RESUMO
Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 µM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor ß-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.
Assuntos
Ginsenosídeos , Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Ginsenosídeos/metabolismo , Miocárdio , Miócitos Cardíacos , ApoptoseRESUMO
BACKGROUND: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. CASE PRESENTATION: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA). CONCLUSION: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.
Assuntos
Acidose/genética , Acil Coenzima A/deficiência , Hidroximetilglutaril-CoA Sintase/genética , Mitocôndrias/enzimologia , Mutação/genética , Acidose/terapia , Acidose/urina , Adipatos/urina , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/urina , Diarreia/complicações , Ácidos Dicarboxílicos/urina , Evolução Fatal , Mutação da Fase de Leitura/genética , Glutaratos/urina , Humanos , Lactente , Masculino , Insuficiência de Múltiplos Órgãos/complicações , Infecções Respiratórias/complicações , Sequenciamento do ExomaRESUMO
The combination of multi-scale transform and the rules which are "high-frequency coefficients combined by selecting the maximum gray value or energy" and "low-pass ones combined by weighting average" is an effective method in dual-band image fusion. However, when these methods are used to fuse multi-band images, sequential weighted average often leads the weakening of the inherent different information of original images, which affects the subsequent target recognition and scene understanding. The problem is more obvious when fusing multi-band images with texture features. In order to describe the scene in a more comprehensive and precise way, a new multi-band texture image fusion method based on embedded multi-scale decomposition and possibility theory is proposed. The method consists of three parts. The original multi-band images are decomposed into their high- and low-frequency components through a multi-scale transform. The high-frequency components are fused per-pixel by extracting the maximum gray value, whereas the last layer of low-frequency components of original multi-band images with the largest standard deviation is blocked through the another multi-scale transform. Based on the specific sizes and positions of these blocks, the remaining two original images are divided. All the blocks from three bands are traversely fused according to the possibility theory, and the low-frequency image is formed by mosaicing these fused blocks. Then, this image is inversely transformed with its high-frequency counterparts to get the final fusion image. This method not only integrates the pixel-level with feature-level fusion methods, but also integrates the space domain with transform domain technologies together, and solves the problem of sawtooth effect on the edge of the target through the different fusion rules with the different sizes of blocks. The validity of the method proposed is proved.
RESUMO
OBJECTIVE: To study the association between body mass index (BMI) and lung function of asthmatic children after inhaling corticosteroids (ICS). METHODS: One hundred and fifty-seven children with asthma were classified into obese (46 cases), over-weight (50 cases) and normal-weight groups (61 cases) based on BMI. All of the children received ICS for one year. Pulmonary functions were evaluated before and after treatment. Large airway function includes forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%). Small airway function includes maximal expiratory flow 25 (MEF25%) and maximal expiratory flow 50 (MEF50%). RESULTS: The bronchial provocation test before treatment showed that the decline rate of pulmonary function (FVC%, FEV1%, MEF25% and MEF50%) in the obese group was higher than the normal-weight group after methacholine inhalation. After salbutamol inhalation, the improvement rate of the large airway (FVC%) and small airway (MEF25% and MEF50%) functions in the obese group was lower than the normal-weight group, and the improvement rate of small airway (MEF25% and MEF50%) function in the over-weight group was lower than in the normal-weight group. After treatment with ICS for one year, large airway function (FVC% and FEV1%) in the normal-weight group was higher than pre-treatment, however only FVC% in the normal-weight and obese groups was higher than pre-treatment. There was no significant difference in small airway function before and after treatment in all three groups. CONCLUSIONS: Obesity can increase the sensitivity to methacholine and restrain the sensitivity to tosalbutamol in children with asthma. ICS can improve the large airway function in asthmatic children with normal body weight, but has no effect on small airway function. Obesity can restrain the effect of ICS on asthmatic children.
Assuntos
Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Índice de Massa Corporal , Administração por Inalação , Asma/fisiopatologia , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Capacidade VitalRESUMO
The fat-soluble vitamins A, D, E and K are micronutrients essential for physiological activity, metabolism and growth. Accurate and sensitive analytical methods are needed to support growing research into fat-soluble vitamins and their impact on children's growth and health. Here we report the first method for simultaneous quantification of fat-soluble vitamins A (retinol), 25-hydroxylvitamin D2, 25-hydroxylvitamin D3, and vitamin E (α-tocopherol) using a Q-Exactive Orbitrap mass spectrometer in high-resolution, parallel reaction monitoring mode. This method can select desired ions with high efficiency, potentially making it superior to triple-quadrupole mass spectrometers that employ multiple reaction monitoring. The proposed method offers excellent accuracy, specificity, and sensitivity, as demonstrated with plasma samples from healthy children.