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1.
J Cell Mol Med ; 27(16): 2290-2307, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37482908

RESUMO

Protocatechuic acid (3,4-dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol-induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high-dose isoproterenol (80 mg/kg body weight) for 14 days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol-induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart-weight-to-body-weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine-3-monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short-interfering RNA against Kmo ameliorated transforming growth factor ß1-induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. Kmo knockdown attenuated the isoproterenol-induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression-induced increases in Nppb mRNA levels. Protocatechuic acid or Kmo knockdown decreased isoproterenol-induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.


Assuntos
Insuficiência Cardíaca , Quinurenina 3-Mono-Oxigenase , Camundongos , Ratos , Animais , Isoproterenol/toxicidade , Quinurenina 3-Mono-Oxigenase/genética , Quinurenina 3-Mono-Oxigenase/metabolismo , Quinurenina 3-Mono-Oxigenase/farmacologia , Cinurenina/metabolismo , Cinurenina/farmacologia , Cinurenina/uso terapêutico , Camundongos Endogâmicos C57BL , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/prevenção & controle , Miócitos Cardíacos/metabolismo
2.
Plant Cell Rep ; 41(8): 1721-1731, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35739429

RESUMO

KEY MESSAGE: In SlHDC-A promoter, SlHDC-A core-ES is an essential region for fruit-specific expression and interacts with GATA, HSF and AP1. Triplication of essential region was proposed as a minimal fruit-specific promoter. In plant biotechnology, fruit-specific promoter is an important tool for the improvement and utilization of tomato fruit. To expand our understanding on fruit-specific expression, it is necessary to determine the promoter region involved in fruit-specific transcriptional activity and transcriptional regulations of the promoter. In previous study, we isolated a fruit-specific SlHDC-A core promoter specifically expressed during tomato ripening stages. In this study, we identified SlHDC-A promoter region (SlHDC-A core-ES) that is essential for fruit-specific expression of the SlHDC-A. To understand the molecular mechanisms of fruit-specific expression of the SlHDC-A promoter, we first identified the putative transcription factor binding elements in the SlHDC-A core promoter region and corresponding putative transcription factors which are highly expressed during fruit maturation. Yeast one hybrid analysis confirmed that GATA, HSF, and AP1 interact with the SlHDC-A core-ES promoter region. Further transactivation analysis revealed that expression of the three transcription factors significantly activated expression of a reporter gene driven by SlHDC-A core-ES promoter. These results suggest that GATA, HSF, and AP1 are involved in the fruit-specific expression of SlHDC-A promoter. Furthermore, the synthetic promoter composed of three tandem repeats of SlHDC-A core-ES showed relatively higher activity than the constitutive 35S promoter in the transgenic tomato fruits at the orange stage. Taken together, we propose a new synthetic promoter that is specifically expressed during fruit ripening stage.


Assuntos
Solanum lycopersicum , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Histidina Descarboxilase/genética , Histidina Descarboxilase/metabolismo , Solanum lycopersicum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
Molecules ; 27(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889464

RESUMO

The annual herb Euphorbia maculata L. produces anti-inflammatory and biologically active substances such as triterpenoids, tannins, and polyphenols, and it is used in traditional Chinese medicine. Of these bioactive compounds, terpenoids, also called isoprenoids, are major secondary metabolites in E. maculata. Full-length cDNA sequencing was carried out to characterize the transcripts of terpenoid biosynthesis reference genes and determine the copy numbers of their isoforms using PacBio SMRT sequencing technology. The Illumina short-read sequencing platform was also employed to identify differentially expressed genes (DEGs) in the secondary metabolite pathways from leaves, roots, and stems. PacBio generated 62 million polymerase reads, resulting in 81,433 high-quality reads. From these high-quality reads, we reconstructed a genome of 20,722 genes, in which 20,246 genes (97.8%) did not have paralogs. About 33% of the identified genes had two or more isoforms. DEG analysis revealed that the expression level differed among gene paralogs in the leaf, stem, and root. Whole sets of paralogs and isoforms were identified in the mevalonic acid (MVA), methylerythritol phosphate (MEP), and terpenoid biosynthesis pathways in the E. maculata L. The nucleotide information will be useful for identifying orthologous genes in other terpenoid-producing medicinal plants.


