RESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Peçonhas/farmacologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Cromonas/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Exenatida , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Insulina/sangue , Masculino , Malondialdeído/análise , Morfolinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Coelhos , Superóxido Dismutase/análiseRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.
Assuntos
Animais , Masculino , Coelhos , Peptídeos/farmacologia , Peçonhas/farmacologia , Substâncias Protetoras/farmacologia , Fígado Gorduroso/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Dioxigenase FTO Dependente de alfa-Cetoglutarato/efeitos dos fármacos , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Técnicas In Vitro , Regulação da Expressão Gênica/efeitos dos fármacos , Morfolinas/metabolismo , Cromonas/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Fígado Gorduroso/patologia , Dieta Hiperlipídica , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Exenatida , Insulina/sangue , Malondialdeído/análise , Obesidade/metabolismoRESUMO
BACKGROUND: Von Zumbusch type of generalized pustular psoriasis is a rare variant of psoriasis in children. It can occur in patients with or without psoriasis vulgaris. OBJECTIVE: The aim of the study was to discuss the precipitating factors, clinical manifestations, laboratory data and therapy of von Zumbusch type of generalized pustular psoriasis in children from southwestern China and to improve the diagnosis and treatment level. METHODS: A retrospective analysis was conducted for inpatients aged 14 years old or less with von Zumbusch type of generalized pustular psoriasis in our department from 2005 to 2014. RESULTS: A total of 26 patients were included, of whom four (15.38%) had previous history of psoriasis vulgaris and one (3.85%) had previous history of psoriasis arthropathica. Mean onset age was 6.90 years. Gender distribution was equivalent. Incidence of the disease in summer and autumn was higher than that in winter and spring. Nineteen (73.08%) cases were triggered by infection, two (7.69%) cases were caused by sudden discontinuation of systemic use of corticosteroid. Twenty-four (92.31%) cases had concomitant fever. The initial lesion manifested as non-follicular sterile pustules on erythema. Sixteen patients responded well to acitretin, 11 to Tripterygium wilfordii Hook F (TwHF), two to cyclosporine, and one to methotrexate. STUDY LIMITATIONS: This study is a retrospective one and the number of cases is small. CONCLUSION: Von Zumbusch type of generalized pustular psoriasis is a rare disease in children, infection is the most common precipitating factor, acitretin is the first-line therapy, traditional Chinese medicine TwHF also can be used.
Assuntos
Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Acitretina/uso terapêutico , Adolescente , Criança , Pré-Escolar , China , Ciclosporina/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Metotrexato/uso terapêutico , Psoríase/classificação , Psoríase/etiologia , Estudos RetrospectivosRESUMO
Abstract Background: Von Zumbusch type of generalized pustular psoriasis is a rare variant of psoriasis in children. It can occur in patients with or without psoriasis vulgaris. Objective: The aim of the study was to discuss the precipitating factors, clinical manifestations, laboratory data and therapy of von Zumbusch type of generalized pustular psoriasis in children from southwestern China and to improve the diagnosis and treatment level. Methods: A retrospective analysis was conducted for inpatients aged 14 years old or less with von Zumbusch type of generalized pustular psoriasis in our department from 2005 to 2014. Results: A total of 26 patients were included, of whom four (15.38%) had previous history of psoriasis vulgaris and one (3.85%) had previous history of psoriasis arthropathica. Mean onset age was 6.90 years. Gender distribution was equivalent. Incidence of the disease in summer and autumn was higher than that in winter and spring. Nineteen (73.08%) cases were triggered by infection, two (7.69%) cases were caused by sudden discontinuation of systemic use of corticosteroid. Twenty-four (92.31%) cases had concomitant fever. The initial lesion manifested as non-follicular sterile pustules on erythema. Sixteen patients responded well to acitretin, 11 to Tripterygium wilfordii Hook F (TwHF), two to cyclosporine, and one to methotrexate. Study limitations: This study is a retrospective one and the number of cases is small. CONCLUSION: Von Zumbusch type of generalized pustular psoriasis is a rare disease in children, infection is the most common precipitating factor, acitretin is the first-line therapy, traditional Chinese medicine TwHF also can be used.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/classificação , Psoríase/etiologia , China , Metotrexato/uso terapêutico , Estudos Retrospectivos , Ciclosporina/uso terapêutico , Acitretina/uso terapêuticoRESUMO
ABSTRACT This study highlights the prevalence of aminoglycoside-modifying enzyme genes and virulence determinants among clinical enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. Screening for high-level aminoglycoside resistance against 117 enterococcal clinical isolates was performed using the agar-screening method. Out of the 117 enterococcal isolates, 46 were selected for further detection and determination of the distribution of aminoglycoside-modifying enzyme-encoding genes and virulence determinants using polymerase chain reaction -based methods. Enterococcus faecium and Enterococcus faecalis were identified as the species of greatest clinical importance. The aac(6')-Ie-aph(2")-Ia and ant(6')-Ia genes were found to be the most common aminoglycoside-modifying enzyme genes among high-level gentamicin resistance and high-level streptomycin resistance isolates, respectively. Moreover, gelE was the most common virulence gene among high-level aminoglycoside resistance isolates. Compared to Enterococcus faecium, Enterococcus faecalis harbored multiple virulence determinants. The results further indicated no correlation between aminoglycoside-modifying enzyme gene profiles and the distribution of virulence genes among the enterococcal isolates with high-level gentamicin resistance or high-level streptomycin resistance evaluated in our study.
