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BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.
Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Filogenia , Proteínas de Plantas , Estresse Salino , Fatores de Transcrição , Oryza/genética , Oryza/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Família Multigênica , Perfilação da Expressão Gênica , Cromossomos de Plantas/genéticaRESUMO
The role of metastasis-associated gene 1 (MTA1) in the metastasis of non-small cell lung cancer (NSCLC) has been proved, but its role in the tumor microenvironment is still insufficient. The study was performed to explore the correlation between MTA1 and tumor-associated macrophages (TAMs) in NSCLC. The expression profile data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from TCGA database. The tumor-infiltrating immune cells in each LUAD and LUSC patient were estimated using the CIBERSORT method. Then, the online TIMER database containing multiple algorithms was used to analyze the relationship between MTA1 and TAMs. Besides, correlations between MTA1 and TAMs markers were also explored. Additionally, the immunohistochemistry staining of MTA1 protein and CD206 was performed in 75 NSCLC tissue specimens. Associations of MTA1 and CD206 with the clinicopathological characteristics were analyzed, as well as the correlation between MTA1 and CD206. Based on different algorithms, MTA1 expression was correlated with the distribution of infiltrating immune cells in the tumor microenvironment and negatively correlated with tumor immune-stromal score. MTA1 was associated with TAMs markers according to TCGA database. In 75 NSCLC tissue specimens, the positive rate of MTA1 was 60.00% (45/75), which of CD206 was 42.67% (32/75). The MTA1 expression was significantly correlated with T stage, lymph node metastasis, and TNM stage. The CD206 expression was significantly correlated with T stage, lymph node metastasis, TNM stage, and tumor type. Additionally, we found that MTA1 was positively correlated with CD206 in NSCLC and LUSC. In NSCLC, MTA1 expression was correlated with the infiltrations of different types of macrophages and the expression of TAMs markers, as well as the M2-TAMs marker CD206, suggesting that MTA1-promoting tumor metastasis may mediate the infiltration of different types of macrophages in the tumor microenvironment.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Proteínas Repressoras , Transativadores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Prognóstico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores/genética , Transativadores/metabolismo , Microambiente Tumoral , Macrófagos Associados a TumorRESUMO
m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.
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BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.
Assuntos
Comportamento Animal , Empatia , Giro do Cíngulo/metabolismo , Ocitocina/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Dopamina D2/metabolismo , Derrota Social , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Agressão , Animais , Arvicolinae , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiopatologia , Abrigo para Animais , Masculino , Neurotransmissores/farmacologia , Transdução de Sinais , Estresse Psicológico/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Alanine aminotransferase (ALT) is referred as liver transaminase and predominantly expressed by hepatocytes. Previous evidences showed that high levels of ALT were reversely associated with short- and long-term outcomes in patients with myocardial infarction. Besides, low lymphocyte has been demonstrated to be significantly correlated with adverse clinical outcomes in coronary artery disease (CAD). However, evidences about the relationship between ALT-to-lymphocyte ratio (ALR) and outcomes in CAD patients with normal liver function are limited. The aim of this study was to assess the relationship between ALR and clinical outcomes in patients with CAD. METHODS: This is a retrospective cohort study, and a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients with liver dysfunction, we finally enrolled 2714 patients. These patients were divided into two groups according to ALR value: the lower group (ALR < 14.06, n = 1804) and the higher group (ALR ≥ 14.06, n = 910). The average follow-up time was 37.59 ± 22.24 months. RESULTS: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P < 0.001) and cardiac mortality (CM) (P=0.010). Kaplan-Meier survival analysis suggested that CAD patients with higher ALR tended to have an increased accumulated risk of ACM and CM (log rank P < 0.001 and P=0.006, respectively). Multivariate Cox regression analysis showed that ALR was an independent predictor of ACM (hazard ratio (HR) = 2.017 (95% confidence interval (CI): 1.289-3.158), P=0.002) and CM (HR = 1.862 (95% CI: 1.047-3.313), P=0.034). We did not find significant difference in the incidence of major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs) between the two groups after adjustments of confounders. CONCLUSION: Our results indicate that ALR is an independent predictor of long-term adverse outcomes in CAD patients who underwent PCI.
