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BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.
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Oryza , Oryza/genética , Sementes/genética , Germinação/genética , Melhoramento Vegetal , Grão Comestível/genética , Proteínas de Ligação ao GTPRESUMO
Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.
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Anestesia , Assistência Terminal , Humanos , Hospitais , UniversidadesRESUMO
Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.
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Objetivos , Complicações Pós-Operatórias , Humanos , Pressão Sanguínea , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Hemodinâmica , Hidratação/métodosRESUMO
End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.
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Anestesia , Humanos , Dor , Hospitais , Cuidados Paliativos , UniversidadesRESUMO
In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. The results show that the optimal conditions for immobilized XOD activity were a dopamine concentration of 2.0 mg/mL in 10.0 mM Tris-HCl buffer (pH 8.5), a modification time of 3.0 h, an XOD concentration of 1000 µg/mL in 10.0 mM phosphate buffer (pH 7.5) and an immobilization time of 3.0 h. Subsequently, the enzymatic reaction conditions such as the pH value and temperature were investigated, and the enzyme kinetics and inhibition parameters were determined. The results indicate that the optimal pH value (7.5) and temperature (37 °C) of the PDA-modified hollow fiber-immobilized XOD were consistent with the free enzyme. Moreover, the PDA-modified hollow fiber-immobilized XOD could still maintain above 50% of its initial immobilized enzyme activity after seven consecutive cycles. The Michaelis-Menten constant (Km) and the half-maximal inhibitory concentration (IC50) of allopurinol on the immobilized XOD were determined as 0.25 mM and 23.2 µM, respectively. Furthermore, the PDA-modified hollow fiber-immobilized XOD was successfully applied to evaluate the inhibitory activity of eight flavonoids. Quercetin, apigenin, puerarin and epigallocatechin showed a good inhibition effect, and their percentages of inhibition were (79.86 ± 3.50)%, (80.98 ± 0.64)%, (61.15 ± 6.26)% and (54.92 ± 0.41)%, respectively. Finally, molecular docking analysis further verified that these four active compounds could bind to the amino acid residues in the XOD active site. In summary, the PDA-modified hollow fiber-immobilized XOD is an efficient method for the primary screening of XOD inhibitors from natural products.
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Inibidores Enzimáticos/química , Enzimas Imobilizadas , Flavonoides/química , Indóis/química , Polímeros/química , Xantina Oxidase , Enzimas Imobilizadas/antagonistas & inibidores , Enzimas Imobilizadas/química , Simulação de Acoplamento Molecular , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/químicaRESUMO
Leaf angle is a key parameter that determines plant architecture and crop yield. Hormonal crosstalk involving brassinosteroid (BR) plays an essential role in leaf angle regulation in cereals. In this study, we investigated whether abscisic acid (ABA), an important stress-responsive hormone, co-regulates lamina joint inclination together with BR, and, if so, what the underlying mechanism is. Therefore, lamina joint inclination assay and RNA sequencing (RNA-Seq) analysis were performed here. ABA antagonizes the promotive effect of BR on leaf angle. Hundreds of genes responsive to both hormones that are involved in leaf-angle determination were identified by RNA-Seq and the expression of a gene subset was confirmed using quantitative real-time PCR (qRT-PCR). Results from analysis of rice mutants or transgenic lines affected in BR biosynthesis and signaling indicated that ABA antagonizes the effect of BR on lamina joint inclination by targeting the BR biosynthesis gene D11 and BR signaling genes GSK2 and DLT, thus forming a multi-level regulatory module that controls leaf angle in rice. Taken together, our findings demonstrate that BR and ABA antagonistically regulate lamina joint inclination in rice, thus contributing to the elucidation of the complex hormonal interaction network that optimizes leaf angle in rice.