Assuntos
Euphorbia , DNA Complementar/genética , Euphorbia/genética , Euphorbia/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Terpenos/metabolismo , Transcriptoma/genética
4.
J Nanosci Nanotechnol ; 14(3): 2343-51, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24745230

RESUMO

Various SBA-15-based catalysts, Si-SBA-15, Pt/Si-SBA-15, Al-SBA-15, and Pt/Al-SBA-15, were applied to the catalytic pyrolysis of miscanthus. Pt nanoparticles with three different sizes, 1.7 nm, 2.9 nm, and 7.1 nm, were used to synthesize Pt/Si-SBA-15 and Pt/Al-SBA-15. Pyrolysis-gas chromatography/mass spectrometry was used for the pyrolysis experiments. The catalysts were characterized by X-ray diffraction patterns, transmittance electron microscopy, N2 adsorption-desorption, and Brunaure-Emmett-Teller surface area. The product species distribution of pyrolysis of miscanthus was significantly affected by the acid property of the catalyst and the presence of Pt. In particular, Pt/Al-SBA-15, which has both acid sites and Pt, changed the product species distribution to the largest extent; the main products were phenolics and furans. The effect of Pt particle size on the species distribution of pyrolysis product was negligible.


Assuntos
Poaceae/metabolismo , Dióxido de Silício/química , Adsorção , Alumínio/química , Fontes de Energia Bioelétrica , Biomassa , Carbono/química , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Oxigênio/química , Tamanho da Partícula , Fenol/química , Platina/química , Silício/química , Propriedades de Superfície , Difração de Raios X
5.
J Nanosci Nanotechnol ; 14(3): 2527-31, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24745258

RESUMO

Low-temperature selective catalytic reduction was carried out over various kinds of manganese oxide (MnOx) catalysts. Mesoporous alpha-Mn2O3, commercial bulk Mn2O3, and Mn/SBA-15 were used as the catalyst. The NOx removal performances of the catalysts were compared. Three different amounts of Mn (5, 10, and 15 wt%) were impregnated on SBA-15 to synthesize Mn/SBA-15. The physical and chemical properties of the catalysts were examined by Brunauer-Emmett-Teller, X-ray diffraction, X-ray photoelectron spectroscopy, and H2-temperature programmed reduction analyses. Of all catalysts examined, mesoporous alpha-Mn2O3 exhibited the highest low-temperature SCR de-NOx efficiency, reaching about 90% at 175 degrees C. This is attributed to strong reducing ability and high oxygen mobility of mesoporous alpha-Mn2O3 and well dispersed Mn2O3 in its mesoporous framework.


Assuntos
Compostos de Manganês/química , Óxidos de Nitrogênio/química , Nitrogênio/química , Óxidos/química , Catálise , Recuperação e Remediação Ambiental , Hidrogênio/química , Espectroscopia Fotoeletrônica , Porosidade , Dióxido de Silício/química , Temperatura
6.
Plants (Basel) ; 12(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37050109

RESUMO

Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.

