Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Nephrol ; 24(1): 286, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773103

RESUMO

BACKGROUND: Endothelial dysfunction is common in patients undergoing chronic haemodialysis, and is a major cause of posterior reversible encephalopathy syndrome (PRES). Recently, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause endothelial dysfunction by infecting vascular endothelial cells. Several cases of neurological complications in patients without kidney dysfunction, and only a few cases in patients with chronic kidney disease, have been reported in the literature. However, no previous report has yet described PRES associated with SARS-CoV-2 infection among patients undergoing maintenance dialysis. CASE PRESENTATION: A 54-year-old woman undergoing maintenance haemodialysis was admitted to our hospital for status epilepticus. She had developed end-stage kidney disease (ESKD) secondary to diabetic nephropathy. Seven days prior to admission, she had developed fever and was diagnosed with COVID-19. Subsequently her blood pressure increased from 160/90 mmHg to 190/100 mmHg. On admission, she presented with severe hypertension (> 220/150 mmHg), unconsciousness, and epilepticus. CT tomography revealed no signs of brain haemorrhage. Cranio-spinal fluid (CSF) examination revealed no signs of encephalitis, and CSF polymerase chain reaction (PCR) for SARS-CoV-2 was negative. MRI findings revealed focal T2/FLAIR hyperintensity in the bilateral parietooccipital regions, leading to the diagnosis of PRES. Deep sedation and strict blood pressure control resulted in a rapid improvement of her symptoms, and she was discharged without sequelae. CONCLUSIONS: We report the first case of PRES associated with SARS-CoV-2 infection in a patient undergoing maintenance haemodialysis. Patients undergoing maintenance haemodialysis are at high risk of PRES because of several risk factors. SARS-CoV-2 infection causes direct invasion of endothelial cells by binding to angiotensin-converting enzyme 2 (ACE2), initiating cytokine release, and hypercoagulation, leading to vascular endothelial cell injury and increased vascular leakage. In the present case, SARS-CoV-2 infection possibly be associated with the development of PRES.


Assuntos
COVID-19 , Síndrome da Leucoencefalopatia Posterior , Doenças Vasculares , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/complicações , COVID-19/complicações , Células Endoteliais , SARS-CoV-2 , Diálise Renal/efeitos adversos , Doenças Vasculares/complicações
2.
Diagnostics (Basel) ; 13(10)2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37238171

RESUMO

This study aimed to evaluate the renal blood flow (RBF) in patients with chronic kidney disease (CKD) using 64Cu(II)-diacetyl-bis(4-methylthiosemicarbazonate) (64Cu-ATSM) for positron emission tomography (PET)/magnetic resonance imaging (MRI). We included five healthy controls (HCs) and ten patients with CKD. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine (cr) and cystatin C (cys) levels. The estimated RBF (eRBF) was calculated using the eGFR, hematocrit, and filtration fraction. A single dose of 64Cu-ATSM (300-400 MBq) was administered for RBF evaluation, and a 40 min dynamic PET scan was performed with simultaneous arterial spin labeling (ASL) imaging. PET-RBF images were obtained from the dynamic PET images at 3 min after injection using the image-derived input function method. The mean eRBF values calculated from various eGFR values differed significantly between the patients and HCs; both groups also differed significantly in terms of the RBF values (mL/min/100 g) measured using PET (151 ± 20 vs. 124 ± 22, p < 0.05) and ASL-MRI (172 ± 38 vs. 125 ± 30, p < 0.001). The ASL-MRI-RBF was positively correlated with the eRBFcr-cys (r = 0.858, p < 0.001). The PET-RBF was positively correlated with the eRBFcr-cys (r = 0.893, p < 0.001). The ASL-RBF was positively correlated with the PET-RBF (r = 0.849, p < 0.001). 64Cu-ATSM PET/MRI demonstrated the reliability of PET-RBF and ASL-RBF by comparing them with eRBF. This is the first study to demonstrate that 64Cu-ATSM-PET is useful for assessing the RBF and is well correlated with ASL-MRI.

