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1.
BMC Plant Biol ; 24(1): 689, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030471

RESUMO

BACKGROUND: Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. RESULTS: We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. CONCLUSION: Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.


Assuntos
Boro , Nicotiana , Proteoma , Transcriptoma , Boro/deficiência , Boro/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Proteoma/metabolismo , Regulação da Expressão Gênica de Plantas , Plântula/genética , Plântula/metabolismo , Plântula/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica
2.
Chemistry ; 30(40): e202401001, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38742479

RESUMO

Photodynamic therapy (PDT) is a rapidly growing discipline that is expected to become an encouraging noninvasive therapeutic strategy for cancer treatment. In the PDT process, an efficient intersystem crossing (ISC) process for photosensitizers from the singlet excited state (S1) to the triplet excited state (T1) is critical for the formation of cytotoxic reactive oxygen species and improvement of PDT performance. Thermally activated delayed fluorescence (TADF) molecules featuring an extremely small singlet-triplet energy gap and an efficient ISC process represent an enormous breakthrough for the PDT process. Consequently, the development of advanced TADF photosensitizers has become increasingly crucial and pressing. The most recent developments in TADF photosensitizers aimed at enhancing PDT efficiency for bio-applications are presented in this review. TADF photosensitizers with water dispersibility, targeting ability, activatable ability, and two-photon excitation properties are highlighted. Furthermore, the future challenges and perspectives of TADF photosensitizers in PDT are proposed.


Assuntos
Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fluorescência , Corantes Fluorescentes/química
3.
BMC Psychiatry ; 24(1): 41, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200532

RESUMO

BACKGROUND: To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic schizophrenia. METHODS: Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included. RESULTS: The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05). CONCLUSIONS: The risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia.


Assuntos
Risperidona , Esquizofrenia , Humanos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Citocromo P-450 CYP2D6/genética , Prolactina , Polimorfismo Genético
4.
Environ Toxicol ; 39(7): 3906-3919, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38567716

RESUMO

Many factors induced by environmental toxicants have made oxidative stress a risk factor for the intestinal barrier injury and growth restriction, which is serious health threat for human and livestock and induces significant economic loss. It is well-known that diquat-induced oxidative stress is implicated in the intestinal barrier injury. Although some studies have shown that mitochondria are the primary target organelle of diquat, the underlying mechanism remains incompletely understood. Recently, mitochondria-associated endoplasmic reticulum membranes (MAMs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and signal transduction. In this study, we investigated whether MAMs involved in intestinal barrier injury and mitochondrial dysfunction induced by diquat-induced oxidative stress in piglets and porcine intestinal epithelial cells (IPEC-J2 cells). The results showed that diquat induced growth restriction and impaired intestinal barrier. The mitochondrial reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased following diquat exposure. The ultrastructure of mitochondria and MAMs was also disturbed. Meanwhile, diquat upregulated endoplasmic reticulum stress marker protein and activated PERK pathway. Furthermore, loosening MAMs alleviated intestinal barrier injury, decrease of antioxidant enzyme activity and mitochondrial dysfunction induced by diquat in IPEC-J2 cells, while tightening MAMs exacerbated diquat-induced mitochondrial dysfunction. These results suggested that MAMs may be associated with the intestinal barrier injury and mitochondrial dysfunction induced by diquat in the jejunum of piglets.


Assuntos
Diquat , Retículo Endoplasmático , Mitocôndrias , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Diquat/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Suínos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Linhagem Celular , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Herbicidas/toxicidade , Células Epiteliais/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/patologia
5.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079984

RESUMO

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Proteínas do Tecido Nervoso , Doença de Parkinson , Mapas de Interação de Proteínas , Vesículas Sinápticas , Autopsia , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Vesículas Sinápticas/genética , Vesículas Sinápticas/metabolismo
6.
Anal Chem ; 94(19): 7004-7011, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35500230