7.
Eur J Haematol ; 87(2): 172-81, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21599753

RESUMO

OBJECTIVES: Acute graft-versus-host disease (GVHD) usually occurs with neutrophil engraftment following allogeneic hematopoietic cell transplantation (HCT), but it can also occur before engraftment. We intended to analyze the effects of timing of acute GVHD on leukemia relapse and mortality. METHODS: The outcomes of pre- and postengraftment GVHD were investigated in 384 patients who underwent allogeneic HCT for acute leukemia. RESULTS: Acute GVHD occurred in 100 patients, pre-engraftment in 22 and postengraftment in 78. Compared with postengraftment GVHD, pre-engraftment GVHD was more severe, as assessed by overall grade, with more frequent and more severe skin involvement and higher incidences of non-infectious fever, diarrhea, hepatic dysfunction, renal insufficiency, and weight gain. Compared with patients without acute GVHD, those with postengraftment GVHD had lower cumulative incidence of relapse [CIR; hazard ratio (HR), 0.470; P=0.006] and higher cumulative incidence of non-relapse mortality (CINRM; HR, 2.568; P<0.001), while those with pre-engraftment GVHD had similar CIR (HR, 0.815; P=0.059) and higher CINRM (HR, 2.872; P=0.036). Overall survival of patients with pre-engraftment GVHD was lower than that of those without acute GVHD (HR, 1.976; P=0.017), which was similar to that of those with postengraftment GVHD (HR, 0.969; P=0.878). Separate analyses of the effects of timing of acute GVHD on post-transplant outcomes in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) showed similar trends. CONCLUSION: Pre-engraftment GVHD might be a 'cytokine storm' type syndrome rather than 'real' GVHD, indicating the need for separate analyses of pre- and postengraftment GVHD in future trials.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doença Aguda , Adolescente , Adulto , Doença Crônica , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Recidiva , República da Coreia/epidemiologia , Fatores de Tempo , Transplante Homólogo , Adulto Jovem
8.
Cancers (Basel) ; 13(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916047

RESUMO

With the introduction of modern sophisticated radiotherapy (RT) techniques, the significance of accuracy has increased considerably. This study evaluated the necessity of pre-treatment and intra-fractional cone-beam computed tomography (CBCT) by analyzing inter- and intra-fractional CBCT images of breast cancer patients receiving RT. From 57 patients, 1206 pre-treatment CBCT and 1067 intra-fractional CBCT images were collected. Geometric movements of patients were measured quantitively in both inter- and intra-fractional CBCT, and changes in dosimetric parameters were evaluated in selected patients with extreme intra-fractional movement. For right-sided breast cancer patients, left-sided breast cancer patients treated using deep-inspiration breath hold (DIBH), and left-sided breast cancer patients treated using continuous positive airway pressure (CPAP), median inter-fractional deviations were 0.53 (range 0.06-2.98) cm, 0.66 (range 0.08-4.41) cm, and 0.69 (range 0.04-3.80) cm, and median intra-fractional deviations were 0.14 (range 0.00-0.62) cm, 0.23 (range 0.02-0.96) cm, and 0.24 (0.00-1.15) cm, respectively. Modified plans reflecting large changes in intra-fractional position in 10 selected cases revealed insufficient target coverage in seven cases and more than 20-fold increase in the volume of heart receiving at least 25 Gy in two cases. Intra-fractional verification, as well as pre-treatment verification, might be considered in patients using DIBH or CPAP.

9.
Mycobiology ; 49(5): 491-497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803437

RESUMO

An endolichenic fungus Xylaria grammica EL000614 produces grammicin, a potent nematicidal pyrone derivative that can serve as a new control option for root-knot nematodes. We optimized an Agrobacterium tumefaciens-mediated transformation (ATMT) protocol for X. grammica to support genetic studies. Transformants were successfully generated after co-cultivation of homogenized young mycelia of X. grammica with A. tumefaciens strain AGL-1 carrying a binary vector that contains the bacterial hygromycin B phosphotransferase (hph) gene and the eGFP gene in T-DNA. The resulting transformants were mitotically stable, and PCR analysis showed the integratin of both genes in the genome of transformants. Expression of eGFP was confirmed via fluorescence microscopy. Southern analysis showed that 131 (78.9%) out of 166 transformants contained a single T-DNA insertion. Crucial factors for producing predominantly single T-DNA transformants include 48 h of co-cultivation, pre-treatment of A. tumefaciens cells with acetosyringone before co-cultivation, and using freshly prepared mycelia. The established ATMT protocol offers an efficient tool for random insertional mutagenesis and gene transfer in studying the biology and ecology of X. grammica.

