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1.
Clin Radiol ; 79(7): e908-e915, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38649313

RESUMO

AIM: To compare the image quality of virtual noncontrast (VNC) and true noncontrast (TNC) CT images and to evaluate the clinical feasibility of VNC CT images for assessing osteochondral lesions of the talus (OLTs). MATERIALS AND METHODS: Forty-five OLT patients who underwent ankle CT arthrography (CTA) using dual-layer spectral detector CT were enrolled. Reconstruction of VNC and three-dimensional volume rendering images was performed. Afterward, image noise, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were measured. For the subjective evaluation, two board-certified musculoskeletal radiologists [R2-1] assessed spatial resolution, overall image quality, and lesion conspicuity. The accuracy rate for OLT grading was determined in 23 patients who underwent arthroscopic surgery. RESULTS: While VNC images showed significantly less noise than TNC images, TNC images showed better SNRs and CNRs (p<.01). In the subjective analysis, TNC images showed better overall image quality (p<.001). For the 3D volume rendering images, VNC images scored significantly higher for lesion conspicuity (p<.001). The accuracy rates of CTA and CTA with VNC images for OLT grading were 79.2% and 83.3%, respectively. Regarding confidence level, when CTA and VNC images were evaluated together, the confidence level was significantly higher than that when only CTA images were evaluated (p<.001). CONCLUSION: VNC imaging can provide better confidence level of OLT grading and evaluation of the integrity of the subchondral bone plate when combined with conventional CTA without additional radiation dose to the patient. In addition, VNC images-based 3D volume rendering reconstruction would be helpful for preoperative planning in OLT patients.


Assuntos
Artrografia , Estudos de Viabilidade , Tálus , Tomografia Computadorizada por Raios X , Humanos , Tálus/diagnóstico por imagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Artrografia/métodos , Imageamento Tridimensional/métodos , Adulto Jovem , Idoso , Adolescente , Razão Sinal-Ruído , Estudos Retrospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
2.
J Endocrinol Invest ; 47(10): 2551-2563, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38493245

RESUMO

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.


Assuntos
Composição Corporal , Fragilidade , Metabolômica , Ovariectomia , Pós-Menopausa , Feminino , Animais , Camundongos , Humanos , Pós-Menopausa/metabolismo , Composição Corporal/fisiologia , Metabolômica/métodos , Fragilidade/metabolismo , Fragilidade/sangue , Pessoa de Meia-Idade , Idoso , Metaboloma/fisiologia , Biomarcadores/sangue , Camundongos Endogâmicos C57BL , Aprendizado de Máquina
3.
Osteoporos Int ; 30(5): 1071-1078, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719549

RESUMO

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.


Assuntos
Densidade Óssea/fisiologia , Ácidos Graxos Ômega-3/sangue , Fraturas do Quadril/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Ácidos Graxos Ômega-3/fisiologia , Ácidos Graxos Ômega-6/sangue , Feminino , Fêmur/fisiopatologia , Fraturas do Quadril/sangue , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Fraturas por Osteoporose/sangue
5.
J Endocrinol Invest ; 41(6): 677-689, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29147952

RESUMO

PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated. METHODS: SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents. RESULTS: In cells treated with gemigliptin or PXD101, cell viability, the percentage of viable cells and ATP levels were reduced, and the percentage of dead cells and cytotoxic activity were elevated. In cells treated with both gemigliptin and PXD101, compared with PXD101 alone, cell death was augmented, and all of the combination index values were lower than 1.0, suggesting the synergism between gemigliptin and PXD101. The percentage of apoptotic cells, and the protein levels of Bcl2 and cleaved poly (ADP-ribose) polymerase were elevated, and the protein levels of xIAP and survivin were reduced. The protein levels of phospho-Akt and phospho-AMPK were elevated, and cell migration was reduced. CONCLUSIONS: Our results demonstrate that gemigliptin induces cytotoxicity in thyroid carcinoma cells. Moreover, gemigliptin has a synergistic activity with PXD101 in the induction of cell death through involvement of Bcl2 family proteins, xIAP and survivin as well as mediation of Akt and AMPK in thyroid carcinoma cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Sinergismo Farmacológico , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Piperidonas/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/patologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Humanos , Transdução de Sinais , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
6.
Br J Surg ; 104(12): 1628-1633, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28975600

RESUMO

BACKGROUND: A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR tour could reduce preoperative anxiety in children. METHODS: Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4-min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m-YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia. RESULTS: A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m-YPAS score than those in the control group (median 31·7 (i.q.r. 23·3-37·9) and 51·7 (28·3-63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group. CONCLUSION: This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr).


