RESUMO
Chronic hepatitis B virus (HBV) poses a significant global health challenge as it can lead to acute or chronic liver disease and hepatocellular carcinoma (HCC). To establish a safety experimental model, a homolog of HBV-duck HBV (DHBV) is often used for HBV research. Hydrodynamic-based gene delivery (HGD) is an efficient method to introduce exogenous genes into the liver, making it suitable for basic research. In this study, a duck HGD system was first constructed by injecting the reporter plasmid pLIVE-SEAP via the ankle vein. The highest expression of SEAP occurred when ducks were injected with 5 µg/mL plasmid pLIVE-SEAP in 10% bodyweight volume of physiological saline for 6 s. To verify the distribution and expression of exogenous genes in multiple tissues, the relative level of foreign gene DNA and ß-galactosidase staining of LacZ were evaluated, which showed the plasmids and their products were located mainly in the liver. Additionally, ß-galactosidase staining and fluorescence imaging indicated the delivered exogenous genes could be expressed in a short time. Further, the application of the duck HGD model on DHBV treatment was investigated by transferring representative anti-HBV genes IFNα and IFNγ into DHBV-infected ducks. Delivery of plasmids expressing IFNα and IFNγ inhibited DHBV infection and we established a novel efficient HGD method in ducks, which could be useful for drug screening of new genes, mRNAs and proteins for anti-HBV treatment.
Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B do Pato , Hepatite B Crônica , Neoplasias Hepáticas , Animais , Humanos , Carcinoma Hepatocelular/patologia , Patos/genética , Hepatite B Crônica/patologia , Neoplasias Hepáticas/patologia , Hidrodinâmica , Fígado , Vírus da Hepatite B do Pato/genética , beta-Galactosidase , DNA Viral/genéticaRESUMO
Adipocytes express several kinds of catecholamine receptors, including adrenergic receptors, and dopamine receptors. Signaling pathways mediated by catecholamine receptors, such as ß3-adrenergic receptor pathway, can induce body energy expenditure via activating thermogenesis of adipose tissue. However, the roles of adipose dopamine receptors on adipocytes are still unclear. Here, we investigate the role of dopamine receptor D1 (DRD1) on adipocytes. To this end, we use DRD1 agonist Fenoldopam and antagonist SCH23390 to stimulate and inhibit DRD1 signaling, respectively. We found that, compared with control group mice, Fenoldopam-treated and SCH23390-treated high-fat-diet (HFD)-fed mice showed smaller and bigger white adipose tissue/adipocyte sizes, respectively. Meanwhile, activating of DRD1 signaling enhanced intracellular levels of cAMP, phosphorylation levels of protein kinase A substrates, and hormone-sensitive lipase, a key enzyme for lipolysis in mature 3T3-L1 adipocytes and white adipose tissue of HFD-fed mice. As a result, the levels of free fatty acid or glycerol were increased, indicating stimulation of lipolysis by DRD1 activation. Moreover, activating DRD1 can induce the browning of adipocytes, as indicated by enhanced phosphorylation of P38 MAP kinase, increased expression of beige cell markers (PGC-1α, UCP-1, and CD81), mitochondrion content, and expression of ß-oxidation related genes. All of these effects were reduced after treating with SCH23390 both in vitro and in HFD-fed mice. Collectively, our study indicated that DRD1 signaling stimulates lipolysis and browning of white adipocytes in vitro and in vivo. Understanding the functions of DRD1 on human adipocytes and adipose tissues will help us to design novel strategies to treat obesity.
Assuntos
Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Lipólise , Receptores de Dopamina D1/metabolismo , Transdução de Sinais , Células 3T3-L1 , Animais , Tamanho Celular , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dieta Hiperlipídica , Comportamento Alimentar , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteína Desacopladora 1/metabolismo , Regulação para Cima/genética , Aumento de Peso/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We present a reverse design method useful for designing and analyzing metamaterial absorbers; we demonstrate its power by designing both a narrowband absorber and a wideband absorber. The method determines the structure of the absorber using an equivalent-circuit model. The narrowband metamaterial absorber structures were based on the equivalent-circuit model, and the narrowband metamaterial absorber designed using the method has an absorption fraction greater than 90% in a bandwidth of 500 nm centered at about 1450 nm. In order to extend the absorption bandwidth for the absorber, the narrowband absorber structure is adjusted based on the equivalent-circuit model, and the broadband metamaterial absorber structure is investigated. The numerical results show that the absorption bandwidth is substantially increased; the absorbance is greater than 90% for a band nearly reaching the limits of our experiment, from about 400 nm (near-ultraviolet) to about 2800 nm (deep infrared). The absorption spectrum of the wideband absorber is more sensitive to the angle of incident polarization due to the asymmetric structure, but the whole band shows polarization independence. For a large angle of 60° (TM polarization) oblique incidence, the average absorption of the broadband metamaterial absorber reaches 81%. The physical mechanism of the wideband high absorption is analyzed, which is mainly caused by Fabry-Perot resonance, surface plasmon resonance, local surface plasmon resonance, and the hybrid coupling among them. Our proposed design with high-broadband absorption has significant potential for thermoelectric and thermal emitters, solar thermal energy harvesting, and invisible device applications.