Assuntos
Masculino , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Enterococcus/fisiologia , Farmacorresistência Bacteriana , Aminoglicosídeos/metabolismo , Aminoglicosídeos/farmacologia , Virulência/genética , Testes de Sensibilidade Microbiana , China/epidemiologia , Prevalência , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Enterococcus/metabolismo , Genes Bacterianos , Antibacterianos/metabolismoRESUMO
This study highlights the prevalence of aminoglycoside-modifying enzyme genes and virulence determinants among clinical enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. Screening for high-level aminoglycoside resistance against 117 enterococcal clinical isolates was performed using the agar-screening method. Out of the 117 enterococcal isolates, 46 were selected for further detection and determination of the distribution of aminoglycoside-modifying enzyme-encoding genes and virulence determinants using polymerase chain reaction -based methods. Enterococcus faecium and Enterococcus faecalis were identified as the species of greatest clinical importance. The aac(6')-Ie-aph(2")-Ia and ant(6')-Ia genes were found to be the most common aminoglycoside-modifying enzyme genes among high-level gentamicin resistance and high-level streptomycin resistance isolates, respectively. Moreover, gelE was the most common virulence gene among high-level aminoglycoside resistance isolates. Compared to Enterococcus faecium, Enterococcus faecalis harbored multiple virulence determinants. The results further indicated no correlation between aminoglycoside-modifying enzyme gene profiles and the distribution of virulence genes among the enterococcal isolates with high-level gentamicin resistance or high-level streptomycin resistance evaluated in our study.(AU)
Assuntos
Aminoglicosídeos/análise , Aminoglicosídeos/síntese química , Aminoglicosídeos/genética , Enterococcus/imunologiaRESUMO
This study highlights the prevalence of aminoglycoside-modifying enzyme genes and virulence determinants among clinical enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. Screening for high-level aminoglycoside resistance against 117 enterococcal clinical isolates was performed using the agar-screening method. Out of the 117 enterococcal isolates, 46 were selected for further detection and determination of the distribution of aminoglycoside-modifying enzyme-encoding genes and virulence determinants using polymerase chain reaction -based methods. Enterococcus faecium and Enterococcus faecalis were identified as the species of greatest clinical importance. The aac(6')-Ie-aph(2â³)-Ia and ant(6')-Ia genes were found to be the most common aminoglycoside-modifying enzyme genes among high-level gentamicin resistance and high-level streptomycin resistance isolates, respectively. Moreover, gelE was the most common virulence gene among high-level aminoglycoside resistance isolates. Compared to Enterococcus faecium, Enterococcus faecalis harbored multiple virulence determinants. The results further indicated no correlation between aminoglycoside-modifying enzyme gene profiles and the distribution of virulence genes among the enterococcal isolates with high-level gentamicin resistance or high-level streptomycin resistance evaluated in our study.
