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1.
Plant Physiol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662408

RESUMO

Brassinosteroids (BRs) play essential roles in regulating plant growth and development, however, gaps still remain in our understanding of the BR signaling network. We previously cloned a grain length quantitative trait locus qGL3, encoding a rice (Oryza sativa L.) protein phosphatase with Kelch-like repeat domain (OsPPKL1), that negatively regulates grain length and BR signaling. To further explore the BR signaling network, we performed phosphoproteomic analysis to screen qGL3-regulated downstream components. We selected a 14-3-3 protein OsGF14b from the phosphoproteomic data for further analysis. qGL3 promoted the phosphorylation of OsGF14b and induced the interaction intensity between OsGF14b and OsBZR1. In addition, phosphorylation of OsGF14b played an important role in regulating nucleocytoplasmic shuttling of OsBZR1. The serine acids (Ser258Ser259) residues of OsGF14b play an essential role in BR-mediated responses and plant development. Genetic and molecular analyses indicated that OsGF14b functions as a negative regulator in BR signaling and represses the transcriptional activation activity of OsBZR1. Collectively, these results demonstrate that qGL3 induces the phosphorylation of OsGF14b, which modulates nucleocytoplasmic shuttling and transcriptional activation activity of OsBZR1, to eventually negatively regulate BR signaling and grain length in rice.

2.
Mol Cell ; 81(16): 3323-3338.e14, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352207

RESUMO

The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m7G) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m7G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. Mechanistically, we find increased abundance of m7G-modified tRNAs, in particular Arg-TCT-4-1, and increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon. Accordingly, Arg-TCT expression is elevated in many tumor types and is associated with patient survival, and strikingly, overexpression of this individual tRNA induces oncogenic transformation. Thus, METTL1-mediated tRNA modification drives oncogenic transformation through a remodeling of the mRNA "translatome" to increase expression of growth-promoting proteins and represents a promising anti-cancer target.


Assuntos
Carcinogênese/genética , Metiltransferases/genética , Neoplasias/genética , tRNA Metiltransferases/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Metilação , Neoplasias/patologia , Oncogenes/genética , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
3.
J Diabetes Res ; 2021: 5495219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368364

RESUMO

Background: Relative to nondiabetic patients, percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with inferior clinical outcomes. We aimed to evaluate the outcomes of drug-coated balloon (DCB) in diabetic versus nondiabetic patients. Methods and Results: In this observational, prospective, multicenter study, we compared the outcomes of patients with and without DM after undergoing PCI with DCBs. Target lesion failure (TLF) was analyzed as primary endpoint. Secondary endpoints were the rates of target lesion revascularization (TLR), major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), and any revascularization. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics. Among 2,306 eligible patients, 578 with DM and 578 without DM had similar propensity scores and were included in the analyses. During follow-up (366 ± 46 days), compared with DM patients, patients without DM were associated with a lower yearly incidence of TLF (2.77% vs. 5.36%; OR, 1.991; 95% CI, 1.077 to 3.681; P = 0.025) and TLR (1.90% vs. 4.15%; OR, 2.233; 95% CI, 1.083 to 4.602; P = 0.026). No significant differences were observed with regards to rates of MACE (OR: 1.580, 95% CI: 0.912-2.735; P = 0.100), cardiac death (OR: 1.608, 95% CI: 0.523-4.946; P = 0.403), MI (OR: 4.042, 95% CI: 0.855-19.117; P = 0.057), and any revascularization (OR: 1.534, 95% CI: 0.983-2.393; P = 0.058). Conclusions: Diabetic patients experience higher TLF and TLR rates following DCB angioplasty without substantial increase in the risk of MACE, cardiac death, MI, or revascularization.

