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1.
Horm Behav ; 127: 104871, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33058835

RESUMEN

Assessing dominance is important for effective social interactions, and prior research suggests that testosterone is associated with men's dominance perceptions. The present study tested for a causal effect of exogenous testosterone on men's sensitivity to vocal cues of other men's dominance, an important parameter in male-male competition across species. One hundred and thirty-nine Chinese men received a single dose (150 mg) of testosterone or placebo gel in a double-blind, placebo-controlled, between-participant design. Participants reported their own dominance and judged other men's dominance from voices. Men's dominance sensitivity was significantly weaker in the testosterone group compared to those in the placebo group. Moreover, men's dominance sensitivity was negatively associated with their self-reported dominance in our Chinese sample, consistent with findings from Western populations. These results indicate that exogenous testosterone has a causal effect in decreasing men's dominance sensitivity, consistent with the Challenge Hypothesis, suggesting that the fluctuation of testosterone concentration mediates individuals' behaviors. Additionally, the present study could motivate further work on vocal assessment in the context of competition in humans and other species.


Asunto(s)
Percepción Auditiva/efectos de los fármacos , Señales (Psicología) , Predominio Social , Testosterona/farmacología , Estimulación Acústica , Adolescente , Adulto , China , Método Doble Ciego , Humanos , Masculino , Motivación/efectos de los fármacos , Placebos , Autoimagen , Conducta Social , Testosterona/administración & dosificación , Voz , Adulto Joven
2.
Mol Pharm ; 16(5): 1839-1850, 2019 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-30974944

RESUMEN

Protein tyrosine phosphatase 1B (PTP1B) is a widely confirmed target of the type 2 diabetes mellitus (T2DM) treatment. Herein, we reported a highly specific PTP1B inhibitor 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (compound 1), which showed promising hypoglycemic activity in diabetic BKS db mice. With the IC50 value of 2.4 µM, compound 1 could directly bind to the catalytic pocket of PTP1B through a series of hydrogen bonds. Surface plasmon resonance analysis revealed that the target affinity [KD (equilibrium dissociation constant) value] of compound 1 binding to PTP1B was 2.90 µM. Moreover, compound 1 could activate the insulin signaling pathway in C2C12 skeletal muscle cells. We further evaluated the long-term effects of compound 1 in diabetic BKS db mice. Notably, oral administration of compound 1 significantly reduced the blood glucose levels of diabetic mice with increasing insulin sensitivity. In addition, the dyslipidemia of diabetic mice was also significantly improved by compound 1 gavage. The histological experiments showed that compound 1 treatment significantly ameliorated the disordered hepatic and pancreatic architecture and increased the glycogen content in the liver tissues as well as improved the insulin secretion function of pancreas. Taken together, our results manifested that the natural product compound 1 was a highly specific PTP1B inhibitor, which could activate insulin signaling pathway and ameliorate hyperglycemia and dyslipidemia in diabetic BKS db mice.


Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Extractos Vegetales , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Animales , Masculino , Ratones , Administración Oral , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Dominio Catalítico , Línea Celular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucógeno/metabolismo , Enlace de Hidrógeno , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Concentración 50 Inhibidora , Insulina/metabolismo , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Simulación del Acoplamiento Molecular , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/aislamiento & purificación , Rhodophyta/química , Transducción de Señal/efectos de los fármacos
3.
Eur J Med Chem ; 166: 178-185, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30711829

RESUMEN

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 µM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20-200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/complicaciones , Fenoles/química , Fenoles/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Animales , Peso Corporal/efectos de los fármacos , Línea Celular , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Insulina/metabolismo , Resistencia a la Insulina , Leptina/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Fenoles/farmacocinética , Fenoles/uso terapéutico , Fosforilación/efectos de los fármacos , Conformación Proteica , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Seguridad , Transducción de Señal/efectos de los fármacos
4.
Bioresour Technol ; 266: 284-290, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29982049

RESUMEN

Microwave pyrolysis of moso bamboo over bamboo-based biochar catalyst was conducted to achieve the bio-oil upgrading and high quality syngas production. The influence of the biochar on bamboo pyrolysis involving the temperature rise, product yield, and bio-oil and gas compositions was studied. The gas production was facilitated by the biochar mainly at the cost of the bio-oil, indicating the biochar had an excellent activity for the bio-oil cracking. The main compositions in bio-oil were acetic acid and phenol with the total contents ranging from 73.145% to 82.84% over the biochar catalysts, suggesting the upgrading of the bio-oil were achieved. The biochar exerted a positive effect on the syngas (CO + H2) production with the maximum content reaching up to 65.13 vol% at the 20 wt% addition amount of biochar under microwave condition. The biochar became more effective on the bio-oil upgrading and syngas production under microwave heating than conventional heating.


Asunto(s)
Biocombustibles , Carbón Orgánico , Microondas , Calor , Aceites de Plantas , Polifenoles
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