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1.
Nano Lett ; 24(34): 10614-10623, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39046153

RESUMO

Because of the challenges posed by anatomical uncertainties and the low resolution of plain computed tomography (CT) scans, implementing adaptive radiotherapy (ART) for small hepatocellular carcinoma (sHCC) using artificial intelligence (AI) faces obstacles in tumor identification-alignment and automatic segmentation. The current study aims to improve sHCC imaging for ART using a gold nanoparticle (Au NP)-based CT contrast agent to enhance AI-driven automated image processing. The synthesized charged Au NPs demonstrated notable in vitro aggregation, low cytotoxicity, and minimal organ toxicity. Over time, an in situ sHCC mouse model was established for in vivo CT imaging at multiple time points. The enhanced CT images processed using 3D U-Net and 3D Trans U-Net AI models demonstrated high geometric and dosimetric accuracy. Therefore, charged Au NPs enable accurate and automatic sHCC segmentation in CT images using classical AI models, potentially addressing the technical challenges related to tumor identification, alignment, and automatic segmentation in CT-guided online ART.


Assuntos
Carcinoma Hepatocelular , Ouro , Neoplasias Hepáticas , Nanopartículas Metálicas , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X , Ouro/química , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Animais , Tomografia Computadorizada por Raios X/métodos , Nanopartículas Metálicas/química , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Camundongos , Radioterapia Guiada por Imagem/métodos , Humanos , Meios de Contraste/química , Inteligência Artificial , Linhagem Celular Tumoral
2.
Plant Dis ; 108(1): 162-174, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37552161

RESUMO

Mulberry zonate leaf spot disease (MZLSD) is an important fungal disease of mulberry trees, which seriously affects the productivity and quality of mulberry leaves. MZLSD has been widely reported in sericultural production areas in Guangxi, China, in recent years. In this study, the causal agent of MZLSD was isolated from symptomatic samples and identified as Gonatophragmium mori (Acrospermaceae) based on morphological characterization and molecular analyses using nucleotide sequences of the internal transcribed spacer (ITS) and large subunit ribosomal DNA (LSU rDNA). Pathogenicity tests confirmed that G. mori is the pathogen responsible for MZLSD. Furthermore, we isolated antagonistic endophytic bacteria (AEB) from healthy mulberry leaves. Plate confrontation experiments showed that the lipopeptide crude extracts (LPCE) of three endophytic bacteria can inhibit the growth of G. mori, and the diameter of the antibacterial circle reaches more than 60 mm when their concentration of LPCE is 200 mg/ml. Light microscopy and scanning electron microscopy revealed that LPCE caused drastic changes in mycelial morphology. Fluorescence microscopy and transmission electron microscopy showed that the LPCE-induced apoptosis-like cell death in G. mori hyphae. Finally, based on morphological and molecular features, we identified the three isolates as Bacillus subtilis DS07, B. subtilis DS32, and B. velezensis Q6, respectively. To our knowledge, this is the first time to identify G. mori by combining characterization and molecular analyses, and we provide timely information about the use of biocontrol agents for suppression of G. mori.


Assuntos
Morus , China , Antibacterianos , DNA Ribossômico , Frutas
3.
Proc Natl Acad Sci U S A ; 117(32): 19578-19589, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32727894

RESUMO

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single-cell RNA-sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we show TAM could exert these drastic effects mainly through dysregulating the Wnt-Dmrta2 signaling pathway. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of TAM on corticogenesis, suggesting that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.


Assuntos
Encéfalo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/patologia , Tamoxifeno/efeitos adversos , Animais , Encéfalo/embriologia , Encéfalo/patologia , Diferenciação Celular , Proliferação de Células , Giro Denteado/efeitos dos fármacos , Giro Denteado/patologia , Feminino , Ventrículos Laterais/efeitos dos fármacos , Ventrículos Laterais/patologia , Camundongos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
4.
Plant Dis ; 107(8): 2500-2505, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36691281

