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1.
J Agric Food Chem ; 68(24): 6715-6725, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32450691

RESUMO

Brown adipocytes, which contain abundant mitochondria, use stored energy as fuel during a process named nonshivering thermogenesis. Thus, the pharmacological activation of thermogenesis in brown adipose tissue (BAT) has become a promising target for treating obesity. We investigated the effect of fruit of Hovenial dulcis Thunb. (FHD), a frequently used herbal treatment for liver diseases, on thermogenesis and its mechanism using primary cultured brown adipocytes and BAT of high-fat-diet (HFD)-induced obese mice. Thermogenesis-related factors including UCP1 and PGC1α increased with FHD treatment. FHD also increased mitochondrial biogenesis and activation factors such as nuclear respiratory factor (NRF)1 and oxidative phosphorylation (OXPHOS) complex. Furthermore, FHD increased the intercellular nicotinamide adenine dinucleotide (NAD+) level and sirtuin 1 (SIRT1) activity, which may be responsible for the activation of the thermogenic reaction. Overall, our results suggest that FHD can be a novel option for obesity treatment due to its thermogenic action through mitochondrial biogenesis and activation.

2.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443565

RESUMO

Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Citrus , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/enzimologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/enzimologia , Tecido Adiposo/enzimologia , Tecido Adiposo/fisiopatologia , Animais , Fármacos Antiobesidade/isolamento & purificação , Citrus/química , Modelos Animais de Doenças , Ativação Enzimática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/enzimologia , Obesidade/fisiopatologia , Extratos Vegetais/isolamento & purificação , Transdução de Sinais
3.
Clin Otolaryngol ; 44(6): 997-1003, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468673

RESUMO

OBJECTIVES: The aim of the current study was to investigate the effectiveness and clinical feasibility of Biyeom-go for the treatment of nasal symptoms associated with rhinitis. DESIGN: Prospective observational study. SETTING: This study was conducted at the Woosuk Korean Medicine Medical Center in South Korea. PARTICIPANTS: Fifty-eight patients with rhinitis participated in this study. All patients received Biyeom-go treatment >3 times daily for a total of 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the total nasal symptom score. Mini-rhinoconjunctivitis quality of life questionnaire, nasal endoscopy index, total serum immunoglobulin E levels and immunologic factors in nasal lavage fluid were also measured. RESULTS: Biyeom-go administration was associated with significant improvements in total nasal symptoms scores (P < .0001) and mini-rhinoconjunctivitis quality of life questionnaire scores (P < .0001) in a time-dependent manner. The nasal endoscopy index also significantly improved at weeks 2 (P = .0049), 3 (P < .0001) and 4 (P = .0001) after Biyeom-go treatment. Significantly, increased interleukin-2 levels (P = .005) and decreased interleukin-8, chemokine (C-C motif) ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL) 9, CCL2 and CXCL10 levels were observed in the nasal lavage fluid. CONCLUSIONS: The present findings suggest that Biyeom-go may be beneficial for the management of rhinitis symptoms and rhinitis-associated quality of life. Further well-designed randomised controlled trials are needed to evaluate the effectiveness of Biyeom-go for rhinitis.

5.
Ultrasound Med Biol ; 45(10): 2672-2678, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31262524

RESUMO

This study evaluated the diagnostic performance of a commercially available computer-aided diagnosis (CAD) system (S-Detect 1 and S-Detect 2 for thyroid) for detecting thyroid cancers. Among 218 thyroid nodules in 106 patients, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the CAD systems were 80.2%, 82.6%, 75.0%, 86.3% and 81.7%, respectively, for the S-Detect 1 and 81.4%, 68.2%, 62.5%, 84.9% and 73.4%, respectively, for the S-Detect 2. The inter-observer agreement between the CAD system and radiologist for the description of calcifications was fair (kappa = 0.336), while the final diagnosis and each ultrasonographic descriptor showed moderate to substantial agreement for the S-Detect 2. To conclude, the current CAD systems had limited specificity in the diagnosis of thyroid cancer. One of the main limitations of the S-Detect 2 was its inaccuracy in recognizing calcifications, which meant that differentiation had to be undertaken by the radiologist.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico por Computador , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
7.
Phytomedicine ; : 152936, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31088684

