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2.
BMC Plant Biol ; 19(1): 362, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426743

RESUMO

BACKGROUND: The MYB transcription factor family is one of the largest transcriptional factor families in plants and plays a multifaceted role in plant growth and development. However, MYB transcription factors involved in pathogen resistance in apple remain poorly understood. RESULTS: We identified a new MYB family member from apple, and named it MdMYB30. MdMYB30 was localized to the nucleus, and was highly expressed in young apple leaves. Transcription of MdMYB30 was induced by abiotic stressors, such as polyethylene glycol and abscisic acid. Scanning electron microscopy and gas chromatograph-mass spectrometry analyses demonstrated that ectopically expressing MdMYB30 in Arabidopsis changed the wax content, the number of wax crystals, and the transcription of wax-related genes. MdMYB30 bound to the MdKCS1 promoter to activate its expression and regulate wax biosynthesis. MdMYB30 also contributed to plant surface properties and increased resistance to the bacterial strain Pst DC3000. Furthermore, a virus-based transformation in apple fruits and transgenic apple calli demonstrated that MdMYB30 increased resistance to Botryosphaeria dothidea. Our findings suggest that MdMYB30 plays a vital role in the accumulation of cuticular wax and enhances disease resistance in apple. CONCLUSIONS: MdMYB30 bound to the MdKCS1 gene promoter to activate its transcription and regulate cuticular wax content and composition, which influenced the surface properties and expression of pathogenesis-related genes to resistance against pathogens. MdMYB30 appears to be a crucial element in the formation of the plant cuticle and confers apple with a tolerance to pathogens.


Assuntos
Ascomicetos/fisiologia , Resistência à Doença , Malus/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Ceras/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/fisiologia , Expressão Ectópica do Gene , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Malus/metabolismo , Malus/microbiologia , Doenças das Plantas/microbiologia , Epiderme Vegetal/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , RNA de Plantas/análise , Alinhamento de Sequência , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo
3.
Planta ; 249(5): 1627-1643, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826884

RESUMO

MAIN CONCLUSION: This study showed that AP2/EREBP transcription factor MdSHINE2 functioned in mediating cuticular permeability, sensitivity to abscisic acid (ABA), and drought resistance by regulating wax biosynthesis. Plant cuticular wax plays crucial roles in protecting plants from environmental stresses, particularly drought stress. Many enzymes and transcription factors involved in wax biosynthesis have been identified in plant species. In this study, we identified an AP2/EREBP transcription factor, MdSHINE2 from apple, which is a homolog of AtSHINE2 in Arabidopsis. MdSHINE2 was constitutively expressed at different levels in various apple tissues, and the transcription level of MdSHINE2 was induced substantially by abiotic stress and hormone treatments. MdSHINE2-overexpressing Arabidopsis exhibited great change in cuticular wax crystal numbers and morphology and wax composition of leaves and stems. Moreover, MdSHINE2 heavily influenced cuticular permeability, sensitivity to abscisic acid, and drought resistance.


Assuntos
Ácido Abscísico/farmacologia , Secas , Malus/metabolismo , Fator de Transcrição AP-2/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Malus/efeitos dos fármacos , Fator de Transcrição AP-2/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Plant Physiol ; 179(1): 88-106, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30333149

