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1.
Eur J Med Res ; 29(1): 13, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173030

RESUMO

BACKGROUND: The WD40 repeat (WDR) domain provides scaffolds for numerous protein-protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported. METHODS: Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results. RESULTS: The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1). CONCLUSIONS: This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.


Assuntos
Glioma , Repetições WD40 , Humanos , Imunoterapia , Ciclo Celular , Perfilação da Expressão Gênica , Glioma/genética , Glioma/terapia , Prognóstico , Proteínas de Ligação a DNA , Proteínas de Ciclo Celular
2.
Materials (Basel) ; 16(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38005034

RESUMO

To assess the freeze-thaw (F-T) durability of coal gangue pervious concrete (CGPC) in different F-T cycle media (water, 3.5 wt% NaCl solution), experimental studies on 36 groups of cube specimens and 6 groups of prismatic specimens were carried out, with designed porosity, F-T cycling media, and F-T failure times as variables. The changes in apparent morphology, mass, compressive behavior, relative dynamic elastic modulus, and permeability coefficient have been analyzed in detail. To predict the compressive strength after F-T cycles, a GM (1,1) model based on the grey system theory was developed and further improved into a more accurate grey residual-Markov model. The results reported that the cement slurry and coal gangue aggregates (CGAs) on the specimen surface continued to fall off as F-T cycles increased, and, finally, the weak point was fractured. Meanwhile, the decrease in compressive behavior and relative dynamic elastic modulus was gentle in the early phase of F-T cycles, and they gradually became faster in the later stage, showing a parabolic downward trend. The permeability coefficient increased gradually. When F-T failure occurred, specimen mass dropped precipitously. The F-T failure of CGPC was more likely to occur in 3.5 wt% NaCl solution, and the F-T failure times of samples were 25 times earlier than that of water. This study lays the foundation for an engineering application and provides a basis for the large-scale utilization of CGPC.

3.
Heliyon ; 9(7): e18185, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37519705

RESUMO

ZNF480 has not yet attracted attention in the study of malignant tumors. Therefore, this study attempts to explain the significance of ZNF480 in the pathological process of lower-grade gliomas (LGG) based on large-scale samples from public database sources and in vitro experiments. Reverse transcription quantitative real-time polymerase chain reaction and immunohistochemistry confirmed that ZNF480 was highly expressed at both the mRNA and protein levels in LGG. Prognostic correlation analysis confirmed that the high expression of ZNF480, as an independent pathogenic gene, significantly correlates with poor survival in patients. Furthermore, the expression level of ZNF480 was significantly inhibited in SHG-44 cells treated with ademetionine disulfate tosylate. Gene set enrichment analysis showed that ZNF480 exists in multiple tumor-related signaling pathways, including the Notch signaling pathway. Immunological correlation analysis showed that ZNF480 can promote the LGG microenvironment to a high immune state and significantly enhance the infiltration of various immune cells, such as M2 macrophages. Finally, Spearman analysis showed a positive correlation of ZNF480 with many immune checkpoints, such as PD-L1. Overall, this study reveals for the first time the adverse effects of ZNF480 on the prognosis of tumor patients, which expands our understanding of the molecular mechanisms behind the regulation of ZNF480. We believe that the high expression of ZNF480 in LGG may be valuable for molecular targeted therapy or combined immunotherapy.

4.
Front Oncol ; 13: 1007198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284202

RESUMO

Nuclear pore complex (NPC) is a major transport pivot for nucleocytoplasmic molecule exchange. Nucleoporin 205 (NUP205)-a main component of NPC-plays a key regulatory role in tumor cell proliferation; however, few reports document its effect on the pathological progression of lower-grade glioma (LGG). Therefore, we conducted an integrated analysis using 906 samples from multiple public databases to explore the effects of NUP205 on the prognosis, clinicopathological characteristics, regulatory mechanism, and tumor immune microenvironment (TIME) formation in LGG. First, multiple methods consistently showed that the mRNA and protein expression levels of NUP205 were higher in LGG tumor tissue than in normal brain tissue. This increased expression was mainly noted in the higher WHO Grade, IDH-wild type, and 1p19q non-codeleted type. Second, various survival analysis methods showed that the highly expressed NUP205 was an independent risk indicator that led to reduced survival time of patients with LGG. Third, GSEA analysis showed that NUP205 regulated the pathological progress of LGG via the cell cycle, notch signaling pathway, and aminoacyl-tRNA biosynthesis. Ultimately, immune correlation analysis suggested that high NUP205 expression was positively correlated with the infiltration of multiple immune cells, particularly M2 macrophages, and was positively correlated with eight immune checkpoints, particularly PD-L1. Collectively, this study documented the pathogenicity of NUP205 in LGG for the first time, expanding our understanding of its molecular function. Furthermore, this study highlighted the potential value of NUP205 as a target of anti-LGG immunotherapy.