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Ácido Abscísico/farmacologia , Brassinosteroides/biossíntese , Oryza/efeitos dos fármacos , Oryza/fisiologia , Transdução de Sinais , Análise de Variância , Biologia Computacional , Perfilação da Expressão Gênica , Fenótipo , Reguladores de Crescimento de Plantas/metabolismo , TranscriptomaRESUMO
BACKGROUND: Endothelial dysfunction has been suggested as a possible causal link between hyperglycemia and microvascular complications in diabetes mellitus. The effect of metformin on endothelial progenitor cells (EPCs) is still unclear. This study was designed to test the hypothesis that metformin could accelerate wound healing by improving the impaired EPC functions in streptozotocin-induced diabetic mice. METHODS: Streptozotocin (STZ, 60 mg/kg/d × 5 d, i.p.) was injected to induce type 1 diabetes in male C57BL/6 mice. Mice were treated with metformin (250 mg/kg/d, i.g.) for consecutive 14 days. Wound closure was evaluated by wound area and number of CD31 stained capillaries. Functions of bone marrow-endothelial progenitor cells (BM-EPCs) were assessed by tube formation and migration assays, and expression of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) was determined by western blot analysis. RESULTS: Metformin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in metformin treated diabetic mice. Abilities of tube formation and migration of BM-EPCs were impaired in diabetic mice, which were improved by metformin. Expression of both phosphorylated-AMPK and phosphorylated-eNOS was significantly increased, and nitric oxide (NO) production was enhanced by metformin in BM-EPCs of diabetic mice. In vitro, metformin improved impaired BM-EPC functions, and increased phosphorylated-eNOS expression and NO production in cultured BM-EPCs caused by high glucose, which was prevented by the AMPK inhibitor compound C. CONCLUSIONS: Our results suggest that metformin could improve BM-EPC functions in STZ-induced diabetic mice, which was possibly dependent on the AMPK/eNOS pathway.
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Movimento Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Células Progenitoras Endoteliais/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Metformina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Tipo 1/metabolismo , Modelos Animais de Doenças , Células Progenitoras Endoteliais/metabolismo , Hiperglicemia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
Objective: To establish the quantitative detection method for Pinellia ternata in Banxia decoction by polymerase chain reaction( PCR) and to explore a suitable quantitative analysis method for medicinal materials in liquid preparation of traditional Chinese medicine. Methods: The PCR method was adopted for analyzing Pinellia ternata in Banxia decoction based on the specific detection of ITS region. The PCR amplification products were analyzed with agarose gel electrophoresis. The relationship between the percentage of Pinellia ternata in Banxia decoction with the PCR products were established. In addition,Real-Time PCR assay and agarose gel electrophoresis were applied in the quantitative detection. Results: Accurate quantitative analysis of Pinellia ternata medicinal materials can be achieved by two methods,and a better linear correlation in the standard curve( r = 0. 9943) were obtained with agarose gel electrophoresis method. Conclusion: A high specificity and sufficient reproducibility PCR technology with agarose gel eletroghoresis method has been established for the quantitative detection of Pinellia ternata in Banxia decoction. The quantitative detection of medicinal materials in decoction based on PCR technology was reported for the first time.
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Pinellia , Medicina Tradicional Chinesa , Reação em Cadeia da Polimerase , Reprodutibilidade dos TestesRESUMO
Three new homometallic lanthanide complexes with mixed carboxylate-modified rigid ligands, [Ln(µ3-OH)(na)(pyzc)]n (na(-) = 1-naphtholate, pyzc(-) = 2-pyrazinecarboxylate, Ln = Dy (1), Yb (2), and Gd (3)), were solvothermally synthesized, and their structures and magnetic as well as photophysical properties were completely investigated. Complexes 1-3 are crystallographically isostructural, exhibiting linear chains with four bidentate bridging µ-COO(-) moieties encapsulated cubic {Ln4(µ3-OH)4}(8+) clusters repeatedly extended by 4-fold chelating-bridging-pyzc(-) connectors. Magnetically, the former two complexes with highly anisotropic Dy(III) and weak anisotropic Yb(III) ions in the distorted NO7 triangular dodecahedron coordination environment display field-induced slow relaxation of magnetization. Fitting the dynamic magnetic data to the Arrhenius law gives energy barrier ΔE/kB = 39.6 K and pre-exponential factor τo = 1.52 × 10(-8) s for 1 and ΔE/kB = 14.1 K and τo = 2.13 × 10(-7) s for 2. By contrast, complex 3 with isotropic Gd(III) ion and weak intracluster antiferromagnetic coupling shows a significant cryogenic magnetocaloric effect, with a maximum -ΔSm value of 30.0 J kg(-1) K(-1) at 2.5 K and 70 kOe. Additionally, the chromophoric na(-) and pyzc(-) ligands can serve as antenna groups, selectively sensitizing the Dy(III)- and Yb(III)-based luminescence of 1 and 2 in the UV-visible region by an intramolecular energy transfer process. Thus, complexes 1-3, incorporating field-induced slow magnetic magnetization and interesting luminescence together, can be used as composite magneto-optical materials. More importantly, these interesting results further demonstrate that the mixed-ligand system with rigid carboxylate-functionalized chromophores can be excellent candidates for the preparations of new bifunctional magneto-optical materials.
