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1.
J Biol Chem ; 300(3): 105661, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246352

RESUMEN

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has emerged as a prevalent cause of liver cirrhosis and hepatocellular carcinoma, posing severe public health challenges worldwide. The incidence of NASH is highly correlated with an increased prevalence of obesity, insulin resistance, diabetes, and other metabolic diseases. Currently, no approved drugs specifically targeted for the therapies of NASH partially due to the unclear pathophysiological mechanisms. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor involved in the development of metabolic diseases such as obesity and diabetes. However, the function of GPER1 in NAFLD/NASH progression remains unknown. Here, we show that GPER1 exerts a beneficial role in insulin resistance, hepatic lipid accumulation, oxidative stress, or inflammation in vivo and in vitro. In particular, we observed that the lipid accumulation, inflammatory response, fibrosis, or insulin resistance in mouse NAFLD/NASH models were exacerbated by hepatocyte-specific GPER1 knockout but obviously mitigated by hepatic GPER1 activation in female and male mice. Mechanistically, hepatic GPER1 activates AMP-activated protein kinase signaling by inducing cyclic AMP release, thereby exerting its protective effect. These data suggest that GPER1 may be a promising therapeutic target for NASH.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Animales , Femenino , Masculino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus/metabolismo , Modelos Animales de Enfermedad , Receptor alfa de Estrógeno/metabolismo , Proteínas de Unión al GTP/metabolismo , Lípidos/farmacología , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Ratones Endogámicos C57BL , Estrógenos/deficiencia , Estrógenos/metabolismo , Dieta Alta en Grasa
2.
Sensors (Basel) ; 24(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38610334

RESUMEN

The network intrusion detection system (NIDS) plays a crucial role as a security measure in addressing the increasing number of network threats. The majority of current research relies on feature-ready datasets that heavily depend on feature engineering. Conversely, the increasing complexity of network traffic and the ongoing evolution of attack techniques lead to a diminishing distinction between benign and malicious network behaviors. In this paper, we propose a novel end-to-end intrusion detection framework based on a contrastive learning approach. We design a hierarchical Convolutional Neural Network (CNN) and Gated Recurrent Unit (GRU) model to facilitate the automated extraction of spatiotemporal features from raw traffic data. The integration of contrastive learning amplifies the distinction between benign and malicious network traffic in the representation space. The proposed method exhibits enhanced detection capabilities for unknown attacks in comparison to the approaches trained using the cross-entropy loss function. Experiments are carried out on the public datasets CIC-IDS2017 and CSE-CIC-IDS2018, demonstrating that our method can attain a detection accuracy of 99.9% for known attacks, thus achieving state-of-the-art performance. For unknown attacks, a weighted recall rate of 95% can be achieved.

3.
BMC Psychiatry ; 23(1): 875, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-38001400

RESUMEN

BACKGROUND: Oculogyric crisis (OGC) is a rare focal dystonia of the ocular muscles that not only interferes with patients' medication adherence but also negatively affects the course and prognosis of the primary disease. Early detection and treatment of OGC can improve patients' medication adherence and quality of life. CASE PRESENTATION: This paper reports a case of a 19-year-old Asian female with a diagnosis of schizophrenia who was treated intermittently with atypical antipsychotics aripiprazole or risperidone for 2 years, with improvement of psychotic symptoms during the course of medication, and then developed double eye rolling and staring with irritability when treated with risperidone 4 mg/d or 6 mg/d. Then, we changed the medication to clozapine, and the patient's psychotic symptoms were controlled and stable. The symptoms of double eye rolling and gaze disappeared. CONCLUSION: Oculogyric crisis (OGC) is a rare focal dystonia of the oculogyric muscle. This case provides clinicians with a basis for the early recognition and management of oculogyric crisis during the use of atypical antipsychotics (risperidone).