Assuntos
Aminoglicosídeos/metabolismo , Aminoglicosídeos/farmacologia , Farmacorresistência Bacteriana , Enterococcus/efeitos dos fármacos , Enterococcus/fisiologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Antibacterianos/farmacologia , China/epidemiologia , Enterococcus/isolamento & purificação , Feminino , Genes Bacterianos , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Virulência/genéticaRESUMO
BACKGROUND: Prunella vulgaris L. is a medical plant cultivated in sloping, sun-shaded areas in China. Recently, owing to air-environmental stress, especially drought stress strongly inhibits plant growth and development, the appropriate fertilizer supply can alleviate these effects. However, these is little information about their effects on P. vulgaris growing in arid and semi-arid areas with limited water and fertilizer supply. RESULTS: In this study, water stress decreased the photosynthetic pigment contents, inhibited photosynthetic efficiency, induced photodamage in photosystem 2 (PS2), and decreased leaf instantaneous WUE (WUEi). The decreased net photosynthetic rate (Pn) under medium drought stress compared with the control might result from stomatal limitations. However, fertilizer supply improved photosynthetic capacity by increasing the photosynthetic pigment contents and enhancing photosynthetic efficiency under water deficit. Moreover, medium fertilization also increased WUEi under the two water conditions, but fertilizer supply did little to alleviate the PS2 photodamage caused by drought stress. Hence, drought stress was the primary limitation in the photosynthetic process of P. vulgaris seedlings, while the photosynthetic characteristics of the seedlings exhibited positive responses to fertilizer supply. CONCLUSIONS: Appropriate fertilizer supply is recommended to improve photosynthetic efficiency, enhance WUEi and alleviate photodamage under drought stress.
Assuntos
Fertilizantes , Fotossíntese/fisiologia , Prunella/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Água/fisiologia , Análise de Variância , Clorofila/fisiologia , Ritmo Circadiano , Secas , Fluorescência , Folhas de Planta , Estresse Fisiológico , Fatores de TempoRESUMO
BACKGROUND: Prunella vulgaris L. is a medical plant cultivated in sloping, sun-shaded areas in China. Recently, owing to air-environmental stress, especially drought stress strongly inhibits plant growth and development, the appropriate fertilizer supply can alleviate these effects. However, these is little information about their effects on P. vulgaris growing in arid and semi-arid areas with limited water and fertilizer supply. RESULTS: In this study, water stress decreased the photosynthetic pigment contents, inhibited photosynthetic efficiency, induced photodamage in photosystem 2 (PS2), and decreased leaf instantaneous WUE (WUEi). The decreased net photosynthetic rate (Pn) under medium drought stress compared with the control might result from stomatal limitations. However, fertilizer supply improved photosynthetic capacity by increasing the photosynthetic pigment contents and enhancing photosynthetic efficiency under water deficit. Moreover, medium fertilization also increased WUEi under the two water conditions, but fertilizer supply did little to alleviate the PS2 photodamage caused by drought stress. Hence, drought stress was the primary limitation in the photosynthetic process of P. vulgaris seedlings, while the photosynthetic characteristics of the seedlings exhibited positive responses to fertilizer supply. CONCLUSIONS: Appropriate fertilizer supply is recommended to improve photosynthetic efficiency, enhance WUEi and alleviate photodamage under drought stress.
Assuntos
Fotossíntese/fisiologia , Água/fisiologia , Prunella/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Fertilizantes , Estresse Fisiológico , Fatores de Tempo , Clorofila/fisiologia , Análise de Variância , Ritmo Circadiano , Folhas de Planta , Secas , FluorescênciaRESUMO
Prunella vulgaris L. (Labiatae) contains a variety of structurally diverse natural products, primarily rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA), which possess a wide array of biological properties. In the present study, P. vulgaris was harvested at three developmental stages (vegetative, full-flowering and mature-fruiting stages), dissected into stem and leaf tissues and assayed for chemical contents using high performance liquid chromatography. Significant changes in the concentrations of the major secondary metabolites (RA, UA and OA) were observed at the different development stages. The highest concentrations of RA, UA and OA were found at the full-flowering stage (15.83 mg/g dry weight (DW) RA, 1.77 mg/g DW UA and 0.65 mg/g DW OA). Among the different aerial parts of the plant, the concentrations of RA, UA and OA were higher in the leaves than in the stems at the different developmental stages. These results suggest that the full-flowering stage is characterized by the highest concentrations of bioactive compounds. Therefore, this stage may be the optimum point for harvesting P. vulgaris plants. In additional, the leaves of P. vulgaris demonstrated higher RA, UA and OA concentrations than the stems, suggesting higher utilization potential.