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1.
Dysphagia ; 39(1): 43-51, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37204525

RESUMO

This study aimed to develop a standardized protocol for the assessment of videofluoroscopic dysphagia scale (VDS) and to demonstrate the inter-rater and intra-rater reliability of the VDS by applying the new standard protocol. A standardized protocol for the VDS was developed by dysphagia experts, including the original developer. To identify the reliability of the VDS using the protocol, 60 patients who underwent videofluoroscopic swallowing study (VFSS) for various etiologies were recruited retrospectively from three tertiary medical centers. Ten randomly selected cases were duplicated to evaluate the intra-rater reliability. Six physicians evaluated the VFSS data sets. Intraclass correlation coefficients were calculated for inter-rater and intra-rater reliability of the VDS score, and Gwet's kappa values for each VDS item were calculated. The inter-rater and intra-rater reliability of the total VDS score was 0.966 and 0.896, respectively. Notably, the evaluators' experience did not appear to have a significant impact on the reliability (physiatrists: 0.933/0.869, residents: 0.922/0.922). The reliability was consistent across different centers and dysphagia etiologies. The inter-rater and intra-rater reliability of the oral and pharyngeal sub-scores were 0.953/0.861 and 0.958/0.907, respectively. The inter-rater agreement of individual items ranged from 0.456 to 0.929, and nine items demonstrated good to very good level of agreement. Assessment of dysphagia using the VDS with the standard protocol showed excellent inter-rater and intra-rater reliabilities regardless of the evaluator's experience, VFSS equipment, and dysphagia etiologies. The VDS can be a useful assessment scale in the quantitative analysis of dysphagia based on VFSS findings.


Assuntos
Transtornos de Deglutição , Humanos , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Deglutição , Estudos Retrospectivos , Reprodutibilidade dos Testes , Cinerradiografia/efeitos adversos
2.
Front Genet ; 14: 1289557, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028631

RESUMO

The glycolytic pathway involves phosphofructokinase (PFK), a rate-limiting enzyme that catalyzes the phosphorylation of fructose-6-phosphate. In plants, the two PFK members are ATP-dependent phosphofructokinase (PFK) and pyrophosphate-fructose-6-phosphate phosphotransferase (PFP). However, the functions of the PFK family members in Quercus rubra are not well understood. The purpose of this study was to investigate the genome-wide distribution of the PFK family members and their roles in Q. rubra by performing a systematic study of the phylogenetic relationships, molecular characteristics, motifs, chromosomal and subcellular locations, and cis-elements of QrPFKs. We identified 14 QrPFK genes in the genome of Q. rubra, followed by examining their expression in different tissues, including the roots, stems, and leaves. The phylogenetic tree divided the 14 QrPFK genes into two groups: 11 belonging to PFK and three belonging to PFP. The expression profiles of all 14 proteins were relatively the same in leaves but differed between stems and roots. Four genes (Qurub.02G189400.1, Qurub.02G189400.2, Qurub.09G134300.1, and Qurub.09G134300.2) were expressed at very low levels in both stems and roots, while two (Qurub.05G235500.1 and Qurub.05G235500.1) were expressed at low levels and the others showed relatively high expression in all tissues.

3.
Plants (Basel) ; 12(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37765403

RESUMO

Drought stress affects plant productivity by altering plant responses at the morphological, physiological, and molecular levels. In this study, we identified physiological and genetic responses in Populus alba × Populus glandulosa hybrid clones 72-30 and 72-31 after 12 days of exposure to drought treatment. After 12 days of drought treatment, glucose, fructose, and sucrose levels were significantly increased in clone 72-30 under drought stress. The Fv/Fo and Fv/Fm values in both clones also decreased under drought stress. The changes in proline, malondialdehyde, and H2O2 levels were significant and more pronounced in clone 72-30 than in clone 72-31. The activities of antioxidant-related enzymes, such as catalase and ascorbate peroxidase, were significantly higher in the 72-31 clone. To identify drought-related genes, we conducted a transcriptomic analysis in P. alba × P. glandulosa leaves exposed to drought stress. We found 883 up-regulated and 305 down-regulated genes in the 72-30 clone and 279 and 303 in the 72-31 clone, respectively. These differentially expressed genes were mainly in synthetic pathways related to proline, abscisic acid, and antioxidants. Overall, clone 72-31 showed better drought tolerance than clone 72-30 under drought stress, and genetic changes also showed different patterns.

