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1.
Nature ; 600(7890): 621-624, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34937892

RESUMO

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.


Assuntos
Astros Celestes , Atmosfera
2.
Nature ; 587(7832): 63-65, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33149293

RESUMO

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

3.
Nature ; 568(7751): 198-201, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30971846

RESUMO

Mergers of neutron stars are known to be associated with short γ-ray bursts1-4. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field5-8 (that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts9,10. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst11,12. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown13. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf13. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref. 14). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do15,16. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.

4.
Zhonghua Bing Li Xue Za Zhi ; 50(10): 1116-1121, 2021 Oct 08.
Artigo em Zh | MEDLINE | ID: mdl-34619863

RESUMO

Objective: To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators. Methods: A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets. Results: The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%. Conclusions: To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.


Assuntos
Inteligência Artificial , Gastrite , Atenção , China , Gastrite/diagnóstico , Humanos , Metaplasia
5.
Fa Yi Xue Za Zhi ; 36(5): 691-698, 2020 Oct.
Artigo em Zh | MEDLINE | ID: mdl-33295173

RESUMO

ABSTRACT: Complex kinship analysis refers to a kind of special kinship analysis taken for the purpose of personal identification or other issues in civil or criminal cases because the father or (and) mother is dead, or cannot participate in the analysis for other reasons. Due to the absence of significant appraised persons in this kind of kinship analysis, grandparents, siblings or collateral relatives are required to participate in the analysis. Complex kinship analysis is widely used and the demand is increasing year by year. This paper analyzes the main types of complex kinships, the genetic markers of complex kinship analysis and their advantages and disadvantages and the calculation methods for complex kinship analysis by referring to the relevant literatures at home and abroad in recent years. At the same time, the shortcomings of the present research on complex kinship and its future development are prospected.


Assuntos
Pesquisa , Irmãos , Marcadores Genéticos , Humanos , Linhagem
6.
J Anim Physiol Anim Nutr (Berl) ; 102(2): e706-e717, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29098735

RESUMO

The purpose of this study was to investigate the effects of long-term treatment with dexamethasone (DEX) on the antioxidation and nutrition metabolism in broiler chickens. Broilers were placed on a high-nutrient diet for 41 days, and half were given orally DEX-supplemented water at 20 mg/L every other day from 19 to 41 days of age. DEX treatment downregulated superoxide dismutase activity as well as the mRNA expression of CuZn-superoxide dismutase and glutathione peroxidase with a decrease in GSH/GSSG ratio and an increase in malondialdehyde level in the liver of broilers. DEX treatment aggravated oxidative damage in the liver and, therefore, increased the sensitivity of broilers to ascites syndrome with higher mortality and reduced growth performance. Serum metabolomics analysis showed that DEX treatment significantly increased the levels of glucose, intermediates in protein metabolism (valine, proline, serine, threonine and urea) and lipid metabolism-related products (palmitic acid, stearic acid and cholesterol) while decreasing the levels of ß-hydroxy butyric acid, succinic acid and malic acid, demonstrating that DEX treatment inhibited the Krebs cycle and the oxidation of fatty acids, and promoted the de novo synthesis of fatty acids as well as protein decomposition in the liver of broilers. Additionally, detection of metabolism-related enzymes revealed that DEX treatment inhibited glycolysis and promoted glycogen decomposition. In summary, DEX treatment resulted in oxidative stress and glucose and lipid metabolism disorders in the broilers.


Assuntos
Dexametasona/toxicidade , Glucose/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doenças das Aves Domésticas/induzido quimicamente , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Galinhas , Dieta/veterinária , Ácidos Graxos/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Doenças das Aves Domésticas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
7.
Genet Mol Res ; 15(4)2016 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-27813555

RESUMO

In higher plants, the transcription factor MYB10 is an important regulator of anthocyanin biosynthesis. In order to study its role in the development of red coloration in peach leaves, the full-length MYB10 complementary DNA sequence of the red-leaf peach cultivar 'Tsukuba No. 5' (Prunus persica f. atropurpurea) was successfully cloned using reverse transcription-polymerase chain reaction. The sequence was assigned the GenBank accession No. KP315904. Bioinformatic analysis identified the complete MYB10 open reading frame, consisting of 678 bp encoding 225 amino acids. The predicted protein has a molecular weight of 26.56 kDa and a theoretical isoelectric point of 8.97. The secondary structure was found to comprise approximately 34.22% alpha helix, 15.11% extended strand, 10.67% beta turn, and 40% random coil. Subcellular analysis indicated that MYB10 may function in the cytoplasm. Assessment of the amino acid sequence suggested the presence of one serine and two threonine phosphorylation sites. Quantitative real-time polymerase chain reaction revealed that MYB10 expression positively correlated with anthocyanin content in red-leaf peach, indicating that this transcription factor plays a role in the biosynthesis of this pigment in peach trees.