RESUMO

A Pantoea ananatis strain, named LCFJ-001 (GDMCC: 1.6101), was isolated for the first time from bacterial wilt-diseased roots of mulberry (Morus atropurpurea) in the western part of the Guangxi Zhuang Autonomous Region, China. Moreover, through Koch's postulates, it was proven that LCFJ-001 can cause mulberry wilt, which is one of the pathogens of mulberry bacterial wilt. Here, we report a complete, annotated genome sequence of P. ananatis LCFJ-001. The entire genome sequence of P. ananatis strain LCFJ-001 was a 4,499,350 bp circular chromosome with 53.50% GC content. In total, 3,521 genes were annotated, of which 3,418 were assigned protein-coding genes. In addition, 22 ribosomal RNAs and 81 transfer RNAs were identified. The presented resource will help explore the pathogenetic mechanisms of mulberry wilt disease caused by the genus Pantoea.


Assuntos
Morus , Pantoea , Genoma Bacteriano , Pantoea/genética , Morus/microbiologia , China
5.
World J Microbiol Biotechnol ; 39(6): 163, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37067654

RESUMO

Endophytes have a wide range of potential in maintaining plant health and sustainable agricultural environmental conditions. In this study, we analysed the diversity of endophytic bacteria in four mulberry cultivars with different resistance capacity against bacterial wilt using metagenomic sequencing and culture-dependent approaches. We further assessed the role of 11 shared genera in the control of bacterial wilt of mulberry. The results of the present study showed that Actinobacteria, Firmicutes, and Proteobacteria were the three dominant phyla in all communities, with the representative genera Acinetobacter and Pseudomonas. The diversity analysis showed that the communities of the highly and moderately resistant varieties were more diverse compared to those of the weakly resistant and susceptible varieties. The control tests of mulberry bacterial wilt showed that Pantoea, Atlantibacter, Stenotrophomonas, and Acinetobacter were effective, with a control rate of over 80%. Microbacterium and Kosakonia were moderately effective, with a control rate between 50 and 80%. At the same time, Escherichia, Lysinibacillus, Pseudomonas, and Rhizobium were found to be less effective, with a control rate of less than 40%. In conclusion, this study provides a reasonable experimental reference data for the control of bacterial wilt of mulberry.


Assuntos
Morus , Morus/microbiologia , Bactérias/genética , Proteobactérias , Firmicutes , Endófitos/genética
6.
Bioorg Med Chem Lett ; 72: 128844, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35697180

RESUMO

Oxidative stress and inflammation were considered to be the major mechanisms in liver damage caused by clofibrate (CF). In order to obtain lipid-lowering drugs with less liver damage, the structure of clofibrate was optimized by O-desmethyl anetholtrithione and got the target compound clofibrate-O-desmethyl anetholtrithione (CF-ATT). CF-ATT significantly reduced the levels of plasma triglycerides (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR-1339. In addition, CF-ATT has a significantly protective effect on the liver compared with CF. The liver weight and liver coefficient were reduced. The hepatic function indexes were also decreased, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Histopathological examination of the liver revealed that inflammatory cell infiltration, nuclear degeneration, cytoplasmic loosening and hepatocyte necrosis were ameliorated by administration with CF-ATT. The hepatoprotective mechanism showed that CF-ATT significantly up-regulated Nrf2 and HO-1 protein expression and down-regulated p-NF-κB P65 expression in the liver. CF-ATT has obviously antioxidant and anti-inflammatory activity. These findings suggested that CF-ATT has significant hypolipidemia activity and exact hepatoprotective effect possibly through the Nrf2/NF-κB-mediated signal pathway.


Assuntos
Anetol Tritiona , Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Anetol Tritiona/metabolismo , Anetol Tritiona/farmacologia , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Clofibrato/farmacologia , Fígado/metabolismo , Hepatopatias/patologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo
7.
Plant Cell Rep ; 41(4): 1131-1145, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35243542