4.
Brain Neurorehabil ; 16(1): e9, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033003

RESUMO

Cardiopulmonary function is exceptionally critical during the early stages of rehabilitation after neurological disorders such as stroke, spinal cord injury and Parkinson's disease. This study aimed to demonstrate how robot-assisted and tilt table exercises affect cardiopulmonary function. In this study, ten healthy young adults performed six combinations of conditions according to robot-assisted mode (on/off), angle of tilt table (20°/60°), and functional electrical stimulation (FES) mode (on/off). Four conditions had FES mode off with combinations of robot-assisted mode (on/off) and tilt angle (20°/60°) and two conditions had robot-assisted mode and FES on with tilt angle (20°/60°). Cardiopulmonary effects (oxygen uptake [VO2], peak oxygen uptake [VO2peak], metabolic energy cost [MET], rate pressure product [RPP], heart rate [HR], maximum heart rate [%HRmax], and minute ventilation [VE]) were compared in each condition. As a result, in the angle and FES mode effect, VO2, VO2peak, MET, RPP, HR, and %HRmax, unlike that for VE, showed major effects in angle. In addition, in the robot-assisted mode and angle effect, when the FES was switched off, VO2, METs, and VE values showed major effects in the robot-assisted mode, whereas all other values showed major effects in angle. Compared to earlier reported findings, we can expect that robot-assisted tilt table training can lead to changes in the cardiopulmonary function.

5.
Plants (Basel) ; 11(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36559641

RESUMO

Physiological response and transcriptome changes were observed to investigate the effects on the growth, metabolism and genetic changes of Pinus densiflora grown for a long time in an environment with an elevated atmospheric CO2 concentration. Pine trees were grown at ambient (400 ppm) and elevated (560 ppm and 720 ppm) CO2 concentrations for 10 years in open-top chambers. The content of nonstructural carbohydrates was significantly increased in elevated CO2. It was notable that the contents of chlorophylls significantly decreased at an elevated CO2. The activities of antioxidants were significantly increased at an elevated CO2 concentration of 720 ppm. We analyzed the differences in the transcriptomes of Pinus densiflora at ambient and elevated CO2 concentrations and elucidated the functions of the differentially expressed genes (DEGs). RNA-Seq analysis identified 2415 and 4462 DEGs between an ambient and elevated CO2 concentrations of 560 ppm and 720 ppm, respectively. Genes related to glycolysis/gluconeogenesis and starch/sucrose metabolism were unchanged or decreased at an elevated CO2 concentration of 560 ppm and tended to increase at an elevated CO2 concentration of 720 ppm. It was confirmed that the expression levels of genes related to photosynthesis and antioxidants were increased at an elevated CO2 concentration of 720 ppm.

6.
J Bone Miner Metab ; 40(4): 602-612, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35347431

RESUMO

INTRODUCTION: Patients with Parkinson's disease (PD) showed an increased risk of fractures in previous studies and a high prevalence of osteoporosis is reportedly a potential contributor. We conducted a nationwide database study on the risk of fractures and the impact of osteoporosis on patients with PD compared to controls. MATERIALS AND METHODS: Using a nationwide database in South Korea, we identified incident patients with PD in 2004-2006 and selected four age- and sex-matched controls. We checked the occurrence rates of overall and hip fractures and plotted Kaplan-Meier curves and a Cox proportional hazards model to determine risk. We also conducted stratified analyses according to the presence or absence of osteoporosis. RESULTS: We identified 9126 patients with PD and 35,601 controls. Patients with PD had a greater probability of fractures throughout the study period in Kaplan-Meier curves, and an increased risk of overall (aHR 1.35, 95% CI 1.297-1.405) and hip (aHR 1.814, 95% CI 1.66-1.983) fractures in a Cox proportional hazards model. In the stratified analysis, the increased risk of overall fracture (aHR 1.333, 95% CI 1.273-1.396 and aHR 1.412, 95% CI 1.301-1.532, respectively) and hip fracture (aHR 1.773, 95% CI 1.604-1.96 and aHR 2.008, 95% CI 1.657-2.434, respectively) due to PD was similar between patients with and without osteoporosis. DISCUSSION: Patients with PD, with or without osteoporosis, are more likely to experience fractures, especially hip fractures. There seems to be no interaction between PD and osteoporosis in regard to the occurrence of fractures, and therefore no effect modification by osteoporosis.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Doença de Parkinson , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Osteoporose/complicações , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco
7.
Genes (Basel) ; 12(5)2021 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-33923067