5.
Int J Biochem Cell Biol ; 158: 106409, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36997057

RESUMO

Extracellular matrix protein 2 (ECM2), which regulates cell proliferation and differentiation, has recently been reported as a prognostic indicator for multiple cancers, but its value in lower grade glioma (LGG) remains unknown. In this study, LGG transcriptomic data of 503 cases in The Cancer Genome Atlas (TCGA) database and 403 cases in The Chinese Glioma Genome Atlas (CGGA) database were collected to analyze ECM2 expression patterns and the relationship with clinical characteristics, prognosis, enriched signaling pathways, and immune-related markers. In addition, a total of 12 laboratory samples were used for experimental validation. Wilcoxon or Kruskal-Wallis tests demonstrated highly expressed ECM2 in LGG was positively associated with malignant histological features and molecular features such as recurrent LGG and isocitrate dehydrogenase (IDH) wild-type. Also, Kaplan-Meier (KM) curves proved high ECM2 expression could predict shorter overall survival in LGG patients, as multivariate analysis and meta-analysis claimed ECM2 was a deleterious factor for LGG prognosis. In addition, the enrichment of immune-related pathways for ECM2, for instance JAK-STAT pathway, was obtained by Gene Set Enrichment Analysis (GSEA) analysis. Furthermore, positive relationships between ECM2 expression with immune cells infiltration and cancer-associated fibroblasts (CAFs), iconic markers (CD163), and immune checkpoints (CD274, encoding PD-L1) were proved by Pearson correlation analysis. Finally, laboratory experiments of RT-qPCR and immunohistochemistry showed high expression of ECM2, as well as CD163 and PD-L1 in LGG samples. This study identifies ECM2, for the first time, as a subtype marker and prognostic indicator for LGG. ECM2 could also provide a reliable guarantee for further personalized therapy, synergizing with tumor immunity, to break through the current limitations and thus reinvigorating immunotherapy for LGG. AVAILABILITY OF DATA AND MATERIALS: Raw data from all public databases involved in this study are stored in the online repository (chengMD2022/ECM2 (github.com)).


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Antígeno B7-H1 , Janus Quinases , Prognóstico , Fatores de Transcrição STAT , Transdução de Sinais , Glioma/genética , Glioma/terapia , Imunoterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia
6.
J Hazard Mater ; 443(Pt A): 130155, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36257108

RESUMO

The ferrite process has been developed to purify wastewater containing heavy metal ions and recycle valuable metals by forming chromium ferrite. However, organic matter has an important influence on the crystallization behavior and stability of chromite synthesized from chromium-containing wastewater. We focused on the influence and effect mechanism of two typical organic acid salts (citrate (CA) and tartrate (TA)) on the process of chromium mineralization. It was found that the presence of organic matter leads to the increase of the residual content of Cr in CA system (0.50 mmol/L) and TA system (0.61 mmol/L) in the solution, and the removal of chromium was mainly due to the surface adsorption of Fe(III) hydrolysate. The decreased crystallinity of mineralized products is ascribed to the completion of organic compounds with Fe(II) and Fe(III), which hinders the formation of ferrite precursors. There was bidentate and monodentate chelation between -COO- and metal ions in the CA system and TA system respectively, which resulted in a stronger affinity between CA and iron. This study provides the underlying mechanism for Cr(III) solid oxidation by the ferrite method in an organic matter environment and is of great significance to prevent and control chromium pollution in the environment.


