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1.
Curr Issues Mol Biol ; 46(7): 7505-7515, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39057086

RESUMEN

Sodium-glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 µL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP. These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.

2.
J Clin Periodontol ; 49(4): 362-377, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35141945

RESUMEN

AIM: To evaluate the intervention effect of omega-3 fatty acids on changes in periodontal parameters. MATERIALS AND METHODS: This meta-analysis included studies published in English language between 2010 and 2020, which were extracted from the Cochrane Library, EMBASE, and PubMed databases. The effects of omega-3 fatty acid intervention were investigated using the amount of omega-3 intake, periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP). The random-effects model was generated for data analysis. To obtain robustness of the model, sensitivity analysis was implemented. Subgroup analyses were performed based on the intervention period for each parameter. RESULTS: All 13 studies included in the meta-analysis were interventional, randomized controlled trials. Two studies implemented omega-3 fatty acid-rich diets, while 11 studies used supplements. Risk of bias was low, and publication bias was not shown. Meta-analysis showed a statistically significant PPD reduction (standardized mean difference [SMD] = -0.81, absolute mean difference [MD] = -0.44 mm), CAL gain (SMD = -0.77, MD = -0.51 mm), and BOP reduction (SMD = -0.65, MD = -9.45%) for the omega-3 fatty acid intervention overall. CONCLUSION: This study suggests that supplemental or dietary intake of omega-3 fatty acids for the treatment of periodontitis may have a positive impact on the disease.


Asunto(s)
Ácidos Grasos Omega-3 , Periodontitis , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Bolsa Periodontal , Periodontitis/tratamiento farmacológico , Periodontitis/prevención & control
3.
Acta Radiol ; 63(8): 1086-1092, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34260321

RESUMEN

BACKGROUND: Even though radiologic diagnosis of bone tumors and tumor-like lesions is usually based on radiographs, radiographically faint imaging features sometimes remain challenging due to overlapping anatomical structures. PURPOSE: To compare tomosynthesis with radiography for the evaluation of bone tumors and tumor-like lesions. MATERIAL AND METHODS: Forty-seven bone tumors and tumor-like lesions were assessed with radiographs and tomosynthesis images. Two radiologists independently analyzed imaging features of lesions, including margin, periosteal reaction, cortical thinning, matrix mineralization, cortical destruction (such as pathologic fracture), and extraosseous soft-tissue extension. Computed tomography (CT) imaging was used as a reference method. Diagnostic performances of radiography and tomosynthesis were analyzed and compared based on sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Effective radiation dose was compared among the three imaging modalities by phantom studies. RESULTS: Inter-observer variability (kappa value) for imaging features was slight to moderate on radiography (0.167-0.588), whereas it was nearly perfect on tomosynthesis (0.898-1.000) except for extraosseous soft-tissue extension (0.647 vs. 0.647). Tomosynthesis showed significantly higher sensitivity than radiography in evaluating the margin for bone tumors or tumor-like lesions (1.00 vs. 0.85; P = 0.016), and significantly higher accuracy than radiography in evaluating the margin and matrix mineralization for those (1.00 vs. 0.85; P = 0.016 and 0.91 vs.0.77; P = 0.023, respectively). In phantom studies, mean effective radiation doses were highest in order of CT, tomography, and radiography. CONCLUSION: Tomosynthesis increases sensitivity and accuracy of the margin as well as accuracy of the matrix mineralization of bone tumors and tumor-like lesions compared to radiography.