Assuntos
Antocianinas/genética , Folhas de Planta/genética , Proteínas de Plantas/genética , Prunus persica/genética , Sequência de Aminoácidos , Antocianinas/metabolismo , Clonagem Molecular , Biologia Computacional , Regulação da Expressão Gênica de Plantas , Pigmentação , Folhas de Planta/metabolismo , Proteínas de Plantas/biossíntese
8.
Ann Oncol ; 26(3): 504-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25515658

RESUMO

BACKGROUND: This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy. PATIENTS AND METHODS: In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life. RESULTS: This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46-0.98; P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14-0.57; P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56-1.16; P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild. CONCLUSION: In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/terapia , Irradiação Craniana/tendências , Neoplasias Pulmonares/terapia , Profilaxia Pós-Exposição/tendências , Procedimentos Cirúrgicos Pulmonares/tendências , Conduta Expectante/tendências , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/tendências , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/tendências , Estudos Prospectivos , Fatores de Risco
9.
Genet Mol Res ; 14(4): 14151-61, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26535732

RESUMO

MicroRNA166 (miR166) is known to have highly conserved targets that encode proteins of the class III homeodomain-leucine zipper (HD-ZIP III) family, in a broad range of plant species. To further understand the relationship between HD-ZIP III genes and miR166, four HD-ZIP III family genes (PpHB14, PpHB15, PpHB8, and PpREV) were isolated from peach (Prunus persica) tissue and characterized. Spatio-temporal expression profiles of the genes were analyzed. Genes of the peach HD-ZIP III family were predicted to encode five conserved domains. Deduced amino acid sequences and tertiary structures of the four peach HD-ZIP III genes were highly conserved, with corresponding genes in Arabidopsis thaliana. The expression level of four targets displayed the opposite trend to that of miR166 throughout fruit development, with the exception of PpHB14 from 35 to 55 days after full bloom (DAFB). This finding indicates that miR166 may negatively regulate its four targets throughout fruit development. As for leaf and phloem, the same trend in expression level was observed between four targets and miR166 from 75 to 105 DAFB. However, the opposite trend was observed for the transcript level between four targets and miR166 from 35 to 55 DAFB. miRNA166 may negatively regulate four targets in some but not all developmental stages for a given tissue. The four genes studied were observed to have, exactly or generally, the same change tendency as individual tissue development, a finding that suggests genes of the HD-ZIP III family in peach may have complementary or cooperative functions in various tissues.


Assuntos
Genes de Plantas , Proteínas de Homeodomínio/genética , Zíper de Leucina , MicroRNAs/genética , Prunus persica/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/biossíntese , MicroRNAs/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Análise de Sequência de Proteína
10.
Genet Mol Res ; 14(1): 763-73, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25730014

RESUMO

The development of a genetic transformation system is needed to address the problem of the low efficiency associated with soybean regeneration. To contribute to the enhancement of the soybean regenerative capacity, we explored the developmental mechanisms of soybean regeneration at the molecular level using a suppression subtractive hybridization cDNA library constructed from cotyledonary nodes of soybean cultivar DN50. A total of 918 positive clones were identified and screened, with most inserted fragments ranging from 100 to 750 bp. Of these, 411 differentially expressed functional expressed sequence tags were identified and annotated based on their similarity to orthologs and paralogs detected in GenBank using the nucleotide and translated nucleotide Basic Local Alignment Search Tools. Functional analysis revealed that the associated genes were involved in signal transduction, synthesis, and metabolism of macromolecules, glucose and protein synthesis and metabolism, light and leaf morphogenesis, regulation of apoptosis, cell defense, cell wall differentiation, and a variety of hormone and cytokinin-mediated signaling pathways. The information uncovered in our study should serve as a foundation for the establishment of an efficient and stable genetic transformation system for soybean regeneration.