Assuntos
Compostos Férricos , Tartaratos , Compostos Férricos/química , Águas Residuárias , Cristalização , Ácido Cítrico , Cromo/química , Metais , Compostos Orgânicos , Íons
7.
Cell Mol Neurobiol ; 43(1): 409-422, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35106666

RESUMO

Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metilação , Prognóstico , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Microambiente Tumoral , Endodesoxirribonucleases/metabolismo
8.
J Mol Neurosci ; 72(10): 2136-2149, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36040678

RESUMO

An increasing number of evidences have shown that the carcinogenic effect of DRAXIN plays an important role in the malignant process of tumors, but the mechanism of its involvement in glioma has not yet been revealed. The main aim of this study is to explore the relationship between DRAXIN and the prognosis and pathogenesis of glioma through a large quality of data analysis. Firstly, thousands of tissue samples with clinical information were collected based on various public databases. Then, a series of bioinformatics analyses were performed to mine data from information of glioma samples extracted from several reputable databases to reveal the key role of DRAXIN in glioma development and progression, with the confirmation of basic experiments. Our results showed that high expression of the oncogene DRAXIN in tumor tissue and cells could be used as an independent risk factor for poor prognosis in glioma patients and was strongly associated with clinical risk features. The reverse transcription-quantitative PCR technique was then utilized to validate the DRAXIN expression results we obtained. In addition, co-expression analysis identified, respectively, top 10 genes that were closely associated with DRAXIN positively or negatively. Finally, in vitro experiments demonstrated that knockdown of DRAXIN significantly inhibited proliferation and invasion of glioma cell. To sum up, this is the first report of DRAXIN being highly expressed in gliomas and leading to poor prognosis of glioma patients. DRAXIN may not only benefit to explore the pathogenesis of gliomas, but also serve as a novel biological target for the treatment of glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo
9.
Curr Res Transl Med ; 70(4): 103345, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35487167

RESUMO

BACKGROUND: The oncogene CLSPN, also known as claspin, has regulatory effects in a variety of tumours; however, it is not clear whether CLSPN is a therapeutic target in low-grade gliomas (LGG). In this study, the prognostic value of CLSPN in LGG and its role as an immunotherapeutic target were evaluated. METHODS: Transcriptome and methylation data for thousands of patients with glioma were collected from various databases, including The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gene Expression Omnibus. Subsequently, a series of bioinformatics methods were used to evaluate the relationships between CLSPN and prognosis, clinical features, methylation status, immune cells, and molecular signaling pathways in LGG. RESULTS: CLSPN expression levels were positively correlated with major malignant characteristics of LGG, and low expression of CLSPN was associated with a better prognosis. The methylation sites cg04263115 and cg06100291 negatively regulated the expression of CLSPN, and increased methylation levels at these sites were related to a longer survival time in patients with LGG. CLSPN was positively correlated with tumour-infiltrating immune cells and showed high copy number variation in these cells. There was a positive regulatory relationship between CLSPN expression and programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1). A gene set enrichment analysis revealed that CLSPN activates a variety of cancer signaling pathways. CONCLUSION: CLSPN was identified as an independent risk factor for LGG with excellent prognostic value.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Encefálicas , Glioma , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Variações do Número de Cópias de DNA , Glioma/diagnóstico , Glioma/genética , Gradação de Tumores , Prognóstico
10.
Int Immunopharmacol ; 104: 108399, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35008004

RESUMO

The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) has an important regulatory effect on cell proliferation and division, which is closely related to the malignant process of glioma cells. Therefore, this study attempts to provide a target for biologically targeted therapy for low-grade glioma (LGG) by demonstrating the regulatory effect of ESCO2 during the pathological process of LGG. First, the 1064 samples of LGG transcriptomic data and corresponding clinicopathological information obtained from various databases were included in the study. Second, the chi-squared test showed that the expression of ESCO2 was associated with the malignant characteristics of LGG (recurrence and grade), and Kaplan Meier and multivariate analysis suggested that ESCO2 was an independent risk factor, resulting in a significant reduction in the overall duration of survival of patients. Third, co-expression analysis showed that the level of mRNA expression of ESCO2 was negatively regulated by multiple methylation sites (cg04108328, cg12564175, and cg26534677), and the hypermethylation status of cg12564175 could prolong the overall survival of patients. Fourth, the Tumor Immune Estimation Resource (TIMER) database shows that ESCO2 can have a positive regulatory relationship with six different immune cells, such as CD8 + T cells and macrophages, and a positive expression relationship with PD-1 and PD-L1. Finally, Gene Set Enrichment Analysis (GSEA) showed that ESCO2 may play a carcinogenic role by affecting cell replication and DNA repair. In summary, this study confirmed the carcinogenic effect of ESCO2 on LGG for the first time. It is speculated that both the mRNA of ESCO2 and its methylation site (cg12564175) can be useful biological targets for molecular targeted therapy of LGG.