RESUMO

In plants, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a main enzyme in the glycolytic pathway. It plays an essential role in glycerolipid metabolism and response to various stresses. To examine the function of PsGAPDH (Pleurotus sajor-caju GAPDH) in response to abiotic stress, we generated transgenic rice plants with single-copy/intergenic/homozygous overexpression PsGAPDH (PsGAPDH-OX) and investigated their responses to salinity stress. Seedling growth and germination rates of PsGAPDH-OX were significantly increased under salt stress conditions compared to those of the wild type. To elucidate the role of PsGAPDH-OX in salt stress tolerance of rice, an Illumina HiSeq 2000 platform was used to analyze transcriptome profiles of leaves under salt stress. Analysis results of sequencing data showed that 1124 transcripts were differentially expressed. Using the list of differentially expressed genes (DEGs), functional enrichment analyses of DEGs such as Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. KEGG pathway enrichment analysis revealed that unigenes exhibiting differential expression were involved in starch and sucrose metabolism. Interestingly, trehalose-6-phosphate synthase (TPS) genes, of which expression was enhanced by abiotic stress, showed a significant difference in PsGAPDH-OX. Findings of this study suggest that PsGAPDH plays a role in the adaptation of rice plants to salt stress.


Assuntos
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética , Oryza/genética , Proteínas de Plantas/genética , Estresse Salino , Transcriptoma , Regulação da Expressão Gênica de Plantas , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Oryza/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Regulação para Cima
8.
Ann Rehabil Med ; 45(2): 83-98, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33849084

RESUMO

OBJECTIVE: To systematically translate the Fugl-Meyer Assessment (FMA) into a Korean version of the FMA (K-FMA). METHODS: We translated the original FMA into the Korean version with three translators and a translation committee, which included physiatrists, physical therapists, and occupational therapists. Based on a test-retest method, each of 31 patients with stroke was assessed by two evaluators twice, once on recruitment, and again after a week. Analysis of intra- and inter-rater reliabilities was performed using the intra-class correlation coefficient, whereas validity was analysed using Pearson correlation test along with the Motricity Index (MI), Motor Assessment Scale (MAS), and Berg Balance Scale (BBS). RESULTS: The intra- and inter-rater reliabilities were significant for the total score, and good to excellent reliability was noted in all domains except for the joint range of motion of the lower extremity domain of the K-FMA. The MI and MAS scores were significantly correlated with all domains, all with p<0.01. The results for the MI ranged from r=0.639 to r=0.891 and those for the MAS from r=0.339 to r=0.555. However, the BBS was not significantly correlated with any domain, as the K-FMA lacks balance evaluation items. CONCLUSION: The K-FMA was found to have high reliability and validity. Additionally, the newly developed manual for the K-FMA may help minimise errors that can occur during evaluation and improve the reliability of motor function evaluation.

9.
J Neuroeng Rehabil ; 18(1): 39, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602254

RESUMO

BACKGROUND: We previously proposed a novel virtual reality-based method to assess human field of perception (FOP) and field of regard (FOR), termed the FOPR test. This study assessed the diagnostic validity of the FOPR test for hemispatial neglect (HSN). METHODS: We included 19 stroke patients with a lesion in the right hemisphere and with HSN (HSN+SS), 22 stroke patients with a lesion in the right hemisphere and without HSN (HSN-SS), and 22 healthy controls aged 19-65 years. The success rate (SR) and response time (RT) in the FOPR test for both FOP and FOR were assessed (FOP-SR, FOR-SR, FOP-RT, and FOR-RT, respectively). Using a Bland-Altman plot, agreements between the FOPR test and conventional tests were confirmed, and the FOPR test accuracy was verified using the support vector machine (SVM). Measured values were analysed using ANOVA and Kruskall-Wallis tests for group comparison. RESULTS: The Bland-Altman plot showed good agreement between FOPR test and conventional tests; individuals within 95% agreement limits were within the range of 94.8-100.0%. The SVM classification accuracy, using FOP and FOR variables from the left hemispace, ranged from 83.3 to 100.0% in a binary classification (HSN vs non-HSN). The FOPR test demonstrated differences in SR and RT for both FOP and FOR across the groups. CONCLUSION: The FOPR test was valid for the HSN diagnosis and provided quantitative and intuitive information regarding visuospatial function. Furthermore, it might enhance our understanding of visuospatial function including HSN by applying the time relative component and concepts of perception and exploration, FOP and FOR. TRIAL REGISTRATION: NCT03463122. Registered 13 March 2018, retrospectively registered.