4.
Clin Res Cardiol ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313800

RESUMO

BACKGROUNDS: Although drug-eluting stents are the most common interventional devices for patients with coronary disease, drug-coated balloons (DCBs) represent a novel therapeutic alternative in certain scenarios. This prospective, observational all-comers study explored the clinical outcomes of DCB use in patients with coronary lesions. METHODS AND RESULTS: All patients treated with DCBs were enrolled in this study, including patients with in-stent restenosis (ISR) or de novo lesions. The primary outcome was the target lesion revascularization (TLR) rate at one year. We enrolled 2306 patients with 2660 lesions and performed DCB angioplasty in 399 patients (17.3%) with ISR and 1907 patients (82.7%) with de novo lesions. During follow-up (366 ± 46 days), the TLR rate was lower in the de novo lesion group (1.31%) compared to the ISR group (7.02%) [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.101-0.305, p < 0.001]. Patients with de novo lesions had a lower yearly incidence of MACE compared to ISR patients (2.73 vs. 9.27%, respectively, OR 0.274, 95% CI 0.177-0.424, p < 0.001) and a lower incidence of any revascularization (5.09 vs. 13.03%, OR 0.358, 95% CI 0.251-0.510, p < 0.001). No significant differences between groups were observed in the rates of cardiac death (OR 0.783, 95% CI 0.258-2.371, p = 0.655) or MI (OR 0.696, 95% CI 0.191-2.540, p = 0.573). CONCLUSIONS: DCB angioplasty in this all-comers, real-world, prospective study was safe and efficient with low TLR and MACE rates. Thus, DCB appears to be an attractive alternative for the stent-less treatment of de novo coronary lesions. ISR in-stent restenosis; OR odds ratio; CI confidence interval; TLR target lesion revascularization; MACE major adverse cardiovascular events; MI myocardial infraction. MACE defined as the composite outcome of cardiac death, myocardial infarction, and target vessel revascularization. Any revascularization includes any percutaneous coronary intervention, and coronary artery bypass grafting.

5.
Brief Bioinform ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279571

RESUMO

Deregulation of gene expression is associated with the pathogenesis of numerous human diseases including cancer. Current data analyses on gene expression are mostly focused on differential gene/transcript expression in big data-driven studies. However, a poor connection to the proteome changes is a widespread problem in current data analyses. This is partly due to the complexity of gene regulatory pathways at the post-transcriptional level. In this study, we overcome these limitations and introduce a graph-based learning model, PTNet, which simulates the microRNAs (miRNAs) that regulate gene expression post-transcriptionally in silico. Our model does not require large-scale proteomics studies to measure the protein expression and can successfully predict the protein levels by considering the miRNA-mRNA interaction network, the mRNA expression, and the miRNA expression. Large-scale experiments on simulations and real cancer high-throughput datasets using PTNet validated that (i) the miRNA-mediated interaction network affects the abundance of corresponding proteins and (ii) the predicted protein expression has a higher correlation with the proteomics data (ground-truth) than the mRNA expression data. The classification performance also shows that the predicted protein expression has an improved prediction power on cancer outcomes compared to the prediction done by the mRNA expression data only or considering both mRNA and miRNA. Availability: PTNet toolbox is available at http://github.com/CompbioLabUCF/PTNet.

6.
Environ Res ; 203: 111772, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34324851

RESUMO

Neonicotinoids (NEOs) are extensively applied in global agricultural production for pest control but have adverse effects on human health. In this study, the concentrations of six NEOs and three characteristic metabolites were investigated by collecting 200 serum samples from an elderly population in China. Results showed that the NEOs and their metabolites were widely detected (89%-98 %) in the serum samples from the osteoporosis (OP) (n = 120) and non-OP (n = 80) population, and their median concentrations ranged from 0.04 ng/mL to 5.99 ng/mL and 0.01 ng/mL to 2.02 ng/mL, respectively. N-desmethyl-acetamiprid (ACE-dm) was the most abundant NEOs in the serum samples. Gender-related differences were found in concentrations of most NEOs and their metabolites in serum, with males having higher target analytes than females. Significantly (p < 0.05) positive correlations were observed among most NEO concentrations, suggesting that exposure source of these substances is common or related. However, associations between the concentrations of characteristic metabolites and their corresponding NEOs were insignificant, probably because the exogenous intake are the primary sources of metabolites of NEOs instead of the internal biotransformation. The associations between NEO concentrations (i.e., ACE-dm, dinotefuran, and olefin-imidacloprid) and OP (OR = 2.33-6.92, 95 % CI = 0.37-16.9, p-trend < 0.05) indicate that NEO exposure is correlated with increased odds of prevalent OP. This study is the first to document the profiles of NEOs and their metabolites in serum samples collected from an elderly population in South China and examine the relationships between NEO exposure and OP.