Assuntos
Alanina Transaminase/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Contagem de Linfócitos , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. METHODS: A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan-Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 [1.264-3.300], P = 0.004) and heart failure (adjusted HR = 1.700 [1.347-2.147], P < 0.001). CONCLUSIONS: An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.
Assuntos
HDL-Colesterol/sangue , Doença das Coronárias/diagnóstico , Insuficiência Cardíaca/diagnóstico , Intervenção Coronária Percutânea , Triglicerídeos/sangue , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Doença das Coronárias/mortalidade , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Cardiac myocytes constitute the first differentiated cell type during mammalian heart formation with the ability to beat spontaneously and rhythmically. Hyperglycemia is a primary risk factor for cardiovascular disease in pre-gestational diabetes mellitus (PGDM). However, the impact that hyperglycemia has on cardiac progenitors or on precursors differentiation remains poorly understood. The aim of the present study is to investigate whether hyperglycemia affects cardiomyogenesis of embryocarcinoma cells. METHODS: P19CL6 cells differentiation induced by 1% DMSO was evaluated under either normal glucose (5.6 mmol/L) or high level of glucose concentrations (20 mmol/L or 40 mmol/L). To investigate the effect of long-term high level of glucose on cardiomyocytes differentiation, sarcomeric α-actinin, peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), transcription factor GATA4 and Nkx2.5 were assessed by qRT-PCR analysis, western blot and immunofluorescence. RESULTS: We observed that long-term high level of glucose markedly reduced P19CL6 cells differentiation into cardiomyocytes. The change in PGC-1α expression was consistent with changes in cardiac muscle myosin expression after exposure to 20 mmol/L or 40 mmol/L of glucose. On the other hand, the high level of glucose concentration profoundly decreased both GATA4 and Nkx2-5 expressions from day 6 to day 12 after differentiation, which was induced by 1% DMSO. CONCLUSION: Our results elucidate that the effect resulting from the long-term exposure of cardiac progenitors to high level of glucose is associated with decreased expression of GATA4 and Nkx2.5, providing a novel mechanism by which high glucose is able to affect cell differentiation.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucose/farmacologia , Actinina/genética , Actinina/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Dimetil Sulfóxido/farmacologia , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo , Proteína Homeobox Nkx-2.5/genética , Proteína Homeobox Nkx-2.5/metabolismo , Camundongos , Microscopia de Fluorescência , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
UNLABELLED: The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4ß7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. IMPORTANCE: In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.
Assuntos
Linfócitos T CD4-Positivos/virologia , Transmissão de Doença Infecciosa , Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , Mucosa Intestinal/virologia , Mastócitos/virologia , Células Cultivadas , Técnicas de Cocultura , Feminino , Infecções por HIV/imunologia , Humanos , Mucosa Intestinal/imunologiaRESUMO
A Gram-positive, aerobic, non-motile and non-spore forming strain, designated CFH S0262(T), was isolated from a soil sample collected from Catba island in Halong Bay, Vietnam. A polyphasic approach was used to study the taxonomic position of this new isolate. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain CFH S0262(T) belongs to the genus Rhodococcus and clustered with Rhodococcus soli DSD51W(T), Rhodococcus hoagii NBRC 103062(T), Rhodococcus defluvii Call(T) and Rhodococcus kunmingensis YIM 45607(T) (98.7, 98.5, 97.9 and 97.6% similarities, respectively). Strain CFH S0262(T) could grow in the presence of NaCl (0-4%, optimum 0-3%), at pH 6.0-8.0 (optimum, pH 7.0) and at 10-40 °C (optimum, 28 °C). The predominant menaquinones of strain CFH S0262(T) were identified as MK-8 (H2) and MK-8 (H4). The major fatty acids (≥10%) were found to be C(16:0) and C(18:1)ω9c. The polar lipids detected were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, a glycolipid and two unidentified phospholipids. The DNA G+C content was determined to be 71.4 mol%. Based on a comparative analysis of phenotypic and genotypic characteristics, in combination with low values of DNA-DNA hybridization between strain CFH S0262(T) and its closest neighbours, it is proposed that strain CFH S0262(T) represents a novel species of the genus Rhodococcus, for which the name Rhodococcus agglutinans sp. nov., is proposed, with the type strain CFH S0262(T) (=CCTCC AB2014297(T)=KCTC 39118(T)).