RESUMO

KEY MESSAGE: The transcription of GhAG2 was strongly enhanced by glyphosate treatment. Overexpression of GhAG2 could improve plant tolerance to salt and salicylic acid stress. Although glyphosate has been widely used as an herbicide over the past decade owing to its high efficacy on weed controls and worldwide commercialization of glyphosate-resistant crops, little is known about the glyphosate-induced responses and transcriptional changes in cotton plants. Here, we report the identification of 26 differentially expressed genes after glyphosate treatment, among which, six highly up-regulated sequences share homology to cotton expressed sequence tags (ESTs) responsive to abiotic stresses. In addition, we cloned GhAG2, a gene whose transcription was strongly enhanced by glyphosate treatment and other abiotic stresses. Transgenic GhAG2 plants showed improved tolerance to salt, and salicylic acid (SA) stress. The results could open the door to exploring the function of the GhAG2 proteins, the glyphosate-induced transcriptional profiles, and the physiological biochemical responses in cotton and other crops. GhAG2 could also be used to improve salt stress tolerance through breeding and biotechnology in crops. Furthermore, these results could provide guidelines to develop a glyphosate-inducible system for controlled expression of targeted genes in plants.


Assuntos
Gossypium , Melhoramento Vegetal , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Glicina/análogos & derivados , Gossypium/genética , Gossypium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Estresse Salino/genética , Estresse Fisiológico/genética , Glifosato
8.
BMC Pregnancy Childbirth ; 22(1): 339, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440017

RESUMO

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Hiperglicemia , Hipoglicemia , Doenças do Recém-Nascido , Analgésicos , Bebidas , Carboidratos , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez
9.
Ecotoxicol Environ Saf ; 233: 113333, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35203006

RESUMO

Zinc (Zn) is an essential micronutrient for plants. However, excess Zn is toxic to non-accumulating plants like Arabidopsis thaliana. To cope with Zn toxicity, non-accumulating plants need to keep excess Zn in the less sensitive root tissues and restrict its translocation to the vulnerable shoot tissues, a process referred to as Zn immobilization in the root. However, the mechanism underlying Zn immobilization is not fully understood. In Arabidopsis, sequestration of excess Zn to the vacuole of root cells is crucial for Zn immobilization, facilitated by distinct tonoplast-localized transporters. As some members of the aquaporin superfamily have been implicated in transporting metal ions besides polar but non-charged small molecules, we tested whether Arabidopsis thaliana tonoplast intrinsic proteins (AtTIPs) could be involved in Zn immobilization and resistance. We found that AtTIP2;2 is involved in retaining excess Zn in the root, limiting its translocation to the shoot, and facilitating its accumulation in the leaf trichome. Furthermore, when expressed in yeast, the tonoplast-localized AtTIP2;2 renders glutathione (GSH)-dependent Zn resistance to yeast cells, suggesting that AtTIP2;2 facilitates the across-tonoplast transport of GSH-Zn complexes. Our findings provide new insights into aquaporins' roles in heavy metal resistance and detoxification in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Vacúolos/metabolismo , Zinco/metabolismo , Zinco/toxicidade
10.
Sensors (Basel) ; 22(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36501806

RESUMO

Landslide susceptibility mapping (LSM) is of great significance for the identification and prevention of geological hazards. LSM is based on convolutional neural networks (CNNs); CNNs use fixed convolutional kernels, focus more on local information and do not retain spatial information. This is a property of the CNN itself, resulting in low accuracy of LSM. Based on the above problems, we use Vision Transformer (ViT) and its derivative model Swin Transformer (Swin) to conduct LSM for the selected study area. Machine learning and a CNN model are used for comparison. Fourier transform amplitude, feature similarity and other indicators were used to compare and analyze the difference in the results. The results show that the Swin model has the best accuracy, F1-score and AUC. The results of LSM are combined with landslide points, faults and other data analysis; the ViT model results are the most consistent with the actual situation, showing the strongest generalization ability. In this paper, we believe that the advantages of ViT and its derived models in global feature extraction ensure that ViT is more accurate than CNN and machine learning in predicting landslide probability in the study area.