Asunto(s)
Neoplasias Óseas , Tomografía Computarizada por Rayos X , Neoplasias Óseas/diagnóstico por imagen , Humanos , Fantasmas de Imagen , Valor Predictivo de las Pruebas , Radiografía , Tomografía Computarizada por Rayos X/métodos
4.
Biochem Biophys Res Commun ; 571: 159-166, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34325132

RESUMEN

Uncontrolled cell proliferation associated with cancer depends on the functional abrogation of at least one of tumor suppressor. In response to nutrient cue, tuberous sclerosis complex (TSC) works as a tumor suppressor which inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). However, the regulation mechanism of nutrient-dependent cell proliferation in TSC-null cells remains unclear. Here, we demonstrate that leucine is required for cell proliferation through the activation of leucyl-tRNA synthetase (LARS1)-mTORC1 pathway in TSC-null cells. Cell proliferation and survival were attenuated by LARS1 knock-down or inhibitors in TSC-null cells. In addition, either rapamycin or LARS1 inhibitors significantly decreased colony formation ability while their combined treatment drastically attenuated it. Taken together, we suggest that LARS1 inhibitors might considered as novel tools for the regression of tumor growth and proliferation in TSC-null tumor cells which regrow upon discontinuation of the mTORC1 inhibition.


Asunto(s)
Leucina-ARNt Ligasa/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa/metabolismo , Animales , Proliferación Celular , Células Cultivadas , Ratones , Ratones Desnudos , Proteína 1 del Complejo de la Esclerosis Tuberosa/deficiencia , Proteína 2 del Complejo de la Esclerosis Tuberosa/deficiencia , Proteína 2 del Complejo de la Esclerosis Tuberosa/metabolismo
5.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34769001

RESUMEN

Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common hereditary axonal neuropathy caused by mutations in MFN2 encoding Mitofusin-2, a multifunctional protein located in the outer mitochondrial membrane. In order to study the effects of a novel MFN2K357T mutation associated with early onset, autosomal dominant severe CMT2A, we generated a knock-in mouse model. While Mfn2K357T/K357T mouse pups were postnatally lethal, Mfn2+/K357T heterozygous mice were asymptomatic and had no histopathological changes in their sciatic nerves up to 10 months of age. However, immunofluorescence analysis of Mfn2+/K357T mice revealed aberrant mitochondrial clustering in the sciatic nerves from 6 months of age, in optic nerves from 8 months, and in lumbar spinal cord white matter at 10 months, along with microglia activation. Ultrastructural analyses confirmed dysmorphic mitochondrial aggregates in sciatic and optic nerves. After exposure of 6-month-old mice to lipopolysaccharide, Mfn2+/K357T mice displayed a higher immune response, a more severe motor impairment, and increased CNS inflammation, microglia activation, and macrophage infiltrates. Overall, ubiquitous Mfn2K357T expression renders the CNS and peripheral nerves of Mfn2+/K357T mice more susceptible to mitochondrial clustering, and augments their response to inflammation, modeling some cellular mechanisms that may be relevant for the development of neuropathy in patients with CMT2A.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Mitocondrias/genética , Dinámicas Mitocondriales/genética , Enfermedades Neuroinflamatorias/genética , Enfermedades Neuroinflamatorias/patología , Animales , Modelos Animales de Enfermedad , Inmunidad/genética , Inflamación/genética , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/patología , Proteínas Mitocondriales/genética
6.
Dig Dis Sci ; 63(3): 619-627, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29372479

RESUMEN

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. AIM: The aim of this study was to discover the novel and reliable biomarker for IBS. METHOD: In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. RESULTS: Male pups developed symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. CONCLUSION: Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.


Asunto(s)
Células Intersticiales de Cajal/patología , Síndrome del Colon Irritable/enzimología , Síndrome del Colon Irritable/etiología , Óxido Nítrico Sintasa/metabolismo , Estrés Psicológico/complicaciones , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Diarrea/enzimología , Diarrea/etiología , Diarrea/patología , Modelos Animales de Enfermedad , Femenino , Motilidad Gastrointestinal , Síndrome del Colon Irritable/patología , Masculino , Privación Materna , Ratones , Ratones Endogámicos C57BL
7.
Molecules ; 23(4)2018 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-29570621

RESUMEN

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.