Assuntos
Transtornos da Percepção/diagnóstico , Máquina de Vetores de Suporte , Realidade Virtual , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/etiologia , Acidente Vascular Cerebral/complicações
10.
J Interv Card Electrophysiol ; 62(3): 565-568, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33421019

RESUMO

PURPOSE: Electrophysiology procedures pose infection risk and require surgical room sterility. Currently, there is no universally approved protocol for disinfecting lead garments in the electrophysiology laboratory. This study explores the feasibility of using ATP testing to assess the microbial burden of lead aprons and evaluates the impact of a sanitary intervention. METHODS: Adenosine triphosphate (ATP) testing is a well-established hospital standard to quantify biological matter on a surface and, by proxy, the microbial burden. It is measured in RLU (relative light units). Pre-intervention ATP testing was performed on 34 lead garments after use for electrophysiology procedures. The thyroid collar, mid-chest vest, and left axillary areas of the garments were swabbed using a Hygiena SystemSure II luminometer with ATP swabs (Hygiena, Camarillo, CA). These sites were then disinfected with disinfectant wipes (PDI Super Sani-cloth Germicidal Disposable Wipe) and ATP testing was repeated. RESULTS: The mean duration of garment wear was 213 min. The thyroid collars had the highest mean RLU before intervention, followed by the mid-chest vest and the left axillary areas. The intervention was found to significantly decrease ATP readings for all three sites (p = 0.0002, p = 0.0001, p = 0.0002 respectively). Linear regression modeling to assess the impact of intervention showed a significant correlation with pre-intervention ATP values for all three sites but no correlation with fluoroscopy time, fluoroscopy dose, or total time spent within the procedure. CONCLUSIONS: Lead garments harbor microbial contamination after use according to ATP testing. A sanitary intervention can decontaminate lead garments and potentially reduce rates of hospital infection.


Assuntos
Desinfecção , Laboratórios , Trifosfato de Adenosina , Eletrofisiologia , Humanos , Roupa de Proteção
11.
Anesth Analg ; 130(5): 1407-1414, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32167976

RESUMO

BACKGROUND: The ventilation/perfusion mismatch in chronic obstructive pulmonary disease (COPD) patients can exacerbate cardiac function as well as pulmonary oxygenation. We hypothesized that inhaled iloprost can ameliorate pulmonary oxygenation with lung mechanics and myocardial function during one-lung ventilation (OLV) in COPD patients combined with poor lung oxygenation. METHODS: A total of 40 patients with moderate to severe COPD, who exhibited the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2) <150 mm Hg 30 minutes after initiating OLV, were enrolled in this study. Patients were randomly allocated into either ILO group (n = 20) or Control group (n = 20), in which iloprost (20 µg) and saline were inhaled, respectively. The PaO2/FIO2 ratio, dead space, dynamic compliance, and tissue Doppler imaging with myocardial performance index (MPI) were assessed 30 minutes after initiating OLV (pre-Tx) and 30 minutes after completion of drug inhalation (post-Tx). Repeated variables were analyzed using a linear mixed-model between the groups. RESULTS: At pre-Tx, no differences were observed in measured parameters between the groups. At post-Tx, PaO2/FIO2 ratio (P < .001) and dynamic compliance (P = .023) were significantly higher and dead space ventilation was significantly lower (P = .001) in iloprost group (ILO group) compared to Control group. Left (P = .003) and right ventricular MPIs (P < .001) significantly decreased in ILO group compared to Control group. CONCLUSIONS: Inhaled iloprost improved pulmonary oxygenation, lung mechanics, and cardiac function simultaneously during OLV in COPD patients with poor lung oxygenation.