RESUMO

BACKGROUND: In Traditional Korean and Chinese medicine, the herbal remedy Yijin (Erchen)-Tang (YJT) is widely used to treat obesity-related disorders, and its therapeutic potential has been demonstrated in numerous studies. However, the systemic effect of YJT on obesity status and change of lipid metabolism by YJT still remains unknown. PURPOSE: This study aimed to investigate the therapeutic mechanism of the YJT on obesity by using lipidomics. METHODS: To evaluate the effects of treatment with YJT on obesity, C57BL/6 J mice were fed a high-fat and high-cholesterol (HFHC, 40% fat and 1% cholesterol) diet for 8 weeks and treated them with YJT for an additional 6 weeks. We then performed untargeted lipidomic analysis using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry mass spectroscopy coupled with multivariate statistical analysis. RESULTS: YJT ameliorated obesity induced systemic inflammation and improved insulin resistance. Additionally, YJT protected against HFHC-diet-induced hepatic inflammation. To explore specific changes in lipid metabolism associated with the therapeutic effects of YJT, we performed untargeted lipid profiling of the plasma. Partial least squares-discriminant analysis (PLS-DA) score plots showed that YJT altered the lipid metabolic pattern of HFHC mice. In particular, ceramides and triglycerides with saturated fatty acids and monounsaturated fatty acids were significantly changed by YJT, which were significantly associated with insulin resistance, the AGE-RAGE signaling pathway in diabetic complications and adipocytokine signaling pathway in pathway enrichment analysis. Thus, we analyzed the changes in adipocytes and adipokine caused by YJT, and confirmed that YJT alleviated adipocytes inflammation and macrophage infiltration, and reversed HFHC-induced alterations in leptin and adiponectin levels in adipose tissue and plasma. CONCLUSION: These data suggest that YJT ameliorates obesity-induced systemic inflammation and insulin resistance by regulating lipid metabolism, and demonstrated that lipidomic profiling is a useful method to investigate the therapeutic effects of herbal decoctions in traditional Korean and Chinese medicine.

8.
Phytomedicine ; 52: 254-263, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599906

RESUMO

BACKGROUND: Platycodi Radix (root of Platycodon grandiflorum) and its active compound platycodin D (PD) has been previously shown to possess anti-obesity properties, but the underlying mechanisms remain poorly understood. PURPOSE: The present study was aimed to evaluate the anti-obese effect of PD and reveal its mechanism of action. STUDY DESIGN/METHODS: Genetically obese db/db mice were orally treated with PD for 4 weeks, and body weight gain, adipose tissue weight, serum parameters were measured. Then, assays on adipogenic factors, thermogenic factors, and AMP-activated protein kinase (AMPK) pathway were performed in PD-treated 3T3-L1 murine adipocytes, human adipose-derived mesenchymal stem cells (hAMSCs), and primary cultured brown adipocytes. RESULTS: PD treatment attenuated body weight gain, suppressed white adipose tissue weight and improved obesity-related serum parameters in db/db mice. Two major adipogenic factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) were decreased by PD treatment in WAT of db/db mice, 3T3-L1 adipocytes and hAMSCs. In BAT of db/db mice and primary cultured brown adipocytes, PD treatment elevated the expressions of uncoupled protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator 1 α (PCG1α), the key regulators of BAT-associated thermogenesis. In addition, PD activated AMPKα both in vivo and in vitro. However, when AMPK was inhibited by compound C, PD treatment failed to suppress adipogenic factors and increase thermogenic factors. CONCLUSIONS: PD improved obesity in db/db mice by AMPK-associated decrease of adipogenic markers including PPARγ and C/EBPα. PD increased thermogenic factors such as UCP1 and PGC1α in db/db mice and primary cultured brown adipocytes. AMPK inhibition nullified the effects of PD, suggesting its anti-adipogenic and thermogenic actions were dependent on AMPK pathway activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Marrons/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Obesidade/tratamento farmacológico , Saponinas/farmacologia , Termogênese/efeitos dos fármacos , Triterpenos/farmacologia , Células 3T3-L1 , Tecido Adiposo Marrom/citologia , Tecido Adiposo Branco/citologia , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Knockout , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Platycodon/química , Proteína Desacopladora 1/metabolismo
9.
Eur Radiol ; 29(4): 1978-1985, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30350161

