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1.
Plant J ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037746

RESUMO

The advanced model of floral morphogenesis is based largely on data from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), but this process is less well understood in the Triticeae. Here, we investigated a sterile barley (Hordeum vulgare) mutant with malformed floral organs (designated mfo1), of which the paleae, lodicules, and stamens in each floret were all converted into lemma-like organs, and the ovary was abnormally shaped. Combining bulked-segregant analysis, whole-genome resequencing, and TILLING approaches, the mfo1 mutant was attributed to loss-of-function mutations in the MADS-box transcription factor gene HvAGL6, a key regulator in the ABCDE floral morphogenesis model. Through transcriptomic analysis between young inflorescences of wild-type and mfo1 plants, 380 genes were identified as differentially expressed, most of which function in DNA binding, protein dimerization, cell differentiation, or meristem determinacy. Regulatory pathway enrichment showed HvAGL6 associates with transcriptional abundance of many MADS-box genes, including the B-class gene HvMADS4. Mutants with deficiency in HvMADS4 exhibited the conversion of stamens into supernumerary pistils, producing multiple ovaries resembling the completely sterile multiple ovaries 3.h (mov3.h) mutant. These findings demonstrate that the regulatory model of floral morphogenesis is conserved across plant species and provides insights into the interactions between HvAGL6 and other MADS-box regulators.

2.
J Stroke Cerebrovasc Dis ; 33(1): 107452, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37931484

RESUMO

OBJECTIVES: To investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). METHODS: This was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. RESULTS: Among all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). CONCLUSIONS: This study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/induzido quimicamente , Anticoagulantes/uso terapêutico , Prognóstico , Fatores de Risco , Administração Oral
3.
BMC Womens Health ; 23(1): 535, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37817158

RESUMO

BACKGROUND: Endometriosis (EMS) occurs when normal uterine tissue grows outside the uterus and causes chronic pelvic pain and infertility. Endometriosis-associated infertility is thought to be caused by unknown mechanisms. In this study, using necroptosis-related genes, we developed and validated multigene joint signatures to diagnose EMS and explored their biological roles. METHODS: We downloaded two databases (GSE7305 and GSE1169) from the Gene Expression Omnibus (GEO) database and 630 necroptosis-related genes from the GeneCards and GSEA databases. The limma package in Rsoftware was used to identify differentially expressed genes (DEGs). We interleaved common differentially expressed genes (co-DEGs) and necroptosis-related genes (NRDEGs) in the endometriosis dataset. The DEGs functions were reflected by gene ontology analysis (GO), pathway enrichment analysis, and gene set enrichment analysis (GSEA). We used CIBERSORT to analyze the immune microenvironment differences between EMS patients and controls. Furthermore, a correlation was found between necroptosis-related differentially expressed genes and infiltrating immune cells to better understand the molecular immune mechanism. RESULTS: Compared with the control group, this study revealed that 10 NRDEGs were identified in EMS. There were two types of immune cell infiltration abundance (activated NK cells and M2 macrophages) in these two datasets, and the correlation between different groups of samples was statistically significant (P < 0.05). MYO6 consistently correlated with activated NK cells in the two datasets. HOOK1 consistently demonstrated a high correlation with M2 Macrophages in two datasets. The immunohistochemical result indicated that the protein levels of MYO6 and HOOK1 were increased in patients with endometriosis, further suggesting that MYO6 and HOOK1 can be used as potential biomarkers for endometriosis. CONCLUSIONS: We identified ten necroptosis-related genes in EMS and assessed their relationship with the immune microenvironment. MYO6 and HOOK1 may serve as novel biomarkers and treatment targets in the future.


Assuntos
Endometriose , Infertilidade , Necroptose , Feminino , Humanos , Dor Crônica , Endometriose/diagnóstico , Endometriose/genética , Necroptose/genética , Marcadores Genéticos
4.
Mar Drugs ; 21(8)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37623738

RESUMO

To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A-F (1-6), along with four known compounds 7-10, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,ß-α',ß'-unsaturated carbonyl, or an α,ß-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 6-10 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads.