Assuntos
Iloprosta/administração & dosagem , Pulmão/efeitos dos fármacos , Ventilação Monopulmonar/métodos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Mecânica Respiratória/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/métodos , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar/efeitos dos fármacos , Ventilação Pulmonar/fisiologia , Mecânica Respiratória/fisiologia , Resultado do Tratamento
12.
Ann Rehabil Med ; 44(6): 438-449, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33440092

RESUMO

OBJECTIVE: To identify the prevalence and characteristics of neuropathic pain (NP) in patients with spinal cord injury (SCI) and to investigate associations between NP and demographic or disease-related variables. METHODS: We retrospectively reviewed medical records of patients with SCI whose pain was classified according to the International Spinal Cord Injury Pain classifications at a single hospital. Multiple statistical analyses were employed. Patients aged <19 years, and patients with other neurological disorders and congenital conditions were excluded. RESULTS: Of 366 patients, 253 patients (69.1%) with SCI had NP. Patients who were married or had traumatic injury or depressive mood had a higher prevalence rate. When other variables were controlled, marital status and depressive mood were found to be predictors of NP. There was no association between the prevalence of NP and other demographic or clinical variables. The mean Numeric Rating Scale (NRS) of NP was 4.52, and patients mainly described pain as tingling, squeezing, and painful cold. Females and those with below-level NP reported more intense pain. An NRS cut-off value of 4.5 was determined as the most appropriate value to discriminate between patients taking pain medication and those who did not. CONCLUSION: In total, 69.1% of patients with SCI complained of NP, indicating that NP was a major complication. Treatment planning for patients with SCI and NP should consider that marital status, mood, sex, and pain subtype may affect NP, which should be actively managed in patients with an NRS ≥4.5.

13.
Invest New Drugs ; 37(4): 796, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937691

RESUMO

The blots of control and docetaxel for caspase-9, caspase-3, caspase-8, Bcl-XL, and tubulin in the Figure 4f were reused from Figure 4 of our previous paper published in Journal of Urology in 2010 ( https://doi.org/10.1016/j.juro.2010.07.035 ).

14.
Mol Cells ; 39(6): 460-7, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27137090

RESUMO

Bacteriophytochromes are phytochrome-like light-sensing photoreceptors that use biliverdin as a chromophore. To study the biochemical properties of the Deinococcus radiodurans bacteriophytochrome (DrBphP) protein, two anti-DrBphP mouse monoclonal antibodies (2B8 and 3H7) were generated. Their specific epitopes were identified in our previous report. We present here fine epitope mapping of these two antibodies by using truncation and substitution of original epitope sequences in order to identify minimized epitope peptides. The previously reported original epitope sequences for 2B8 and 3H7 were truncated from both sides. Our analysis showed that the minimal peptide sequence lengths for 2B8 and 3H7 antibodies were nine amino acids (RDPLPFFPP) and six amino acids (PGEIEE), respectively. We further characterized these peptides in order to investigate their reactivity after single deletion and single substitution of the original peptides. We found that single-substituted 2B8 epitope (RDPLPAFPP) and dual-substituted 3H7 epitope (PGEIAD) showed significantly increased reactivity. These two antibodies with high reactivity for the short modified peptide sequences are valueble for developing new peptide tags for protein research.


Assuntos
Anticorpos Monoclonais/metabolismo , Proteínas de Bactérias/imunologia , Deinococcus/metabolismo , Epitopos/genética , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Análise Mutacional de DNA , Deinococcus/genética , Deinococcus/imunologia , Mapeamento de Epitopos , Epitopos/imunologia , Camundongos
15.
Bioorg Med Chem Lett ; 26(7): 1844-8, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26905830

RESUMO

In this study, a series of bis(4-hydroxy)benzophenone oxime ether derivatives such as 12c, 12e and 12h were identified as novel estrogen receptor (ER) agonists that have additional and complementary anti-proliferative activities via ER-independent mechanism in cancer cells. These compounds are expected to overcome the therapeutic limitation of existing ER agonists such as estradiol and tamoxifen, which have been known to induce the proliferation of cancer cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Estrogênios/química , Estrogênios/farmacologia , Oximas/química , Oximas/farmacologia , Benzofenonas/química , Benzofenonas/farmacologia , Linhagem Celular Tumoral , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
16.
Org Biomol Chem ; 14(2): 777-784, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26592753

RESUMO

A variety of flavones were expediently synthesized from readily accessible chromanones via a one-pot sequence involving Pd(II)-catalyzed dehydrogenation and oxidative boron-Heck coupling with arylboronic acid pinacol esters. In particular, the use of arylboronic acid pinacol esters was found to significantly improve the yield of the reaction.