3.
CEN Case Rep ; 12(1): 32-38, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35749014

RESUMO

We report on an 80-year-old man diagnosed with Fanconi syndrome induced by mizoribine after 4 weeks of administration to treat membranous nephropathy. Mizoribine is an oral immunosuppressant that inhibits inosine monophosphate dehydrogenase and is widely used in Japan for the treatment of autoimmune diseases and nephrotic syndrome, as well as after renal transplantation. Acquired Fanconi syndrome is often caused by drugs (antibacterial, antiviral, anticancer, and anticonvulsant drugs) and is sometimes caused by autoimmune diseases, monoclonal light chain-associated diseases, or heavy metal poisoning. In our patient, hypokalemia, hypophosphatemia, glucosuria, hypouricemia, and severe proteinuria resolved gradually after discontinuation of mizoribine administration, despite oral administration of prednisolone followed by a single intravenous injection of rituximab. The patient was ultimately diagnosed with Fanconi syndrome induced by mizoribine based on his clinical course and his typical laboratory data with the absence of proximal tubular acidosis. To our knowledge, this is the first report of Fanconi syndrome possibly induced by mizoribine. Although the precise mechanism by which mizoribine induces proximal tubular dysfunction is unknown, we suggest that nephrologists should be aware of the onset of Fanconi syndrome, a rare complication during mizoribine treatment.


Assuntos
Acidose Tubular Renal , Síndrome de Fanconi , Glomerulonefrite Membranosa , Ribonucleosídeos , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Imunossupressores/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamento farmacológico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/complicações , Ribonucleosídeos/efeitos adversos , Acidose Tubular Renal/complicações
4.
Ther Adv Med Oncol ; 12: 1758835920913432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014144

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide and establishment of new chemotherapies for HCC is urgently needed. GPR41 [free fatty acid receptor 3 (FFA3)] is a G protein-coupled receptor for short chain fatty acids, including acetate, propionate, and butyrate. In our previous study, we showed that propionate enhances the cytotoxic effect of cisplatin in HCC cells and that this mechanism is dependent on inhibition of histone deacetylases (HDACs) via GPR41/FFA3. However, the antitumor action of GPR41/FFA3 has not been elucidated. METHODS: In this study, we examined AR420626 as a GPR41-selective agonist in HepG2 and HLE cells. Nude mice were used for HepG2 xenograft studies. The apoptotic effect of AR420626 was evaluated using flow cytometry analysis. Expression of apoptosis-related proteins and HDACs was evaluated by Western immunoblot. Gene silencing of HDAC 3/5/7 and GPR41 was performed using small interfering RNA. Expression of TNF-α mRNA was evaluated by TaqMan real-time polymerase chain reaction. RESULTS: We found that AR420626, a selective GPR41/FFA3 agonist, suppressed growth of HepG2 xenografts and inhibited proliferation of HCC cells by inducing apoptosis. AR420626 induced proteasome activation through mTOR phosphorylation, which reduced HDAC proteins, and then increased expression of TNF-α. CONCLUSION: AR420626, a selective GPR41/FFA3 agonist, may be a candidate as a therapeutic agent for HCC.

5.
Transplant Proc ; 52(9): 2750-2753, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951864

RESUMO

Common management of renal transplant recipients includes episodic renal biopsy based on clinical findings such as an increase in proteinuria or serum creatinine. When antibody-related rejection is suspected from the renal biopsy, subsequent testing for donor-specific antibodies (DSAs) is performed. We instead performed preemptive screening of asymptomatic post-renal transplant recipients for DSAs prior to renal biopsy. In this case, a 30-year-old woman with a secondary transplant was positive for 61 anti-HLA antibodies of class I and class II, among which DQ2 was a DSA with a mean fluorescence index of 2039. The patient had a living kidney transplant 9 years earlier. She had never been diagnosed with rejection, her serum creatinine was around 1.0 mg/dL, and her proteinuria was negative. Following the positive DSA result, a renal biopsy was performed, and she was diagnosed as C4d-negative chronic-active antibody-mediated rejection (CAABMR) with a Banff score of cg1b, (g + ptc) ≥ 2, and C4d 0. Intravenous steroid pulse, deoxyspagarin, antithymocyte globulin, rituximab, and oral everolimus were administrated. The treatment resulted in a gradual decrease in the DSA, which became negative 1 year later. The patient's serum creatinine remains around 1.0 mg/dL, and proteinuria remains negative. Treatments for advanced CAABMR are often expensive and ineffective. Our present case suggests that early detection and treatment through preemptive HLA antibody screening could improve the prognosis of renal transplants.