7.
Psychophysiology ; 58(10): e13886, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34173239

RESUMO

Although the neural correlates of novelty and appropriateness of creative insight during cognitive tasks have been investigated in several studies, they have not been examined during mental distress in a psychotherapeutic setting. This study aimed to reveal the promoting effects of novelty and appropriateness processing on therapeutic insight in a micro-psychotherapeutic setting. We examined the effects of appropriateness (between-subject factor: appropriateness group, 20 participants; inappropriateness group, 21 participants) by manipulating the preceding negative scenarios that either fit or did not fit the subsequent solutions, and those of novelty (within-subject factor) by varying the linguistic expressions for describing solutions (metaphorical, literal, or problem-restatement). Event-related functional magnetic resonance images were collected. We found the following effects: an interactive effect of the two factors on insightfulness and activation in the bilateral hippocampus and amygdala, right superior frontal gyrus, and left superior/middle temporal gyrus; a simple effect of novelty on activation in the bilateral inferior frontal gyrus, fusiform gyrus, and inferior/middle occipital gyrus; and a simple effect of appropriateness on activation in the left inferior parietal lobule. Our findings indicate that solutions with high novelty and appropriateness generate the highest levels of therapeutic insightfulness as well as the strongest activation in the hippocampus and amygdala, which may be involved in episodic memory encoding.

8.
J Neuroinflammation ; 18(1): 64, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653377

RESUMO

BACKGROUND: Immune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. γδ T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether γδ T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI. METHODS: Basso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes. RESULTS: In this study, we demonstrated that TCRδ-/- mice present improved neurological recovery after SCI. γδ T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2-/- and CCR2-/- mouse strains. Furthermore, reconstitution of TCRδ-/- mice with γδ T cells extracted from CCR2-/- mice also showed similar results to CCL2 and CCR2 deficient mice. CONCLUSIONS: In conclusion, γδ T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of γδ T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.

9.
Front Immunol ; 11: 580304, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193380

RESUMO

Gamma-delta (γδ) T cells are a subset of T cells that promote the inflammatory responses of lymphoid and myeloid lineages, and are especially vital to the initial inflammatory and immune responses. Given the capability to connect crux inflammations of adaptive and innate immunity, γδ T cells are responsive to multiple molecular cues and can acquire the capacity to induce various cytokines, such as GM-CSF, IL-4, IL-17, IL-21, IL-22, and IFN-γ. Nevertheless, the exact mechanisms responsible for γδ T cell proinflammatory functions remain poorly understood, particularly in the context of the central nervous system (CNS) diseases. CNS disease, usually leading to irreversible cognitive and physical disability, is becoming a worldwide public health problem. Here, we offer a review of the neuro-inflammatory and immune functions of γδ T cells, intending to understand their roles in CNS diseases, which may be crucial for the development of novel clinical applications.