Assuntos
Boro/química , Cromonas/química , Flavonas/síntese química , Compostos Organometálicos/química , Paládio/química , Catálise , Flavonas/química , Hidrogenação , Estrutura Molecular , Oxirredução
17.
Bioorg Med Chem Lett ; 25(17): 3694-8, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26115577

RESUMO

A series of hybrid molecules consisting of benzophenones and N-cyclopropyl-3-methylbenzamides were synthesized and biologically evaluated as novel p38 mitogen activated protein kinase (MAPK) inhibitors. In particular, we found that compound 10g displayed potent p38α MAPK inhibitory activity (IC50=0.027 µM), high kinase selectivity, and significant anti-inflammatory activity in THP-1 monocyte cells.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzofenonas/química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/química , Benzamidas/química , Linhagem Celular/efeitos dos fármacos , Técnicas de Química Sintética , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Concentração Inibidora 50 , Monócitos/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Int J Oncol ; 47(1): 280-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25964080

RESUMO

Estrogens act through interactions with estrogen receptors (ERs) to play diverse roles in various pathophysiological conditions. A number of synthetic selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, have been developed and used to treat ER-related diseases, including breast cancer and osteoporosis. Here, we identified a novel compound, bis(4-hydroxyphenyl)methanone-O-isopentyl oxime, designated NJK14013, as an ER agonist. NJK14013 activated ER-dependent transcription in a concentration-dependent manner, while suppressing androgen receptor-dependent transcriptional activity. It induced the activation-related phosphorylation of ER and enhanced the transcription of growth regulation by estrogen in breast cancer 1 (GREB1), further supporting its ER-stimulating activity. NJK14013 exerted anti-proliferative effects on various cancer cell lines, including an ER-negative breast cancer cell line, suggesting that it is capable of suppressing the growth of cancer cells independent of its ER-modulating activity. In addition, NJK14013 treatment resulted in significant apoptotic death of MCF7 and Ishikawa cancer cells, but did not induce apoptosis in non-cancer human umbilical vein endothelial cells. Collectively, our findings demonstrate that NJK14013 is a novel SERM that can activate ER-mediated transcription in MCF7 cells and suppress the proliferation of various cancer cells, including breast cancer cells and endometrial cancer cells. These results suggest that NJK14013 has potential as a novel SERM for anticancer or hormone-replacement therapy with reduced risk of carcinogenesis.


Assuntos
Antineoplásicos Hormonais/farmacologia , Receptor alfa de Estrogênio/agonistas , Neoplasias/genética , Oximas/síntese química , Oximas/farmacologia , Receptores de Estrogênio/genética , Moduladores Seletivos de Receptor Estrogênico/síntese química , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Antineoplásicos Hormonais/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Masculino , Proteínas de Neoplasias/genética , Neoplasias/tratamento farmacológico
19.
Protein Sci ; 23(6): 812-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24677487

RESUMO

Bacteriophytochromes (BphP) are phytochrome-like light sensing proteins in bacteria, which use biliverdin as a chromophore. In order to study the biochemical properties of the DrBphP protein, five (2B8, 2C11, 3B2, 3D2, and 3H7) anti-DrBphP monoclonal antibodies were produced through the immunization of mice with purified full-length DrBphP and DrBphN (1-321 amino acid) proteins, and epitope mapping was then carried out. Among the five antibodies, 2B8 and 2C11 preferentially recognized the N-terminal region of BphP whereas 3B2, 3D2, and 3H7 showed preference for the C-terminal region. We performed further epitope mapping using recombinant truncated BphP proteins to narrow down their target sequences. The results demonstrated that each of the five monoclonal antibodies recognized different regions on the DrBphP protein. Additionally, epitopes of 2B8 and 3H7 antibodies were discovered to be shorter than 10 amino acids (2B8: RDPLPFFPP, 3H7: PGEIEEA). These two antibodies with such specific recognition epitopes could be especially valuable for developing new peptide tags for protein detection and purification.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Deinococcus/imunologia , Deinococcus/metabolismo , Mapeamento de Epitopos/métodos , Fitocromo/química , Fitocromo/imunologia
20.
Invest New Drugs ; 30(4): 1434-42, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21773733

RESUMO

We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl-(XL). Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Naftalenos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Taxoides/uso terapêutico , Proteína bcl-X/metabolismo , Acetilação/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel , Sinergismo Farmacológico , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacologia , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides , Naftalenos/química , Naftalenos/farmacologia , Neoplasias da Próstata/patologia , Taxoides/farmacologia , Tubulina (Proteína)/metabolismo
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