Assuntos
Fontes de Energia Elétrica , Redes Neurais de Computação , Aprendizado de Máquina , Algoritmos , Análise de Dados
11.
Sensors (Basel) ; 23(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36616685

RESUMO

Landslide susceptibility mapping (LSM) is an important decision basis for regional landslide hazard risk management, territorial spatial planning and landslide decision making. The current convolutional neural network (CNN)-based landslide susceptibility mapping models do not adequately take into account the spatial nature of texture features, and vision transformer (ViT)-based LSM models have high requirements for the amount of training data. In this study, we overcome the shortcomings of CNN and ViT by fusing these two deep learning models (bottleneck transformer network (BoTNet) and convolutional vision transformer network (ConViT)), and the fused model was used to predict the probability of landslide occurrence. First, we integrated historical landslide data and landslide evaluation factors and analysed whether there was covariance in the landslide evaluation factors. Then, the testing accuracy and generalisation ability of the CNN, ViT, BoTNet and ConViT models were compared and analysed. Finally, four landslide susceptibility mapping models were used to predict the probability of landslide occurrence in Pingwu County, Sichuan Province, China. Among them, BoTNet and ConViT had the highest accuracy, both at 87.78%, an improvement of 1.11% compared to a single model, while ConViT had the highest F1-socre at 87.64%, an improvement of 1.28% compared to a single model. The results indicate that the fusion model of CNN and ViT has better LSM performance than the single model. Meanwhile, the evaluation results of this study can be used as one of the basic tools for landslide hazard risk quantification and disaster prevention in Pingwu County.


Assuntos
Desastres , Deslizamentos de Terra , Sistemas de Informação Geográfica , Redes Neurais de Computação , Probabilidade
12.
Sensors (Basel) ; 22(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36236693

RESUMO

There is a critical need for detection of administrative regions through network map pictures in map censorship tasks, which can be implemented by target detection technology. However, on map images there tend to be numerous administrative regions overlaying map annotations and symbols, thus making it difficult to accurately detect each region. Using a RetinaNet-based target detection model integrating ResNet50 and a feature pyramid network (FPN), this study built a multi-target model and a single-target cascading model from three single-target models by taking Taiwan, Tibet, and the Chinese mainland as target examples. Two models were evaluated both in classification and localization accuracy to investigate their administrative region detection performance. The results show that the single-target cascading model was able to detect more administrative regions, with a higher f1_score of 0.86 and mAP of 0.85 compared to the multi-target model (0.56 and 0.52, respectively). Furthermore, location box size distribution from the single-target cascading model looks more similar to that of manually annotated box sizes, which signifies that the proposed cascading model is superior to the multi-target model. This study is promising in providing support for computer map reading and intelligent map censorship.


Assuntos
Inteligência , Taiwan
13.
Environ Monit Assess ; 194(10): 786, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103056

RESUMO

Wetlands in semiarid regions have important ecological functions and provide services that are partly dependent on the landscape pattern and structure; therefore, it is important to assess the heterogeneity of wetland landscape conditions for wetland conservation and management. Widespread wetland degradation resulting from main factors in semiarid regions highlights the need for exploring the heterogeneity of wetland landscapes and their relationships with anthropogenic disturbances and precipitation. Wetlands in our study referred to natural wetlands, including marshes, rivers, and lakes. We used overall landscape metrics to assess wetland landscape conditions and used grid landscape metrics at a scale of 30 km using a moving window method to explore the heterogeneity of wetland landscapes during the period (1986-2019) for western Jilin Province. We performed Spearman correlation analyses of the landscape metrics with the Hemeroby index (HI) and mean annual precipitation (MAP). We suggested that wetland landscape composition metrics (e.g., NP and PD) and configuration metrics (e.g., ED and AI) had positive correlations with HI by 2019 (p < 0.01); in addition, wetland landscape composition metrics (e.g., NP and PD) and configuration metrics (e.g., ED) were negatively correlated with MAP during 1986-2019. In conclusion, wetland landscapes have become increasingly fragmented over the past few decades (1986-2019) in western Jilin Province and the reasons for this result mainly include the household contract responsibility system, along with rural productivity, severe overgrazing and reclamation, and climate change. Wetland landscape composition was positively correlated with human interference and negatively correlated with mean annual precipitation.