Assuntos
Antozoários , Animais , Humanos , População do Leste Asiático , Antibacterianos/farmacologia , Esteroides/farmacologia
5.
Curr Issues Mol Biol ; 44(11): 5622-5637, 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36421665

RESUMO

The NAC (NAM, ATAF1/2, and CUC2) gene family, one of the largest transcription factor families in plants, acts as positive or negative regulators in plant response and adaption to various environmental stresses, including cold stress. Multiple reports on the functional characterization of NAC genes in Arabidopsis thaliana and other plants are available. However, the function of the NAC genes in the typical woody mangrove (Kandelia obovata) remains poorly understood. Here, a comprehensive analysis of NAC genes in K. obovata was performed with a pluri-disciplinary approach including bioinformatic and molecular analyses. We retrieved a contracted NAC family with 68 genes from the K. obovata genome, which were unevenly distributed in the chromosomes and classified into ten classes. These KoNAC genes were differentially and preferentially expressed in different organs, among which, twelve up-regulated and one down-regulated KoNAC genes were identified. Several stress-related cis-regulatory elements, such as LTR (low-temperature response), STRE (stress response element), ABRE (abscisic acid response element), and WUN (wound-responsive element), were identified in the promoter regions of these 13 KoNAC genes. The expression patterns of five selected KoNAC genes (KoNAC6, KoNAC15, KoNAC20, KoNAC38, and KoNAC51) were confirmed by qRT-PCR under cold treatment. These results strongly implied the putative important roles of KoNAC genes in response to chilling and other stresses. Collectively, our findings provide valuable information for further investigations on the function of KoNAC genes.

6.
Anal Chem ; 94(18): 6874-6881, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35483064

RESUMO

In this work, a novel electrochemiluminescence (ECL) biosensor was developed for ultrasensitive detection of microRNA let-7a (miRNA let-7a) based on MnS:CdS@ZnS core-shell quantum dots (QDs) as ECL luminophores with high ECL efficiency. Impressively, compared to the CdS:Mn@ZnS QDs prepared by ionic doping with ECL efficiency of 0.87%, MnS:CdS@ZnS QDs synthesized by bimetallic clusters (Cd2Mn2O4) doping exhibited high ECL efficiency of up to 15.84% with S2O82- as cathodic coreactant due to the elimination of the dopants size mismatch and "self-purification" effect, which could achieve the surface defect passivation of MnS:CdS@ZnS QDs for effectively improving the ECL emission. Furthermore, with the help of strand displacement amplification (SDA), the trace target miRNA let-7a was able to be converted to a number of output DNA labeled with ferrocene (Fc) to construct an ultrasensitive ECL biosensor. The well-designed ECL biosensor for miRNA let-7a exhibited high stability and excellent sensitivity of a concentration variation from 10 aM to 1 nM and a low detection limit of 4.1 aM, which was further applied to the analysis of miRNA let-7a from cancer cell (MCF-7) lysate. Thus, this strategy provides a novel method to prepare high-efficient ECL emitters for the construction of ECL biosensing platforms in biological fields and clinical diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Pontos Quânticos , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Medições Luminescentes/métodos , MicroRNAs/análise , Sulfetos , Compostos de Zinco
7.
BMC Oral Health ; 22(1): 445, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243707

RESUMO

OBJECTIVES: Relationship between lipid profile and periodontitis has been reported. However, the association between lipid parameters and edentulism is unclear. This study aimed to investigate the association between lipid profile and reported edentulism in the elder population using a national cohort. METHODS: A total of 3 100 participants aged 65 or above were enrolled in 2011 from China Health and Retirement Longitudinal Study, which was a national population-based survey. We used adjusted logistics models to investigate the relationship between lipid profile and reported edentulism before and after propensity score matching. RESULTS: The mean (SD) age was 71.96 (5.63) years, and 1 581 (51.0%) were men. There were 254 (8.2%) individuals reporting edentulism, and the low-density lipoprotein cholesterol (LDL-C) was significantly higher in the reported edentulism group, compared with the non-edentulism (122.48 vs. 116.91 mg/dl, P = 0.015). In the multivariable model, LDL-C was significantly associated with a higher odds of reported edentulism (adjusted OR [95% CI], 1.004 [1.001-1.008]). In the matched population, LDL-C, non high-density lipoprotein cholesterol, remnant cholesterol, total cholesterol and triglycerides were positively associated with reported edentulism, while HDL-C was negatively associated. CONCLUSIONS: Lipid profiles are probably associated with edentulism, indicating the interaction between oral health and metabolic status in the elder population.