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BACKGROUND: Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice). METHODS: LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis. RESULTS: STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1ß and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1ß and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1ß level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment. CONCLUSIONS: We conclude that glibenclamide could attenuate myocardial injury induced by LPS challenge in STZ-mice, which was possibly related to inhibiting inflammation through Nalp3 inflammasomes.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Glibureto/uso terapêutico , Traumatismos Cardíacos/prevenção & controle , Hipoglicemiantes/uso terapêutico , Lipopolissacarídeos/toxicidade , Animais , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Endotoxemia/induzido quimicamente , Endotoxemia/patologia , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/induzido quimicamenteRESUMO
Patients with hematological tumors experience physical and psychological stress, and negative psychological states. Baduanjin, an emerging psychological rehabilitation method combined with resistance exercise, has received widespread attention. This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects. Through a literature review and comprehensive analysis, the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated. The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors, which can alleviate anxiety, depression, and other adverse emotions, and improve quality of life. However, there is a lack of unified and standardized exercise intervention programs for practical application, and patient participation and compliance must be improved. Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors; however, it is still necessary to further standardize and improve the exercise program improving patient participation and compliance. Future studies should strengthen theoretical exploration and empirical research, providing more effective psychological rehabilitation strategies for patients with hematological tumors.
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OBJECTIVE: To develop a UPLC method for the simultaneous determination of liquiritin, narirutin, hesperidin, ammonium glycyrrhetate, honokiol and magnolol in Huoxiang Zhengqi oral liquid. METHOD: A Zorbax Eclipse C18 column was used with the mobile phase of acetonitrile and 0. 05% phosphate acid by gradient elution at the detection wavelength of 220 nm. The flow rate was 0.42 mL x min(-1) and the column temperature was 30 degrees C. RESULT: The calibration curves were linear in the ranges of 0.001 7-0.034, 0.003 4-0.068, 0.006 4-0.128, 0.012 8-0.256, 0.003 2-0.064, 0.006 4-0.128 microg, respectively. The average recoveries were 103.3%, 98.39%, 98.29%, 102.1%, 98.45%, 102.2% with RSDs of 2.1%,1.0%, 0.50%, 2.3%, 0.9%, 2.0%, respectively. CONCLUSION: The UPLC method was simple, rapid and accurate, it could be used for quality control of Huoxiang Zhengqi oral liquid.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Administração Oral , Compostos de Bifenilo/química , Dissacarídeos/química , Flavanonas/química , Glucosídeos/química , Hesperidina/química , Lignanas/química , Soluções Farmacêuticas/químicaRESUMO
Polyphyllin I (PPI), a bioactive component extracted from Paris polyphylla, was reported to have potent anticancer activities in previous studies. However, there were few reports on the effects and underlying mechanism of PPI in human acute myeloid leukemia cells. The present study demonstrated that PPI had an inhibitory effect through inducing apoptosis and autophagy in THP-1 and NB4 cells. PPI induced apoptosis via activating JNK pathway, as evidenced by the decreased Bcl-2 levels and increased Bax, cleaved-caspase-3 and phosphorylated-JNK expressions. In addition, PPI promoted autophagy as evidenced with increased expressions of LC3-II and Beclin-1 in western blot and autophagic vacuoles in MDC staining, which was associated with the inhibition of AKT-mTOR pathway. Furthermore, JNK inhibitor SP600125 and autophagy inhibitor 3-MA were employed to evaluate the role of apoptosis and autophagy in PPI-induced cell death. We found that autophagy and apoptosis were both causes of cell death induced by PPI. These data suggested that PPI could be a potent therapeutic agent for the treatment of human acute myeloid leukemia.