RESUMO

PURPOSE: To evaluate the diagnostic performance and reproducibility of a computer-aided diagnosis (CAD) system for thyroid cancer diagnosis using ultrasonography (US) based on the operator's experience. MATERIALS AND METHODS: Between July 2016 and October 2016, 76 consecutive patients with 100 thyroid nodules (≥ 1.0 cm) were prospectively included. An experienced radiologist performed the US examinations with a real-time CAD system integrated into the US machine, and three operators with different levels of US experience (0-5 years) independently applied the CAD system. We compared the diagnostic performance of the CAD system based on the operators' experience and calculated the interobserver agreement for cancer diagnosis and in terms of each US descriptor. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 88.6, 83.9, 81.3, 90.4, and 86.0%, respectively. The sensitivity and accuracy of the CAD system were not significantly different from those of the radiologist (p > 0.05), while the specificity was higher for the experienced radiologist (p = 0.016). For the less-experienced operators, the sensitivity was 68.8-73.8%, specificity 74.1-88.5%, PPV 68.9-73.3%, NPV 72.7-80.0%, and accuracy 71.0-75.0%. The less-experienced operators showed lower sensitivity and accuracy than those for the experienced radiologist. The interobserver agreement was substantial for the final diagnosis and each US descriptor, and moderate for the margin and composition. CONCLUSIONS: The CAD system may have a potential role in the thyroid cancer diagnosis. However, operator dependency still remains and needs improvement. KEY POINTS: • The sensitivity and accuracy of the CAD system did not differ significantly from those of the experienced radiologist (88.6% vs. 84.1%, p = 0.687; 86.0% vs. 91.0%, p = 0.267) while the specificity was significantly higher for the experienced radiologist (83.9% vs. 96.4%, p = 0.016). • However, the diagnostic performance varied according to the operator's experience (sensitivity 70.5-88.6%, accuracy 72.0-86.0%) and they were lower for the less-experienced operators than for the experienced radiologist. • The interobserver agreement was substantial for the final diagnosis and each US descriptor and moderate for the margin and composition.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Sistemas Computacionais , Diagnóstico por Computador/normas , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Variações Dependentes do Observador , Exame Físico/normas , Estudos Prospectivos , Radiologistas/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
10.
Hepatology ; 69(4): 1599-1613, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30365164

RESUMO

Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, surveillance using magnetic resonance imaging (MRI) with liver-specific contrast showed markedly higher sensitivity in detecting early-stage HCC than US. This study aimed to compare the cost-effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost-effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality-adjusted life-years (QALYs), between MRI and US, with a 20-year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus-associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost-effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost-effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life-years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost-effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver-specific contrast may be more cost-effective than US in patients with virus-associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.