Asunto(s)
Antipsicóticos , Clozapina , Trastornos Distónicos , Humanos , Femenino , Adulto Joven , Adulto , Risperidona/efectos adversos , Calidad de Vida , Antipsicóticos/efectos adversos , Clozapina/uso terapéutico , Trastornos Distónicos/tratamiento farmacológico
4.
Sensors (Basel) ; 23(19)2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37837019

RESUMEN

A robust and scientifically grounded teaching evaluation system holds significant importance in modern education, serving as a crucial metric that reflects the quality of classroom instruction. However, current methodologies within smart classroom environments have distinct limitations. These include accommodating a substantial student population, grappling with object detection challenges due to obstructions, and encountering accuracy issues in recognition stemming from varying observation angles. To address these limitations, this paper proposes an innovative data augmentation approach designed to detect distinct student behaviors by leveraging focused behavioral attributes. The primary objective is to alleviate the pedagogical workload. The process begins with assembling a concise dataset tailored for discerning student learning behaviors, followed by the application of data augmentation techniques to significantly expand its size. Additionally, the architectural prowess of the Extended-efficient Layer Aggregation Networks (E-ELAN) is harnessed to effectively extract a diverse array of learning behavior features. Of particular note is the integration of the Channel-wise Attention Module (CBAM) focal mechanism into the feature detection network. This integration plays a pivotal role, enhancing the network's ability to detect key cues relevant to student learning behaviors and thereby heightening feature identification precision. The culmination of this methodological journey involves the classification of the extracted features through a dual-pronged conduit: the Feature Pyramid Network (FPN) and the Path Aggregation Network (PAN). Empirical evidence vividly demonstrates the potency of the proposed methodology, yielding a mean average precision (mAP) of 96.7%. This achievement surpasses comparable methodologies by a substantial margin of at least 11.9%, conclusively highlighting the method's superior recognition capabilities. This research has an important impact on the field of teaching evaluation system, which helps to reduce the burden of educators on the one hand, and makes teaching evaluation more objective and accurate on the other hand.


Asunto(s)
Aprendizaje , Estudiantes , Humanos , Señales (Psicología)
5.
Sensors (Basel) ; 22(14)2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35890921

RESUMEN

Most machine learning algorithms only have a good recognition rate on balanced datasets. However, in the field of malicious traffic identification, benign traffic on the network is far greater than malicious traffic, and the network traffic dataset is imbalanced, which makes the algorithm have a low identification rate for small categories of malicious traffic samples. This paper presents a traffic sample synthesizing model named Conditional Tabular Traffic Generative Adversarial Network (CTTGAN), which uses a Conditional Tabular Generative Adversarial Network (CTGAN) algorithm to expand the small category traffic samples and balance the dataset in order to improve the malicious traffic identification rate. The CTTGAN model expands and recognizes feature data, which meets the requirements of a machine learning algorithm for training and prediction data. The contributions of this paper are as follows: first, the small category samples are expanded and the traffic dataset is balanced; second, the storage cost and computational complexity are reduced compared to models using image data; third, discrete variables and continuous variables in traffic feature data are processed at the same time, and the data distribution is described well. The experimental results show that the recognition rate of the expanded samples is more than 0.99 in MLP, KNN and SVM algorithms. In addition, the recognition rate of the proposed CTTGAN model is better than the oversampling and undersampling schemes.


Asunto(s)
Algoritmos , Aprendizaje Automático
6.
Entropy (Basel) ; 24(3)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35327829

RESUMEN

(k,n)-threshold secret image sharing (SIS) protects an image by dividing it into n shadow images. The secret image will be recovered as we gather k or more shadow images. In complex networks, the security, robustness and efficiency of protecting images draws more and more attention. Thus, we realize multiple secret images sharing (MSIS) by information hiding in the sharing domain (IHSD) and propose a novel and general (n,n)-threshold IHSD-MSIS scheme (IHSD-MSISS), which can share and recover two secret images simultaneously. The proposed scheme spends less cost on managing and identifying shadow images, and improves the ability to prevent malicious tampering. Moreover, it is a novel approach to transmit important images with strong associations. The superiority of (n,n)-threshold IHSD-MSISS is in fusing the sharing phases of two secret images by controlling randomness of SIS. We present a general construction model and algorithms of the proposed scheme. Sufficient theoretical analyses, experiments and comparisons show the effectiveness of the proposed scheme.