10.
Plants (Basel) ; 10(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203474

RESUMO

Berberis koreana is a medicinal plant containing berberine, which is a bioactive compound of the benzylisoquinoline alkaloid (BIA) class. BIA is widely used in the food and drug industry for its health benefits. To investigate the berberine biosynthesis pathway, gene expression analysis was performed in leaves, flowers, and fruits at different stages of growth. This was followed by full-length cDNA sequencing analysis using the PacBio sequencer platform to determine the number of isoforms of those expressed genes. We identified 23,246 full-length unigenes, among which 8479 had more than one isoform. The number of isoforms ranged between two to thirty-one among all genes. Complete isoform analysis was carried out on the unigenes encoding BIA synthesis. Thirteen of the sixteen genes encoding enzymes for berberine synthesis were present in more than one copy. This demonstrates that gene duplication and translation into isoforms may contribute to the functional specificity of the duplicated genes and isoforms in plant alkaloid synthesis. Our study also demonstrated the streamlining of berberine biosynthesis via the absence of genes for enzymes of other BIAs, but the presence of all the genes for berberine biosynthesize in B. koreana. In addition to genes encoding enzymes for the berberine biosynthesis pathway, the genes encoding enzymes for other BIAs were not present in our dataset except for those encoding corytuberine synthase (CTS) and berbamunine synthase (BS). Therefore, this explains how B. koreana produces berberine by blocking the pathways leading to other BIAs, effectively only allowing the pathway to lead to berberine synthesis.

11.
Mycobiology ; 49(3): 294-296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290553

RESUMO

An endolichenic fungus, Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin. We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

12.
Microbiol Resour Announc ; 9(14)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241861

RESUMO

The fungus Daldinia childiae strain JS-1345, isolated from stem tissue of Abies koreana (Korean fir), has shown strong anti-inflammatory activity. Here, we report the genome sequence of D. childiae JS-1345. The final assembly consisted of 133 scaffolds totaling 38,652,569 bp (G+C content, 44.07%).

13.
Mycobiology ; 48(3): 240-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-37970559

RESUMO

Alternaria alternata JS-1623 is an endophytic fungus isolated from a stem tissue of Korean fir, Abies koreana. Ethyl acetate extracts of culture filtrates exhibited anti-inflammatory activity in LPS induced microglia BV-2 cell without cytotoxicity. Here we report a 33.67 Mb sized genome assembly of JS-1623 comprised of 13 scaffolds with N50 of 4.96 Mb, and 92.41% of BUSCO completeness. GC contents were 50.97%. Of the 11,197 genes annotated, gene families related to the biosynthesis of secondary metabolites or transcription factors were identified.

14.
Front Oncol ; 9: 366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139564

RESUMO

Background: Sarcopenia, defined as skeletal muscle loss, has been known as a poor prognosis factor in various malignant diseases The aim of this study is to investigate the effect of sarcopenia on prognosis in patients with esophageal cancer who received concurrent chemo- and radiotherapy (CCRT). Methods: We retrospectively collected clinical data of 287 patients with esophageal cancer who were treated by definite CCRT at Gangnam Severance and Severance hospital from August 2005 to December 2014. The cross-sectional area of muscle at the level of the third lumbar vertebra was measured using pre- and post-CCRT computed tomography images. Sarcopenia was defined as skeletal muscle index <49 cm2/m2 for men and of <31 cm2/m2 for women by Korean-specific cutoffs. Overall survival (OS) and progression free survival (PFS) were analyzed according to sarcopenia. Results: Sarcopenia identified before CCRT did not affect OS and PFS. However, patients with post-CCRT sarcopenia showed shorter OS and PFS than patients without it (median OS: 73 months vs. 28 months; median PFS: 34 months vs. 25 months, respectively). Post-CCRT sarcopenia was an independent prognostic factor of poor OS (hazards ratio: 1.697; 95% confidence interval: 1.036-2.780; P = 0.036). In multivariate analysis, male sex (P = 0.004) and presence of CCRT-related complications, such as esophagitis or general weakness were significantly associated with post-CCRT sarcopenia (P = 0.016). Conclusions: Sarcopenia after CCRT can be a useful predictor for long-term prognosis in patients with esophageal cancer. To control CCRT-related complications may be important to prevent skeletal muscle loss during CCRT.