Assuntos
Rhodococcus/classificação , Rhodococcus/isolamento & purificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Rhodococcus/genética , Rhodococcus/metabolismoRESUMO
Two closely related thermophilic bacterial strains, designated YIM 71031(T) and YIM 71039, were isolated from a hot spring in Tengchong county, Yunnan province, south-western China. The novel isolates were observed to be Gram-negative, aerobic, rod-shaped and yellow-pigmented bacteria. The strains were found to be able to grow at 37-65 °C, pH 6.0-9.0 and with a NaCl tolerance up to 1.0 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences placed these two isolates in the genus Meiothermus. They were found to be closely related to Meiothermus timidus DSM 17022(T) (98.6 % similarity), and formed a cluster with this species. The predominant menaquinone was identified as MK-8 and the major fatty acids (>10 %) as anteiso-C15:0, iso-C15:0, anteiso-C17:0, iso-C16:0 and C16:0. The genomic DNA G+C contents of strains YIM 71031(T) and YIM 71039 were determined to be 64.0 and 65.4 mol%, respectively. DNA-DNA hybridizations showed low values between strains YIM 71031(T) and YIM 71039 and their closely related neighbour M. timidus DSM 17022(T). Morphological phylogenetic and chemotaxonomic results suggest that strains YIM 71031(T) and YIM 71039 are representatives of a new species within the genus Meiothermus, for which the name Meiothermus roseus sp. nov. is proposed. The type strain is YIM 71031(T) (=KCTC 42495(T) =NBRC 110900(T)).
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Bactérias Aeróbias/classificação , Bactérias Aeróbias/isolamento & purificação , Fontes Termais/microbiologia , Bactérias Aeróbias/genética , Bactérias Aeróbias/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Filogenia , Pigmentos Biológicos/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura , Vitamina K 2/análiseRESUMO
A novel actinobacterial strain, designated CFH S0499(T), was isolated from a soil sample collected from Catba island in Halong Bay, Vietnam. The cells were observed to be Gram-stain positive, aerobic, non-motile, curved rods. The strain was found to grow optimally at 28 °C and pH 7.0. Growth was found to occur at 0-7 % NaCl. Chemotaxonomically, the peptidoglycan type was determined to be of the A3α type, with glutamic acid, glycine, alanine and lysine as the major cell wall amino acids. The whole cell sugars were found to contain mannose, galactose, glucose, ribose and rhamnose. The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipids and two unidentified phospholipids. The major fatty acids were identified as anteiso-C15:0, iso-C15:0, anteiso-C17:0 and iso-C16:0 and the predominant respiratory quinone as MK-9 (H2), with a minor amount of MK-10 (H4) and MK-8 (H2). The G+C content of the genomic DNA was determined to be 71.8 mol%. The 16S rRNA gene sequence analysis showed that strain CFH S0499(T) should be assigned to the genus Sinomonas and is closely related to members of the species Sinomonas atrocyanea DSM 20127(T) (98.3 %), Sinomonas soli CW 59(T) (98.28 %), Sinomonas flava CW 108(T) (98.26 %), Sinomonas mesophila MPLK 26(T) (97.5 %) and Sinomonas notoginsengisoli SYP-B 575(T) (95.8 %). DNA-DNA hybridizations showed low values (49.1-54.5 %) between strain CFH S0499(T) and its four closest neighbours. Based on phenotypic, chemotaxonomic and phylogenetic analysis, strain CFH S0499(T) is concluded to represent a novel species of the genus Sinomonas, for which the name Sinomonas halotolerans sp. nov. is proposed, with CFH S0499(T) as the type strain (=CCTCC AB2014300(T) = KCTC 39116(T)).