RESUMO

SIZ1 (a SIZ/PIAS-type SUMO E3 ligase)-mediated small ubiquitin-like modifier (SUMO) modification of target proteins is important for various biological processes related to abiotic stress resistance in plants; however, little is known about its role in resistance toward iron (Fe) deficiency. Here, the SUMO E3 ligase MdSIZ1 was shown to be involved in the plasma membrane (PM) H+-ATPase-mediated response to Fe deficiency. Subsequently, a basic helix-loop-helix transcription factor, MdbHLH104 (a homolog of Arabidopsis bHLH104 in apple), which acts as a key component in regulating PM H+-ATPase-mediated rhizosphere acidification and Fe uptake in apples (Malus domestica), was identified as a direct target of MdSIZ1. MdSIZ1 directly sumoylated MdbHLH104 both in vitro and in vivo, especially under conditions of Fe deficiency, and this sumoylation was required for MdbHLH104 protein stability. Double substitution of K139R and K153R in MdbHLH104 blocked MdSIZ1-mediated sumoylation in vitro and in vivo, indicating that the K139 and K153 residues were the principal sites of SUMO conjugation. Moreover, the transcript level of the MdSIZ1 gene was substantially induced following Fe deficiency. MdSIZ1 overexpression exerted a positive influence on PM H+-ATPase-mediated rhizosphere acidification and Fe uptake. Our findings reveal an important role for sumoylation in the regulation of PM H+-ATPase-mediated rhizosphere acidification and Fe uptake during Fe deficiency in plants.


Assuntos
Ferro/metabolismo , Malus/enzimologia , ATPases Translocadoras de Prótons/metabolismo , Ubiquitinas/fisiologia , Membrana Celular/metabolismo , Malus/metabolismo , RNA Mensageiro/metabolismo , Rizosfera , Sumoilação , Ubiquitinas/genética , Ubiquitinas/metabolismo
5.
Plant Physiol Biochem ; 132: 320-332, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30248518

RESUMO

Long-chain acyl-CoA synthetases (LACSs) are members of the acyl-activating enzyme superfamily that have important roles in lipid synthesis and storage, fatty acid catabolism, vectorial acylation, and synthesis of cutin and wax. Here, 11 apple MdLACS genes were identified based on the Malus × domestica reference genome, clustered into six groups and mapped to ten chromosomes. Multiple sequence alignment and conserved motifs analyses showed that the sequences of the AtLACS and MdLACS proteins were highly conserved. A cis-element analysis in the promoter regions of the MdLACS genes revealed various elements related to stress responsiveness and plant hormones. Subsequently, expression analysis demonstrated that the MdLACS genes had different expression profiles in different tissues in response to various abiotic stresses. To further study the function of MdLACS genes in apple, MdLACS1 was isolated to identify its basic function, which the function of MdLACS1 in response to apple abiotic stress resistance was determined by the transgenic method. The results showed the MdLACS1 enhanced tolerance to polyethylene glycol, salt, and abscisic acid in the apple callus, suggesting that MdLACS1 is an important regulator in response to abiotic stresses. Finally, the functional interoperability network among the MdLACS proteins was predicted and analyzed, which could the understanding of the possible interactions among proteins and genes regulatory networks concerned with wax biosynthesis and regulatory mechanisms in response to abiotic stresses in apple.


Assuntos
Coenzima A Ligases/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Malus/enzimologia , Malus/genética , Estresse Fisiológico/genética , Ácido Abscísico/farmacologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Arabidopsis/metabolismo , Cromossomos de Plantas/genética , Coenzima A Ligases/química , Coenzima A Ligases/metabolismo , Sequência Conservada/genética , Evolução Molecular , Ácidos Graxos/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Polietilenoglicóis/farmacologia , Regiões Promotoras Genéticas/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Ceras/metabolismo
6.
J Cell Biochem ; 119(5): 3957-3967, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29227545

RESUMO

Sirt family has been reported playing a significant role in the cancer development, especial its deacetylase activity plays a key function, but whether SIRT6 plays a role in mediating tumor epithelial-mesenchymal transition (EMT) and metastasis in colon cancer has not been explored. Here, the mass spectrometry and co-immunoprecipitation assays were utilized to detect that SIRT6 was physically associated with transcription factor snail. Most important, HCT116 cells transfected with SIRT6 shRNA reversed EMT, while increased the expression of TET1, and the HCT116 cells transfected with SIRT6 displayed the contrary tendency. Transwell invasion assay, soft agar assay, as well as colony formation together showed that SIRT6 promoted cell EMT and tumorigenesis in vitro. We also found SIRT6 is a reader of snail. ChIP as well as qChIP suggested H3K9 binding on the promoter of TET1 dependent on SIRT6. SIRT6 promoted EMT process through two different ways, one is as a reader of snail, and other way was the suppression of TET1 transcription. These two ways are all dependent on its H3K9 deacetylase activity. Further, patient samples collected showed that SIRT6 was significantly increased in colon cancer samples, and its higher expression was correlated with poor prognosis, worse overall survivals. Together, our experiments revealed the mechanism for SIRT6 in facilitating tumorigenesis and metastasis of colon cancer cells, suggesting that SIRT6 might be a potential therapeutic target for treating colon cancer.