15.
Mol Cell Endocrinol ; 270(1-2): 79-86, 2007 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-17416458

RESUMO

We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 microM), but not by low doses RO 31-8220 (0.1-1.0 microM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCzeta activity. Interestingly, like LH, forskolin was also able to activate PKCzeta. Treatment with the cell-permeable PKCzeta-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCzeta. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCzeta pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCzeta in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.


Assuntos
Colforsina/farmacologia , Proteínas de Ligação a DNA/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/enzimologia , Hormônio Luteinizante/farmacologia , Ovulação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismo , Fatores de Transcrição/metabolismo , Adenoviridae , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Genes Dominantes , Vetores Genéticos , Indóis/farmacologia , Isoenzimas/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Ésteres de Forbol/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos
16.
Oncotarget ; 8(15): 25660-25668, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-27784001

RESUMO

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia Conformacional/métodos , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Resultado do Tratamento , Carga Tumoral
17.
Arch Pharm Res ; 28(8): 942-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16178421

RESUMO

Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and superoxide and induces NO-mediated inflammation under neuropathological conditions. Previously, we reported that glucose deprivation induced ATP depletion and cell death in immunostimulated astrocytes, which was mainly due to peroxynitrite. In this study, the role of MAPKs (ERK1/2, p38MAPK, and JNK1SAPK) signal pathway in the SIN-1/glucose deprivation-induced death of astrocytes was examined. A combined treatment with glucose deprivation and 50 microM SIN-1, an endogenous peroxynitrite generator, rapidly and markedly increased the death in rat primary astrocytes. Also, SIN-1/glucose deprivation resulted in the activation of MAPKs, which was significantly blocked by the treatment with 20 microM MAPKs inhibitors (ERK1/2, PD98059; p38MAPK, SB203580; JNK/SAPK, SP600125). Interestingly, SIN-1/glucose deprivation caused the loss of intracellular ATP level, which was significantly reversed by MAPKs inhibitors. These results suggest that the activation of MAPKs plays an important role in SIN-1/glucose deprivation-induced cell death by regulating the intracellular ATP level.


Assuntos
Astrócitos/metabolismo , Astrócitos/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Ácido Peroxinitroso , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antracenos/farmacologia , Astrócitos/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Técnicas de Cultura de Células , Morte Celular/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Glucose/deficiência , Imidazóis/farmacologia , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Doadores de Óxido Nítrico/farmacologia , Ácido Peroxinitroso/biossíntese , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
18.
Anticancer Res ; 33(9): 3715-23, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24023301