Assuntos
Ansiedade/prevenção & controle , Criança Hospitalizada/psicologia , Procedimentos Cirúrgicos Eletivos/psicologia , Salas Cirúrgicas , Interface Usuário-Computador , Anestesia Geral , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Cooperação do Paciente
7.
Psychol Med ; 45(8): 1601-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25388623

RESUMO

BACKGROUND: Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children. METHOD: A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated. RESULTS: Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri. CONCLUSIONS: The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/urina , Córtex Cerebral/patologia , Ácidos Ftálicos/urina , Adolescente , Análise de Variância , Criança , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , República da Coreia , Índice de Gravidade de Doença
8.
Muscle Nerve ; 50(6): 991-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24692104

RESUMO

INTRODUCTION: Protease-activated receptors (PARs) may play a role in skeletal muscle development. We compared the contractile properties of slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles from PAR-1 null and littermate control mice. METHODS: Contractile function was measured using a force transducer system. Fiber type proportions were determined using immunohistochemistry. RESULTS: Soleus muscles from PAR-1 null mice exhibited longer contraction times, a leftward shift in the force-stimulation frequency relationship, and decreased fatiguability compared with controls. PAR-1 null soleus muscles also had increased type 1 and decreased type IIb/x fiber numbers compared with controls. In PAR-1 null EDL muscles, no differences were found, except for a slower rate of fatigue compared with controls. CONCLUSIONS: The absence of PAR-1 results in a slower skeletal muscle contractile phenotype, likely due to an increase in type I and a decrease in type IIb/x fiber numbers. Muscle Nerve 50: 991-998, 2014.


Assuntos
Contração Muscular/fisiologia , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Músculo Esquelético/fisiologia , Receptor PAR-1/deficiência , Animais , Estimulação Elétrica , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fadiga Muscular/fisiologia , Força Muscular/fisiologia , Fenótipo , Receptor PAR-1/genética , Receptor PAR-1/fisiologia
9.
Psychol Med ; 43(1): 209-19, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22608159

RESUMO

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Cotinina/urina , Deficiências da Aprendizagem/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/urina , Criança , Estudos Transversais , Feminino , Humanos , Inibição Psicológica , Deficiências da Aprendizagem/urina , Masculino , Modelos Psicológicos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , República da Coreia
10.
Horm Metab Res ; 45(1): 9-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22918703

RESUMO

SU5416, vascular endothelial cell growth factor receptor inhibitor, suppresses hypoxia-induced angiogenesis, growth, proliferation, and metastasis in cancer cells. CCAAT/enhancer-binding protein-homologous protein (CHOP) has pivotal roles in regulation of growth and survival. In the present study, we evaluated the effects of SU5416 on cell survival, p21, and PI3K/Akt signal pathway in FRO anaplastic thyroid carcinoma (ATC) cells. Moreover, we investigated the roles of CHOP in cell survival under condition of SU5416 treatment in FRO ATC cells. After SU5416 treatment, cell viability, PARP-1, and caspase-3 protein levels were not changed. p53 and p27 protein levels decreased while p21 protein levels increased. Phospho-Akt protein levels were not altered. In SU5416-treated situation, cell viability was not different before and after administration of either p21 siRNA or LY294002 whereas it was lessened after co-administration of p21 siRNA and LY294002. Compared to SU5416 treatment alone, cell viability was reduced with CHOP plasmid but it was unchanged with CHOP siRNA. PARP-1 and caspase-3 protein levels with CHOP plasmid were elevated whereas the protein levels with CHOP siRNA were similar. While CHOP plasmid transfection diminished p21 and phospho-Akt protein levels, CHOP siRNA transfection did not alter the protein levels. In conclusion, these results suggest that CHOP may sensitize FRO ATC cells to SU5416 thereby inhibiting cell survival by modulating p21 and PI3K/Akt signal pathway. Furthermore, these findings imply that CHOP may be a possible candidate as the chemosensitizing factor for induction of cytotoxicity in ATC cells exposed to SU5416.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Indóis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição CHOP/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas de Silenciamento de Genes , Humanos , Carcinoma Anaplásico da Tireoide , Proteína Supressora de Tumor p53/metabolismo
11.
Horm Metab Res ; 45(6): 408-14, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23386415