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Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Diosgenina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Diosgenina/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the value of fluorescence in situ hybridization (FISH) in diagnosis and prognosis evaluation of chronic lymphocytic leukemia (CLL). METHODS: R banding technique was used for karyotype analysis in 43 cases of CLL, and fluorescence in situ hybridizationï¼FISHï¼ technique was used for analysis of 5 genes in 43 cases of CLL, including D13S25, RB1,ATM, P53 and CEP 12 . RESULTS: The detection rate of chromosome abnormality was 9.3ï¼ for the 43 cases. The chromosome karyotype abnormality was involoved in the number abnormality and the structural abnormality, including No. 2, 6, 14, and sex chromosome. The patients with normal chromosome karyotype were more commonï¼79.1ï¼ ï¼. At the same time, mitotic figure in 5 CLL patients did not observed. The positive rate of FISH detection was 55.8ï¼ (24/43). Among which, D13S25 deletion was the highest and reached to 37.2ï¼ , followed by RB1 deletionï¼20.9ï¼ ï¼, CEP 12 amplificationï¼16.3ï¼ ï¼, ATM deletionï¼9.3ï¼ ï¼ and P53 deletionï¼7.0ï¼ ï¼. In 24 FISH-positive cases, 20 cases displayed the normal chromosome karyotype, and in 3 cases the mitotic figure was absent. There was only one case of abnormal chromosome, which was not involved in the positive gene tested by FISH. CONCLUSION: FISH is an important means of CLL genetic detection, which can greatly raise the detection rate of cytogenetics abnormalities in CLL, but the probe quantity is limited, so it is necessary to use FISH technology combined with chromosome karyotype analysis so as to improve the detection rate of abnormal cytogenetics, and provide the basis for the clinical diagnosis and prognosis of CLL.
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Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Citogenética , Humanos , Hibridização in Situ Fluorescente , CariotipagemRESUMO
BZR1 and BES1 are key transcription factors of brassinosteroid (BR) signaling and represent the integration node of numerous signaling cascades. Their direct target genes have been identified, and BZR1/BES1-DNA interactions have been experimentally verified. Importantly, BZR1/BES1 also integrate different growth and development events via direct protein-protein interactions. For instance, DELLAs, PIFs, ARF6, and PKL, all directly interact with BZR1/BES1, forming a BZR1/BES1-centered regulatory network to coordinate cell elongation. By dissecting various BZR1/BES1-mediated BR responses, the concept that BZR1/BES1 act as an integration hub in multisignal-regulated plant growth and development was developed. The regulation of BZR1/BES1 is dynamic and multifaceted, including phosphorylation status, activity, and stability. Moreover, certain epigenetic modification mechanisms are involved in BZR1/BES1's regulation of gene expression. Herein, we review recent advances in BZR1/BES1-mediated molecular connections between BR and other pathways, highlighting the central role of the BZR1/BES1 interactome in optimizing plant growth and development.
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Proteínas de Arabidopsis/metabolismo , Epigênese Genética/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Redes Reguladoras de Genes/fisiologia , Proteínas Nucleares/metabolismo , Fenômenos Fisiológicos Vegetais , Transdução de Sinais/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA , Proteínas Nucleares/genéticaRESUMO
Brassinosteroids (BRs) are essential plant-specific steroidal hormones that regulate diverse growth and developmental processes in plants. We evaluated the effects of OsDWF4, a gene that encodes a rate-limiting enzyme in BR biosynthesis, on both rice yield and quality when driven by the Gt1 or Ubi promoter, which correspond to seed-specific or constitutive expression, respectively. Generally, transgenic plants expressing OsDWF4 showed increased grain yield with more tillers and longer and heavier seeds. Moreover, the starch physicochemical properties of the transgenic rice were also improved. Interestingly, OsDWF4 was found to exert different effects on either rice yield or quality when driven by the different promoters. The overall performance of the pGt1::OsDWF4 lines was better than that of the pUbi::OsDWF4 lines. Our data not only demonstrate the effects of OsDWF4 overexpression on both rice yield and quality but also suggest that a seed-specific promoter is a good choice in BR-mediated rice breeding programs.