Assuntos
Anticorpos/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim , Adulto , Biópsia , Diagnóstico Precoce , Feminino , Humanos , Doadores de Tecidos , Transplantados , Transplantes/imunologia
6.
Clin Chim Acta ; 507: 271-279, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32348784

RESUMO

BACKGROUND: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. METHODS: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. RESULTS: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria

Assuntos
Injúria Renal Aguda/urina , Luminescência , Tiorredoxinas/urina , Injúria Renal Aguda/diagnóstico , Adulto , Idoso , Biomarcadores/urina , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
8.
Artigo em Inglês | MEDLINE | ID: mdl-32061840

RESUMO

Short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, are produced when colonic bacteria in the human gastrointestinal tract ferment undigested fibers. Free fatty acid receptor 2 (FFA2) and FFA3 are G-protein-coupled receptors recently identified as SCFA receptors that may modulate inflammation. We previously showed through in vitro experiments that SCFAs activate FFA2 and FFA3, thereby mitigating inflammation in human renal cortical epithelial cells. This study used a murine model of adenine-induced renal failure to investigate whether or not SCFAs can prevent the progression of renal damage. We also examined whether or not these FFA2 and FFA3 proteins have some roles in this protective mechanism in vivo. Immunohistochemical analyses of mouse kidneys showed that FFA2 and FFA3 proteins were expressed mainly in the distal renal tubules and collecting tubules. First, we observed that the administration of propionate mitigated the renal dysfunction and pathological deterioration caused by adenine. Consistent with this, the expression of inflammatory cytokines and fibrosis-related genes was reduced. Furthermore, the mitigation of adenine-induced renal damage by the administration of propionate was significantly attenuated in FFA2-/- and FFA3-/- mice. Therefore, the administration of propionate significantly protects against adenine-induced renal failure, at least in part, via the FFA2 and FFA3 pathways. Our data suggest that FFA2 and FFA3 are potential new therapeutic targets for preventing or delaying the progression of chronic kidney disease.


Assuntos
Propionatos/administração & dosagem , Receptores Acoplados a Proteínas G/metabolismo , Insuficiência Renal Crônica/prevenção & controle , Adenina/toxicidade , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Túbulos Renais Coletores/efeitos dos fármacos , Túbulos Renais Coletores/imunologia , Túbulos Renais Coletores/patologia , Túbulos Renais Distais/efeitos dos fármacos , Túbulos Renais Distais/imunologia , Túbulos Renais Distais/patologia , Masculino , Camundongos , Camundongos Knockout , Receptores Acoplados a Proteínas G/genética , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
9.
J Agric Food Chem ; 68(4): 1007-1014, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31914311

RESUMO

Induction of beige adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity because beige adipocytes release excess energy via uncoupling-protein-1-associated thermogenesis. In this study, we investigated how artepillin C (ArtC) promotes thermogenesis in vivo. We demonstrated that 28 day administration of ArtC (10 mg/kg of body weight) to mice significantly induced thermogenesis in beige adipocytes in inguinal WAT (iWAT) and suppressed reductions in core body temperature induced by cold exposure at 4 °C. Moreover, ArtC-induced thermogenesis in iWAT was significantly inhibited by treatment with a creatine metabolism inhibitor, and ArtC significantly upregulated the expression of creatine-metabolism-related enzymes in the thermogenic pathway. These results indicate that ArtC induces thermogenesis in beige adipocytes in iWAT, and the observed ArtC-induced thermogenesis is associated with the creatine-metabolism-related thermogenic pathway, which is characteristically observed in beige adipocytes.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Creatina/metabolismo , Obesidade/tratamento farmacológico , Fenilpropionatos/administração & dosagem , Própole/análise , Termogênese/efeitos dos fármacos , Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Temperatura Corporal , Brasil , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia , Própole/administração & dosagem
10.
Biosci Biotechnol Biochem ; 84(2): 428-431, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31608764

RESUMO

The effect of oral administration of all-E-isomer-rich and Z-isomer-rich lycopene on liver accumulation in mice was investigated. When a diet rich in the Z-isomers was administered for 4 weeks, the total lycopene concentration in the liver was more than 3 times higher than that of all-E-isomer administration. This result clearly indicates that lycopene Z-isomers show greater bioavailability and/or liver accumulation than the all-E-isomer in mice.