7.
Entropy (Basel) ; 24(3)2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35327821

RESUMEN

In order to detect the incipient fault of rolling bearings and to effectively identify fault characteristics, based on amplitude-aware permutation entropy (AAPE), an enhanced method named hierarchical amplitude-aware permutation entropy (HAAPE) is proposed in this paper to solve complex time series in a new dynamic change analysis. Firstly, hierarchical analysis and AAPE are combined to excavate multilevel fault information, both low-frequency and high-frequency components of the abnormal bearing vibration signal. Secondly, from the experimental analysis, it is found that HAAPE is sensitive to the early failure of rolling bearings, which makes it suitable to evaluate the performance degradation of a bearing in its run-to-failure life cycle. Finally, a fault feature selection strategy based on HAAPE is put forward to select the bearing fault characteristics after the application of the least common multiple in singular value decomposition (LCM-SVD) method to the fault vibration signal. Moreover, several other entropy-based methods are also introduced for a comparative analysis of the experimental data, and the results demonstrate that HAAPE can extract fault features more effectively and with a higher accuracy.

8.
Int J Obes (Lond) ; 44(5): 1075-1086, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31911660

RESUMEN

BACKGROUND/OBJECTIVES: Mitochondrial dysfunction, oxidative stress, or fatty liver are the key pathophysiological features for insulin resistance and obesity. Dehydroepiandrosterone (DHEA) can ameliorate obesity and insulin resistance; however, the mechanisms of these actions are poorly understood. The present study aimed to investigate the effect and possible mechanism of DHEA against glycolipid metabolic disorder and insulin resistance. SUBJECTS/METHODS: Rats fed a high-fat diet (HFD) and palmitic acid (PA)-induced BRL-3A cells were employed to analyze the effect of DHEA on factors related to metabolic disorder and insulin resistance in vivo and in vitro. RESULTS: DHEA prevented lipid metabolism disorders by enhancing phospho (p)-protein kinase AMP-activated catalytic subunit alpha (AMPKα) (Thr172) protein level and its downstream lipid metabolism-related factors in liver of rats fed an HFD or in PA-induced BRL-3A cells. Meanwhile, DHEA ameliorated mitochondrial dysfunction through activation of the AMPK-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-nuclear respiratory factor-1 (NRF-1) pathway, which represented as the enhancing of the mtDNA copy number, ATP level, and membrane potential, and decreasing of reactive oxygen species production. Moreover, DHEA alleviated insulin resistance via increasing the phosphorylated insulin receptor substrate 1 (p-IRS1) (Tyr612) level and decreasing that of p-IRS1 (Ser307) level in liver of rats fed an HFD or in PA-induced BRL-3A cells, which subsequently enhanced p-protein kinase B (AKT) (Ser473) and membrane glucose transporter type 2 (GLUT2) expression levels. CONCLUSIONS: The protective effect of DHEA on high-fat-induced hepatic glycolipid metabolic disorder and insulin resistance are achieved through activation of the AMPK-PGC-1α-NRF-1 and IRS1-AKT-GLUT2 signaling pathways. The results provide compelling evidence for the mechanism by which DHEA prevents glycolipid metabolic disorder, and suggest its potential applications for controlling diabetes and obesity in animals and humans.