Asunto(s)
Melatonina/metabolismo , Memoria a Largo Plazo/fisiología , Transducción de Señal/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Calcio/metabolismo , Línea Celular Tumoral , Senescencia Celular/genética , Senescencia Celular/fisiología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Humanos , Fosforilación/genética , Fosforilación/fisiología , Receptor de Melatonina MT1/metabolismo , Transducción de Señal/genética
8.
Exp Dermatol ; 26(11): 1053-1059, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28423200

RESUMEN

Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86-/- ) mice. Incidence and severity of alopecia were analysed in 58 B6.CD80CD86-/- mice using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR and CD25 inhibition test. Both male and female B6.CD80CD86-/- mice showed almost 100% incidence of hair loss at 40 weeks of age. Moreover, CD4+FoxP3+Treg (Treg) cell population in B6.CD80CD86-/- mice was significantly lower than in B6 mice, which presumably underlined autoimmune reaction. Histologically, B6.CD80CD86-/- mice showed CD4+ and CD8+ T-cell infiltration around terminal follicle region and exhibited hair follicle destruction in the anagen or catagen stage. Negative correlation between the number of CD4+FoxP3+ Tregs and ALA was confirmed by the CD25 depletion test in B6 mice, as follicle destruction was similar to that observed in B6.CD80CD86-/- animals. CD80CD86 deficiency disrupted CD4+FoxP3+ Treg homoeostasis and prompted the development of ALA. We demonstrated that B6.CD80CD86-/- mice might have several advantages as an ALA model, because they exhibited high incidence of disease phenotype and epipathogenesis similar to that observed in human AA.


Asunto(s)
Alopecia/inmunología , Enfermedades Autoinmunes/inmunología , Antígeno B7-1/genética , Antígeno B7-2/genética , Linfocitos T Reguladores/inmunología , Factores de Edad , Alopecia/patología , Animales , Enfermedades Autoinmunes/patología , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Folículo Piloso/patología , Homeostasis , Interferón gamma/sangre , Interferón gamma/genética , Interleucina-10/sangre , Interleucina-12/sangre , Interleucina-12/genética , Subunidad alfa del Receptor de Interleucina-2/antagonistas & inhibidores , Interleucina-4/sangre , Masculino , Ratones , Ratones Noqueados , Índice de Severidad de la Enfermedad , Factores Sexuales , Linfocitos T Reguladores/patología , Células TH1/inmunología , Células TH1/metabolismo
9.
Biosci Biotechnol Biochem ; 80(12): 2318-2324, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27485250

RESUMEN

Recently, we found that maternal stress could induce premature mammary gland involution in interleukin 10 knock out (IL-10-/-) mice. To elucidate correlation between stress, IL-10, and mammary gland involution, corticosterone was injected into the lactating wild type and IL-10-deficient mice and assessed mammary gland phenotype. Repetitive corticosterone injection developed premature mammary gland involution only in B6.IL-10-/- mice; moreover, it induced alopecia in nursing pups. Corticosterone injection induced several typical changes such as mammary gland epithelial cell apoptosis, macrophage infiltration, fat deposition in adipocyte, STAT3 phosphorylation, and upregulation of tyrosine hydroxylase gene in adrenal gland. Overall incidence of pup alopecia and mammary gland involution was relatively high in corticosterone than control B6.IL-10-/- group (57% vs. 20%). Our finding demonstrates that IL-10 is important for stress modulation, and B6.Il-10-/- with corticosterone has several advantage such as simple to establish, well-defined onset of mammary gland involution, high incidence, and inducing pup alopecia.