RESUMO

The development of efficient sensors for detecting water content in organic solvents is highly desirable for various cases in the chemical industry. Relevant sensors based on luminescent materials are promising due to their superior sensitivity and visualization. However, reported luminescent probes are either aggregation-caused quenching-type molecules, which present an emission quenching effect in high water content, or aggregation induced emission-type luminogens, which exhibit weak emission in organic solvents. This factor narrows the targeted water-content sensing range. Herein, we developed a series of indoline-based donor-acceptor-donor luminogens involving twist intramolecular charge transfer and an aggregation-induced emission effect, which exhibited a unique "on-off-on" emission behavior in tetrahydrofuran with the continuous increase of water content from 0% to 99%. Simultaneously, the emission wavelength underwent a process of first red-shift and then blue-shift. Three-dimensional working curves based upon the log value of wavelength and emission intensity ratio versus water content in tetrahydrofuran were established with two-stage characteristics, aiming to visually detect a wide range of water content in organic solvents. Such a sensing method offers extra sensitivity, convenience, and accuracy.


Assuntos
Corantes Fluorescentes , Água , Corantes Fluorescentes/química , Furanos , Solventes/química , Espectrometria de Fluorescência , Água/química
7.
BMC Cancer ; 22(1): 352, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361159

RESUMO

BACKGROUND: This study aims to construct a new prognostic gene signature in survival prediction and risk stratification for patients with Head and neck squamous cell carcinoma (HNSCC). METHOD: The transcriptome profiling data and hallmark gene sets in the Molecular Signatures Database was used to explore the cancer hallmarks most relevant to the prognosis of HNSCC patients. Differential gene expression analysis, weighted gene co-expression network analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct the prognostic gene signature. The predictive ability of gene signature was verified in the TCGA HNSCC cohort as the training set and the GEO HNSCC cohorts (GSE41613 and GSE42743) as the validation sets, respectively. Moreover, the correlations between risk scores and immune infiltration patterns, as well as risk scores and genomic changes were explored. RESULTS: A total of 3391 differentially expressed genes in HNSCC were screened. Glycolysis and hypoxia were screened as the main risk factors for OS in HNSCC. Using univariate Cox analysis, 97 prognostic candidates were identified (P < 0.05). Top 10 important genes were then screened out by random forest. Using multiple combinatorial screening, a combination with less genes and more significant P value was used to construct the prognostic gene signature (RNF144A, STC1, P4HA1, FMNL3, ANO1, BASP1, MME, PLEKHG2 and DKK1). Kaplan-Meier analysis showed that patients with higher risk scores had worse overall survival (p < 0.001). The ROC curve showed that the risk score had a good predictive efficiency (AUC > 0.66). Subsequently, the predictive ability of the risk score was verified in the validation sets. Moreover, the two-factor survival analysis combining the cancer hallmarks and risk scores suggested that HNSCC patients with the high hypoxia or glycolysis & high risk-score showed the worst prognosis. Besides, a nomogram based on the nine-gene signature was established for clinical practice. Furthermore, the risk score was significantly related to tumor immune infiltration profiles and genome changes. CONCLUSION: This nine-gene signature associated with glycolysis and hypoxia can not only be used for prognosis prediction and risk stratification, but also may be a potential therapeutic target for patients with HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Perfilação da Expressão Gênica , Glicólise/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Hipóxia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
8.
J Clin Lab Anal ; 36(8): e24584, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35792028