RESUMO

SU6656 is a small-molecule indolinone that selectively inhibits Src family kinase and induces death of cancer cells. The aim of the present study was to investigate the influence of SU6656 on cell survival and to assess the role of p21 and PI3K/Akt signaling in cell survival resulting from SU6656 treatment in anaplastic thyroid carcinoma (ATC) cells. When 8505C, CAL62, and FRO ATC cells were treated with SU6656, the viability of 8505C and CAL62 ATC cells decreased only after treatment with SU6656 at a dosage of 100 µM for 72 h, while the viability of FRO ATC cells decreased after treatment with SU6656 in a concentration- and time-dependent manner. Cell viability was not changed by pretreatment with the broad-spectrum caspase inhibitor z-VAD-fmk. Phospho-Src protein levels were reduced, and p21 protein levels were elevated. Phospho-ERK1/2 protein levels were multiplied without alteration of total ERK1/2, total Akt, and phospho-Akt protein levels. Regarding FRO ATC cells, the decrement of cell viability, the increment of cleaved PARP-1 protein levels, and the decrement of phospho-Src protein levels were shown in p21 siRNA- or LY294002-pretreated cells compared to SU6656-treated control cells. ERK1/2 siRNA transfection did not affect cell viability and protein levels of cleaved PARP-1, p21, and Akt. In conclusion, these results suggest that SU6656 induces caspase-independent death of FRO ATC cells by overcoming the resistance mechanism involving p21 and Akt. Suppression of p21 and Akt enhances the cytotoxic effect of SU6656 in FRO ATC cells.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/fisiopatologia , Caspases/genética , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
12.
Pharmacopsychiatry ; 46(5): 169-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23824524

RESUMO

INTRODUCTION: Given the shortage of pharmacogenetic studies on treatment response according to subtype of attention-deficit hyperactivity disorder (ADHD), we investigated the associations between the MspI and DraI polymorphisms of the alpha-2 A-adrenergic receptor gene (ADRA2A) and treatment response to methylphenidate according to subtype of ADHD. METHODS: We enrolled 115 medication-naïve children with ADHD into an open label 8-week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical -Global Impression (CGI), ADHD rating scale, and Continuous Performance Test (CPT) pre- and post-treatment. RESULTS: There was no statistically significant association between the MspI or DraI genotypes and the relative frequency of CGI-improvement (CGI-I) 1 or 2 status among any of the groups (all types of ADHD, ADHD-C, or ADHD-I). However, among the children with ADHD-C, those subjects with the C/C genotype at the ADRA2A DraI polymorphism tended to have a CGI-I 1 or 2 status post-treatment (OR=4.45, p=0.045). DISCUSSION: The results of this study do not support the association between the the MspI or DraI genotypes and treatment response to methylphenidate in ADHD. However, our results -suggest that subtypes might influence pharmacogenetic results in ADHD.·available online at http://www.thieme-connect.de/ejournals/toc/pharmaco.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Metilfenidato/uso terapêutico , Receptores Adrenérgicos alfa 2/genética , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Feminino , Genótipo , Humanos , Masculino , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único/genética , Resultado do Tratamento
13.
J Endocrinol Invest ; 36(11): 1099-104, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24084189

RESUMO

Aim of the present study was to evaluate the effect of apigenin in combination with BRAFV600E inhibitor PLX4032 on cell survival, and to investigate the influence of Akt inhibition on the combined effect of apigenin and PLX4032 in ATC cells harboring BRAFV600E. In 8505C and FRO cells harboring BRAFV600E, after treatment of apigenin and PLX4032, the cell viability decreased, and the percentage of dead cells increased in a time- and concentration-dependent manner, respectively. In apigenin- and PLX4032- treated cells, compared with apigenin alone-treated cells, the cell viability was lessened, and the percentage of dead cells was multiplied. In the addition of PLX4032 to apigenin, compared with the treatment of apigenin alone, the protein levels of cleaved PARP-1 and cleaved caspase-3 were elevated, and phospho-ERK protein levels were reduced, and the protein levels of total ERK, c-Myc, BRAF, phospho-Akt, phospho-p70S6K and phospho-4EBP1 were not varied. Compared with the treatment of PLX4032 alone, phosphop70S6K protein levels were reduced, and the other protein levels were not altered. Phospho-ERK protein levels were reduced only in 8505C cells. Under the co-treatment of apigenin and PLX4032, administration of the PI3K inhibitor wortmannin further decreased the cell viability, and increased the percentage of dead cells. In conclusion, our results suggest that PLX4032 augments apigenin-induced cytotoxicity in ATC cells harboring BRAFV600E. Moreover, Akt suppression potentiates the combined effect of apigenin and PLX4032 in ATC cells harboring BRAFV600E.