11.
Front Pharmacol ; 9: 773, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30061836

RESUMO

Benign prostate hyperplasia (BPH) is a common disease in elderly men, characterized by proliferated prostate and urinary tract symptoms. The hormonal cascade starting by the action of 5-alpha-reductase (5AR) is known to be one of the pathways responsible for the pathogenesis of BPH. Present investigation evaluated the capacity of berberine (BBR), a nature-derived compound abundant in Coptis japonica, in testosterone-induced BPH rats. Experimental BPH was induced by inguinal injection with testosterone propionate (TP) for 4 weeks. BBR or finasteride, a 5AR inhibitor as positive control, was treated for 4 weeks during BPH. BPH induced by TP evoked weight gaining and histological changes of prostate and BBR treatment improved all the detrimental effects not only weight reduction and histological changes but also suppression of prostate-specific antigen (PSA), which is elevated during BPH. Additionally, BBR suppressed TP-associated increase of 5AR, androgen receptor (AR) and steroid coactivator-1 (SRC-1), the key factors in the pathogenesis of BPH. To evaluate the underlying molecular mechanisms responsible for beneficial effects of BBR, we investigated whether these effects were associated with the mitogen-activated protein kinase pathway. BPH induced by TP showed increased phosphorylation of extracellular signal-regulated kinase (ERK), whereas this was suppressed by BBR treatment. On the other hand, c-jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase was not changed in BPH rats. In in vitro study using RWPE-1 cells, a human prostate epithelial cell line. TP increased cell proliferation and BPH-related key factors such as PSA, AR, and 5AR in RWPE-1 cells, and those factors were significantly decreased in the presence of BBR. Furthermore, these proliferative effects in RWPE-1cells were attenuated by treatment with U0126, an ERK inhibitor, confirming BBR can relieve overgrowth of prostate via ERK-dependent signaling. The cotreatment of U0126 and BBR did not affect the change of 5AR nor proliferation compared with U0126 alone, suggesting that the effect of BBR was dependent on the action of ERK. In conclusion, this study shows that BBR can be used as a therapeutic agent for BPH by controlling hyperplasia of prostate through suppression of ERK mechanism.

12.
Korean J Radiol ; 19(4): 665-672, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962872

RESUMO

Objective: To prospectively evaluate the diagnostic performance of computer-aided diagnosis (CAD) for detection of thyroid cancers via ultrasonography (US). Materials and Methods: This study included 50 consecutive patients with 117 thyroid nodules on US during the period between June 2016 and July 2016. A radiologist performed US examinations using real-time CAD integrated into a US scanner. We compared the diagnostic performance of radiologist, the CAD system, and the CAD-assisted radiologist for the detection of thyroid cancers. Results: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 80.0, 88.1, 83.3, 85.5, and 84.6%, respectively, and were not significantly different from those of the radiologist (p > 0.05). The CAD-assisted radiologist showed improved diagnostic sensitivity compared with the radiologist alone (92.0% vs. 84.0%, p = 0.037), while the specificity and PPV were reduced (85.1% vs. 95.5%, p = 0.005 and 82.1% vs. 93.3%, p = 0.008). The radiologist assisted by the CAD system exhibited better diagnostic sensitivity and NPV than the CAD system alone (92.0% vs. 80.0%, p = 0.009 and 93.4% vs. 88.9%, p = 0.013), while the specificities and PPVs were not significantly different (88.1% vs. 85.1%, p = 0.151 and 83.3% vs. 82.1%, p = 0.613, respectively). Conclusion: The CAD system may be an adjunct to radiological intervention in the diagnosis of thyroid cancer.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Diagnóstico por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
14.
BMJ Open ; 8(3): e020825, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29567854

RESUMO

OBJECTIVES: Asthma exacerbation, associated with many risks factors, can reflect management failure. However, little is known about how risk factors are associated with exacerbation, according to asthma severity. We aimed to investigate differences in risk factors in patients with different asthma severity and evaluate whether risk factors differed between frequent exacerbators and patients with single exacerbation. DESIGN: Nationwide population-based observational study. SETTING: Korean National Sample Cohort database. PARTICIPANTS: We included 22 130 adults with asthma diagnoses more than twice (ICD-10 (International Classification of Diseases, Tenth revision) codes J45 and J46) and one prescription for asthma medication from 2010 to 2011. OUTCOME MEASURES: Asthma exacerbation was defined as having a corticosteroid (CS) burst characterised by a prescription of high-dose oral CS for ≥3 days or one systemic CS injection, hospitalisation or emergency department visit. RESULTS: Among severities, history of CS bursts was significantly associated with exacerbation. In mild and moderate asthma, exacerbation was significantly associated with age ≥45 years, being female, gastro-oesophageal reflux disease and chronic rhinitis. High medication possession ratio (MPR≥50%), compared with low MPR (<20%) showed adjusted ORs of 0.828 (95% CI 0.707 to 0.971) and 0.362 (0.185 to 0.708) in moderate and severe asthma, respectively. In severe asthma, compared with mild asthma, only allergic rhinitis and history of hospitalisation were strongly associated with exacerbation. When comparing frequent exacerbators to patients with single exacerbation, age ≥45 years, atopic dermatitis, anxiety and history of CS burst were significant risk factors in mild and moderate asthma, whereas no risk factors were significant in severe asthma. CONCLUSIONS: Different associations between risk factors and asthma exacerbations based on asthma severity suggest that patients with mild asthma require greater attention to their age and comorbidities, whereas those with severe asthma require greater attention to hospitalisation history and drug adherence.