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Micrococcaceae/classificação , Micrococcaceae/isolamento & purificação , Microbiologia do Solo , Aerobiose , Técnicas de Tipagem Bacteriana , Composição de Bases , Carboidratos/análise , Parede Celular/química , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Glicolipídeos/análise , Concentração de Íons de Hidrogênio , Micrococcaceae/genética , Micrococcaceae/fisiologia , Dados de Sequência Molecular , Peptidoglicano/análise , Fosfolipídeos/análise , Filogenia , Quinonas/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura , VietnãRESUMO
Phosphorus (P) is one of the essential nutrient elements for plant development. In this work, BnPht1;4 gene, encoding a phosphate transporter of PHT1 family, was isolated from Brassica napus. BnPht1;4 possesses the major characteristic of PHT1 high-affinity Pi transporters in plants, such as plasma-membrane localization and 12 transmembrane-spanning domains. Quantitative reverse-transcription PCR analysis and promoter activity assay showed BnPht1;4 was inert in plants under Pi sufficient conditions. However, expression of this gene was remarkably enhanced in roots under Pi deficient conditions. Interestingly, under low Pi conditions, its promoter activity is impaired in tips of elongated roots, suggesting that the high-affinity Pi transporter may be not involved in low Pi response at root tip area. The experimental results also indicated that BnPht1;4 induction by Pi deficiency is dependent on the existence of sugar. In 35S:BnPht1;4 transgenic Arabidopsis, the increase of Pi availability resulted in the change of root architecture under Pi deficient conditions, showing longer primary roots and lower lateral root density than that of wild type. By cis-element analysis, two P1BS and two W-box elements were found in BnPht1;4 promoter. Yeast one-hybrid assay indicated that PHR1 could bind to the BnPht1;4 promoter. P1BS elements in BnPht1;4 promoter are essential for BnPht1;4 induction in Pi starvation response. Furthermore, WRKY75 could bind to the BnPht1;4 promoter, in which W-box elements are important for this binding. These results indicated BnPht1;4 may be dually controlled by two family regulators under low Pi responses. Thus, our data on the regulative mechanism of high-affinity Pi transporter in Pi starvation response will be valuable for B. napus molecular agriculture.
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Brassica napus/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Transporte de Fosfato/genética , Fosfatos/metabolismo , Sequência de Aminoácidos , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Brassica napus/metabolismo , Genes Reporter , Dados de Sequência Molecular , Proteínas de Transporte de Fosfato/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
BACKGROUND: TBX1 and CRKL haploinsufficiency is thought to cause the cardiac phenotype of the 22q11.2 deletion syndrome. However, few unequivocal mutations of TBX1 and CRKL have been discovered in isolated conotrucal heart defects (CTDs) patients. The aim of the study was to screen the mutation of TBX1 and CRKL in isolated CTDs Chinese patients without 22q11.2 deletion and identify the pathomechanism of the missense mutations. METHODS: We enrolled 199 non-22q11.2 deletion patients with CTDs and 139 unrelated healthy controls. Gene sequencing were performed for all of them. The functional data of mutations were obtained by in vitro transfection and luciferase experiments and computer modelling. RESULTS: Screening of the TBX1 coding sequence identified a de novo missense mutation (c.385G â A; p.E129K) and a known polymorphism (c.928G â A; p.G310S). In vitro experiments demonstrate that the TBX1E129K variant almost lost transactivation activity. The TBX1G310S variant seems to affect the interaction of TBX1 with other factors. Computer molecular dynamics simulations showed the de novo missense mutation is likely to affect TBX1-DNA interaction. No mutation of CRKL gene was found. CONCLUSIONS: These observations suggest that the TBX1 loss-of-function mutation may be involved in the pathogenesis of isolated CTDs. This is the first human missense mutation showing that TBX1 is a candidate causing isolated CTDs in Chinese patients without 22q11.2 deletion.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Síndrome de DiGeorge/genética , Cardiopatias Congênitas/genética , Proteínas Nucleares/genética , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Animais , Povo Asiático/genética , Células COS , Estudos de Casos e Controles , Chlorocebus aethiops , DNA/química , DNA/metabolismo , Síndrome de DiGeorge/patologia , Éxons , Feminino , Células HEK293 , Cardiopatias Congênitas/patologia , Humanos , Masculino , Simulação de Dinâmica Molecular , Mutação de Sentido Incorreto , Filogenia , Conformação Proteica , Estrutura Secundária de Proteína , Análise de Sequência de DNA , Proteínas com Domínio T/químicaRESUMO
BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.