Assuntos
Colesterol , Aposentadoria , Idoso , China/epidemiologia , HDL-Colesterol , LDL-Colesterol , Feminino , Humanos , Estudos Longitudinais , Masculino , Triglicerídeos
8.
BMC Pregnancy Childbirth ; 21(1): 332, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902475

RESUMO

BACKGROUND: Although maternal deaths are rare in developed regions, the morbidity associated with severe postpartum hemorrhage (SPPH) remains a major problem. To determine the prevalence and risk factors of SPPH, we analyzed data of women who gave birth in Guangzhou Medical Centre for Critical Pregnant Women, which received a large quantity of critically ill obstetric patients who were transferred from other hospitals in Southern China. METHODS: In this study, we conducted a retrospective case-control study to determine the prevalence and risk factors for SPPH among a cohort of women who gave birth after 28 weeks of gestation between January 2015 and August 2019. SPPH was defined as an estimated blood loss ≥1000 mL and total blood transfusion≥4 units. Logistic regression analysis was used to identify independent risk factors for SPPH. RESULTS: SPPH was observed in 532 mothers (1.56%) among the total population of 34,178 mothers. Placenta-related problems (55.83%) were the major identified causes of SPPH, while uterine atony without associated retention of placental tissues accounted for 38.91%. The risk factors for SPPH were maternal age < 18 years (adjusted OR [aOR] = 11.52, 95% CI: 1.51-87.62), previous cesarean section (aOR = 2.57, 95% CI: 1.90-3.47), history of postpartum hemorrhage (aOR = 4.94, 95% CI: 2.63-9.29), conception through in vitro fertilization (aOR = 1.78, 95% CI: 1.31-2.43), pre-delivery anemia (aOR = 2.37, 95% CI: 1.88-3.00), stillbirth (aOR = 2.61, 95% CI: 1.02-6.69), prolonged labor (aOR = 5.24, 95% CI: 3.10-8.86), placenta previa (aOR = 9.75, 95% CI: 7.45-12.75), placenta abruption (aOR = 3.85, 95% CI: 1.91-7.76), placenta accrete spectrum (aOR = 8.00, 95% CI: 6.20-10.33), and macrosomia (aOR = 2.30, 95% CI: 1.38-3.83). CONCLUSION: Maternal age < 18 years, previous cesarean section, history of PPH, conception through IVF, pre-delivery anemia, stillbirth, prolonged labor, placenta previa, placental abruption, PAS, and macrosomia were risk factors for SPPH. Extra vigilance during the antenatal and peripartum periods is needed to identify women who have risk factors and enable early intervention to prevent SPPH.


Assuntos
Cesárea/efeitos adversos , Complicações do Trabalho de Parto/epidemiologia , Assistência Perinatal , Hemorragia Pós-Parto , Complicações na Gravidez , China/epidemiologia , Estado Terminal/epidemiologia , Feminino , Idade Gestacional , Necessidades e Demandas de Serviços de Saúde , Humanos , Idade Materna , Assistência Perinatal/métodos , Assistência Perinatal/normas , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Prevalência , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença
9.
Mol Plant Microbe Interact ; 33(7): 902-910, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32282260

RESUMO

Clonostachys chloroleuca is a mycoparasite used for biocontrol of numerous fungal plant pathogens. Sequencing of the transcriptome of C. chloroleuca following mycoparasitization of the sclerotia of Sclerotinia sclerotiorum revealed significant upregulation of a mitogen-activated protein kinase (MAPK)-encoding gene, crmapk. Although MAPKs are known to regulate fungal growth and development, the function of crmapk in C. chloroleuca mycoparasitism is unclear. In this study, we investigated the role of crmapk in C. chloroleuca mycoparasitism through gene knockout and complementation. Deletion of crmapk had no influence on the C. chloroleuca morphological characteristics but could significantly reduce the mycoparasitic ability to sclerotia and biocontrol capacity to soybean Sclerotinia stem rot; crmapk complementation restored these abilities. Transcriptome analysis between Δcrmapk and the wild-type strain revealed numerous genes were significantly down-regulated after crmapk deletion, including cytochrome P450, transporters, and cell wall-degrading enzymes (CWDEs). Our findings indicate that crmapk influences C. chloroleuca mycoparasitism by regulation of genes controlling the activity of CWDEs or antibiotic production. This study provides a basis for further studies of the molecular mechanism of C. chloroleuca mycoparasitism.