Asunto(s)
Corticosterona/farmacología , Interleucina-10/deficiencia , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/fisiología , Adipocitos/citología , Adipocitos/efectos de los fármacos , Alopecia/etiología , Animales , Apoptosis/efectos de los fármacos , Femenino , Lactancia/efectos de los fármacos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL
10.
J Clin Periodontol ; 42(2): 131-41, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25483802

RESUMEN

AIM: The aim is to assess the effect of desensitizing toothpaste on dentin hypersensitivity. METHODS: We searched PubMed, CENTRAL, and Embase on December 20, 2013. RESULTS: Out of the 626 articles searched, a total of 31 randomized controlled clinical trials were included. The Standardized mean differences (SMD) for potassium-containing toothpaste (n = 8) was -1.28 (95% Confidence interval (CI) -2.05 to -0.51; I(2) = 93%); Stannous fluoride- (n = 6) was -1.37 (95% CI, -2.30 to -0.44; I(2) = 95%); Potassium and stannous fluoride- (n = 3) was -2.50 (95% CI, -4.10 to -0.91; I(2) = 95%); Calcium sodium phosphosilicate- (n = 4) was -2.36 (95% CI, -3.72 to -1.00; I(2) = 92%); Arginine- (n = 8) was -3.25 (95% CI, -3.87 to -2.63; I(2) = 86%). The desensitizing effect was favoured in the intervention group treated with potassium-, stannous fluoride-, potassium and stannous fluoride-, calcium sodium phosphosilicate-, and arginine-containing toothpaste compared to placebo. Whereas, strontium-containing toothpaste (SMD, 0.05; 95% CI, -0.34 to 0.44; I(2) = 64%) was found to have no statistically significant desensitizing effect in the meta-analysis of four studies. CONCLUSIONS: The study reports that there is sufficient evidence to support the use of potassium-, stannous fluoride-, potassium and stannous fluoride-, calcium sodium phosphosilicate-, and arginine-containing desensitizing toothpastes for dentin hypersensitivity, but not the use of strontium-containing desensitizing toothpaste.


Asunto(s)
Desensibilizantes Dentinarios/uso terapéutico , Sensibilidad de la Dentina/tratamiento farmacológico , Pastas de Dientes/uso terapéutico , Arginina/uso terapéutico , Carbonato de Calcio/uso terapéutico , Fluoruros/uso terapéutico , Humanos , Nitratos/uso terapéutico , Fosfatos/uso terapéutico , Placebos , Compuestos de Potasio/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Silicatos/uso terapéutico , Estroncio/uso terapéutico , Fluoruros de Estaño/uso terapéutico
11.
Sleep Breath ; 19(4): 1335-41, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26407962

RESUMEN

PURPOSE: Continuous positive airway pressure (CPAP) devices can estimate apnea-hypopnea index (AHI) using respiratory event detection algorithms. In 2012, rules for manually scoring respiratory events during sleep were updated to version 2.0. The purpose of the present study was to compare residual AHI determined using the Sleepstyle HC608 CPAP device (HC) with those determined by the new manual scoring (NM) rules during CPAP titration in patients with obstructive sleep apnea (OSA). METHODS: Fifty-seven patients underwent CPAP titration with HC. Correlations were assessed between AHI determined by NM and HC. The AHI, the apnea index (AI), and the hypopnea index (HI) were evaluated separately. RESULTS: The mean AHI as assessed using diagnostic polysomnography (PSG) was 53.9 ± 22.4. During CPAP titration, respiratory events were effectively suppressed (HC-AHI, 4.2 ± 6.0; NM-AHI, 6.0 ± 5.8). Lower HI and AHI were obtained using HC compared to NM (HC-HI, 2.9 ± 3.6 and NM-HI, 5.2 ± 4.2, p < 0.001; HC-AHI, 4.2 ± 6.0 and NM-AHI, 6.0 ± 5.8, p < 0.001). Additionally, HC reported higher AI compared to NM (HC-AI, 1.3 ± 2.8; NM-AI, 0.9 ± 2.2, p = 0.002). NM-AI (ß = 1.017, p < 0.001), NM-HI (ß = -0.599, p < 0.001), and NM-arousal index (ß = -0.058, p = 0.042) were associated with greater differences between HC-AHI and NM-AHI in multivariate regression analysis. CONCLUSIONS: Our findings indicate differences in scoring respiratory events between our CPAP device and new version 2.0 manual scoring and suggest that residual AHI values should be carefully interpreted.