Assuntos
Neoplasias Hepáticas , Camundongos Nus , Simulação de Acoplamento Molecular , Microambiente Tumoral , Macrófagos Associados a Tumor , Via de Sinalização Wnt , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Camundongos , Células Hep G2 , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Masculino , Farmacologia em Rede , beta Catenina/metabolismo , Medicina Tradicional Chinesa/métodosRESUMO
Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.
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AIMS: To analyze the association between hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). METHODS: Predicted glycated hemoglobin (HbA1c) level was calculated using an established formula and HGI represented the difference between laboratory measured HbA1c and predicted HbA1c. A total of 1780 patients were stratified into three subgroups (HGI < -0.4, -0.4 ⦠HGI < 0.12 and HGI ⧠0.12). The primary endpoints included all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: ACM occurred in 54 patients: 22 (3.7) in the low-HGI subgroup, 8 (1.3) in the moderate-HGI subgroup and 24 (4.1) in the high-HGI subgroup (p = .012). After adjusting for the traditional clinical prognostic factors, multivariate Cox regression analysis showed that patients in both the low and high HGI subgroups had significantly increased risk of ACM as compared with patients in the moderate HGI subgroup (hazard ratio [HR] = 4.979, 95% confidence interval [CI]: 1.865-13.297, p = .001 and HR = 2.918, 95% CI: 1.075-7.922, p = .036). However, we did not find significant differences in the incidence of CM, MACEs and MACCEs. CONCLUSION: HGI can predicts risk for long-term mortality in patients undergoing PCI. This index could be helpful for the effective clinical management of the CAD population.
Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Hemoglobinas Glicadas , Estudos Retrospectivos , Reação de Maillard , Intervenção Coronária Percutânea/efeitos adversos , PrognósticoRESUMO
The NAC protein family is one of the novel classes of plant-specific transcription factors. In this study, two genes (BnNAC2 and BnNAC5) encoding the putative NAC transcription factors were identified in Brassica napus. Sequence analysis revealed that the deduced BnNAC proteins contain conserved N-terminal region (NAC domain) and highly divergent C-terminal domain. Yeast transactivation analysis showed that BnNAC2 could activate reporter gene expression, suggesting that BnNAC2 functions as a transcriptional activator. Quantitative RT-PCR analysis revealed that BnNAC2 was preferentially expressed in flowers, whereas BnNAC5 mRNAs accumulated at the highest level in stems. Further experimental results indicated that the two genes are high-salinity-, drought- and abscisic acid (ABA)-induced. Overexpression of BnNAC2 and BnNAC5 genes in yeast (Schizosaccharomyces pombe) remarkably inhibited the growth rate of the host cells, and enhanced the cells sensitive to high-salinity and osmotic stresses. Complementation test indicated that BnNAC5 could recover the defects such as salt-hypersensitivity and accelerated-leaf senescence of vni2 T-DNA insertion mutant. Several stress-responsive genes including COR15A and RD29A were enhanced in the complemented plants. These results suggest that BnNAC5 may perform the similar function of VNI2 in response to high-salinity stress and regulation of leaf aging. Key message BnNAC2 and BnNAC5 are salt-, drought- and ABA-induced genes. Overexpression of BnNAC5 in Arabidopsis vni2 mutant recovered the mutant defects (salt-hypersensitivity and accelerated-leaf senescence) to the phenotype of wild type.