Assuntos
Neoplasias do Colo/epidemiologia , Transição Epitelial-Mesenquimal , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Sirtuínas/biossíntese , Biomarcadores Tumorais , Neoplasias do Colo/genética , Células HCT116 , Humanos , Proteínas de Neoplasias/genética , Sirtuínas/genética
7.
J Int Med Res ; 46(2): 612-618, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28703631

RESUMO

A 76-year-old woman was admitted to the hospital four times from November 2007 to June 2009. In this complex case, the patient had silicosis complicated by broncholithiasis, oesophagobronchial fistulas, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium oesophagography, gastroesophageal endoscopy, and biopsy suggested oesophageal-related chronic inflammation and ulceration, which may have caused the repeated oesophagobronchial fistulas. Bronchoscopy revealed a free broncholithiasis in the left mainstem bronchus. The patient was admitted a fourth time because of silicotuberculosis relapse. After 9 months of antituberculosis treatment, the patient recovered and was still clinically well at the time of this writing.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Fístula Brônquica/diagnóstico por imagem , Fístula Esofágica/diagnóstico por imagem , Litíase/diagnóstico por imagem , Silicotuberculose/diagnóstico por imagem , Idoso , Fístula Brônquica/tratamento farmacológico , Fístula Brônquica/patologia , Fístula Brônquica/cirurgia , Fístula Esofágica/tratamento farmacológico , Fístula Esofágica/patologia , Fístula Esofágica/cirurgia , Esofagoscopia , Feminino , Humanos , Isoniazida/uso terapêutico , Litíase/tratamento farmacológico , Litíase/patologia , Litíase/cirurgia , Pirazinamida/uso terapêutico , Rifampina/análogos & derivados , Rifampina/uso terapêutico , Silicotuberculose/tratamento farmacológico , Silicotuberculose/patologia , Silicotuberculose/cirurgia , Stents , Resultado do Tratamento
8.
Biochem Biophys Res Commun ; 493(2): 1018-1025, 2017 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-28942143

RESUMO

ARID1A as a subunit of SWI/SNF chromatin complexes is frequently mutated in human pancreatic cancer, however its exact role in pancreatic tumorigenesis remain unclear. In this study, we investigated the effects of ARID1A loss on human pancreatic epithelial cell lines HPNE, BxPC-3 with KRAS mutant (KRASG12D) expression. We found that ARID1A knockdown promoted cell proliferation and colony formation in cooperation with active mutant KRASG12D. Function assay revealed that ARID1A knockdown accelerated cell cycle progression, and repressed KRASG12D-induced cell senescence. Transcriptome analysis revealed ARID1A knockdown led to miR-503 upregulation. CDKN2A was identified as a target of miR-503, which contributes to cell senescence. Thus, our data suggests that ARID1A deficiency promote KRASG12D-driven pancreatic tumorigenesis through miR-503/CDKN2A-mediated senescence.