Asunto(s)
Deshidroepiandrosterona/farmacología , Hígado Graso/metabolismo , Resistencia a la Insulina/fisiología , Hígado , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Transportador de Glucosa de Tipo 2/metabolismo , Glucolípidos/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Factor Nuclear 1 de Respiración/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley
9.
J Cell Biochem ; 120(2): 1258-1270, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30317645

RESUMEN

(-)-Hydroxycitric acid [(-)-HCA] is widely used as a nutritional supplement to control body weight and fat accumulation in animals and humans, whereas the underlying biochemical mechanism is unclear. Broiler chicken was used as a model for studies of obesity due to its natural hyperglycemia and being insulin resistant. The current study aimed to obtain a systematic view of serum metabolites and hepatic proteins and well understand the mechanism of hepatic metabolic response to (-)-HCA treatment in chick embryos. The results showed that 22, 90, and 82 of differentially expressed proteins were identified at E14d, E19d, and H1d in chick embryos treated with (-)-HCA, respectively. Meanwhile, 5, 83, and 88 of serum metabolites significantly changed at E14d, E19d, and H1d in chick embryos after (-)-HCA treatment. Bioinformatics analysis showed that the key proteins and metabolites, which were significantly altered in chick embryos treated with (-)-HCA, were mainly involved in the citrate cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and pyruvate metabolism. Our data indicated that (-)-HCA treatment might promote fat metabolism via regulating the key protein expression levels and metabolite contents in the citrate cycle, glycolysis/gluconeogenesis, and oxidative phosphorylation during chicken embryonic development. These results will deepen our understanding of the mechanism of fat reduction by (-)-HCA and provide substantial information for (-)-HCA as a nutritional supplement to control body weight gain and curb obesity-related diseases.

10.
Int J Mol Sci ; 20(1)2019 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-30609807

RESUMEN

It has been reported that the miR-125 family plays an important role in regulating embryo development. However, the function of miR-125b-2 in spermatogenesis remains unknown. In this study, we used a model of miR-125b knockout (KO) mice to study the relationship between miR-125b-2 and spermatogenesis. Among the KO mice, the progeny test showed that the litter size decreased significantly (p = 0.0002) and the rate of non-parous females increased significantly from 10% to 38%. At the same time, the testosterone concentration increased significantly (p = 0.007), with a remarkable decrease for estradiol (p = 0.02). Moreover, the sperm count decreased obviously (p = 0.011) and the percentage of abnormal sperm increased significantly (p = 0.0002). The testicular transcriptome sequencing revealed that there were 173 up-regulated genes, including Papolb (PAP), and 151 down-regulated genes in KO mice compared with wild type (WT). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis showed that many of these genes were involved in sperm mitochondrial metabolism and other cellular biological processes. Meanwhile, the sperm mitochondria DNA (mtDNA) copy number increased significantly in the KO mice, but there were no changes observed in the mtDNA integrity and mutations of mt-Cytb, as well as the mt-ATP6 between the WT mice and KO mice. In the top 10 up-regulated genes, PAP, as a testis specific expressing gene, affect the process of spermatogenesis. Western blotting and the Luciferase assay validated that PAP was the target of miR-125b-5p. Intriguingly, we also found that both miR-125b and PAP were only highly expressed in the germ cells (GC) instead of in the Leydig cells (LC) and Sertoli cells (SC). Additionally, miR-125b-5p down regulated the secretion of testosterone in the TM3 cell by targeting PAP (p = 0.021). Our study firstly demonstrated that miR-125b-2 regulated testosterone secretion by directly targeting PAP, and increased the sperm mtDNA copy number to affect semen quality. The study indicated that miR-125b-2 had a positive influence on the reproductive performance of animals by regulating the expression of the PAP gene, and could be a potential drugs and diagnostic target for male infertility.


Asunto(s)
ADN Mitocondrial/metabolismo , MicroARNs/metabolismo , Proteínas Asociadas a Pancreatitis/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Regiones no Traducidas 3' , Animales , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Femenino , Células Germinativas/citología , Células Germinativas/metabolismo , Masculino , Ratones , Ratones Noqueados , MicroARNs/genética , Mitocondrias/genética , Proteínas Asociadas a Pancreatitis/química , Proteínas Asociadas a Pancreatitis/genética , Espermatogénesis , Testosterona/metabolismo , Transcriptoma , Regulación hacia Arriba
11.
J Cell Physiol ; 233(8): 6262-6272, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29521449