Assuntos
Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Asma/epidemiologia , Progressão da Doença , Adulto , Distribuição por Idade , Idoso , Comorbidade , Bases de Dados Factuais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Adulto Jovem
15.
Eur J Pharmacol ; 820: 235-244, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29269018

RESUMO

Flaxseeds are used to treat metabolic diseases such as type 2 diabetes, fatty liver, hyperlipidemia and obesity. Secoisolariciresinol diglucoside (SDG) is a main substance of lignan which belongs to the phytoestrogen family and exists abundantly in flaxseeds. In this study, SDG reduced the body weight and size of adipose tissue, and decreased protein expressions of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα) in the high fat diet-fed-induced obese mice model. In the vitro study, we examined the anti-adipogenic effect of SDG during differentiation of 3T3-L1 cells into adipocytes. 3T3-L1 preadipocytes were differentiated and treated with various concentrations of SDG. Oil Red O staining was done to measure the quantity of lipid contents. As a result, SDG reduced lipid accumulation and decreased the expressions of adipogenic-related genes such as adipocyte fatty-acid-binding protein 2, adiponectin, and resistin. SDG also decreased the mRNA and protein levels of PPARγ and C/EBPα. Furthermore, phosphorylation levels of AMP-activated protein kinase α (AMPK α) and its upstream activator, liver kinase B1, were significantly increased by SDG in 3T3-L1 cells. These results suggest that SDG inhibits adipogenesis by activating AMPKα, suggesting it could be an attractive therapeutic candidate for the treatment of obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Butileno Glicóis/farmacologia , Glucosídeos/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Animais , Butileno Glicóis/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Glucosídeos/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
16.
FASEB J ; 32(3): 1388-1402, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29141998

RESUMO

Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro. High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice. Furthermore, VA inhibited lipid accumulation and reduced hepatotoxic/inflammatory markers in liver tissues of mice and HepG2 hepatocytes. VA treatment also decreased differentiation of 3T3-L1 adipocytes by regulating adipogenic factors including PPARγ and C/EBPα. AMPKα small interfering RNA was used to examine whether AMPK was associated with the actions of VA. In AMPKα-nulled 3T3-L1 cells, the inhibitory action of VA on PPARγ and C/EBPα was attenuated. Furthermore, in brown adipose tissues of mice and primary cultured brown adipocytes, VA increased mitochondria- and thermogenesis-related factors such as uncoupling protein 1 and PPARγ-coactivator 1-α. Taken together, our results suggest that VA has potential as an AMPKα- and thermogenesis-activating antiobesity agent.-Jung, Y., Park, J., Kim, H.-L., Sim, J.-E., Youn, D.-H., Kang, J., Lim, S., Jeong, M.-Y., Yang, W. M., Lee, S.-G., Ahn, K. S., Um, J.-Y. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Obesidade/tratamento farmacológico , Termogênese/efeitos dos fármacos , Ácido Vanílico/farmacologia , Células 3T3-L1 , Tecido Adiposo Marrom/patologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT , Ativação Enzimática/efeitos dos fármacos , Masculino , Camundongos , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
17.
Oncotarget ; 8(50): 87194-87208, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152074

RESUMO

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34ßE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