Assuntos
Fígado/metabolismo , Licopeno/metabolismo , Animais , Disponibilidade Biológica , Isomerismo , Licopeno/farmacocinética , Solanum lycopersicum/metabolismo , Camundongos
11.
J Pharmacol Sci ; 142(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31757742

RESUMO

Ketone bodies, including acetoacetate and ß-hydroxybutyrate (ßOHB), are produced from acetyl coenzyme A in the liver and then secreted into the blood. These molecules are a source of energy for peripheral tissues during exercise or fasting. ßOHB has been reported to inhibit histone deacetylases (HDACs) 1, 3, and 4 in human embryonic kidney 293 cells. Thus, ßOHB may regulate epigenetics by modulating HDACs. There have been several reports that the administration of ßOHB or induction of a physiological state of ketosis has an antitumor effect; however, the mechanism remains unclear. The aim of this study was to investigate whether ßOHB enhances cisplatin-induced apoptosis in hepatocellular carcinoma (HCC) cells by modulating activity and/or expression of HDACs. We found that ßOHB significantly enhanced cisplatin-induced apoptosis and cleavage of caspase-3 and -8 in HCC cells. Further, ßOHB significantly decreased the expression of HDCA 3/5/6 and survivin in liver hepatocellular (HepG2) cells. In HDAC3/6 gene silencing, survivin expression was significantly decreased, and cisplatin-induced cleavage of caspase-3 was significantly enhanced compared with control in HepG2 cells. In conclusion, ßOHB enhanced cisplatin-induced apoptosis via HDAC3/6 inhibition/survivin axis in HepG2 cells, which suggests that ßOHB could be a new adjuvant agent for cisplatin chemotherapy.


Assuntos
Ácido 3-Hidroxibutírico/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Ácido 3-Hidroxibutírico/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Survivina/genética , Survivina/metabolismo
12.
J Nutr Sci Vitaminol (Tokyo) ; 65(4): 328-334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474682

RESUMO

Classical brown adipocytes, characterized by interscapular depots, have multilocular fat depots and are known to release excess energy. Recent studies have shown that induction of brown-like adipocytes, also referred to as beige or brite cells, in white adipose tissue (WAT) results in the release of excess energy through mitochondrial heat production via uncoupling protein 1. This has potential a therapeutic strategy for obesity and related diseases as well as classical brown adipocytes. In our previous studies, we found that artepillin C (ArtC, 10 mg/kg body weight), a characteristic constituent of Brazilian propolis, significantly induced the development of brown-like adipocytes in inguinal WAT (iWAT) of mice. Furthermore, we recently demonstrated that curcumin (Cur, 4.5 mg/kg) also significantly induced the development of brown-like adipocytes in mice. The combined administration of several food-derived factors can enhance their bioactivity and reduce their required functional doses. In this study, we showed that co-administration of Cur and ArtC at lower doses (Cur, 1.5 mg/kg; ArtC, 5 mg/kg) additively induce brown-like adipocyte development in mouse iWAT. Moreover, this induction is associated with the localized production of norepinephrine following accumulation of alternatively activated macrophages in iWAT. These findings suggest that co-administration of Cur and ArtC is significantly effective to reduce the dose and enhance the formation of brown-like adipocyte via a unique molecular mechanism.


Assuntos
Adipócitos Marrons/fisiologia , Curcumina/administração & dosagem , Macrófagos/metabolismo , Norepinefrina/biossíntese , Fenilpropionatos/administração & dosagem , Adipócitos Marrons/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Fitoquímicos/administração & dosagem , Própole/química
13.
J Agric Food Chem ; 67(7): 1948-1954, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30691268

RESUMO

Hesperidin (HES) is a flavanone glycoside found in citrus peel that contributes to its bitter taste. It has low water solubility and poor oral bioavailability. To improve its solubility and bioavailability, α-monoglucosyl hesperidin (αGH) has been synthesized from HES by transglucosylation using cyclodextrin glucanotransferase. Several reports indicate that αGH significantly decreases body fat, but the underlying molecular mechanism remains unclear. We hypothesized that the antiobesity effects of αGH occur through the induced formation of brown-like adipocytes. The present study verified that dietary αGH induces brown-like adipocytes to form in mouse inguinal white adipose tissue (iWAT), thereby significantly decreasing the weight of white adipose tissue (WAT). Furthermore, dietary αGH significantly induced thermogenesis in iWAT. Dietary αGH also significantly suppressed high-fat-diet-induced WAT accumulation in mice, which may be mediated by brown-like adipocyte formation. These results indicate that dietary αGH induces increased energy expenditure by stimulating the formation of brown-like adipocytes.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Hesperidina/química , Hesperidina/farmacologia , Adipócitos Marrons/fisiologia , Tecido Adiposo Branco/crescimento & desenvolvimento , Animais , Fármacos Antiobesidade , Disponibilidade Biológica , Composição Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Glucosiltransferases/metabolismo , Glicosilação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Relação Estrutura-Atividade , Termogênese/efeitos dos fármacos
14.
Mol Nutr Food Res ; 62(5)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29334590