Assuntos
Ascomicetos/patogenicidade , Agentes de Controle Biológico , Hypocreales/fisiologia , Proteínas Quinases Ativadas por Mitógeno/genética , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Genes Fúngicos , Teste de Complementação Genética , Hypocreales/genética , Doenças das Plantas/microbiologia , Glycine max/microbiologia
10.
Anal Chem ; 92(21): 14723-14729, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33054154

RESUMO

Herein, the boron radical active sites of boron carbon oxynitride quantum dots (BCNO QDs) are electrically excited to produce boron radicals (B•) for catalyzing peroxydisulfate (S2O82-) as a coreactant to accelerate the generation of abundant sulfate radicals (SO4•-) for significant enhancement in the electrochemiluminescence (ECL) efficiency of BCNO QDs, which overcome the defect of traditional carbon-based QDs with low ECL efficiency. Impressively, under extremely low concentration of S2O82- solution, the BCNO QDs/S2O82- system could exhibit high ECL emission, realizing environmental friendliness and excellent biocompatibility for sensitive bioanalysis. As a proof-of-concept, BCNO QDs, a new generation of ECL emitters with high ECL efficiency, were successfully used in the ultrasensitive determination of microRNA-21, which pushes the exploration of new ECL emitters and broadens the application in the field of clinical diagnosis, ECL imaging, and molecular devices.


Assuntos
Compostos de Boro/química , Limite de Detecção , Medições Luminescentes/métodos , MicroRNAs/análise , Pontos Quânticos/química , Catálise , Eletroquímica , MicroRNAs/química
11.
Neurol Sci ; 41(4): 903-909, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31828679

RESUMO

BACKGROUND AND PURPOSE: The role of bilirubin in patients treated with mechanical thrombectomy (MT) is unknown. We investigated the relationship between admission bilirubin levels and hemorrhagic complication in acute ischemic stroke (AIS) patients treated with MT and detailed the roles of direct bilirubin (DB), indirect bilirubin (IDB), and total bilirubin (TB). METHODS: Consecutive AIS patients treated with MT were enrolled from two stroke centers. Outcome measures included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 48 h. An independent association of bilirubin with outcomes was identified by multivariate logistic regression analysis. The accuracies of bilirubin in predicting outcome were evaluated using receiver operating characteristic curve analysis. RESULTS: Of the 153 enrolled patients, 64 (41.8%) were diagnosed with HT, of which 28 (18.3%) had sICH. In univariate analyses, DB, IDB, and TB were higher in patients with HT and sICH than in patients without. After adjustment for potential confounders, DB (odds ratio [OR], 1.364; 95% confidence interval [CI], 1.133-1.641; p = 0.001), IDB (OR, 1.143; 95% CI, 1.052-1.242; p = 0.002), and TB (OR, 1.106; 95% CI, 1.041-1.175; p = 0.001) were independently associated with HT. IDB (OR, 1.177; 95% CI, 1.064-1.303; p = 0.002) and TB (OR, 1.102; 95% CI, 1.027-1.182; p = 0.007) were independently associated with sICH. Receiver operating characteristic curve analysis showed no significant difference between the three indicators of predicting HT and sICH. CONCLUSIONS: Elevated admission bilirubin is an independent predictor of HT and sICH in AIS patients treated with MT.