RESUMEN

This study aimed to investigate the molecular mechanism of dehydroepiandrosterone (DHEA) rehabilitated BRL-3A cells oxidative stress damage induced by hydrogen peroxide (H2 O2 ). Results showed that DHEA reversed the decrease of cell viability and ameliorated nuclear chromatin damage in H2 O2 -induced BRL-3A cells. DHEA increased the activities of superoxide dismutase, catalase, peroxidase, and glutathione peroxidase, and decreased the reactive oxygen species (ROS) production in H2 O2 -induced BRL-3A cells. DHEA attenuated the protein damage and lipid peroxidation, and reduced the apoptosis in H2 O2 -induced BRL-3A cells. The mRNA levels of Bax, Caspase-9, and Caspase-3 were decreased, while the Bcl-2 mRNA level was increased in H2 O2 -induced BRL-3A cells treated with DHEA. Our results showed that DHEA treatment increased the PI3K and p-Akt protein levels, while decreased the Bax and capase-3 protein levels in H2 O2 -induced BRL-3A cells. However, the rise in PI3K and p-Akt protein levels, and the decrease in Bax and capase-3 protein levels induced by DHEA treatment were reversed when the cells pretreated with LY294002 (PI3K inhibitor). These results indicated that DHEA ameliorated H2 O2 -induced oxidative damage by increasing anti-oxidative enzyme activities and ameliorating the protein damage and lipid peroxidation in BRL-3A cells. In addition, DHEA decreased the apoptosis by inhibiting caspase-3 and Bax protein levels and this action mainly achieved via the activation of PI3K/Akt signaling pathways in H2 O2 -induced BRL-3A cells. These results provided substantial information for DHEA as a nutritional supplement to treat oxidative stress and it related diseases in animals and humans.


Asunto(s)
Deshidroepiandrosterona/farmacología , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Oxidación-Reducción/efectos de los fármacos , Peroxidasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismo
12.
BMC Genomics ; 19(1): 29, 2018 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-29310583

RESUMEN

BACKGROUND: Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. RESULTS: In this study, the abundances of 293 hepatic proteins in 19-day old of chicken embryos compared with 14-day old and 160 hepatic proteins at hatching compared with 19-day old embryos were significantly changed. Pathway analysis showed that fatty acid degradation (upregulated ACAA2, CPT1A, and ACOX1), protein folding (upregulated PDIs, CALR3, LMAN1, and UBQLN1) and gluconeogenesis (upregulated ACSS1, AKR1A1, ALDH3A2, ALDH7A1, and FBP2) were enhanced from embryonic day 14 (E14) to E19 of chicken embryo development. Analysis of the differentially abundant proteins indicated that glycolysis was not the main way to produce energy from E19 to hatching day during chicken embryo development. In addition, purine metabolism was enhanced, as deduced from increased IMPDH2, NT5C, PGM2, and XDH abundances, and the decrease of growth rate could be overcome by increasing the abundance of ribosomal proteins from E19 to the hatching day. CONCLUSION: The levels of certain proteins were coordinated with each other to regulate the changes in metabolic pathways to satisfy the requirement for growth and development at different stages of chicken embryo development. Importantly, ACAA2, CPT1A, and ACOX1 might be key factors to control fat deposition during chicken embryonic development. These results provided information showing that chicken is a useful model to further investigate the mechanism of obesity and insulin resistance in humans.


Asunto(s)
Desarrollo Embrionario , Hígado/embriología , Hígado/metabolismo , Proteoma , Proteómica , Animales , Embrión de Pollo , Cromatografía Liquida , Biología Computacional/métodos , Modelos Animales de Enfermedad , Desarrollo Embrionario/genética , Humanos , Obesidad/etiología , Obesidad/metabolismo , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Proteómica/métodos , Transducción de Señal , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
13.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(6): 625-638, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29571766