Assuntos
Doenças do Sistema Nervoso Central/imunologia , Inflamação/imunologia , Linfócitos Intraepiteliais/imunologia , Células Th17/imunologia , Animais , Sistema Nervoso Central , Citocinas/metabolismo , Humanos , Imunidade Inata , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo
10.
Chemosphere ; 261: 127682, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32711240

RESUMO

Neonicotinoid insecticides (NEOs) have become the most widely used insecticides worldwide, and they are ubiquitous in food (i.e., fruit juices). In the present study, occurrence of seven NEOs and four metabolites (m-NEOs) in 400 fruit juice samples were investigated. NEOs and m-NEOs were frequently detected (65%-86%) in fruit juice samples. The median residues of NEOs and m-NEOs were ranged from 0.06 ng/mL to 0.94 ng/mL. Seasonal variations in NEOs and m-NEOs in fruit juices were found, indicating that the target analyte residues during the dry season were remarkably higher than those of residues during wet season. The relative potency factor (RPF) method was used to integrate individual NEOs into a single metric [imidacloprid (IMIRPF)] representing the intakes of IMI equivalent to total NEOs for each fruit juice sample. The estimated daily intake (EDI) of total NEOs for the general Chinese population was obtained. The median IMIRPF for total fruit juices was 13.4 ng/g, and the median EDI of NEOs was 18.2 ng/kg bw/day for the general population. Although the EDIs in this study were considerably lower than the acceptable daily intake (60 µg/kg bw/day, ADI), the dietary exposure risks for total NEOs should not be ignored because of the increasing usage of NEOs and their ubiquitous presence in fruit juices in China. To the best of our knowledge, this report was the first time to document residues of NEO and m-NEO in fruit juice samples collected from China.


Assuntos
Exposição Dietética/estatística & dados numéricos , Sucos de Frutas e Vegetais/análise , Inseticidas/análise , Neonicotinoides/análise , Grupo com Ancestrais do Continente Asiático , China , Coleta de Dados , Frutas/química , Humanos , Nitrocompostos , Nível de Efeito Adverso não Observado , Projetos de Pesquisa , Estações do Ano , Verduras/química
11.
Front Chem ; 8: 242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411654

RESUMO

In this paper, the effect of sodium alginate (SA) on the flotation separation of molybdenite (MoS2) from chalcopyrite using kerosene as collector was systematically investigated. The results of single-mineral micro-flotation tests indicated that SA exhibited strong depression on chalcopyrite flotation while it imposed no impact on the floatability of molybdenite. However, in the chalcopyrite-molybdenite mixed-mineral flotation system, the presence of chalcopyrite significantly increased the depressing effect of SA on molybdenite flotation, leading to a considerable reduction in the flotation selectivity. The negative impact of chalcopyrite on the performance of SA in molybdenite flotation was eliminated by adding a certain dosage of kerosene prior to SA. A concentrate containing 53.43% of molybdenum (Mo) was obtained at 76.90% of recovery using 19 mg/L kerosene and 40 mg/L SA at pH 5.4. Zeta potential measurements indicated that the adsorption of SA on chalcopyrite surfaces was stronger than that on molybdenite surfaces, which agreed with the single-mineral flotation test results. The adsorption of SA on chalcopyrite was further confirmed to be chemisorption by Fourier-transform infrared spectroscopy (FTIR) spectra analyses. When Cu2+ appeared in solution, the flotation of molybdenite was strongly depressed by SA. Mechanism analyses indicated that more active sites were generated on molybdenite surfaces after the addition of Cu2+, thus promoting the adsorption of SA.

12.
Front Behav Neurosci ; 14: 8, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116589

RESUMO

Little evidence exists to confirm whether the sensory-related neural activity that occurs when observing others in pain is highly responsive to empathy for pain. From a perspective of intervention, the present study employed placebo manipulation with a transferable paradigm to explore whether the sensory regional activation that occurs when viewing pictures of others in pain could be modulated by the placebo effect. We first performed a screening behavioral experiment for selecting placebo responders and then entered them into a functional magnetic resonance (fMRI) experiment in which they were exposed to the same conditions as before. Participants were informed that it was equally possible to be assigned to the treatment group (placebo manipulation) or the no-treatment group (control); they all, in fact, received treatment and placebo effect would be detected by comparing placebo conditions and no-placebo control condition. Each participant experienced a phase of reinforcing placebo belief with pain in self and a phase of testing transferable placebo effect on empathy for pain. As a result, we found significant activation in sensory areas, including the posterior insula (PI) and the postcentral gyrus, and in the middle cingulate cortex while participants observed pictures of others in pain. More importantly, for the first time, we observed relieved activation in the PI modulated by the placebo effect only associated with pain pictures but not with no-pain pictures. This suggests that sensory activity in the PI might be involved in the processing for empathic pain. This new approach sheds light on research and applications in clinical settings.