Assuntos
Bilirrubina/sangue , Hemorragias Intracranianas , AVC Isquêmico , Trombólise Mecânica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/etiologia , AVC Isquêmico/sangue , AVC Isquêmico/complicações , AVC Isquêmico/terapia , Masculino , Trombólise Mecânica/efeitos adversos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 365-370, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32543144

RESUMO

OBJECTIVE: To investigate the effect of down-regulation of SND1 expression on senescence of human diploid fibroblasts. METHODS: Western blot and immunohistochemistry were used to detect the expression of SND1 in young or senescent 2BS cells and aged tissues. Immunofluorescence was conducted to detect the localization of SND1 in young 2BS cells. CCK8 and EDU were performed to detect the proliferation of 2BS. Colony formation analysis was used to evaluate the capacity of colony formation of 2BS. Expression chip and RT-qPCR analysis were performed to detect the change of SASP expression level. ß-galactosidase staining was employed to indicate the senescent 2BS cells. RESULTS: The expression of SND1 in the senescent 2BS cells was significantly down-regulated compared with in the younger 2BS cells, and in human colon adenomas, its expression was also significantly down-regulated compared with in non-lesion colon tissues. In young 2BS, knockdown of SND1 inhibited the proliferation and colony formation of 2BS, and led to stronger senescence-associated beta-galactosidase staining (SA-ß-gal). Expression chip and RT-qPCR analysis indicated that knockdown of SND1 up-regulated the expression of senescence-associated secretory phenotype components (SASP). CONCLUSIONS: Our data indicated that down-regulation of SND1 regulated human diploid cell senescence by up-regulating the expression of SASP components.


Assuntos
Senescência Celular , Diploide , Endonucleases , Fibroblastos , Regulação para Baixo , Fibroblastos/metabolismo , Humanos , Proteínas Nucleares/genética
13.
BMC Genomics ; 20(1): 570, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291889

RESUMO

BACKGROUND: Cucumber Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Foc), is one of the most notorious diseases in cucumber production. Our previous research showed the virulence of Foc significantly increases over consecutive rounds of infection in a resistant cultivar. To understand the virulence variation of Foc under host pressure, the mildly virulent strain foc-3b (WT) and its virulence-enhanced variant Ra-4 (InVir) were selected and their transcriptome profiles in infected cucumber roots were analyzed at 24 h after inoculation (hai) and 120 hai. RESULTS: A series of differentially expressed genes (DEGs) potentially involved in fungal pathogenicity and pathogenicity variation were identified and prove mainly involved in metabolic, transport, oxidation-reduction, cell wall degradation, macromolecules modification, and stress and defense. Among these DEGs, 190 up- and 360 down-regulated genes were expressed in both strains, indicating their importance in Foc infection. Besides, 286 and 366 DEGs showed up-regulated expression, while 492 and 214 showed down-regulated expression in InVir at 24 and 120 hai, respectively. These DEGs may be involved in increased virulence. Notably, transposases were more active in InVir than WT, indicating transposons may contribute to adaptive evolution. CONCLUSIONS: By a comparative transcriptome analysis of the mildly and highly virulent strains of Foc during infection of cucumber, a series of DEGs were identified that may be associated with virulence. Hence, this study provides new insight into the transcriptomic profile underlying pathogenicity and virulence differentiation of Foc.


Assuntos
Cucumis sativus/microbiologia , Fusarium/genética , Fusarium/patogenicidade , Perfilação da Expressão Gênica , Adaptação Fisiológica/genética , Fusarium/fisiologia , Redes Reguladoras de Genes , Raízes de Plantas/microbiologia , Especificidade da Espécie , Virulência/genética
14.
Anal Chem ; 91(12): 7765-7773, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31134798

RESUMO

In this work, a novel three-dimensional cadmium telluride quantum dots-DNA nanoreticulation (3D CdTe QDs-DNA-NR) was used as a signal probe with the dual-legged DNA walker circular amplification as target conversion strategy to establish a pioneering electrochemiluminescence (ECL) biosensing strategy for ultrasensitive detection of microRNA-21 form cancer cells. Herein, such a 3D luminous nanomaterial with reticular structure not only supported abundant CdTe QDs to avoid the inner filter effect for obtaining a high ECL efficiency but also contained the hemin/G-quadruplex as coreaction accelerator in the 3D CdTe QDs-DNA-NR/S2O82- system for the enhancement of ECL intensity. Furthermore, with the target-induced dual-legged DNA walker circular amplification strategy, a mass of output DNA was produced to connect with the 3D CdTe QDs-DNA-NR for the construction of the ECL biosensor, which realized the ultrasensitive detection of microRNA-21 from 100 aM to 100 pM and the detection limit down to 34 aM. Significantly, this work could be readily extended for the detection of other biomolecules to provide a neoteric channel for disease diagnosis.