Assuntos
Brassica napus/fisiologia , Regulação da Expressão Gênica de Plantas , Cloreto de Sódio/farmacologia , Estresse Fisiológico/fisiologia , Fatores de Transcrição/metabolismo , Ácido Abscísico/farmacologia , Sequência de Aminoácidos , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Sequência de Bases , Brassica napus/efeitos dos fármacos , Brassica napus/genética , Expressão Gênica , Manitol/farmacologia , Dados de Sequência Molecular , Mutagênese Insercional , Filogenia , Folhas de Planta/citologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Plantas Geneticamente Modificadas , Salinidade , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/genética , Schizosaccharomyces/fisiologia , Plântula/citologia , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/fisiologia , Alinhamento de Sequência , Análise de Sequência de DNA , Fatores de Transcrição/genética , Regulação para CimaRESUMO
OBJECTIVE: To analysis liposoluble constituents of Holotrichia diomphalia by GC-MS and measure their anti-inflammatory and analgesic activities. METHODS: The composition of liposoluble constituents were determined by GC-MS. The dimethylbenzene-induced mice inflammatory models were established. The pain models were obtained by hot plate and acetic acid in mice. RESULTS: Twenty-two components were identified from the petroleum ether extract of Holotrichia diomphalia. The major components were oleic acid, palmitic acid and palmitoleic acid. The petroleum ether extract was able to significantly inhibit the mice ear edema induced by dimethyl-benzene. The pain in mice caused by acetic acid and hot plate were evidently suppressed by the petroleum ether extract. CONCLUSION: The petroleum ether extract of Holotrichia diomphalia has obvious anti-inflammation and analgesic effects.
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Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Besouros , Ácidos Graxos/análise , Materia Medica/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Besouros/química , Edema/induzido quimicamente , Edema/prevenção & controle , Ácidos Graxos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Masculino , Materia Medica/química , Materia Medica/isolamento & purificação , Camundongos , Camundongos Endogâmicos ICR , Dor/prevenção & controle , Medição da Dor/efeitos dos fármacos , SolubilidadeRESUMO
STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.
Assuntos
Delírio do Despertar , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Criança , Pré-Escolar , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Delírio do Despertar/prevenção & controle , Humanos , Incidência , Estudos ProspectivosRESUMO
Rice is a major food crop that sustains approximately half of the world population. Recent worldwide improvements in the standard of living have increased the demand for high-quality rice. Accurate identification of quantitative trait loci (QTLs) for rice grain quality traits will facilitate rice quality breeding and improvement. In the present study, we performed high-resolution QTL mapping for rice grain quality traits using a genotyping-by-sequencing approach. An F2 population derived from a cross between an elite japonica variety, Koshihikari, and an indica variety, Nona Bokra, was used to construct a high-density genetic map. A total of 3,830 single nucleotide polymorphism markers were mapped to 12 linkage groups spanning a total length of 2,456.4 cM, with an average genetic distance of 0.82 cM. Seven grain quality traits-the percentage of whole grain, percentage of head rice, percentage of area of head rice, transparency, percentage of chalky rice, percentage of chalkiness area, and degree of chalkiness-of the F2 population were investigated. In total, 15 QTLs with logarithm of the odds (LOD) scores >4 were identified, which mapped to chromosomes 6, 7, and 9. These loci include four QTLs for transparency, four for percentage of chalky rice, four for percentage of chalkiness area, and three for degree of chalkiness, accounting for 0.01%-61.64% of the total phenotypic variation. Of these QTLs, only one overlapped with previously reported QTLs, and the others were novel. By comparing the major QTL regions in the rice genome, several key candidate genes reported to play crucial roles in grain quality traits were identified. These findings will expedite the fine mapping of these QTLs and QTL pyramiding, which will facilitate the genetic improvement of rice grain quality.