RESUMO

BACKGROUND: The development of cardiac fibrosis involves the activation of cardiac fibroblasts (CFs) and their differentiation into myofibroblasts, which leads to the disruption of the extracellular matrix network. In the past few years, microRNAs (miRNA) have been described as potential targets for treating cardiac diseases. Although miR-338-3p has been shown to participate in the development of carcinoma, whether it affects cardiac fibrosis is unclear. METHODS: We examined the expression profiles of microRNAs in left ventricular samples of heart failure mice established by thoracic aortic constriction (TAC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-338-3p. CCK-8 assay/Transwell migration assay was used to measure the proliferation rate/migration of CFs. Luciferase reporter gene assay was used to test the binding between miR-338-3p and FGFR2. RESULTS: This study demonstrated that miR-338-3p was significantly decreased in thoracic aortic constriction mice. Cardiac miR-338-3p amounts were also reduced in patients with dilated cardiomyopathy (DCM). Interestingly, miR-338-3p overexpression inhibited α-SMA, COL1A1, and COL3A1 expression, as well as cell proliferation and migration in CFs. Bioinformatics analysis and dual-luciferase reporter assays revealed FGFR2 was targeted by miR-338-3p, whose antifibrotic effect could be alleviated by overexpression of FGFR2. Moreover, in DCM cases, serum miR-338-3p levels were markedly elevated in individuals with worse outcomes. CONCLUSIONS: The present study provides evidence that miR-338-3p suppresses cardiac fibroblast activation, proliferation, and migration by directly targeting FGFR2 in mice. Besides, serum miR-338-3p might constitute a potential prognostic biomarker of dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada , MicroRNAs , Animais , Proliferação de Células/genética , Fibrose , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos
9.
Molecules ; 26(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067825

RESUMO

Lupeol, a natural lupane-type pentacyclic triterpene, possesses various pharmacological properties, and its production attracts attention. Significant quantities of lupeol are deposited on the castor aerial organ surface and are easily extractable as a predominant wax constituent. Thus, castor might be considered as a potential bioreactor for the production of lupeol. The lupeol biosynthesis pathway is well known, but how it is regulated remains largely unknown. Among large numbers of castor cultivars, we targeted one accession line (337) with high levels of lupeol on its stem surface and low levels thereof on its hypocotyl surface, implicating that lupeol synthesis is differentially regulated in the two organs. To explore the underlying mechanisms, we did comparative transcriptome analysis of the first internode of 337 stem and the upper hypocotyl. Our results show that large amounts of auxin-related genes are differentially expressed in both parts, implying some possible interactions between auxin and lupeol production. We also found that several auxin-responsive cis-elements are present in promoter regions of HMGR and LUS genes encoding two key enzymes involved in lupeol production. Furthermore, auxin treatments apparently induced the expression levels of RcHMGR and RcLUS. Furthermore, we observed that auxin treatment significantly increased lupeol contents, whereas inhibiting auxin transport led to an opposite phenotype. Our study reveals some relationships between hormone activity and lupeol synthesis and might provide a promising way for improving lupeol yields in castor.


Assuntos
Ácidos Indolacéticos/metabolismo , Triterpenos Pentacíclicos/metabolismo , Ricinus/metabolismo , Óleo de Rícino/isolamento & purificação , Óleo de Rícino/metabolismo , Epiderme/metabolismo , Expressão Gênica/genética , Regulação da Expressão Gênica de Plantas/genética , Ácidos Indolacéticos/análise , Triterpenos Pentacíclicos/análise , Transdução de Sinais , Transcriptoma/genética
10.
Angew Chem Int Ed Engl ; 59(39): 17018-17025, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32701183

RESUMO

The fact that the lifetime of photoluminescence is often difficult to access because of the weakness of the emission signals, seriously limits the possibility to gain local bioimaging information in time-resolved luminescence probing. We aim to provide a solution to this problem by creating a general photophysical strategy based on the use of molecular probes designed for single-luminophore dual thermally activated delayed fluorescence (TADF). The structural and conformational design makes the dual TADF strong in both diluted solution and in an aggregated state, thereby reducing sensitivity to oxygen quenching and enabling a unique dual-channel time-resolved imaging capability. As the two TADF signals show mutual complementarity during probing, a dual-channel means that lifetime mapping is established to reduce the time-resolved imaging distortion by 30-40 %. Consequently, the leading intracellular local imaging information is serialized and integrated, which allows comparison to any single time-resolved signal, and leads to a significant improvement of the probing capacity.