Assuntos
Técnicas Biossensoriais/métodos , Compostos de Cádmio/química , DNA/química , Limite de Detecção , MicroRNAs/metabolismo , Nanoestruturas/química , Pontos Quânticos/química , Telúrio/química , Eletroquímica , Quadruplex G , Células HeLa , Hemina/química , Humanos , Medições Luminescentes , Células MCF-7
15.
J Neuroinflammation ; 16(1): 149, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324254

RESUMO

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. RESULTS: Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. CONCLUSIONS: Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Quinazolinonas/farmacologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Animais , Inibidores Enzimáticos/farmacologia , Feminino , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas de Ligação a RNA/antagonistas & inibidores , Linfócitos T Auxiliares-Indutores/imunologia
16.
J Immunol ; 197(7): 2880-90, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27566823

RESUMO

Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3). Using a genetic inactivation approach together with pharmacological perturbations in mouse cells, we show that PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages, via metabolically supporting the engulfment and removal of virus-infected cells. Furthermore, the antiviral function of PFKFB3, as well as some contribution of its action from the hematopoietic compartment, was confirmed in a mouse model of respiratory syncytial virus infection. Therefore, different from the long-standing perception of glycolysis as a proviral pathway, our findings establish an antiviral, immunometabolic aspect of glycolysis that may have therapeutic implications.


Assuntos
Glicólise , Imunidade Inata , Macrófagos/imunologia , Macrófagos/metabolismo , Fosfofrutoquinase-2/metabolismo , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Animais , Glicólise/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfofrutoquinase-2/deficiência , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/metabolismo
17.
J Vasc Res ; 54(6): 329-343, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29040972

RESUMO

AIM: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance Ca2+-activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin-induced diabetic rats. METHODS: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRT-PCR and Western blots. The coronary artery tension and coronary SMC Ca2+ concentrations were measured using a myograph system and fluorescence Ca2+ indicator. RESULTS: Compared to nondiabetic control rats, the BK channel function was impaired with a reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral administration of n-3 PUFAs had no effects on protein expressions of BK channel subunits in nondiabetic rats, but significantly enhanced those of BK-ß1 in diabetic rats without altering BK-α protein levels. Moreover, coronary ring tension induced by iberiotoxin (a specific BK channel blocker) was increased and cytosolic Ca2+ concentrations in coronary SMCs were decreased in diabetic rats, but no changes were found in nondiabetic rats. CONCLUSIONS: n-3 PUFAs protect the coronary BK channel function and coronary vasoreactivity in diabetic rats as a result of not only increasing BK-ß1 protein expressions, but also decreasing coronary artery tension and coronary smooth muscle cytosolic Ca2+ concentrations.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Potenciais da Membrana , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Ratos Sprague-Dawley , Fatores de Tempo
18.
Biochem Biophys Res Commun ; 474(3): 503-508, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27130824

RESUMO

Clonostachys rosea is a promising biocontrol agent that parasitizes various fungal plant pathogens. In this paper, transaldolase gene Tal67 was found to be greatly upregulated in C. rosea isolate 67-1 during mycoparasitism of Sclerotinia sclerotiorum sclerotia. Quantitative real-time PCR revealed a significant increase in expression at 0-48 h after induction by sclerotia, and the level peaked at 13.9-fold higher than the control at 24 h. Gene disruption led to a decrease in the growth rate of the Tal67-deficient strain ΔTal67 to 5.3 mm/day, which was much lower than the wild type and the complemented strain ΔTal67+ (P < 0.05). The antagonistic activity of ΔTal67 against Botrytis cinerea was 15.8% lower than the wild type, and the parasitic rate to S. sclerotiorum decreased by 24.6%. However, reinsertion of the transaldolase gene recovered the fungicidal activity of C. rosea. The efficacy of the mutants against soybean Sclerotinia stem rot was evaluated in the greenhouse, and the control efficiency of isolate 67-1 reached 65.3%, while the efficiency of the ΔTal67 strain decreased sharply to 17.8%, and the complemented strain ΔTal67+ recovered to 64.8%. These results suggest that Tal67 plays an important role in the growth and biocontrol activity of C. rosea.