Assuntos
Transformação Celular Neoplásica/patologia , Inibidor de Quinase Dependente de Ciclina p18/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Fatores de Transcrição/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/metabolismo , Perfilação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Pâncreas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Mutação Puntual , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética
9.
Plant Cell Environ ; 40(10): 2068-2080, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28440563

RESUMO

MdMYB1 acts as a crucial component of the MYB-bHLH-WD40 complex to regulate anthocyanin biosynthesis in red-skinned apples (Malus domestica), but little is known about its post-translational regulation. Here, a small ubiquitin-like modifier E3 ligase MdSIZ1 was screened out as an MdMYB1-interacting protein with a yeast two-hybridization approach. The interaction between MdSIZ1 and MdMYB1 was further verified with pull-down and CoIP assays. Furthermore, it was found that MdSIZ1 directly sumoylated MdMYB1 proteins in vivo and in vitro, especially under moderately low temperature (17 °C) conditions, and that this sumoylation was required for MdMYB1 protein stability. Moreover, the transcription level of MdSIZ1 gene was remarkably induced by low temperature and phosphorus deficiency, and MdSIZ1 overexpression exerted a large positive influence on anthocyanin accumulation and red fruit coloration, suggesting its important role in the regulation of anthocyanin biosynthesis under stress conditions. Our findings reveal an important role for a small ubiquitin-like modifier modification of MYB transcription factors in regulation of anthocyanin biosynthesis in plants.


Assuntos
Antocianinas/metabolismo , Temperatura Baixa , Malus/metabolismo , Proteínas de Plantas/metabolismo , Sumoilação , Ubiquitina-Proteína Ligases/metabolismo , Antocianinas/biossíntese , Vias Biossintéticas , Frutas/metabolismo , Modelos Biológicos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Estabilidade Proteica , Proteólise
10.
Int J Occup Environ Med ; 8(1): 50-55, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28051197

RESUMO

A 69-year-old woman was admitted to hospital 4 times from November 2007 to June 2009. The patient had silicosis complicated by broncholithiasis, esophagobronchial fistula, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium esophagography, gastroesophageal endoscopy, and biopsy suggested esophageal-related chronic inflammation and ulcer, which probably caused the repeated esophagobronchial fistulas observed. Bronchoscopy revealed a free broncholithiasis in the left main bronchus. The patient was readmitted a fourth time, for the relapse of silicotuberculosis. After 9 months of antituberculous therapy, she was doing well until the recent last follow-up visit.


Assuntos
Fístula Brônquica/diagnóstico por imagem , Fístula Esofágica/diagnóstico por imagem , Litíase/diagnóstico por imagem , Silicotuberculose/diagnóstico por imagem , Idoso , Fístula Brônquica/tratamento farmacológico , Fístula Esofágica/tratamento farmacológico , Feminino , Humanos , Litíase/tratamento farmacológico , Recidiva , Silicotuberculose/tratamento farmacológico
11.
Food Chem ; 215: 124-8, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27542458

RESUMO

Phloridzin is a nutraceutical. Its use in food, medicine and cosmetics is limited because of its low aqueous solubility and stability limits, but it can be improved by complexing with cyclodextrins. In this study, we investigated the inclusion mechanism between phloridzin and hydroxylpropyl-ß-cyclodextrin (HP-ß-CD) using isothermal titration calorimetry (ITC), ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), proton nuclear magnetic resonance spectroscopy ((1)H NMR) and molecular docking simulations. The ITC results found that the equilibrium binding constant of HP-ß-CD with phloridzin was higher than that of ß-CD. Their inclusion was a spontaneous process with negative ΔG, ΔH and ΔS values. UV spectra showed that the aqueous solubility of phloridzin was enhanced by HP-ß-CD. Our IR analysis verified the inclusion complexation of phloridzin into the HP-ß-CD cavity. The Autodock determined that the substitution distribution of HP-ß-CD influenced not only the orientation and depth degree of phloridzin within the cavity, but also the binding energies.


Assuntos
Florizina/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Calorimetria , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Solubilidade , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
13.
World J Gastroenterol ; 22(18): 4585-93, 2016 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-27182168

RESUMO

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.