RESUMO

SCOPE: The induction of brown-like adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity and metabolic disorders via the ability of these cells to release excess energy as heat in association with uncoupling protein 1. Some experimental trials suggest that curcumin (a yellow pigment from turmeric) has a suppressive effect on the accumulation of body fat. However, there is little evidence to show that curcumin induces the formation of brown-like adipocytes and the molecular mechanisms involved remain elusive. In addition, in most experimental trials, high doses of curcumin are administered. METHODS AND RESULTS: Highly dispersible and bioavailable curcumin (HC, i.e., 4.5 mg native curcumin kg-1 ) but not the same dose of native curcumin induces the formation of brown-like adipocytes in mouse inguinal WAT. Moreover, the formation of brown-like adipocytes induced by HC in inguinal WAT may be mediated by the production of local norepinephrine from accumulated alternatively activated macrophages. CONCLUSION: These novel findings suggest that curcumin increases energy expenditure by inducing the formation of brown-like adipocytes via a unique molecular mechanism. Importantly, they show that HC has significant bioactive effects in vivo at lower doses of curcumin.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Curcumina/farmacologia , Adipócitos Marrons/fisiologia , Animais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Metabolismo Energético/efeitos dos fármacos , Lectinas Tipo C/análise , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Masculino , Receptor de Manose , Lectinas de Ligação a Manose/análise , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Superfície Celular/análise , Tirosina 3-Mono-Oxigenase/análise
15.
Food Sci Nutr ; 5(4): 929-933, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28748082

RESUMO

Glucagon-like peptide-1 (GLP-1) is an incretin that is secreted from enteroendocrine L-cells. Dietary factor-stimulation of endogenous GLP-1 is a promising strategy for increasing the action of GLP-1. Recent studies have shown that berries rich in anthocyanins improve insulin sensitivity and reduce the risk of type 2 diabetes. Our previous study found that the anthocyanin delphinidin 3-rutinoside (D3R) significantly increases GLP-1 secretion in GLUTag cells (enteroendocrine L cell line). Blackcurrants are berries that contain high levels of anthocyanins, particularly D3R. Pre-administered blackcurrant extract (BCE) 5 mg/kg body weight (1 mg D3R/kg) significantly ameliorated glucose tolerance after intraperitoneal glucose injection in rats by stimulating the secretion of GLP-1 and subsequently inducing insulin secretion. D3R did not break down significantly in the gastrointestinal tract for at least 45-60 min after BCE was administered, suggesting that BCE-induced GLP-1 secretion is mainly mediated by D3R and not its degradation products. These findings demonstrate the novel biological function of D3R-rich BCE as a GLP-1 secretagogue. An increase in endogenous GLP-1 secretion induced by BCE may help to reduce the dosages of diabetic medicines and prevent diabetes.

16.
Mol Nutr Food Res ; 61(3)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27990751

RESUMO

SCOPE: Glucagon-like peptide-1 (GLP-1) is a type of incretin secreted from enteroendocrine L-cells. Our previous studies demonstrated that curcumin (a yellow pigment of turmeric) significantly increases the secretion of GLP-1 in enteroendocrine L cell line (GLUTag cells). However, it is not clear whether its action in vivo directly enhances GLP-1 secretion, which then leads to a reduction in blood glucose levels via the stimulation of insulin secretion. In addition, the molecular target of curcumin-induced GLP-1 secretion has not been clarified. METHODS AND RESULTS: Glucose tolerance was significantly improved in rats after pre-administered curcumin (1.5 mg/kg) followed by intraperitoneal glucose injections via the stimulation of GLP-1 secretion and the induction of insulin secretion. In GLUTag cells, curcumin-induced GLP-1 secretion was associated with G protein-coupled receptor (GPR) 40/120. Furthermore, the glucose-lowering effect induced by curcumin was significantly reduced after the administration of a GPR40/120 antagonist in rats. CONCLUSION: These findings demonstrate the biological function of curcumin as a GLP-1 secretagogue and the possible molecular target that mediates GLP-1 secretion. Increases in the secretion of endogenous GLP-1 induced by curcumin may allow the dosages of other diabetic medicines to be reduced and aid in the prevention of diabetes.