RESUMEN

Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to control fat deposition, but the mechanism of this action is poorly understood. In this study, we demonstrated that DHEA increased phosphorylation of AMP-activated protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid synthase and enhanced expression of peroxisome proliferators-activated receptor α and carnitine palmitoyl transferase-I, ultimately leading to the reduction of lipid droplet accumulation in primary chicken hepatocytes. We found that DHEA activates the cyclic adenosine 3', 5'-monophosphate/protein kinase A - extracellular signal-regulated kinase 1/2 (cAMP/PKA-ERK1/2) signaling pathway, which regulates the conversion of DHEA into testosterone and estradiol by increasing the 17ß-hydroxysteroid dehydrogenase and aromatase protein expression. Importantly, the fat-reducing effects of DHEA are more closely associated with the conversion of DHEA into estradiol than with the action of DHEA itself as an active biomolecule, or to its alternative metabolite, testosterone. Taken together, our results indicate that DHEA is converted into active hormones through activation of the cAMP/PKA-ERK1/2 signaling pathway; the fat-reducing effects of DHEA are achieved through its conversion into estradiol, not testosterone, and not through direct action of DHEA itself, which led to the activation of the p-AMPK in primary chicken hepatocytes. These data provide novel insight into the mechanisms underlying the action of DHEA in preventing fat deposition, and suggest potential applications for DHEA treatment to control fat deposition or as an agent to treat disorders related to lipid metabolism in animals and humans.


Asunto(s)
AMP Cíclico/metabolismo , Deshidroepiandrosterona/metabolismo , Hepatocitos/metabolismo , Gotas Lipídicas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Sistemas de Mensajero Secundario , Animales , Proteínas Aviares/metabolismo , Pollos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
14.
Bioorg Med Chem Lett ; 28(1): 49-52, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29162455

RESUMEN

A series of novel or known water-soluble derivatives of chiral gossypol were synthesized and screened in vitro for their anti-HIV-1 activity. (-)-gossypol derivative was more active against HIV-1 than the corresponding (+)-gossypol derivative, respectively. Among these derivatives, d-glucosamine derivative of (-)-gossypol, oligopeptide derivative of (-)-gossypol and taurine derivative of (-)-gossypol, such as compounds 1a, 3a and 14a, showed significant inhibitory activities against HIV-1 replication, HIV-1 mediated cell-cell fusion and HIV gp41 6-helix bundle formation as some amino acid derivatives of (-)-gossypol.


Asunto(s)
Gosipol/química , Proteína gp41 de Envoltorio del VIH/antagonistas & inhibidores , Inhibidores de Fusión de VIH/síntesis química , VIH-1/fisiología , Sitios de Unión , Diseño de Fármacos , Gosipol/metabolismo , Gosipol/farmacología , Proteína gp41 de Envoltorio del VIH/metabolismo , Inhibidores de Fusión de VIH/metabolismo , Inhibidores de Fusión de VIH/farmacología , Humanos , Enlace de Hidrógeno , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Estructura Terciaria de Proteína , Solubilidad , Estereoisomerismo , Replicación Viral/efectos de los fármacos , Agua/química
15.
Cell Physiol Biochem ; 43(2): 812-831, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28954258

RESUMEN

BACKGROUND/AIMS: (-)-Hydroxycitric acid (HCA) had been shown to suppress fat accumulation in animals and humans, while the underlying biochemical mechanism is not fully understood, especially little information is available on whether (-)-HCA regulates energy metabolism and consequently affects fat deposition. METHODS: Hepatocytes were cultured for 24 h and then exposed to (-)-HCA (0, 1, 10, 50 µM), enzyme protein content was determined by ELISA; lipid metabolism gene mRNA levels were detected by RT-PCR. RESULTS: (-)-HCA significantly decreased the number and total area of lipid droplets. ATP-citrate lyase, fatty acid synthase and sterol regulatory element binding protein-1c mRNA level were significantly decreased after (-)-HCA treatment, whereas peroxisome proliferator-activated receptor α mRNA level was significantly increased. (-)-HCA significantly decreased ATP-citrate lyase activity and acetyl-CoA content in cytosol, but significantly increased glucose consumption and mitochondrial oxygen consumption rate. (-)-HCA promoted the activity/content of glucokinase, phosphofructokinase-1, pyruvate kinase, pyruvate dehydrogenase, citrate synthase, aconitase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and ATP synthase remarkably. CONCLUSIONS: (-)-HCA decreased lipid droplets accumulation by reducing acetyl-CoA supply, which mainly achieved via inhibition of ATP-citrate lyase, and accelerating energy metabolism in chicken hepatocytes. These results proposed a biochemical mechanism of fat reduction by (-)-HCA in broiler chickens in term of energy metabolism.