Asunto(s)
Algoritmos , Presión de las Vías Aéreas Positiva Contínua/instrumentación , Polisomnografía/clasificación , Polisomnografía/instrumentación , Procesamiento de Señales Asistido por Computador/instrumentación , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/terapia , Adulto , Nivel de Alerta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Apnea Obstructiva del Sueño/clasificación , Fases del Sueño , Estadística como Asunto
12.
Cell Biochem Funct ; 32(3): 249-57, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24122936

RESUMEN

The enzyme 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) is known to catalyse inactive glucocorticoids into active forms, and its dysregulation in adipose and muscle tissues has been implicated in the development of metabolic syndrome. To delineate the molecular mechanism by which active cortisol has an antagonizing effect against insulin, we optimized the metabolic production of cortisol and its biological functions in myotubes (C2C12). Myotubes supplemented with cortisone actively catalysed its conversion into cortisol, which in turn abolished phosphorylation of Akt in response to insulin treatment. This led to diminished uptake of insulin-induced glucose. This was corroborated by the application of 11ß-HSD1 inhibitor glycyrrhetinic acid and a glucocorticoid receptor antagonist RU-486, which reversed completely the antagonizing effects of cortisol on insulin action. Therefore, development of specific inhibitors targeting 11ß-HSD1 might be a promising way to improve impaired insulin-stimulated glucose uptake.


Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Cortisona/metabolismo , Glucocorticoides/metabolismo , Resistencia a la Insulina/fisiología , Fibras Musculares Esqueléticas/metabolismo , Receptores de Glucocorticoides/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Comunicación Autocrina , Línea Celular , Cortisona/farmacología , Glucocorticoides/farmacología , Glucosa/metabolismo , Ácido Glicirretínico/farmacología , Humanos , Hidrocortisona/metabolismo , Insulina/farmacología , Insulina/fisiología , Mifepristona/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Receptores de Glucocorticoides/antagonistas & inhibidores
13.
Implant Dent ; 23(2): 138-43, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24637527

RESUMEN

Recently, techniques have been reported that involve the preparation of extracted teeth from patients used as particulated bone graft materials for bone graft purposes. For implant placement and bone graft, autogenous teeth bone graft materials were used in 15 patients, and clinically excellent results were obtained. In histological examination, favorable bony healing by osteoconduction was observed.


Asunto(s)
Regeneración Ósea , Trasplante Óseo/métodos , Implantación Dental/métodos , Diente/trasplante , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
14.
Diabetes Res Clin Pract ; 210: 111640, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38548110

RESUMEN

AIMS: We explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. METHODS: We retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). RESULTS: At baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (ß: 0.045, p < 0.001; ß: -0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9-2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. CONCLUSIONS: The TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Adulto , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Glucosa , Prueba de Tolerancia a la Glucosa , Glucemia , Estudios Retrospectivos , Triglicéridos
15.
BMC Complement Altern Med ; 12: 260, 2012 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-23259680

RESUMEN

BACKGROUND: Postmenopausal women experience estrogen deficiency-related menopausal symptoms (e.g., hot flashes and mood swings) and a dramatic increase in the incidence of chronic diseases. Although estrogen-replacement therapy (ERT) can reduce mortality from cardiovascular disease and improve osteoporosis and menopausal symptoms, its side effects have limited recent use. This study investigated the estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb. METHODS: The estrogenic activity of A. pilosa was investigated by using several in vitro assays. The binding activity of A. pilosa on estrogen receptors was examined using a fluorescence polarization-based competitive binding assay. The proliferative activity of A. pilosa was also examined using MCF-7 cells. Furthermore, the effect of A. pilosa on the expression of 3 estrogen-dependent genes was assessed. RESULTS: Using liquid chromatography-mass spectrometry, the 3 major peaks of A. pilosa aqueous extract were identified as apigenin-hexose, luteolin-glucuronide, and apigenin-glucuronide. The aqueous extract induced the proliferation of estrogen receptor-positive MCF-7 cells (p < 0.05). A. pilosa-stimulated proliferation was blocked on adding the estrogen antagonist ICI 182,780. Moreover, A. pilosa treatment increased the mRNA expression of the estrogen-responsive genes pS2 and PR (p < 0.05). CONCLUSIONS: These results suggest A. pilosa can be used to improve estrogen deficiency-related menopausal symptoms or to treat diseases in postmenopausal women.