Assuntos
Acetiltransferases/genética , Neoplasias Encefálicas/genética , Proteínas Cromossômicas não Histona/genética , Glioma/genética , Adulto , Antígeno B7-H1/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Metilação de DNA , Células Dendríticas/imunologia , Glioma/imunologia , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucócitos/imunologia , Macrófagos/imunologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Microambiente Tumoral/imunologia
11.
ISA Trans ; 122: 472-485, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34023153

RESUMO

This paper addresses the tracking control problem for the uncertain steer-by-wire (SbW) system with the controller area network (CAN) communication and unavailable variables. First, an adaptive interval type-2 fuzzy logic system (IT2 FLS) and sliding mode observer are constructed to estimate the uncertain nonlinearity and unavailable variables of SbW control systems. Further, an event-triggered sliding mode control (ET-SMC) is presented to achieve the transient steering performance of SbW systems while saving CAN communication resources. Much importantly, the dynamic gain and nested technologies are incorporated in this scheme to deal with estimation error and the chattering phenomenon of the sliding mode control system. It is shown that the practical fixed-time stability of the closed-loop system can be guaranteed without the initial condition of tracking errors. Finally, simulations and vehicle experiments are presented to verify the designed scheme.

12.
New Phytol ; 231(3): 1220-1235, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33904185

RESUMO

Trichome initiation and leaf growth are two critical developmental processes in the plant life cycle, which need to be optimized in accordance with developmental stage and immediate surroundings. To a large extent, this optimization is achieved by fine-tuning of hormonal pathways, including the gibberellin (GA) pathway. However, the mechanism by which plants control GA homeostasis to optimize these two developmental processes is unknown. Here, we report that HAT1, a HD-ZIP II transcription factor, negatively regulates GA-mediated trichome initiation and cotyledon expansion. Both protein and transcript levels indicated that HAT1 was induced by GA, while an increased abundance of HAT1, in turn, was found to suppress GA biosynthesis and signaling, thus forming a regulatory negative feedback loop that controls GA homeostasis to fine-tune trichome development and cotyledon expansion. We also found that HAT1 interacts with DELLAs, including GAI and RGA. GAI inhibits both protein stability and the binding activity of HAT1 to its target genes. Overexpression of HAT1 in della5 can completely suppress the enhanced trichome initiation and enlarged cotyledon of della5. Our findings demonstrate that HAT1 functions as a critical repressor to regulate GA-mediated trichome initiation and cotyledon growth; in addition, we describe a novel mechanism by which the plant regulates trichome initiation and cotyledon expansion through a HAT1-DELLA regulatory module under various GA concentrations.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Giberelinas , Histona Acetiltransferases , Homeostase , Folhas de Planta/metabolismo , Fatores de Transcrição , Tricomas/metabolismo
13.
Sci Rep ; 10(1): 10011, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561796

RESUMO

Chitosan oligosaccharide functionalized silver nanoparticles with synergistic bacterial activity were constructed as a multivalent inhibitor of bacteria. Placing the chitosan oligosaccharide on silver nanoparticles can dramatically enhance the adsorption to the bacterial membrane via multivalent binding. The multicomponent nanostructures can cooperate synergistically against gram-positive and gram-negative bacteria. The antibacterial activity was increased via orthogonal array design to optimize the synthesis condition. The synergistic bacterial activity was confirmed by fractional inhibitory concentration and zone of inhibition test. Through studies of antimicrobial action mechanism, it was found that the nanocomposites interacted with the bacteria by binding to Mg2+ ions of the bacterial surface. Then, the nanocomposites disrupted bacterial membrane by increasing the permeability of the outer membrane, resulting in leakage of cytoplasm. This strategy of chitosan oligosaccharide modification can increase the antibacterial activity of silver nanoparticles and accelerate wound healing at the same time. The nanomaterial without cytotoxicity has promising applications in bacteria-infected wound healing therapy.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Nanocompostos/uso terapêutico , Oligossacarídeos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/uso terapêutico , Quitosana/química , Quitosana/uso terapêutico , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanocompostos/química , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Prata/química
14.
Sensors (Basel) ; 19(1)2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30597918