13.
Int J Biol Sci ; 16(8): 1335-1348, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210723

RESUMO

Cardiac remodeling is a major early event of heart failure, which is regulated by multiple signaling pathways. Here, we demonstrate that TBC1D25 is upregulated during pathological cardiac remodeling. The aim of this study is to determine the role of TBC1D25 in cardiac remodeling and to illustrate the underlying molecular mechanism. Specifically, cardiac remodeling was induced in TBC1D25-KO mice and their wild-type control mice through partial transverse aortic constriction (TAC) of aortic arch. Knockout TBC1D25 exacerbated cardiac hypertrophy, fibrosis and dysfunction. Meanwhile, TBC1D25 overexpression in both H9C2 cells and NRCMs alleviate Angiotensin II-induced cardiomyocyte hypertrophy in vitro. Moreover, TBC1D25 deficiency increases the phosphorylation levels of TAK1 and its downstream molecular (JNK and p38), whereas overexpressed TBC1D25 inhibits phosphorylation of TAK1, JNK and p38. And TAK1 is the key molecule in this process. Furthermore, we demonstrated that TBC1D25 could directly interacts with TAK1 by immunoprecipitation assay and GST pull-down assay, and the interaction needs the amino acids from at least 138 to 226 in the C-terminal region of TBC1D25 and from 1 to 300 in the C-terminal region of TAK1. We conclude that TBC1D25 suppresses pathological cardiac remodeling via regulating TAK1-JNK/p38 signaling pathway, which suggests that TBC1D25 will likely become a promising therapeutic target for heart failure.

14.
Cell Cycle ; 18(23): 3263-3274, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31627713

RESUMO

Objective: To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury.Methods: The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITCH, TNF-α and IL-6 were measured by qRT-PCR. Protein levels of ITCH, NF-κB, TNF-α and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITCH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox.Results: Dox reduced HL-1 cell viability and activated NF-κB pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITCH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITCH. Besides, ITCH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITCH expression, increased TNF-α and IL-6 level, and promoted NF-κB expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITCH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy.Conclusion: miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITCH/NF-κB pathway.


Assuntos
Cardiomiopatias/genética , Traumatismos Cardíacos/genética , Miocárdio/metabolismo , Ubiquitina-Proteína Ligases/genética , Animais , Antagomirs/farmacologia , Apoptose/efeitos dos fármacos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/patologia , Humanos , Interleucina-6/genética , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Miocárdio/patologia , NF-kappa B/genética , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/genética
15.
Waste Manag ; 98: 144-150, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446254

RESUMO

It is critical to separate carbon from fly ash due to its increasing amount being produced per year and component requirements for secondary utilizations. Flotation is an efficient technique to fulfill this task. Effects of diesel emulsification using sodium petroleum sulfonate on unburned carbon flotation from a fly ash sample were studied. Flotation tests showed that carbon recovery was increased from 41% to 86% using the emulsified collector at the same dosage level (0.5 kg/ton) as diesel. Zeta potential measurements indicated that both the carbon and emulsified collector droplets carried negative charges within the studied pH range. For fly ash particles with high carbon content, adsorption bands of carbonyl bond (CO) were detected in the FTIR spectra, which agreed with the XPS characterization findings. XPS analysis indicated that the emulsified diesel (ED) collector interacted more intensively with the surface carbon-oxygen groups relative to the normal diesel collector. Finally, the improved efficiency of ED is proved to be related to its polar groups and reduced oil droplet size. The polar groups of ED (mainly sulfonate) interacted with the surface oxygen containing groups (e.g., CO and COOH) through hydrogen bonding and Lewis acid base interaction.