Assuntos
Apigenina/farmacologia , Indóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Androstadienos/farmacologia , Apigenina/uso terapêutico , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Carcinoma Anaplásico da Tireoide , Vemurafenib , Wortmanina
14.
Horm Metab Res ; 43(7): 445-51, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21590646

RESUMO

Alpha-lipoic acid (ALA) has been shown to modulate cell death via PI3K/Akt signal pathway in various cells. In the present study, the effects of ALA on cell death and PI3K/Akt signal pathway linked to cell death-related proteins during endoplasmic reticulum (ER) stress in FRTL5 thyroid cells were evaluated. In FRTL5 thyroid cells, cell viability increased by ALA pretreatment in tunicamycin (TN)-treated cells. When TN was treated, CCAAT/enhancer-binding protein-homologous protein (CHOP) and Bax protein levels were elevated while Bcl-2 protein levels were reduced. ALA diminished CHOP and Bax protein levels, and augmented Bcl-2 protein levels in TN-treated cells. After exposure to TN, phospho-Akt protein levels were repressed whereas total Akt protein levels were not changed. ALA increased phospho-Akt protein levels but not total Akt protein levels in both non-TN-treated and TN-treated cells. After LY294002 administration in non-TN-treated cells, cell viability was reduced, and CHOP and Bax protein levels were elevated, and Bcl-2 protein levels were reduced. The CHOP, Bcl-2 and Bax protein levels were not different after LY294002 administration in TN-treated cells. LY294002 and wortmannin decreased cell viability, and increased CHOP and Bax protein levels, and decreased Bcl-2 protein levels in ALA-pretreated and TN-treated cells. In conclusion, these results suggest that ER stress may induce cell death by modulating PI3K/Akt signal pathway linked to cell death-related proteins in FRTL5 thyroid cells. Moreover, these findings imply that ALA may ameliorate ER stress-induced cell death by activating PI3K/Akt signal pathway and attenuating changes of cell death-related proteins in FRTL5 thyroid cells.


Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Ácido Tióctico/farmacologia , Glândula Tireoide/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Fator de Transcrição CHOP/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Horm Metab Res ; 43(5): 331-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21225541

RESUMO

In thyroid cells, the effects of all- TRANS retinoic acid (ATRA) on sodium/iodide symporter (NIS) and CCAAT/enhancer-binding protein-homologous protein (CHOP) under condition of endoplasmic reticulum (ER) stress have not been evaluated. In the present study, the relationships between NIS, CHOP, and p38 MAPK, and the effects of ATRA on NIS and CHOP expression as well as on p38 MAPK activation under condition of ER stress in thyroid cells were investigated. In FRTL5 thyroid cells, NIS mRNA and protein levels decreased following tunicamycin (TN) treatment, while CHOP mRNA and protein levels increased. In addition, while CHOP mRNA levels decreased after administration of tauro-UDCA and siCHOP, NIS mRNA levels were not altered. After pretreatment with SB203580, NIS mRNA levels decreased in non-TN-treated cells but increased in TN-treated cells. In contrast, CHOP mRNA levels decreased in both non-TN-treated and TN-treated cells. Exposure to ATRA decreased NIS mRNA levels in non-TN-treated cells but increased NIS mRNA levels in TN-treated cells. ATRA decreased CHOP mRNA levels in both non-TN-treated and TN-treated cells although the response was significant only in TN-treated cells. Phospho-p38 MAPK protein levels but not total p38 MAPK protein levels increased in TN-treated cells. ATRA attenuated this increase in phopho-p38 MAPK protein levels. In conclusion, our results demonstrate that ER stress may induce reciprocal changes in NIS and CHOP expression via p38 MAPK in FRTL5 thyroid cells, and that ATRA may attenuate ER stress-induced alterations in NIS and CHOP expression by modulating the phosphorylation of p38 MAPK in FRTL5 thyroid cells.


Assuntos
Retículo Endoplasmático/metabolismo , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Fator de Transcrição CHOP/metabolismo , Animais , Linhagem Celular , Retículo Endoplasmático/genética , Ratos , Simportadores/genética , Fator de Transcrição CHOP/genética , Tretinoína , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Diabetes Metab ; 47(3): 101195, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33039669

RESUMO

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.