Assuntos
Antibacterianos/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Dispepsia/tratamento farmacológico , Esvaziamento Gástrico/efeitos dos fármacos , Gastroparesia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/microbiologia , Dor Abdominal/fisiopatologia , Adulto , Distribuição de Qui-Quadrado , Dispepsia/diagnóstico , Dispepsia/microbiologia , Dispepsia/fisiopatologia , Eructação/tratamento farmacológico , Eructação/microbiologia , Eructação/fisiopatologia , Feminino , Gastroparesia/diagnóstico , Gastroparesia/microbiologia , Gastroparesia/fisiopatologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/patogenicidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/microbiologia , Náusea/fisiopatologia , Razão de Chances , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(3): 327-32, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27236891

RESUMO

OBJECTIVE: To observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism. METHODS: Thirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot. RESULTS: HE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01). CONCLUSION: BHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Falência Renal Crônica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Calcificação Vascular/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Rim/patologia , Falência Renal Crônica/metabolismo , Testes de Função Renal , Túbulos Renais/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
15.
Oncol Lett ; 11(1): 770-774, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870282

RESUMO

Myeloid tumor possessing platelet-derived growth factor receptor ß (PDGFRß) gene rearrangement is a rare hematological malignancy, which presents with typical characteristics of myeloid proliferation disorders and eosinophilia. In the present study, an elderly chronic myelomonocytic leukemia patient was diagnosed with chromosome rearrangement. Fluorescence in situ hybridization (FISH) was conducted with a PDGFRß isolate probe, and gene translocation between PDGFRß on chromosome 5 and genes on the chromosomes of group D (13-15) was detected. Karyotype analysis revealed a chromosome 5 break, and PDGFRß-thyroid hormone receptor interactor 11 (CEV14) gene fusion was confirmed via reverse transcription-polymerase chain reaction (RT-PCR), which additionally revealed the chromosome rearrangement t(5;14)(q33;q32). Due to the correlation between PDGFRß-CEV14 expression and effectiveness of treatment with tyrosine kinase inhibitors, this fusion gene is considered to be an oncogene. In the present study, an elderly patient was diagnosed with a myeloid tumor associated with the fusion gene PDGFRß-CEV14, using the methods of FISH and RT-PCR. These methods were confirmed to be of significant value in improving diagnosis, guiding treatment and increasing the cure rate of patients, due to their ability to detect multiple rearrangement genes associated with PDGFRß in myelodysplastic and myeloproliferative neoplasms.

16.
Zhen Ci Yan Jiu ; 41(6): 521-7, 2016 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29071895

RESUMO

OBJECTIVE: To observe changes of urinary microprotein, and serum creatinine, urea nitrogen and uric acid levels in focal segmental glomerulosclerosis (FSGS) rats treated by mild moxibustion, so as to explore the mechanism of moxibustion underlying improvement of FSGS. METHODS: SD rats were randomized into normal control (normal), sham operation (sham), model, medication (Losartan), moxibustion-Shenshu (BL 23) and moxibustion-Geshu (BL 17) groups. The latter two moxibustion groups were further divided into 10 min, 20 min and 30 min subgroups (n=6 in each group/subgroups). The FSGS model was established by unilateral nephrectomy combined with injection of Losartan into the tail vein twice. Mild moxibustion was applied to bilateral BL 17 and BL 23 for 10, 20 and 30 min, respectively, once every other day, for 12 weeks. The contents of urinary microglobulin α 1, micro-albumin, transferring and IgG were assayed using enzyme linked immunosorbent assay (ELISA), and serum creatinine, urea nitrogen and uric acid contents (indexes of renal function) determined using an automatic biochemical analyzer. The pathological changes of the kidney tissue was observed by using a microscope after periodic acid schiff (PAS) staining. RESULTS: No significant differences were found between the normal control and sham groups in the levels of all the urinary and serum indexes (P>0.05) and pathological changes of the renal tissues. Compared with the normal control group, the contents of urinary microglobulin α 1, micro-albumin, transferrin and IgG, and serum creatinine, urea nitrogen and uric acid were significantly increased in the model group (P<0.01). Following medication and moxibustion, the contents of the aforementioned 7 indexes in the Losartan group, and urinary microglobulin α 1, micro-albumin, transferrin and IgG, and serum creatinine levels in the moxibustion BL 23-20 min and 30 min groups, and the micro-albumin and transferrin contents in the BL-17 10 min group and IgG level in the BL-23 10 min group, the serum creatinine and urea nitrogen levels at the 3 time-points of both moxibustion BL 23 and BL 17 groups, and serum uric acid in the moxibustion BL 23 30 min, and BL17 20 and 30 min groups were all considerably down-regulated (P<0.05, P<0.01). The therapeutic effects of moxibustion 30 min were notably better than moxibustion 10 min in reducing urinary microglobulin α 1, micro-albumin, transferring and IgG levels (P<0.05, P<0.01). Results of PAS staining showed that the injury of the renal tissue as the endothelial and mesangial cellular proliferation, collagen proteinosis, interstitial fibrosis, etc were relatively milder in the Losartan and moxibustion 20 and 30 min groups. CONCLUSIONS: Mild moxibustion may reduce proteinuria, and improve the kidney function and pathological changes in FSGS rats, and longer duration of moxibustion is better in achieving therapeutic effect.