18.
Front Pharmacol ; 8: 654, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29033835

RESUMO

Brown adipocytes dissipate energy as heat and hence have an important therapeutic capacity for obesity. Development of brown-like adipocytes (also called beige) is also another attractive target for obesity treatment. Here, we investigated the effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the browning of white adipose tissue (WAT) as well as on the weight gain of high-fat diet (HFD)-induced obese mice. Farnesol inhibited adipogenesis and the related key regulators including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α through the up-regulation of AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). Farnesol markedly increased the expression of uncoupling protein 1 and PPARγ coactivator 1 α in differentiated hAMSCs. In addition, farnesol limited the weight gain in HFD obese mice and induced the development of beige adipocytes in both inguinal and epididymal WAT. These results suggest that farnesol could be a potential therapeutic agent for obesity treatment.

19.
Metabolism ; 73: 85-99, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28732574

RESUMO

OBJECTIVE: Brown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro. MATERIALS/METHODS: Human adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF. Male C57BL/6J mice (n=5 per group) were fed a high-fat diet (HFD) for six weeks with or without AF. Brown preadipocytes from the interscapular BAT of mice were cultured with or without AF. RESULTS: In white adipogenic differentiation of hAMSCs, AF treatment significantly reduced the formation of lipid droplets and the expression of adipogenesis-related genes. In HFD-induced obese C57BL/6J mice, AF treatment significantly reduced body weight gain as well as the weights of the white adipose tissue, liver and spleen. Furthermore, AF induced the expression of genes involved in thermogenic function in BAT. In primary brown adipocytes, AF effectively stimulated the expressions of thermogenic genes and markedly up-regulated the AMP-activated protein kinase (AMPK) signaling pathway. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 nullified the induction of the thermogenic genes by AF in primary brown adipocytes. Moreover, AF activated beige cell marker genes induced by the pharmacological activation of peroxisome proliferator-activated receptor γ in hAMSCs. CONCLUSION: This study shows that AF prevents the development of obesity in hAMSCs and mice fed an HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes by AMPK and PI3K/AKT.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Células-Tronco Mesenquimais/citologia , Obesidade/tratamento farmacológico , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Termogênese/genética , Adipócitos Marrons/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Diferenciação Celular , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ativação Transcricional
20.
Clin Exp Rheumatol ; 35(4): 689-699, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28079510

RESUMO

OBJECTIVES: The purpose of this study was to compare the discontinuation rates of tofacitinib and biologics (tumour necrosis factor inhibitors (TNFi), abatacept, rituximab, and tocilizumab) in rheumatoid arthritis (RA) patients considering inadequate responses (IRs) to previous treatment(s). METHODS: Randomised controlled trials of tofacitinib and biologics - reporting at least one total discontinuation, discontinuation due to lack of efficacy (LOE), and discontinuation due to adverse events (AEs) - were identified through systematic review. The analyses were conducted for patients with IRs to conventional synthetic disease-modifying anti-rheumatic drugs (cDMARDs) and for patients with biologics-IR, separately. Bayesian network meta-analysis was used to estimate rate ratio (RR) of a biologic relative to tofacitinib with 95% credible interval (CrI), and probability of RR being <1 (P[RR<1]). RESULTS: The analyses of 34 studies showed no significant differences in discontinuation rates between tofacitinib and biologics in the cDMARDs-IR group. In the biologics-IR group, however, TNFi (RR 0.17, 95% CrI 0.01-3.61, P[RR<1] 92.0%) and rituximab (RR 0.20, 95% CrI 0.01-2.91, P[RR<1] 92.3%) showed significantly lower total discontinuation rates than tofacitinib did. Despite the difference, discontinuation cases owing to LOE and AEs revealed that tofacitinib was comparable to the biologics. CONCLUSIONS: The comparability of discontinuation rate between tofacitinib and biologics was different based on previous treatments and discontinuation reasons: LOE, AEs, and total (due to other reasons). Therefore, those factors need to be considered to decide the optimal treatment strategy.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Desprescrições , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Teorema de Bayes , Humanos , Metanálise em Rede
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