Asunto(s)
Agrimonia/química , Proliferación Celular/efectos de los fármacos , Estrógenos/deficiencia , Flavonoides/farmacología , Fitoestrógenos/farmacología , Extractos Vegetales/farmacología , Receptores de Estrógenos/efectos de los fármacos , Antagonistas de Estrógenos/farmacología , Femenino , Flavonoides/análisis , Humanos , Células MCF-7 , Menopausia , Fitoestrógenos/análisis , Fitoterapia , Extractos Vegetales/química , ARN Mensajero/metabolismo , Receptores de Estrógenos/metabolismo , Factor Trefoil-1 , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
16.
Phytother Res ; 26(8): 1107-12, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22162275

RESUMEN

In this study we investigated the inhibitory effects and possible mechanisms of action of 8'-hydroxydaidzein and 3'-hydroxydaidzein, two ortho-dihydroxyisoflavone derivatives from Korean fermented soybean paste, on melanogenesis in B16 murine melanoma cells. The two hydroxydaidzeins reduced melanin synthesis comparably to treatment with kojic acid, a proven whitening agent, in B16 melanoma cells. Furthermore, when in vitro human skin equivalents were treated with the hydroxydaidzeins, the levels of melanogenesis were significantly reduced relative to a kojic acid control. The RT-PCR results demonstrated that depigmentation was due to transcriptional repression of several melanogenesis genes, including microphthalmia-associated transcription factor (MITF), by the hydroxydaidzeins. The immunoblotting results confirmed that diminution of MITF expression subsequently decreased expression of tyrosinase, and tyrosinase-related proteins 1 and 2. Cumulatively, these results suggest that hydroxydaidzeins would be potent attenuators of melanin synthesis as well as effective inhibitors of hyperpigmentation in human skin.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Glycine max/química , Isoflavonas/farmacología , Melaninas/biosíntesis , Melanoma Experimental/patología , Animales , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Activación Enzimática , Fermentación , Humanos , Hiperpigmentación/metabolismo , Hiperpigmentación/patología , Melaninas/metabolismo , Ratones , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Pironas/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Transcripción Genética
17.
Clin Nutr ; 41(3): 680-686, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35151124

RESUMEN

BACKGROUND & AIMS: Osteoporosis is the most common bone disease and is characterized by low bone mineral density (BMD) and a high risk of fracture. Despite advances in our understanding of the pathogenesis of osteoporosis, complex gene-environment interactions that influence osteoporosis development remain largely unexplored. In this study, we aimed to identify genetic loci associated with low BMD and to evaluate these genetic variants under individual and environmental factors. METHODS: A genome-wide association analysis was conducted using 500,568 single-nucleotide polymorphisms (SNPs) in 8842 individuals aged 40-69 years using clinical, demographic, and dietary data (>260 traits) established by the Korean Genome and Epidemiology Study. The gPLINK program was used to detect SNPs associated with osteoporosis at a genome-wide significance level (P < 1.0 × 10-05) and conduct a haplotype analysis. Statistical differences between the osteoporosis and control groups in categorical variables (sex and dietary profiles) were assessed based on frequency distributions using the chi-squared test. RESULTS: Of the seven SNPs that were associated with osteoporosis, both rs10977574 and rs4390000 lay in the PTPRD locus encoding a protein tyrosine phosphatase-receptor type D, which has been implicated in bone metabolism. Haplotype analysis identified two minor alleles, C and G, at the rs10977574 and rs4390000 loci, respectively, forming a linkage disequilibrium block. The subsequent gender-stratified analysis using dietary calcium intake revealed an increased correlation between the CG haplotype and osteoporosis (OR = 2.069) in the low-calcium-intake-female group but not in the high-calcium-intake-female or any male group. CONCLUSIONS: This study revealed novel evidence of the sex-specific association of the CG haplotype in the PTPRD locus with osteoporosis and indicated that the association can be influenced by dietary calcium intake.