Asunto(s)
Acetilcoenzima A/metabolismo , Pollos/metabolismo , Citratos/metabolismo , Metabolismo Energético , Hepatocitos/metabolismo , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos , Animales , Células Cultivadas
16.
Nanotechnology ; 28(16): 164005, 2017 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-28273049

RESUMEN

Molecular dynamics simulations on nanoindentation of circular monolayer molybdenum disulfide (MoS2) film are carried out to elucidate the deformation and failure mechanisms. Typical force-deflection curves are obtained, and in-plane stiffness of MoS2 is extracted according to a continuum mechanics model. The measured in-plane stiffness of monolayer MoS2 is about 182 ± 14 N m-1, corresponding to an effective Young's modulus of 280 ± 21 GPa. More interestingly, at a critical indentation depth, the loading force decreases sharply and then increases again. The loading-unloading-reloading processes at different initial unloading deflections are also conducted to explain the phenomenon. It is found that prior to the critical depth, the monolayer MoS2 film can return to the original state after completely unloading, while there is hysteresis when unloading after the critical depth and residual deformation exists after indenter fully retracted, indicating plasticity. This residual deformation is found to be caused by the changed lattice structure of the MoS2, i.e. a phase transformation. The critical pressure to induce the phase transformation is then calculated to be 36 ± 2 GPa, consistent with other studies. Finally, the influences of temperature, the diameter and indentation rate of MoS2 monolayer on the mechanical properties are also investigated.

17.
Lipids Health Dis ; 15: 37, 2016 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-26912252

RESUMEN

BACKGROUND: Chicken as a delicious food for a long history, and it is well known that excess fat deposition in broiler chickens will not only induced metabolic diseases, but also lead to adverse effect in the consumer's health. (-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress fat accumulation in animals and humans. While, the precise physiological mechanism of HCA has not yet been full clarified, especially its action in broiler chickens. Thus, this study aimed to assess the effect of (-)-HCA on lipid metabolism in broiler chickens. METHODS: A total of 120 1-day-old broiler chickens were randomly allocated to four groups, with each group was repeated three times with 10 birds. Birds received a commercial diet supplemented with (-)-HCA at 0, 1000, 2000 or 3000 mg/kg, respectively, for a period of 4 weeks ad libitum. RESULTS: Body weight (BW) in the 2000 and 3000 mg/kg (-)-HCA groups was significantly decreased (P < 0.05) than that in control group. A significantly decreased of serum triglyceride (TG) and density lipoprotein-cholesterol (LDL-C) content were observed in 3000 mg/kg (-)-HCA group (P < 0.05). Broiler chickens supplmented with 2000 and 3000 mg/kg (-)-HCA had pronouncedly higher hepatic lipase (HL) activity, hepatic glycogen and non-esterified fatty acid (NEFA) contents in liver (P < 0.05). Serum free triiodothyronine (FT3) and thyroxin (T4) contents were significantly higher in 3000 mg/kg (-)-HCA group (P < 0.05) compared with the control group. Supplemental (-)-HCA markedly decreased fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c) (P < 0.05) mRNA levels, while the mRNA abundance of adenosine 5'-monophosphate-activated protein kinaseß2 (AMPKß2) (P < 0.05) was significantly increased. In addition, ATP-citrate lyase (ACLY) mRNA level (P < 0.05) was significantly decreased in broiler chickens supplemented with 3000 mg/kg (-)-HCA. No differences was observed on carnitine palmitoyl transferase-I(CPT-I), while peroxisome proliferators-activated receptor α (PPARα) mRNA level (P < 0.05) was significantly increased in broiler chickens supplemented with 2000 and 3000 mg/kg (-)-HCA. CONCLUSIONS: Supplemental (-)-HCA inhibited lipogenesis by inhibiting ACLY, SREBP-1c and FAS expression, and accelerated lipolysis through enhancing HL activity and PPARα expression, which eventually led to the reduced abdominal fat deposition in broiler chickens. Graphical abstract Mechanism of (-)-HCA effect on hepatic lipids metabolism.