11.
Angew Chem Int Ed Engl ; 59(19): 7548-7554, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073698

RESUMO

Developing luminescent probes with long lifetime and high emission efficiency is essential for time-resolved imaging. However, the practical applications usually suffer from emission quenching of traditional luminogens in aggregated states, or from weak emission of aggregation-induced emission type luminogens in monomeric states. Herein, we overcome this dilemma by a rigid-and-flexible alternation design in donor-acceptor-donor skeletons, to achieve a thermally activated delayed fluorescence luminogen with high emission efficiency both in the monomeric state (quantum yield up to 35.3 %) and in the aggregated state (quantum yield up to 30.8 %). Such a dual-phase strong and long-lived emission allows a time-resolved luminescence imaging, with an efficiency independent of probe pretreatment and probe concentration. The findings open opportunities for developing luminescent probes with a usage in larger temporal and spatial scales.

12.
Analyst ; 144(13): 4073-4080, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31165805

RESUMO

Ratiometric electrochemical sensors can provide a relatively accurate analysis of target analytes due to their self-calibration function. Herein, we report a simple ratiometric strategy for achieving the electrochemical detection of Cd(ii), Hg(ii), Pb(ii) and Zn(ii), as well as multiple cancer biomarkers by using metal sulfide nanoparticles as signal tags. A conductive polymer film of poly(2-amino terephthalic acid) (ATA) was electrochemically produced on a glassy carbon electrode (GCE) and doped with carbon nanotubes (CNTs) and mercaptosuccinic acid (MSA). Using Bi(iii) as an enhancer and internal reference in anodic stripping voltammetry, the MSA-CNT-ATA/GCE exhibited sensitive and distinguishable voltammetric responses to Cd(ii), Hg(ii), Pb(ii) and Zn(ii), with detection limits of 0.13, 0.49, 0.16 and 0.089 µg L-1, respectively. By using CdS, HgS, PbS and ZnS labeled secondary antibodies as the signal tags, alpha-fetoprotein, carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen were determined simultaneously according to the amounts of metal sulfide in the sandwich-type complexes, with detection limits of 0.11 pg mL-1, 0.68 mU mL-1, 1.4 mU mL-1 and 0.23 pg mL-1, respectively. This ratiometric approach has a wide scope in the electrochemical detection of heavy metal ions as well as immunoassays with metal ions serving as signal tags.


Assuntos
Biomarcadores Tumorais/sangue , Bismuto/química , Nanopartículas Metálicas/química , Metais Pesados/análise , Sulfetos/química , Anticorpos/imunologia , Biomarcadores Tumorais/imunologia , Antígeno Ca-125/sangue , Antígeno Ca-125/imunologia , Antígeno CA-19-9/sangue , Antígeno CA-19-9/imunologia , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/imunologia , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Imunoensaio/métodos , Limite de Detecção , Proteínas de Membrana/sangue , Proteínas de Membrana/imunologia , Metais Pesados/química , Nanotubos de Carbono/química , Ácidos Ftálicos/química , Polímeros/química , Reprodutibilidade dos Testes , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia
13.
Proc Natl Acad Sci U S A ; 112(16): 5225-30, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25847999

RESUMO

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipirina/análogos & derivados , Transtornos Cognitivos/tratamento farmacológico , Administração Oral , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Amiloide/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Antipirina/administração & dosagem , Antipirina/química , Antipirina/farmacologia , Antipirina/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Dendritos/efeitos dos fármacos , Dendritos/patologia , Edaravone , Humanos , Inflamação/patologia , Camundongos Transgênicos , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Presenilina-1/metabolismo , Agregação Patológica de Proteínas/complicações , Agregação Patológica de Proteínas/tratamento farmacológico , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas tau/metabolismo
14.
J Gene Med ; 19(11): 360-365, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28990350