Assuntos
Efeitos Antropogênicos , Áreas Alagadas , China , Monitoramento Ambiental/métodos , Rios
14.
Biol Reprod ; 104(2): 430-444, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33571374

RESUMO

Corpus luteum (CL) plays a critical role in mammalian reproductive physiology. Its dysfunction will lead to infertility or habitual abortion. In the current study, by use of melatonin specific membrane receptor 2 (MT2) knocking out (KO) mice model combined with RNA-Seq, immunohistochemistry, and immunofluorescence analyses, the genes of melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT) and MT2 were identified to strongly express in the CL of sows and mice. KO MT2 significantly impaired the reproductive performance in mice indicated by the reduced litter sizes. Melatonin treatment elevated the progesterone production in sows suggesting the improved CL function. Mechanistic analysis showed that melatonin upregulated a set of progesterone synthesis-related genes including cytochrome P450 family 11 subfamily A member 1 (Cyp11a1), aldo-keto reductase family 1, member C18 (Akr1c18), isopentenyl-diphosphate delta isomerase 1 (Idi1), and luteinizing hormone/choriogonadotropin receptor (Lhcgr). The upregulation of these genes directly related to the increased progesterone production. The regulatory effects of melatonin on these gene expressions were mediated by MT2 and MT2KO diminished the effects of melatonin in this respect. Thus, the presence of melatonergic system of AANAT, melatonin, and its receptor MT2 in CL is essential for reproductive success in mammals.


Assuntos
Arilalquilamina N-Acetiltransferase/metabolismo , Transtornos de Estresse por Calor/veterinária , Melatonina/metabolismo , Melatonina/farmacologia , Receptores de Melatonina/metabolismo , Ração Animal , Animais , Arilalquilamina N-Acetiltransferase/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Fertilidade , Regulação da Expressão Gênica/efeitos dos fármacos , Transtornos de Estresse por Calor/metabolismo , Células Lúteas/efeitos dos fármacos , Células Lúteas/metabolismo , Melatonina/administração & dosagem , Camundongos , Camundongos Knockout , Receptores de Melatonina/genética , Suínos
15.
Neurochem Res ; 46(7): 1844-1858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33891262

RESUMO

Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. Baicalin (BC), geniposide (GP), and their combination (BC/GP) have been shown to inhibit post-ischemic inflammatory injury by inhibiting the 5-LOX/CysLTs pathway. The aims of this study were to observe the inhibitory effects of BC/GP on the activation of microglial cells induced by oxygen glucose deprivation and reoxygenation (OGD/R) and to investigate whether the 5-LOX/LTB4 pathway was involved in these effects. Molecular docking showed that BC and GP exhibited considerable binding activity with LTB4 synthase LTA4H. BV-2 microglia were transfected with a 5-LOX overexpression lentiviral vector, and then OGD/R was performed. The effects of different concentrations of BC, GP, and BC/GP (6.25 µM, 12.5 µM, and 25 µM) on cell viability and apoptosis of microglia were evaluated by MTT and flow cytometry. The expression of TNF-α, IL-1ß, NF-κB, and pNF-κB also was measured by ELISA, Western blots and immunofluorescence. Western blots and qRT-PCR analysis were used to determine the levels of CD11b, CD206, and 5-LOX pathway proteins. Results showed that BC, GP, and BC/GP reduced the apoptosis caused by OGD/R in a dose-dependent manner, and cell viability was significantly increased at a concentration of 12.5 µM. OGD/R significantly increased the release of TNF-α, IL-1ß, NF-κB, pNF-κB, and CD11b. These effects were suppressed by BC, GP, and BC/GP, and the OGD/R-induced transfer of NF-κB p65 from the ctytoplasm to the nucleus was inhibited in microglia. Interestingly, the LTB4 inhibitor, U75302, exhibited the same effect. Also, BC, GP, and BC/GP significantly reduced the expression of 5-LOX pathway proteins. These results demonstrated that BC/GP inhibited OGD/R-induced polarization in BV2 microglia by regulating the 5-LOX/LTB4 signaling pathways and attenuating the inflammatory response. Our results supported the theoretical basis for additional in-depth study of the function of BC/GP and the value of determining its unique target, which might provide a new therapeutic strategy for ischemic cerebrovascular disease.