RESUMO
Background: Patients with atrial septal defect (ASD) exhibit distinctive electrocardiogram (ECG) patterns. However, ASD cannot be diagnosed solely based on these differences. Artificial intelligence (AI) has been widely used for specifically diagnosing cardiovascular diseases other than arrhythmia. Our study aimed to develop an artificial intelligence-enabled 8-lead ECG to detect ASD among adults. Method: In this study, our AI model was trained and validated using 526 ECGs from patients with ASD and 2,124 ECGs from a control group with a normal cardiac structure in our hospital. External testing was conducted at Wuhan Central Hospital, involving 50 ECGs from the ASD group and 46 ECGs from the normal group. The model was based on a convolutional neural network (CNN) with a residual network to classify 8-lead ECG data into either the ASD or normal group. We employed a 10-fold cross-validation approach. Results: Statistically significant differences (p < 0.05) were observed in the cited ECG features between the ASD and normal groups. Our AI model performed well in identifying ECGs in both the ASD group [accuracy of 0.97, precision of 0.90, recall of 0.97, specificity of 0.97, F1 score of 0.93, and area under the curve (AUC) of 0.99] and the normal group within the training and validation datasets from our hospital. Furthermore, these corresponding indices performed impressively in the external test data set with the accuracy of 0.82, precision of 0.90, recall of 0.74, specificity of 0.91, F1 score of 0.81 and the AUC of 0.87. And the series of experiments of subgroups to discuss specific clinic situations associated to this issue was remarkable as well. Conclusion: An ECG-based detection of ASD using an artificial intelligence algorithm can be achieved with high diagnostic performance, and it shows great clinical promise. Our research on AI-enabled 8-lead ECG detection of ASD in adults is expected to provide robust references for early detection of ASD, healthy pregnancies, and related decision-making. A lower number of leads is also more favorable for the application of portable devices, which it is expected that this technology will bring significant economic and societal benefits.
RESUMO
To evaluate the efficacy of interferon-α (IFN-α) combined with homoharringtonine (HHT) in the treatment of patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CML), an IFN-α combined with HHT scheme was used as induction and maintenance therapy for 42 patients with CML in chronic phase. Thirty-five patients treated with IFN-α alone were used as the control group. It was found that the cytogenetic response rate and estimated 2-year survival rate were higher in the IFN-α + HHT group than in the IFN-α group (52.4% vs. 28.6% and 90% vs. 73%, respectively). No grade 3 or 4 hematological toxicity, severe infections, hemorrhage or non-hematological adverse reactions were observed. From this research it can be concluded that an IFN-α combined with HHT scheme is safe and effective for CML induction and long-term maintenance therapy. It may be a good choice for patients with CML who cannot accept a hematopoietic stem cell transplant and imatinib or who fail IFN-α therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Seguimentos , Harringtoninas/administração & dosagem , Mepesuccinato de Omacetaxina , Humanos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
The study was aimed to investigate the synergistically effect of interferon-α (IFN-α) and homoharringtonine (HHT) on the proliferation, apoptosis, cell cycle of K562 cells and the expression of ß-catenin. The proliferation, apoptosis, cell cycle and ß-catenin mRNA expression of K562 cells treated with IFN-α and/or HHT were assayed with MTT, flow cytometry or RT-PCR respectively. The results showed that HHT alone, but not IFN-α alone, displayed a proliferation inhibition, apoptosis induction, G(0)/G(1) phase block and down-regulation of ß-catenin expression in K562 cells with concentration- and time-dependent manners. The expression level of ß-catenin mRNA after being treated with HHT was 0.5576 ± 0.0373, which were lower than that in control group (0.9369 ± 0.0142). The down-regulation of ß-catenin expression in group of IFN-α combined with HHT was higher significantly than that in HHT group (0.3737 ± 0.0529 vs 0.5576 ± 0.0373, P < 0.05). Otherwise, HHT combined with IFN-α did not demonstrate obvious toxicologic effect on bone marrow mononuclear cells. It is concluded that IFN-α combined with HHT can enhance the cytotoxic effect of HHT on K562 cells, which may be associated with down-regulation of ß-catenin expression.