Assuntos
Cinza de Carvão , Petróleo , Carbono , Minerais , Material Particulado , Sódio
16.
Neuroimage ; 200: 540-551, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254647

RESUMO

Although the effects of cognitive reappraisal in regulating negative emotion are generally well documented, its regulatory effects are usually not very strong because the ordinary reappraisals employed in previous studies were insufficient to overcome the mental set or response bias toward negative situations. In this study, we developed a new strategy employing creative reappraisals that provides an insightful reinterpretation of the negative stimulus. We believe this approach, through adopting a guided (creative) reappraisal rather than self-generation strategy, will greatly improve the emotion regulation effect of reappraisal through activating the neural networks representing the process of deep and structural mental representational change accompanied by the feeling of positive emotion and mental reward. The behavioral results suggested that 1) regarding the transient regulatory effect, creative reappraisal resulted in a positive rating for standardized negative pictures; 2) creative reappraisal had a long-lasting effect in reducing negative affect. In parallel with these behavioral results, the imaging data indicated that 1) creative reappraisal was specifically associated with greater engagement of the amygdala and hippocampus as well as regions in the ventral striatum, and 2) the engagement of the amygdala predicted the transient regulatory effect of creative reappraisal, while the involvement of the hippocampus and the ventral striatum predicted long-term regulatory effects. These findings suggest that the superior regulatory effect of creative reappraisal could be mediated by amygdala-based salient emotional arousal, hippocampus-based new association formation, and striatum-based mental rewarding to lead to a novel and positive experience that could be kept in long-term memory. This research indicates the key role of creative insight in reappraisal and presents a novel and highly efficient reappraisal strategy.


Assuntos
Afeto/fisiologia , Tonsila do Cerebelo/fisiologia , Associação , Mapeamento Encefálico/métodos , Corpo Estriado/fisiologia , Regulação Emocional/fisiologia , Hipocampo/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Recompensa , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
17.
Cogn Affect Behav Neurosci ; 19(4): 1022-1035, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30809763

RESUMO

This study was designed to determine whether metaphorical solutions to mental distress problems result in an insightful mental experience and activate the hippocampus and amygdala: areas associated with insight. We recruited 22 healthy university students. Trials presented 75 micro-counseling scenarios while event-related functional magnetic resonance imaging (fMRI) was applied to detect neural responses. Each scenario included a mental distress problem and one of the following solution types: metaphorical, literal, or problem-restatement. The results revealed that, compared with literal solutions or problem-restatement solutions, metaphorical solutions activated two neural networks: one associated with basic metaphorical language processing (i.e., the left inferior frontal gyrus and middle and superior temporal gyri), and a specific network associated with insightful problem solving (i.e., the bilateral hippocampus, amygdala, and fusiform gyrus). Our findings indicate that the use of metaphorical solutions to mental distress problems reliably produces salient neural activities for insight.


Assuntos
Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Hipocampo/fisiologia , Metáfora , Rede Nervosa/fisiologia , Resolução de Problemas/fisiologia , Angústia Psicológica , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
18.
Biol Chem ; 400(4): 533-544, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30265647