Assuntos
Glycine max/genética , Regeneração/genética , Técnicas de Hibridização Subtrativa/métodos , Diferenciação Celular/genética , Etiquetas de Sequências Expressas , Regulação da Expressão Gênica de Plantas , Biblioteca Gênica , Glycine max/crescimento & desenvolvimento
11.
Diabetes Obes Metab ; 15(10): 954-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23551951

RESUMO

Antihyperglycaemic therapy on bone was evaluated in the ovariectomized (OVX), non-diabetic adult rat. Animals were treated daily for 12 weeks with various doses of sitagliptin, pioglitazone, rosiglitazone, combinations of sitagliptin with pioglitazone or vehicle alone. Sitagliptin target engagement was confirmed by assessing inhibition of plasma dipeptidyl peptidase-4 (DPP-4) and oral glucose tolerance. Parameters related to bone health were evaluated in femur and vertebrae by dual-energy X-ray absorptiometry and histomorphometry. Bone mineral density (BMD) generally did not differ significantly between OVX-sitagliptin-treated animals and OVX-vehicle controls. In lumbar vertebrae, however, there was significantly less BMD loss with increasing sitagliptin dose. Thiazolidinedione (TZD) treatment generally resulted in lower BMD; OVX-TZD-treated (but not OVX-sitagliptin-treated) animals also had lessened cortical thickness in central femur and profoundly greater bone marrow adiposity in lumbar vertebrae. These findings support prior findings with TZDs and suggest a neutral or beneficial impact of DPP-4 inhibition on bone health.


Assuntos
Densidade Óssea/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Pirazinas/farmacologia , Tiazolidinedionas/farmacologia , Triazóis/farmacologia , Absorciometria de Fóton , Animais , Progressão da Doença , Estrogênios/deficiência , Feminino , Fêmur/efeitos dos fármacos , Fêmur/patologia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Ovariectomia , Ratos , Fosfato de Sitagliptina
12.
Eur J Cancer Care (Engl) ; 22(5): 617-25, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23731124

RESUMO

Although a number of genetic studies have attempted to link the multidrug resistance (MDR1) C3435T polymorphism to risk of leukaemia, the results were often inconsistent. The present study aimed at investigating the pooled association using a meta-analysis on the published studies. 1933 cases and 2215 controls of 11 published studies in English before June 2012 were involved in the updated meta-analysis. Furthermore, subgroup analysis was performed in different ethnic and leukaemia subtype groups. This meta-analysis suggests that the MDR1 C3435T polymorphism associate with risk of leukaemia. The effect of the variant on the expression levels and the possible functional role of the variant in leukaemia should be addressed in further studies.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Leucemia/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Humanos , Fatores de Risco
13.
Clin Exp Immunol ; 170(1): 1-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22943195

RESUMO

Allergic asthma is associated with excessive T helper type 2 (Th2) cells activation and airway hyperreactivity (AHR), implicated in the context of significant morbidity and mortality. Soluble ST2, a member of the interleukin (IL)-1 receptor family, has been shown to play a critical role in modulation of inflammatory disorders, yet the function of soluble ST2 in allergic inflammation remains unclear. In this study, we examined the possibility of regulating ovalbumin (OVA)-challenged airway inflammation by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc before allergen challenge in OVA-immunized mice profoundly reduced serum immunoglobulin (Ig)E secretion, eosinophil infiltration and concentrations of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared with administration of a control Ad vector. Histopathological examination of the lungs revealed that sST2-Fc over-expression markedly suppressed allergen-induced peribronchial inflammation and disruption of the alveolar architecture. Moreover, the beneficial effect of sST2-Fc in allergic lung inflammation is related to blocking the IL-33/ST2L signalling. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of OVA-mediated allergic pulmonary diseases.