Assuntos
Glicemia , Jejum , Doença de Parkinson , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Jejum/sangue , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Fatores de Risco
17.
Clin Endocrinol (Oxf) ; 73(5): 588-94, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20618345

RESUMO

OBJECTIVE: A relationship between visceral fat accumulation and metabolic syndrome (MetS) has been established. However, the effect of a relative increase in visceral fat and a decrease in muscle mass on metabolic disorders has not been investigated. The aim of the present study was to examine the association between the ratio of visceral fat to thigh muscle area (VMR) and MetS in Korean adults. STUDY SUBJECT/MEASUREMENTS: A total of 264 age-and gender-matched subjects recruited from the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study, were categorized into four groups based on their body mass index (BMI) and VMR. We measured visceral fat area and thigh muscle area using computed tomography. RESULTS: Subjects with MetS showed a significantly higher VMR than those without MetS. In both obese and nonobese groups, the subjects with a higher VMR had a higher prevalence of MetS than those in the lower VMR groups. VMR was significantly related to components of the metabolic syndrome, especially in women, and was positively correlated with a number of MetS components in both men and women. In multiple logistic regression analysis, the odds ratio for MetS was 6·72 (highest vs lowest quartile, 95% confidence interval, 1·60-28·14) after an adjustment of potential confounders, including BMI and waist-to-hip ratio. CONCLUSION: VMR is significantly increased in subjects with MetS and independently associated with MetS. These results suggest that the VMR may be a potential indicator for MetS risk in Korean adults.


Assuntos
Gordura Intra-Abdominal/anatomia & histologia , Síndrome Metabólica/fisiopatologia , Músculo Esquelético/anatomia & histologia , Sarcopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Obesidade/epidemiologia , Obesidade/metabolismo , Estudos Prospectivos , República da Coreia/epidemiologia
18.
Int J Obes (Lond) ; 33(8): 885-92, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19564878

RESUMO

OBJECTIVES: To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height(2), skeletal muscle mass index (SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome. METHODS: Our study sample included 526 participants (328 women, 198 men) for whom complete data on body composition were collected using available dual X-ray absorptiometry. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify the individuals with metabolic syndrome. RESULTS: The prevalence of sarcopenia and SO is higher in older adults. Using two s.d. of ASM/height(2) below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in older (> or =60 years) men and 4.1% and 0.8% in older women, respectively. The prevalence of sarcopenia using the residuals method was 15.4% in older men and 22.3% in older women. In addition, using two s.d. of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1%, respectively, in older men and 14.2% and 12.5%, respectively, in older women. Among women, SO subjects defined by the SMI had three times the risk of metabolic syndrome (odds ratios (OR)=3.24, 95% confidence interval (CI)=1.21-8.66) and non-sarcopenic obese subjects had approximately twice the risk of metabolic syndrome (OR=2.17, 95% CI=1.22-3.88) compared with normal subjects. Similar trends were observed in men. CONCLUSION: The prevalence and cutoff values of sarcopenia and SO in the Korean population were evaluated using different methods. Among the different indices of sarcopenia and SO, SO only defined using the SMI was associated with the risk of metabolic syndrome. As the Korean population gets older and more obese, the problematics of SO need to be elucidated.


Assuntos
Envelhecimento/fisiologia , Músculo Esquelético/fisiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Índice de Massa Corporal , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Prevalência , Sarcopenia/fisiopatologia , Adulto Jovem
19.
Clin Endocrinol (Oxf) ; 70(4): 569-74, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18710473

RESUMO

OBJECTIVE: Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. STUDY SUBJECTS: Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. DESIGN: Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. RESULTS: Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. CONCLUSION: Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.


Assuntos
Exercício Físico/fisiologia , Proteínas de Ligação a Ácido Graxo/sangue , Lipocalinas/sangue , Obesidade/sangue , Proteínas Proto-Oncogênicas/sangue , RNA Polimerase II/sangue , Proteínas de Fase Aguda , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Colesterol/sangue , Feminino , Humanos , Coreia (Geográfico) , Lipocalina-2 , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/fisiopatologia , Treinamento Resistido
20.
Diabet Med ; 26(6): 628-35, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19538239

RESUMO

AIMS: The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension. METHODS: We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre. RESULTS: After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group. CONCLUSIONS: The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.


Assuntos
Automonitorização da Glicemia/métodos , Monitorização Ambulatorial da Pressão Arterial/métodos , Telefone Celular , Atenção à Saúde/métodos , Internet , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Cooperação do Paciente , Educação de Pacientes como Assunto
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