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people. The present study aimed to investigate the association of the DNMT3b variants rs2424913, rs998382 and rs2424932 with PD in a Chinese Han population. METHODS: We studied 487 Chinese Han patients with sporadic PD and 485 healthy age-, sex- and ethnicity-matched controls. DNA was extracted from peripheral blood leukocytes and the individual genotypes were determined using the SNaPshot method. RESULTS: We found that the rs2424932 and rs998382 variants were significantly associated with an increased risk of PD compared to the controls [rs2424932: odds ratio (OR) = 1.632, 95% confidence interval (CI) = 1.108-2.406, p = 0.013; rs998382: OR = 1.612, 95% CI = 1.103-2.382, p = 0.014]. Subgroup analysis suggested that female patients carrying the rs2424932 or rs998382 variants were more likely to develop PD than female controls (rs2424932: OR = 3.863, 95% CI = 2.004-7.445, p < 0.001; rs998382: OR = 3.679, 95% CI = 1.943-6.964, p < 0.001). Haplotype analysis indicated that the three variants comprised one block and that the Trs2424913 -Crs998382 -A rs2424932 haplotype was correlated with an increased risk of PD (p = 0.0046), especially for Chinese Han females (p < 0.0001). CONCLUSIONS: The results of the present study strongly suggest that DNMT3b variants are associated with PD in the Chinese Han people, especially females.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Povo Asiático/genética , China , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/enzimologia , Doença de Parkinson/etnologia , Fatores de Risco , Fatores Sexuais , DNA Metiltransferase 3B
15.
Growth Factors ; 34(1-2): 19-32, 2016 02.
Artigo em Inglês | MEDLINE | ID: mdl-27144323

RESUMO

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Proliferação de Células , Células-Tronco Embrionárias/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neurais/metabolismo , Via de Sinalização Wnt , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/fisiologia , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Células-Tronco Neurais/fisiologia , Regulação para Cima , beta Catenina/metabolismo
16.
Mol Cell Biochem ; 399(1-2): 229-36, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25336270

RESUMO

L-arginine (L-Arg) uptake is mediated by members of cationic amino acid transporter (CAT) family and may coincide with the induction of nitric oxide synthases (NOS). The present study was conducted to investigate the extracellular concentrations of L-Arg regulating the CAT-1, CAT-4 and inducible NOS (iNOS) in chick intestinal epithelial cells. The cells were cultured for 4 days in Arg-free Dulbecco's modified Eagle's medium containing 10, 100, 200, 400, or 600 µM L-Arg. Cell viability, nitric oxide (NO) concentrations, uptake and metabolism of L-[3H]-Arg as well as expression of CAT-1, CAT-4, and iNOS were determined. Our results showed that L-Arg enhances cell growth with a maximal response at 10-400 µM. Addition of 100, 200, or 400 µM L-Arg increased the L-[3H]-Arg uptake, which was associated with greater conversion of L-[3H]-citrulline and NO production in comparison with 10 µM L-Arg group. Increasing extracellular concentrations of L-Arg from 10 to 400 µM dose dependently increased the levels of CAT-1 mRNA and protein, while no effect on CAT-4 mRNA abundance was found. Furthermore, supplementation of 100, 200, or 400 µM L-Arg upregulated the expression of iNOS mRNA, and the relative protein levels for iNOS in 200 and 400 µM L-Arg groups were higher than those in 10 and 100 µM L-Arg groups. Collectively, we conclude that the CAT-1 isoform plays a role in L-Arg uptake, and L-Arg-mediated elevation of NO via iNOS promotes the growth of chick intestinal epithelial cells.


Assuntos
Arginina/fisiologia , Proteínas Aviárias/metabolismo , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Proliferação de Células , Células Epiteliais/fisiologia , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Transporte Biológico , Células Cultivadas , Embrião de Galinha , Expressão Gênica , Mucosa Intestinal/citologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética
17.
Int J Gynecol Pathol ; 34(2): 126-31, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25675180

RESUMO

Tumor-to-tumor metastasis is a rare phenomenon. On the basis of our review of international literature, there have been 7 reports of tumor-to-tumor metastasis cases involving ovary neoplasms as the recipient. However, an ovarian granulosa cell tumor has not been reported to be a recipient. Here, we report the first case of gastric signet-ring cell carcinoma metastasis to a bilateral ovarian granulosa cell tumor. Awareness of this phenomenon is important to avoid incorrect diagnoses when encountering unusual morphologic features in ovarian granulosa cell tumors.