RESUMO

This paper considers satellite communication networks where each satellite terminal is equipped with energy harvesting (EH) devices to supply energy continuously, and randomly transmits bursty packets to a geostationary satellite over a shared wireless channel. Packet replicas combined with a successive iteration cancellation scheme can reduce the negative impact of packet collisions but consume more energy. Hence, appropriate energy management policies are required to mitigate the adverse effect of energy outages. Although centralized access schemes can provide better performance on the networks' throughput, they expend extra signallings to allocate the resources, which leads to non-negligible communication latencies, especially for the satellite communication networks. In order to reduce the communication overhead and delay, a distributed random access (RA) scheme considering the energy constraints is studied. Each EH satellite terminal (EH-ST) decides whether to transmit the packet and how many replicas are transmitted according to its local energy and EH rates to maximize the average long-term network throughput. Owing to the nonconvexity of this problem, we adopted a game theoretic method to approximate the optimal solution. By forcing all the EH-STs to employ the same policy, we characterized and proved the existence and uniqueness of the symmetric Nash equilibrium (NE) of the game. Moreover, an efficient algorithm is proposed to calculate the symmetric NE by combining a policy iteration algorithm and the bisection method. The performance of the proposed RA scheme was investigated via numerous simulations. Simulation results showed that the proposed RA scheme is applicable to the EH devices in the future low-cost interactive satellite communication system.

15.
Sci Rep ; 6: 35392, 2016 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-27739520

RESUMO

Crosstalk between phytohormone pathways is essential in plant growth, development and stress responses. Brassinosteroids (BRs) and ethylene are both pivotal plant growth regulators, and the interaction between these two phytohormones in the tomato response to salt stress is still unclear. Here, we explored the mechanism by which BRs affect ethylene biosynthesis and signaling in tomato seedlings under salt stress. The activity of 1-aminocyclopropane-1-carboxylate synthase (ACS), an ethylene synthesis enzyme, and the ethylene signaling pathway were activated in plants pretreated with BRs. Scavenging of ethylene production or silencing of ethylene signaling components inhibited BR-induced salt tolerance and blocked BR-induced activities of several antioxidant enzymes. Previous studies have reported that BRs can induce plant tolerance to a variety of environmental stimuli by triggering the generation of H2O2 as a signaling molecule. We also found that H2O2 might be involved in the crosstalk between BRs and ethylene in the tomato response to salt stress. Simultaneously, BR-induced ethylene production was partially blocked by pretreated with a reactive oxygen species scavenger or synthesis inhibitor. These results strongly demonstrated that ethylene and H2O2 play important roles in BR-dependent induction of plant salt stress tolerance. Furthermore, we also investigated the relationship between BR signaling and ethylene signaling pathways in plant processes responding to salt stress.


Assuntos
Brassinosteroides/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Tolerância ao Sal/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Adaptação Fisiológica/efeitos dos fármacos , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismo , Plântula , Transdução de Sinais/efeitos dos fármacos
16.
Biochem Biophys Res Commun ; 477(4): 626-632, 2016 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-27346129

RESUMO

Arabidopsis thaliana GOLDEN2-LIKE (GLKs) transcription factors play important roles in regulation of photosynthesis-associated nuclear genes, as well as participate in chloroplast development. However, the involvement of GLKs in plants resistance to virus remains largely unknown. Here, the relationship between GLKs and Cucumber mosaic virus (CMV) stress response was investigated. Our results showed that the Arabidopsis glk1glk2 double-mutant was more susceptible to CMV infection and suffered more serious damages (such as higher oxidative damages, more compromised in PSII photochemistry and more reactive oxygen species accumulation) when compared with the wild-type plants. Interestingly, there was little difference between single mutant (glk1 or glk2) and wild-type plants in response to CMV infection, suggesting GLK1 and GLK2 might function redundant in virus resistance in Arabidopsis. Furthermore, the induction of antioxidant system and defense-associated genes expression in the double mutant were inhibited when compared with single mutant or wild-type plants after CMV infection. Further evidences showed that salicylic acid (SA) and jasmonic acid (JA) might be involved in GLKs-mediated virus resistance, as SA or JA level and synthesis-related genes transcription were impaired in glk1glk2 mutant. Taken together, our results indicated that GLKs played a positively role in virus resistance in Arabidopsis.


