due to the luminescence resonance energy transfer (LRET) between UCNPs and the cyanine dye (P-cy7), the irradiation changed from visible light at 660 nm to near infrared (NIR) light at 980 nm; therefore, the issues of poor photostability and severe photobleaching of cyanine dye can be effectively solved. After injecting via the tail vein, the nanoprobes are rapidly concentrated in the liver. Since the level of ONOO- is up-regulated during the drug-induced liver injury, the LRET between UCNPs and P-cy7 is disrupted to release the upconversion luminescence at 656 nm, while the upconversion luminescence at 800 nm remains constant, thus achieving the ratio-fluorescent imaging (RFLI) of ONOO- in the liver to calibrate the influence of the environment. In addition, the reduction in the absorption of nanoprobes in the presence of ONOO- allows for sensitive photoacoustic imaging (PAI). Based on the RFLI and PAI of the liver, the real-time monitoring and accurate diagnosis of different degrees of hepatotoxicity using the model of Acetaminophen (APAP) induction was achieved successfully, providing a new approach for the clinical evaluation of drug-induced hepatotoxicity.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Corantes Fluorescentes/química , Ácido Peroxinitroso/metabolismo , Técnicas Fotoacústicas/métodos , Acetaminofen/toxicidade , Animais , Carbocianinas/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Transferência Ressonante de Energia de Fluorescência , Raios Infravermelhos , Fígado/química , Fígado/metabolismo , Fígado/patologia , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Ácido Peroxinitroso/química , Regulação para CimaRESUMO
Manganese dioxide (MnO2) nanostructures have aroused great interest among analytical and biological medicine researchers as a unique type of tumor microenvironment (TME)-responsive nanomaterial. However, reliable approaches for synthesizing yolk-shell nanostructures (YSNs) with mesoporous MnO2 shell still remain exciting challenges. Herein, a YSN (size, â¼75 nm) containing a mesoporous MnO2 shell and Er3+-doped upconversion/downconversion nanoparticle (UCNP) core with a large cavity is demonstrated for the first time. This nanostructure not only integrates diverse functional components including MnO2, UCNPs, and YSNs into one system but also endows a size-controllable hollow cavity and thickness-tunable MnO2 layers, which can load various guest molecules like photosensitizers, methylene blue (MB), and the anticancer drugs doxorubicin (DOX). NIR-II fluorescence and photoacoustic (PA) imaging from UCNP and MB, respectively, can monitor the enrichment of the nanomaterials in the tumors for guiding chemo-photodynamic therapy (PDT) in vivo. In the TME, degradation of the mMnO2 shell by H2O2 and GSH not only generates Mn2+ for tumor-specific T1-MR imaging but also releases O2 and drugs for tumor-specific treatment. The result confirmed that imaging-guided enhanced chemo-PDT combination therapy that benefited from the unique structural features of YSNs could substantially improve the therapeutic effectiveness toward malignant tumors compared to monotherapy.
Assuntos
Portadores de Fármacos/química , Compostos de Manganês/química , Nanoestruturas/química , Óxidos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Células HeLa , Humanos , Raios Infravermelhos , Azul de Metileno/química , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Transplante HeterólogoRESUMO
The BABY BOOM2 gene, designated LkBBM2, and its promoter were isolated from hybrid larch (Larix kaempferiâ¯×â¯L. olgensis). The open reading frame of LkBBM2 was 2574â¯bp, encoding 857 amino acids. The LkBBM2 protein contains two AP2 DNA binding domains and a BBM specific motif, but lacks the euANT5 motif common to AP2 family members. The LkBBM2 promoter contains several hormone response and root-specific expression elements. LkBBM2 expression was significantly higher in larch adventitious roots (ARs) than in stems, leaves or stem tips, and increased after auxin treatment. The fused protein LkBBM2-GFP was localized in both the nucleus and cytoplasm whereas LkBBM1-GFP was only localized in the nucleus. Over-expression of LkBBM2 and LkBBM1 in Arabidopsis significantly elongated the roots. Furthermore, over-expression those two genes in the hybrid poplar (Populus albaâ¯×â¯P. glandulosa) significantly increased ARs number. We speculated that these two genes regulate AR development.
Assuntos
Núcleo Celular/metabolismo , Larix/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Clonagem Molecular , Citoplasma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Larix/genética , Larix/metabolismo , Fases de Leitura Aberta , Organogênese Vegetal , Filogenia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Populus/genética , Regiões Promotoras Genéticas , Proteínas Recombinantes/metabolismoRESUMO
Superoxide dismutase is a key enzyme that scavenges superoxide anion and plays vital roles in plant antioxidant system. This study identified six SOD genes from the deciduous conifer Larix kaempferi, which is widely distributed across the cooler regions of the northern hemisphere. These six SOD genes were classified into three types: Cu/Zn-SOD (LkSOD1, 2, 3 and 4), Fe-SOD (LkSOD5) and Mn-SODs (LkSOD6). Three Cu/Zn-SOD proteins (LkSOD1, 3 and 4) were cytosolic-localized, while the other three proteins (LkSOD2, 5 and 6) were chloroplast-localized. Larix SOD proteins displayed catalytic activities toward superoxide anion, and retained >55% of its maximum enzymatic activity between 10⯰C and 40⯰C. Over expressions of three Larix SOD genes (LkSOD2, 4 and 6) in Arabidopsis thaliana, respectively, showed increased germination rates and root lengths during salt stress. LkSOD5 gene could rescue pale green and dwarf phenotype of Arabidopsis atfsd2-2 mutant. Taken together, this study provided comprehensive insight into the gymnosperm SOD gene family.
Assuntos
Estudo de Associação Genômica Ampla , Larix , Proteínas de Plantas , Superóxido Dismutase , Arabidopsis/enzimologia , Arabidopsis/genética , Larix/enzimologia , Larix/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genética , Superóxidos/metabolismoRESUMO
Glutathione S-transferases are ubiquitous enzyme in plants, playing vital roles in several physiological and developmental processes. In this study we identified 73 GST genes from the genome of Medicago truncatula. The Medicago GSTs were divided to eight classes with tau and phi being the most numerous. Six clusters were found on four Medicago chromosomes. The local gene duplication mainly contributed to the expansion of this large gene family. Functional divergence was found in their gene structures, gene expression patterns, and enzyme properties. A genomic comparative analysis revealed lineage-specific loss/gain events between Medicago and Glycine. This study offered new insights into the evolution of gene family between closely related species.
Assuntos
Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Glutationa Transferase , Medicago , Família Multigênica/fisiologia , Proteínas de Plantas , Estudo de Associação Genômica Ampla , Glutationa Transferase/biossíntese , Glutationa Transferase/genética , Medicago/enzimologia , Medicago/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genéticaRESUMO
The complete chloroplast genome of Populus wilsonii was reconstructed by reference-based assembly using whole-genome sequencing data. The total chloroplast genome size of P. wilsonii was 158,080 bp in length, including a pair of inverted repeat regions (IRs) of 27,749 bp each, a large single-copy region (LSC) of 85,949 bp and a small single-copy region (SSC) of 16,633 bp. A total of 133 genes were predicted from the chloroplast genome, including 86 protein-coding genes, 39 tRNA genes and eight rRNA genes. Among these genes, 20 genes occurred in IRs, containing nine protein-coding genes, seven tRNA genes and four rRNA genes. The GC content of P. wilsonii chloroplast genome was 36.6%. The phylogenetic analysis with 15 other species showed that P. wilsonii was closely clustered with Populus cathayana. The complete chloroplast genome of P. wilsonii provides new insights into Populus evolutionary and genomic studies.