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Brassinosteroides/biossíntese , Oryza/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Oryza/enzimologia , Oryza/genética , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismoRESUMO
Light and brassinosteroid (BR) are master environmental stimulus and endogenous cue for plant growth and development respectively. Great progress has been made in elucidating the molecular mechanisms on the cross-talk between light and BR. However, little is known about how BZR1, the pivotal integration node, is regulated by light and dark. Here, we demonstrated that an intact BR signaling pathway is essential for dark-induced hypocotyl elongation. Consequent expression assay showed that light-dark switch affected BZR1 phosphorylation and accumulation. Moreover, blocking the 26S proteasome pathway promoted the accumulation of both phosphorylated and dephosphorylated BZR1 proteins. Restriction of new protein biosynthesis had multiple effects on BZR1 phosphorylation status and stability, relying on the availability of light and the 26S proteasome pathways. Furthermore, sugar treatment strikingly enhanced the accumulation of total BZR1 under either light or dark conditions, likely by repressing transcript abundance of MAX2, a gene encoding an E3 ligase for BZR1. Finally, light-regulated phosphorylation change of BZR1 requires the existence of endogenous BR as well as functional BIN2 and protein phosphatase 2A (PP2A). Taken together, our results depicted a light-involved complex regulation network of BZR1 stability and phosphorylation status.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas Nucleares/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/análise , Brassinosteroides/metabolismo , Proteínas de Ligação a DNA , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Luz , Proteínas Nucleares/análise , Fosforilação , Reguladores de Crescimento de Plantas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Biossíntese de Proteínas , Estabilidade Proteica , Transdução de SinaisRESUMO
Functional studies in non-small cell lung cancer (NSCLC) patients revealed that hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor growth. We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in NSCLC. Tumor and adjacent non-tumor tissue samples were collected from 215 NSCLC patients who had tumor resections between 2006 and 2011. Immunohistochemistry was performed to detect Nrf2 or NQO1 expression. The correlation between Nrf2 or NQO1 expression and survival outcomes was evaluated using the Kaplan-Meier method and Cox proportional hazards regression model. Levels of Nrf2 and NQO1 were elevated in tumor tissues. In particular, Nrf2 was elevated in nearly all tumor cells. NQO1 expression positively correlated with Nrf2 expression (P = 0.039). Nrf2 expression positively correlated with lymph node metastasis (P = 0.001) and negatively correlated with tumor differentiation (P = 0.032). As compared with either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more predictive of superior overall survival (P = 0.020) and disease free survival (P = 0.037). Subgroup analyses showed that females, nonsmokers, and patients with advanced-stage NSCLC were suitable populations in which to evaluate prognosis based on Nrf2 and NQO1 co-expression. These results indicate that dual-negative expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , NAD(P)H Desidrogenase (Quinona)/genética , Fator 2 Relacionado a NF-E2/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND & AIMS: Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice. METHODS: Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the daily amount of food and water intake were measured. Pancreatic tissues were collected for histologic analyses. Pathological assessment and immunohistochemistry analysis were used to determine the effect of metformin on insulitis. Inflammatory cytokines in the pancreas and insulin levels were measured through ELISA analysis. RESULTS: Metformin significantly reduced blood glucose levels and improved aberrant water intake behavior in experimental diabetic mice. No significant differences were observed in terms of body weight and food intake behavior in metformin-treated animals. In the STZ-induced model of diabetes, we found the appearance of pronounced insulitis. However, metformin administration reduced the severity of insulitis assessed by blind pathological scoring. In addition, metformin treatment improved insulin levels in experimental diabetic mice. ELISA assay revealed decreased levels of inflammatory response marker IL-1ß and TNF-α in the pancreatic tissues following metformin treatment. CONCLUSION: Metformin attenuated insulitis in the STZ-induced mice model of diabetes. This islet-protective effect might be partly correlated with the anti-inflammatory action of metformin.