Asunto(s)
Calcio de la Dieta , Osteoporosis , Adulto , Anciano , Densidad Ósea/genética , Calcio , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Osteoporosis/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética
18.
Cells ; 11(18)2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36139445

RESUMEN

The control of exosome release is associated with numerous physiological and pathological activities, and that release is often indicative of health, disease, and environmental nutrient stress. Tuberous sclerosis complex (TSC) regulates the cell viability via the negative regulation of the mammalian target of rapamycin complex (mTORC1) during glucose deprivation. However, the mechanism by which viability of TSC-null cells is regulated by mTORC1 inhibition under glucose deprivation remains unclear. Here, we demonstrated that exosome release regulates cell death induced by glucose deprivation in TSC-null cells. The mTORC1 inhibition by rapamycin significantly increased the exosome biogenesis, exosome secretion, and cell viability in TSC-null cells. In addition, the increase in cell viability by mTORC1 inhibition was attenuated by two different types of inhibitors of exosome release under glucose deprivation. Taken together, we suggest that exosome release inhibition might be a novel way for regression of cell growth in TSC-null cells showing lack of cell death by mTORC1 inhibition.


Asunto(s)
Exosomas , Fibroblastos , Animales , Supervivencia Celular , Exosomas/metabolismo , Fibroblastos/citología , Glucosa , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/metabolismo , Proteínas Supresoras de Tumor/metabolismo
19.
Psychiatry Investig ; 19(6): 435-442, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35753682

RESUMEN

OBJECTIVE: Facial affect recognition is associated with neuropsychological status and psychiatric diseases. We hypothesized that facial affect recognition is associated with psychological status and perception of other affects. METHODS: A total of 80 images depicting facial affect, including 20 Neutral, 20 Angry, 20 Fear, and 20 Sad, were screened for use in our research. A total of 100 healthy individuals were asked to rate these images using a 10-point Likert scale and complete psychological scales assessing the emotional statuses and cognitive functions. RESULTS: The participants' emotional state of aggression, attention, and impulsivity may have been associated with their interpretation of the Angry facial expressions. The participants often rated the Angry facial expressions as Fear. The participants rated Fear images as Angry or Sad. In response to a Sad facial expression, the participants reported psychological statuses of attention and impulsivity which were associated with the facial expression rating. The participants rated the Sad expression as Angry or Fear. CONCLUSION: The psychological statuses of the participants were significantly correlated with their interpretation of facial affects. In particular, a psychological state of attention was often correlated with incorrect affect ratings. Attention and impulsivity could affect the rating of the sad facial expressions.

20.
Bioorg Med Chem Lett ; 21(21): 6482-4, 2011 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-21917453

RESUMEN

Lamin A-dependent nuclear aberration and DNA damage was found in premature aging disease or normally old individuals. In this study, UVB irradiation was used as a cellular senescence inducer, and it was found that Lamin A and phospho-H2AX protein was increased by UVB treatment on normal human fibroblast. Lamin A-dependent morphological nuclear defect was observed in UVB treated fibroblast. Amentoflavone, a well known biflavonoid, inhibited the increase of Lamin A or phospho-H2AX protein in dose dependent manner which was induced by UVB irradiation, and also protected nuclear aberration dramatically. These results indicated that amentoflavone is an anti-aging candidate for UVB related skin aging process.


Asunto(s)
Biflavonoides/farmacología , Núcleo Celular/efectos de los fármacos , Lamina Tipo A/metabolismo , Rayos Ultravioleta , Núcleo Celular/metabolismo , Núcleo Celular/efectos de la radiación , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Humanos
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