RESUMO

Acute myocardial infarction (AMI) induced by ischemia hypoxia severely threatens human life. Cell apoptosis of neurocytes was identified to mediate the pathogenesis, while the potential mechanism was still unclear. Sprague Dawley (SD) rats were used to establish the AMI rat model. Real-time polymerase chain reaction (PCR) and Western blot were performed to detect gene expression in mRNA and protein levels, respectively. A TUNEL assay was carried out to determine cell apoptosis. The relationship between SRY-related HMG-box (SOX7) and miR-128 was verified using luciferase reporter assay. The expression of SOX7 was decreased, while miR-128 was increased in AMI rats and ischemia hypoxia (IH) induced H9c2 cells. Hypoxia induction significantly promoted the expression of interleukin (IL)-33 and soluble ST2 (sST2), and also promoted cell apoptosis. MiR-128 targets SOX7 to regulate its expression. Down-regulated miR-128 reversed the effects of IH on expression of SOX7, sST2 and cell apoptosis, while down-regulated sST2 abolished the effects of miR-128 inhibitor. In addition, overexpressed IL-33 abolished the effects of miR-128 inhibitor that induced by IH on the expression of SOX7 and cell apoptosis. In vivo experiments validated the expression of miR-128 on cell apoptosis. The present study indicated that miR-128 modulated cell apoptosis by targeting SOX7, which was mediated by IL-33/sST2 signaling pathway.


Assuntos
Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , MicroRNAs/metabolismo , Isquemia Miocárdica/metabolismo , Fatores de Transcrição SOXF/metabolismo , Doença Aguda , Animais , Apoptose , Células Cultivadas , Isquemia Miocárdica/patologia , Ratos , Ratos Sprague-Dawley
19.
Front Psychiatry ; 9: 629, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555358

RESUMO

Objective: To detect the changes of gray matter volume (GMV) and their correlation with severity of symptom in patients with post-traumatic stress disorder (PTSD) who were defined with updated DSM-5 diagnostic criteria. Method: 71 participants were assigned into PTSD group (n = 35) or trauma-exposed control (TEC) group (n = 36) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Voxel-based morphometry analysis was used to detect alterations in GMV in the PTSD group. Results: We found that the PTSD group had larger GMV in the left middle temporal gyrus (MTG) and in the right dorsal medial prefrontal cortex (dmPFC), and smaller GMV in the region of the right temporal pole (TP) than the TEC group. We also found that PTSD Checklist for DSM-5 (PCL-5) scores correlated positively with the left MTG and right dmPFC GMV, and negatively with left TP GMV. These correlations were consistent with the findings of the between-group comparisons. Conclusions: GMV alterations in the MTG, dmPFC, and TP are detected in the group comparisons and correlated with symptom severity when classifying PTSD individuals according to DSM-5 diagnostic criteria within an earthquake-exposed population.

20.
Nature ; 561(7724): 556-560, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30232453

RESUMO

N6-methyladenosine (m6A) modification of mRNA is emerging as an important regulator of gene expression that affects different developmental and biological processes, and altered m6A homeostasis is linked to cancer1-5. m6A modification is catalysed by METTL3 and enriched in the 3' untranslated region of a large subset of mRNAs at sites close to the stop codon5. METTL3 can promote translation but the mechanism and relevance of this process remain unknown1. Here we show that METTL3 enhances translation only when tethered to reporter mRNA at sites close to the stop codon, supporting a mechanism of mRNA looping for ribosome recycling and translational control. Electron microscopy reveals the topology of individual polyribosomes with single METTL3 foci in close proximity to 5' cap-binding proteins. We identify a direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h). METTL3 promotes translation of a large subset of oncogenic mRNAs-including bromodomain-containing protein 4-that is also m6A-modified in human primary lung tumours. The METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformation. METTL3 depletion inhibits tumorigenicity and sensitizes lung cancer cells to BRD4 inhibition. These findings uncover a mechanism of translation control that is based on mRNA looping and identify METTL3-eIF3h as a potential therapeutic target for patients with cancer.


Assuntos
Carcinogênese , Fator de Iniciação 3 em Eucariotos/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metiltransferases/metabolismo , Biossíntese de Proteínas , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Animais , Linhagem Celular Tumoral , Ciclização , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Conformação de Ácido Nucleico , Polirribossomos/química , Polirribossomos/metabolismo , Ligação Proteica , RNA Mensageiro/genética
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