Assuntos
Curcumina/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Administração Oral , Animais , Benzoatos/farmacologia , Glicemia/metabolismo , Linhagem Celular , Curcumina/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Hipoglicemia/tratamento farmacológico , Hipoglicemia/metabolismo , Injeções Intraperitoneais , Insulina/sangue , Masculino , Camundongos , Pirimidinas/farmacologia , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo
17.
PLoS One ; 11(9): e0162512, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27598888

RESUMO

Induction of brown-like adipocytes (beige/brite cells) in white adipose tissue (WAT) suggests a new approach for preventing and treating obesity via induction of thermogenesis associated with uncoupling protein 1 (UCP1). However, whether diet-derived factors can directly induce browning of white adipocytes has not been well established. In addition, the underlying mechanism of induction of brown-like adipocytes by diet-derived factors has been unclear. Here, we demonstrate that artepillin C (ArtC), which is a typical Brazilian propolis-derived component, significantly induces brown-like adipocytes in murine C3H10T1/2 cells and primary inguinal WAT (iWAT)-derived adipocytes. This significant induction is due to activation of peroxisome proliferator-activated receptor γ and stabilization of PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16). Furthermore, the oral administration of ArtC (10 mg/kg) for 4 weeks significantly induced brown-like adipocytes accompanied by significant expression of UCP1 and PRDM16 proteins in iWAT of mice, and was independent of the ß3-adrenergic signaling pathway via the sympathetic nervous system. These findings may provide insight into browning of white adipocytes including the molecular mechanism mediated by dietary factors and demonstrate that ArtC has a novel biological function with regard to increasing energy expenditure by browning of white adipocytes.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Metabolismo Energético/efeitos dos fármacos , Obesidade/prevenção & controle , Fenilpropionatos/farmacologia , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Administração Oral , Animais , Fármacos Antiobesidade/isolamento & purificação , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Metabolismo Energético/genética , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/agonistas , PPAR gama/genética , PPAR gama/metabolismo , Fenilpropionatos/isolamento & purificação , Cultura Primária de Células , Própole/química , Transdução de Sinais , Termogênese/efeitos dos fármacos , Termogênese/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/agonistas , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
18.
Sci Rep ; 4: 4057, 2014 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-24531845

RESUMO

Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-κB (NF-κB) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-κB in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-κB signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-κB inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-κB participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-κB signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-κB inhibition. Therefore, we suggest that NF-κB is a master switch in both ER-positive and ER-negative breast cancers.


Assuntos
Antineoplásicos Hormonais/toxicidade , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , NF-kappa B/metabolismo , Tamoxifeno/toxicidade , Animais , Antineoplásicos Hormonais/uso terapêutico , Benzamidas/uso terapêutico , Benzamidas/toxicidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêutico , Transplante Heterólogo
19.
Cancer Med ; 3(2): 416-25, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24510578

RESUMO

Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Animais , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Glutamatos/farmacologia , Guanina/análogos & derivados , Guanina/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mesotelioma/metabolismo , Mesotelioma/patologia , Mesotelioma Maligno , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Terapia de Alvo Molecular , Pemetrexede , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Res Vet Sci ; 96(1): 124-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24269079

RESUMO

Mast cell tumor (MCT) is the most common cutaneous tumor in dogs. We recently revealed that production of stem cell factor (SCF) contributes to the proliferation of neoplastic mast cells in an autocrine/paracrine manner. The aim of the present study was to determine the contribution of the mechanism in clinical MCTs. In consequence, high SCF expression (>10 times compared to HRMC cells) was observed in 5 of 7 MCT samples used in the study regardless of KIT mutation, which was confirmed in immunohistochemical analysis. In addition, production of SCF was observed in Ki-67-positive cells in the MCT xenograft. These results indicate the broad contribution of SCF autocrine/paracrine mechanism on clinical MCTs, providing the rationale for the clinical use of KIT inhibitors regardless of KIT mutation.


Assuntos
Doenças do Cão/metabolismo , Mastócitos/metabolismo , Neoplasias Cutâneas/metabolismo , Fator de Células-Tronco/metabolismo , Animais , Doenças do Cão/genética , Cães , Feminino , Citometria de Fluxo , Imuno-Histoquímica/veterinária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Neoplásico/química , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Neoplasias Cutâneas/genética , Fator de Células-Tronco/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...