RESUMO

The metastatic potential of non-small cell lung cancer (NSCLC) has been shown to be associated with interactions with the tumor microenvironment, which primarily comprises of cancer-associated fibroblasts (CAFs). Heterotypic cell-cell interactions occur via released signaling molecules and direct physical contact. To investigate the differential contribution of direct cell-cell contact and paracrine signaling factors to NSCLC metastasis, we performed two types of co-cultures: direct co-cultures of the NSCLC cell line H358 with primary cultures of CAFs from patients with resected NSCLC; and indirect co-cultures across a separable membrane. We showed that CAFs more potently induce epithelial-to-mesenchymal transition (EMT) in NSCLC H358 cells through direct contacts than through indirect interactions, as indicated by an elongated and disseminated appearance. Immunocytochemical experiments show that EMT accompanies the expression of mesenchymal cytoskeletal proteins, including vimentin. However, H358 cells proliferate more slowly in direct co-culture than in indirect co-culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed that H358 cells in direct contact with CAFs up-regulate the expression of the pan-mesenchymal markers α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), transforming growth factor-ß (TGFß) signaling effector SMAD family number-3 (SMAD3), and hedgehog signaling effector GLI family zinc finger-1 (GLI1), compared with the indirect co-culture system. Furthermore, we found that the direct GLI1 transcription targets snail family zinc finger-1 (SNAI1) and SNAI2 are up-regulated, suggesting that the hedgehog signaling pathway is active in direct co-culture. A scratch wound assay showed that direct contact co-culture increases the motility of H358 cells. In conclusion, these findings provide evidence that paracrine factors and direct physical contact between NSCLC cells and CAFs might control the metastatic potential of NSCLC through the hedgehog signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Hedgehog/metabolismo , Neoplasias Pulmonares/patologia , Comunicação Parácrina , Células Estromais/patologia , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Divisão Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Primers do DNA , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Pulmonares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Anticancer Res ; 33(5): 2001-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23645749

RESUMO

The metastatic potential of non-small cell lung cancer (NSCLC) cells has been shown to be associated with the tumor microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment, regulating tumor cell function by secreting growth factors, chemokines, and extracellular matrix (ECM). In this study, we examined the role of CAFs in the tumor progression of NSCLC. Firstly, we established primary cultures of CAFs and matched normal fibroblasts (NFs) from patients with resected NSCLC. CAFs exhibited greater expression of the pan-mesenchymal marker α-smooth muscle actin (α-SMA) than did NFs, although they displayed similar morphology. Furthermore, we employed a direct co-culture assay with human NSCLC A549 and H358 cells, and found that CAFs were more potent in inducing the epithelial-to-mesenchymal transition (EMT) phenotype than NFs, as indicated by an elongated and disseminated appearance. CAF-induced EMT led to an increase in motility and a decrease in proliferation of NSCLC cells through SMAD family number-3 (SMAD3)-dependent up-regulation of the growth inhibitory gene p21(CIP1) [cyclin-dependent kinase inhibitor-1A (CDKN1A)] and α-SMA. Taken together, these findings provide evidence that lung CAFs have tumor-promoting capacity distinct from NFs and might play a significant role in the metastatic potential of NSCLC.


Assuntos
Adenocarcinoma Bronquioloalveolar/patologia , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Transição Epitelial-Mesenquimal , Fibroblastos/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Bronquioloalveolar/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Adesão Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Fibroblastos/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/citologia , Pele/metabolismo , Cicatrização
20.
Nanoscale Res Lett ; 7(1): 18, 2012 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-22221540

RESUMO

Catalytic fast pyrolysis of waste rice husk was carried out using pyrolysis-gas chromatography/mass spectrometry [Py-GC/MS]. Meso-MFI zeolite [Meso-MFI] was used as the catalyst. In addition, a 0.5-wt.% platinum [Pt] was ion-exchanged into Meso-MFI to examine the effect of Pt addition. Using a catalytic upgrading method, the activities of the catalysts were evaluated in terms of product composition and deoxygenation. The structure and acid site characteristics of the catalysts were analyzed by Brunauer-Emmett-Teller surface area measurement and NH3 temperature-programmed desorption analysis. Catalytic upgrading reduced the amount of oxygenates in the product vapor due to the cracking reaction of the catalysts. Levoglucosan, a polymeric oxygenate species, was completely decomposed without being detected. While the amount of heavy phenols was reduced by catalytic upgrading, the amount of light phenols was increased because of the catalytic cracking of heavy phenols into light phenols and aromatics. The amount of aromatics increased remarkably as a result of catalytic upgrading, which is attributed to the strong Brönsted acid sites and the shape selectivity of the Meso-MFI catalyst. The addition of Pt made the Meso-MFI catalyst even more active in deoxygenation and in the production of aromatics.

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