Assuntos
Asma/terapia , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Receptores de Interleucina/genética , Adenoviridae , Administração Intranasal , Alérgenos/imunologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoglobulina E/sangue , Imunoglobulina E/efeitos dos fármacos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-13/análise , Interleucina-13/metabolismo , Interleucina-33 , Interleucina-4/análise , Interleucina-4/metabolismo , Interleucina-5/análise , Interleucina-5/metabolismo , Interleucinas/antagonistas & inibidores , Interleucinas/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Receptores de Interleucina-1/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Células Th2/imunologia
14.
Science ; 378(6620): 659-663, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36356141

RESUMO

Creep, the time-dependent deformation of materials stressed below the yield strength, is responsible for a great number of component failures at high temperatures. Because grain boundaries (GBs) in materials usually facilitate diffusional processes in creep, eliminating GBs is a primary approach to resisting high-temperature creep in metals, such as in single-crystal superalloy turbo blades. We report a different strategy to inhibiting creep by use of stable GB networks. Plastic deformation triggered structural relaxation of high-density GBs in nanograined single-phased nickel-cobalt-chromium alloys, forming networks of stable GBs interlocked with abundant twin boundaries. The stable GB networks effectively inhibit diffusional creep processes at high temperatures. We obtained an unprecedented creep resistance, with creep rates of ~10-7 per second under gigapascal stress at 700°C (~61% melting point), outperforming that of conventional superalloys.

15.
Zhonghua Er Ke Za Zhi ; 60(11): 1196-1201, 2022 Nov 02.
Artigo em Zh | MEDLINE | ID: mdl-36319157

RESUMO

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.


Assuntos
Hormônio do Crescimento Humano , Resistência à Insulina , Criança , Feminino , Humanos , Masculino , Estatura , Idade Gestacional , Hormônio do Crescimento Humano/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional , Insulina , Proteínas Recombinantes , Pré-Escolar
16.
Diabetologia ; 54(9): 2381-91, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21695571

RESUMO

AIMS/HYPOTHESIS: Antagonism of the glucagon receptor (GCGR) represents a potential approach for treating diabetes. Cpd-A, a potent and selective GCGR antagonist (GRA) was studied in preclinical models to assess its effects on alpha cells. METHODS: Studies were conducted with Cpd-A to examine the effects on glucose-lowering efficacy, its effects in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor, and the extent and reversibility of alpha cell hypertrophy associated with GCGR antagonism in mouse models. RESULTS: Chronic treatment with Cpd-A resulted in effective and sustained glucose lowering in mouse models in which endogenous murine Gcgr was replaced with human GCGR (hGCGR). Treatment with Cpd-A also led to stable, moderate elevations in both glucagon and glucagon-like peptide 1 (GLP-1) levels, which were completely reversible and not associated with a hyperglycaemic overshoot following termination of treatment. When combined with a DPP-4 inhibitor, Cpd-A led to additional improvement of glycaemic control correlated with elevated active GLP-1 levels after glucose challenge. In contrast to Gcgr-knockout mice in which alpha cell hypertrophy was detected, chronic treatment with Cpd-A in obese hGCGR mice did not result in gross morphological changes in pancreatic tissue. CONCLUSIONS/INTERPRETATION: A GRA lowered glucose effectively in diabetic models without significant alpha cell hypertrophy during or following chronic treatment. Treatment with a GRA may represent an effective approach for glycaemic control in patients with type 2 diabetes, which could be further enhanced when combined with DPP-4 inhibitors.


Assuntos
Glicemia/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue , Células Secretoras de Glucagon/patologia , Glucagon/sangue , Obesidade/sangue , Obesidade/patologia , Receptores de Glucagon/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Gorduras na Dieta/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipertrofia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Knockout , Obesidade/etiologia , Receptores de Glucagon/deficiência , Receptores de Glucagon/genética , Estreptozocina/efeitos adversos
17.
Int J Obes (Lond) ; 35(2): 217-25, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20603627

RESUMO

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.


Assuntos
Adipócitos/metabolismo , Peso Corporal/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Obesidade/genética , Interferência de RNA , Animais , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Proteínas de Ligação a Ácido Graxo/genética , Técnicas de Silenciamento de Genes/métodos , Mutação em Linhagem Germinativa , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Knockout , Camundongos Obesos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Obesidade/metabolismo , RNA Mensageiro/metabolismo
18.
Clin Exp Immunol ; 164(2): 248-55, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21352201

RESUMO

Acute lung injury is characterized by a diffuse inflammatory parenchymal process, implicated in the context of significant morbidity and mortality. Previously, we have reported that soluble ST2 (sST2), a member of the Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production of macrophage exposed to lipopolysaccharide (LPS). In this study, we examined the possibility of modulating LPS-induced murine inflammatory pulmonary damage by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc led to a profound decrease in LPS-induced bronchoalveolar lavage leucocyte exudation and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with inflammatory cell infiltration and alveolar haemorrhage in the alveolar airspace was less severe in Ad-sST2-Fc-treated mice when compared with control groups. In addition, high levels of sST2-Fc in vivo reduced the transcription of tumour necrosis factor-α, IL-6 and Toll-like receptor-4 gene remarkably, and suppressed the nuclear translocation of nuclear factor-κB in lung tissues in response to LPS challenge. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of LPS-mediated inflammatory lung injury.