Assuntos
Adaptação Fisiológica/fisiologia , Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Cucumovirus/patogenicidade , Fatores de Transcrição/fisiologia , Arabidopsis/metabolismo , Arabidopsis/virologia , Proteínas de Arabidopsis/genética , Ciclopentanos/metabolismo , Estresse Oxidativo , Oxilipinas/metabolismo , Fotossíntese , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Fatores de Transcrição/genética
17.
Am J Chin Med ; 44(4): 721-36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27222070

RESUMO

Traditional medicinal formulation of Yin-zhi-huang (YZH) is widely used in the clinic for the treatment of jaundice and chronic liver diseases in East Asian countries. However, the pharmacologically active components of YZH and the underlying mechanism are still unknown. Geniposide (GEN) was recently identified as one of the most abundant circulating components in YZH. In this study, we investigated the protective effect of GEN against liver injuries induced by alpha-naphthylisothiocyanate (ANIT). 50[Formula: see text]mg/kg of GEN was administered to ICR mice once daily for 5 days, and challenge of ANIT 75[Formula: see text]mg/kg was performed on the 4th day. Blood and liver tissues were collected on day 6 and subjected to biochemical, histopathological and pathway analyses. The biochemical and pathological findings showed that GEN almost totally attenuated ANIT-induced cholestasis and liver injury compared with the vehicle/ANIT group. The altered gene transcription related to bile acid metabolism and transport was normalized by co-treatment with GEN. The expressions of tumor necrosis factor-[Formula: see text] and the suppressor of cytokine signaling 3 were significantly decreased in the GEN/ANIT group. Western blot revealed that GEN inhibited the activation and expression of STAT3 and NF[Formula: see text]B. These data suggest GEN inhibits ANIT-induced hepatotoxicity. The protective effect is associated with the downregulation of STAT3 and NF[Formula: see text]B signaling.


Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Iridoides/administração & dosagem , NF-kappa B/genética , Fator de Transcrição STAT3/genética , 1-Naftilisotiocianato/efeitos adversos , Animais , Colestase Intra-Hepática/induzido quimicamente , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa
18.
Pharmazie ; 71(4): 205-12, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27209701

RESUMO

BACKGROUND: Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established. METHODS: In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis. RESULTS: Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice. CONCLUSIONS: Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.


Assuntos
Fenofibrato/farmacologia , Genfibrozila/farmacologia , Glucose/metabolismo , Hipolipemiantes/farmacologia , PPAR alfa/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Glicogênio/metabolismo , Hepatomegalia/genética , Hepatomegalia/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , PPAR alfa/genética , Piruvato Quinase/biossíntese
19.
Front Plant Sci ; 6: 982, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26617622

RESUMO

Effects of brassinosteroids (BRs) on cucumber (Cucumis sativus L.) abiotic stresses resistance to salt, polyethylene glycol (PEG), cold and the potential mechanisms were investigated in this work. Previous reports have indicated that BRs can induce ethylene production and enhance alternative oxidase (AOX) pathway. The mechanisms whether ethylene is involved as a signal molecule which connected BR with AOX in regulating stress tolerance are still unknown. Here, we found that pretreatment with 1 µM brassinolide (BL, the most active BRs) relieved stress-caused oxidative damage in cucumber seedlings and clearly enhanced the capacity of AOX and the ethylene biosynthesis. Furthermore, transcription level of ethylene signaling biosynthesis genes including ripening-related ACC synthase1 (C S ACS1), ripening-related ACC synthase2 (C S ACS2), ripening-related ACC synthase3 (C S ACS3), 1-aminocyclopropane-1-carboxylate oxidase1 (C S ACO1), 1-aminocyclopropane-1-carboxylate oxidase2 (C S ACO2), and C S AOX were increased after BL treatment. Importantly, the application of the salicylhydroxamic acid (SHAM, AOX inhibitor) and ethylene biosynthesis inhibitor aminooxyacetic acid (AOA) decreased plant resistance to environmental stress by blocking BRs-induced alternative respiration. Taken together, our results demonstrated that ethylene was involved in BRs-induced AOX activity which played important roles in abiotic stresses tolerance in cucumber seedlings.

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