Assuntos
Pontos de Acupuntura , Glomerulosclerose Segmentar e Focal/terapia , Rim/fisiopatologia , Moxibustão , Animais , Creatinina/sangue , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Ácido Úrico/metabolismo
17.
Molecules ; 20(11): 20460-72, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26593891

RESUMO

Peach blossoms were harvested and classified into six developmental stages: (I) bud emerging stage; (II) middle bud stage; (III) large bud stage; (IV) initial-flowering stage; (V) full-flowering stage; and (VI) end-flowering stage. The contents of total phenolics, flavanoids, individual phenolic compounds as well as antioxidant and tyrosinase inhibitory activity of peach blossoms at different developmental stages were investigated. The total phenolic contents varied from 149.80 to 74.80 mg chlorogenic acid equivalents/g dry weight (DW), and the total flavanoid contents ranged from 93.03 to 44.06 mg rutin equivalents/g DW. Both the contents of total phenolics and flavanoids decreased during blossom development. Chlorogenic acid was the predominant component, accounting for 62.08%-71.09% of the total amount of identified phenolic compounds in peach blossom. The antioxidant capacities determined by different assays and tyrosinase inhibitory activity also showed descending patterns during blossom development. Significant correlations were observed between antioxidant capacities with contents of total phenolics and total flavanoids as well as chlorogenic acid, cinnamic acid and kaempferol-3-O-galactoside, while the tyrosinase inhibitory activity had lower correlations with total phenolics and total flavanoids as well as chlorogenic acid, quercetin-3-O-rhamnoside, kaempferol-3-O-galactoside and cinnamic acid. The antioxidant activities of peach blossom seemed to be more dependent on the phenolic compounds than tyrosinase inhibitory activity.


Assuntos
Antioxidantes/química , Inibidores Enzimáticos/química , Flavonoides/química , Flores/química , Fenóis/química , Extratos Vegetais/química , Prunus persica/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Concentração Inibidora 50 , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fenóis/farmacologia , Extratos Vegetais/farmacologia
18.
J Cell Biochem ; 116(2): 268-76, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25187230

RESUMO

MicroRNAs (miRNAs) play an important role in the development and progression of non-small cell lung cancer (NSCLC). Recently, several studies have shown that miR-99a is downregulated in various cancers, which can affect tumor initiation and maintenance. Herein, we found that miR-99a was downregulated in NSCLC tissues and suppressed tumor metastasis of NSCLC cells. Down-regulation of miR-99a is significantly associated with last-stage and tumor metastasis in NSCLC patients. Further functional experiments found that overexpression of miR-99a inhibit cell proliferation, migration, and invasion of NSCLC cells in vitro and tumor metastasis of NSCLC in vivo. In addition, we also found that AKT1 is directly involved in miR-99a-mediated tumor suppression. Restored the expression of AKT1 partially abolished the suppressive effects miR-99a on proliferation and invasion of NSCLC cells. Collectively, our data suggest that miR-99a plays an important role in the tumorigenesis and metastasis of NSCLC and may serve as a therapeutic target to avoid dissemination of NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Immunoblotting , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
19.
Cancer Lett ; 344(1): 129-137, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24189459