Assuntos
Lesão Pulmonar Aguda/terapia , Adenoviridae/genética , Terapia Genética , Vetores Genéticos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Receptores de Interleucina/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/complicações , Lesão Pulmonar Aguda/patologia , Administração Intranasal , Animais , Anti-Inflamatórios/uso terapêutico , Líquido da Lavagem Broncoalveolar/citologia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Fatores Imunológicos/genética , Fatores Imunológicos/fisiologia , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-6/biossíntese , Interleucina-6/genética , Leucócitos/imunologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/fisiologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/fisiologia , Proteínas Recombinantes de Fusão/uso terapêutico , Solubilidade , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/genética , Transgenes , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética
19.
J Appl Microbiol ; 107(4): 1149-56, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19486424

RESUMO

AIMS: To produce and purify a recombinant laccase from Pichia pastoris and to test its ability in decolourization of synthetic dyes. METHODS AND RESULTS: A cDNA encoding for a laccase was isolated from Pycnoporus sanguineus and was expressed in P. pastoris strain SMD1168H under the control of the alcohol oxidase (AOX1) promoter. The laccase native signal peptide efficiently directed the secretion of the recombinant laccase in an active form. Factors influencing laccase expression, such as cultivation temperature, pH, copper concentration and methanol concentration, were investigated. The recombinant enzyme was purified to electrophoretic homogeneity, and was estimated to have a molecular mass of about 62.8 kDa. The purified enzyme showed a similar behaviour to the native laccase produced by P. sanguineus. Four different synthetic dyes including azo, anthraquinone, triphenylmethane and indigo dyes could be efficiently decolourized by the purified recombinant laccase without the addition of redox mediators. CONCLUSIONS: Heterologous production of P. sanguineus laccase in P. pastoris was successfully achieved. The purified recombinant laccase could efficiently decolourize synthetic dyes in the absence of mediators. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report on the synthetic dye decolourization by the recombinant P. sanguineus laccase. The decolourization capacity of this recombinant enzyme suggested that it could be a useful biocatalyst for the treatment of dye-containing effluents.


Assuntos
Corantes/metabolismo , Lacase/biossíntese , Pichia/enzimologia , Biodegradação Ambiental , Clonagem Molecular , Corantes/química , DNA Complementar/genética , Concentração de Íons de Hidrogênio , Lacase/genética , Lacase/metabolismo , Pichia/genética , Engenharia de Proteínas/métodos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Temperatura , Transformação Genética
20.
Zhonghua Xue Ye Xue Za Zhi ; 40(5): 384-387, 2019 May 14.
Artigo em Zh | MEDLINE | ID: mdl-31207702

RESUMO

Objective: To analyze the clinical features of patients with hemophagocytic lymphohistiocytosis (HLH) during perinatal stage. Methods: From January 2011 to October 2016, the obstetric materials, clinical features, associated disease/factors and therapeutic outcomes were studied in 11 patients with HLH in perinatal period. Results: In these 11 patients, 9 were primipara. As for the onset time of HLH, 5 were before delivery and 6 were after delivery. Six were complicated with other associated disease/factors, and infection was the commonest (5/6) . Treatment included glucocorticoid + fludarabine in 1 case, HLH-94/04 protocols in 9 cases, and monotherapy corticosteroids in 1 case. Two patients died eventually. Conclusions: Perinatal HLH is commonly observed in the pregnancy/postpartum related HLH (28th week of pregnancy to one week after delivery) . Infection is still the commonest associated factors. HLH-94/04 protocols after the cessation of pregnancy may be effective, but the cessation of pregnancy itself may not be enough for the perinatal stage related-HLH. The perinatal stage related-HLH still has a better outcome than the other subtype of secondary-HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica , Corticosteroides , Feminino , Humanos , Gravidez
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