Assuntos
Carcinoma de Células em Anel de Sinete/patologia , Tumor de Células da Granulosa/patologia , Metástase Neoplásica/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Adulto , Feminino , Humanos
18.
Proc Natl Acad Sci U S A ; 109(38): 15389-94, 2012 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-22908272

RESUMO

Conditional mutations are essential for determining the stage- and tissue-specific functions of genes. Here we achieve conditional mutagenesis in zebrafish using FT1, a gene-trap cassette that can be stably inverted by both Cre and Flp recombinases. We demonstrate that intronic insertions in the gene-trapping orientation severely disrupt the expression of the host gene, whereas intronic insertions in the neutral orientation do not significantly affect host gene expression. Cre- and Flp-mediated recombination switches the orientation of the gene-trap cassette, permitting conditional rescue in one orientation and conditional knockout in the other. To illustrate the utility of this system we analyzed the functional consequence of intronic FT1 insertion in supv3l1, a gene encoding a mitochondrial RNA helicase. Global supv311 mutants have impaired mitochondrial function, embryonic lethality, and agenesis of the liver. Conditional rescue of supv311 expression in hepatocytes specifically corrected the liver defects. To test whether the liver function of supv311 is required for viability we used Flp-mediated recombination in the germline to generate a neutral allele at the locus. Subsequently, tissue-specific expression of Cre conditionally inactivated the targeted locus. Hepatocyte-specific inactivation of supv311 caused liver degeneration, growth retardation, and juvenile lethality, a phenotype that was less severe than the global disruption of supv311. Thus, supv311 is required in multiple tissues for organismal viability. Our mutagenesis approach is very efficient and could be used to generate conditional alleles throughout the zebrafish genome. Furthermore, because FT1 is based on the promiscuous Tol2 transposon, it should be applicable to many organisms.


Assuntos
Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Alelos , Animais , DNA Nucleotidiltransferases/metabolismo , Elementos de DNA Transponíveis , Hepatócitos/citologia , Integrases/metabolismo , Fígado/metabolismo , Fígado/patologia , Mitocôndrias/enzimologia , Modelos Genéticos , Mutagênese , Mutagênicos , Mutação , Fenótipo , Reação em Cadeia da Polimerase/métodos , RNA Helicases/metabolismo , Recombinação Genética
19.
J Basic Microbiol ; 55(1): 121-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24115208

RESUMO

The legume species of Astragalus as traditional Chinese medicine source and environmental protection plants showed an extensive distribution in the arid region of northwestern China. However, few rhizobia associating with Astragalus have been investigated in this region so far. In this study, 78 endophytic bacteria were isolated from root nodules of 12 Astragalus species and characterized by the PCR-RFLP of 16S rRNA gene and symbiotic genes together with the phylogenetic analysis. Results showed that the majority (53%) of isolates are non-nodulating Agrobacterium sp. and the rest are Mesorhizobium genomic species (41%), Ensifer spp. and Rhizobium gallicum (6%), respectively. Mesorhizobium genomic species are broadly distributed in the Astragalus symbioses and most of them share similar symbiotic genes. It seems that horizontal gene transfer occurred frequently among different genomic species independent of their original hosts and sites. Astragalus adsurgens is nodulated by a widely range of rhizobial species in the nodulation test, revealing that it could play an important role in diversification of Astragalus symbionts and that might be a reason for its wide adaptation to diverse environments.


Assuntos
Astrágalo/microbiologia , Endófitos/isolamento & purificação , Endófitos/fisiologia , Rhizobiaceae/isolamento & purificação , Rhizobiaceae/fisiologia , Nódulos Radiculares de Plantas/microbiologia , Agrobacterium/genética , Agrobacterium/isolamento & purificação , Agrobacterium/fisiologia , China , Endófitos/classificação , Transferência Genética Horizontal , Genes Bacterianos , Genes de RNAr , Variação Genética , Mesorhizobium/genética , Mesorhizobium/isolamento & purificação , Mesorhizobium/fisiologia , Filogenia , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Rhizobiaceae/genética , Rhizobium/genética , Rhizobium/isolamento & purificação , Rhizobium/fisiologia , Análise de Sequência de DNA , Simbiose/genética
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