Assuntos
Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Iridoides/farmacologia , Microglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Epóxido Hidrolases/metabolismo , Flavonoides/metabolismo , Glucose/deficiência , Humanos , Inflamação/metabolismo , Iridoides/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Oxigênio/metabolismo , Ligação Proteica
16.
Bioorg Med Chem Lett ; 44: 128121, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015506

RESUMO

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Benzodioxóis/farmacologia , Ácido Clofíbrico/farmacologia , Hipolipemiantes/farmacologia , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antioxidantes/síntese química , Antioxidantes/química , Benzodioxóis/sangue , Benzodioxóis/química , Ácido Clofíbrico/sangue , Ácido Clofíbrico/química , Relação Dose-Resposta a Droga , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/síntese química , Hipolipemiantes/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/sangue , Fenóis/química , Polietilenoglicóis , Substâncias Protetoras/síntese química , Substâncias Protetoras/química , Relação Estrutura-Atividade
17.
Bioorg Med Chem Lett ; 43: 127898, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33684440

RESUMO

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.


Assuntos
Dioxóis/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Lipídeos/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Dioxóis/síntese química , Dioxóis/química , Relação Dose-Resposta a Droga , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/metabolismo , Hipolipemiantes/síntese química , Hipolipemiantes/química , Camundongos , Estrutura Molecular , Substâncias Protetoras/síntese química , Substâncias Protetoras/química , Relação Estrutura-Atividade
18.
Bioorg Chem ; 117: 105454, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34740054

RESUMO

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.


Assuntos
Benzodioxóis/farmacologia , Ácidos Fíbricos/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , PPAR alfa/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Benzodioxóis/administração & dosagem , Benzodioxóis/química , Relação Dose-Resposta a Droga , Ácidos Fíbricos/administração & dosagem , Ácidos Fíbricos/química , Hiperlipidemias/metabolismo , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Simulação de Acoplamento Molecular , Estrutura Molecular , PPAR alfa/metabolismo , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Relação Estrutura-Atividade
19.
Plant Dis ; 105(3): 688-690, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32840429

RESUMO

An Enterobacter roggenkampii strain, named KQ-01, was isolated for the first time from the diseased roots of the bacterial wilt-resistant mulberry (Morus atropurpurea) cultivar YS283 in the western part of Guangxi Zhuang Autonomous Region, China. E. roggenkampii KQ-01 was characterized by a single, circular chromosome of 4,667,006 bp in size, with a 56.16% GC content. In total, 4,396 genes were annotated, of which 4,281 were assigned as protein-coding genes. In addition, 25 ribosomal RNA, 84 transfer RNA, and 6 noncoding RNA genes as well as 34 pseudogenes were predicted. The resource herein presented will help to explore the pathogenetic mechanisms of mulberry wilt disease caused by genus Enterobacter.


Assuntos
Morus , China , Enterobacter/genética , Raízes de Plantas
20.
BMC Plant Biol ; 20(1): 122, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188405

RESUMO

BACKGROUND: In Arabidopsis, the aluminum (Al) exclusion mechanism is mainly facilitated by ALMT1-mediated malate exudation and MATE-mediated citrate releases from the root. Recently, we have demonstrated that coordinated functioning between an ALMT1-mediated Al exclusion mechanism, via exudation of malate from the root tip, and a NIP1;2-facilitated internal detoxification mechanism, via removal of Al from the root cell wall and subsequent root-to-shoot Al translocation, plays critical roles in achieving overall Al resistance. However, the genetic relationship between ALMT1 and NIP1;2 in these processes remained unclear. RESULTS: Through genetic and physiological analyses, we demonstrate that unlike ALMT1 and MATE, which function independently and additively, ALMT1 and NIP1;2 show an epistatic relationship in Al resistance. These results indicate that ALMT1 and NIP1;2 function in the same biochemical pathway, whereas ALMT1 and MATE in different ones. CONCLUSION: The establishment of the epistatic relationship and the coordinated functioning between the ALMT1 and NIP1;2-mediated exclusion and internal detoxification mechanisms are pivotal for achieving overall Al resistance in the non-accumulating Arabidopsis plant. We discuss and emphasize the indispensable roles of the root cell wall for the implementation of the Al exclusion mechanism and for the establishment of an epistatic relationship between the ALMT1-mediated exclusion mechanism and the NIP1;2-facilitated internal detoxification mechanism.


Assuntos
Alumínio/metabolismo , Aquaporinas/genética , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Epistasia Genética , Transportadores de Ânions Orgânicos/genética , Aquaporinas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Inativação Metabólica , Transportadores de Ânions Orgânicos/metabolismo
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