RESUMO

Myocardin-related transcription factor-A (MRTF-A) is a Rho signal-responsive transcriptional coactivator of serum response factor (SRF). Recent studies indicated that MRTF-A might be an important regulator of mammary gland and be involved in cancer metastasis. However, the roles of histone modification in the MRTF-A-dependent signal pathway and tumor migration are still not very clear. Here, we report that histone methylation is required for the MRTF-A-mediated upregulation of myosin regulatory light chain 9 (MYL9), an important cytoskeletal component which is implicated in cell migration. Furthermore, we demonstrate that SET and MYND domain containing protein 3 (SMYD3), a hitone methyltransferase (HMT) associated with carcinogenesis, might be the one which is responsible for the histone methylation occurred in the MRTF-A-mediated- transactivation of MYL9 and migration of breast cancer cells. Overexpression of SMYD3 promotes MRTF-A-mediated upregulation of MYL9 and migration of MCF-7 breast cancer cells, while contrary results were observed when the endogenous MRTF-A and SMYD3 were suppressed with specific siRNAs. In addition, the mutation analysis suggested that this cooperative transactivation is mainly mediated via the proximal binding element of MRTF-A in the promoter of MYL9, and the HMT activity of SMYD3 is required as well. Our findings reveal a new mechanism by which MRTF-A and SMYD3 functions in transcriptional regulation and cell migration, and provide a better understanding for metastasis of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular , Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteínas Supressoras de Tumor/metabolismo , Western Blotting , Neoplasias da Mama/patologia , Humanos , Imuno-Histoquímica , Imunoprecipitação , Células MCF-7 , Invasividade Neoplásica , Proteína da Leucemia Promielocítica , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores , Transfecção
20.
J Ethnopharmacol ; 148(2): 610-6, 2013 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-23702037

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hong Yao aerosol (HYA) is a new dosage form developed from Hong Yao, a traditional Chinese medicine preparation, which has the efficacy of promoting soft tissue contusion repair, anti-inflammation, and analgesia. AIM: To evaluate the soft tissue contusion repairing, anti-inflammatory and analgesic effects of HYA formulations with different penetration enhancers (PE) and to quantify the transdermal absorption of HYA component. MATERIALS AND METHODS: Three preparations of HYA with different PEs were made: DMSO preparation (5% DMSO as additional PE), Azone preparation (3% azone as additional PE), and NAPE preparation (no additional PE). Four in vivo rodent models were employed to evaluate the pharmacodynamic effects of the HYAs: mouse soft tissue contusion model, rat paw edema model, mouse ear swelling model, and mouse analgesia model of electric-stimulated foot. In vitro skin penetration experiment was applied to evaluate the transdermal absorption of HYA components. RESULTS: All HYA preparations showed effects on soft tissue contusion repairing, anti-inflammation, and analgesia compared with the blank control (p<0.05). There was no significant difference among the three preparations. Pathological variation of mice skin and the pain response time (PRT) reduction phenomena indicated that DMSO preparation induced skin irritation. In vitro skin penetration experiment showed no significant difference between DMSO and NAPE on absorption enhancement of ferulic acid from HYA. CONCLUSIONS: NAPE preparation was considered as best and Menthol/borneol (6.3%, W/W, 4:1.75) in HYA might be a good PE combination.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Contusões/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Administração Cutânea , Animais , Contusões/metabolismo , Modelos Animais de Doenças , Edema/tratamento farmacológico , Feminino , Masculino , Camundongos , Dor/tratamento farmacológico , Distribuição Aleatória , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos
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