Asunto(s)
Citratos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Carnitina O-Palmitoiltransferasa/genética , Pollos , LDL-Colesterol/sangre , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Masculino , PPAR alfa/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/sangre , Triglicéridos/sangre
18.
Appl Opt ; 55(11): 2980-4, 2016 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-27139863

RESUMEN

Optical bistable behaviors induced by tunneling coupling are demonstrated in an asymmetric double quantum-well structure including a unidirectional ring cavity. We analytically find that optical bistability can be obtained with the existence of resonant tunneling. Furthermore, the threshold of the optical bistability can be modulated by the intensity or the detuning of the driving fields.

19.
Phytother Res ; 30(8): 1316-29, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27145492

RESUMEN

(-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress body weight gain and fat accumulation in animals and humans. While, the underlying mechanism of (-)-HCA has not fully understood. Thus, this study was aimed to investigate the effects of long-term supplement with (-)-HCA on body weight gain and variances of amino acid content in rats. Results showed that (-)-HCA treatment reduced body weight gain and increased feed conversion ratio in rats. The content of hepatic glycogen, muscle glycogen, and serum T4 , T3 , insulin, and Leptin were increased in (-)-HCA treatment groups. Protein content in liver and muscle were significantly increased in (-)-HCA treatment groups. Amino acid profile analysis indicated that most of amino acid contents in serum and liver, especially aromatic amino acid and branched amino acid, were higher in (-)-HCA treatment groups. However, most of the amino acid contents in muscle, especially aromatic amino acid and branched amino acid, were reduced in (-)-HCA treatment groups. These results indicated that (-)-HCA treatment could reduce body weight gain through promoting energy expenditure via regulation of thyroid hormone levels. In addition, (-)-HCA treatment could promote protein synthesis by altering the metabolic directions of amino acids. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Peso Corporal/efectos de los fármacos , Citratos/química , Garcinia cambogia/química , Extractos Vegetales/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Aminoácidos , Animales , Humanos , Masculino , Ratas
20.
PLoS One ; 19(3): e0281226, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483917

RESUMEN

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is increasingly recognized as a major problem for children and their families in China. However, its influence on parental mental health has been seldom explored. OBJECTIVE: To examine the prevalence of attention deficit hyperactivity disorder in a community sample of children aged 6-13 years, and the extent to which it impacts parental mental health. METHOD: Cross-sectional study of primary school pupils (number = 2497) in Deyang, Sichuan Province, South-West China. We used standardized instruments to identify children with ADHD symptoms and parent depression. RESULTS: The prevalence of ADHD was 9.8%. Factors associated with the likelihood of ADHD, included family environment(P = 0.003), time spent with children(P = 0.01), parenting style(P = 0.01), and parental relationship, pupils self-harm and lower academic ability (P = 0.001). After controlling for other factors, having a child with ADHD increased the likelihood of parents' depression (OR = 4.35, CI = 2.68~7.07), additional factors included parent relationship. CONCLUSIONS: ADHD may be a common disorder among Chinese children, the symptoms of which may increase the likelihood of parent depression. There is a need for greater detection of ADHD in schools, acknowledgement of the challenges the disorder creates for academic success and family wellbeing, and psychoeducational tools for supporting parents of children with ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/psicología , Estudios Transversales , Depresión/epidemiología , Prevalencia , Padres/psicología , Responsabilidad Parental/psicología
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