Assuntos
Ascomicetos/fisiologia , Melhoramento Genético/métodos , Glycine max/microbiologia , Controle Biológico de Vetores/métodos , Transaldolase/metabolismo , Ascomicetos/patogenicidade , Transaldolase/genética
19.
Cereb Cortex ; 25(9): 2741-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24735674

RESUMO

Rats generate sweeping whisker movements in order to explore their environments and identify objects. In somatosensory pathways, neuronal activity is modulated by the frequency of whisker vibration. However, the potential role of rhythmic neuronal activity in the cerebral processing of sensory signals and its mechanism remain unclear. Here, we showed that rhythmic vibrissal stimulation with short duration in anesthetized rats resulted in an increase or decrease in the amplitude of somatosensory-evoked potentials (SEPs) in the contralateral barrel cortex. The plastic change of the SEPs was frequency dependent and long lasting. The long-lasting enhancement of the vibrissa-to-cortex evoked response was side- but not barrel-specific. Local application of dl-2-amino-5-phosphonopentanoic acid into the barrel cortex revealed that this vibrissa-to-cortex long-term plasticity in adult rats was N-methyl-d-aspartate receptor-dependent. Most interestingly, whisker trimming through postnatal day (P)1-7 but not P29-35 impaired the long-term plasticity induced by 100 Hz vibrissal stimulation. The short period of rhythmic vibrissal stimulation did not induce long-lasting plasticity of field potentials in the thalamus. In conclusion, our results suggest that natural rhythmic whisker activity modifies sensory information processing in cerebral cortex, providing further insight into sensory perception.


Assuntos
Plasticidade Neuronal/fisiologia , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologia , Sinapses/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Masculino , Microinjeções , Plasticidade Neuronal/efeitos dos fármacos , Estimulação Física , Psicofísica , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Fatores de Tempo , Vibrissas/inervação
20.
J Craniofac Surg ; 27(6): 1440-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27300460

RESUMO

Severe forms of bilateral cleft lip and palate remain a challenging issue. Although nasoalveolar molding dramatically improves overall treatment success, the position of the premaxilla often remains dislocated. The authors attempted to relocate the malpositioned premaxilla into the correct position to obtain the correct three-dimensional (3D) maxillary arch structure and growth. Eight patients with severe bilateral cleft lip and palate were treated with premaxillary osteotomy for premaxilla repositioning. The position of the premaxilla was measured directly using cephalometry. Two raters including orthodontists evaluated the 3D (anteroposterior, transverse, and sagittal) outcomes. Regarding the long-term effects of premaxillary repositioning on midfacial growth, 3D computed tomography scan data were used, including the measurement of the SNA, SNB, and ANB angles according to the time period (T0: preoperative; T1: immediate postoperative; T2: long-term postoperative). All bilateral cleft lips and palates were satisfactorily repaired without any complications, including any premaxillary vascular compromise, nonunion, and occlusal instability. The average visual analog scale scores (0-5) of the anteroposterior, vertical, and transverse dimensions were 3.9, 3.7, and 3.2, respectively. Regarding the effect of premaxillary repositioning on midfacial hypoplasia, the change in the ANB between T1 and T2 was not significant, implying that premaxillary repositioning did not affect the long-term harmony between the maxilla and mandible (ANB of T2-T1: P = 0.1016) based on interim growth data at the time of follow-up and study completion. Premaxillary repositioning effectively corrected the malpositioned premaxilla and repaired the accompanying wide alveolar cleft, achieving successful restoration of maxillary arch coordination. In addition, premaxillary osteotomy after 8 years of age does not seem to cause significant maxillary retrusion.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Maxila/cirurgia , Osteotomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Cefalometria , Criança , Pré-Escolar , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Feminino , Humanos , Imageamento Tridimensional , Masculino , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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